Guide to Pain Management in Low-Resource Settings

Home , House of Stolberg, James Leonard Corning, Neurolytic block, Pahlen, Paradiso (Amsterdam), Serous fluid

Edited by Andreas Kopf and Nilesh B. Patel

INTERNATIONAL ASSOCIATION FOR THE STUDY OF PAIN®

Guide to Pain Management in Low-Resource Settings

Educational material written for general distribution to health care providers by a multidisciplinary and multinational team of authors

Editors

Andreas Kopf, MD Department of Anesthesiology Charité Medical University Berlin, Germany

Nilesh B. Patel, PhD Department of Medical Physiology University of Nairobi Nairobi, Kenya

IASP® • SEATTLE © 2010 IASP® International Association for the Study of Pain® All rights reserved. Th is material may be used for educational and training purposes with proper citation of the source. Not for sale or commercial use.

Timely topics in pain research and treatment have been selected for publication, but the information provided and opinions expressed have not involved any verifi cation of the fi ndings, conclusions, and opinions by IASP®. Th us, opinions expressed in Guide to Pain Management in Low-Resource Settings do not necessarily refl ect those of IASP or of the Offi cers and Councilors.

No responsibility is assumed by IASP for any injury and/or damage to persons or property as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends that there should be independent veriﬁ cation of diagnoses and drug dosages. Th e mention of speciﬁ c pharmaceutical products and any medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text. Errors and omissions are expected.

Supported by an educational grant from the International Association for the Study of Pain A preliminary version of this text was printed in 2009 Contents

Foreword vii Introduction ix

Basics 1. History, Defi nitions, and Contemporary Viewpoints 3 Wilfried Witte and Christoph Stein 2. Obstacles to Pain Management in Low-Resource Settings 9 Olaitan A Soyannwo 3. Physiology of Pain 13 Nilesh B. Patel 4. Psychological Factors in Chronic Pain 19 Harald C. Traue, Lucia Jerg-Bretzke, Michael Pfi ngsten, and Vladimir Hrabal 5. Ethnocultural and Sex Infl uences in Pain 27 Angela Mailis-Gagnon 6. Pharmacology of Analgesics (Excluding Opioids) 33 Kay Brune 7. Opioids in Pain Medicine 39 Michael Schäfer 8. Principles of Palliative Care 47 Lukas Radbruch and Julia Downing 9. Complementary Th erapies for Pain Management 59 Barrie Cassileth and Jyothirmai Gubili

Physical and Psychological Patient Evaluation 10. Pain History and Pain Assessment 67 Richard A. Powell, Julia Downing, Henry Ddungu, and Faith N. Mwangi-Powell 11. Physical Examination: Neurology 79 Paul Kioy and Andreas Kopf 12. Physical Examination: Orthopedics 87 Richard Fisher 13. Psychological Evaluation of the Patient with Chronic Pain 93 Claudia Schulz-Gibbins

Management of Acute Pain 14. Pain Management after Major Surgery 103 Frank Boni 15. Acute Trauma and Preoperative Pain 115 O. Aisuodionoe-Shadrach 16. Pain Management in Ambulatory/Day Surgery 119 Andrew Amata 17. Pharmacological Management of Pain in Obstetrics 123 Katarina Jankovic

iii iv Contents Management of Cancer Pain 18. Abdominal Cancer, Constipation, and Anorexia 137 Andreas Kopf 19. Osseous Metastasis with Incident Pain 147 M. Omar Tawﬁ k 20. Lung Cancer with Plexopathy 155 Rainer Sabatowski and Hans J. Gerbershagen 21. Lung Cancer with Breathing Problems 163 Th omas Jehser 22. Hematologic Cancer with Nausea and Vomiting 169 Justin Baker, Paul Ribeiro, and Javier Kane

Management of Neuropathic Pain 23. Painful Diabetic Neuropathy 179 Gaman Mohammed 24. Management of Postherpetic Neuralgia 183 Maged El-Ansary 25. Central Neuropathic Pain 189 Maija Haanpää and Aki Hietaharju 26. Th e Management of Pain in Adults and Children Living with HIV/AIDS 195 Glenda E. Gray, Fatima Laher, and Erica Lazarus

Management of Chronic Noncancer Pain 27. Chronic Nonspeciﬁ c Back Pain 207 Mathew O.B. Olaogun and Andreas Kopf 28. Headache 213 Arnaud Fumal and Jean Schoenen 29. Rheumatic Pain 221 Ferydoun Davatchi

Diﬃ cult Th erapeutic Situations and Techniques 30. Dysmenorrhea, Pelvic Pain, and Endometriosis 229 Susan Evans 31. Pain Management Considerations in Pregnancy and Breastfeeding 235 Michael Paech 32. Pain in Sickle Cell Disease 245 Paula Tanabe and Knox H. Todd 33. Complex Regional Pain Syndrome 249 Andreas Schwarzer and Christoph Maier 34. Pain Management in Children 255 Dilip Pawar and Lars Garten 35. Pain in Old Age and Dementia 269 Andreas Kopf 36. Breakthrough Pain, the Pain Emergency, and Incident Pain 277 Gona Ali and Andreas Kopf 37. Pain Management in the Intensive Care Unit 283 Josephine M. Th orp and Sabu James 38. Diagnostic and Prognostic Nerve Blocks 293 Steven D. Waldman Contents v 39. Post-Dural Puncture Headache 299 Winfried Meissner 40. Cytoreductive Radiation Th erapy 303 Lutz Moser 41. Th e Role of Acupuncture in Pain Management 307 Natalia Samoilova and Andreas Kopf

Planning and Organizing Pain Management 42. Setting up a Pain Management Program 317 M.R. Rajagopal 43. Resources for Ensuring Opioid Availability 321 David E. Joranson 44. Setting up Guidelines for Local Requirements 329 Uriah Guevara-Lopez and and Alfredo Covarrubias-Gomez

Pearls of Wisdom 45. Techniques for Commonly Used Nerve Blocks 337 Corrie Avenant 46. Psychological Pearls in Pain Management 341 Claudia Schulz-Gibbins 47. Clinical Physiology Pearls 345 Rolf-Detlef Treede 48. Herbal and Other Supplements 349 Joel Gagnier 49. Proﬁ les, Doses, and Side Eﬀ ects of Drugs Commonly Used in Pain Management 351 Barbara Schlisio

Appendix Glossary 359 Andreas Kopf

Foreword

Th e belief that pain treatment is a human right has been therefore, that 91% said that lack of education was the accepted by many for a long time, but in 2004 the state- main barrier to good pain management in their part of ment that “the relief of pain should be a human right” the world. was felt to be of suffi cient importance for it to be pub- It is clear that in many developing countries, re- lished following the launch of the fi rst Global Campaign lief of pain is not a priority, and that concern with infec- Against Pain in Geneva in 2004 by the International tious diseases such as malaria, tuberculosis, and above Association of Pain (IASP), the European Federation all HIV/AIDS takes precedence. In fact, 75% of those of Chapters of the IASP (EFIC), and the World Health who responded to the IASP survey considered a lack of Organization (WHO). Unfortunately, however, a large government priorities for pain management as the sec- number of those who suff er pain, and especially the ond most common barrier to good treatment. Almost as people of developing countries, do not receive treat- many reported that a fear of addiction to opioids among ment for acute and, more especially, chronic pain. doctors, nurses, and health providers was a barrier to Th ere are various reasons for this problem, the availability and use of those drugs, although, in fact, which include a lack of adequately trained health pro- such fear is primarily a consequence of poor education. fessionals, the unavailability of drugs, especially opi- Th e production of this manual is timely because oids, and a fear of using opioids because there is an it will fi ll a major gap in the knowledge of those who erroneous belief that inevitably the use of these drugs deal with people in pain in developing countries. It cov- will cause addiction. Th e fi rst major step in improv- ers the basic science of pain, and perhaps uniquely, the ing services for pain patients is to provide an educated rationale for the use of natural medicines. It also pro- workforce in developing countries—not only doctors vides background knowledge and advice on the man- and nurses, but district offi cers and other health work- agement of the major painful disorders occurring in de- ers. A survey by IASP in 2007 revealed that among its veloping countries, including the two major scourges of members in developing countries, very few believed the present time—cancer and HIV/AIDS. they had received an adequate education in the under- Th is is a book that should be available to all standing and management of pain as undergraduates. who are responsible for providing treatment for pain, In most regions of the world, less than half had been whether acute or chronic, and whether they work in trained in pain management, even though it was a sig- cities, towns, or in a much more rural settings, because nifi cant part of their daily work. It is not surprising, all will fi nd it an invaluable aid to their practice.

Professor Sir Michael Bond Glasgow, Scotland August 2009

vii

Introduction

Pain is widely undertreated, causing suff ering and fi - provide confi dence in clinical decision-making, im- nancial loss to individuals and to society. It is believed proving practical skills and attitudes to care. that health care of all patients should include assess- Information on pain and pain management is ment of pain and its impact on the patient, specifi c ef- crucial. All health care workers will see patients suf- forts by health care professionals to control pain, and fering from pain. Pain is the main reason for seeking the development of programs to generate experts in medical help. Th us, any physician, nurse, or other clini- pain management. Additionally, clinical and basic sci- cal worker needs to have basic knowledge about the ence research is to be encouraged to provide better pathophysiology of pain and should be able to use at care in the future. Th e aim of these eff orts is to ensure least simple fi rst-line treatments. Unlike “special pain that pain control receives high priority in the health management,” which should be reserved for specialist care system. physicians with specifi c postgraduate training in com- Th is book, Guide to Pain Management in Low- plex pain syndromes, knowledge of “general pain man- Resource Settings, is intended to encourage research agement” is a must for all other health care workers to on pain mechanisms and pain syndromes and help prepare them for the majority of patients in pain with improve the management of patients with acute and common pain syndromes. chronic pain by bringing together basic scientists, phy- Th e editors intend that with the help of this sicians, and other health professionals of various disci- Guide the reader will be know how to identify patients plines and backgrounds who have an interest in pain. suff ering from pain, understand the nature of pain and Th e target audience is basic research and preclinical its infl uence on the patient’s life, know the methods of staff , surgical and internal medicine practitioners of all analgesia that can provide eff ective pain management disciplines, anesthetists and anesthesiologists, all ad- for most patients, know how to apply those methods vanced nursing staff , and local health care workers in and how to classify them in graduated schemes in- district and mission hospitals, as well as medical and cluding nonpharmacological approaches, and know nursing students. how to evaluate the effi ciency of pain management. In low-resource settings, many health care Th e main focus of the Guide is to address the follow- workers have little or no access to basic, practical in- ing four pain syndromes: acute post-traumatic post- formation. Indeed, many have come to rely on obser- operative pain, cancer pain, neuropathic pain, and vation, on advice from colleagues, and on building chronic noncancer pain. experience empirically through their own treatment Th e editors understand the barriers and future successes and failures. Th e disparity of theoretical and needs regarding good pain management. Th ese barriers practical availability of information is due to several include lack of pain education and a lack of emphasis factors, including unequal distribution of Internet ac- on pain management and pain research. In addition, cess, and also a failure of international development when pain management does feature in government policies and initiatives, which have tended to focus health priorities, there are fears of opioid addiction, on innovative approaches for higher-level health pro- the high cost of certain drugs, and in some cases, poor fessionals and researchers while ignoring, relatively patient compliance. In developing countries, the avail- speaking, other approaches that remain essential for able resources for health care understandably focus on the vast majority of primary and district health work- the prevention and treatment of “killer” diseases. Yet ers. Th e information poverty of health workers in most such disease conditions are accompanied by un- low-resource settings is exacerbating what is clearly a relieved pain, which is why pain control matters in the public health emergency. Primary and district health developing world, according to Prof. Sir Michael Bond. workers should be at the center of eff orts to address Th e WHO recommends that “since in most parts of this crisis. Th e availability of health information may the world, the majority of cancer patients present with ix x Introduction advanced disease … the only realistic treatment option concise and up-to-date-information in a novel curricu- is pain relief and palliative care.” Due to the limited re- lum structure for the medical practitioner in countries sources for health care, the WHO further proposes that belonging to the developing world. It will also serve in the future, palliative instead of curative approaches to medical faculties by suggesting core curriculum topics treatment should be encouraged. on pain physiology and management. It is believed that However, it is a sad reality that the medicines the project will encourage medical colleges to integrate that are essential for relieving pain often are not avail- these educational objectives into their local student and able or accessible. Th ere are numerous reports, some of nursing curriculums. It will provide the non-pain spe- them published in major medical and science journals, cialist with basic relevant information—in a form that about the defi cits of adequate pain management, pre- is easily understood—about the physiology of pain and dominantly in developing countries in all regions of the the diff erent management and treatment approaches world. It is sincerely believed that with relatively minor for diff erent types and syndromes of pain. input (referring not to eff orts to change the situation Any practitioner who deals with pain problems but to the availability of essential drugs and techniques), must be aware of the entire range of pathophysiological the quality of analgesic treatment for cancer and HIV/ and psychopathological problems that are commonly AIDS patients in low-resource countries might be con- encountered in pain patients, and must therefore have siderably improved, as documented by local initiatives access to a reasonable range of medical, physical, and around the world. Th e IASP has recently produced an psychological therapies to avoid imposing on the pa- atlas of pain training and pain facilities in developing tients and society any additional fi nancial and person- countries. More information on this atlas can be found al costs. Th e aim of these eff orts is to ensure that pain on the IASP website (www.iasp-pain.org). control receives higher priority, especially in the treat- For the pain specialist in developed countries, ment of cancer and HIV/AIDS patients, as well as for plenty of detailed information is available, but for the postoperative and injury-related acute pain. Th erefore, non-pain specialist and other health care providers, in- this book will encourage the management of patients cluding nurses and clinical staff in many other regions with acute and chronic pain, since it is well understood of the world, who have to deal with patients in pain, from the literature that even basic education has a con- there is a lack of a basic guide or manual on pain mech- siderable impact on the quality of analgesic therapy for anisms, management, and treatment rationales. Th is is the patient. of particular concern in areas of the world where, out- Th e editors appreciate the enthusiasm and ef- side the main urban areas, there is no access to infor- forts put in by the volunteer authors of this Guide, mation about pain etiology or management and no ac- without whom this book would not have been possible. cess to a pain specialist. Many have experience in the problems faced by health Th e IASP Developing Countries Task Force care providers in the developing world. Th ey have (now the Developing Countries Working Group) was tried to project their thoughts into particular situations founded to encourage ongoing medical education and and settings: “Can I cope with what is expected of me, clinical training in low-resource countries and is sup- working as a doctor or nurse or health care provider in porting local eff orts to raise awareness of pain. Th e ed- a developing country and facing a wide range of pain ucational grant program, the “Initiative for Improving problems?” Th is question has presumably passed uneas- Pain Education,” addresses the need for improved edu- ily through the minds of many practitioners. Th e pur- cation about pain and its treatment in developing coun- pose is to provide the reader with various approaches to tries by providing educational support grants. Th ese the management of some common pain management grants are intended to improve the scope and availabil- problems. It is by no means intended to be a defi nitive ity of essential education for pain clinicians of all disci- reference. Treatment algorithms presented are based plines, taking into account specifi c local needs. Follow- on the review of available literature and experience in ing a joint proposal by the University of Nairobi (N. B. pain clinics, with a specifi c view on the potential local Patel) and the Charité University Medicine Berlin (A. limitations in the developing world. Instead of a text- Kopf), the IASP awarded one of the grants to a book book approach with independent chapters written in a project on pain management in low-resource countries. systematic manner, the Guide tries to follow a problem- Th e result is this Guide, which is intended to provide orientated learning path. Th e chapters are intended to Introduction xi be suffi ciently broad and understandable to be of value incorporated pain management in their training pro- to the nonspecialist. Th e structure, including questions grams for students, residents, clinical offi cers, and and answers, pearls of wisdom, and illustrative case re- nurses. Th erefore, knowledge about the local charac- ports, as well as valuable literature suggestions for fur- teristics of pain and treatment-related modalities is ther reading, will, we hope, make the Guide a helpful scarce, which has made it diffi cult for us to determine companion and aid to pain management. All readers the relevance of some of the topics but will, we hope, are invited to contribute to the improvement of further not limit the usefulness of the Guide. Th e authors, editions by sending their comments and suggestions to with their wide international background, have tried the editors. to provide an ubiquitous view on pain management. It Th e Guide does have some shortcomings. is the hope of the editors that the Guide will be use- Although pain management has been a topic of in- ful to readers from a variety of regions of the world creased interest for at least two decades, developing and from a variety of medical health care providers. countries have few initiatives in this direction, and Depending on feedback from the readers, the editors little is known about the needs, characteristics, and plan to produce a second volume with an emphasis on treatment modalities with regard to pain. Refresher the general terms and requirements of good pain man- courses, workshops, medical schools, conferences, agement, and possibly revised editions as well as edi- and schools of anesthesia usually have not actively tions in other common languages.

Andreas Kopf, Berlin, Germany Nilesh Patel, Nairobi, Kenya September 2009

Th e guide is dedicated to Professor Mohammed Omar Tawﬁ k, Cairo, Egypt, whose professional life was dedicated to the teaching and dissemination of pain management.

Acknowledgment Since its founding in 1973, IASP has consistently supported pain research and treatment eﬀ orts in developing countries. Th e editors wish to express their gratitude towards the IASP, which has supported this project continuously with advice and review of the material and an educational grant enabling the dissemination of this Guide to Pain Management in Low-Resource Settings. Contributing Authors

Comments and questions to the editors and authors via email are welcomed.

Oseremen Aisuodionoe-Shadrach, MBBS Ferydoun Davatchi, MD Department of Surgery Rheumatology Research Center University of Abuja Division of Rheumatology Abuja, Nigeria Tehran University for Medical Sciences [email protected] Tehran, Iran [email protected] Dr Gona Ali Faculty of Medicine Dr Henry Ddungu, MD University of Sulaymaniyah African Palliative Care Association Sulaymaniyah, Iraq Kampala, Uganda [email protected] [email protected] Andrew O. Amata, MBBS Julia Downing, PhD Department of Anaesthesia and Intensive Care African Palliative Care Association Georgetown Public Hospital Corporation Kampala, Uganda Georgetown, Guyana [email protected] [email protected] Maged El-Ansary, MD Corrie C. Avenant, MB ChB Department of Anesthesiology Fontainebleau, Randburg Al-Azhar University South Africa Cairo, Egypt [email protected] [email protected] Justin N. Baker, MD Susan Evans, MD Department of Pediatric Medicine Endometriosis Care Centres of Australia Division of Palliative and End-of-Life-Care Adelaide, Australia St. Jude Children’s Research Hospital [email protected] Memphis, Tennessee, USA [email protected] Richard C. Fisher, MD Orthopedic Overseas Division Dr Frank Boni Health Volunteers Overseas Department of Anesthesiology Washington, DC, USA University of Ghana Medical School richard.ﬁ [email protected] Accra, Ghana [email protected] Arnaud Fumal, MD Neurology and Headache Research Unit Kay Brune, MD University of Liège Institute of Pharmacology and Toxicology Liège, Belgium Friedrich-Alexander University of Erlangen-Nürnberg [email protected] Erlangen, Germany [email protected] Joel Gagnier, ND, MSc, PhD Department of Epidemiology Barrie Cassileth, PhD School of Public Health Integrative Medicine Service University of Michigan Memorial Sloan-Kettering Cancer Centre Ann Arbor, Michigan, USA New York, New York, USA [email protected] [email protected] Dr Lars Garten Alfredo Covarrubias-Gomez, MD Otto Heubner Centre for Pediatric and Adolescent Medicine Vasco De Quiroga 15, Col. Seccion XVI Charité University Hospitals Torelio Guerra, Tlalpan Berlin, Germany Mexico City 14000, Mexico [email protected] [email protected]

xii Contributing Authors xiii Hans J. Gerbershagen, MD, PhD Lucia Jerg-Bretzke, PhD Department of Anesthesiology Medical Psychology Division of Perioperative and Emergency Care Department of Psychosomatic Medicine and Psychotherapy University Medical Center Utrecht University of Ulm Utrecht, Th e Netherlands Ulm, Germany [email protected] [email protected] Glenda E. Gray, MD David E. Joranson, MSSW Perinatal HIV Research Unit Pain & Policy Studies Group University of Witwatersrand University of Wisconsin Carbone Cancer Center Diepkloof, South Africa School of Medicine and Public Health [email protected] Madison, Wisconsin, USA [email protected] Jyothirmai Gubili, MS Integrative Medicine Service Javier R. Kane, MD Memorial Sloan-Kettering Cancer Centre Department of Pediatric Medicine New York, New York, USA Division of Palliative and End-of-Life Care [email protected] St. Jude Children’s Research Hospital Memphis, Tennessee, USA Uriah Guevara-Lopez, MD, MSc [email protected] Department of Pain Medicine and Palliative Care National Institute of Medical Sciences Paul G. Kioy, MBchB, MMed Mexico City, Mexico Department of Medical Physiology [email protected] University of Nairobi Nairobi, Kenya Maija Haanpää, MD, PhD [email protected] Department of Neurosurgery Helsinki University Hospital Andreas Kopf, MD Helsinki, Finland Pain Unit, Department of Anesthesiology maija.haanpaa@orton.fi Charité University Hospitals Berlin, Germany Aki Hietaharju, MD, PhD Visiting Professor, Department of Medical Physiology Pain Clinic University of Nairobi, Kenya Department of Neurology and Rehabilitation [email protected] Tampere University Hospital Tampere, Finland Fatima Laher, MBBCh aki.hietaharju@pshp.fi Perinatal HIV Research Unit University of Witwatersrand Vladimir Hrabal, Dr phil. Diepkloof, South Africa Department of Medical Psychology [email protected] University of Ulm Ulm, Germany Dr Erica Lazarus [email protected] Perinatal HIV Research Unit University of Witwatersrand Sabu Kumar James, MBBS Diepkloof, South Africa Department of Anaesthesiology University of Glasgow Christoph Maier, MD Glasgow, Scotland Department of Pain Management United Kingdom Clinic for Anesthesiology [email protected] University Clinic Bergmannsheil Ruhr-University Katarina Jankovic, MD Bochum, Germany Department of Anesthesiology [email protected] MP Shah Hospital Nairobi, Kenya Angela Mailis-Gagnon, MD [email protected] Comprehensive Pain Program Toronto Western Hospital Th omas Jehser, MD Toronto, Ontario, Canada Pain and Palliative Care Department [email protected] Havelhöhe Hospital Berlin, Germany [email protected] xiv Contributing Authors Winfried Meissner, MD Lukas Radbruch, MD Department of Internal Medicine Palliative Care Unit University Medical Centre University Hospital Aachen Jena, Germany Aachen, Germany [email protected] [email protected] Dr Gaman Mohammed M.R. Rajagopal, MD Diabetes Centre Pallium India (Trust) Avenue Healthcare Trivandrum, Kerala Nairobi, Kenya India [email protected] [email protected] Lutz Moser, MD Dr. Raul Ribeiro, MD Department of Radiology Department of Oncology Charité University Hospitals International Outreach Program Berlin, Germany St. Jude Children’s Research Hospital [email protected] Memphis, Tennesee, USA [email protected] Faith N. Mwangi-Powell, PhD African Palliative Care Association Rainer Sabatowski, MD Kampala, Uganda Interdisciplinary Pain Clinic [email protected] University Hospital Carl-Gustav Carus Dresden, Germany Mathew O.B. Olaogun, PT [email protected] Department of Medical Rehabilitation Obafemi Awolowo University Dr Natalia Samoilova Ife-Ife, Nigeria Department of Pain Medicine [email protected] National Research Centre of Surgery B.V. Petrosky Russian Academy of Medical Science Michael Paech, MBBS, FRCA, FANZCA, Moscow, Russia FFPMANZCA [email protected] Division of Anaesthesiology University of Western Australia Michael Schäfer, MD, PhD Crawley, Western Australia Department of Anesthesiology Australia Charité University Hospitals [email protected] Berlin, Germany [email protected] Nilesh B. Patel, PhD Department of Medical Physiology Barbara Schlisio, MD University of Nairobi Department of Anesthesiology Nairobi, Kenya University Medical Centre [email protected] Tübingen, Germany [email protected] Dilip Pawar, MBBS Department of Anesthesiology Dr Jean Schoenen All India Institute of Medical Sciences Headache Research Unit New Delhi, India Department of Neurology and GIGA Neurosciences [email protected] Liège University Liège, Belgium Michael Pfi ngsten, PhD [email protected] Pain Clinic Department of Anaesthesiology Claudia Schulz-Gibbins, Dipl.-Psych. University Medicine Department of Anesthesiology Göttingen, Germany Charité University Hospitals michael.pfi [email protected] Berlin, Germany [email protected] Richard A. Powell, MA, MSc African Palliative Care Association Kampala, Uganda [email protected] Contributing Authors xv Andreas Schwarzer, MD, PhD Knox H. Todd, MD, MPH Department of Pain Management Department of Emergency Medicine Clinic for Anesthesiology Beth Israel Medical Center University Clinic Bergmannsheil New York, New York, USA Ruhr-University [email protected] Bochum, Germany [email protected] Dr Harald C. Traue Medical Psychology Olaitan A Soyannwo, MB BS, MMed Department of Psychosomatic Medicine and Psychotherapy Department of Anesthesia University of Ulm Ibadan College of Medicine Ulm, Germany Ibadan, Nigeria [email protected] [email protected] Rolf-Detlef Treede, MD Christoph Stein, MD Department of Neurophysiology Department of Anesthesiology Faculty of Medicine Mannheim, University of Heidelberg Charité University Mannheim, Germany Berlin, Germany [email protected] [email protected] Steven Waldman, MD Paula Tanabe, RN, PhD Th e Headache and Pain Centre Department of Emergency Medicine Leawood, Kansas, USA Institute for Healthcare Studies sdwaldman@ptfi rst.org Northwestern University Chicago, Illinois, USA Wilfried Witte, MA ptanabe2@nmff .org Department of Anaesthesiology Charité University Hospitals Mohamed Omar Tawfi k, MD, MBBCh Free University of Berlin (deceased, June 2009) Berlin, Germany Pain Unit [email protected] National Cancer Institute Cairo University Cairo, Egypt Josephine M. Th orp, MRCP, FFARCS Anaesthetic Department, Monklands Hospital Airdrie, Lanarkshire Scotland, United Kingdom [email protected]

Basics

Guide to Pain Management in Low-Resource Settings

Chapter 1 History, Deﬁ nitions, and Contemporary Viewpoints

Wilfried Witte and Christoph Stein

Th e experience of pain is fundamental and has been proved by Job’s humility toward God. Humility is still part of the cultural development of all societies. In the an ideal in Christian thought today. In the New Testa- history of pain, “supernatural” powers played an equally ment, Jesus Christ fi nishes his life on earth as a mar- important role as natural factors. To view pain as the re- tyr hanging and dying at the cross. His suff ering marks sult of a “communication” between mankind and divine the way to God. To bear suff ering in life is necessary to powers has been a fundamental assumption in many be absolved from sin. Th e message of pain is to show societies. Th e more societies are separated from West- mankind the insuffi ciency of life on earth and the bril- ern medicine or modern medicine, the more prevalent liance of being in heaven. Th us, whatever science may is this view of pain. On the other hand, a purely medi- say about pain, an approach based only on a physiological theory based on natural phenomena independent of cal concept does not take into account the religious or divine powers developed very early on. It happened to a spiritual meaning of pain. greater extent in ancient China, while in ancient India Th e most important and radically mechanis- medicine was heavily infl uenced by Hinduism and Bud- tic scientifi c theory of pain in early modern age derives dhism. Pain was perceived in the heart—an assumption from the French philosopher René Descartes (1596– familiar to ancient Egyptians. Th e medical practitioners 1650). In his concept, the former assumption that pain in pharaonic times believed that the composition of was represented in the heart was relinquished. Th e body fl uids determined health and disease, and magic brain took the place of the heart. In spite of (or because was indiscriminable from medicine. of) its one-sidedness, Descartes’ theory opened the gate Ancient Greek medicine borrowed heavily for neuroscience to explain the mechanisms of pain. from its Asian and Egyptian predecessors. Th e intro- Th e question of how pain should be treated has duction of ancient medical knowledge into medieval led to diff erent answers over time. If supernatural pow- Europe was mainly mediated through Arabic medicine, ers had to be pleased to get rid of pain, certain magi- which also added its own contributions. Latin was the cal rituals had to be performed. If scientifi cally invented language of scholars in medieval Europe, and ideology remedies were not used or not available, ingredients was guided by Judeo-Christian beliefs. Despite mul- from plants or animals had to be used to ease the pain. tiple adaptations, medical theory remained committed Especially, the knowledge that opium poppies have anal- to ancient models for centuries. Pain had an important gesic eff ects was widespread in ancient societies such as role. Th e Bible illustrates the need to withstand catas- Egypt. For a long time, opium was used in various prep- trophes and pain in the story of Job. Strength of faith is arations, but its chemical constituents were not known.

Th e isolation of the opium alkaloid morphine was fi rst Th e fi rst decades of morphine use may be seen accomplished in 1803 by the German pharmacist Fried- as a period of high expectations and optimism regard- rich Wilhelm Sertürner (1783–1806). Th e industrial ing the ability to control pain. Th e fi rst drawback to production of morphine began in Germany during the this optimism was the discovery made in the Ameri- 1820s, and in the United States in the 1830s. During the can Civil War (1861–1865), when cases of morphine late 18th to the mid-19th century, the natural sciences dependence and abuse appeared. As a consequence, took over the lead in Western medicine. Th is period restrictions on the distribution of opiates were begun. marked the beginning of the age of pathophysiological Th e negative view of morphine use was enhanced by pain theories, and scientifi c knowledge about pain in- experiences in Asia, where an extensive trade in opium creased step by step. and morphine for nonmedical purposes was already Th e discovery of drugs and medical gases was established during the 19th century. Th erefore, at the a cornerstone of modern medicine because it allowed beginning of the 20th century, societal anxiety regard- improvements in medical treatment. It was modern an- ing the use of morphine became strong and developed esthesia in particular that promoted the development of into opiophobia (i.e., the fear of using opioids), which surgery. General anesthesia using ether was introduced was a major step backwards for pain management in successfully in Boston on October 16, 1846, by the phy- the following decades. sician William Th omas Morton (1819–1868). Th e im- Wars stimulated pain research because soldiers portance of this discovery, not only for surgery but for returned home with complex pain syndromes, which the scientifi c understanding of pain in general, is under- posed insurmountable problems for the available ther- scored by the inscription on his tombstone: “Inventor apeutic repertoire. Following his experience after 1915 and Revealer of Inhalation Anesthesia: Before Whom, in during the First World War, the French surgeon René All Time, Surgery was Agony; By Whom, Pain in Sur- Leriche (1879–1955) began to concentrate on “pain gery was Averted and Annulled; Since Whom, Science surgery,” mainly addressing the autonomic nervous has Control of Pain.” Th is statement suggested that pain system. Leriche applied methods of regional anesthe- would vanish from mankind just by applying anesthesia (infi ltration with procaine, sympathetic ganglionic sia. Surgery itself changed to procedures that were not blockade) as well as surgery, particularly periarterial necessarily connected with a high level of pain. Th us, sympathectomy. He not only rejected the idea of pain the role of surgery changed. Surgeons had more time to as a necessary evil but also criticized the reductionist perform operations, and patients were no longer forced scientifi c approach to experimental pain as a purely to suff er pain at the hands of their surgeons. neuroscientifi c phenomenon. He viewed chronic pain Further innovations followed. One year later, as a disease in its own right (“douleur-maladie”), not in 1847, chloroform was used for the fi rst time for an- just as a symptom of disease. esthesia in gynecology by the Scottish physician James Regional anesthesia was the mainstay of pain Young Simpson (1811–1879). In Vienna, the physi- therapy applied by the French surgeon Victor Pauchet cian Carl Koller (1857–1944) discovered the anesthetic (1869–1936). Already, before his experiences in the properties of cocaine in 1884. At about the same time, war, he had authored the fi rst edition of his textbook during the last two decades of the 19th century, the U.S. L’Anesthésie Régionale in 1912. Th rough Louis Gas- neurologist James Leonard Corning (1855–1923) and ton Labat (1876–1934), a physician from Paris who the German surgeon August Bier (1861–1949) carried later practiced in the United States, his wisdom be- out trials of spinal anesthesia with cocaine solutions. came known in the New World and was an important Modern anesthesia enabled longer and more complex stimulus for the dissemination of regional anesthesia in surgical procedures with more successful long-term the United States between the two World Wars. In the outcomes. Th is advance promoted the general consen- 1920s, the notion that regional anesthesia could be used sus that the relief of somatic pain was good, but it was not only for surgery but also for chronic pain spread secondary to curative therapy: no pain treatment was throughout the United States. possible without surgery! Th us, within the scope of an- After the Second World War these ideas esthetic practice, pain management as a therapeutic were taken up by John Joseph Bonica (1914–1994), goal did not exist at that time. Chronic pain was not a who had emigrated with his parents from Sicily to topic at all. the United States at the age of 11 years. As an army History, Defi nitions, and Contemporary Viewpoints 5 surgeon entrusted with the responsibility of giv- ever, the “gate control theory” emphasized a strictly ing anesthesia, he realized that the care of wounded neurophysiological view of pain, ignoring psychologi- soldiers was inadequate. Th e patients were left alone cal factors and cultural infl uences. with their pain after surgery. Bonica observed that Medical ethnology examines cultural infl u- pain frequently became chronic and that many of these ences on perception and expression of pain. Th e most patients fell prey to alcohol abuse or depressive disor- important early study was published in 1952 and was ders. Bonica’s answer to this problem, which also affi nanced by the U.S. Public Health Service. On the fected other pain patients, was to establish pain clinics basis of about 100 interviews with veterans of both where physicians of diff erent disciplines, psycholo- World Wars and the Korean War, who were accommo- gists, and other therapists worked together in teams to dated in a Veterans’ Hospital in the Bronx, New York understand the complexity of chronic pain and treat it City, the investigators examined how diff erent cultural adequately. Anesthesiology remained Bonica’s special- backgrounds infl uence pain perception. Th e veter- ty. Only a few pain clinics existed in the United States ans were diff erentiated into those of Italian, Irish, or when he published the fi rst edition of his textbook Jewish origin—besides the group of the “Old Ameri- Pain Management in 1953. Th is landmark may be re- cans,” comprising U.S.-born Whites, mostly Protestant garded as the date of birth of a new medical discipline. Christians. One result of this investigation was that Nevertheless, it took many years before a the “Old Americans” presented the strongest stoicism broader audience became interested in pain therapy. In in the experience of pain, while their attitude towards the year 1973, to make this topic more popular, Bonica pain was characterized as “future-oriented anxiety.” founded the International Association for the Study of According to the interpretation of the investigators, Pain (IASP). In the following years, national chapters of this anxiety demonstrated an attempt to be conscious the IASP were founded around the globe. In 1979, IASP about one’s own health. Th e more a Jew or Italian or coined the important defi nition of pain as “an unpleas- Irish immigrant was assimilated into the American ant sensory and emotional experience associated with way of life, the more their behavior and attitudes were actual or potential tissue damage or described in terms similar to those of the “Old Americans.” However, pain of such damage,” which is still valid. Th is defi nition was was still seen merely as a symptom, and non-Western important because for the fi rst time it implied that pain cultures were not a focus of interest. is not always a consequence of tissue damage but may It took about another three decades to change occur without it. Western science then began to realize this situation. During the 1990s, studies demonstrated that “somatic” factors (tissue damage) cannot be sepa- that diff erent attitudes and beliefs in diff erent ethnic rated from “psychological” factors (learning, memory, groups around the world play a role in the variation of the soul, and aff ective processes). Together with the rec- intensity, duration, and subjective perception of pain. As ognition of social infl uences on pain perception, these a consequence, health workers have to realize that pa- factors form the core of the modern biopsychosocial tients with (chronic) pain value therapists who recog- concept of pain. nize their cultural and religious beliefs. During the 20th century multiple pain theo- Another important aspect that attracted inter- ries were conceived. Th e most important theory—to est was the relief of pain in patients with advanced dis- which Bonica also subscribed—came from the Ca- ease. It was the nurse, social worker, and later physi- nadian psychologist Ronald Melzack (1929–) and cian Cicely Saunders (1918–2005) who developed the the British physiologist Patrick D. Wall (1925–2001). “Total Pain” concept. Chronic pain in advanced disease Th eir theory was published in 1965 and is known as totally changes everyday life and challenges the will to the “gate control theory.” Th e term “gate” was sup- live. Th is problem is continuously present, so Saunders posed to describe spinal cord mechanisms regulating drew the conclusion that “constant pain needs con- the transmission of pain impulses between the periph- stant control.” According to this concept, pain cannot ery and the brain. Th is theory was important because be separated from the personality and environment of it no longer regarded the central nervous system as a a patient with advanced and fatal illness. Th e founda- simple passive medium for transmission of nerve sig- tion of St. Christopher’s Hospice in London, England, nals. It implied that the nervous system was also “ac- in 1967 by Saunders may be seen as the starting point tively” altering transmission of nerve impulses. How- of palliative medicine. It refl ects a change of interest in 6 Wilfried Witte and Christoph Stein medicine from acute (infectious) diseases to cancer and brochure, the WHO fi lled the gap by “forcing” health other chronic diseases in the fi rst half of the 20th cen- care systems to use opioids according to the now tury. Th e term “palliative care” (or palliative therapy) widely known three-step “analgesic ladder.” Th e suc- comes from the Latin word “pallium” (cover, coat) and cess of this initiative was, unfortunately, not the same is supposed to alleviate the last phase of life if curative in diff erent regions of the world. While opioid avail- therapy is no longer possible. Palliative care is, a priori, ability and opioid consumption multiplied in the An- designed to concentrate on quality of life. It has roots in glo-American and Western European countries, other non-Christian societies, but it is mainly regarded to be regions of the world observed only minor increases or in the tradition of medieval hospices. However, the his- even falling numbers of opioid prescriptions. It must torical background of the hospices was not the same in be added, though, that in the Anglo-American and every European country, and neither was the meaning Western European sphere, facilitated access to opioids of the word “pallium”; sometimes it was used by healers has promoted an uncritical extension of opioid use to to disguise their inability to treat patients curatively. noncancer pain patients as well. Th is use might be jus- Palliative care became even more important tifi ed in cases of neuropathic or chronic infl ammatory when another totally unexpected pandemic occurred pain, but it should be regarded as a misapplication in in the mid-1980s—HIV/AIDS. Particularly in Africa, most other noncancer pain syndromes. Opioids should this new “plague” rapidly developed into an enormous not be used as a panacea (one remedy working for all), health problem that could no longer be ignored. Cancer and current practice in some countries might threaten and neuropathic pain play important roles in patients opioid availability in the future if health care authori- with HIV/AIDS. Th e development of palliative medi- ties decide to intervene and restrict opioid use even cine in Africa began in Zimbabwe in 1979, followed more than today. by South Africa in 1982, Kenya in 1989, and Uganda In conclusion, the understanding of pain as a in 1993. Th e institutions in Uganda became models in major health care problem has come a long way. From the 1990s, based on the initiative of the physician Anne the old days, when pain often was regarded as an un- Marriman (1935-), who spent a major part of her life in avoidable part of life, which humans could only par- Asia and Africa. Uganda provided a favorable environ- tially infl uence because of its presumed supernatural ment for her project “Hospice Africa Uganda” because etiology, a physiological concept has developed, where at the time Uganda was the only African country whose pain control is now possible. In the last few decades government declared “palliative care for AIDS and can- the “natural science” concept has been revised and ex- cer victims” a priority within its “National Health Plan.” tended by the acceptance of psychosocial and ethno- Th e rate of curative cancer treatment in Uganda is low, cultural infl uencing factors. Although basic research as in most economically disadvantaged countries. Th is has helped to uncover the complex mechanisms of situation makes problems associated with cancer and pain and facilitated the development of new strategies AIDS all the more urgent. to treat pain, the age-old opioids are still the mainstay Broad acceptance of chronic pain manage- of pain management for acute pain, cancer pain, and ment in the 20th century required the leadership of neuropathic pain. While the understanding and treat- the World Health Organization (WHO), stimulated ment of other chronic noncancer pain syndromes are by Jan Stjernswärd from Sweden (1936–). In 1982, still demanding, cancer pain, acute pain, and neuro- Stjernswärd invited a number of pain experts, includ- pathic pain may be relieved in a large number of pa- ing Bonica, to Milan, Italy, to develop measures for tients with easy treatment algorithms and “simple” the integration of pain management into common opioid and nonopioid analgesics. Th erefore, the future knowledge and medical practice. Cancer was cho- of pain management in both high- and low-resource sen as a starting point. At that time, the experts were environments will depend on access to opioids and on concerned about the increasing gap between success- the integration of palliative care as a priority in health ful pain research, on the one hand, and decreasing care systems. Pain Management in Low-Resource Set- availability of opioids to patients, especially cancer tings intends to contribute to this goal in settings patients, on the other. A second meeting took place where the poor fi nancing of health care systems high- in Geneva in 1984. As a result, the brochure “Cancer lights the importance of pain management in pallia- Pain Relief” was published in 1986. In distributing this tive care. History, Defi nitions, and Contemporary Viewpoints 7

[6] Karenberg A, Leitz C. Headache in magical and medical papyri of An- References cient Egypt. Cephalgia 2001;21:545–50. [7] Loeser JD, Treede RD. Th e Kyoto protocol of IASP basic pain terminol- [1] Bates, MS, Edwards WT, Anderson KO. Ethnocultural inﬂ uences on ogy. Pain 2008;137:473–7. variation in chronic pain perception. Pain 1993;52:101–12. [8] Meldrum ML. A capsule history of pain management. JAMA [2] Brennan F, Carr DB, Cousins M. Pain management: a fundamental hu- 2008;290:2470–5. man right. Pain Med 2007;105:205–21. [9] Merskey H. Some features of the history of the idea of pain. Pain [3] El Ansary M, Steigerwald I, Esser S. Egypt: over 5000 years of pain 1980;9:3–8. management—cultural and historic aspects. Pain Pract 2003;3:84–7. [10] Stolberg M. “Cura palliativa”: Begriﬀ und Diskussion der palliativen [4] Eriksen J, Sjøgren P, Bruera E. Critical issues on opioids in chronic non- Krankheitsbehandlung in der vormodernen Medizin (ca. 1500–1850). cancer pain: an epidemiological study. Pain 2006;125:172–9. Medizinhist J 2007;42:7–29. [5] Jagwe J, Merriman A. Uganda: Delivering analgesia in rural Africa: opioid availability and nurse prescribing. J Pain Symptom Manage 2007;33:547–51.

Guide to Pain Management in Low-Resource Settings

Chapter 2 Obstacles to Pain Management in Low-Resource Settings

Olaitan A Soyannwo

Why is eff ective pain management of diseases even in poor countries is now noticeable as diffi cult to achieve in low-resource noncommunicable diseases, injuries, and violence are as important as communicable diseases as causes of death countries? and disability. Many of these conditions have accompa- Low-income and middle-income economies of the nying pain (acute and chronic), which is inadequately ad- world are sometimes referred to as developing coun- dressed and treated. While there is consensus that stron- tries, although there are wide diff erences in their eco- ger health systems are key to achieving improved health nomic and development status, politics, population, and outcomes, there is less agreement on how to strengthen culture. Poverty is, however, a common factor in the them. In countries where the average income is below the health situation of low-resource countries, and it is the “breadline,” there is little priority specifi cally for pain is- main determinant of disease, since most of the popu- sues as most people concentrate on working to earn an lation lives on less than US$1 a day (below the “bread- income regardless of any pain problem. line”). Malnutrition, infections, and parasitic diseases are prevalent, with high rates of morbidity and mortal- Is pain management a problem ity, especially in rural areas and among pregnant wom- in resource-poor countries? en and children. Most countries therefore defi ne and Pain is the most common problem that makes patients implement an “essential health package” (EHP), which is visit a health care practitioner in low-resource coun- a minimum package of cost-eff ective public health and tries. In a WHO study, persistent pain was a commonly clinical interventions provided for dealing with major reported health problem among primary care patients sources of disease burden. and was consistently associated with psychological ill- Th ese health priorities were addressed in the ness. Both acute and chronic cancer and noncancer 2000 United Nations Millennium Development Goals pains are undertreated, and analgesics may not even be (MDG), which emphasized the eradication of poverty available in rural hospitals. and hunger, universal primary education, gender equal- ity, reduction of child mortality, improvement of ma- How do patients handle ternal health, combating HIV/AIDS, malaria, and other major diseases, environmental sustainability, and global their pain problems? partnership for development. Although communicable Usually, the fi rst attempt at pain management in these diseases are the emphasis, a transition in the epidemiology patients is the use of home remedies, including herbal

References

[1] Charlton E. Th e management of postoperative pain. Update Anaesth 1997;7:1–7. [2] Gureje O, Von Korﬀ M, Simon GE, Gater R. Persistent pain and well- being: a World Health Organization study in primary health care. JAMA 1998;280:147–51.

Guide to Pain Management in Low-Resource Settings

Chapter 3 Physiology of Pain

Nilesh B. Patel

Pain is not only an unpleasant sensation, but a complex may show no behavior indicating pain. Nociception can sensory modality essential for survival. Th ere are rare lead to pain, which can come and go, and a person can cases of people with no pain sensation. An often-cited have pain sensation without obvious nociceptive activi- case is that of F.C., who did not exhibit a normal pain ty. Th ese aspects are covered in the IASP defi nition: “An response to tissue damage. She repeatedly bit the tip of unpleasant sensory and emotional experience associ- her tongue, burned herself, did not turn over in bed or ated with actual or potential tissue damage, or described shift her weight while standing, and showed a lack of in terms of such damage.” autonomic response to painful stimuli. She died at the age of 29. Physiology of pain Th e nervous system mechanism for detection of stimuli that have the potential to cause tissue damage is Nociceptors and the transduction very important for triggering behavioral processes that of painful stimuli protect against current or further tissue damage. Th is is Th e nervous system for nociception that alerts the done by refl ex reaction and also by preemptive actions brain to noxious sensory stimuli is separate from the against stimuli that can lead to tissue damage such as nervous system that informs the brain of innocuous strong mechanical forces, temperature extremes, oxy- sensory stimuli. gen deprivation, and exposure to certain chemicals. Nociceptors are unspecialized, free, unmyelin- Th is chapter will cover the neuronal recep- ated nerve endings that convert (transduce) a variety of tors that respond to various painful stimuli, substances stimuli into nerve impulses, which the brain interprets that stimulate nociceptors, the nerve pathways, and the to produce the sensation of pain. Th e nerve cell bodies modulation of the perception of pain. Th e term nocicep- are located in the dorsal root ganglia, or for the trigemi- tion (Latin nocere, “to hurt”) refers to the sensory pro- nal nerve in the trigeminal ganglia, and they send one cess that is triggered, and pain refers to the perception nerve fi ber branch to the periphery and another into the of a feeling or sensation which the person calls pain, spinal cord or brainstem. and describes variably as irritating, sore, stinging, ach- Th e classifi cation of the nociceptor is based on ing, throbbing, or unbearable. Th ese two aspects, noci- the classifi cation of the nerve fi ber of which it is the ter- ception and pain, are separate and, as will be described minal end. Th ere are two types of nerve fi bers: (1) small- when discussing the modulation of pain, a person with diameter, unmyelinated nerves that conduct the nerve tissue damage that should produce painful sensations impulse slowly (2 m/sec = 7.2 km/h), termed C fi bers,

Released by bation of the nociceptive system with peripheral and/or tissue damage: Skin Bradykinin central sensitization.) K+ Prostaglandins d) Hyperesthesia: Increased sensitivity to stimulation, excluding the special senses, e.g., increased cuta- C fibers neous sensibility to thermal sensation without pain. Aδ fibers Histamine Injury To spinal cord With the knowledge of pain pathways and sensitization mechanisms, therapeutic strategies to interact specifi cally with the pain generation mechanisms

Mast can be developed. Cell Fig. 1. Some chemicals released by tissue damage that stimulates Central pain pathways nociceptors. In addition release of substance-P, along with histamine, produce vasodilation and swelling. Th e spinothalamic pathway and the trigeminal pathway are the major nerve routes for the transmission of pain In addition, local release of chemicals such and normal temperature information from the body and substance P causes vasodilation and swelling as well face to the brain. Visceral organs have only C-fi ber noci- as release of histamine from the mast cells, further in- ceptive nerves, and thus there is no refl ex action due to creasing vasodilation. Th is complex chemical signaling visceral organ pain. protects the injured area by producing behaviors that keep that area away from mechanical or other stimuli. Th e spinothalamic pathway Promotion of healing and protection against infection The nerve fibers from the dorsal root ganglia en- are aided by the increased blood fl ow and infl ammation ter the spinal cord through the dorsal root and send (the “protective function of pain”). branches 1–2 segments up and down the spinal cord Physiology of Pain 15 (dorsolateral tract of Lissauer) before entering the spi- ing painful sensations (“phantom pain”) and nonpainful nal gray matter, where they make contacts with (inner- sensations (e.g., “telescoping phenomena”). vate) the nerve cells in Rexed lamina I (marginal zone) Appreciating the complexity of the pain path- and lamina II (substantia gelatinosa). Th e Aδ fi bers in- way can contribute to understanding the diffi culty in as- nervate the cells in the marginal zone, and the C fi bers sessing the origin of pain in a patient and in providing innervate mainly the cells in the substantia gelatinosa pain relief, especially in chronic pain. layer of the spinal cord. Th ese nerve cells, in turn, innervate the cells in the nucleus proprius, another area Pathophysiology of pain of the spinal cord gray matter (Rexed layers IV, V, and VI), which send nerve fi bers across the spinal midline Pain sensations could arise due to: and ascend (in the anterolateral or ventrolateral part of 1) Infl ammation of the nerves, e.g., temporal neuritis. the spinal white matter) through the medulla and pons 2) Injury to the nerves and nerve endings with scar and innervate nerve cells located in specifi c areas of formation, e.g., surgical damage or disk prolapse. the thalamus. Th is makes up the spinothalamic path- 3) Nerve invasion by cancer, e.g., brachial plexopathy. way for the transmission of information on pain and 4) Injury to the structures in the spinal cord, thala- normal thermal stimuli (<45°C). Dysfunctions in the mus, or cortical areas that process pain information, thalamic pathways may themselves be a source of pain, which can lead to intractable pain; deaff erentation, e.g., as is observed in patients after stroke with central pain spinal trauma. (“thalamic pain”) in the area of paralysis. 5) Abnormal activity in the nerve circuits that is perceived as pain, e.g., phantom pain with cortical re- Th e trigeminal pathway organization. Noxious stimuli from the face area are transmitted in the nerve fi bers originating from the nerve cells in the Modulation of the perception of pain trigeminal ganglion as well as cranial nuclei VII, IX, and X. Th e nerve fi bers enter the brainstem and descend to It is well known that there is a diff erence between the the medulla, where they innervate a subdivision of the objective reality of a painful stimulus and the subjec- trigeminal nuclear complex. From here the nerve fi bers tive response to it. During World War II, Beecher, an from these cells cross the neural midline and ascend to anesthesiologist, and his colleagues carried out the innervate the thalamic nerve cells on the contralateral fi rst systematic study of this eff ect. Th ey found that side. Spontaneous fi ring of the trigeminal nerve gan- soldiers suff ering from severe battle wounds often ex- glion may be the etiology of “trigeminal neuralgia” (al- perienced little or no pain. Th is dissociation between though most of the time, local trigeminal nerve dam- injury and pain has also been noted in other circum- age by mechanical lesion through a cerebellar artery is stances such as sporting events and is attributed to the found to be the cause, as seen by the positive results of eff ect of the context within which the injury occurs. Janetta’s trigeminal decompression surgery). Th e existence of dissociation implies that there is a Th e area of the thalamus that receives the pain mechanism in the body that modulates pain percep- information from the spinal cord and trigeminal nuclei tion. Th is endogenous mechanism of pain modulation is also the area that receives information about nor- is thought to provide the advantage of increased sur- mal sensory stimuli such as touch and pressure. From vival in all species (Überlebensvorteil). this area, nerve fi bers are sent to the surface layer of the Th ree important mechanisms have been de- brain (cortical areas that deal with sensory informa- scribed: segmental inhibition, the endogenous opioid tion). Th us, by having both the nociceptive and the nor- system, and the descending inhibitory nerve system. mal somatic sensory information converge on the same Moreover, cognitive and other coping strategies may cortical area, information on the location and the in- also play a major role in pain perception, as described in tensity of the pain can be processed to become a “local- other chapters in this guide. ized painful feeling.” Th is cortical representation of the body—as described in Penfi eld’s homunculus—may also Segmental inhibition be a source of pain. In certain situations, e.g., after limb In 1965, Melzack and Wall proposed the “gate theory amputations, cortical representation may change, caus- of pain control,” which has been modifi ed subsequently 16 Nilesh B. Patel but which in essence remains valid. Th e theory propos- system of internal pain modulation and the subjective es that the transmission of information across the point variability of pain. of contact (synapse) between the Aδ and C nerve fi bers (which bring noxious information from the periphery) Descending inhibitory nerve system and the cells in the dorsal horn of the spinal cord can Nerve activity in descending nerves from certain brain- be diminished or blocked. Hence, the perception of the stem areas (periaqueductal gray matter, rostral me- painfulness of the stimulus either is diminished or is not dulla) can control the ascent of nociceptive informa- felt at all. Th e development of transcutaneous electrical tion to the brain. Serotonin and norepinephrine are the nerve stimulation (TENS) was the clinical consequence main transmitters of this pathway, which can therefore of this phenomenon. be modulated pharmacologically. Selective serotonin Th e transmission of the nerve impulse across reuptake inhibitors (SSRIs) and tricyclic antidepressants the synapse can be described as follows: Th e activation (e.g., amitriptyline) may therefore have analgesic prop- of the large myelinated nerve fi bers (Aβ fi bers) is associ- erties (Fig. 3). ated with the low-threshold mechanoreceptors such as touch, which stimulate an inhibitory nerve in the spinal Cerebral Cortex cord that inhibits the synaptic transmission. Th is is a possible explanation of why rubbing an injured area reduces the pain sensation (Fig. 2). Thalamus

C fiber (nociceptive signals) Midbrain PAG Brain Stem Projection neuron (nociceptive signal) + Raphe nucleus Locus ceruleus Inhibitory Spinal Cord Spinothalamic tract interneuron − + SPINAL CORD Aα and Aβ (mechanoceptors) Aδ & C nociceptive fibers Fig. 2. Th e gate control theory of Pain (Melzack and Wall). + excitatory synapse; – inhibitory synapse Fig. 3. Ascending (solid lines) and descending pain pathways. Th e raphe nucleus and locus ceruleus provide serotoninergic (5-HT) and adrenergic modulation. PAG = periaqueductal gray matter, part of Endogenous opioid system the endogenous opioid system. Besides the gating of transmission of noxious stimuli, another system modulates pain perception. Since 4000 Referred pain BCE, it has been known that opium and its derivatives Visceral organs do not have any Aδ nerve innervation, such as morphine, codeine, and heroin are powerful but the C fi bers carrying the pain information from the analgesics, and they remain the mainstay of pain relief visceral organs converge on the same area of the spinal therapy today. In the 1960s and 1970s, receptors for the cord (substantia gelatinosa) where somatic nerve fi bers opium derivatives were found, especially in the nerve from the periphery converge, and the brain localizes the cells of the periaqueductal gray matter and the ventral pain sensation as if it were originating from that somatic medulla, as well as in the spinal cord. Th is fi nding im- peripheral area instead of the visceral organ. Th us, pain plied that chemicals must be produced by the nervous from internal organs is perceived at a location that is system that are the natural ligands of these receptors. not the source of the pain; such pain is referred pain. Th ree groups of endogenous compounds (enkephalins, endorphins, and dynorphin) have been discovered that Spinal autonomic refl ex bind to the opioid receptors and are referred to as the Often the pain information from the visceral organs endogenous opioid system. Th e presence of this system activates nerves that cause contraction of the skeletal and the descending pain modulation system (adrener- muscles and vasodilation of cutaneous blood vessels, gic and serotoninergic) provides an explanation for the producing reddening of that area of the body surface. Physiology of Pain 17 Conclusion References

Chemical or mechanical stimuli that activate the noci- [1] Westmoreland BE, Benarroch EE, Daude JR, Reagan TJ, Sandok BA. Medical neuroscience: an approach to anatomy, pathology, and physiol- ceptors result in nerve signals that are perceived as pain ogy by systems and levels. 3rd ed. Boston: Little, Brown and Co.; 1994. by the brain. Research and understanding of the basic p. 146–54. [2] Bear MF, Connors BW, Paradiso. Neuroscience: exploring the brain. mechanism of nociception and pain perceptions pro- 2nd ed. Lippincott Williams & Wilkins; 2001. p. 422–32. vides a rationale for therapeutic interventions and po- [3] Melzack R, Wall P. Th e challenge of pain. New York: Basic Books; 1983. tential new targets for drug development.

Guide to Pain Management in Low-Resource Settings

Chapter 4 Psychological Factors in Chronic Pain

Harald C. Traue, Lucia Jerg-Bretzke, Michael Pﬁ ngsten, and Vladimir Hrabal

Everyone is familiar with the sensation of pain. It usually pain. Concluding the reverse, that the lack of somatic aff ects the body, but it is also infl uenced by psychologi- causes indicates a psychological etiology, would be just cal factors, and it always aff ects the human conscious- as wrong. ness. Th is connection between the mind and body is Th e International Association for the Study of illustrated by the many widely known metaphors and Pain (IASP) has defi ned pain as “an unpleasant senso- symbols. Unsolved problems and confl icts have us rack- ry and emotional experience associated with actual or ing our brains over them, and the folk term for low back potential tissue damage, or described in terms of such pain in German (Hexenschuss—witch’s shot) entails the damage.” Th is defi nition is fairly lean, but it encom- medieval psychosomatic belief that a proud man can be passes the complexity of pain processing, contradicts shot in the back by a witch’s magical powers, producing oversimplifi ed pain defi nitions that pain is a purely no- the kind of agonizing pain that can cripple him. Many ciceptive event, and also draws attention to the various cultures believe in magical (often evil) powers that can psychological infl uences. cause pain. Th is belief in magical powers refl ects the ex- Pain is often accompanied by strong emotions. perience that the cause of pain cannot always be deter- It is perceived not only as a sensation described with mined. Sometimes, the somatic structures of the body words such as burning, pressing, stabbing, or cutting, are completely normal and it is not possible to fi nd a le- but also as an emotional experience (feeling) with words sion or physiological or neuronal dysfunction that is a such as agonizing, cruel, terrible, and excruciating. Th e potential source of pain. Th e belief in magical powers association between pain and the negative emotional is also rooted in the experience that psychological fac- connotation is evolutionary. Th e aversion of organ- tors are just as important for coping with pain as is ad- isms to pain helps them to quickly and eff ectively learn dressing the physical cause of the pain. Modern placebo to avoid dangerous situations and to develop behaviors research has confi rmed such psychological factors in that decrease the probability of pain and thus physical many diff erent ways. damage. Th e best learning takes place if we pay atten- It should be mentioned, however, that certain tion and if the learned content is associated with strong lay theories such as the modern legend of the “worn- feelings. With regard to acute pain—and particularly out disk” only describe the actual cause of these symp- when danger arises outside the body—this connection toms in very few cases. In more than 80% of all cases is extremely useful, because the learned avoidance be- of back pain, there is no clear organic diagnosis. Th e havior with regard to acute pain stimulation dramatical- diagnosis for these cases is usually “nonspecifi c” back ly reduces health risks. When it comes to chronic pain,

Table 1 Psychological interventions and therapy targets Need for Psychological Intervention Th erapeutic Targets Treatment Context Expertise* Patient training Educate, i.e., expand patient’s sub- General medicine + jective pain theory (integration of psychosocial aspects) Handling of medications Reduce medication, use correct General medicine ++ medication, and prevent misuse Relaxation training Learn how to use relaxation to Psychologist + physiotherapist + cope with pain and stress Resource optimization Analyze and strengthen own General medicine + resources for coping with pain Activity regulation Optimize activity levels (balance Physician + psychologist/psychiatrist ++ between rest and activity): reduce fear-motivated avoidance and increase activity level Pain and coping Optimize pain-coping capabilities Psychologist/psychiatrist ++ Involvement of caregivers Involve patient’s caregivers in General medicine + reaching therapy targets Improvement of self-observation Find a personal connection Psychologist/psychiatrist +++ between the pain and internal or external events, which can help establish ways to control the pain. Analyze conditions that increase pain and stress Stress management Learn systematic problem-solving Psychologist/psychiatrist +++ tools and how to cope with stress Learning how to enjoy activities Strengthen activities the patient General medicine/physiotherapist + enjoys and likes to do Communication Change inadequate pain commu- General medicine or psychologist + nication and interaction Developing perspectives for the Develop realistic perspectives for General medicine + future the future (professional, private) and initiate action plans Special Th erapies Cognitive restructuring Modify catastrophizing and Psychologist/psychiatrist +++ depressive cognitions Biofeedback Learn how to activate specifi c Psychologist ++++ motor and neuronal (vegetative and central nervous) functions and learn better self-regulation Functional restoration Restore private and professional Interdisciplinary: orthopedic physician + ++++ functionality; reduce subjec- physiologist tive impairment perception and movement-related anxiety * Low (+) to high (++++). Psychological Factors in Chronic Pain 23 these activities after the end of therapy. Often, however, Educating the pain patient therapists must not only encourage activities, but also plan phases of rest and relaxation to make sure patients Fear of pain and anxiety about having a “serious” dis- do not overly exert themselves. ease are important factors in the chronifi cation process. Cognitive-emotional modifi cation strategies, Uncertainty and the lack of explanations are signifi cant on the other hand, predominantly focus on changing factors contributing to the patient’s worries. Fearful as- thought processes (convictions, attitudes, expecta- sumptions regarding the presence of a serious illness tions, patterns, and “automatic” thoughts). Th ey focus have negative behavioral consequences and foster pas- on teaching coping strategies and mechanisms. Th ese sive pain behavior. To reduce this uncertainty, patients are various techniques that teach patients a new, more should be provided with information and knowledge appropriate set of cognitive (and behavioral) skills to using written or graphic materials as well as videos. It help them cope with pain and limitations. Patients is especially important that the training should not are taught, for example, how to identify thoughts that criticize the patient’s often very simplistic somatic pain trigger and sustain pain, how to perceive situational concept, but rather expand on the patient’s subjective characteristics, and how to develop alternative cop- theories about the disorder, thus opening up new ways ing strategies. If patients are taught appropriate coping of how the patient can be actively involved. Based on techniques, they are better able to control a situation; easy-to-understand information on pain physiology and new confi dence in their abilities leads to a decrease psychology, psychosomatic medicine, and stress man- in feelings of helplessness, and patients become more agement, patients should be able to understand that proactive. One of the goals of therapy is for patients to pain is not only a purely somatic phenomenon, but is learn to monitor the function of expressing symptoms also infl uenced by psychological aspects (perception, at- (something patients are usually not aware of) to be tention, thoughts, and feelings). Informational materials able to better manage and manipulate their social en- are an important addition to therapist-linked activity, vironment. Th e therapy should teach appropriate so- and patient education is an important therapeutic ele- cial skills, for example, about how to assert one’s own ment that can form the basis for other interventions. interests to prevent the pain behavior from taking on Successful, informative training provides patients with this (so-called “instrumental”) function. the foundation they need to jointly develop and select Functional problem analysis is another im- therapy goals. portant tool of behavior therapy. During the course of this analysis, patients and their therapists system- Relaxation techniques atically collect information on how internal or external events are connected to the pain experience and pain Relaxation techniques are the most commonly used behavior. At the same time, detailed information is col- techniques in psychological pain therapy and consti- lected on the eff ects of the behavior and the functions tute a cornerstone of cognitive-behavioral therapy. the behavior might have (e.g., in the professional en- Th ey are eff ective because they teach patients to inten- vironment or in personal relationships). By analyzing tionally produce a relaxation response, which is a psy- these situations, it is possible to develop an overview chophysiological process that reduces stress and pain. of how the pain experience is incorporated into situ- Well-done relaxation exercises can counteract short- ational, cognitive-emotional, and behavioral aspects term physiological responses (at the neuronal level) and how it is maintained. Th is analysis can then be and prevent a positive feedback loop between pain and used to make further assumptions about the patient’s stress reactions, for example, by intentionally creat- pain triggers and maintenance conditions, followed by ing a positive aff ective state. As patients progressively goals and initiatives that could break the pain cycle. learn these techniques, they are better able to recog- Particularly important for the analysis of these condi- nize internal tension, which also makes them more tions is the patient’s self-observation with the help of aware of their personal stress situations and triggers pain diaries. Th e analysis can also be the basis for the (at the cognitive level). Some techniques (e.g., progres- patient’s own education, especially if the patient’s de- sive muscle relaxation) often lead to better body per- scription specifi es overall assumptions regarding the ception in terms of tight muscles, which can help iden- pain, its prognosis, and its treatment. tify stressful situations. 24 Harald C. Traue et al. Th e most commonly known relaxation tech- on the basis of physiological abnormalities—on the basis niques are progressive muscle relaxation as per Jacob- of muscle activity on the surface EMG or physical diag- son (PMR), autogenic training (AT), and other imagi- nostic parameters such as active myogeloses (localized nation, breathing, and meditation techniques. All these muscle tension that is painful to the touch). One specifi c techniques must be practiced for quite some time be- application is a portable biofeedback device that can be fore they can be mastered. Sustainable success can only used under normal day-to-day conditions. be achieved through prolonged eff ort. Relaxation techniques are less successful in acute pain situations, which Multimodal processes is why they are more usually used to treat chronic pain. Multimodal pain psychotherapy is based on two as- Biofeedback sumptions: 1) Chronic pain does not have individually identifi - Biofeedback therapy involves physiological learning by able causes, but is the result of various causes and infl u- measuring physiological pain components such as mus- ential factors. cle activity, vascular responses, or arousal of the auto- 2) A combination of various therapeutic interven- nomic nervous system and providing visual or acoustic tions has proven successful in the treatment of chronic feedback to the patient. Biofeedback therapy is helpful pain (usually independent of the specifi c pain disorder). for migraines, tension headaches, and back pain. Several In a modern pain therapy, therapeutic pro- diff erent methods are used for migraines, such as hand- cesses are usually not isolated, but are used within the warming techniques and vascular constriction training context of an umbrella concept. Th e process is centered (targeting the temporalis artery). on a reduction of the (subjectively perceived) handicap In the hand-warming or thermal biofeedback by changing the patient’s general situational conditions technique, the patient receives information on the and cognitive processes. Th ese kinds of programs can blood supply to one fi nger, usually by measuring the be applied according to the shotgun principle, e.g., all skin temperature with a temperature sensor. Th e pa- modules are used with the view that we will defi nitely tient is asked to increase the blood supply to the hand hit upon the most important areas, or the therapist can (and thereby reduce vasodilatation in the arteries of use the diagnosis to put together a specifi c modular the head). In autogenic feedback training, the hand treatment plan. Th e latter method should be used if an warming is supported by the development of formu- individual diagnosis is possible. In a group setting, the la-type intentions from autogenic training (heat exer- standardized process works better due to the expected cises). Th e processes are demonstrated and used only diff erences between the patients. during pain-free periods. First, the patient practices with feedback and heat imagery. Th en, the conditions Functional restoration programs of the exercise are made harder, and the patient, supported by the temperature feedback, is asked to re- Th ese programs are characterized by their clear focus main relaxed while imagining a stressful situation. And on sports medicine and underlying behavioral therapy fi nally, the patient is asked to increase the temperature principles. Pain reduction as a treatment goal plays a of the hand without any direct feedback, and is told minor role. Due to learning theory considerations per- subsequently if he or she was successful. taining to the “enhancement character” of pain behavior, In electromyography (EMG) biofeedback for the pain itself is basically pushed out of the therapeu- tension headaches or back pain, the feedback usual- tic focus. Th ese programs try to help patients function ly consists of the level of tension in the forehead, neck again in their private and professional lives (functional muscles or lumbar muscles and is used to teach patients restoration). Th e primary goal of therapy is to reduce how to reduce tension. Patients with pain in the loco- the subjective adverse eff ect and the consequent fear motor apparatus might also, however, practice certain and anxiety. movement patterns. Th ese patterns are then practiced Th e treatment integrates sport, work therapy, not only in a reclined position or while resting, but also physical exercises, and psychotherapeutic interven- in other body positions and during dynamic physical actions into one standardized overall concept. Th e physi- tivity. It is important that the muscle groups are selected cal therapy components usually include an increase in Psychological Factors in Chronic Pain 25 overall fi tness level, improvement in cardiovascular and professional requirements [behavior prevention]) and pulmonary capacity, coordination and body percep- a change in the variables of the professional environ- tion, and an improved capacity to handle stress. Th e mental (e.g., transfer within the workplace or retraining psychotherapeutic interventions try to change adverse [conditional prevention]). emotional eff ects (antidepressive therapy). Th e patient’s behavior is based on rest and relaxation, along with Eff ectiveness of psychologically changing cognitively represented attitudes or anxieties based therapies with regard to activity and the ability to work. Th e focus of this psychological (cognitive-be- Th e eff ectiveness of psychological pain therapy for havioral) therapy is similar to that of the psychological chronic pain patients is suffi ciently documented. Several methods described above. Th e therapy is highly somati- meta-analytical studies have shown that about two out cally oriented, but the psychological eff ects of the train- of three chronic patients were able to return to work af- ing are just as important as the changes achieved in ter having undergone cognitive-behavioral pain therapy. terms of muscle strength, endurance, and coordination. Cognitive-behavioral therapy techniques, compared to Intense physical activity is included in order to: exclusively medication-based therapy, are eff ective in 1) Decrease movement-related anxiety and func- terms of a reduction of the pain experience, an improve- tional motor blockages. ment in the ability to cope with pain, a reduction of pain 2) Sever the learned connection between pain and behavior, and an increase in functionality; most eff ects activity. can be maintained over time. 3) Provide the necessary training to cope with stress. Behavioral therapy is not just one homog- 4) Provide fun and enjoyment, which is usually ex- enous therapy, but consists of several intervention perienced during the playful parts of therapy and can methods, each of which is geared toward a specifi c lead to new emotional experiences. modifi cation goal. However, this multidimensional ad- Insights gleaned from the theory of learning vantage is also a disadvantage, because it is often not show that pain must lose its discriminating function quite clear what kind of content is needed. Th e eff ect for patients to be able to manage their pain behavior. itself has been proven without a doubt, but it is much Th erefore, the entire physical training cannot be geared less clear why and in which combination the interven- toward the pain it causes, or be limited by it, but must tions are eff ective. instead be geared toward personalized preset goals. Goal plans strengthen the patient’s experience of man- Pearls of wisdom ageability and self-effi cacy. Failures at the beginning of therapy (e.g., if goals are not reached) could signifi cantly • Psychogenic processes play an important role in reduce the patient’s motivation, initial goals should be the complex processing of pain information. Th e very simple (weight, number of repetitions). Patients’ pain, therefore, aff ects not only the body, but the beliefs about their illness, particularly with regard to human being as a whole. It becomes more se- movement-related fears, must be given particular atten- vere if the patient does not know the causes or tion during therapy. Th ese fears must be specifi cally re- the signifi cance of the pain, which, in turn, leads corded and decreased in a gradual training process that to anxiety and increased pain levels. mimics the behavior as closely as possible. • In terms of chronic disorders, various factors in Physical training machinery can be used dur- their individual development have an additive ef- ing the training (the patient feels safe due to the guid- fect. Th erefore, an explanatory model can help ed, limited movements), but they constitute “artifi - determine the best therapeutic approach, which cial” conditions and thus hinder the necessary transfer equally includes biological (somatic), psycho- to daily life. Consequently, routine everyday activi- logical, and sociological components. Th is model ties should be incorporated into the training as early focuses not on details that are no longer identifi - as possible. Since there is a close connection between able, but on the interactive whole. back pain and the workplace, the therapy must be en- • Th e patient himself is only a fi xed, actively func- hanced by socio-therapeutic interventions (adjustment tioning component of the process, if he is willing of the individual’s capabilities to his or her profi le of to actively participate in the necessary behavioral 26 Harald C. Traue et al. changes and to generally take on more responsi- References bility for himself, his disease, and the course of [1] Chen ACN. New perspectives in EEG/MEG brain mapping and PET/ his disease. Th e results of many years of psycho- fMRI neuroimaging of human pain. Int J Psychophysiol 2001;42:147–59. logical pain research provide important insights [2] Enck P, Benedetti F, Schedlowski M. New insights into the placebo and nocebo responses. Neuron 2008;59:195–206. for this process. [3] Haldorsen EMH, Grasdal AL, Skouen JS, Risa AE, Kronholm K, Ur- sin H. Is there a right treatment for a particular patient group? Pain • Th is is not about replacing medical therapy with 2002;95:49–63. psychological therapy, but about using the in- [4] Le Breton D. Anthropologie de la douleur. Paris: Éditions Métaillié; 2000. sights of diff erent specialties in an integrated [5] Linton SJ, Nordin E. A 5-year follow-up evaluation of the health and manner to treat this diffi cult group of patients in economic consequences of an early cognitive behavioral intervention for back pain: a randomized, controlled trial. Spine 2006;31:853–858. the best possible way. [6] McCracken LM, Turk DC. Behavioral and cognitive-behavioral treatment for chronic pain. Spine 2002;15:2564–73. • On the other hand, chronic patients are im- [7] Nilges P, Traue HC. Psychologische Aspekte des Schmerzes, Verhalten- pressed by reports on medical interventions such stherapie Verhaltensmedizin 2007;28:302–22. [8] Schmutz U, Saile H, Nilges P. Coping with chronic pain: fl exible goal as surgeries, injections, or medications, which adjustment as an interactive buff er against pain-related distress. Pain raise high expectations for a quick removal of the 1996;67:41–51. [9] Sharp TJ, Harvey AG. Chronic pain and posttraumatic stress disorder: pain without their own active involvement as a mutual maintenance? Clin Psychol Rev 2001;21:857–77. patients. Repeatedly, high hopes of curing pain are raised by the medical system, and usually Websites

dashed in careful long-term studies. IASP: www.iasp-pain.org • Neither opiates nor the development of specific medications or surgery for certain types of pain have led to the expected solutions to end chronic pain. Guide to Pain Management in Low-Resource Settings

Chapter 5 Ethnocultural and Sex Inﬂ uences in Pain

Angela Mailis-Gagnon

Case reports health care providers. Maryann Bates [1], a professor at the School of Education and Human Development at A 40-year-old male patient comes to see you. He is Chi- the State University of New York, studied pain patients nese and has been in a Western country for 2 years. His of diff erent ethnic backgrounds. Bates proposed that English is barely functional. While you try to obtain in- culture refl ects the patterned ways that humans learn formation for the neck pain that brought him to you, he to think about and act in their world. Culture involves keeps looking to the ground and avoids eye contact. Is he styles of thought and behavior that are learned and depressed or does he simply disrespect you? shared within the social structure of our personal world. A 25-year-old woman with a hijab and tradi- In this context, culture is diff erent than ethnicity. Th e tional Moslem attire is brought in by her husband in re- latter refers specifi cally to the sense of belonging in a par- gard to diff use body pain complaints. She looks uncom- ticular social group within a larger cultural environment. fortable when she realizes that the clinic doctor who will Th e members of an ethnic group may share common see her is a male. Given the fact that this doctor is the traits such as religion, language, ancestry, and others. only one available at that time, how is he going to handle the problem? Why is it important to understand A 75-year-old farmer with elementary school education sees you for severe knee arthritis. He cannot ethnicity and culture when it comes tolerate nonsteroidal anti-infl ammatory medications to pain diagnosis and management? and refuses knee surgery. His pain responds very well to Culture and ethnicity aff ect both perception and ex- small doses of controlled-release morphine. However, he pression of pain and have been the focus of research becomes very nauseated and throws up every time. He since the 1950s. Research with adult twins supports becomes visibly upset when you off er him Gravol sup- the view that it is the cultural patterns of behavior and positories after you explain to him how to use them. Why not our genes that determine how we react to pain. do you think he became angry, and how are you going to Examples of how culture and ethnicity aff ect pain per- address this problem? ception and expression are numerous, both in the lab- Th ese are common clinical problems seen by oratory and in clinical settings. primary care physicians as well as pain clinics and are In the laboratory, an earlier classic study showed examples of how cultural and ethnic background af- that persons of Mediterranean origin described a form fects pain perception, expression, and interactions with of radiant heat as “painful,” while Northern European

Guide to Pain Management in Low-Resource Settings

Chapter 6 Pharmacology of Analgesics (Excluding Opioids)

Kay Brune

Th e classes of analgesic drugs mentioned below are How does diclofenac, a member of the class available worldwide and are constantly replaced by of COX inhibitors, work? new compounds that are often too costly to be sold in COX inhibitors inhibit peripheral and central hyperal- all countries. However, pain therapy need not suff er gesia. Like all commonly used analgesic compounds, in- from this limitation because the essential drugs includ- cluding morphine (an opioid), pregabalin (an antiepilep- ing cyclooxygenase inhibitors, antiepileptic drugs, opi- tic), ziconotide (an N-type calcium channel blocker), and ates and opioids, and ketamine are available in almost ketamine (a blocker of the NMDA-receptor-attached all countries, and the value of the novel compounds re- sodium channel), COX inhibitors exert a major eff ect mains unclear. in the dorsal horn of the spinal cord (and therefore it is incorrect to call them “peripheral analgesics”). Com- Case report 1: Choosing pared to the above drug classes, COX inhibitors have a the right analgesic distinctly diff erent mode of action. A peripheral trauma will initiate peripheral hyperalgesia, which results from a Recently, a good friend of mine drove home on his bi- prostaglandin-induced increase in nociceptor sensitivity. cycle. He was hit by a car and fell to the ground. Th ere- Also, central hyperalgesia is initiated from the blockade after, he suff ered from chest pain and asked his doctor of the activity of interneurons due to the production of for help. He received 10 mg morphine s.c. He called me prostaglandin E2 (PGE2). Following a peripheral trauma, in the middle of the night and told me that the pain was the enzyme COX-2 is expressed in the dorsal horn cells still devastating, but in addition he felt awful, was nause- by means of hormonal cytokines and neuronal messages. ated and had vomited. I suggested taking 75 mg diclof- PGE2 activates protein kinase A (pKA). Th e activation enac resinate. He called the next morning telling me that results in phosphorylation of the glycine-receptor-asso- he had fallen asleep shortly after having taken diclofenac. ciated chloride channel. Th is, in turn, reduces the prob- Th is example demonstrates that so-called ability of chloride channel opening. Th e blockade of the “strong analgesics,” such as morphine and other opioids, chloride channel reduces the hyperpolarization of the are not always eff ective. In acute musculoskeletal or second neuron and therefore makes it more excitable to traumatic pain, cyclooxygenase (COX) inhibitors may glutamate-transmitted stimuli. In other words, trauma, be preferable. A drug like diclofenac (an aspirin-like infl ammation, and tissue damage activate the production drug) often does a better job. A detailed commentary of COX-2 enzyme in the dorsal horn cells of the spinal on this case report follows later. cord, which reduces the hyperpolarization of the second

Table 1 Physicochemical and pharmacological data of acidic, nonselective COX inhibitors Binding Pharmacokinetic/Chemical to Plasma Oral Single Dose (Max. Daily

Subclass PKA Protein Bioavailability tmax t50 Dose) for Adults Short Elimination Half-Life Aspirin* (acetylsalicylic acid) 3.5 (3.0) 50–70% 50%, dose depen- 15 min 15 min 0.05–1 g (6 g) (not in use) (~80%) dent (1–5 h, dose (15–60 dependent) min) Ibuprofen 4.4 99% 100% 0.5–2 h 2 h 200–800 mg (2.4 g) Flurbiprofen 4.2 >99% ~ 90% 1.5–3 h 2.5–4 (8) h 50–100 mg (200 mg) Ketoprofen 5.3 99% 90% 1–2 h 2–4 h 25–100 mg (200 mg) Diclofenac 3.9 99.7% 50%, dose depen- 1–12 h, 1–2 h 25–75 mg (150 mg) dent very variable Long Elimination Half-Life Naproxen 4.2 99% 90–100% 2–4 h 12–15 h 250–500 mg (1.25 g) 6–Methoxy-2–naphthyl- 4.2 99% 20–50% 3–6 h 20–24 h 0.5–1 g (1.5 g) acetic acid (active metabolite of nabumetone) Piroxicam 5.9 99% 100% 3–5 h 14–160 20–40 mg; initial dose: h 40 mg Meloxicam 4.08 99.5% 89% 7–8 h 20 h 7.5–15 mg * Aspirin releases salicylic acid (SA) before, during, and after absorption. Values in brackets refer to the active (weak) COX-1/COX-2 inhibitor SA.

combining COX-2 inhibition with opiates (opioids), a How does gabapentin work against pain? maximum of eff ect was achieved. Naproxen was chosen Neuropathic pain results from damage to aff erent neu- because it is eliminated slowly and—in the right dose— rons and changes in pain transmission in the dorsal is suffi cient for a full night of pain relief. horn of the spinal cord and above. It comprises a growing therapeutic problem. In post-traumatic, posther- Case report 3: Choosing analgesics petic (chronic) pain, antiepileptics can be a drugs can or other than opioids or COX inhibitors morphine. Th e dose of both typesthus be kept relatively low. Th e addition of COX inhibitors does not further in- A woman, aged 78, fell down the stairs of her house crease the eff ectiveness of these drugs. Still, since most and suff ered a complete compression of the spinal cord neuronal cells in our body comprise voltage-gated so- between C4 and C5. She became tetraplegic instantly. dium channels, the therapeutic use of blockers of these Emergency neurosurgery was impossible in her vicinity. channels goes along with many central nervous system Furthermore, she had taken an aspirin-containing an- (CNS) side eff ects such as dizziness, sleepiness, lack of algesic mixture the day before. Th is meant inhibition of attention, and lack of alertness. Th ese compounds must blood coagulation for up to 5 days and consequently se- therefore be dosed cautiously in order to produce thera- rious risks for neurosurgery. She remained tetraplegic for peutic eff ects without unacceptable CNS depression. 2 years and then developed untreatable burning pain in the legs. Her standard medication of dipyrone was not Are there options to block calcium channels eff ective. Low doses of morphine were dissatisfying, but more eff ectively? adding gabapentin to low-dose morphine reduced the Neuronal cells have specifi c calcium channels (N-type pain considerably. However, it caused the woman to be calcium channels) that play a role in the communication sleepy and dizzy all the time to an extent that did not between cells. Th e release of glutamate in nociception permit to her to watch TV as she liked to do. from the fi rst neuron for the activation of the second 36 Kay Brune neuron is also regulated by N-type calcium channels. Nevertheless, low-dose ketamine (<0.2 mg/kg/h S- Th e blockade of these channels blocks the infl ow of ketamine or <0.4 mg/kg/h ketamine) maybe helpful as calcium into glutamate cells, thus reducing glutamate a “rescue medication” in uncontrolled pain, e.g., due to release and activation of NMDA receptors. However, nerve plexus infi ltration in cancer. Unfortunately, as oral as these N-type channels are present in most neuronal bioavailability is unpredictable, only the intravenous cells, a general blockade would be incompatible with route can be used. life. But recently ziconotide, a toxin from a sea snail, has been found to block these channels when administered Pearls of wisdom directly into the spinal column, with tolerable side effects. Unfortunately, intrathecal administration of drugs • Th e drugs discussed in this chapter allow for suc- is quite a sophisticated and expensive option for pain cessful treatment of most pain conditions, but control, and presently it is done only at a few highly spe- not all. cialized pain centers for exceptional cases. • It should be kept in mind that the most important prototypes of the nonopioid analgesics are What other—more practical—options are the COX inhibitors, which comprise the most available, when antiepileptic drugs fail to help? widely used drugs worldwide because they are Another option for treating pain in the clinical setting also given against fever, infl ammation, and many is the use of ketamine, which blocks use-dependent so- states of discomfort, including migraine. Due to dium channels of the glutamate NMDA receptor. Such their mode of action, their eff ect plateaus. In oth- receptors are not limited to the pain pathway, but are er words, the normalization of hyperalgesia ends ubiquitously involved in neuronal communication. when prostaglandin E2 production is completely Consequently, the blockade of this sodium channel can- suppressed. Increasing the dose will not increase not be limited to pain pathways, but a certain degree of the eff ect any further. selectivity is achieved by the use dependence. In other • Constant inhibition of COXs in the vascular wall words, painful stimuli lead to a higher probability of (selectively or nonselectively) leads to a constant opening of this channel, which can be accessed only in blockade of the production of the vasoprotective the open position by ketamine, which can then block it. factor prostacyclin (PGI2). Th is appears to be the Still, the relatively low specifi city of ketamine’s action main reason for the increased incidence of car- causes many unwanted drug eff ects, ranging from “bad diovascular events (heart attack, stroke, athero- trips” (dysphoria) to lack of coherent thinking and at- sclerosis), seen with the use of COX inhibitors, tention. Consequently, the use of ketamine is restricted including acetaminophen (paracetamol). to the clinical setting, in particular analgesic sedation.

Table 2 Physicochemical and pharmacological data of nonselective COX-2 inhibitors COX-1/ Binding Primary Metabolism Single Dose (Max. Pharmacokinetic/ COX-2 to Plasma Oral Bio- (Cytochrome Daily Dose) for

Chemical Subclass Ratio Protein VD availability tmax t50 P-450 Enzymes) Adults Acetaminophen ~ 20% ~70 L ~ 90% 1 h 1–3 h Oxidation (direct sul- 1 g (4 g) (paracetamol) fation) Celecoxib 30 91% 400 L 20–60% 2–4 h 6–12 h Oxidation (CYP2C9, 100–200 mg (400 CYP3A4) mg) for osteoarthrosis and rheumatoid arthritis Etoricoxib 344 92% 120 L 100% 1 h 20–26 h Oxidation to 6’-hydroxy- 60 mg (60 mg) for methyl-etoricoxib (major osteoarthrosis, 90 role: CYP3A4; ancillary mg (90 mg) for role: CYP2C9, CYP2D6, rheumatoid arthri- CYP1A2) tis, 120 mg (120 mg for acute gouty arthritis Pharmacology of Analgesics (Excluding Opioids) 37

• Still, comparing the unwanted drug side effects in serious pain, but not as a means to decrease of all analgesic compounds, including opiates, daily discomfort; only then is their use mean- one would come to the conclusion that they ingful and justifiable. all have their problems. They should be used

Table 3 Major side eff ects, drug interactions, and contradictions of COX inhibitors Adverse Drug Drug Reactions* Drug Interactions Contradictions (Absolute and Relative) Nonselective, Acidic Drugs Aspirin Inhibition of platelet Vitamin K antagonists Hypersensitivity to the active substance or to any of the aggregation for days, excipients, impaired blood coagulation, pregnancy and all aspirin-induced asthma, contradictions listed below ulcerations, bleeds Diclofenac GI ulcerations, dys- ACE inhibitors, glucocor- Asthma, acute rhinitis, nasal polyps, angioedema, urti- Ibuprofen pepsia, increased BP, ticoids, diuretics, lithium, caria or other allergic-type reactions after taking ASA or Indomethacin water retention, allergic SSRIs, ibuprofen: reduction NSAIDs; active peptic ulceration or GI bleeds; infl am- Ketoprofen (asthmatic) reactions, of low-dose aspirin cardio- matory bowel disease; established ischemic heart disease, Ketorolac vertigo, tinnitus protection peripheral arterial disease and/or cerebrovascular disease; Naproxen renal failure Meloxicam Selective (Preferential) COX-2 Inhibitors Acetaminophen Liver damage Not prominent Liver damage, alcohol abuse (paracetamol) Celecoxib Allergic reactions (sul- Blocks CYP2D6; interac- Existing pronounced atherosclerosis, renal failure fonamide) tions with SSRIs and beta- blockers Etoricoxib Water retention, in- Reduces estrogen metabo- As with celecoxib, plus insuffi cient control of blood pres- creased blood pressure lism sure; cardiac insuffi ciency * More pronounced in highly potent and/or slowly eliminated drugs (all except ibuprofen)

Table 4 Pharmacokinetic data on non-COX, nonopioid analgesics

Type (Drug) t50 Common Dosing Adverse Reactions Antiepileptics Carbamazepine ~2 days ~0.5 g b.i.d.1 Diplopia, ataxia (aplastic anemia)

Gabapentin ~6 hours ~1 g b.i.d. Somnolence, dizziness, ataxia, headache, tremor Pregabalin ~5 hours ~200 mg t.i.d. Blockers of NMDA-receptor Na+-channels Ketamine (race- Fast,2 ~50 mg/d 0.5 mg/kg/h Hypersalivation, hypertension, tachycardia, bad dreams mic) S+-Ketamine As racemic, comp. S+- ketamine, twice as active N-Type Ca-Channel Blockers3 Ziconotide Permanent intrathecal CNS disturbances from nausea to coma depending on the dose administration and distribution of the toxin, granuloma-formation 1 No hard evidence for analgesic eﬀ ects aside of trigeminal neuralgia; no dose recommendations for neuropathic pain available. 2 Ketamine is highly lipophilic and sequesters into fat tissue (t50, distribution ~ 20 min); continuous infusion requires attention (to avoid overdosing). 3 Only in desperate patients if intrathecal administration is possible. 38 Kay Brune

[5] Hinz B, Renner B, Brune K. Drug insight: cyclo-oxygenase-2 inhibi- References tors—a critical appraisal. Nat Clin Pract Rheumatol 2007;3:552–60. [6] Zeilhofer HU, Brune K. Analgesic strategies beyond the inhibition of [1] Brune K, Hinz B, Otterness I. Aspirin and acetaminophen: should they cyclooxygenases. Trends Pharmacol Sci 2006;27:467–74. be available over the counter? Curr Rheumatol Rep 2009;11:36–40. [7] Croff ord LJ, Breyer MD, Strand CV, Rushitzka F, Brune K, Farkouh ME, [2] Hinz B, Brune K. Can drug removals involving cyclooxygenase-2 inhibi- and Simon LS. Cardiovascular eff ects of selective COX-2 inhibition: is tors be avoided? A plea for human pharmacology. Trends Pharmacol there a class eff ect? Th e International COX-2 Study Group. J Rheumatol Sci 2008;8:391–7. 2006;33:1403–8. [3] Brune K, Katus HA, Moecks J, Spanuth E, Jaff e AS, Giannitsis E. N- [8] Brune K, Hinz B. Th e discovery and development of antiinfl ammatory terminal pro-B-type natriuretic Peptide concentrations predict the risk drugs. Arthritis Rheumatol 2004;50:2391–9. of cardiovascular adverse events from antiinfl ammatory drugs: a pilot [9] Brune K, Hinz B. Selective cyclooxygenase-2 inhibitors: similarities and trial. Clin Chem 2008;54:1149–57. diff erences. Scandinavian Journal of Rheumatol 2004;33:1–6. [4] Knabl J, Witschi R, Hösl K, Reinold H, Zeilhofer UB, Ahmadi S, Brock- haus J, Sergejeva M, Hess A, Brune K, Fritschy JM, Rudolph U, Möhler H, Zeilhofer HU. Reversal of pathological pain through specifi c spinal

GABAA receptor subtypes. Nature 2008;451:330–4. Guide to Pain Management in Low-Resource Settings

Chapter 7 Opioids in Pain Medicine

Michael Schäfer

Classifi cation of opioids introduction of the glass syringe by the French orthopedic surgeon Charles Pravaz (1844), much easier han- Treatment of pain very quickly reaches its limits. Any- dling of this unique opioid substance became possible one who has suff ered from a severe injury, a renal or gall with fewer side eff ects. bladder colic, a childbirth, a surgical intervention, or an Today we distinguish naturally occurring opi- infi ltrating cancer has had this terrible experience and oids such as morphine, codeine, and noscapine from may have experienced the soothing feeling of gradual semisynthetic opioids such as hydromorphone, oxy- pain relief, once an opioid has been administered. In codone, diacetylmorphine (heroin) and from fully syn- contrast to many other pain killers, opioids are still the thetic opioids such as nalbuphine, methadone, pentazo- most potent analgesic drugs that are able to control se- cine, fentanyl, alfentanil, sufentanil, and remifentanil. vere pain states. Th is quality of opioids was known dur- All these substances are classifi ed as opioids, including ing early history, and opium, the dried milky juice of the the endogenous opioid peptides such as endorphin, en- poppy fl ower, Papaver somniferum, was harvested not kephalin, and dynorphin which are short peptides se- only for its euphoric eff ect but also for its very powerful creted from the central nervous system under moments analgesic eff ect. Originally grown in diff erent countries of severe pain or stress, or both. of Arabia, the plant was introduced by traders to other places such as India, China, and Europe at the begin- Opioid receptors and ning of the 14th century. mechanism of action At that time, the use of opium for the treatment of pain had several limitations: it was an assortment Opioids exert their eff ects through binding to opi- of at least 20 diff erent opium alkaloids (i.e., substances oid receptors which are complex proteins embedded isolated from the plant), with very divergent modes of within the cell membrane of neurons. Th ese recep- action. Overdosing occurred quite often, with many tors for opioids were fi rst discovered within specif- unwanted side eff ects including respiratory depres- ic, pain related brain areas such as the thalamus, the sion, and, because of irregular use, the euphoric eff ects midbrain region, the spinal cord and the primary sen- quickly resulted in addiction. sory neurons. Accordingly, opioids produce potent With the isolation of a single alkaloid, mor- analgesia when given systemically (e.g., via oral, intra- phine, from poppy fl ower juice by the German phar- venous, subcutaneous, transcutaneous, or intramus- macist Friedrich Wilhelm Sertürner (1806) and the cular routes), spinally (e.g., via intrathecal or epidural

Table 1 List of diff erent opioids that activate opioid receptors within the central nervous system Opioid Alkaloids Semisynthetic Opioids Synthetic Opioids Opioid Peptides Morphine Hydromorphone Nalbuphine Endorphin Codeine Oxycodone Levorphanol Enkephalin Th ebaine Diacetylmorphine (heroin) Butorphanol Dynorphin Noscapine Etorphine Pentazocine Papaverine Naloxone (antagonist) Methadone Naltrexone (antagonist) Tramadol Meperidine Fentanyl Alfentanil Sufentanil Remifentanil routes), and peripherally (e.g., via intra-articular or unpleasantness. Also, respiratory depression may be a topical routes). problem at the beginning, particularly when large doses Today, three diff erent opioid receptors, the are given without adequate assessment of pain intensity. μ-, δ-, and κ-opioid receptor, are known. However, the Dose titration and regular assessments of pain intensity most relevant is the μ-opioid receptor, since almost all and breathing rate are recommended. During prolonged clinically used opioids elicit their eff ects mainly through and regular opioid application, respiratory depression is its activation. Th e three-dimensional structure of opioid usually not a problem. Cognitive impairment is an im- receptors within the cell membrane forms a pocket at portant issue at the beginning, particularly while driving which opioids bind and subsequently activate intracellu- a car or operating dangerous machinery such as power lar signaling events that lead to a reduction in the excit- saws. However, patients on regular opioid treatment ability of neurons and, thus, pain inhibition. According usually do not have these problems, but all patients have to their ability to initiate such events, opioids are dis- to be informed about the occurrence and possible treat- tinguished as full opioid agonists (e.g., fentanyl, sufen- ment of these side eff ects to prevent arbitrary discon- tanil) that are highly potent and require little receptor tinuation of medication. Constipation is a typical opioid occupancy for maximal response, partial opioid agonists side eff ect that does not subside, but persists over the (e.g., buprenorphine) that require greater receptor oc- entire course of treatment. It can lead to serious clinical cupancy even for a low response, and antagonists (e.g., problems such as ileus, and should be regularly treated naloxone, naltrexone) that do not elicit any response. with laxatives or oral opioid antagonists (see below). Mixed agonists/antagonists (e.g., pentazocine, nalbuphine, butorphanol) combine two actions: they bind to Sedation the κ-receptor as agonists and to the μ-receptor as an- Opioid-induced reduction of central nervous system tagonists. activity ranges from light sedation to a deep coma depending on the opioid used, the dose, route of applica- Opioid-related side eff ects tion, and duration of medication. In clinically relevant doses, opioids do not have a pure narcotic eff ect, but Th e fi rst time opioids are taken, patients frequently they also lead to a considerable reduction in the maxi- report acute side eff ects such as sedation, dizziness, mal alveolar concentration (MAC) of volatile anesthet- nausea, and vomiting. However, after a few days these ics used to induce unconsciousness during surgical pro- symptoms subside and do not further interfere with the cedures. regular use of opioids. Patients should be slowly titrated to the most eff ective opioid dose to reduce the severity Muscle rigidity of the side eff ects. In addition, symptomatic treatments Depending on the speed of application and dose, opi- such as antiemetics help to overcome the immediate oids can cause muscle rigidity particularly in the trunk, Opioids in Pain Medicine 41 abdomen, and larynx. Th is problem is rstfi recognized to 3 × 40 mg/day orally), which is mandatory during by the impairment of adequate ventilation followed by chronic opioid use. hypoxia and hypercarbia. Th e mechanism is not well understood. Life-threatening diffi culty in assisted venti- Pruritus lation can be treated with muscle relaxants (e.g., succi- Opioid-induced pruritus (itch) commonly occurs fol- nylcholine 50–100 mg i.v., i.m.). lowing systemic administration and even more commonly following intrathecal/epidural opioid adminis- Respiratory depression tration. Although pruritus may be due to a generalized Respiratory depression is a common phenomenon histamine release following the application of morphine, of all μ-opioid agonists in clinical use. Th ese drugs it is also evoked by fentanyl, a poor histamine liberator. reduce the breathing rate, delay exhalation, and pro- Th e main mechanism is thought to be centrally medi- mote an irregular breathing rhythm. Opioids reduce ated in that inhibition of pain may unmask underlying the responsiveness to increasing CO2 by elevating activity of pruritoreceptive neurons. Opioid-induced the end-tidal pCO2 threshold and attenuating the hy- pruritus can be successfully attenuated by naltrexone (6 poxic ventilation response. Th e fundamental drive mg orally) or with less impact on the analgesic eff ect by for respiration is located in respiratory centers of the mixed agonists such as nalbuphine (e.g., 4 mg i.v.). brainstem that consist of diff erent groups of neuronal networks with a high density of μ-opioid receptors. Life-threatening respiratory arrest can be reversed by Routes of opioid administration titration with the i.v. opioid antagonist naloxone (e.g., Oral 0.4–0.8–1.2 mg). Th e majority of opioids are easily absorbed from the Antitussive eff ects gastrointestinal tract with an oral bioavailability of 35% In addition to respiratory depression, opioids suppress (e.g., morphine) to 80% (e.g., oxycodone) entering the the coughing refl ex, which is therapeutically produced circulation. However, they undergo to a high degree by antitussive drugs like codeine, noscapine, and dex- (40–80%) immediate fi rst-pass metabolism in the liver, tromethorphan (e.g., codeine 5–10–30 mg orally). Th e where glucuronic acid binding makes the drug inactive main antitussive eff ect of opioids is regulated by opioid and ready for renal excretion. Exceptions are metabo- receptors within the medulla. lites of morphine, e.g., morphine-6-glucuronide, which is itself analgesic, or morphine-3-glucuronide, which Gastrointestinal eff ects is neurotoxic and can accumulate during renal impair- Opioid side eff ects on the gastrointestinal system are ment as well as cause serious side eff ects such as re- well known. In general, opioids evoke nausea and spiratory depression or neurotoxicity. Oral opioids are vomiting, reduce gastrointestinal motility, increase commonly available in two galenic preparations, an circular contractions, decrease gastrointestinal mu- immediate-release formula (onset: within 30 min, du- cus secretion, and increase fl uid absorption, which ration: 4–6 hours) and an extended-release formula eventually results in constipation. In addition, they (onset: 30–60 min, duration: 8–12 hours). Th ere is pre- cause smooth muscle spasms of the gallbladder, bili- liminary evidence for ethnic diff erences, e.g., between ary tract, and urinary bladder, resulting in increased Caucasians and Africans, with regard to the hepatic me- pressure and bile retention or urinary retention. Th ese tabolism of opioids, i.e., opioids exert a longer duration gastrointestinal eff ects of opioids are mainly due to of action in Africans. Th is may be due in part to specifi c the involvement of peripheral opioid receptors in the genetic subtypes of the hepatic enzyme cytochrome mesenteric and submucous plexus, and are due to a P-450, and in part due to the individual patient’s lifestyle lesser extent to central opioid receptors. Th erefore, ti- and habits. tration with methylnaltrexone (100–150–300 mg orally), which does not penetrate into the central nervous Intravenous/intramuscular/subcutaneous system, successfully attenuates opioid-induced consti- Th ese diff erent forms of parenteral opioid application pation. More common practice, however, is the coad- follow the same goals: a convenient and reliable way of ministration of laxatives such as lactulose (3 × 10 mg application, a fast onset of analgesic eff ect, and bypass 42 Michael Schäfer of hepatic metabolism. While intravenous application Table 2 gives immediate feedback about the analgesic eff ect, in- Equianalgesic doses of diff erent routes of tramuscular and subcutaneous routes of administration administrations of opioids have some delay (about 15–20 min) and should be given Conversion Drug Dose (mg) Factor on a fi xed schedule to avoid large fl uctuations in plasma Morphine, oral 30 1 concentrations. Th e faster rise in opioid plasma con- Morphine, i.v., i.m., s.c. 10 0.3 centration with parenteral versus enteral applications Morphine, epidural 3 0.1 enables better and more direct control of opioid eff ects; Morphine, intrathecal 0.3 0.01 however, it increases the risk of a sudden overdose with Oxycodone, oral 20 1.5 sedation, respiratory depression, hypotension, and car- Hydromorphone, oral 8 3.75 diac arrest. After parenteral administration, a fi rst phase Methadone, oral 10 0.3 of opioid distribution within the central nervous system, Tramadol, oral 150 0.2 but also in other tissues such as fat and muscles, is fol- Tramadol, i.v. 100 0.1 lowed by a second, slower phase of redistribution from Meperidine, i.v. 75 0.13 fat and muscles into the circulation with the possibility Fentanyl, i.v. 0.1 100 of the re-occurrence of some opioid eff ects. Th is phe- Sufentanil, i.v. 0.01 1000 nomenon is particularly important following repeated Buprenorphine, s.l. 0.3 100 administration.

Sublingual/nasal Only highly lipophilic substances such as fentanyl and mg, and a 24-h dose of 3.0–10 mg; and for intrathecal buprenorphine can be administered by these routes, morphine a bolus dose of 0.1–0.3 mg, and a 24-h dose because they easily penetrate the mucosa and are ab- of 0.3–1.0–5.0 mg. sorbed by the circulation. Time of onset of analgesia is fast with fentanyl (0.05–0.3 mg; 5 min) but slower with Morphine buprenorphine (0.2–0.4 mg; 30–60 min). However, the duration of analgesia is much longer with buprenor- Morphine, a strong μ-opioid agonist that is recommend- phine (6–8 hours) than with fentanyl (15–45 min). Sim- ed in step 3 of the WHO ladder, is commonly used as ilar to the other parenteral applications, there is no he- a reference for all other opioids. It can be applied by all patic fi rst-pass metabolism. routes of administration. Morphine’s active metabolites morphine-6-glucuronide and morphine-3-glucuronide Intrathecal/epidural can increase side eff ects such as respiratory depression Opioids administered intrathecally or epidurally pen- and neurotoxicity (excitation syndrome: hyperalgesia, etrate into central nervous system structures depend- myoclonia, epilepsia), particularly when accumulation ing on their chemical properties: less ionized, i.e. more occurs due to impairment of renal function. Its main in- lipophilic, compounds such as sufentanil, fentanyl, or dications of use are for postoperative and chronic malig- alfentanil penetrate much (800 times) more easily than nant pain; however, it is also used for other severe pain more ionized, i.e. hydrophilic, compounds such as mor- conditions (e.g., colic pain, angina pectoris). In acute phine. While the lipophilic opioids are quickly taken up, pain states, morphine can be quickly titrated to optimal not only by the neuronal tissue, but also by epidural fat pain relief by the parenteral route (e.g., i.v. boluses of and vessels, a substantial amount of morphine remains 2.5–5 mg morphine), upon which the morphine plasma within the cerebrospinal fl uid for a prolonged period concentration should be kept constant by regular timed of time (up to 12–24 hours) and is transported via its intervals of subsequent administrations (e.g., 6–12 mg rostral fl ow to the respiratory centers of the midbrain, i.v. morphine/h). In chronic pain conditions, daily mor- leading to delayed respiratory depression. Th e eff ects of phine doses should be given in an extended-release opioids within the central nervous system are terminat- formula, and breakthrough pain is best treated by ad- ed by their redistribution into the circulation and not by ministration of a fi fth of the daily morphine dose in an their metabolism, which is negligible. Doses for epidu- immediate-release formula. Regular monitoring of pain ral morphine, for example, are a bolus dose of 1.0–3.0 intensity and morphine consumption is desirable. Opioids in Pain Medicine 43 Oxycodone with methadone doses that are 10% of the calculated equianalgesic doses of conventional opioids. Excretion Oxycodone is a strong oral μ-opioid agonist belonging occurs almost entirely in the feces, which makes it a to step 3 of the WHO ladder, with 1.5 times the anal- good candidate for patients with renal failure. Metha- gesic potency of morphine. Oxycodone has a high oral done has a much lower propensity for euphoric eff ects bioavailability of 60–80%. It is metabolized in multiple and is therefore used in maintenance programs for steps to diff erent metabolites, of which oxymorphone drug addicts. In addition, there is incomplete cross- is the most active and 8 times more potent than mor- tolerance to other opioids. Unfortunately, methadone phine. Oxycodone has a similar therapeutic profi le to has the potential to initiate Torsades de Pointes, a po- morphine; however, it is only available as an oral ex- tentially fatal arrhythmia caused by a lengthening of tended-release formulation (10–80 mg tablets). Since the QT interval in the ECG. these tablets have a relatively high dose, they can be pul- verized and made into an aqueous solution, which has Tramadol been misused for its euphoric eff ects by addicts. Tramadol, a weak opioid, belongs to step 2 of the Hydromorphone WHO ladder. Tramadol itself binds to norepinephrine and serotonin reuptake inhibitors, which increases lo- Hydromorphone is a μ-opioid agonist belonging to step cal concentrations of norepinephrine and serotonin, 3 of the WHO ladder (strong opioids) with 4–5 times leading to subsequent pain inhibition. In addition, one the analgesic potency of morphine. After oral applica- of its metabolites (M1) binds to the μ-opioid receptor, tion (single dose 4 mg), the onset of analgesia occurs af- which elicits additional analgesia. Tramadol has a high ter 30 min and lasts up to 4–6 hours. Because of its high bioavailability of 60% and 0.2 times the analgesic po- water solubility, it is available as both an oral and par- tency of morphine. Since the opioid component is de- enteral formulation (2 mg/1 amp.) that can be adminis- pendent on hepatic metabolism to the M1 compound, tered i.v., i.m., or s.c. Hydromorphone is extensively me- genetic variations may diff erentiate poor from exten- tabolized in the liver, with metabolism of approximately sive metabolizers, and hence the respective diff erences 60% of the oral dose. Th e metabolite hydromorphone- in analgesic eff ects. Tramadol exists as an oral (50– 3-glucuronide can cause neurotoxic eff ects (excitation 100–150–200 mg tablets) and parenteral formulation syndrome: hyperalgesia, myoclonus, epilepsy), similar to (50–100 mg). As with all opioids, hepatic and renal morphine-3-glucuronide. impairment may lead to accumulation of the drug with an increased risk of respiratory depression. Because of Methadone potential interactions, tramadol should not be given together with monoamine oxidase inhibitors, since the Methadone is a μ-opioid receptor agonist with 0.3 combination may produce severe respiratory depres- times the analgesic potency of morphine. In addition sion, hyperpyrexia, central nervous system excitation, to its opioid receptor activity, it is also an antagonist delirium, and seizures. of the N-methyl-D-aspartate (NMDA) receptor, which might be advantageous in chronic pain states such as Meperidine neuropathic pain in which the NMDA receptor seems to be responsible for the persistent pain hypersensi- Meperidine, a weak μ-opioid agonist, belongs to step 2 tivity. Methadone is a lipophilic drug with good CNS of the WHO ladder with 0.13 times the analgesic po- penetrability and high bioavailability (40–80%). It ex- tency of morphine and signifi cant anticholinergic and ists as an oral (5–40 mg tablets) and parenteral for- local anesthetic properties. Meperidine is most often mulation (levomethadone: 5 mg/mL). Methadone is used postoperatively, since in addition to its analgesic metabolized with no active metabolites by multiple eff ects, it has anti-shivering properties. Meperidine ex- diff erent enzymes of the liver in a highly variable ists as an oral (50 mg/mL solution) and parenteral for- manner, which explains its broad variation of half-life mulation (50–100 mg/2 mL). It is metabolized in the (up to 150 h) and makes regular dosing quite diffi cult liver to normeperidine with a half-life of 15–30 hours, for patients. In general, pain relief is better obtained and has signifi cant neurotoxic properties. Meperidine 44 Michael Schäfer should not be given to patients being treated with (s.l.) (0.2–0.4 mg capsules) and parenteral (0.3 mg/ monoamine oxidase inhibitors (MAOI), since the mL) formulations. Its metabolites are inactive and are combination may produce severe respiratory depres- mainly excreted via the biliary duct. Oral bioavailabil- sion, hyperpyrexia, central nervous system excitation, ity is 20–30% and sublingual bioavailability is 30–60%. delirium, and seizures. For acute pain, 0.2–0.4 mg s.l. buprenorphine or 0.15 mg i.v. is applied every 4–6 hours. Because of its very Fentanyl stable and long duration of action, buprenorphine is used for substitution therapy for drug addicts (4–32 Fentanyl, a strong μ-opioid agonist, belongs to step 3 of mg/daily). Similar to fentanyl, there is a transdermal the WHO ladder with 80–100 times the analgesic po- application system. Buprenorphine’s respiratory de- tency of morphine. Fentanyl mainly exists as a paren- pressant eff ects are reversed only by relatively large teral formulation (0.1 mg/2 mL); however, sublingual and repeated doses of naloxone (2–4 mg). application is sometimes used. A transdermal application system is widely used in industrial countries, but Naloxone/naltrexone because of its costs and the delayed delivery system with additional risks (delayed respiratory depression), it Both substances are classical opioid receptor antago- may only be of use in rare cases. Fentanyl is metabo- nists with a preference for μ-opioid receptors. Naloxone lized in the liver to inactive metabolites. Th e rapid on- is available only as a parenteral formulation (0.4 mg/1 set, high potency, and short duration of fentanyl is an mL), and it has a fast onset (within 5 min) and a short advantage in the titration and controllability of periop- duration (30–60–90 min) of action. It is commonly used erative pain. However, incorrect use may lead to large preoperatively to treat opioid overdosing and needs to fl uctuations in plasma concentration and increase the be titrated and administered repeatedly under constant risk of psychological dependence and addiction. Impor- monitoring. Naltrexone exists only as an oral formula- tantly, repeated administration of fentanyl may lead to tion (50 mg/tablet) with a delayed onset (within 60 min) drug accumulation due to redistribution from fat and and a long duration (12–24 h) of action. Naltrexone is muscle tissue into the circulation with increased risk of mainly used for maintenance treatment for alcohol and respiratory depression. drug dependence. Both substances can precipitate acute life-threatening withdrawal symptoms when improperly Sufentanil used, e.g., hyperexcitability, delirium, hallucinations, hyperalgesia, hypertension, tachycardia, arrhythmia, and Sufentanil, a very strong μ-opioid agonist, with 800– increased sweating. 1000 times the analgesic potency of morphine, is exclusively available as a parenteral formulation (0.25 Pearls of wisdom mg/5 mL) and can be given i.v. (10–100 μg boluses) as well as epidurally (initially: 5–10 μg, repeated bo- • Although they have been available for almost lus: 0.5–1 μg). Because of its very high potency, suf- 200 years, opioids still remain the mainstay of entanil is mainly used intraoperatively. In comparison pain management. While opioids are effective to fentanyl, it is much less prone to drug accumula- in most postoperative and cancer patients, and tion, because of its low tissue distribution, low proin some patients with neuropathic pain, most tein binding, and high hepatic metabolization rate to other noncancer pain is hardly responsive to inactive metabolites. opioid medication. • While opioids are regarded with a lot of preju- Buprenorphine dice because of their side eff ects and abuse potential, clinical practice and research have dem- Buprenorphine belongs to the mixed agonist/antago- onstrated in the last few decades that opioid nist opioids binding to μ- and k-opioid receptors. It medication for short- and long-term treatment usually has a slow onset (45–90 min), a delayed maxi- can be accomplished safely. Th ere is no evidence mal eff ect (3 hours), and a long duration of action about a diff erential indication of the opioids (8–10 hours). Buprenorphine is available as sublingual available. Consequently, availability, costs, and Opioids in Pain Medicine 45 personal experience should be the guiding prin- References ciples when choosing an opioid. • Because there is—as opposed to most drugs [1] Kaszor A, Matosiuk D. Non-peptide opioid receptor ligands—recent advances. Part I: Agonists. Curr Med Chem 2002;9:1567. used in medicine—no organ toxicity, even at [2] Kurz A, Sessler DI. Opioid-induced bowel dysfunction. Drugs 2003;63:649–71. high doses and with long-term treatment, and [3] Massotte D, Kieff er BL. A molecular basis for opiate action. Essays Bio- because some important side eff ects diminish chem 1998;33:65–77. [4] Trescot AM, Datta S, Lee M, Hansen H. Opioid pharmacology. Pain over time and other potential harmful side ef- Physician 2008;11:S133–53. [5] Pergolizzi J, Böger RH, Budd K, Dahan A, Erdine S, Hans G, Kress HG, fects may be avoided with correct use, it may Langford R, Likar R, Raff a RB, Sacerdote P. Opioids and the manage- be that opioids will remain the mainstay of pain ment of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often management for most of our patients for some used World Health Organization Step III opioids (buprenorphine, fen- time to come. tanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract 2008;8:287–313.

Guide to Pain Management in Low-Resource Settings

Chapter 8 Principles of Palliative Care

Lukas Radbruch and Julia Downing

What is palliative care? What are the principles of palliative care? Palliative care is an approach that improves the quality of life of patients and their families facing the problems Palliative care is a philosophy of care that is applicable associated with life-threatening illness, through the pre- from diagnosis (or beforehand as appropriate) until vention and relief of suff ering by means of early identifi - death and then into bereavement care for the family. cation and impeccable assessment and treatment of pain Often palliative care is seen as focusing on end-of-life and other problems, physical, psychosocial, and spiritual. care only, and while this is an important aspect of pallia- Th is widely accepted defi nition of the World Health Or- tive care, it is only one component of the continuum of ganization from 2002 includes some changes compared care that should be provided. It is focused on the needs to an older WHO defi nition from 1990. Th e defi nition of the patient, their families and carers. It is the provi- explains and reinforces the holistic approach, which not sion of comprehensive holistic care with the patient at only covers the physical symptoms, but extends to other the center of that care, and is dependent on attitudes, dimensions and aims of care for patients as they suff ers expertise, and understanding. It is a philosophy that can now with their disease, with their own personal story, be applied anywhere—across a range of skills, settings, and in their actual setting and social context. and diseases. Th e WHO has outlined several principles Th e WHO provides a similar defi nition for pal- that underpin the provision of palliative care, including liative care for children—the active total care of the child’s statements that palliative care: body, mind, and spirit—and also involves giving support • Provides relief from pain and other distressing to the family. It begins when illness is diagnosed, and symptoms; continues regardless of whether or not a child receives • Affi rms life and regards dying as a normal process; treatment directed at the disease. Health providers must • Intends neither to hasten nor postpone death; evaluate and alleviate a child’s physical, psychological, and • Integrates the psychological and spiritual aspects social distress. Eff ective children’s palliative care requires of patient care; a broad multidisciplinary approach that includes the fam- • Off ers a support system to help patients live as ily and makes use of available community resources; it can actively as possible until death; be successfully implemented even if resources are limited. • Offers a support system to help the family It can be provided in tertiary care facilities, in community cope during the patient’s illness and in their health centers, and wherever children call home. own bereavement;

Table 1 Th e essence of symptom control: fi rst-line medication for predominant symptoms Medication Dosage Drug Class Comments Dyspnea Morphine As required, or 10–30 Opioid (μ-agonist) AE: constipation, nausea, sedation, mg/d initially p.o., titrate cognitive impairment to eff ect; maximum dosage may exceed 600 mg/d Hydromorphone As required, or 4–8 mg/d Opioid (μ-agonist) AE: constipation, nausea, sedation, initially p.o., titrate to cognitive impairment eff ect, maximum dosage may exceed 100 mg/d Lorazepam As required, or 1–5 mg/d Benzodiazepine Cumulation with repeated use sublingual Respiratory Tract Secretions Hyoscine butylbromide (butyl- As required, 20–40 mg s.c. Antimuscarinergic drug (periph- No antiemetic eff ect scopolamine) (4-hourly) eral action) Hyoscine hydrobromide As required, 400 μg s.c. Antimuscarinergic drug (central Antiemetic eff ect; (scopolamine) and peripheral action) AE: sedation Nausea and Vomiting

Metoclopramide 30 mg/d; high dose: up to 5-HT4 antagonist Extrapyramidal AE; do not use in pa- 180 mg/d tients with gastrointestinal obstruction! Haloperidol 2 mg/d up to 5 mg/d Neuroleptic drug Extrapyramidal AE Constipation Macrogol 1 bag orally Sodium picosulfate 10–40 drops orally Octreotide 0.3–0.6 mg/d s.c. Reduces gastrointestinal secretions eff ectively, indicated for patients with gastrointestinal obstruction Methylnaltrexone 0.8–1.2 mg/d Opioid antagonist (peripheral Eff ective for opioid-induced constipa- action) tion Fatigue, Weakness Dexamethasone 12–24 mg/d initially, Corticosteroid Gastric ulcers, hallucinations, night- stepwise reduction after a mares, weight gain, only eff ective for a couple of days restricted time period Anxiety Lorazepam 1–5 mg/d Benzodiazepine AE: paradoxical eff ects Mirtazapine 15 mg initially, stepwise Antidepressant (SNRI) Also eff ective for treatment of panic at- increase after 2–3 weeks tacks, pruritus; AE: sedation, increased up to 45 mg/d appetite, liver dysfunction

Depression Mirtazapine 15 mg initially, stepwise Antidepressant (SNRI) Also eff ective for treatment of anxiety, increase after 2–3 weeks panic attacks, pruritus; AE: sedation, up to 45 mg/d increased appetite, liver dysfunction Methylphenidate 5 mg in the morning ini- Stimulant AE: agitation, restlessness, extrapyra- tially, stepwise increase to midal eff ects, tachycardia, arrhythmia 30 (40) mg/d Agitation, Confusion Haloperidol 2 × 1 mg, up to 20 mg/d Neuroleptic drug AE: extrapyramidal eff ects Levomepromazine (metho- 25–50 mg, up to 200 mg/d Neuroleptic drug AE: sedation, anticholinergic eff ects trimeprazine) Abbreviations: AE = adverse eff ect; SNRI = serotonin norepinephrine reuptake inhibitor. Principles of Palliative Care 53 off ers a selective and eff ective option for treatment of However, these symptoms may overburden the patient opioid-induced constipation, but high costs will prevent and will then require treatment to restore quality of life its use in resource-poor settings. Nondrug interventions for the remainder of the lifespan. such as increased activity, more fl uid intake, or change Anxiety may be most pronounced at night, pre- of diet usually are very eff ective, if appropriate for the venting sleep and adding to tiredness during the day. patient’s condition. Benzodiazepines at night provide a good night’s rest and prevent endless brooding. Lorazepam off ers a pro- How should you treat fatigue? fi le with rapid onset and little hangover the next day, but Fatigue has been named as the most frequent symp- other sedatives will do as well. Treatment with benzo- tom of cancer patients, and it is a predominant feature diazepines will also help with the treatment of dyspnea in noncancer palliative care patients as well. As the and other symptoms, as these symptoms may have been concept of fatigue is often not clearly understood by augmented by anxiety. patients or by all health care professionals, it is recom- Some patients with advanced disease suff er mended to consider the symptoms tiredness and weak- from major depression and require treatment with an- ness instead of fatigue. However, there are only a few tidepressants. Mirtazapine is included in the IAHPC list medical interventions for these symptoms. Treatment of essential drugs for palliative care. Mirtazapine is also with erythropoietin, where available, has been used with indicated for anxiety and panic attacks, and has been good eff ect in cancer patients, but in the palliative care reported to alleviate pruritus. However, for treatment setting with reduced life expectancy there seems to be of depression, other antidepressants will do as well. Se- no indication for erythropoietin. Drugs such as methyl- lective serotonin reuptake inhibitors (SSRIs) should be phenidate and modafi nil are under investigation. How- preferred as they produce less side eff ects compared to ever, the most eff ective medication seems to be dexa- older tricyclic antidepressants. Eff ect of antidepressant methasone or other steroids. Th eir eff ect tends to wear therapy usually will take 2–3 weeks, and as treatment off within a few days or weeks, and often is accompa- should be started at a low dose with stepwise titration nied by adverse events, so steroids should be reserved until eff ective, many patients with reduced life expec- for situations where a clear goal is visible within a short tancy will not live long enough to benefi t from antide- time frame, such as a family celebration. pressants. For these patients methylphenidate is an al- Reduction of other medications may alleviate ternative, as the onset of action takes only a few hours. tiredness dramatically, and a review of the drug regi- However, many patients will suff er not from men is advocated in patients with reduced performance major depression, but from feeling depressed, which status, as many medications may not be required any is not the same. A feeling of sadness and grief may be more. In selected patients with severe anemia, blood completely appropriate and may even help with coping transfusions are an option to reduce tiredness and with the disease. Treatment with antidepressants for weakness, with repeated transfusions even over a pro- these patients may impede coping and add burdensome longed period of time. side eff ects such as dry mouth or constipation. Th e de- However, for most patients, nondrug interven- cision to treat depression therefore requires careful bal- tions will be eff ective, such as counseling, energy con- ancing of eff ectiveness and side eff ects. serving and restoration strategies, and keeping a diary of daily activities. Physical training has been shown to How should you treat agitation and confusion? reduce fatigue eff ectively. Physical activity is possible In the fi nal phase of life, agitation and confusion are even for patients with advanced disease, although it has frequent symptoms that can cause considerable stress to be adapted to reduced performance status and cogni- not only on the patient, but also on caregivers and staff . tive function. Neurological causes may include focal seizures, ischemic insult, cerebral bleeding, or brain metastases. How should you treat anxiety and depression? Many drugs as well as withdrawal of drugs or more fre- Anxiety and depression are among the major psycho- quently of alcohol may lead to delirium, typically with logical problems in palliative care. Patients facing the fl uctuating symptomatology after sudden onset. Fever, diagnosis of an incurable disease and limited progno- infection, electrolyte disturbance such as hypercalcemia, sis may have every right to feel anxious and depressed. or dehydration also may trigger or aggravate delirium. 54 Lukas Radbruch and Julia Downing Neuroleptic medication may be required, with halo- hours, and care has to be delivered by auxiliary staff or peridol as a fi rst-line approach. High dosages may be family caregivers. required, with doses as high as 20–30 mg per day. Oth- er neuroleptics such as levomepromazine have more What is rescue or breakthrough medication? sedative properties and may be benefi cial in severely Rescue or breakthrough medication should be pre- agitated patients. For patients with HIV disease, HIV- scribed for patients with advanced disease, where ex- related brain impairment can cause agitation and confu- acerbations of pain or other symptoms are possible, sion earlier on in the disease trajectory, and thus similar and rapid treatment of these exacerbations is required. symptoms may have to be controlled prior to the fi nal Rescue medications can include diff erent drugs, but phase of life. for most patients they should include at least an opioid with fast onset for treatment of pain, dyspnea, and Emergency interventions anxiety as well as a benzodiazepine such as lorazepam for the treatment of dyspnea, anxiety, and agitation What constitutes an emergency (Table 2). in palliative care? Respiratory secretions may lead to labored Exacerbation of pain and other symptoms as well as se- breathing in dying patients, and may cause distress in vere psychological distress with anxiety or even panic patients as well as in caregivers. Anticholinergic drugs may lead to emergency situations that require immedi- such as hyoscine butylbromide may alleviate this “death ate action. In these emergencies, the onset of symptom rattle” quickly. relief should not be delayed unduly by prolonged assess- For all drug interventions, the route of admin- ment or diff erential diagnosis. However, the usual medi- istration should be considered. Oral application may cal emergency procedures may also be detrimental, for be much easier if no professional help is available, but example when pain exacerbation leads to a hospital ad- in some patients oral intake is not possible. Opioids as mission with transport time as well as radiographic and well as many other drugs used in palliative care can be laboratory investigations, but without analgesic inter- injected subcutaneously, with little risk of complications vention or comforting care. and with a faster onset of action than with oral applica- Emergencies that have to be treated rapidly and tion. Intravenous application off ers the option for rapid adequately are exacerbations of preexisting symptoms, titration with small bolus administrations if trained staff new symptoms with sudden and intense onset, or rare are available. complications such as massive hemorrhage. Individual treatment plans in palliative care should try to foresee What should be done in the case such emergencies and provide adequate interventions. of massive hemorrhage? Prescription (or even better, provision) of rescue medi- Cancer growth in the skin or mucous membranes may cation for emergencies is especially important when lead to excessive bleeding if major blood vessels are health care professionals are not available out of offi ce ruptured. Th is can manifest with sudden onset or with

Table 2 Th e essence of symptom control: emergency intervention Medication Dosage Drug Class Comments Rescue Medication (Given as Required) Morphine 10 mg 10–20 mg orally Opioid (μ-agonist) Indication: pain, dyspnea 10 mg s.c. (or i.v. in small steps) Hydromorphone 1.3–2.6 mg orally Opioid (μ-agonist) Indication: pain, dyspnea 2–4 mg s.c. Hyoscine butylbromide 40 mg 20 mg s.c. Antimuscarinergic drug Indication: respiratory tract secretions Lorazepam 1 mg 1 mg sublingually Benzodiazepine Indication: agitation, anxiety Palliative Sedation Midazolam 3–5 mg/h s.c., i.v. Benzodiazepine Paradoxical eff ect/ or 3–5 mg bolus as required inadequate eff ect Principles of Palliative Care 55 increasing intensity, or with sudden vomiting of clot- Psychosocial and spiritual care ted blood from gastrointestinal bleeding. With minor bleeding sometimes blood transfusions may be indicat- What is the impact of psychosocial issues ed. For more severe bleeding, benzodiazepines or mor- on medical care? phine via subcutaneous bolus administration may be indicated, but often they will not take eff ect fast enough. Psychosocial issues are often neglected by medical staff , With massive hemorrhage the patient will quickly be- even though they are paramount for many patients. come unconscious and die with little distress, and treat- Fears about the progression of the disease, about death ment should be restricted to comfort measures. Enough and dying, about fi nancial problems, or about stigmati- towels or similar material should be available to cover zation with diseases such as HIV/AIDS may overwhelm the blood. patients, alienate them from their family and friends, and often aggravate the impact of physical symptoms. What is palliative sedation? For most patients in resource-poor countries the loss of Rarely, patients with extreme distress from pain, dys- support is an immediate implication of a life-threaten- pnea, agitation, or other symptoms that are resistant ing disease, often endangering the survival of the patient to palliative treatment, or do not respond fast enough as well as of the family. Social support that provides the to adequate interventions, should be off ered palliative means to sustain basic requirements is as mandatory as sedation. Th is means that benzodiazepines are used the medical treatment of symptoms. to lower the level of consciousness until distress is re- Most patients with life-threatening disease also lieved. In some patients deep sedation is required, ren- have spiritual needs, depending on their religious back- dering the patient unconsciousness. However, for other ground and cultural setting. Spiritual support from patients mild sedation may be enough, so that patients caregivers as well as from specialized staff , for example can be roused and can interact with families and staff to religious leaders, may be helpful. some degree. Intravenous or subcutaneous midazolam How do you communicate bad news? is used most often, as it can be titrated to eff ect easily. It should be realized that palliative sedation is Palliative care staff should have special communication the last resort if symptomatic treatment fails. Before skills. Health care professionals should be able to col- the initiation of this treatment, other treatment op- laborate with other staff and volunteers who care for the tions have to be considered, and the priorities of the patient, and agree on treatment regimens and common patient should be clarifi ed. Some patients prefer to suf- goals for the patient. Th ey must also be able to commu- fer from physical symptoms instead of losing cognitive nicate with patients and families on diffi cult topics, for capacity, and sedation should only be initiated if the example ethical decisions such as treatment withdrawal patient agrees. Eff ective services will fi nd an indication or withholding of treatment. Specifi c models are avail- for sedation in only a few selected patients with very able, for example the SPIKES model for breaking bad severe symptoms. news (Table 3).

Table 3 SPIKES model for breaking bad news Setting Choose the setting for the talk, talk on same eye level with patient, avoid disturbances and interruptions, allow for family members to be present. Perception Check the capacity of the patient, impairment from medication or from disease, or from interaction with family members, use verbal and nonverbal cues for perception. Invitation Ask the patient about his level of information, what does he know about his disease and about the topic of the talk, and ask the patient how much he wants to know. Knowledge Inform the patient about the bad news, in a structured way with clear terminology, allow for questions and give as many details as the patient requires. Empathy Leave time for emotional reactions of the patient, explore emotional reactions and react empathically. Summary Provide a concise summary, if possible with some written summary, and off er a follow-up talk if possible. 56 Lukas Radbruch and Julia Downing How do you provide bereavement support? significance may be supported by medical staff who Bereavement support is an important, yet often forgot- explain that the withholding of anticancer therapies ten, part of palliative care provision, which should not is linked to the poor nutritional status of the patient. end with the death of the patient. Grief and loss are However, it has to be realized that cachectic patients expressed in a multiplicity of words and languages by with cancer or with HIV/AIDS most often do not ben- diff erent peoples. A wealth of diverse ritual serves to efi t from nutrition. In most cases, a catabolic metabo- guide people in societies through the grief process, and lism is the major reason for cachexia, and the provi- it is important for the health professional to be aware sion of additional calories does not change that status. of such rituals. Grief not only aff ects relatives, but also Patients in the fi nal stage of the disease may even de- patients themselves, who may experience anticipatory teriorate with parenteral fl uid substitution, when ede- grief prior to their death as they grieve the various loss- ma or respiratory secretions are increased. Th irst and es that they are experiencing such as the loss of their hunger, on the other hand, are not increased when future and the loss of seeing their children grow up. Pa- fl uids and nutrition are withheld. In many cases, and tients need support to work through some of these is- nearly always in dying patients, nutritional supple- sues prior to their death and to plan for the future of ments, parenteral nutrition, and fl uid replacement are their loved ones, where possible. not indicated and should be withdrawn or withheld. If Many diff erent factors can aff ect the bereave- necessary, small amounts of fl uid (500–1000 mL) may ment process for family members, including their re- be infused with a subcutaneous line. lationship with the person who died, the way that they How should we react if patients ask died, whether they were experiencing symptoms and for hastened death? were seen to be suff ering, stigma, a lack of disclosure Palliative care by defi nition neither hastens nor post- about their illness, local cultural practices and beliefs, pones death. Active euthanasia is not a medical treat- personality traits, other stresses that they may also be ment and cannot be part of palliative care. However, experiencing, and bereavement overload if they have there are a few patients receiving palliative care who ask lost several friends and relatives in a short space of time. for assisted suicide or for active euthanasia or for other Ongoing bereavement support may be provided to rela- forms of hastened death. tives, either by the palliative care team or by referral to In most countries, withholding or withdrawing local community networks and support systems. It is life-sustaining treatment is legally and ethically accept- important that the need for bereavement support be able, and so treatment reduction may off er an option. recognized and support provided as appropriate. In selected cases with intolerable suff ering, palliative sedation may be indicated. However, for most patients Ethical decision making asking for hastened death, a more detailed exploration Whereas guidelines and recommendations are avail- and more empathic care should be off ered. Often the able for most areas of symptom control, there are statement “I do not want to live anymore” means “I do some issues in palliative care that are loaded with ethi- not want to live like this anymore,” and communica- cal implications. tion about problems or fears may help to alleviate the wish for hastened death. For most patients it is possible Are nutrition and fl uid substitution necessary to fi nd a solution that allows them to spend the rest of if oral intake is not possible? their days with an acceptable quality of life. Patients and more often other caregivers and health care professionals insist on enteral or parenteral nutri- References tion or at least fl uid substitution if patients are no lon- [1] Baile WF, Buckman R, Lenzi R, Glober G, Beale EA, Kudelka AP. ger able to eat or drink. If the therapist does not com- SPIKES: a six-step protocol for delivering bad news: application to the cancer patient. Oncologist 2000;5:302–11. ply with this wish, it is often considered as inhumane, [2] Buccheri G, Ferrigno D, Tamburini M. Karnofsky and ECOG perfor- as the patient then will starve or die of thirst. Nutri- mance status scoring in lung cancer: a prospective, longitudinal study of 536 patients from a single institution. Eur J Cancer 1996;32:1135–41. tion often has an overwhelming symbolic signifi cance, [3] Chang VT, Hwang SS, Feuerman M. Validation of the Edmonton Symp- and as long as the patient is nourished, caregivers tom Assessment Scale. Cancer 2000;88:2164–71. [4] Conill C, Verger E, Salamero M. Performance status assessment in can- will perceive a chance for the patient to get well. This cer patients. Cancer 1990;65:1864–6. Principles of Palliative Care 57

[5] Downing J, Finsch L, Garanganga E, Kiwanuka R, McGilvary M, Pa- [10] Powell RA, Downing J, Harding R, Mwangi-Powell F, Connor S. Devel- winski R, Willis N. Role of the nurse in resource-limited settings. In: opment of the APCA African Palliative Outcome Scale. J Pain Symptom Gwyther L, Merriman A, Mpanga Sebuyira L, Schietinger H, editors. Manage 2007;33:229–32. A clinical guide to supportive and palliative care for HIV/AIDS in Sub- [11] Puchalski C, Romer AL. Taking a spiritual history allows clinicians to Saharan Africa. Kampala: African Palliative Care Association; 2006. understand patients more fully. J Palliat Med 2000;3:129–37. [6] Gwyther L, Merriman A, Mpanga Sebuyira L, Schietinger H. A clini- [12] Sepulveda C, Marlin A, Yoshida T, Ullrich A. Palliative care: the World cal guide to supportive and palliative care for HIV/AIDS in sub-Saharan Health Organization’s global perspective. J Pain Symptom Manage Africa. Kampala: APCA; 2006. 2002;24:91–6. [7] Hearn J, Higginson IJ. Development and validation of a core outcome [13] World Health Organization. Cancer pain relief and palliative care—re- measure for palliative care: the palliative care outcome scale. Palliative port of a WHO expert committee. WHO Technical Report Series No. Care Core Audit Project Advisory Group. Qual Health Care 1999;8: 804. Geneva: World Health Organization; 1990. 219–27. [8] Materstvedt LJ, Clark D, Ellershaw J, Forde R, Gravgaard AM, Muller- Busch HC, Porta i Sales J, Rapin CH. Euthanasia and physician-assisted suicide: a view from an EAPC Ethics Task Force. Palliat Med 2003;17: Websites 97–101; discussion 102–79. [9] Nieuwmeyer SM, Deﬁ lippi K, Marcus;C., Nasaba R. Loss, grief and World Health Organization (2004) Integrated Management of Adult Ill- bereavement. In: Gwyther L, Merriman A, Mpanga Sebuyira L, Schi- nesses, palliative care: symptom management and end of life care, http:// etinger H, editors. A clinical guide to supportive and palliative care for www.who.int/3by5/publications/documents/imai/en/ (Accessed November HIV/AIDS in Sub-Saharan Africa. Kampala: African Palliative Care As- 25, 2008). sociation; 2006.

Guide to Pain Management in Low-Resource Settings

Chapter 9 Complementary Th erapies for Pain Management

Barrie Cassileth and Jyothirmai Gubili

Is conventional pharmacotherapy have an important role to play everywhere, and espe- always the best option cially in the low-resource setting. for pain control? How often are complementary Both acute and chronic pain may be treated with pre- therapies used by the patient? scription pharmaceuticals, but they also may be controlled by complementary therapies such as acupunc- Complementary therapies are increasingly used to al- ture, massage therapy, and other modalities discussed leviate pain and other symptoms, such as nausea and in this chapter at less cost and typically with fewer fatigue. Internationally, 7% to more than 60% of can- side effects. cer patients use complementary therapies, depend- Each year about nine million cancer patients ing on definitions used in numerous surveys. These worldwide experience moderate to severe pain most of therapies also are frequently used for pain that is not the time. Th irty percent of newly diagnosed cancer pa- cancer-related. tients and 70–90% of patients with advanced disease suff er signifi cant pain. Pain experienced by cancer pa- How do complementary tients can be chronic, caused directly by tumor inva- therapies work? sion or by cancer treatment itself, or acute pain, such as following surgery. Pain in terminal stages of disease has Complementary therapies may work by direct analgesic its own characteristics and special issues. Th e World eff ects (e.g., acupuncture), by anti-infl ammatory action Health Organization (WHO) recommends use of anal- (e.g., herbs), or by distraction (e.g., music therapy), to gesics for pain, starting with nonopioid drugs followed aff ect pain perception, assist relaxation, improve sleep, by opioids for uncontrolled and persistent pain. But, or reduce symptoms such as nausea, neuropathy, vomit- pharmacological interventions, although eff ective, do ing, anxiety, or depressed mood, as well as pain. Th ese not always meet patients’ needs, and they may produce therapies often work when used alone, but they are also diffi cult side eff ects. Th ey are also costly and may be dif- used with pharmaceuticals, often reducing the dos- fi cult to obtain. Th ese issues pose a great challenge for ages required, and thus decreasing side eff ects and cost. patients requiring long-term pain management, often When complementary therapies work synergistically forcing them to choose between living in pain or living with a pharmaceutical pain regimen, eff ectiveness may with undesirable side eff ects. Complementary therapies be improved and costs reduced.

[3] Cassileth BR and Vickers AJ. Massage therapy for symptom control: outcome study at a major cancer center. J Pain Symptom Manage Websites 2004;28:244–9. [4] Ernst E, Cassileth BR. Th e prevalence of complementary/alternative A CD developed at Memorial Sloan-Kettering teaches patients self-hypnosis medicine in cancer: a systematic review. Cancer 1998;83:777–82. for use prior to surgery or at any time to control pain: www.mskcc.org/ [5] Good M, Stanton-Hicks M, Grass JA, Anderson GC, Lai HL, Roykul- mskcc/html/5707.cfm charoen V, Adler PA. Relaxation and music to reduce postsurgical pain. Because accurate information is essential, the Integrative Medicine Service J Adv Nurs 2001;33:208–15. at Memorial Sloan-Kettering Cancer Center developed and maintains a [6] Liossi C, White P. Eﬃ cacy of clinical hypnosis in the enhancement of free website with continually updated and objective data on more than 240 quality of life of terminally ill cancer patients. Contemporary Hypn entries: www.mskcc.org/mskcc/html/11570.cfm 2001;18:145–50. [7] Park RL. Voodoo science: the road from foolishness to fraud. Oxford Information on traditional medicine may be accessed via: www.who.int/ University Press; 2002. mediacentre/factsheets/fs134/en/ Physical and Psychological Patient Evaluation

Guide to Pain Management in Low-Resource Settings

Chapter 10 Pain History and Pain Assessment

Richard A. Powell, Julia Downing, Henry Ddungu, and Faith N. Mwangi-Powell

Th e eff ective clinical management of pain ultimately treatment may be delivered to manage the pain. It is depends on its accurate assessment. Th is entails a com- important, however, that this treatment interven- prehensive evaluation of the patient’s pain, symptoms, tion be evaluated via subsequent pain assessments to functional status, and clinical history in a series of as- determine its eff ectiveness. Th e patient’s pain should sessments, depending on the patient’s presenting needs. therefore be assessed on a regular basis and the result- Such assessments rely in part on the use of evaluation ing treatment options modifi ed as required to ensure tools. To varying degrees, these tools attempt to locate eff ective pain relief. and quantify the severity and duration of the patient’s subjective pain experience in a valid and reliable man- Are there key elements to the pain ner to facilitate, structure, and standardize pain communication between the patient and potentially diff er- assessment process? ent health care providers. Bates (1991) suggests that the critical components of the pain assessment process include a determination of How do you learn about a its: location; description; intensity; duration; alleviating patient’s pain? What is the pain and aggravating factors (e.g., the former might include assessment process? herbal medications, alcohol or incense); any associative factors (e.g., nausea, vomiting, constipation, confusion, Where pain levels permit (i.e., where severe clinical or depression), to ensure that the pain is not treated in needs do not demand immediate intervention), the as- isolation from comorbidities; and its impact upon the sessment process is essentially a dialogue between the patient’s life. patient and the health care provider that addresses the Th ese components are most commonly embod- nature, location, and extent of the pain, looks at its im- ied in the “PQRST” approach: Provokes and Palliates, pact on the patient’s daily life, and concludes with the Quality, Region and Radiation, Severity, and Time (or pharmaceutical and nonpharmaceutical treatment op- Temporal). In this approach, typical questions asked by tions available to manage it. a health care provider include: P = Provokes and Palliates Is pain assessment a one-off process? • What causes the pain? • What makes the pain better? Rather than an isolated event, the assessment of pain • What makes the pain worse? is an ongoing process. Following the initial assessment,

Q = Quality culturally acceptable levels of “complaining,” a sense • What does the pain feel like? of hopelessness, diminished morale, coping and ad- • Is it sharp? Dull? Stabbing? Burning? Crushing? aptation abilities, and the meaning attached to the R = Region and Radiation experienced pain). Consequently, the health care pro- • Where is the pain located? vider should accept the patient as an expert on his or • Is it confi ned to one place? her own body, and accept that while some patients • Does the pain radiate? If so, where to? may exaggerate their pain (e.g., to be seen earlier in • Did it start elsewhere, and is it now localized to a hospital), this will generally be the exception rath- one spot? er than the norm. Moreover, evidence suggests that health care providers’ observational pain report can- S = Severity not be assumed to be an accurate indicator of the pa- • How severe is the pain? tient’s pain. T = Time (or Temporal) Second, as much as is possible within a time- • When did the pain start? constrained service setting, allow patients to describe • Is it present all the time? their pain in their own words (the fact that patients may • Are you pain-free at night or during the day? report socially acceptable answers to the health care • Are you pain-free on movement? provider demands a sensitive exploration of what is ex- • How long does the pain last? pressed). For patients who feel uncomfortable express- At the patient’s fi rst assessment, the pain assessing themselves, the health care provider can provide a ment process should be a constituent part of a wider sample of relevant words written on cards from which comprehensive patient assessment that could include the patient can select the most appropriate descriptors. additional questions: Th e primary intention here is to listen to the patient • Is there a history of pain? rather than make any potentially false assumptions and • What is the patient’s diagnosis and past medical erroneous clinical decisions. history (e.g., diabetes, arthritis)? Th ird, listen actively to what the patient says. • Is there a history of surgical operations or medi- Rather than engage the patient in a distracted man- cal disorders? ner, the health care provider should focus attention on • Has there been any recent trauma? the patient, observing behavioral and body language, • Is there a history of heart disease, lung problems, and paraphrasing words when necessary to ensure that stroke, or hypertension? what is expressed is clearly understood. In emotionally • Is the patient taking any medication (e.g., to re- charged encounters, the health care provider must also duce the pain; if so, did it help the patient?) actively listen for nonverbal descriptors. • Does the patient have any allergies (e.g., to food Fourth, the location of the pain across the body or medicines)? can be determined by showing the patient a picture of • Does the pain hurt on deep inhalation? the human body (at least the front and back) (see Ap- • What is the patient’s psychological status (e.g., pendix 1 for an example of a body diagram), requesting depression, dementia, anxiety)? that they indicate the primary and multiple (if appropri- • What is the patient’s functional status, including ate) areas of pain, and demonstrate the direction of any activities of daily living? radiated pain. Fifth, pain scales (of varying complexity and What can be done to ensure an methodological rigor) can be used to determine the se- eff ective pain assessment process? verity of the expressed pain (see below for some examples). First, in general, accept the patient’s self-reported pain Sixth, while it is important to manage an indi- as accurate and the primary source of information. vidual’s pain as soon as is possible (i.e., one is not obli- Pain is an inherently subjective experience, and the pa- gated to wait for a diagnosis), in the assessment process tient’s expression of this experience (be it behavioral the health care provider should also diagnose the cause or verbal) can be infl uenced by multiple factors (e.g., of that pain and treat if possible, thus ensuring a longer- gender diff erences, socially acceptable pain thresholds, term resolution to the presenting pain problem. Pain History and Pain Assessment 69 How long should an assessment take? What are the challenges for pain assessment with the young? Th e time needed for assessment will vary according to individual patients, their presenting problems, and the Th e term “the young” refers to children of varying ages specifi c demands on clinic time. For example, the pa- and cognitive development: neonates (0–1 month); in- tient may be in such severe pain that they are unable fants (1 month to 1 year); toddlers (1–2 years); pre- to provide any meaningful information to produce a schoolers (3–5 years); school-aged children (6–12 comprehensive pain history. Similarly, there will be oc- years); and adolescents (13–18 years). Children at each casions when the assessment has to be relatively brief stage of development pose distinct challenges to eff ec- (investigating the intensity, quality, and location of the tive pain assessment. pain) so that urgently required eff ective pain management can be provided quickly. Neonates (0–1 month) It is also important to remember that, in gen- At this age, behavioral observation is the only way to eral terms, it is the quality of the pain assessment that assess a child. Observation can be conducted with the results in eff ective pain management rather than the involvement of the child’s family or guardian, who can quantity of time spent on it. advise on what are “normal” and “abnormal” behavior patterns (e.g., whether or not the child is unusu- Does pain assessment diff er ally tense or relaxed). Importantly, for all children, with children and young people? the health care provider should follow national ethical guidelines concerning the presence of a parent or Th e response to this question is mixed. On the one guardian at the assessment process and any associated hand, no, it does not, because, despite the previously issues (e.g., informed consent). Additionally, it must be held misconception that children do not experience remembered that behavior is not necessarily an accurate pain due to underdeveloped neurological systems, indicator of the patient’s pain level and that the absence children do feel pain. Consequently, an eff ective pain of behavioral responses (e.g., facial expressions such as assessment process is as important for children as it is crying and movements indicating discomfort) does not for adults. always equate with the absence of pain. On the other hand, yes it does, because the expression and detection of children’s pain can be more Infants (1 month to 1 year) challenging than it is for adults (see below). At this age, the child may exhibit body rigidity or thrashing, exhibit facial expression of pain (e.g., brows Is there a specifi c assessment lowered and drawn together, eyes tightly closed, mouth open and squarish), cry intensely or loudly, be inconsol- process for children able, draw the knees to the chest, exhibit hypersensitiv- and young people? ity or irritability, have poor oral intake, or be unable to sleep. Th e issues raised above for neonates resonate for Th e specifi cs of assessing pain in children have given infants, too. rise to the “QUESTT” approach: Question the child if verbal, and the parent or guardian Toddlers (1–2 years) in both the verbal and nonverbal child. Toddlers may be verbally aggressive, cry intensely, exhibit Use pain rating scales if appropriate. regressive behavior or withdraw, exhibit physical resis- Evaluate behavior and physiological changes. tance, guard the painful area of the body, or be unable to Secure the parent’s involvement. sleep. While toddlers may still be unable to communicate their feelings verbally, their behavior can express their Take the cause of pain into account. emotional and physical disposition. At this age, generat- Take action and evaluate the results (Baker and Wong ing an accurate assessment of the location and severity of 1987). the child’s pain may require the use of play and drawings, off ering children a nonverbal means of expressing what they are feeling and thinking. However, some children, 70 Richard A. Powell et al. even at this age, are able to express their pain using sim- Adolescents (13–18 years) ple language. Health care providers should be sensitive Adolescents may verbalize their pain, deny pain in the to such developmental diff erences. presence of their peers, have changes in sleep patterns Preschoolers (3–5 years) or appetite, be infl uenced by cultural beliefs, exhibit muscle tension, display regressive behavior in the pres- Preschool children may verbalize the intensity of their ence of their family, or be unable to sleep. pain, see pain as a punishment, thrash their arms and At this age, the child can appear relatively un- legs, attempt to push stimuli away before they are ap- communicative or express a disdainful disposition. plied, be uncooperative, need physical restraint, cling Th is tendency can in part be countered by the health to their parent or guardian, request emotional support care provider expressing genuine interest in what the (e.g., hugs and kisses), or be unable to sleep. adolescent has to say, avoiding confrontation or gener- At this age, as for school-aged children (see be- ally negative sentiments (which can cause anxiety and low), the child needs to be able to trust the health care avoidance), focusing the conversation on the adoles- provider, who needs to overcome the child’s potential cent rather than the problem (e.g., by asking informal reservations concerning strangers and perceived au- questions about friends, school, hobbies, family), and thority fi gures. Th is aim can be achieved by conducting avoiding deliberate moments of silence, which generally the assessment process at a tempo, in a language, and prove unproductive. with a demeanor that is suited to the child (e.g., taking As a consequence of this diversity across age more time, where possible, using open-ended questions groups (especially in children’s cognitive abilities to to encourage children to discuss what they are experi- comprehend what is being asked, and verbal abilities to encing, and using appropriately supportive and encour- articulate what is being thought or felt), the pain evalu- aging body language). ation tool selected for the assessment process must be School-aged children (6–12 years) appropriate to the individual child. Moreover, given that behavior alone is not necessarily a reliable indica- Th e school-aged child may verbalize pain, use an objec- tor of experienced pain, and self-reporting has potential tive measure of pain, be infl uenced by cultural beliefs, limitations, a pain rating scale should ideally be used in experience pain-related nightmares, exhibit stalling be- conjunction with an investigation of physiological pain haviors (e.g., “Wait a minute” or “I’m not ready”), show indicators, such as changes in blood pressure, heart rate, muscular rigidity (e.g., clenched hands, white knuckles, and the patient’s respiratory rate (see Chapter 26 on gritted teeth, contracted limbs, body stiff ness, closed Pain Management in Children for additional informa- eyes, or wrinkled forehead), engage in the same behav- tion). iors as preschoolers, or be unable to sleep. At this age, the child may be more reserved, feeling genuine fears and anxieties (e.g., they may deny the presence of pain Does pain assessment diff er because they fear the consequences, such as a physical with the aged? examination or injection). Aged patients present additional challenges in that However, school-aged children are more articu- they may be visually or cognitively challenged, hearing late and cognitively advanced. As such, they are more impaired, or infl uenced by socially determined norms curious about their own body and health and may ask regarding the reporting of negative feelings (e.g., not spontaneous questions of the health care provider (e.g., wanting to appear to be a social burden). Geriatric pa- “What is happening to me?” “Why do I have a stomach- tients (i.e., patients with advanced biological age with ache?”). Th ey can also begin to understand cause and multiple morbidities and—potentially—multiple medi- eff ect issues, enabling the health care provider to give cations) are especially problematic when they have de- them age-sensitive explanations (e.g., “You have a pain mentia. Such patients normally receive inadequate an- in your stomach because you have a lump there which algesia due to their inability to communicate their need is making it hurt”). Th ey also may want to be involved for it. (Defi ning “the aged” in low-resource settings can in their own clinical care and, where possible, be given be problematic. Th e United Nations defi nition of “older choices about what will happen to them. people” is commonly associated with a legal entitlement Pain History and Pain Assessment 71 to age-specifi c pension benefi ts arising from the formal Scale, the Depressivity Scale; the University of Ala- employment sector, but in regions such as sub-Saharan bama in Birmingham (UAB) Pain Behavior Scale, the Africa such a chronological defi nition is problematic, Neonatal/Infant Pain Scale, and the Children’s Hospi- often replaced by more complex, multidimensional tal Eastern Ontario Pain Scale.) Importantly, it is es- sociocultural defi nitions, such as the person’s senior- sential that the health care provider selects the most ity status within their community and the number of appropriate tool (depending on the aims of the pain grandchildren they have.) assessment, and on the practicality, applicability, and Consequently, the principal rule, especially for acceptability of the instrument to particular patient the geriatric patient, is to ask for pain. Among those populations) and uses it consistently over time. who have suffi cient cognitive functioning to express Th e most commonly used tools for assessing themselves, the health care provider can increase the pain in cognitively unimpaired adults and the elderly text size of word descriptors for the visually impaired, are the visual analogue scale (VAS), the numerical rat- include relatives in the pain assessment process where ing scale (NRS), the verbal descriptor scale (VDS). A it is considered appropriate and helpful, and avoid tool that has been evaluated in a low-resource setting, “mental overload” (i.e., discussing multiple topics and the APCA (African Palliative Care Association)’s Af- providing insuffi cient explanatory guidance in the rican Palliative Outcome Scale (POS). One tool used pain assessment). among cognitively impaired adults is the Pain Assess- In noncommunicative patients, however, assessment in Advanced Dementia (PAINAD) Scale. Th e ments of the extent of presenting pain will be primar- most commonly used tools for assessing children’s pain, ily based on behaviorally based proxies (e.g., facial im- in addition to the VAS, NRS, and VDS (for some chil- pression, daily activity, emotional reactions, the eff ect of dren aged over seven years old), include the FLACC consolation, and vegetative reactions) rather than rely- (i.e. Face, Legs, Activity, Cry, and Consolability) Behav- ing upon any scale whose use is premised on communi- ioral Pain Scale, the Touch Visual Pain (TVP) Scale, the cation (see Chapter 27 on Pain in Old Age and Demen- Wong-Baker FACES Pain Rating Scale, and the Pain tia for additional information). Th ermometer. Th ese tools, and how they are used, are described below, along with an outline of the compara- How do you measure a patient’s pain? tive advantages and disadvantages of each. A number of unidimensional and multidimension- Adult pain tools al tools exist that to varying degrees lend themselves to everyday use. One-dimensional assessment tools i) Visual analogue scale (VAS) simplify the pain experience by focusing on one par- Th e VAS pain rating scale uses a 10-cm-long horizon- ticular aspect or dimension, and in a challenging low- tal line, anchored by the verbal descriptors “No pain” resource, nonresearch, clinical setting they take less and “Worst pain imaginable,” on which patients make time to administer and require less patient cognitive a mark to indicate what they feel best represents their functionality than do multidimensional instruments. perception of the intensity of their current pain (Fig. 1). Often these tools have been validated in linguistically and culturally diverse settings. Additionally, they are not usually used in isolation (e.g., a body diagram may No Worst be used in conjunction with a scale indicating the se- pain pain verity of the pain experienced). (Examples of multidi- imaginable mensional tools not discussed in this chapter, which Fig. 1. Visual analogue scale. could be used for clinical and research purposes, include the McGill Pain Questionnaire (short- and long- form); the Brief Pain Inventory; the Dartmouth Pain ii) Numerical rating scale Questionnaire; the West Haven-Yale Multidimensional Using this scale, the health care provider asks patients Pain Inventory; the Minnesota Multiphasic Personal- to rate their pain intensity on a numerical scale that ity Inventory; the State-Trait Anxiety Inventory; the usually ranges from 0 (indicating “No pain”) to 10 (indi- Beck Depression Inventory, the Self-Rating Depression cating the “Worst pain imaginable”). 72 Richard A. Powell et al.

0 12345678910 0 13572 4 6 8 910 No Worst No Mild pain Moderate Severe Very Worst pain pain pain (mild) pain pain severe pain imaginable (discom- (distres- (horrible) (excruci- forting) sing) ating) Fig. 2. Numerical rating scale. Fig. 3. Verbal descriptive scale iii) Verbal descriptor scale When using this scale, the health care provider describes pain, but do not focus exclusively on pain. Th e health the meaning of pain to the patient (e.g., signifi cant feel- care provider interviews patients and their carers us- ings of unpleasantness, discomfort, and distress, and the ing a 10-item scale over four time periods on a scale signifi cance of the experience for the individual). of 0–5 that can also be completed using the “hand Th en either verbally or visually, the patient is scale.” Promoted by the WHO, the hand scale ranges asked to choose one of six descriptors (i.e. “No pain,” from a clenched hand (which represents “No hurt”) to “Mild pain,” “Moderate pain,” “Severe pain,” “Very severe fi ve extended digits (which represents “Hurts worse”), pain,” and “Worst pain possible”) that best represents with each extended digit indicating increasing levels of the level of pain intensity he or she is experiencing. pain. A pediatric version of the APCA African POS is Sometimes (as in Fig. 3), numbers are also used to ease currently being developed. the recording of the results. v) Pain Assessment in Advanced Dementia iv) African Palliative Outcome Scale (PAINAD) Scale Th e APCA African POS is a simple and brief multi- The PAINAD is an observational tool that assesses dimensional outcome measure, specifi cally for pallia- pain in patients who are cognitively impaired with tive care, that uses patient-level indicators that include advanced dementia, who as a result of their condition

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Items* 0 1 2 Score

Breathing independent Normal Occasional labored breathing. Noisy labored breathing. Long of vocalization Short period of hyperventilation period of hyperventilation. Cheyne-Stokes respirations.

Negative Vocalization None Occasional moan or groan. Repeated troubled calling out. Lowlevel speech with a negative Loud moaning or groaning. or disapproving quality. Crying.

Facial expression Smiling or inexpressive Sad. Frightened. Frown. Facial grimacing.

Body language Relaxed Tense. Distressed pacing. Rigid. Fists clenched. Knees Fidgeting. pulled up. Pulling or pushing away. Striking out.

Consolability No need to console Distracted or reassured by voice Unable to console, distract or touch. or reassure.

Total** Fig. 5. Pain Assessment in Advanced Dementia Scale. Used with permission. Copyright, Elsevier. can experience more pain or prolonged pain due to bally unable to report their pain. Each of the scale’s ﬁ ve its undertreatment. measurement categories—i.e. Face; Legs; Activity; Cry; Th e tool consists of ﬁ ve items (i.e. breathing, and Consolability—is scored from 0–2, which results negative vocalizations, facial expressions, body language, in a total score per patient of between 0 and 10 (Merkel and consolability), with each item assessed on a three- et al, 1997). Scores can be grouped as: 0 = Relaxed and point score ranging in intensity from 0–2, resulting in comfortable; 1–3 = Mild discomfort; 4–6 = Moderate an overall score ranging from 0 (meaning “No pain”) to pain; 7–10 = Severe discomfort/pain. 10 (meaning “Severe pain”). Before deciding upon a rating score, for patients who are awake, the health care provider observes the pa- Children’s pain tools tient for at least 2–5 minutes, with their legs and body uncovered. Th e health care provider then repositions the Children under 3 years old patient or observes their activity, assessing their body i) Th e FLACC Behavioral Pain Scale for tenseness and tone. Consoling interventions are ini- Th e FLACC Behavioral Pain Scale (Fig. 6) is a pain as- tiated if needed. For patients who are asleep, the health sessment instrument for use with patients who are ver- care provider observes for at least 5 minutes or longer,

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Fig. 6. FLACC Behavioral Pain Scale (used with permission). Copyright 2002, Th e Regents of the University of Michigan. 74 Richard A. Powell et al. with the patient’s body and legs uncovered. If possible, the patient is repositioned, with the health care provider touching their body to assess for tenseness and tone. ii) Touch Visual Pain (TVP) Scale Th e 10-point TVP Scale, which uses touch and observation to assess not only a child’s pain but also any anxiety or discomfort that may be experienced, is based on a Fig. 8. Wong-Baker FACES Pain Rating Scale. Used with permission. (Wilson and Hockberry 2008.) search for signs of pain and anxiety that can be assessed either by looking at, or touching, an ill child. Signs of pain and anxiety include an asymmetrical head, verbalizations describes the pain they feel, with the number assigned of pain, facial tension, clenched hands, crossed legs, shal- to that face recorded by staff . low breathing, and an increased or irregular heartbeat. On the fi rst assessment, the health care provid- Children over 7 years old er assigns a score of 1 (for present) and 0 (for not pres- i) Pain thermometer ent) across 10 items to establish a baseline score. De- An adaptation of the VDS (Fig. 9), this tool aligns a pending on the degree of pain and anxiety, medication thermometer against a range of words that describe is administered when necessary. After 20–30 minutes, varying levels of pain intensity. Th is scale was developed the child is assessed once more using the TVP scale. for patients with moderate to severe cognitive defi cits, If there is no positive change in these signs, a diff erent or with diffi culty communicating verbally, but a sub- approach to managing the child’s pain can be consid- sequent revised version (the Iowa Pain Th ermometer) ered. Importantly, whilst the TVP has yet to be rigor- has been shown to be useable among the young, too. ously validated, it is being used in low-resource settings. Patients are shown the tool and asked to imagine that, Children over 3 years old just as temperature rises in a thermometer, pain also increases as you move to the top of the scale. Th ey are i) Wong-Baker FACES Pain Rating Scale then asked to indicate which descriptors best indicate Th is scale (Fig. 8) comprises of six cartoon faces, with the intensity of their pain, either by marking the ther- expressions ranging from a broad smile (representing mometer or circling the relevant words. “No hurt”) to very sad and tearful (representing “Hurts Th e health professional documents the relevant worst”) (Wilson and Hockberry 2008), with each be- descriptor and evaluates changes in pain over time by coming progressively sadder. Th e health care provider comparing the diff erent descriptors chosen. Some re- points to each face, using the words to describe pain in- searchers have converted the indicated descriptors into tensity, and asks the patient to choose the face that best a pain score by attributing scores to each.

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Fig. 7. Touch Visual Pain Scale (Used with permission. Copyright, Dr Rene Albertyn, School of Child and Adolescent Health, University of Cape Town, South Africa.) Pain History and Pain Assessment 75 to fi nd an elderly woman with end-stage cancer curled up on her bed and crying, who periodically drifts into a semi-conscious state. How do you assess her pain? Answer: From the patient’s initial presenting behavior (crying and in a fetal position), it would appear that she is in pain. Th e severity of her condition means that she is unable to respond verbally to a pain chart or scale. Th e health care provider would therefore need to take a history from one of the patient’s carers (assuming that one is present), asking what makes her pain better or worse, how long she has been in pain, where they Fig. 9. Pain thermometer. (Used with permission. Copyright, Dr Keela Herr, PhD, RN, FAAN, College of Nursing, Th e University of think the pain is, and whether they think it is localized Iowa, 2008.) or referred, and using an observational tool such as the PAINAD. Additional questions should explore how long the patient has been in a curled position and crying, Case studies whether she is on any medication (including pain medi- Case 1 cation), and whether her pain is getting worse. In moments of consciousness, even if the patient is unable to You are working in a small, rural hospital when a verbalize responses to questions based on a pain scale, 7-year-old girl is brought in by her 13-year-old brother. she may be able to respond by squeezing the health She has AIDS and is not on antiretroviral therapy. care provider’s hand or by nodding. In that instance, She appears to be in some pain. How do you assess the health care provider should provide the patient that pain? with closed questions (e.g., with simple “Yes” and “No” Answer: Th e imperative in this instance is to control responses), providing very clear instructions on, for ex- the patient’s pain as quickly as possible; to achieve this, ample, squeezing their hand if the answer is “Yes.” Th is the health care provider has to assess her pain. Because questioning could be supplemented by a quick physical she is 7 years old, the patient should be able to verbal- examination to determine what might be causing the ize her pain. As such, the body diagram and the Wong- patient’s pain. Consequently, the health care provider’s Baker FACES Pain Rating Scale could be used in combi- assessment would be based on observation, a physi- nation to achieve an initial assessment of the location, cal examination, simple questions for the patient, and a radiation, and severity of her pain. Depending on how more comprehensive history from her carer. severe the patient’s pain is, the health care provider may be unable to complete a full assessment until the pain Case 3 has been managed. Th e assessment process should, You are working in a regional hospital. A week-old baby subject to her agreement, involve both the girl and her boy is brought in by his mother. He is experiencing pro- older brother. It would additionally be important to ex- jectile vomiting (a symptom typical of congenital hyper- plore a brief family history to determine if the child has trophic pyloric stenosis, a condition that 1 out of 500 an adult carer or whether she is being looked after ex- babies are born with) and will need surgery. Th e baby clusively by her older brother to ensure that appropriate appears tense and agitated and you suspect that he is in consent is obtained to undertake possible therapeutic pain. How do you assess the pain? interventions with the child. If an adult carer cannot be Answer: Th e FLACC scale could be used to assess the located quickly, it may be necessary to assess and treat baby’s pain. What is the expression on the baby’s face? the girl’s pain while waiting for the carer to begin to Is he lying with his legs in a relaxed position, or are they make her comfortable. restless and tense, or is he kicking? Is he lying quietly, or is he squirming or rigid? Is he crying and inconsolable? Case 2 Alongside the FLACC score, the health care You are working in a home-based care team that visits provider should speak to his mother to determine how people in a rural setting. You have arrived at a house long he has been in this condition, whether he has 76 Richard A. Powell et al. any other symptoms, whether he has a known medi- pain may be present and that cognitive restruc- cal condition, when the pain started, and what makes turing will be indicated. Another example would it worse or better? While it is possible that the under- be a decrease of pain with movement, when pos- lying cause of the pain may be treatable (and it is im- sibly osteoarthritis might be present. portant to ascertain what the underlying cause is), it is • Localization: probably the most important critical to manage his pain quickly, which should also question. Localization of the pain may differen- allow him to become more relaxed, making it easier to tiate between a radicular and nonradicular eti- ascertain the cause. ology of pain. • The items mentioned are only rough indicators Pearls of wisdom of certain etiologies. Further questioning and examination must to be undertaken to confirm • An understanding of the need to undertake an as- suspicions. sessment of pain that is sensitive to the individual patient (e.g., age, regarding cognitive ability, and References literacy). • An appreciation of the potential value of stan- [1] Baker CM, Wong DL. QUEST: a process of pain assessment in children. Orthop Nurs 1987;6:11–21. dardized pain assessment scales. [2] Breivik H, Borchgrevink PC, Allen SM, Rosseland LA, Romundstad L, • Th e ability to use pain assessment tools and make Breivik Hals EK, Kvarstein G, Stubhaug A. Assessment of pain. Br J An- aesth 2008;101:17–24. decisions within the clinical setting of the most [3] Carlsson AM. Assessment of chronic pain: I. Aspects of the reliability and validity of the visual analogue scale. Pain 1983;16:87–101. appropriate in diff erent situations. [4] Eland JM, Coy JA. Assessing pain in the critically ill child. Focus Crit • Pain assessment is not an academic exercise! Ev- Care 1990;17:469–75. [5] Gracely RH, Dubner R. Reliability and validity of verbal descriptor ery question potentially provides the therapist scales of painfulness. Pain 1987;29:175–85. [6] Herr KA, Mobily PR. Comparison of selected pain assessment tools for with essential information about the etiology of use with the elderly. Appl Nurs Res 1993;6:39–46. pain and certain fi rst steps to be undertaken to [7] Herr K, Bjoro K, Decker S. Tools for assessment of pain in nonverbal older adults with dementia: a state-of-the-science review. J Pain Symp- treat it. tom Manage 2006;31:170–92. • Pain intensity: asking for pain intensity helps you [8] McLaff erty E, Farley A. Assessing pain in patients. Nurs Stand 2008;22:42–6. to assess the need for treatment: 0–3 would mean [9] Norval DA, Adams V, Downing J, Gwyther L, Merriman A. Pain management. In: Gwyther L, Merriman A, Mpanga Sebuyira L, Schietinger generally that no change of therapy is necessary, H, editors. A clinical guide to supportive and palliative care for HIV/ 4–7 that analgesic therapy has to be changed, and AIDS in Sub-Saharan Africa. Kampala, Uganda: African Palliative Care Association; 2006. pp. 43–64. 8–10 that analgesic therapy has to be changed [10] Powell RA, Downing J, Harding R, Mwangi-Powell F, Connor S; APCA. immediately (a pain emergency). Development of the APCA African Palliative Outcome Scale. J Pain Symptom Manage 2007;33:229–32. • Pain quality: this helps you to diff erentiate the [11] Royal College of Physicians, British Geriatrics Society, and British Pain Society. Th e assessment of pain in older people: national guidelines. etiology of pain (“burning,” “shooting,” “electri- Concise guidance to good practice series, No. 8. London: Royal College cal,” etc. would be indicators of neuropathic pain; of Physicians; 2007. [12] Schofi eld P. Assessment and management of pain in older adults with “dull,” “aching,” etc. would be indicators of no- dementia: a review of current practice and future directions. Curr Opin ciceptive pain; and “terrible,” “unbearable,” etc. Support Palliat Care 2008;2:128–32. [13] Wilson D, Hockberry MI. Wong’s Clinical Manual of Pediatric Nursing, would suggest an aff ective valuation of pain). 7th ed. St. Louis: Mosby; 2008. [14] World Health Organization. Palliative care: symptom management and • Pain increase: pain increase after certain move- end-of-life care. Integrated management of adolescent and adult illness. ments or at certain times of the day helps to Geneva: World Health Organization; 2004. identify the etiology of pain (e.g., pain because of infl ammation will be often worst in the early Websites morning hours, while constant high pain levels might suggest a chronic pain disease). International Association for Hospice and Palliative Care: www.hospicecare. com/resources/pain-research.htm • Pain decrease: positions or situations in which National Institute of Health Pain Consortium: http://painconsortium.nih. the pain decreases are also helpful for assessment; gov/pain_scales/index.html e.g., if only rest—and no other coping strategies— Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) www.immpact.org is considered useful for the patient, this is important information for the therapist that chronic Pain History and Pain Assessment 77 Appendix 1

When using the body diagram (in children a broad equivalent is the Eland Colour Scale), patients are requested to indicate, using a marker, the location of their pain (which could include several sites) by shading the relevant areas. Th e severity of pain experienced can then be determined using one of the adult pain assessment tools (Appendix 2).

Fig. 10. Body diagram.

Appendix 2: Pain intensity scales Children’s pain intensity scales

Scale Advantages Disadvantages (i) Faces, Legs, Activity, Cry and Con- Th is tool is useful among children who It has not been validated among chil- solability Scale are unable or unwilling to report pain; dren with special needs, neonates, or it is quick to use and easily reproduc- ventilated children. ible. (ii) Touch Visual Pain Scale Th is tool is useful among children who Additional research is required to vali- are unable or unwilling to report pain; date the tool in diﬀ erent populations it is quick to use and easily reproduc- and settings. ible. (iii) Wong-Baker FACES Pain Rating Th is tool is simple and quick to ad- Th e tool is sometimes described as Scale minister, is easy to score, requires no measuring mood instead of pain, and reading or verbal skills, is unaﬀ ected sad or crying faces are not culturally by issues of gender or ethnicity, and universal. provides three scales in one (i.e., facial expressions, numbers, and words). (iv) Pain Th ermometer Th e tool is simple and quick to use and While overcoming some of the limita- is intuitively preferred by some patients tions of the VDS by providing an ac- instead of attempting to express their companying illustration of pain intensi- pain intensity numerically. ty, the tool may be problematic among the cognitively or visually impaired. 78 Richard A. Powell et al. Adult pain intensity scales

Scale Advantages Disadvantages Cognitively Unimpaired (i) Visual analogue scale Th e tool is quick and simple to administer, Th e tool is highly sensitive to changes is easy to score and compare to previ- in pain levels, which can hinder its use. ous ratings, is easily translated into other Some adults can fi nd the tool too abstract languages, has been validated extensively, to understand, especially among patients and is considered one of the best tools for with cognitive dysfunction, non-English- assessing variations in pain intensity. speaking patients, postoperative patients (whose levels of consciousness and attention may be altered after receiving general anesthesia or certain analgesics), and patients with physical disability such as reduced visual acuity or manual dexterity (the health practitioner marking the scale can introduce bias). (ii) Numeric rating scale Th e tool is quick and simple to use, and it Some patients are unable to complete the is easy to score and document the results tool with only verbal instructions. Conse- and compare with previous ratings. Th e quently, there is decreased reliability at the tool is well validated, can be translated age extremes and with nonverbal patients into other languages, and can be used to and the cognitively impaired. detect treatment eff ects. It is easy to teach patients its correct use. Unlike the VAS, the scale can be administered verbally, thereby overcoming problems for those with physical or visual impairments and enabling those who are physically and visually disabled to quantify their pain intensity over the telephone. (iii) Verbal descriptor scale Th e tool is quick and simple to use, easily Based on the use of language to describe comprehended, well validated and sensi- pain, the tool depends upon a person’s tive to treatment eff ects, and intuitively interpretation and understanding of the preferred by some patients instead of descriptors; which can prove to be a attempting to express their pain intensity challenge in diff erent cultures. Th e tool is numerically. problematic for use among the very young or old, the cognitively impaired, and the illiterate. (iv) APCA African Palliative Th e tool is quick and simple to use, and Th is tool, which only addresses pain as Outcome Scale provides three scales in one (i.e. numbers, a single domain in addition to others af- words, and the physical hand). fecting a patient’s life, requires a degree of staff training to ensure its consistent application. Additional research is ongoing to validate the tool in diff erent populations and settings. Cognitively Impaired (v) Pain Assessment in Advanced Th is tool is useful among adults who are Relies upon proxy indicators of pain Dementia Scale unable to report pain; it is quick to use rather than verbal self-reporting. and easily reproducible.

Note: Th e table above draws on McLaﬀ erty and Farley (2008). Guide to Pain Management in Low-Resource Settings

Chapter 11 Physical Examination: Neurology

Paul Kioy and Andreas Kopf

Why do a neurological examination? Find out the type of headache, its character, anatomical site, severity, frequency, and duration; the na- Th e main objective in a neurological examination for ture of onset, timing and periodicity; precipitating fac- a patient with pain is to identify the abnormality in tors (straining, coughing, posture, sex, etc.); relieving the nervous system that may be related to the pain factors; and associations (visual, auditory, tactile, and experience and separate central nervous from periph- dysautonomic associations etc.). Other symptoms can eral nervous lesions. It is also important not only to largely be evaluated along the same lines with variations establish a clinical diagnosis, but also to follow this up as necessary, since not all aspects apply to all symptoms. with anatomical, pathophysiological, etiological, and A history of common neurological symptoms such as possibly pathological diagnoses, if possible. Pain is the loss or impairment of consciousness, visual disturbanc- most common reason that patients seek medical con- es, speech and language disturbances, sensory distur- sultations, and it should be remembered that the pain bances, and motor disturbances (including sphincters) may not be neurological. Indeed, in origin it often is should be obtained along the same lines where possible. not. In a general overview, a quick evaluation of the Further details regarding individual symptoms can be mental state and psychological makeup of the patient added as appropriate during direct questioning to es- must be included as part of the neurological examina- tablish potential etiological factors, including exposure tion as these factors may have a signiﬁ cant impact on to drugs (alcohol included), environmental toxins, past pain behavior. injuries, and systemic illnesses. In the history, the presenting symptoms are In conclusion, at least basic neurological ex- evaluated in the usual manner, which we exemplify here aminations are indicated in every patient to detect using one of the most common symptoms in pain pa- somatic etiologies of pain, mainly lesions of the cere- tients—headaches. Headaches are important as they brum, spinal cord, and peripheral nerves, including are a very common type of pain and one that alerts pa- myopathies. Although in pain management the psy- tients to a potential neurological problem, although for- chological factors and symptomatic treatment options tunately the cause is rarely neurological. Headache still are emphasized, it is crucial for the adequate under- calls for a thorough neurological examination, however, standing of the patient’s pain to take a thorough his- as missing those uncommon neurological headaches tory and perform a thorough physical examination. (raised intracranial pressure, meningitis, tumors, etc.) It would be harmful to our patients to overlook pain may have catastrophic consequences. etiologies that could be treated causatively! Th erefore,

Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. All rights reserved. Th is material may be used for educational and training purposes with proper citation of the source. Not for sale or commercial use. No responsibility is assumed by IASP for any injury and/or damage to persons or property 79 as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends that there should be independent verifi cation of diagnoses and drug dosages. Th e mention of specifi c pharmaceutical products and any medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text. 80 Paul Kioy and Andreas Kopf an basic neurological examination is inevitable for ev- the neurological status. If cooperation is impaired, it erybody dealing with pain patients (together with an should be noted in the progress notes (e.g., “unexpect- orthopedic and psychosocial evaluation). ed/inadequate fi nding”). Th us, objective fi ndings such as muscle atrophy have greater value, since they may What is a systematic diagnostic not be voluntary infl uenced! Every examiner will experience at times “inade- procedure in a neurological quate” or “unexpected” results from the examination. To examination? diagnose a “psychogenic” etiology, however, thorough Th e examiner has to use a certain systematic ap- experience is needed. Th e patient should never be con- proach when examining the patient. Starting with fronted with the suspicion of aggravation or simulation, the symptoms presented by the patient, it is advisable so as to avoid an irreversible loss of mutual trust, but to continue trying to identify a syndrome, which in- the suspicion should be integrated into the whole pic- cludes all symptoms. A topical diagnosis may then be ture of the patient evaluation. made (which is the “level” of neurological dysfunction), which should lead to the fi nal etiological diagno- What technical support do I need sis. Paraclinical testings, such as electrophysiology and for the physical neurological imaging techniques, help by confi rming or ruling out a examination? certain etiological diagnosis. However, the availability of such technical examinations is not a prerequisite to Everything necessary for an orientating neurological make a diagnosis in many cases. Th erefore, in environ- examination should be easily available. A small collec- ments without the possibility for further testing, careful tion of instruments should be at hand. With a patellar and thorough history taking and physical examination hammer, a sharp instrument (e.g., a wooden stick or will be able to collect relevant and most often suffi - sterile cannulas), a soft brush or a piece of cotton wool, cient fi ndings to make a diagnosis, helping the clinician a wooden tongue depressor, a small fl ashlight, a tuning to understand and possibly treat neurological diseases fork (128 Hz), spatulas, and a pair of glass test tubes it causing pain. should be possible to detect relevant motor, coordination, trophic, and vegetative dysfunctions of the nervous How do I prepare the patient system. If available, an ophthalmoscope would complete the test battery. Remember that in a very busy clinic, for the examination? one may not be able to do a thorough examination for In the usual clinical manner, establish a rapport with the all patients. But with experience, one develops a quick patient and explain the nature and purpose of the exami- and effi cient personal examination protocol. nation to reassure him or her. Endeavour to gain the patient’s confi dence and trust in order to achieve the level What is the stepwise approach of cooperation that is essential for the interpretation of to performing a neurological fi ndings. Th e patient should be comfortable on the ex- examination? amination couch and adequately but decently exposed. Th e physician normally begins the examination of any How can I draw conclusions from patient with an examination of the appearance of the the neurological examination? subject in general, his/her skin and mucous membranes, followed by palpation for lumps, lymph nodes, pulses, To be able to draw conclusions from the neurological ex- and any superfi cial points of tenderness. An evalua- amination, it is advisable to follow a certain stepwise ap- tion of vital functions should normally be done at this proach to avoid imperfection. However, following a step- time, including blood pressure, pulse, respiration, and wise approach does not mean being overly schematic! temperature. Care should of course be exercised during It is important to explain the examination to palpation to avoid the obvious points of severe pain and the patient before starting because the patient’s co- tenderness this early in the examination so as to retain operation and alertness are necessary to ascertain the patient’s cooperation. Physical Examination: Neurology 81 Th e examiner develops a quick plan of the se- a general familiarization with a coma scale (such as the quence of steps in the examination, which should be famous Glasgow Coma Scale) may be useful. followed, because otherwise important aspects of the Establish that the patient is fully conscious, able examination may be missed. A checklist of activities is to understand and follow instructions, and fully orient- often useful for the non-neurologist who is not yet ex- ed in time, space, and person. Th e patient’s mood and perienced. For many, it is easy to follow the examina- emotional state (level of anxiety, depression, apathy, dis- tion in a rostral caudal direction, but one may fi nd other interest, posturing, and behavior) should be assessed. If methods equally eff ective. As a bare minimum, the ar- any impairment is noted, a full description should be re- eas listed below must be assessed in an adult patient. corded as precisely as possible. Cognitive skills can quickly assessed using sim- What items do I look for in the ple observations during history taking and can then be neurological examination? supplemented by direct examination of specifi c skills. Assessment of language pattern and fl uency can easily • Higher functions and general examination: (look pick up those patients with motor dysphasia, while abil- for level of consciousness, maybe use the Mini- ity to follow instruction in the course of general exami- Mental State Examination [MMSE] to test cogni- nation may raise the suspicion of receptive dysphasia. tive function, and check vital functions) Th e MMSE examination of Folstein et al (Mini- • Examination of the head and neck: (look for men- Mental State Examination) is a quick formal test con- ingeal irritation, such as neck stiff ness or a posi- sisting of some 30 items which can quickly be car- tive Kernig’s test, check neck muscle function and ried out in less than 10 minutes, should suspicion of a neck movement) cognitive defi cit be raised. With this tool, orientation, • Examination of the cranial nerves memory and recall, abstraction, comprehension, read- • Examination of the motor and musculoskeletal ing, drawing, and writing ability can be assessed. Where system (look for deformities, bulk, muscle tone, dysphasia is marked, testing other elements of cognition and bilateral strength) is diffi cult, if not impossible. • Examination of the sensory system (distinguish radicular and nonradicular defi cits or pain radia- How do I examine the head tion; check deep tendon refl exes and the “primi- and neck? tive” refl exes) • Cerebellar functions (test coordination with rap- Observe and palpate for deformities and tenderness id alternating hand movements, fi nger-nose and in the scalp and over the muscles—especially the tem- heel to shin test, tandem walk, one-leg stance, poralis muscles. Tenderness over the insertion of the and Romberg test) paraspinal and mastoids on the skull may be elicited • For special diagnostic questions only, certain in patients with neck muscle spasms, while occasional “technical” testing could be useful (laboratory tenderness at the vertex may be elicited in patients with tests, blood tests, cerebrospinal fl uid, electro- tension and depression headaches. physiology, electroencephalography, electroneu- Check for meningeal irritation by fl exing the romyography, testing of autonomic functions, neck and observing for stiff ness and pain along the and imaging) spine, and follow this with the Kernig’s test. Brudzin- ski’s sign is rarely observed in adults. Palpation for the How do I evaluate “higher functions”? carotid pulse will establish the presence and symmetry of the pulsations. Superfi cial and deep palpation of Th e patient’s degree of consciousness should be evalu- the neck muscles may elicit spasticity and tenderness ated and established as this is probably the most impor- and should then be followed by an assessment of neck tant point in the evaluation of a patient neurologically. movements in all directions, which may be restrict- Most patients who will be reviewed outside the emer- ed by pain, spasms, and/or osteoarthritis of the spine. gency department presenting with pain will not be in a Lhermitte’s sign may occasionally be elicited in patients coma, and an elaborate description of how to evaluate a with multiple sclerosis and spinal canal stenosis, among patient in a coma may not be necessary. Nevertheless, other pathologies. 82 Paul Kioy and Andreas Kopf What does examination of the (8th nerve) system and occasionally cerebellar lesions, cranial nerves tell us? although mentioned here with the eye motor nerves. Th e fi fth nerve is examined by assessing sen- Th e fi rst cranial nerve is commonly examined using ar- sation in the face and part of the scalp in front of the omatic non-irritant or pungent materials, such as soap, ear, together with motor activity of muscles of masti- which is easily available. Each nostril should be exam- cation (jaw clenching and opening against resistance). ined separately with the other blocked, and the patient Fast (touch) and slow (pinprick) sensations are handled is asked to determine the smell by sniffi ng. Abnormali- separately as they follow diff erent pathways and may be ties of smell are more commonly from local pathologies impaired diff erentially. Th e corneal refl ex has its aff erent in the realm of otorhinolaryngology, but they can occur arm in the ophthalmic division of the trigeminal nerve with base of skull and anterior fossa pathologies such as and would normally be included as part of its assess- fractures and tumors. ment. Examination of the second cranial nerve is the Th e seventh nerve is examined by observing most involved, but it aff ords the best source of informa- for facial symmetry at rest and when the patient at- tion about intracranial pathology. Th e optic pathways tempts to wrinkle the forehead (lift the eyebrows), close traverse the whole of the brain from the frontal to the the eyes, show the teeth, or blow out the cheeks. Taste, occipital pole, with the optic radiation opening out to which is also a function of the seventh nerve, is rarely traverse the parietal as well as the temporal lobes. As- tested routinely, but it can be tested in the anterior two- sess visual acuity roughly using a newspaper, which con- thirds of the tongue using sugar or salt on the protruded veniently has type of diff erent sizes. More accurate vi- tongue. sual acuity measurements can be done using hand-held Th e eighth nerve function may crudely be tested Snellen charts (i.e., eye charts). using a ticking watch or by rubbing the fi ngers near the Visual fi elds can be examined using the con- ear. If a hearing defi cit is suspected, ensure the patency frontation method in all four quadrants separately for of the external auditory meatus and then carry out more each eye. Th e method compares the visual fi elds of the elaborate tests such as Weber’s test or Rinne’s test to patient with that of the examiner using a colored ob- distinguish conduction from nerve deafness, or refer the ject—usually a pin head advanced from the periphery patient for more sophisticated audiometry. of each quadrant. More accurate assessment can be car- Th e ninth, 10th, and 12th nerves are examined ried out using perimetry or tangent screens. together. One should note the presence of dysphonia, Examination of the optic fundus may reveal in- palatal movement symmetry (when the patient says valuable information regarding raised intracranial pres- aaah), the gag refl ex, and tongue movement symme- sure and the state of the arteries. All patients with head- try. Pharyngeal sensation may be tested using a wooden aches should have a funduscopy done. Th e state of the probe tipped with cotton wool, testing each side sepa- arteries, silver-wiring, venous pulsations, disc color and rately, normally as part of the gag refl ex. margins should be examined and noted together with Th e 11th nerve or the spinal accessory nerve is hemorrhages and exudates if present. normally examined with the rest of the motor system. Th e examination of the papillary reactions and Th e movement of shrugging the shoulders and turning eye movements yields further information on the sec- the neck against resistance applied to the side of the jaw ond, the third, the fourth, and the sixth cranial nerves. will give an indication of any weakness in the trapezius Pupil size, shape, and reaction should be checked using or the sternocleidomastoid muscles, respectively. a bright light for direct, consensual, and accommodation reactions and noting the symmetry and prompt- ness of the responses. Check for ptosis (eyelid droop), How do I examine the motor and and note whether it is partial or complete. Eye move- musculoskeletal system? ments should be tested in all directions and include tests of conjugation. Th e presence of nystagmus should General observation for muscle wasting or hypertro- be noted and described, remembering that nystagmus phy, deformities, posturing, and presence of involun- at extremes of lateral gaze may be normal. Abnormali- tary movements (fasciculations, tremors, chorea, or ties of nystagmus refl ect abnormalities in the vestibular athetosis) should be done. When necessary, changes Physical Examination: Neurology 83 in muscle mass can further be evaluated by palpating Fast (posterior column, lemniscal, or discrimi- as the muscle contracts and/or by measuring the girth natory) sensations that include light touch (tested with of the limbs. Localized atrophy may be due to disuse a wisp of cotton wool), joint position sense, two point because of chronic pain and should be kept in mind as discrimination, and vibration. a non-neurological cause of changes in muscle mass. Slow (spinal thalamic) sensations that tradition- Ensure the patient is calm and comfortable before test- ally are represented by pain (pinprick) and temperature ing tone and limb mobility. Decreased tone is usually sensations. a feature of lower motor neuron pathology, whereas Th e patient is normally requested to close his/ increased tone (spasticity, rigidity) is a feature of up- her eyes during the tests. Th e stimulus is applied on per motor neuron pathology. Limb mobility at joints one side initially and then on two sides simultaneously should be tested in all directions allowed by the joint in corresponding parts of the body. Th e latter tests for and any restrictions noted. One should be aware that sensory extinction where the patient may fail to regis- there may be some modifi cations of tone and limb mo- ter stimulation of one side (the left usually) in lesions of bility by pain. the nondominant hemisphere. If any abnormalities are Muscle power is then tested in muscle groups detected, attempts should then follow to accurately map around the joints and in the axial musculature. A good the area of the defi cit and establish the anatomical site knowledge of segmental and peripheral nerve innerva- of the lesion or the structure involved. tion of the various muscles or muscle groups is essen- Pain and temperature tests yield information on tial in evaluating the etiopathology of any weakness. If the same systems, and therefore it may not be necessary nerve-related weakness is noted, then it is imperative to test for both in the routine patient without neuro- that it be graded according to an established scaling pathic pain. However, a positive increase or pathologi- system such as the Medical Research Council (MRC) cal increase in sensation (like dysesthesia) that may have scale. Also, establish whether it is upper motor neuron partly been picked up during history taking will need to or lower motor neuron and whether it is segmental, be elucidated further. Regions of hyperesthesia and al- diff use, distal, or peripheral in distribution. Myopathic lodynia need to be mapped out accurately, noting that weakness does not respect peripheral nerve or segmen- skin hypersensitivity to various stimuli (touch, cold, and tal demarcations and is usually more marked proximal- warmth) may be diff erent and therefore should be test- ly. Neuropathic weakness needs to be delineated and ed separately. assessed for the anatomical site of the pathology (spinal Light touch, joint position, and vibration should cord, roots, specifi c peripheral nerve, or diff use neu- be tested even though they are physiologically related in ropathy). Subtle weakness in the lower limbs may occa- that they are all fast sensations, because they may be af- sionally be picked up by requesting patients to rise from fected diff erentially in certain clinical situations. a squatting position, walk on their tiptoes or on their Higher sensory functions such as two point dis- heels, while in the upper limbs one may look for prona- crimination, graphesthesia (recognition of numbers or tor drift. letters drawn on the skin), and stereognosis (ability to Other tests may be done to elicit specifi c defi - recognize familiar objects placed in the hand) are not ciencies such as the straight leg raise to identify lumbar normally part of a routine neurological examination but disk protrusion or the femoral stretch if higher disk pa- can be performed where a cerebral lesion is suspected. thology is suspected. Th ere are numerous maneuvers in clinical practice aimed at eliciting specifi c joint or struc- What does examination ture pathology, and these can be obtained from books of the refl exes tell us? on neurology and orthopedic surgery if they are needed. Th e deep tendon refl exes are normally tested after the How do I examine the sensory examination of the sensory systems. Th e jaw jerk, the su- system? pinator, the biceps, the triceps jerks in the upper limbs and the knee and the ankle jerks in the lower limbs are The sensory system is examined guided by func- routinely tested. Others like fi nger fl exion and adductor tion and anatomy. There are two types of sensations refl exes in the upper and lower limbs respectively are not physiologically: routine. Th eir responses are usually graded in a simple 84 Paul Kioy and Andreas Kopf fi ve point system from 0 to 4: 0 = absent, 1 = decreased, Pearls of wisdom 2 = normal, 3 = increased, and 4 = increased with clonus. Of particular interest is the symmetry of responses and Suggested neurological examination tests for the pain the least force necessary to elicit the responses which patient by the non-neurologist: may be a more sensitive measure than the grading sys- Trendelenburg-test: descending of the hip to tem above. Comparison between the upper limbs and the unaff ected site with pain when walking for longer the lower limbs may yield some information regarding distances (insuffi cience of the gluteal muscles) spinal cord lesions. Before recording a refl ex as absent, “Nerve stretching” tests: the Lasègue test is a re-enforcing technique (like contracting muscles in performed in the sitting and the supine position, and other limbs or clenching the jaws) should be tried. Th e is positive if pain is felt in the back radiating to the leg hall mark of upper motor neuron defi cit remains the in- with <70° of straight leg raise, especially if fl exing the creased deep tendon refl exes, disappearance of superfi - foot on the ipsilateral site increases the pain (Bragard cial refl exes and appearance of pathological refl exes. test), which would be highly positive if pain starts at Th e pathological refl exes include Hoff man’s re- <35° and/or if pain is provoked with contralateral test- fl ex, the Trömner refl ex, the abdominal refl exes, and the ing (malingering should be suspected if the test has plantar responses, which are useful in identifying upper diff erent results in the sitting and supine position, or if motor neuron defi cits. Th e so-called primitive or frontal fl exion of the head does not increase the pain). lobe release refl exes (grasp, pouting, rooting, etc.) are • Allocation of nerve roots: hardly ever part of a routine clinical examination (with Hip fl exion (when sitting) and patellar refl ex is the possible exception of neonates) but can be carried negative (L2) out if the clinical situation demands it. Knee extension (when sitting) and patellar refl ex Th e cerebellum coordinates muscle contrac- is negative (L3) tions and movements in all voluntary muscles, and cer- Supination in ankle joint (when supine) and heel ebellar dysfunction results in symptoms of ataxia that standing negative (L4) is truncal if the fl occulonodular lobe is aff ected or limb Extension of big toe (when supine) and heel ataxia if the hemispheres are at fault. Truncal ataxia is standing negative (L5) associated with disturbed gait that is typically broad Atrophy of gluteal muscles and standing on one based and reeling and does not get worse when eyes leg negative (L5/S1/S2) are closed. Th is can be observed when the patient walks • Valleix pressure point test: provoking radiating into the examination room or when he/she is request- pain in the leg when palpating along the pathway ed to walk naturally in the room. Tandem walking (10 of the sciatic nerve on the dorsal site of the thighs steps), heel walking, and one leg stances (holding form • Leg-holding test: lifting of the straight leg by 20° more than 10 seconds) can also be tested. Th e Rom- in the supine position for >30 seconds (if <30 sec- berg’s test is usually included among the tests of coordi- onds, suspicious for myelopathy, especially when nation, although it largely assesses the posterior column the Babinski test is positive) functions and joint position sense rather than strict cer- • Tuning fork test: vibration sensitivity (negative ebellar function. result indicates polyneuropathy) Th e neurophysiological process of movement • Babinski test: forced brushing of the sole of the foot, coordination is a complex one requiring an intact as- positive when slow extension of the big toe is ob- cending sensory system, basal ganglia, the pyramidal served (indicates myelopathy with pyramidal lesion) system and the vestibular apparatus. Lesions in one of • Brudzinski test: refl exive fl exion in the hip and these structures may impair one or other aspect of co- knee joints when bending the head ordination. Fortunately such lesions will usually be ac- • Jackknife test: no spasticity at rest, but after pas- companied by other neurological manifestations that sive movement of the joints, increasing spasticity help discriminate lesions. Limb coordination to assess followed by a sudden muscle relaxation cerebellar function may be tested using a variety of • Paresis grading test: the severity of paresis is tests: the fi nger-nose test, rapid fi nger tapping, and rap- graded according to Janda at six levels (0= no id alternating hand movements in the upper limbs, and muscle contraction, 1 = <10%, 2 = <25%, 3 = the heel to shin test and foot tapping in the lower limbs. <50%, 4 = <75%, 5 = normal strength) Physical Examination: Neurology 85 • Finger-nose test: a test for coordination, and the patient trying to touch his nose with his index fi nger in a uninterrupted ample movement with his eyes closed • Romberg test: the patient should be able to stand stable with eyes closed, feet together, arms extended 90° to the front • Use a simple body scheme to document the pain reported from the patient and your fi ndings (see Fig. 1)

References

[1] Campbell WW. Pocket guide and toolkit to Dejong’s neurologic examination. Lippincott, Williams and Wilkins; 2007. [2] Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpää M, Jørum E, Serra J, Jensen TS. EFNS guidelines on neuropathic pain assessment. Eur J Neurol 2004;3:153–62. [3] Weisberg LA, Garcia C, Stub R. Essentials of clinical neurology: neurology history and examination. Available at: www.psychneuro.tulane.edu/ neurolect.

Websites

http://www.brooksidepress.org/Products/OperationalMedicine/DATA/ operationalmed/Manuals/SeaBee/clinicalsection/Neurology.pdf http://library.med.utah.edu/neurologicexam/html/home_exam.html Fig. 1. A neurological body scheme, useful for diff erentiating and lo- calizing radicular and nonradicular pain with the patient’s subjective http://www.neuroexam.com reports and the results from the physical examination. http://edinfo.med.nyu.edu/courseware/neurosurgery http://meded.ucsd.edu/clinicalmed/neuro2.htm • Refl ex testing: biceps = C5–6, triceps = C6–7, fi n- ger II + III fl exion (“Trömner”) = C7–T1, patellar ligament = L2–4, and Achilles tendon = L5–S2

Guide to Pain Management in Low-Resource Settings

Chapter 12 Physical Examination: Orthopedics

Richard Fisher

Clinical case story 1 (extremities) call anesthesiologist and instruct the operating theater to perform a closed manipulation of the fracture and apply You have been asked to see a patient in the emergency a long leg plaster splint. Th ey tell you they will be ready room of your hospital. Th e patient is a 46-year-old male in 2 hours. who was pinned between a loading dock and a truck Th e manipulation seems to work, and you apply bumper several hours ago. His left lower extremity is in a a plaster splint to three sides of the limb—leaving the an- temporary cardboard splint, and after a primary evalua- terior aspect open to allow room for swelling. Th e patient tion, he seems not to have other signifi cant injuries. He is is comfortable with oral or intramuscular pain medica- alert and will talk to you. tion, and things seem to be going well. Th e vascular and Your initial examination of the left lower ex- neurological function of the left foot and ankle seems to tremity shows a swollen calf with a mild angular defor- be improved following your reduction, although not com- mity and bruised but closed skin. Examination of the pletely normal. knee shows no eff usion, but range of motion and ligament Th e next day, just before you begin rounds, the testing are not possible because of calf pain. Likewise, the nurse calls you because the patient is having extreme range of motion of the hip cannot be tested. pain in his left calf. She has given all the pain medi- Th e patient can move his toes and ankle in both cation ordered, and it is not helping. You go quickly to directions. He states he can feel you touch the toes and examine him and fi nd that his splint is intact, but his foot, but they have a tingling feeling; slightly diff erent left leg below the knee is swollen and tense. He cannot than the right. Th e left foot is slightly cooler and seems extend or fl ex his toes. You can passively extend them paler. You cannot palpate a dorsalis pedis or posterior with mild discomfort, but if you try to passively fl ex tibial pulse. Capillary refi ll at the toes seems slower than them he screams with pain. Th ere is a diff use decrease on the right, but intact. in sensation about the foot and calf, and there is no X-ray is available, so you ask to have an X-ray feeling between the fi rst and second toes on the dorsal taken of the tibia and fi bula. Th e X-ray shows transverse surface of the foot. Yesterday you could palpate weak mid-shaft fractures of both bones with some angulation posterior tibial and dorsalis pedis pulses, but now there and minimal displacement—but little comminution. is no dorsalis pedis pulse by palpation. His capillary You decide that the fracture should be “reduced” refi ll is slower, and the foot feels cooler and looks paler [placed in proper alignment], and so you contact the on- than yesterday.

Chapter 13 Psychological Evaluation of the Patient with Chronic Pain

Claudia Schulz-Gibbins

Why is psychological assessment Th e cause of increased pain perception can in- of pain important? clude emotional components such as despair, sadness, anger or fear, but it can also be a reaction to impair- People who have painful conditions or injuries are often ment due to pain. In correlation with these processes, additionally aff ected by emotional distress, depression, the cognitive component is the belief that it is not pos- and anxiety. Chronic pain involves more than the sub- sible to have any relief of pain after unsuccessful treat- jective experience of the intensity of pain. In the last 30 ments. Believing this can, for example, increase feelings years a biopsychosocial model for understanding chron- of helplessness. Th e loss of belief in the functionality of ic pain has evolved. According to this model, chronic one’s own body is experienced as a psychological threat. pain is a syndrome with consequences such as physical Th oughts will increasingly focus on the apparently un- and psychosocial impairment. Th is model contains vari- changeable pain problem. Very often the result is a re- ables such as central processes on the biological dimen- striction of one’s whole perspective on life through sion as well as on psychological dimensions, including the focus on pain. Th e consequence is that the person somatic, cognitive, and aff ective dimensions. concerned very often retires from physical and social Th e cognitive dimension contains, besides at- activities. Family confl icts arise because of the feeling tention processes, attempts to come to terms with the of being misunderstood. Self-esteem is aff ected by the pain experienced. For example, thoughts like “the pain subsequent inability to work. Th e main focus is on con- is unbearable” or “the pain will never end” can have an sulting a doctor and obtaining a cure. Th e increasing eff ect on the aff ective dimension and intensify reactions consumption of medication is accompanied by fear and like anxiety. apprehension of side eff ects. Inactivity because of the Suff ering from chronic pain has social conse- impairment by the pain and the whole symptomatol- quences, for example, on activities of daily living, fam- ogy can cause and intensify depressive reactions such ily environment, and cultural factors, or it may be af- as passivity, increasing cogitation, lack of sleep, and fected by previous treatment experiences. Illness can be decreased self-esteem. In a vicious circle, chronic pain viewed as the eff ect of the complex interaction of bio- can lead to depressive reactions, which infl uence the logical, psychological, and social factors [2]. Emotional perception of and reactions to the pain. For example, and cognitive aspects like anxiety or helplessness in biological processes such as muscle tension can cause coping with chronic pain are correlates that can signifi - pain but can also be caused by increased depression. cantly strengthen pain perception and intensity. Depression can lead to more physical passivity, and in

Case report 2 Case report 3

A 62-year-old salesman, Mr. Andrew, reports increased A 32-year-old bank accountant, Mrs. Agbori, describes back pain after a back surgery. In the same room, he abdominal pain of several years’ duration. She had been says, there has been another patient who had the same diagnosed as having endometriosis and has had several operation. His roommate was mobilizing 2 days after surgeries, which were unsuccessful in relieving her pain. the operation and was almost pain free at the time of Th e only measure that had any eff ect on her pain, each discharge. Mr Andrew believes that during his own op- time for several months, was treatment with a “hor- eration, an error must have occurred. He considered mone preparation,” which, however, has made her “ster- that this was no surprise, given the number of proce- ile.” Th is upsets her very much because she and her hus- dures that were done daily and the stress on the doctors. band wanted children. Apart from the pain she has no He has tried to speak with his surgeon several times, other physical problems, she says. Th e relationship with only to be told that the pain would settle down soon. Th e her husband is stable, and Mrs. Agbori is very content surgeon, he thought, seemed quite abrupt with him, and at work. Her entire family is very loving and caring, and did not really take time to explain things. He cannot support her. understand the explanation of the surgeon because his During further interviews, Mrs. Agbori reports former roommate at the hospital felt fi ne immediately of having constant back pain for several years. As a afterwards. He has talked to a lot of people with similar 10-year-old she had to wear a body cast for almost half Psychological Evaluation of the Patient with Chronic Pain 99 a year. She knows that her back is “unstable and endan- quency of his headaches can interfere with everyday life, gered,” but she can deal with that; only the abdominal which puts a lot of strain on him. His wife cares about pain is a burden to her as it also impairs her sexual re- him very much and tries her best not to stress him, and lationship with her husband. Since about a year ago she has taken over doing more housework. He worries that has tried to avoid sex, because of increasing abdominal this may cause problems in the relationship. Usually, he pain afterwards. In a subsequent interview, Mrs. Ag- has looked after everything; but now his self-esteem is bori reports that she has a pronounced fear of becoming starting to be aff ected. Additionally, he has become very pregnant. She could not talk to anyone about this fear irritable because of the headaches. He has begun to lash because everyone in the family wanted her to have chil- out at small things, which he would regret afterwards. dren. She is afraid that she will not be able to go through Further psychological analysis reveals that the the pregnancy and look after her child properly. In other patient has suff ered from headaches since early child- words, she would not make a good mother. She also fears hood. His single mother had been very ill, and he had that hear back might “break apart” and she would be to take over the responsibility for the family since a very confi ned to a wheelchair. young age. Since her pregnancy, his wife has stopped working. Th is has confl icted with his wishes to off er his What does this case report show us? child a better childhood that he has had himself. Finan- Th is case report illustrates how an innate psychological cially supporting the family on his own would be very confl ict can contribute to the chronicity of pain. Th e pa- stressful; it creates feelings of being overwhelmed, and he tient has a pronounced fear of pregnancy, although she, often feels that he is not up to his tasks. During the fur- as well as her family, had a strong desire for her to have ther course of counseling, issues such as sharing responsi- a child. At the same time she harbors guilty feelings be- bilities and feelings of guilt were discussed. cause she could not fulfi l this desire. Th e pain in this context is probably made more intense by a feeling of guilt. What confl icts may prevent healing? In the framework of a family-based therapeu- A signifi cant confl ict of goals that may impede the treat- tic approach, the family is considered as a system of ment of chronic pain is the desire for retirement. Often, relationships in which the well-being of each member continuing disability leads to long periods of absen- depends on that of the others. Th is system strives for teeism at work. If the individual is forced to return to homoeostasis. A sick member of the family can, for work, there are further periods of increased absentee- example, have a stabilizing eff ect when the illness is ism. Th is can cause a change in attitude toward work a distraction from other problems, such as marital or and the workplace, including colleagues. Restoration of pregnancy problems. Th e confl ict of goals, here, could an amiable attitude to work now seems impossible. Pa- be that it is not easy for the sick person to “give up the tients very often start to think that continuing work will disease” without risking the stability of the family. In aff ect their health, and retirement is the only possibility behavioral theory, operant, respondent, and model- for a sane existence. Sometimes, employers and insurers learning mechanisms can play a role in the chronicity of demand a solution diff erent from ongoing further treat- pain. An increase in illness behavior may, for example, ment, which is expensive for them. happen when a partner gives too much emotional support. Th e illness behavior thus ensures also the attention How do we implement psychological treatment? and emotional support of third parties, which might not happen without the disease. It is more useful if the part- According to current knowledge, multimodal treatment ner helps to cope with pain, for example, by supporting concepts should be considered as soon as possible when daily activities. risks of chronifi cation become evident. A precondition for psychological pain therapy is the results of the so- Case report 4 matic examination and the psychological diagnosis. Th e aim is to reach an adequate description of the chronic A 38-year-old man reports increasing headaches since pain syndrome and an analysis of the sustained condi- his wife has become pregnant. He cannot understand it, tions of the illness process, so that an individual care he says, because the expectation of becoming a father has plan can be plotted and discussed with the patient, made him very happy. Th e increasing intensity and fre- along with a relative if possible. 100 Claudia Schulz-Gibbins What are specifi c indications for a [2] Gatchel RJ. Comorbidity of chronic pain and mental health: the biopsychosocial perspective. Am Psychol 2004;59:794–805. psychological pain therapy and interventions? [3] Jensen MP, Turner JA, Romano JM, Strom SE. Th e Chronic Pain Coping Inventory: development and preliminary validation. Pain • Evidence of a psychiatric disorder such as depres- 1995;60:203–16. sion, anxiety, somatoform disorders, and post- [4] Kendall NA, Linton SJ, Main CJ. Guide to assessing psychosocial yellow fl ags in acute low back pain. Accident Rehabilitation and Compensation traumatic stress disorder, which is causing or Insurance Corporation of New Zealand and the National Health Com- mittee; 1997. contributing to the chronifi cation of pain. [5] Koes BW, van Tulder MW, Ostelo R, Kim BA, Waddell G. Clinical • Inability to cope with chronic pain. guidelines for the management of low back pain in primary care: an international comparison. Spine 2001;26:2504–13. • High risk of chronifi cation (yellow fl ags). [6] Lazarus RS, Folkman S. Stress, appraisal, and coping. New York: Spring- • Abuse of or addiction to medication. er; 1984. [7] Lovering S. Cultural attitudes and beliefs about pain. J Transcult Nurs • Psychosocial impacts (e.g., death or illness of rela- 2006;17:389–95. [8] Magni G, Caldieron C, Rigatti-Luchini S. Chronic musculoskeletal tives, fi nancial problems, loss of job) in connec- pain and depressive symptoms in the general population: an analysis of tion with or independent of the pain. the 1st National Health and Nutrition Examination Survey data. Pain 1990;43:299–307. [9] Main CJ, Spanswick C. Pain management: an interdisciplinary approach. Edinburgh: Churchill Livingstone; 2001. Pearls of wisdom [10] Melzack R, Casey KL. Sensory, motivational and central control deter- minants of pain: A new conceptual model. In: Kenshalo D, editor. Th e skin senses. Springfi eld, IL: Charles C. Th omas; 1968. p. 423–43. • After a trusting relationship has been developed, [11] Melzack R, Wall PD. Pain mechanisms: a new theory. Science the indication for psychiatric or psychological 1965;150:971–9. [12] Murray SA, Grant E, Grant A, Kendall M. Dying from cancer in devel- treatment should be discussed with the patient. oped and developing countries: lessons from two qualitative interview studies of patients and their carers. BMJ 2003;326:368. Particularly, educative aspects (for example, the [13] Pfi ngsten M, Leibing E, Harter W, Kröner-Herwig B, Hempel D, Kro- provision of a biopsychosocial treatment con- nshage U, Hildebrandt J. Fear avoidance behaviour and anticipation of pain in patients with chronic low back pain: a randomized controlled cept) play an important role within the frame- study. Pain Med 2001;2:259–66. work, in helping the patient to acquire a better [14] Rippentrop EA, Altmaier EM, Chen JJ, Found EM, Keff al VJ. Th e relationship between religion/spirituality and physical health, mental understanding of the complexity of pain. health, and pain in a chronic pain population. Pain 2005;116:311–21. [15] Rosenstiel AK, Keefe FJ. Th e use of coping strategies in chronic low • Strategies should be developed to enable the pa- back pain patients: relationship to patient’s characteristics and current tient to cope with pain. adjustment. Pain 1983;17:33–44. [16] Turner JA, Romano JM. Behavioural and psychological assessment of • Guidelines for the management of chronic low chronic pain patients. In: Loeser JD, Egan KJ, editors. Th eory and practice at the University of Washington Multidisciplinary Pain Centre. back pain off er similar advice: Maintain physical New York: Raven Press; 1989. p. 65–79. activity and daily activities, return to work on a [17] van Tulder M, Becker A, Bekkering T, Breen A, del Real MT, Hutchin- son A, Koes B, Laerum E, Malmivaara A; COST B13 Working Group permanent basis, and avoid passive careful behav- on Guidelines for the Management of Acute Low Back Pain in Primary ior [1,5,17]. Care. European guidelines for the management of acute non-specifi c low back pain in primary care. Eur Spine J 2006;15(Suppl 2):169–91. • Th e aim is not freedom from pain but support in developing improved quality of life and coping with pain. Websites

http://www.ﬁ nd-health-articles.com/msh-pain-psychology.htm References

[1] Airaksinen O, Brox JI, Cedraschi C, Hildebrandt J, Klaber-Moﬀ ett J, Kovacs F, Mannion AF, Reis S, Staal JB, Ursin H, Zanoli G; COST B13 Working Group on Guidelines for Chronic Low Back Pain. European guidelines for the management of chronic non-speciﬁ c low back pain. Eur Spine J 2006;15(Suppl 2):192–300. Management of Acute Pain

Guide to Pain Management in Low-Resource Settings

Chapter 14 Pain Management after Major Surgery

Frank Boni

What types of surgery infectious disease. The patient should be able to tol- are we talking about? erate diagnostic and therapeutic procedures in the postoperative period and have calm periods of wake- Surgery can be grouped into four grades, as follows: fulness or sleep. The pain management should not Grade 1: Minor: examples are excision of skin le- have any detrimental effect on the already compro- sions and evacuation of the uterus; mised vital organs. Grade 2: Intermediate: examples are inguinal hernia repair and tonsillectomy; What problems do we have to deal with during the pain management plan? Grade 3: Major: examples are thyroidectomy, hysterectomy, and bowel resections; and Th e patient may be unresponsive or confused and unco- Grade 4: Very major: examples include cardiotho- operative because of his altered state of consciousness. racic surgery and joint replacements. He was probably ill for about 2–3 weeks and has had Th is grading depends on the extent and com- various kinds of treatment. plexity of the surgical operation. Th ere may be some Septicemia comes with gastrointestinal tract, problems with the classiﬁ cation when endoscopies and cardiac, respiratory, renal, and other organ dysfunctions. some newer surgical techniques are used. We will con- Th ere may be hypovolemic, cardiogenic, or septic shock sider grades 3 and 4 for our discussions. with their associated problems. Fluid and electrolyte and nutritional problems are very common in these patients.

Case report 1 Eﬀ ect of the operation and anesthesia An 18-year-old male had small-bowel resection for Th e sympathetic system might have been stimulated to multiple typhoid perforations. He has not regained con- the extreme by the illness, and any further stress may sciousness fully, 6 hours after the operation. cause the patient to decompensate. Th e patient may therefore get worse temporarily in the postoperative pe- Does he need pain relief? How would you riod as a result of the added stress of the surgery and manage his pain, if any? What objectives do we anesthesia. hope to achieve with our pain management? Although communicating with the patient may be a Methods of pain relief options problem, we still have to provide a pain-free period dur- Postoperative pain management must start with drugs ing which the patient recovers from this multisystem given intraoperatively.

Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. All rights reserved. Th is material may be used for educational and training purposes with proper citation of the source. Not for sale or commercial use. No responsibility is assumed by IASP for any injury and/or damage to persons or property 103 as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends that there should be independent verifi cation of diagnoses and drug dosages. Th e mention of specifi c pharmaceutical products and any medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text. 104 Frank Boni Local anesthetic infi ltration of the wound, how- patient. Th e fact that the patient cannot complain does ever, may not be advisable because of the generalized not mean there is no pain! Careful titration, use of mul- systemic nature of the disease and the increased risk of tiple analgesics, and good monitoring hold the key to wound infection, and the reduced eff ectiveness and in- safe and successful management. creased chances of undesirable eff ects of the local anesthetic drugs. Case report 2 After the operation, intravenous, intramuscular, or rectal paracetamol (acetaminophen) will be preferred A 75-year-old man is due for bilateral total knee replace- to nonsteroidal anti-infl ammatory drugs (NSAIDs) or ment. How would you manage his pain perioperatively? dipyrine for analgesia and antipyretic eff ects. Th is is be- What objectives do we hope to achieve cause of the high incidence of multiple organ failure. with pain management in this patient? Th ese patients will need to have small regular Th is patient must be pain-free to mobilize quickly and intermittent doses or continuous infusions of tramadol, have physiotherapy in the perioperative period. Pre- fentanyl, morphine, or any other suitable opioids that are existing comorbidity should be considered at all times. available in combination with the mild to moderate anal- Complications from drug interactions and complica- gesics mentioned above. Th ere is little evidence that one tions from multiple drug usage should be avoided. opioid is superior to another in the postoperative setting as long as equipotent doses are used and application is What is the incidence and severity of according to the specifi c drug kinetics. If the clinician is postoperative pain in joint replacement very worried about hypotension and respiratory depres- patients? sion, small doses of ketamine can be given intermittently, Joint replacements constitute some of the most destruc- as a continuous infusion with a drip or infusion pumps. tive types of surgery and are usually very painful. Most Small analgesic doses should limit the unwanted eff ects, of these patients have been in a lot of pain even before and the sympathetic eff ects may actually be benefi cial. It surgery and are already on many drugs and other forms must be stressed that all drugs have to be carefully titrat- of treatment. Th eir pain will be moderate (Grade 3) or ed according to response. Many patients in low-resource severe (Grade 4), and bad enough to limit movement countries have had limited exposure to opioids and can and normal activity. Th ere are other associated prob- be very sensitive to them. Th is applies especially to very lems of old age and immobility. Many patients come for ill patients like this one. Poor renal and liver function surgery as a last resort to get rid of their pain. We can could lead to reduced metabolism and excretion, in- therefore assume that most will have unbearable pain creasing the cumulative eff ects of drugs. after their surgery, especially when physiotherapists start mobilizing them within one or two days after the What other special actions should we take regarding his pain? operation. Very poor-risk patients like this one ideally will require What other problems do we have to consider respiratory and cardiovascular support in a high-de- regarding pain management? pendency or intensive care unit. Since most hospitals Th ese patients are usually on analgesics which may in- in low-resource countries do not have these facilities, clude combinations of acetaminophen (paracetamol), great caution must be exercised when using any drugs NSAIDs, and opioids. Some may be on steroids and for pain relief, and careful monitoring of the cardiovas- other drugs for rheumatoid arthritis and other medi- cular, respiratory, and urine output should be routine. cal conditions. Th ese drugs may have been taken for Central nervous system manifestations such as agitation long periods, and side eff ects or drug interactions are or coma may make it diffi cult to interpret the sedation not uncommon in the perioperative period. Th e el- score. Th e delayed recovery of consciousness could also derly have considerable multisystem pathology, and be due to the cumulative eff ects of sedatives and long- they may be on cardiovascular, respiratory, central acting opioids used for sedation and ventilation. nervous system, and genitourinary drugs. Th ey may be Th e take-home message would be: the general on blood-thinning drugs such as warfarin, aspirin, and poor state of the patient and the fear of hypotension any of the heparins, which may aff ect our regional and should not be reasons to avoid the use of opioids in this local anesthetic blocks. Pain Management after Major Surgery 105 The socioeconomic status of these patients be carefully conducted. In this situation, strong opioids is very important. The patients may not have family combined with NSAIDs can provide good intraopera- and financial support. If they have dementia and can- tive and postoperative analgesia. not communicate very well, pain management can be Syringe and volumetric pumps are expensive very difficult. and diffi cult to maintain, but large teaching hospitals should have them for patient-controlled analgesia What are the best pain management options (PCA) or continuous infusions in operations such as for this patient? joint replacement. Regular acetaminophen, either intra- For pain relief during and immediately after the opera- venously or orally, should be given with other oral an- tion, regional anesthesia is probably best for this group algesics such as codeine, tramadol, or NSAIDs as soon of patients. Th e duration of the operation, patient co- as patients can take oral medications. Antiemetics, ant- operation, and technical diffi culties, as well as antico- acids, and mild laxatives may be prescribed as required. agulant therapy, may make general anesthesia manda- Intravenous acetaminophen is now more aff ordable and tory. Spinal anesthesia with long-acting local anesthetic convenient than rectal acetaminophen and should be drugs together with intrathecal opioids will provide a used more often, even in low-resource countries. It is simple and eff ective anesthesia and good postopera- probably the safest multipurpose analgesic that we have tive analgesia. Th is method is well suited for any low- at the moment. resource country because patients receiving this type of anesthesia require less resources and care than patients What roles should the patient, relatives, who have general anesthesia. Small doses of diamor- and medical personnel play in the pain phine given intrathecally with the local anesthetic drugs management of this patient? can provide good analgesia for up to 24 hours post- Perioperative pain management plans should be me- operatively. Diamorphine may, however, not be freely ticulously put in place well in advance of operations like available in low-resource countries. Morphine may be this one. Th e surgeon, anesthetist, and acute pain team easier and cheaper to procure and can be an alternative. (if available) should involve the patient and the rela- Th e clinician should, however, only use preservative- tives before the operation to discuss the options. Special free morphine in the intrathecal or epidural space and forms, written instructions, and guidelines make things should be aware of the problems associated with mor- easier for patients and hospital staff . Th e appropriate phine use, which include delayed respiratory depres- scoring systems, and the use of equipment like PCA sion, itching, nausea, vomiting, and urinary retention. pumps, should be practiced with the patient before the Patients on aspirin and some prophylactic an- operation. In uncooperative or demented patients with ticoagulation can have spinal anesthesia, provided that no family support, the safest and most appropriate tech- hematological profi les are kept within normal ranges and niques should be used, and extra care should be taken in that care is taken with timing and concurrent use of pro- monitoring them. phylactic heparins. Clopidogrel and some newer drugs Th ese are just two examples of major surgery used in richer countries cause more problems and have that one can come across in poorly resourced countries. to be stopped at least 7 days before surgery and regional Th ere are many other operations, types of patients, and anesthesia. Th e timing of the dural puncture should not issues that one will come across in managing pain after be within 2 hours of giving low-molecular-weight hepa- major surgery in these countries. Some of these issues rin (LMWH) such as enoxaparin. Unfractionated hepa- will now be discussed. rin is more aff ordable but not as eff ective as LMWH in preventing deep vein thrombosis in these patients. Why is postoperative analgesia Th e single-shot spinal may, however, not be an issue? suitable for a bilateral knee replacement in this patient, and so a combined spinal epidural (CSE) can be used. Major surgical operations normally cause considerable Th is treatment is more expensive, and the incidences of tissue damage and pain. It only became possible to per- complications with anticoagulants are higher. If the du- form major operations safely and painlessly after mod- ration of the operation or the patient’s condition do not ern anesthesia was introduced about a century ago. In favor a regional technique, general anesthesia should the perioperative period, certain pathophysiological 106 Frank Boni changes caused by pain threaten the wellbeing and the need treatment, these fi gures suggest that only about rehabilitation of the patient. Pain is part of the “stress half of patients will need postoperative analgesia after response complex” to prepare the patient for “fi ght or major surgery. A closer look at publications, which are fl ight.” Poorly administered analgesia can have some mostly from developed countries, reveals that these fi g- unwanted eff ects. When we decide to treat pain, we ures are for patients who have had analgesia during and have to consider the cost implications involved. One after operations and yet still had pain. A good propor- must therefore understand the pain process and make tion of patients in developing countries will not com- good use of available resources judiciously, wherever plain of pain—although they may be in agony—because one is practicing. of cultural and other reasons. In the absence of reliable data in poorly re- Some frequently asked questions sourced countries, we can only assume that most pa- regarding pain after major tients will have moderate to severe pain after major sur- surgery include: gery. Th e real incidence of untreated postoperative pain may never be known because it would be unethical to • How common is pain after major surgery? carry out properly controlled studies by deliberately al- • What is the nature of pain and how do we mea- lowing some patients to have pain after major surgery. sure the severity? • What are the consequences of inadequate analge- What type of pain is caused sia after major surgery? by surgical trauma? • What are our goals in postoperative pain management? All patients (except a few with abnormal physiology) • How do patients and type of surgery aff ect our will have acute pain due to actual tissue damage. Most pain management? pain experts will call such pain “nociceptive pain.” Th e • Do newborn and unconscious patients have pain tissue damage will provoke chemical and nerve stimula- after surgery? tion at the local as well as the systemic levels, which can • What are the pain therapy methods available to provoke many complex responses. us after major surgery? Th e pain may be due to surgical incisions, tis- • What roles can patients, relatives, and medical sue manipulation, injury during operations, or position- staff s play? ing of the patient. On the other hand, the pain may have • Can we justify the costs and the risks involved in nothing to do with the surgery or the positioning on the the management of pain? operating room table. It may, for example, be due to pre- • Does opioid use postoperatively lead to addiction existing arthritis, chest pain, or headache from any cause. in later life? Whatever the cause or nature of the pains, it is • Should strong opioids be avoided in very ill poor- the severity that matters most to the patient. A simple risk patients? and frequently used classifi cation has four levels of pain: • Is pain threshold higher in patients in less affl uent No pain Grade 0 countries? Mild pain Grade 1 Th ere are many more questions, some of which Moderate pain Grade 2 have been partly answered by the two case scenarios Severe pain Grade 3 presented. Th ese questions can, however, be generalized It is generally accepted that grades 0 and 1 may not to cover a wider range of patients and issues found in need any treatment, but grades 2 and 3 should be treat- poorly resourced countries. ed because they can cause signifi cant morbidity. What is the incidence of pain after What consequences of pain do we major surgery? expect after major surgery? Moderate pain has been estimated to be present in Pain, as part of the so-called “postoperative stress syn- about 33% and severe pain in 10% of patients after ma- drome,” can cause considerable morbidity and even jor surgery. If all patients with moderate and severe pain mortality. Pain is usually accompanied by hormonal, Pain Management after Major Surgery 107 metabolic, and psychological responses to trauma. Ex- numeric analogue scales should not be diffi cult to use amples include the neuroendocrine changes involving routinely in even the poorest environments. Th e assess- hypophysis-adrenal responses, which can have pro- ment should tell us about the nature and severity of pain found eff ects on the body. Some of these detrimental ef- and help us to initiate and evaluate treatment. fects are summarized below. Quantifying pain may, however, be diffi cult because pain is subjective and unique to the individual. Cardiovascular system One has to be able to communicate with patients and Pain can cause a number of diff erent types of arrhyth- measure their responses. Assessor and patient factors mias, hypertension leading to myocardial ischemia, and are therefore important. To improve the accuracy of congestive cardiac failure, especially in the elderly and the various assessment methods available, we have to those with cardiac disease. educate the patients as well as medical staff in their use. Preferably, patient education and practice in using these Respiratory system methods should take place in the preoperative period. Tachypnea and low tidal volume due to painful respiratory eff orts, reduced thoracic excursions, and sputum Is the assessment of pain with retention can lead to atelectasis or chest infections. an analogue scale suffi cient Gastrointestinal system for all situations? Delayed gastric emptying can lead to nausea, vomiting, Sometimes one cannot use the most common assess- and bowel distension. ment methods such as the visual analogue scale, or they Metabolic eff ects may not be suffi cient for certain situations. In babies, and with uncooperative and unconscious patients, we Sympathetic stimulation can lead to hyperglycemia and cannot use the analogue scale. In preschool and older acid-base abnormalities such as respiratory acidosis or children, modifi ed scales can be used, but one may have alkalosis, which can lead to electrolyte imbalances and to rely on physiological parameters such as pulse rate, fl uid retention. respiration, crying, sweating, limitation of movement CNS and socioeconomic eff ects and many others. Unfortunately, pain is not the only cause of these changes, and they should be interpreted Pain can lead to uncooperative patients and can cause with caution. anxiety, depression, or agitation. Prolonged stay in the In settings like intensive care units, physiologi- hospital can put stress on individuals, families, and cal data may be the only methods that can be used. Th e health institutions. equipment required can be very expensive to purchase, Secondary consequences of pain maintain, and operate. Th ere are also some eff ects that may not initially appear to be linked to pain. Pain delays the mobilization What are our goals in postoperative of patients out of bed and, therefore, increases the risk pain management? of postoperative complications like thromboembolism, Clinicians will want to treat pain in order to prevent the bedsores, and many infections such as chest, gastroin- detrimental eff ects mentioned earlier. We would like the testinal tract, and wound infections. Th ese can be re- patients to be able to mobilize quickly out of bed. Pa- ferred to as secondary consequences. tients should be able to tolerate physiotherapy, tracheal suctioning and coughing, and other potentially painful Do we have to measure pain therapeutic and diagnostic procedures. postoperatively, and how do Patients want to breathe, talk, walk, and carry we go about it? out other functions as quickly and comfortably as possible. Th ey also want peaceful uninterrupted periods of It is very useful, but not always possible, to assess rest and sleep. When on pain treatment, they do not pain in the postoperative period. Simple and reliable want to be unduly drowsy, or have any nausea and vom- methods of pain assessment like the verbal, visual, or iting or inconveniences such as constipation. 108 Frank Boni Whatever the method of analgesia chosen, the How do we monitor the side eff ects method must be: of the analgesics we are using? • Eff ective, • Safe, and When using systemic analgesia, we are particularly con- • Aff ordable. cerned about the use of opioids. Th e side eff ects we should One should try and initiate analgesia before be most concerned about are the respiratory eff ects. Re- the pain becomes intolerable and established because spiratory depression can be diffi cult and unreliable to de- the pain cycle is more diffi cult to break once it be- tect at the initial stages. Since excessive sedation usually comes established. Once good analgesia is achieved, comes before respiratory depression, if we monitor seda- it should be maintained as long as the patient needs tion carefully and regularly, we should be able to prevent it. After major surgery, the fi rst 48 hours will be the respiratory depression. A simple sedation score like the critical period, but some patients will need analgesia one below should be used for all patients on opioids: for weeks. Analgesia can be started with intravenous Grade 0 patient wide awake strong opiates, with or without regional and local an- Grade 1 mild drowsiness, easy to rouse esthetic techniques, and gradually tapered to weaker Grade 2 moderate drowsiness, easy to rouse drugs by the oral or rectal routes over several days. Grade 3 severe drowsiness, diffi cult to rouse Th e intramuscular use of drugs immediately after op- Grade S asleep, but easy to rouse erations is not advisable because the results are not Th e key to safe use of opioids in poorly resourced coun- very predictable and they are diffi cult to control. It is tries is therefore to monitor the sedation score very close- preferable to use more than one technique or drugs to ly and avoid Grade 3 sedation. Regular monitoring, e.g., achieve our goals. by a nurse, may be considered as safe as monitoring with technical equipment! Does good acute pain control have any long-term eff ects? What other parameters should we measure in wards Although we still do not fully understand the develop- after major surgery? ment of chronic pain after surgery, we now know a lot about the incidence of chronic pain after surgery and All patients should have the following monitored after about ways to prevent its occurrence. Although the all major surgery: numbers tend to vary after most types of surgery, about • Level of consciousness one out of every 10–20 patients will have long-term • Position and posture of the patient pain after surgery, and for half of them, the pain will be • Rate and depth of respiration severe enough to need treatment. We now know that • Blood pressure, pulse, and central venous pres- good pain control, no matter how it is achieved, will sure, when indicated reduce the number of patients experiencing long-term • Hydration state and urine output pain after major surgery. • All medications being administered along with We also know that only a negligible number of analgesics patients who receive opioids for acute pain after sur- • Patient activity and satisfaction. gery will become addicted or dependent on opioids if • History, examination, and good record-keeping the drugs are used in a controlled manner. Th ere is, will reveal any problems. therefore, no justifi cation for withholding strong opi- Complications such as nausea and vomiting oids from patients because of the fear of addiction, can be troublesome and should be controlled with an- as is done in many developing countries. Ironically, tiemetics. Constipation may be a problem after pro- many patients in these countries can barely tolerate longed use of opioids, and mild laxatives like lactulose the euphoria, drowsiness, and other eff ects caused by can be used. the opioids. Some patients in poorly resourced coun- Renal, bleeding, and other problems can be tries will not accept opioids postoperatively when giv- worsened by the use of nonsteroidal anti-infl ammato- en the choice. ry drugs and other analgesics, and patients should be Pain Management after Major Surgery 109 monitored more closely if there is any cause of suspi- Invariably the following will determine the type cion from the history and examination. of methods to choose • Type and condition of the patient What pain management options do • Type of the surgery and healing period we have to choose from? • Th e training and experience of the anesthetist and other staff Peripheral analgesics • Th e resources available to treat and monitor the Peripheral analgesics are sometimes described as weak patient to moderate analgesics, and they can be used intrave- Which pharmacological alternatives may I nously, intramuscularly, rectally or orally. Examples are choose from? acetaminophen (paracetamol), ibuprofen, and diclof- Th e drugs included in the table are mostly the drugs from enac. Although they may not be able to control pain the latest essential drug list proposed by the World Health alone after major surgery, they are very useful in combi- Organization (WHO). Th e drugs marked are not included nations with one another or with opioids and other an- in that list but can be very useful. Th is applies to diamor- algesic techniques. One of the new major developments phine and some other drugs mentioned in the text. in postoperative pain management is the regular use of peripheral analgesics after all grades of surgery. Should very ill patients receive Local and regional anesthetics strong analgesics postoperatively? Th ese include wound infi ltrations during operations, Many patients are not well resuscitated and may be fi eld blocks, nerve blocks, and regional blocks of the hypovolemic after major surgery. Severe pain causes limbs and trunk. Th ese are particularly useful in the first a lot of adrenergic stimulation, which tends to tempo- 12 to 24 hours, when we are very worried about cardio- rarily keep the blood pressure up. Th is occurs at great vascular and respiratory postoperative complications. cost to the patient because of the accompanying tachy- “Central” analgesics cardia and increased oxygen consumption, and also peripheral and renal shutdown. When pain is abolished, Opioids are the most useful in this group, but in some these patients may reveal their “true” blood pressure specifi c situations, general anesthetic drugs such as in- and become hypotensive. Some medical staff therefore travenous ketamine in “subanesthetic” doses can be used avoid opioids in such patients. Th e hypotension should for pain relief without making patients unconscious. prompt medical staff to treat the patient more aggres- sively and correct the real causes. Morphine causes his- “Coanalgesics” tamine release, which may cause vasodilatation, but it is Drugs such as antidepressants and anticonvulsants are usually mild and benefi cial to the heart. frequently used in chronic pain, but they are not very Some hospital staff looking after very ill patients useful in acute pain. Intravenous steroids such as dexa- prefer to see a patient struggling and showing signs of methasone are becoming more popular for use as anti- life rather than pain free and sleeping quietly. Some tie emetics after surgery, but they have not been proven to up such patients to their beds when they are struggling. reduce postoperative pain signifi cantly. Others resort to sedatives and hypnotics, such as diazepam or even chlorpromazine. Many patients are rest- Nonpharmacological methods less because they have pain or a full bladder. Sedating or Tender loving care (“TLC”), heat and cold applica- restraining such patients may do more harm than good tions, massage, and good positioning of the patient and should not replace adequate pain relief. can all reduce pain after surgery and do not add much to the costs of treatment. Th ese methods should be Is the pain threshold higher in used more whenever possible. Transcutaneous electri- patients from poorer countries? cal nerve stimulation (TENS), acupuncture, and other methods are not currently considered clinically useful Th ere is no real evidence for this surmise. Although after major surgery. expressions and the reactions to pain may diff er from 110 Frank Boni

Drug Dose Route Frequency Acetaminophen 0.5–1 g i.m., i.v., rectal t.i.d. or q.i.d. Diclofenac* 50–100 mg i.m., rectal b.i.d. or t.i.d. Ketorolac* 10–30 mg i.m. or i.v. Morphine 2.5–15 mg i.m. 4–6 hourly 0.5–2 mg i.v. Titrate 2 mg Epidural Once daily 0.1–0.2 mg better recommend titration Intrathecal One dose only Pethidine (meperidine) 25–150 mg i.m. 3–4 hourly 5–10 mg i.v. Titrate 10–25 mg Intrathecal One dose only Dipyrone* 10–15 mg/kg i.m., i.v. t.i.d. Ketamine 0.25–0.5 mg/kg i.m., i.v., epidural Titrate i.v. dose Bupivacaine 1 mg/kg Wound inﬁ ltration End of operation 1–2 mg/kg Epidural or caudal

Tramadol 50–100 mg Oral/i.v. 8-hourly p.r.n. Hyoscine butylbromide 20–40 mg as gastrointestinal Oral/i.v. 8-hourly p.r.n. or genitourinary antispasmodic Abbreviations: b.i.d., twice daily; i.m., intramuscular; i.v., intravenous; q.i.d., four times daily; t.i.d., three times daily; * Not on the WHO essential drug list, but can be useful in poorly resourced countries.

one region to another, one cannot make such general- resources, to carry out audits and compare outcomes to ized statements about pain after major surgery. Many other countries. patients in developed countries may be more exposed Acute pain services may vary but share some to analgesics, and their expectations for pain relief basic structures: may be higher, compared to patients in developing • Patients and the general public need to be edu- countries. Th ey may, therefore, request more drugs cated about acute pain and its management in the and will be able to tolerate them better. Pain is, how- perioperative period. Consent is not normally re- ever, no respecter of race or class, and every individ- quired except for experimental and research pur- ual must be treated as unique. Th e modern defi nition poses. of pain acknowledges the role of the person’s environ- • Protocols and guidelines need to be developed for ment, culture, and upbringing and these should be all health personnel taken into account when evaluating or managing pain • Th e use of mild and moderate analgesics such as from any cause. acetaminophen, NSAIDs, and dipyrine should be encouraged as much as possible. Intravenous, How to organize pain management rectal, or oral routes can be used in an upward or downward stepladder manner depending on the after major surgery circumstances. • Intraoperative wound infi ltration by surgeon is Minimum services for maximum eff ect usually eff ective in the immediate postoperative Every hospital, no matter how remote or small, should period and should be used whenever feasible. endeavor to provide eff ective pain relief after every • Local and regional-pain relieving techniques have major surgery. Pain relief may require the barest mini- an important role in any acute pain service and mum of staff drugs and equipment. Th e type of acute should be encouraged. pain service provided will diff er depending on the cir- • Opioid analgesics should be readily available and cumstances. Th e World Health Organization and other used routinely. world bodies recognize the need for universal guide- • Antagonists to drugs, resuscitation drugs and lines like those developed for chronic cancer pain. Such equipment, and good monitoring are essential in guidelines help countries, especially those with the least all institutions where major surgery is done. Pain Management after Major Surgery 111 • Th e acute pain service should organize regular • Optimum monitoring of the patient should in- ward rounds, run emergency services for com- clude equipment for respiratory monitoring, in- plications, carry out research, and conduct audits cluding pulse oximetry and cardiovascular moni- on pain management. toring, and fl uid input/output charts. • It should, however, be emphasized that the best Advanced pain management services in monitors are the doctors, nurses, and other teaching hospitals and other specialized units health personnel with the help of relatives and • Th ese facilities should aim to have acute pain any other persons around. Simple sedation ob- service with guidelines and protocols to cover servation charts and early warning charts for ad- children and adults in accident and emergency verse events will help manage even the most dif- wards, operating rooms, and recovery wards as fi cult patients in the least well-resourced areas. well as general wards. • At least one or two doctors and an identifi ed What are pain considerations pain nurse should be able to follow up diffi cult and problematic postoperative cases and to man- after some specifi c major surgical age any complications arising from postoperative operations? pain or its treatment. General surgery (e.g., thyroidectomy, gastric and bowel • A recovery ward and a high-dependency unit and resections, major burns, and abdominal trauma) if possible an intensive care unit will be required Patients will have moderate to severe pain for some of the major operations or for very ill (Score 2–3). It does not matter if they are emergency or patients in order to treat pain eff ectively in the elective cases. More care must be taken with emergency immediate postoperative period. Relying on the cases because systemic analgesic drugs may mask symp- sympathetic responses caused by pain to artifi - toms and signs of diseases. cially prop up the patient’s blood pressure is not • Antispasmodics such as hyoscine butylbromide acceptable and may cause more harm than good. are useful in colic pains. • Th ere should be staff training programs to train • General surgery covers a wide spectrum of opera- personnel to manage pain safely at all levels and tions and pain-relieving techniques. Local and re- especially in high-risk patients after major sur- gional anesthetic blocks are grossly underused. gery. Obstetrics and gynecology (e.g., abdominal hysterectomy, cesarean sections, pelvic clearance for cancer) What equipment and what drugs Patients will have moderate to severe pain are required for postoperative (Score 2–3). Considerations include: pain management? • First trimester. Choose drugs carefully and avoid those that aff ect the fetus. • Simple hypodermic needles or preferably can- • Before delivery of the baby by cesarian section, nulas and syringes and intravenous infusion lines opioid use should be avoided as it aff ects the fe- may be all that is needed to treat most patients. tus. Syringe and infusion pumps are being increas- • Deep vein thrombosis, bleeding, and other hema- ingly used for continuous, patient-controlled, or tological problems aff ect pain management. nurse-controlled analgesia. Th e prices and avail- • Women may seem to tolerate pain better than ability of these pumps should improve sooner or men, but this is not a general rule. later and make it possible for poorly resourced • Nausea and vomiting are very common and countries to procure them. should be adequately treated. • Th ere should be a wide range of drugs to refl ect Trauma and orthopedic operations (e.g., fractures of the the range of patients and operations carried out. neck of the femur with moderate pain or shoulder, knee, Th e WHO essential drug list may not be ade- or hip reconstruction with very severe pain) quate for managing pain after major operations, • Head injuries. Some clinicians are reluctant to even in poorly resourced countries. use opioids, but they can be used safely. 112 Frank Boni • Acute abdomen. Analgesics may mask acute ab- • Scalp and other head and neck nerve blocks can domen signs perioperatively. be very useful. • Regional and nerve blocks can be used in many • Nausea and vomiting may be a problem. clinical situations. • Dihydrocodeine or other “weak” opioids are pre- • Multi-organ failure must be considered when ferred by some health workers to stronger opi- choosing and titrating drug doses. oids, because of the view that they causes less Major pediatric operations (e.g., cleft palate repair with respiratory depression. However, if doses are severe pain, pyloric and bowel surgery with moderate titrated carefully to the desired eff ect and ade- to severe pain, anal and genitourinary malformation quately monitored, any opioid may be used safely. repair with severe pain, exomphalus and gastroschi- Ear, nose, throat, dental, and maxillofacial operations sis with severe pain, and thoracic surgery such as dia- (e.g., jaw fracture fi xation with moderate pain, tonsillec- phragmatic hernia and tracheoesophageal fi stulae with tomies with moderate but sometimes severe pain) very severe pain) Common problems include: Problems related to the management of pediat- • Airway concerns, especially with bleeding, in- ric patients include: creased secretions, and opioids. • Technical, physiological, and biochemical diff er- • Danger of sleep apnea, restlessness, or dimin- ences from adult patients. ished states of consciousness. • Drugs doses and drug delivery systems require • Nausea, vomiting, and retching are to be avoided special training. as much as possible. • Parents and staff role are more critical than in • Pethidine (meperidine) may have advantages of adults. anticholinergic eff ects over other opioids. • Th e view that newborns do not need pain relief is Genitourinary operations (e.g., prostatectomy, urethral no longer valid. reconstruction, and nephrectomy, which can all be very Cardiothoracic operations (facilities for cardiopulmo- painful, but fortunately these are easy to manage with nary bypass are not usually found in poorly resourced regional techniques) countries, but one may still need to do thoracotomies • Th e patients are usually elderly with geriatric and and lung resection for tuberculosis and chest tumors. major medical problems. Chest trauma, repair of aneurysms, esophageal surgery, • Intrathecal and epidural local anesthetics with and some valve repairs and closure of congenital mal- opioids are commonly used. formations can all be very painful, especially when the • Some theoretical problems, such as spasm of sternum and ribs are split). sphincters caused by morphine, are rarely en- Special problems include: countered. • Use of anticoagulants and problems with regional and local anesthetic blocks. Septicemia • Heavy sedation and ventilation ideally will re- Septic patients are common in poor countries. Many of quire intensive care units. these patients may not be suitable for regional and local • Heart and lung function may be compromised, anesthesia and analgesia if there is frank septicemia. but good pain management can prevent or control Th ere may also be unpredictable drug eff ects major complications and help with physiotherapy. from opioids, nonsteroidal anti-infl ammatory and Neurosurgical operations (e.g., major spinal surgery with other potent drugs because of multiorgan failure. Ac- severe pain, craniotomy and resection of brain tumors etaminophen and dipyrine, if they are not contraindi- with moderate pain, trauma and skull fractures with cated, will help with the pain and the pyrexia seen in moderate pain) septic patients. • Care should be taken in interpreting the Glasgow Coma Scale with opioids. Pearls of wisdom • Large doses of opioids can cause hypoventilation and increase intracranial pressure. • Acute pain after major operations provides few • It may be advisable to avoid nonsteroidal anti- benefi ts and numerous problems for patients and infl ammatory drugs. should be treated whenever possible. Pain Management after Major Surgery 113 • Treatment of pain may, however, cause its own • International and national drug regulatory bodies problems and should be planned and practiced in partnership with governments and local sup- with clear written guidelines and protocols. pliers should make opioids more available and • Education and involvement of the patient, the reduce restrictions on their use for pain manage- family, and all medical staff are all important for ment in developing countries. any pain management program to succeed. • Universal acute pain management protocols and References guidelines need to be encouraged by WHO and other professional and regulatory bodies. Region- [1] Allman KG, Wilson I, editors. Oxford handbook of anaesthesia, 2nd ed. New York: Oxford University Press; 2006. al and local modifi cations will be required to re- [2] Amata AO, Samaroo LN, Monplaisir SN. Pain control after major sur- fl ect the type of patients and the type of surgery, gery. East Afr Med J 1999;76:269–71. [3] Matta JA, Cornett PM, Miyares RL, Abe K, Sahibzada N, Ahern GP. as well as the resources available. General anesthetics activate a nociceptive ion channel to enhance pain and infl ammation. Proc Natl Acad Sci USA 2008;105:8784–9. • Even in poorly resourced countries, eff orts [4] Scott NB, Hodson M. Public perceptions of postoperative pain and its should be made to provide enough funds to im- relief. Anaesthesia 1997;52:438–42. [5] Wheatley RG, Madej TH, Jackson IJ, Hunter D. Th e fi rst year’s experi- prove standards of postoperative care, especially ence of an acute pain service. Br J Anaesth 1991;67:353–9. pain management. • All medical personnel should be trained to over- Websites come the fear of strong opioid analgesics and other methods of pain relief, and to develop a www.anaesthesia-az.com positive attitude toward all patients who have had Anesthesia, pain, and intensive care management www.postoppain.org major surgery. Good site for pain management in ideal situations • More use of local anesthetic drugs and tech- www.nda.ox.ac.uk/wfsa niques, and also the use of peripheral analgesics, Updates aimed at poorly resourced countries www.who.int/medicines should be encouraged after all types of surgery. Drug policies and control, including essential drugs list

Guide to Pain Management in Low-Resource Settings

Chapter 15 Acute Trauma and Preoperative Pain

O. Aisuodionoe-Shadrach

When acute trauma occurs, the diagnosis and purposeful ries that may pose a potential danger to life besides the management of pain should be of paramount concern. obvious left ankle injury. Intravenous access is obtained for the admin- Case report istration of fl uids and/or medications, and Dr Omoy- emen then performs a thorough evaluation of the pa- A 38-year-old man, John Bakor, is brought to the ac- tient’s pain using a standardized assessment tool, the cident and emergency room after being knocked down verbal rating scale (VRS). John’s VRS = 7/10, suggesting by a small vehicle. He was transported in the back seat that he is having acute severe pain. Th e doctor admin- of a saloon car without any splint to his injured leg isters 50 mg of pethidine (meperidine) intramuscularly and had jolts of pain every time the car stopped on its (i.m.) as a preliminary analgesic before the injury is bumpy ride to the hospital. formally reviewed and dressings are changed, and i.m. John is received by Dr Omoyemen, the attend- tetanus toxoid is administered to prevent tetanus. ing resident, who after putting a full-length aluminium After dressings are complete, adequate regular gully-splint to immobilize his left lower limb, asks for analgesia is commenced (pethidine 50 mg i.m., 6-hour- a helping hand to move him onto a hospital stretcher. ly). Finally, while John is awaiting formal orthopedic Fracture immobilization on its own minimizes pain surgical review, his pain is reassessed regularly to deter- due to the fracture injury by limiting movement of the mine the eff ectiveness of the analgesic regimen, which is aff ected parts. A quick review reveals that John had also periodically reviewed as required. sustained an open fracture with dislocation of the left ankle and has multiple skin bruises over his left fore- Questions you should ask yourself arm and thigh. He is fully conscious, knows who he is, and their probable answers and is well oriented as to time and place. He is then checked for other injuries that he may have ignored as What is pain? inconsequential or may be unaware of, such as other Acute pain results from tissue damage, which can be bruises or lacerations. Dr Omoyemen obtains a brief caused by an infection, injury, or the progression of a history of the nature of the accident and proceeds to metabolic dysfunction or a degenerative condition. specifi cally evaluate for secondary injuries such as Acute pain tends to improve as the tissues heal and blunt abdominal injuries, or chest wall or pelvic frac- responds well to analgesics and other pain treatments. tures. Th e benefi t of this evaluation is to identify inju- We know that pain is a subjective sensation, although

Mild pain VAS=1-3/10

IM/IV Pentazocine IM/IV NSAID’s Cold/Hot compresses

Tolerable pain

Yes Re-evaluate Moderate pain No VAS=4-6/10 Proceed to planned denitive Rx Cold/Hot compresses IM/IV Tramadol IM/IV Pethidine

Tolerable pain

Yes Severe pain No Re-evaluate VAS=7-10/10 Proceed to planned IV/IM Morphine denitive IV/IM Fentanyl Rx Proceed to planned denitive treatment

Fig. 1. An algorithm of the management of pain in the acute trauma/perioperative setting. favor of getting them prepared as quickly as possible for • Opioids may be required for moderate to se- surgery. Adequate analgesia facilitates the evaluation and vere pain. subsequent treatment of the underlying injury or disease. • Combined treatment with opioids and nonopioids is often appropriate, and nonopioids may be What is the attitude of the patient to pain? employed to reduce the opioid dose requirement. Except when the cause is very obvious, as in the case of • Nonpharmacological treatments may be helpful a fractured limb, the patient does not know the diagno- but should not preclude drug treatment. sis, but only knows the symptoms—pain. Often, pain What are the principles of eff ective management is poor. acute pain management ? When or how soon should active • Unrelieved pain may have negative physical and management of pain be instituted in the acute psychological consequences. trauma/preoperative setting? • Aggressive pain prevention and control before, Immediately after diagnosis, the principles of eff ec- during, and after surgery and medical procedures tive management of acute pain should be adopted and does result in both short- and long-term benefi ts. pain control instituted immediately (Fig. 1). Th e goals of • Successful evaluation and management of pain treatment are to relieve pain as quickly as possible and is partly dependent on a positive relationship be- prevent any adverse physical and psychological respons- tween the patient and his or her relatives on the es to acute pain. one hand, and the doctor and nurses on the other. • Patients should be actively involved in pain evalu- Th e general principles of acute pain relief ation and control. include the following: • Pain control must be evaluated and reevaluated at • Analgesic selection is based on the pathophysi- specifi c regular intervals. ological mechanism of pain and its severity. • Attending physicians and nurses must have a • Both opioid and nonopioid analgesics are highly high index of suspicion for pain. eff ective for nociceptive pain. • Total elimination of all pain is not practically • Nonopioid agents are preferred for mild pain. attainable. 118 O. Aisuodionoe-Shadrach What specifi c roles should the doctors and • Don’t believe that the ability to tolerate pain is a nurses play in ensuring that patients in this measure of “manhood.” scenario are pain-free? • Th e truth is that pain is not meant to be tolerated. Th e clinicians should proceed to quantify the patient’s • It may not be practical to expect patients in the degree of pain using the following methodical ap- acute trauma/preoperative setting to be absolute- proaches: ly pain-free. • A brief oral pain history documented at the time • However, pain can be reduced to tolerable levels of admission. by using widely available techniques. • A measurement of the patient’s pain using a self- • Develop an algorithm for the management of reporting instrument, e.g., VAS or VRS. pain in the acute trauma/perioperative setting, as • Th e use of behavioral observation as an adjunct shown in Fig. 1. to the self-report instruments. • Monitoring of the patient’s vital signs (although References this is not a specifi c or sensitive test for pain). Th ese procedures should be repeated at peri- [1] Aisuodionoe-Shadrach IO, Olapade-Olaopa EO, Soyanwo OA. Preop- erative analgesia in emergency surgical care in Ibadan. Tropical Doctor odic intervals by the attending health professional with 2006;36:35–6. [2] Reuben SS, Ekman EF. Th e eff ect of initiating a preventive multi- a view to assessing the effi cacy of the analgesic regimen. modal analgesic regimen on long-term patient outcomes for outpa- Further measures include ensuring good patient posi- tient anterior cruciate ligament reconstruction surgery. Anesth Analg 2007;105:228–32. tioning with the use of pillows and blankets in addition [3] Reuben SS, Buvanendran A. Preventing the development of chronic to the application of hot or cold compresses as needed. pain after orthopedic surgery with preventive multimodal analgesic techniques. J Bone Joint Surg 2007;89:1343–58.

Pearls of wisdom Websites

• Avoid misconceptions and recognize culturally Pain: current understanding of assessment, management, and treatments. determined beliefs about pain. (2001). National Pharmaceutical Council and Joint Commission on Accredi- tation of Healthcare Organizations. • Always remember that pain cannot be ignored. Available at: http://www.npcnow.org/resources/PDFs/painmonograph.pdf Guide to Pain Management in Low-Resource Settings

Chapter 16 Pain Management in Ambulatory/Day Surgery

Andrew Amata

Case report should be given at regular intervals for the fi rst 48 hours, and oral tramadol or codeine ordered as required (rescue John, a 5-year-old boy, had an orchidopexy done un- analgesia) for unrelieved moderate to severe pain. der general anesthesia. Th e perioperative period was uneventful, and the child (accompanied by his mother) was discharged home, fully awake and comfortable Why is analgesia for minor about 5 hours after the procedure with a prescription surgical procedures a topic of oral paracetamol (acetaminophen). Problems began worth reading about ? later that night when the child woke up complaining of signifi cant pain around the operation site. Th e mother In this section, I will explain why pain may be a com- gave him the prescribed analgesic, but the pain per- mon and signifi cant problem in seemingly minor sur- sisted, and the child had now become inconsolable and gical procedures and how such pain can be eff ectively unable to go back to sleep, keeping the parents and the managed. Postoperative pain should be considered a other siblings awake. complication of surgery with signifi cant adverse eff ects, Th is sort of scenario is unfortunately very com- and every eff ort should therefore be made to avoid or mon and causes unnecessary pain, distress, and suff er- minimize it. It is obvious that there are various options ing, not only to the patient but often to the whole house- for providing eff ective and safe analgesia after minor hold. Th e good news is that this type of situation is easily surgical procedures. Satisfactory analgesia should be preventable or at least eff ectively treatable in most cases feasible for every patient, irrespective of geographical by applying simple and safe methods of pain relief. location or level of resources. For our illustrative case above, an example of a typical pharmacological analgesia therapy can be as fol- What is minor surgery? lows. Paracetamol and/or a nonsteroidal anti-infl ammatory drug (NSAID) is given orally as a premedication Surgery is commonly classifi ed as major or minor de- about 1 hour before surgery or as a suppository after in- pending on the seriousness of the illness, the parts of duction of anesthesia. A caudal block or a fi eld block or the body aff ected, the complexity of the operation, and local infi ltration with bupivacaine or ropivacaine local the expected recovery time. Minor surgical procedures anesthetic is administered after induction of anesthe- now constitute the majority of procedures carried out sia. Postoperatively, oral paracetamol and/or an NSAID in health care facilities because of greater awareness and

Guide to Pain Management in Low-Resource Settings

Chapter 17 Pharmacological Management of Pain in Obstetrics

Katarina Jankovic

Case report Systemic administration includes the intravenous, intramuscular, and inhalation routes. Regional techniques Charity, a 28-year-old offi ce worker living in Nyeri, ar- are comprised of spinal and epidural anesthesia. Epidu- rives late one evening at Consolata Hospital. She is in ral anesthesia has gained popularity in the last decade her fi rst pregnancy and is accompanied by her mother and has almost replaced systemic analgesia in many Jane, an experienced mother who thought it would be obstetric departments, mostly in developed countries. about the right time to see the obstetrician, since Char- Regional techniques are widely acknowledged to be the ity’s contractions had become more and more regular. only consistently eff ective means of relieving the pain On admission, Charity says she would like to try to go of labor and delivery, with signifi cantly better analgesia through the labor without pain killers, but as contrac- compared to systemic opioids. tions become stronger, she starts screaming for help. What could you do to relieve the pain? What are the advantages of systemic analgesics? Do all women in labor have pain that requires analgesic treatment? Systemic analgesics may be administered by individuals who are not qualifi ed to perform epidural or spinal Th e pain of labor and delivery varies among women, blocks, and so they are often used in situations when an and even for an individual woman, each childbirth may anesthesiologist is not available. Th ey also are useful for be quite diff erent. As an example, an abnormal fetal pre- patients in whom regional techniques are contraindicat- sentation, such as occiput posterior, is associated with ed. Th e most popular agents are opioids (e.g., morphine, more severe pain and may be present in one pregnancy, fentanyl, butorphanol, pethidine [meperidine], and tram- but not the next. It may be estimated that one in four adol). While the sedative side eff ects of opioids are gener- women in labor require analgesia. ally unwanted and irritating for the patient, in the labor- ing woman sedation induces relief and general relaxation. What are the application routes Analgesic eff ects sometimes appear to be secondary. for analgesia if needed? A systematic review of randomized trials of parenteral opioids for labor pain relief was able to Pharmacological approaches to manage childbirth pain show that satisfaction with pain relief provided by can be broadly classifi ed as either systemic or regional. opioids during labor was low, and the analgesia from

Table 1 Relative infant dose and clinical signifi cance of selected analgesic agents Relative Infant AAP* Drug Dose (%) Clinical Signifi cance Approval Ibuprofen 0.6 None detected in infants; no adverse eff ects. Yes Ketorolac 0.16 to 0.4 Milk concentrations are very low; no untoward eff ects reported. Yes Naproxen 3.0 Long half-life; may accumulate in infant. Bleeding, diarrhea reported in one infant. Short-term use acceptable; avoid chronic use. Yes Indomethacin 0.4 Milk concentrations low; plasma concentrations low-to-un- detectable in infants; caution with chronic administration. Yes Morphine 5.8 Oral bioavailability poor; milk concentrations generally low; considered safe; observe for sedation. Yes Methadone 2.6, 5.6, 2.4, 1.0 Milk concentrations low; approved for use in breastfeeding mothers; will not prevent neonatal abstinence syndrome. Yes Meperidine (pethidine) 1 Neurobehavioral delay, sedation noted from long half-life metabolite; avoid. Yes Fentanyl <3 Milk concentrations low; no untoward eff ects from exposure in milk. Yes *American Academy of Pediatrics. Transfer of drugs and other chemicals into human milk. Pediatrics 2001. without active metabolites, such as ibuprofen, should Postpartum anesthesia perhaps be preferred. Th e use of aspirin (acetylsalicylic acid) in sin- Nonopioid analgesics gle doses should not pose any signifi cant risks to the Non-opioid analgesics generally should be the fi rst suckling infant. Aspirin, due to its causal association choice for pain management in breastfeeding postpar- with Reye syndrome, generally is not recommended in tum women, as they do not aff ect maternal or infant breastfeeding mothers. However, the absolute transfer alertness. of aspirin into milk is negligible (< 2.4%), about 1 mg/L • Acetaminophen and ibuprofen are safe and eff ec- of milk, when following clinical doses. It is unlikely that tive for analgesia in postpartum mothers. there is enough aspirin in milk after the mother’s use of • Parenteral ketorolac may be used in mothers who an 82-mg tablet to predispose the infant to Reye syn- are not subject to hemorrhage and have no his- drome, but this is not certain. tory of gastritis, aspirin allergy, or renal insuffi - Th e use of pethidine (meperidine) in the peri- ciency. natal period is increasingly controversial. Although the • Diclofenac suppositories are available in some drug is used commonly in obstetrics, such use is gain- countries and are commonly used for postpartum ing disfavor as more sedation is reported in newborns. analgesia. Levels in breast milk are extremely low. When administered to mothers, the drug has been • COX-2 inhibitors such as celecoxib may have found to produce neonatal respiratory depression, de- some theoretic advantages if maternal bleeding is creased Apgar scores, lower oxygen saturation, respi- a concern. Th e possible advantages must be bal- ratory acidosis, and abnormal neurobehavioral scores. anced against higher cost and possible cardiovas- Pethidine is metabolized to norpethidine, which is ac- cular risks, which should be minimal with short- tive and has a half-life of approximately 62 to 73 hours in term use in healthy young women. newborns. Because of this prolonged half-life, neonatal Both pain and opioid analgesia can have a depression after exposure to pethidine may be profound negative impact on breastfeeding outcomes; thus, and prolonged. Th e transfer of fentanyl into human milk mothers should be encouraged to control their pain is low. In women receiving doses varying from 50 to 400 with the lowest medication dose that is fully eff ective. μg intravenously during labor, the amount found in milk Opioid analgesia postpartum may aff ect babies’ alert- was generally below the limit of detection (<0.05 μg/L). ness and suckling vigor. However, when maternal pain 126 Katarina Jankovic is adequately treated, breastfeeding outcomes improve. breastfeeding because of negligible maternal plas- Especially after cesarean birth or severe perineal trauma ma levels achieved. Extremely low doses of mor- requiring repair, mothers should be encouraged to ad- phine are eff ective. equately control their pain. • Continuous postcesarean epidural infusion may be an eff ective form of pain relief that minimizes Intravenous medications opioid exposure. A randomized study that com- • Pethidine should be avoided because of reported pared spinal anesthesia for elective cesarean with neonatal sedation when given to breastfeeding or without the use of postoperative extradural mothers postpartum, in addition to the concerns continuous bupivacaine found that the continu- of cyanosis, bradycardia, and risk of apnea, which ous group had lower pain scores and a higher vol- have been noted with intrapartum administra- ume of milk fed to their infants. tion. In general, if treatment of a lactating mother • Th e administration of moderate to low doses of with an analgesic drug is considered necessary, the low- intravenous (i.v.) or intramuscular (i.m.) mor- est eff ective maternal dose should be given. Moreover, phine is preferred because transfer to breast milk infant exposure can be further reduced if breastfeeding and oral bioavailability in the infant are lowest is avoided at times of peak drug concentration in milk. with this agent. As breast milk has considerable nutritional, immuno- • When patient-controlled i.v. analgesia (PCA) is logical, and other advantages over formula milk, the chosen after cesarean section, morphine or fen- possible risks to the infant should always be carefully tanyl is preferred to meperidine. weighed on an individual basis against the benefi ts of • Although there are no data on the transfer of na- continuing breastfeeding. lbuphine, butorphanol, or pentazocine into milk, there have been numerous anecdotal reports of a psychotomimetic eff ect when these agents are If I have no opioids available, used in labor. Th ey may be suitable in individuals do I have any pharmacological with certain opioid allergies or other conditions options to relieve the discomfort described in the preceding section on labor. of childbirth in my patients? • Hydromorphone (approximately 7 to 11 times as potent as morphine) is sometimes used for ex- A variety of diff erent drug classes are used in obstetrics treme pain in a PCA, i.m., i.v., or orally. Following when regional techniques and opioids are not available. a 2-mg intranasal dose, levels in milk were quite While neuroleptics (promethazine) and antihistamines low, with a relative infant dose of about 0.67%. (hydroxyzine) are specifi cally indicated in nausea and Th is correlates with about 2.2 μg/day via milk. vomiting, other drug classes have a direct eff ect on the Th is dose is probably too low to aff ect a breast- distress of childbirth through their anxiolytic, sedative, feeding infant, but this drug is a strong opioid, and dissociative activity. Above all, a single small dose and some caution is recommended. of benzodiazepines may be used (mainly midazolam or diazepam). In prodromal and early stages of childbirth, Oral medications barbiturates (secobarbital or pentobarbital) may be a • Hydrocodone and codeine have been used world- choice, and in experienced hands ketamine or S-ket- wide in millions of breastfeeding mothers. Th is amine may be helpful. With “analgesic doses,” which are history suggests that they are suitable choices, only a fraction of the anesthetic dose, cholinergic and even though there are no data reporting their central nervous system eff ects are usually absent. Tram- transfer into milk. Higher doses (10 mg hydroco- adol, which has some opioid-like eff ects but acts mostly done) and frequent use may lead to some seda- by a unique mechanism, would be another alternative tion in the infant. choice for analgesia. Tramadol is recommended at a dose of 50–100 mg i.m. or i.v.; with effi cacy similar to that of Epidural/spinal medications pethidine or morphine, it has fewer maternal side eff ects • Single-dose opioid medications (e.g., neurax- and no neonatal depression. All of these drugs pass the ial morphine) should have minimal eff ects on placental barrier and may induce sedation (“sloppy child”) Pharmacological Management of Pain in Obstetrics 127 in the neonate. Th erefore, if the use of these drugs is un- method. “Her Majesty is a model patient,” declared Dr avoidable, postpartum observation of the neonate (for Snow. He refused to disclose any more details, despite approximately 8–12 hours) is required. many importunate inquiries from the Queen’s loyal subjects. Th e social elite in London soon followed the What is the oldest analgesia Queen’s lead, adding further credibility to the use of method still in use, and can it still anesthesia. Th e Lancet deplored the use of this “un- be recommended? natural novelty for natural labor”; however, royal sanc- tion helped make anesthesia respectable in midwifery On Queen Victoria’s request, Dr. John Snow provided as well as surgery. Chloroform is no longer in use, but for her eighth childbirth (Prince Leopold) the newly the method has withstood the test of time. Th e inhala- developed chloroform anesthesia with an open-drop tion method of analgesia in labor now uses 50% nitrous

Table 2 Use of analgesics in pregnancy Medication Risk Comments Opioids and Opioid Agonists Meperidine 1 Morphine 1 Neonatal narcotic withdrawal is seen in women using long-term opioids Fentanyl 2 Hydrocodone 1 Almost all cause respiratory depression in the neonate when used near delivery

Oxycodone 2 Used for treatment of acute pain: nephrolithiasis, cholelithiasis, appendicitis, injury, Propoxyphene 2 postoperative pain Codeine 1 Hydromorphone 2 Methadone 3 Nonsteroidals Associated with third-trimester (after 32 weeks) pregnancy complications: oligohy- Diclofenac 4 dramnios, premature closure of ductus arteriosus Etodolac 4

Ibuprofen 2/4 Both ibuprofen and indomethacin have been used for short courses before 32 weeks Indomethacin 2/4 of gestation without harm; indomethacin is often used to arrest preterm labor Ketoprofen 4 Ketorolac 4 Naproxen 4 Sulindac 4 Aspirin Full-strength aspirin 4 Full-strength aspirin can cause constriction of the ductus arteriosus Low-dose (baby) aspirin 1 Low-dose (baby) aspirin is safe throughout pregnancy Salicylates Acetaminophen 1 Widely used Salicylate-Opioid Combinations Acetaminophen-codeine 1 Widely used for treatment of acute pain Acetaminophen-hydrocodone 1 Acetaminophen-oxycodone 1 Acetaminophen-propoxyphene 2 1 = Primary recommended agent 2 = Recommended if currently using or if their primary agent is contraindicated 3 = Limited data to support or prescribe use 4 = Not recommended. 128 Katarina Jankovic oxide in oxygen. It was introduced in clinical practice are inadequate for mid-forceps delivery (see paragraph more than 100 years ago, and it remains a standard on “pudendal and paracervical block”). analgesia method in obstetrics departments (“anaesthesia de la reine”). Later on, other inhalation (“vola- If epidural analgesia is available, tile”) agents such as halothane also came into use. Th e parturient self-administers the anesthetic gas using which patients will benefi t most? a hand-held face mask. Th e safety of this technique Indications for epidural analgesia include maternal reis that the parturient will be unable to hold the mask quest, anticipated diffi culty with intubation for surgi- if she becomes too drowsy, and thus will cease to in- cal delivery, a history of malignant hyperthermia, some hale the anesthetic. It is easy to administer and safe for cardiovascular and respiratory disorders, AV malforma- both mother and fetus. Th e analgesia is considered to tions, brain tumors, and morbid obesity, as well as pre- be superior to opioids, but less eff ective than epidural eclampsia and HELLP syndrome (hemolytic anemia, el- analgesia. Although there are data on maternal desatu- evated liver enzymes, and low platelet count). ration, recent studies have not demonstrated any ad- Absolute contraindications include patient reverse eff ects on mothers or neonates. Inhalation agents fusal, allergy (although “true” allergy to local anesthetics such as 0.25–1% enfl urane and 0.2–0.25% isofl urane is rare), coagulopathy (to avoid spinal/epidural hema- in nitrous oxide have given better analgesia in labor toma; negative history is considered suffi ciently eff ective than nitrous oxide alone. Desfl urane has been used to identify patients at risk), skin infections at the site of as 1–4.5% in oxygen for the second stage of labor, but needle entry (to avoid epidural abscess formation), hy- 23% of women reported unwanted amnesia during the povolemia (to avoid profound hypotension from the period of usage. sympathetic block that comes with epidural analgesia of the lumbar and sacral segments), and increased in- What is a simple and eff ective tracranial pressure (herniation of the cerebral contents regional anesthesia method for the through the foramen magnum with distal pressure loss second stage of labor that is easy after dural puncture). to learn and may be applied by the non-anesthetist? If epidural analgesia is used, could it be a single-shot technique? Th e pudendal nerve block is useful for alleviating pain Which drugs should be selected, arising from vaginal and perineal distension during the and where should the catheter second stage of labor. It may be used as a supplement for epidural analgesia if the sacral nerves are not suffi - should be placed? ciently anesthetized, and as a supplement for systemic For labor analgesia, epidural catheters are usually in- analgesia. Pudendal nerve blocks may also be performed serted at the level of L2–3 or L3–4. Th e main drugs to provide analgesia for low-forceps delivery, but they used for this method are local anesthetics and opioids.

Table 3 Chemical characteristics of commonly used local anesthetics in labor Lidocaine Ropivacaine Bupivacaine L-Bupivacaine Molecular weight 234 274 288 325 pKa 7.7 8.0 8.2 8.1 Lipid solubility 2.9 3 28 25 Mean tissue uptake ratio 1 1.8 3.3 ? Uv/Mvtot ratio* 0.6 0.28 0.3 0.3 Protein binding (%) 65 98 95 98 * Uv/Mvtot ratio represents fetal/maternal concentration ratio of the total drug plasma concentration (protein bound + unbound) of maternal and umbilical venous plasma. Pharmacological Management of Pain in Obstetrics 129

Table 4 Characteristics of commonly used opioids in labor Morphine Fentanyl Sufentanil Pethidine Diamorphine Lipid solubility 816 1727 39 1.4 280 Normal epidural 50–100 μg 5–10 μg 25–50 mg 3–5 mg 2.5–5 mg doses Onset time (min) 5–10 5–10 5–10 30–60 9–15 Duration (h) 1–2 1–3 2–4 4–12 6–12

Epidural requirements diff er in pregnancy, and in- Midwives can be trained to give low-dose inter- jection of a dose of local anesthetic results in a 35% mittent top-ups as the mother requires. Th e resulting increase in segmental spread compared to the non- analgesia is excellent, and there is no need for expen- pregnant state. Bupivacaine is the most popular local sive devices. Th e main benefi t of the intermittent tech- anesthetic in use. Care has to be taken to avoid high nique—compared to continuous infusion—is the reduc- blood levels by overdosing or accidental i.v. or intra- tion in the use of bupivacaine and fentanyl throughout arterial injection (high blood concentrations may pro- labor, along with reduced side eff ects, especially motor duce arrhythmias of the reentry type). Whether other block. local anesthetics (e.g., levobupivacaine or ropivacaine) Patient-controlled analgesia is a choice for the have less toxicity or less motor-fi ber-blocking poten- technically sophisticated obstetrics department. Th e pa- tial, or both, is under discussion. tient can receive self-administered boluses by pressing a Th e most commonly used epidural opioids are button. An electronic pump is required, and the patient fentanyl and sufentanil. Th ey are sometimes eff ective in must be thoroughly educated about using the device. early labor, but they usually need supplementation with For a background infusion, usually a dose of 10 mL/h a local anesthetic as labor progresses. Th e main advan- is used, with a preset lockout interval of about 15–30 tage of epidural opioids is that they improve the qual- minutes. Mothers have welcomed the reduction in mo- ity of analgesia and reduce the dose of local anesthetic tor block with this method and some of them decide to needed. Th is reduction is considered an advantage, get up to use the toilet and to sit in a comfortable chair since local anesthetics can produce unwanted motor by the bedside. Although not necessary in most cases, block. Th erefore, most obstetric anesthesiologists com- someone should be at the patient’s side to support her bine a diluted mixture of a local anesthetic with a small whenever she wants to get in case orthostatic hypoten- opioid dose to achieve what is called a “walking epidu- sion develops. Mobilization is safe if the mother can ral.” perform a bilateral straight leg raise while sitting in bed Th e most commonly used combination is a low- and a deep knee bend while standing, provided she feels dose mixture of fentanyl (2–2.5 μg/mL) and bupivacaine steady on her feet. Unfortunately, there is no evidence (0.0625–0.1%). Continuous infusions or intermittent that active mobilization reduces the risk of assisted de- boluses or both of these agents can be given throughout livery. Cardiotocography (CTG) (monitoring of fetal labor, but the initial loading dose of 10–30 mL of the heartbeat and uterine contractions) can be performed same mixture has to be given initially in divided doses. intermittently. If continuous monitoring is indicated for Epidural solutions for labor may be continuous- obstetric reasons, the mother can be seated in a chair or ly given for 12 hours or more. Drugs can be adminis- standing by the bedside. tered via a catheter, and the analgesia can be maintained Complications of labor analgesia include hy- by varying the infusion rate to provide an upper sensory potension (with much lower incidence nowadays with level to T10. Low-dose local anesthetic/opioid mixtures low concentration of local anesthetic), accidental i.v. are commonly started at 8–15 mL/h with the rate in- injection, unexpected high block (total spinal/subdural creased or top-ups of 5–10 mL given for breakthrough blockade), urinary retention, pruritus, accidental dural pain (minimum time between boluses: 45–60 min). Al- puncture (the more troublesome and common prob- ternatively, a mixture of 0.0625% bupivacaine and sufen- lem), catheter migration, unilateral/partial blockade, tanil 0.25 μg/mL can be used at the same dose. and shivering. 130 Katarina Jankovic Accidental intravascular injection usually oc- mL), low-concentration formulation of bupivacaine/fen- curs as a result of accidental placement of the epidural tanyl will initiate good analgesia. Additional 3-mL dos- catheter into an epidural vein. Th us, even a small dose es are given if pain persists after 15 minutes. Another can produce central nervous system eff ects. Care should reasonable option for providing second-stage analgesia be taken to avoid accidental placement in the fi rst place is to perform a spinal or combined spinal and epidural with repeated aspiration tests and applying only smaller (CSE) using a local anesthetic-opioid combination (e.g., doses of local anesthetics at any one time (avoiding large 2 mg isobaric bupivacaine intrathecally). Th is method volumes of bolus applications). Unexpected high block is has a rapid onset, so that the patient is comfortable and often the result of the catheter being placed advertently can even be ready for cesarian section within 5 minutes. into the subarachnoid space. Low-dose local anesthetic/ opioid mixtures, if given accidently intrathecally, will not If vaginal delivery is unsuccessful produce total spinal block with respiratory depression, and caesarian section is necessary, but can cause motor block and dysesthesias and will how should one proceed with intra- frighten the patient (and the physician). For intrathecal (“spinal”) application of local anesthetics, the total dose and postoperative analgesia? of drug injected is more important than the total volume Our patient from the beginning of the chapter has been in which it is given. A high block can also, very rarely, monitored for fetal heart rate, and the obstetrician is be the result of a subdural block. Th e subdural space is indicating urgent cesarian section due to fetal distress. located between the dura and the arachnoidea. While Th en you might think about using spinal instead of gen- the epidural space extends only up to the foramen mag- eral anesthesia, since it is easy, cheap, safe, and provides num, the subdural space extends all the way upward. prolonged analgesia. Th is space can be entered unintentionally at any stage of Over the past 15 years, there has been a large labor. Subdural block should be recognized by an unex- increase in the number of cesarian sections done under pected increase in anesthesia level and presentation with regional anesthesia. It is therefore tempting to advocate slow onset, patchy blockade, minimal sacral analgesia, that general anesthesia is no longer indicated, but cer- cranial nerve palsies, and a relative lack of sympathetic tain factors must be taken into account when changing blockade. Subsequent injection of large volumes of local the standard anesthesia technique from general to spi- anesthetic into the subdural space may rupture the ar- nal anesthesia. It is important to remember that when achnoidal mater and exert intrathecal eff ects. spinal anesthesia is used, the standard of care cannot be lower than for general anesthesia. Is there a “best time” for initiating Th e work-up for the mother having an elective epidural analgesia? or emergency cesarian section is the same regardless of the anesthesia plan. Th is must include preoperative fast- Occasionally, a parturient reaches the second stage of ing, if possible, and preparation of gastric content with labor before neuraxial analgesia is requested. Th e pa- appropriate antacids. Th e anesthetist must have access tient may not have wanted an epidural catheter earlier, to all the equipment (including diffi cult airways equip- or the fetal heart rate tracing or position may necessi- ment) and recovery facilities required for both tech- tate assisted delivery (e.g., using forceps or vacuum ex- niques. tractor). Initiation of epidural analgesia is still possible Spinal anesthesia is probably safer (one study at this point, but the prolonged latency between cathe- calculated 16 times safer) than general anesthesia, pro- ter placement and start of adequate analgesia may make vided it is performed carefully with good knowledge of this choice less desirable than a spinal technique. On the maternal physiology. Diffi cult airways and obesity-relat- other hand, the initiation of an epidural catheter cannot ed edema become less of an issue, but remember that be done be too early. Th e argument that early catheter a pregnant woman lying supine can become hypoten- placement may prolong the fi rst stage of labor has not sive, even without augmenting the problem by giving be confi rmed in studies. If an epidural is used, ultra-low local anesthetics intrathecally. Poor management of this concentrations of local anesthetics may not be adequate problem can cause severe hypotension, vomiting, and to relieve the intense pain of the second stage. Adding 3 loss of consciousness, which can lead to aspiration of mL 0.25% bupivacaine to the standard high-volume (20 gastric contents. Pharmacological Management of Pain in Obstetrics 131 Fundamental diff erences in the spread of local cell volume. Minimal preload of 200–500 mL is good anesthetic between a pregnant and nonpregnant woman enough in most situations in combination with a vaso- must be respected, and an unacceptably high block can re- pressor. Th ere is some evidence that a combination of sult in spinal (or epidural) anesthesia. Some medical con- colloid and crystalloid i.v. infusion can decrease the in- ditions can cause additional problems, all related to poor cidence of hypotension. Vasopressin agents commonly compensatory response to rapid change in afterload in low used to correct hypotension are ephedrine (6–10 mg cardiac output states, e.g., aortic stenosis, cyanotic congen- i.v. bolus or as an infusion) and phenylephrine (25–100 ital heart disease, and worsening of venous shunting. μg i.v. intermittent boluses). Phenylephrine is a drug of choice when tachycardia is undesirable. What are the other pros and Th ere are certain situations when a general anes- cons for regional anesthesia thetic will be more appropriate than a regional one. Th ese in caesarian section? situations include maternal refusal of regional blockade, coagulopathy, low platelet count, anticipated or actual Regarding the risk of hemorrhage, it appears that there severe bleeding, local infection of the site of insertion of is less bleeding to be expected in cesarian section under the spinal or epidural needle, anatomical problems, and regional blocks. In contrast, general anesthesia, when certain medical conditions. Lack of time is the most com- using inhalation agents, carries the risk of uterine relax- mon reason to choose general anesthesia, although for a ation and increased venous bleeding from pelvic venous skilled clinician, time is not an issue. If there is an epidu- plexuses. Although there is a traditionally held view that ral catheter in place, assessment and top-up should not regional anesthesia should be avoided whenever hemor- take more than 10 minutes, which is usually more than rhage is expected in gestosis, the favorable infl uence of enough time for the majority of circumstances. regional blocks on this disease may on the contrary be Maternal hypotension is a common complica- an argument for regional anesthesia. tion of blockade of sympathetic nerves, most character- Postoperative pain is better managed after re- istically cardiac sympathetic nerves. Th is complication gional anesthesia in both obstetric and nonobstetric can lead to a sudden drop in heart rate with low cardiac patients, perhaps due to a reduction in centrally trans- output, and if aorto-caval compression is not avoided mitted pain, as suggested in laboratory work. Postopera- there will be persistent hypotension that can compro- tive recovery is improved, and mothers are able to bond mise the baby. Th e height of a sympathetic block can be with their babies sooner. Th e lack of drug eff ects in the a few dermatomes higher than the measured sensory newborn, seen when regional anesthesia is used, means level. Th is complication is seen more in women who less intervention for the baby. Poor condition of the come for elective sections more often than in those who newborn after a regional technique is related to a pro- are already in labor, because the reduced amount of fl u- longed time from uterine incision to delivery and to ma- ids after the rupture of the membranes causes less aor- ternal hypotension, fetal acidosis, and asphyxia, unlike to-caval compression, and because maternal physiologi- after general anesthesia, where the baby’s low APGAR cal adjustments have already taken place. score will probably be due to sedation. Supplementation of intraoperative analgesia can Whenever the newborn is already distressed be used, when performed with vigilance for sedation. and acidotic, attention must be paid to avoiding aorto- Fifty percent nitrous oxide in oxygen, i.v. ketamine 0.25 caval compression and maternal hypotension. Th e full mg/kg, and fentanyl 1 μg/kg have been shown to be safe lateral position must be adopted in all mothers expected and eff ective. Intravenous sedatives such as diazepam to develop severe hypotension. Traditionally used i.v. can help a very anxious mother. crystalloid infusion preload has been shown to be unreliable in eliminating hypotension. Rapid infusion of a Is there a “cookbook” large volume of fl uid can cause a sudden rise in central approach to spinal anesthesia venous pressure and lead to pulmonary edema in pre- for cesarian section? disposed parturients. Intravenous crystalloid preload will not reduce the need for vasopressors, and the in- With the smaller needles, with their atraumatic pencil- fusion must consist of a very large quantity, e.g., 40–59 point tips, the rate of headache is less than 1% unless mL/kg, and must signifi cantly aff ect maternal packed the mother is very short or very tall. Factors like patient 132 Katarina Jankovic positioning and the size of pregnancy can infl uence the involved early on, if surgery seems likely. Th e epidural spread and extent of the block. Reducing the dose of must be topped up as soon as possible, unless a very local anesthetic to less than 10 mg hyperbaric or plain recent top-up has been given during labor, and then 0.5% bupivacaine without any opioid added can give an 20 mL of plain 0.5% bupivacaine seems to be the best inadequate block. Fentanyl can be added at a dose range choice. Once the top-up has been given, the anesthe- of 12.5–15 μg. Increasing the dose beyond this recom- siologist must stay with the patient all the time, check mended dose does not seem to provide better analgesia her blood pressure, and have diluted ephedrine at intra- or postoperatively. Patient positioning does not hand. Th e safest position for the mother during trans- seem to infl uence the fi nal level or height of the block, port to the operating room is the full lateral position. but it interferes with the rate of onset and spread of the If there is any inequality in the spread of the block on local anesthetic. Th e sitting position is commonly used initial assessment, put the mother in the full lateral po- by many anesthesiologists, but a lateral position can be sition on the side of the poor block and give the top- used too. up. Th e average time for this block to take eff ect is Th e block extended to T5 to light touch is an about 15 minutes. eff ective level for this type of surgery, using either the epidural or spinal technique. Th e only diff erence may be Pearls of wisdom that a more profound block is achieved more easily with the intrathecal block. Th ere are a variety of pharmacological options for managing the pain of parturition. Opioids administered systemically act primarily by inducing somno- How to test the block lence, rather than by producing analgesia. Moreover, It has been found that absence of sensation to cold is placental transfer of opioids to the fetus may produce two dermatomes higher than sensation of pinprick, neonatal respiratory depression. Th e advantage of sys- which in turn is two dermatomes higher than sensation temic analgesia is its simplicity. Fancy techniques such to light touch. Th at means that light touch is the best as intravenous patient-controlled analgesia (PCA) are method to test the level of the block. If sensation to light nice but not necessary to achieve good analgesia. An touch is lost at the level of S1 to T8–6 (the level of the adequately trained midwife or obstetrician is able to nipples is around T5), there is adequate anesthesia for provide excellent nurse- or physician-controlled an- the surgery. Th e extent of the motor block mirrors the algesia in locations where an anesthesiologist is not block of light touch (with the corner of a tissue or a ny- available or if regional analgesia (epidural and/or spinal) lon fi lament) and is mostly adequate with complete ab- is contraindicated. sence of hip fl exion and ankle dorsifl exion. Th e anesthe- Regional analgesic techniques are the most reli- tist should always use the same technique to assess the able means of relieving the pain of labor and delivery. block, and it is important to do so bilaterally. Measuring Furthermore, by blocking the maternal stress response, the thoracic dermatomes must be done about 5 cm lat- epidural and spinal analgesia may reverse the untow- eral to the midline. ard physiological consequences of labor pain. Another advantage of the epidural technique is that an in situ epidural catheter may be used to administer anesthet- If an epidural is already in use ics to provide pain relief for instrumental or cesarean for a vaginal delivery, but cesarean delivery, if required. If no epidural catheter is in place section is necessary, how should already, spinal anesthesia—a safe and easy technique— one proceed? may be a good and perhaps even preferable alternative for general anesthesia. Th e volume of epidural top-up to convert epidural an- For cesarean delivery under neuraxial anesthe- algesia for labor into epidural anesthesia for cesarian sia, the primary drug used is a local anesthetic. If an section is variable. If surgery is urgent, a large initial epidural approach is used, 2% lidocaine with epineph- bolus of local anesthetic is required for fast and reli- rine, 5 μg/mL, is a reasonable choice, because systemic able onset of anesthesia. Initially, the existing block cardiotoxic eff ects are relatively unlikely to occur. Al- must be assessed, and the anesthesiologist must be ternatively, 0.5% bupivacaine or ropivacaine may also Pharmacological Management of Pain in Obstetrics 133 be used. If a spinal approach is used, 10 to 15 mg of Websites hyperbaric bupivacaine provides reliable anesthesia. Hyperbaric lidocaine has fallen into disfavor because www.oaa-anaes.ac.uk Obstetric Anaesthetists Association of a high incidence of neurotoxic eff ects, even though www.rcoa.ac.uk these eff ects have been reported primarily in nonpreg- Royal College of Anaesthetists nant patients. www.aagbi.org Association of Anaesthetists of Great Britain and Ireland www.eguidelines.co.uk References Electronic guidelines http://bnfc.org BNF for Children [1] American College of Obstetricians and Gynecologists and American Academy of Pediatrics. Guidelines for perinatal care, 6th ed. 2007. www.bnf.org [2] Larsson C, Saltvedt S, Wiklund I, Pahlen S, Andolf E. Estimation of British National Formulary (BNF) blood loss after cesarean section and vaginal delivery has low va- www.world-anaesthesia.org lidity with a tendency to exaggeration. Acta Obstet Gynecol Scand World Anaesthesia Society 2006;85:1448. [3] Penn Z, Ghaem-Maghami S. Indications for caesarean section. Best www.britishpainsociety.org Pract Res Clin Obstet Gynaecol 2001;15:1. British Pain Society

Management of Cancer Pain

Guide to Pain Management in Low-Resource Settings

Chapter 18 Abdominal Cancer, Constipation, and Anorexia

Andreas Kopf

Case report fl ammation,” said he just needed some rest, and gave him diclofenac (75 mg t.i.d.) as a painkiller. Yohannes Kassete, 52 years old, and married with Taking diclofenac regularly in an adequate dose four children (12, 15, 21, and 23 years old), is a cook instead of irregular 500-mg doses of aspirin actually re- born in Addis Ababa, who has found work in the rail- lieved most of the pain for some time, so that Mr. Kassete way restaurant of Nazret. About four times a year he could resume his job in Nazret. Being a cook, he was a travels on the Djibouti-Addis Ababa railway to see his little overweight, so he did not mind that he was losing family at home. weight over the next 3 months, since he did not feel like When he fi rst experienced stomach pain, he sus- eating. When he started to have some nausea, he also pected that he did not tolerate food as well as when he reduced his fl uid intake. Unfortunately, he then started was younger. Also, he attributed it to his increasing sor- to experience increasing diffi culty relieving himself. Pa- rows because business was deteriorating. Common aids paya seeds, he knew, would help, but that did not relieve such as aspirin and an occasional smoke of “bhanghi” him of the abdominal pain, which he attributed solely to did relieve some of the symptoms, but not all. Th e next constipation. With decreasing weight, increasing upper time he was traveling to Addis Ababa he felt almost re- abdominal pain, and recurrent nausea, he was seen at stored, but when he was with his family, he was struck the local health station. Since the pain was radiating to with the most intense pain he had ever felt in his life. his back, they suspected some spinal problem due to his When the pain did not go away the next day, his brother, constant standing and bending in the kitchen, and a x- who works at the Ambassador Bar, which caters lunch ray of the spine was taken, which showed no spinal prob- for the doctors of the Tikur Ambessa Hospital across lem. Nevertheless, codeine 50 mg p.r.n. was prescribed. Churchill Avenue, made an “unoffi cial” appointment Mr. Kassete felt weaker and weaker, and when the pain with a doctor of internal medicine. increased, he increased his dose of codeine. Since he was Although Yohannes was reluctant to see the doc- worried, he used his next trip to his family in Addis Aba- tor, his brother pushed him until he agreed. On physical ba for another visit to the doctor his brother knew. examination, the doctor suspected a “mass” in the upper When this doctor was not available, he was seen left abdomen and scheduled an abdominal sonography. by another colleague from the internal medicine depart- Th e results were devastating; cancer of the head of the ment, who admitted him immediately when seeing him: pancreas was most likely. Th e doctor did not dare to re- he had a maximally extended abdomen, with no bowel veal the diagnosis to Mr. Kassete and talked of “some in- movements on auscultation. Rectal examination revealed

Th e nociceptive pain conducting aff erent nerve fi bers of some of the visceral organs meet sympathetic eff er- Why are some people reluctant to ent fi bers before reaching the spinal cord in knots called use morphine or other opioids in nerve plexuses. From here, the pain-conducting fi bers patients with gastrointestinal cancer? continue via the preganglionic splanchnic nerves to the spinal cord (T5–T12). Th is situation allows an interest- From early studies, we know that one of the undesired ing therapeutic option: interruption of the nociceptive eff ects of morphine is the induction of spasticity at the pathway with a neurolytic block at the site of the celiac sphincter of Oddi and bile duct. Th is opioid side eff ect plexus. Th is is one of the few remaining “neurodestruc- is mediated through the cholinergic action of opioids tive” therapeutic options still considered useful today. as well as through direct interaction of the opioids with Nerve destruction at other locations has been shown to mu-opioid receptors. Consequently, in the past there cause more disadvantages than benefi ts to the patient, was some reluctance to use morphine. Instead pethidine such as anesthesia dolorosa (pain in the location of (meperidine) was preferred. Recent studies have not nerve deaff erentation). confi rmed these fi ndings, and so morphine can be used without reservations. How does the patient typically describe his intra-abdominal pain? Where and how should neurodestructive techniques be Generally, pain of the intra-abdominal organs originates used? from the stimulation of terminal nerve endings, and is referred to as visceral-somatic pain, as opposed to pain For upper abdominal cancer, the target structure would from nerve lesions, which is called neuropathic pain. Th e be the celiac plexus. For colon and pelvic organ can- pain characteristic most often reported by the patient is cers, the target is the myenteric plexus, and for bladder that it is not well localized. Patients typically describe the and rectosigmoid cancers, the hypogastric plexus is the pain as generally “dull” or “pressing,” but sometimes “col- target. Usually these structures are easy to identify us- icky.” Pain intensity is assessed as in all other pain etiolo- ing landmarks and fl uoroscopy. If available, a comput- gies, with the visual or numeric analogue scale. ed tomography (CT) scan would be the gold standard 140 Andreas Kopf for identifying the targets. However, these techniques months in the past year: should only be used by experienced therapists—book • Two or fewer discharges weekly. knowledge is defi nitely insuffi cient. • Physical eff ort to discharge with major pressing. Th e indication for a neurolytic block in pancre- • Hard and bulbous feces. atic cancer is well recognized because of the rapid pro- • Feeling of incomplete discharge. gression of the disease and its insuffi cient sensitivity to • Manual maneuvers for discharge. radiotherapy and chemotherapy. From the literature, we know that up to 85% of patients do benefi t from a neuro- Are patient complaints lytic block. Some patients can even be taken off opioids. Although serious side eff ects from neurolysis of the ce- about constipation similar liac plexus are rare, the facts have to be explained to the around the world? patient, and an informed consent form should be signed. It is estimated that worldwide 1 in 8 individuals suff er, at least from time to time, from constipation. Regional In gastrointestinal cancer, pain is diff erences in prevalence have been described in North frequent, but what other symptoms and Latin America as well as in the Pacifi c region, cause the patient suff ering? where the prevalence is approximately double compared to the rest of the world. Higher age and female sex may Pain is not the only problem for cancer patients. Actual- increase the prevalence to 20–30%. In advanced stages ly, the complaint with the highest prevalence is fatigue, of abdominal cancer, especially in palliative treatment followed by anorexia. Discomfort due to constipation situations, incidences are higher than 60%. is also a frequent complaint. Unfortunately, constipation may often be considered unimportant by the therapist, and therefore overlooked or ignored. In fact, con- Which tests are indicated? stipation may be a frequent cause of anorexia, nausea, Basically, the diagnosis of constipation is made by taking and abdominal pain. Th erefore, constipation must be the history of the patient. If constipation is diagnosed ac- checked for on a regular basis, and attempts should be cording to the criteria listed above and abdominal cancer made to relieve or at least reduce it. is present, the etiology of constipation may be obvious. For safety, a digital examination of the anal canal and— Everybody seems to know what if available—a proctoscopy are indicated. Rectal exami- constipation is, but most people nation should be carried out—with the consent of the would not agree on when to make the patient—during initial examination in most patients. In special cases manometric testing and evaluation of the diagnosis, so what is the defi nition? oral-anal transit time may be done to diff erentiate be- Constipation is precisely defi ned: delayed bowel move- tween a functional or a morphological problem of the ments with a frequency of less than twice weekly, com- terminal intestines or more proximal structures. bined with painful discharge, abdominal swelling, and irregularity. Nausea and vomiting, disorientation, col- What may be the conclusions ics, and paradoxical diarrhea may be also present. Th e from rectal examination? “Rome criteria for the diagnosis of constipation” are used to defi ne constipation. Unfortunately, the patient When the rectum is found to be fi lled by hard fecal may not agree and may feel constipated with less or oth- masses it would not be advised to give fecal expanders er symptoms. Th e diagnosis is made solely by taking a since they would make the problem even more diffi cult patient history. to resolve—manual removal is indicated. In terminal illness, when recurrent hard fecal masses will be ex- What are the “Rome criteria”? pected, the family should be instructed to perform this procedure. When the rectum is found empty, but “bal- According to the “Rome criteria,” at least two of the fol- looned,” laxatives with “softening” and “pushing” eff ects lowing symptoms must be fulfi lled for a minimum of 3 are indicated. After descent of the feces into the rectum, Abdominal Cancer, Constipation, and Anorexia 141 enemas will help to evacuate the feces. If the rectum is Why do opioids induce found to be empty and collapsed, fecal impaction is not constipation? probable, then oral fecal expanders (combined with peristaltic stimulants) should be used. To understand opioid-induced constipation, we have to remember that peristaltic movement is the con- Which etiologies apart from the sequence of longitudinal contractions of the smooth cancer must be considered? muscles proximal to descending food and intestinal compliance. Th e excitatory motoneurons in the intes- Certain factors infl uence the motility of the colon. Th e tines responsible for longitudinal contractions have most important “extrinsic” factor is pharmacotherapy cholinergic innervation. Since opioids have anticholin- (e.g., opioids and all anticholinergic drugs such as an- ergic eff ects, they inhibit peristaltic movements. Addi- tidepressants, calcium, and aluminum-containing ant- tionally, opioids enhance local concentrations of 5-HT acids), and the most important “intrinsic” factor are and norepinephrine, thereby reducing the secretions of plexopathies (e.g., with autonomous neuropathy in dia- the intestinal wall, which further impedes movement of betes or Parkinson disease). Dehydration, immobiliza- the feces. A central peristalsis-reducing eff ect from the tion, hypokalemia (e.g., as a result of diuretic therapy), opioids may add to the problem. Although opioid use is and physical weakness are additional factors. Th e latter one of the most frequent causes of constipation, there conditions are the main reasons for constipation in gas- is no evidence-based treatment protocol or prophylaxis troenterological cancer patients in addition to the direct protocol for this therapeutic situation, but it is advisable eff ects of the cancer tissue growth (obstruction and in- to always use a prophylaxis to prevent opioid-induced fl ammation). Sometimes overlooked, depression and constipation, whether constipation is already present or anxiety disorders, which have a higher incidence in cannot. cer patients, may be another predisposing factor. Do all patients with constipation What are the specifi c risk require special laxative therapy, factors for cancer patients to get and what would be the most simple constipated? treatment algorithm?

• Dehydration, e.g., following repeated vomiting As usual, simple solutions are the best. Specifi c laxative • Reduced nutritional intake due to cancer-related therapy is only indicated in special situations, one of the anorexia most important one being the prophylactic treatment of • Multiple surgical or diagnostic manipulations opioid-induced constipation. (e.g., barium use for radiology is a potent consti- “Unspecifi c” techniques to reduce constipation pating agent) may be eff ective if used in combination, e.g., fi ber-rich • Gastrointestinal metastasis nutrition, regular daily activities, colonic massage, and • Continuous opioid medication suffi cient oral hydration. Unfortunately, the eff ective- • Coanalgesics with anticholinergic eff ects (e.g., tri- ness of this prophylactic regimen is limited if opioids or cyclic antidepressants and anticonvulsants) other constipation-causing medications are used. Addi- • Chemotherapeutics (e.g., vinca alkaloids) tionally, in most cases it will be not appropriate in pa- • Hypercalcemia (frequent with osseous metasta- tients who will be unable to follow such a diet and ac- sis) tivities most of the time. Th erefore, constipating drugs • Immobilization in inpatient treatment (plus loss should be limited to those that are absolutely necessary. of privacy, causing a “psychological inhibition” of If therapy cannot be done without these drugs, specifi c normal defecation) regimens should be instituted in every patient, starting • Uncontrolled pain (from surgery or the cancer with a stepwise approach. Th e fi rst step would be lo- itself), depressive disorders, and anxiety (causing cally available laxatives, e.g., dried and crushed pawpaw “arousal” of sympathetic stimulation with conse- seeds (1–5 teaspoons daily, at bedtime) combined with quent reduction of bowel motility) vegetable oil (1 teaspoon daily) or alternative remedies 142 Andreas Kopf patients have found to be helpful in their personal expe- What are the mechanisms of action rience. If these laxatives are insuffi cient, the second step of typical laxatives? is to combine them with either senna or bisacodyl tablets. Th ese tablets also should be taken at bedtime and Th e simplest mechanism is the “softening of stool,” which increased by one tablet daily until there are successful usually is suffi cient to allow stool regulation in non-can- bowel movements. Th e permanent dose would be the cer patients who have normal daily activities and a nor- result of careful up-and-down titration at the beginning mal daily fl uid intake. Th e cheap and available polysac- of laxative therapy. At step three, the laxatives have to charide lactulose is non-resorbable and attracts water be combined with local therapy, either suppositories into the intraluminal space of the intestines. By increas- with bisacodyl or glycerine. If suppositories are unavail- ing intraluminal volume and dilating the intestinal wall, a able, custom-made petroleum jelly will do as well (a propulsive eff ect is triggered. Unfortunately, fermentation lump of it has to be held inside by the patient, preferably is a side eff ect of lactulose, resulting in gas formation. for about 20 minutes). Always try to avoid bedpans and Th e artifi cial polyethylene glycol macrogol has allow the patient to sit or squat to have more eff ective a similar osmotic eff ect but does not need as much abdominal muscle contractions. fl uid intake and therefore may be better suited for the abdominal cancer patient, whose daily fl uid intake is If laxatives are indicated, what often reduced. Macrogol has saline eff ects and is not would be the most “advanced” metabolized, therefore there is no fermentation or in- treatment algorithm? creased gas production. Lactulose and macrogol have a dose-dependent laxative eff ect and do suff er from tol- Always consider local herbal laxatives and foods that erance eff ects. the patient has found useful previously, such as crushed Another class of laxatives are the nonresorbable papaya seeds or crushed coff ee beans from the coff ee oils (paraffi ns), which have both softening and lubricant senna tree. Th erefore, always listen to the patient and eff ects. Since they may irritate the intestinal wall, cause change therapy according to the needs of your patient. serious pulmonary damage when aspirated, and interact For patients on permanent opioid medication, with the absorption of lipophilic vitamins, they should prophylactic laxatives have to be prescribed simultane- only be used for a short time in complicated constipation. ously at all times. An exception to this rule are patients A third class of laxatives has mainly stimulating with chronic diarrhea, including many patients with ad- (propulsive) eff ects on the intestinal wall, causing inhi- vanced HIV/AIDS who are receiving opioids to control bition of the reabsorption of fl uids in the colon and in- neuropathic pain and who may even benefi t from the creasing the secretion of fl uids and electrolytes into the constipating eff ects of opioids. intraluminal cavity. Laxatives belonging to this class in- Some laxatives are not recommended for exclude the anthraquinone glycosides (aloe, senna leaves), tended use, especially antiresorptive and secretory laxa- diphenols (bisacodyl und sodium picosulfate), as well as tives, because they may cause considerable potassium fatty acids (castor oil). In some patients the “stimulat- and fl uid loss, which increases constipation in the long ing” eff ects—especially from castor oil—may cause con- term. Patients with advanced cancer and/or permanent siderable discomfort through colicky abdominal pains. opioid therapy should not use these substances but in- Th e fourth class of laxatives are the “prokinetic” stead should be treated stepwise with: ones, which are rarely used. Th ese include the 5-HT4-re- 1) Macrogol or lactulose ceptor-agonist tegaserod, the macrolide antibiotic eryth- 2) Macrogol plus sodium picosulfate or senna (“soft- romycin, and the prostaglandin analogue misoprostol. ener”) 3) Macrogol plus senna + bisacodyl (“pusher”) Is there a way to antagonize 4) Senna plus bisacodyl and paraffi n the intestinal eff ects 4) Suppositories (glycerine or bisacodyl) of opioids directly? 5) Enemas (soap and water) 6) Manual removal of feces Using selective opioid antagonists to block the intes- 7) In “emergencies”: castor oil, radiocontrast agent, tinal side eff ects of opioids would be an “intelligent” or naloxone/methylnaltrexone approach to constipation therapy in patients with an Abdominal Cancer, Constipation, and Anorexia 143 indication for permanent or long-term opioid therapy. Can we do something about the In fact, this approach is based on an interesting hepatic weight loss? mechanism: morphine is metabolized in the liver into its active products, while the opioid antagonist nalox- Although it would be tempting to give the patient par- one is completely metabolized in its fi rst pass through enteral nutrition, if available, it is well known that this the liver into inactive forms. Th erefore, the antagonist method does not infl uence the course of the weight would only be active at the intestinal opioid receptors, loss and even poses a risk for the patient (e.g., refeed- specifi cally antagonizing the constipation side eff ects of ing syndrome, infections from catheters). Th e excep- morphine or other opioids. tion to this rule is the special situation when the pa- Some opioids are now available that are a com- tient requires surgery, when perioperative parenteral bination of agonist and antagonist. Unfortunately, they nutrition is indicated to reduce further weight loss. are available in only a handful of countries, and due to In general, our main target is to educate patients and patent protection, they are rather expensive. A cheap help them, if possible, with some symptomatic treat- alternative is to provide the patient with oral naloxone, ment to increase appetite. Th is support may be very which—if available—is a low-cost substance and has an- helpful for the patient, since eating is one of our main ticonstipation eff ects in a dose range of 2–4 mg q.i.d. A “social” activities. Although there will be no relevant recent development is methylnaltrexone, which is a se- weight gain, the increased appetite will have a positive lective opioid antagonist. It is administered subcutane- eff ect on the patient’s general well-being. Two sub- ously and has a predictable eff ect within 120 minutes stances have been shown to have a positive eff ect on for more than 80% of treated patients. Due to its route appetite and may be tried if they are locally available. of application and high costs, its use is limited to “emer- First, the patient should be encouraged to smoke or gency situations,” when intestinal paralysis, not merely eat cannabis, if available. An artifi cial cannabis prod- obstruction, is imminent. uct is available on the pharmaceutical market (delta- 9-tetrahydrocannabinol), but it is unaff ordable for If my patient complains about most people if it is not covered by insurance, as is the case in most countries of the world. Th e second op- fatigue and loss of appetite, tion would be the use of steroids. A low dose of dexa- what do I tell him? methasone (2–4 mg once daily), prednisolone (20 mg once daily), or another steroid at an equipotent dose Patients must be educated about the fact that the may improve anorexia. cancer induces certain changes in the central regulation of appetite. In abdominal cancer, about three- quarters of patients experience weight loss of more Is there also a good than 5% monthly in the advanced stage of cancer recommendation for my patient (breast cancer and prostate cancer are exceptions complaining of fatigue? to the rule, causing only moderate weight loss). We know now that cytokines, which play a prominent Fatigue is a term describing major exhaustion and role in infections, are released from cancer cells should not be confused with depression or sedation. and are involved in changes in appetite. They influ- Depression usually goes along with diffi culties in fall- ence the melanocortin system in the central nervous ing asleep, constant “thinking in circles,” lacking drive, system (the hypothalamus), thereby reducing the especially in the morning hours, and general loss of patient’s appetite. Even high caloric intake cannot interest, while sedation means falling asleep again and prevent weight loss. Therefore, patients should be in- again for short periods (maybe the opioid dose is too structed to continue eating what they like best, but high?). If fatigue is diagnosed, we have to admit to the they should not be encouraged to force their nutri- patient that it can hardly be infl uenced and is a “pro- tional intake. The patient’s family should be instruct- tective” function of the body to save energy because ed likewise, because they might feel that they have to of the cancer. While pharmacological options such as “feed” the patient more since they see the continuous methylphenidate have been very disappointing, some reduction in body weight. patients have reported having less fatigue with a high 144 Andreas Kopf intake of coff ee, or from chewing coca leaves (in the radiochemotherapy and those who are at ad- Andean mountains in Latin America) or khat (in the vanced stages of disease. Arab Peninsula and East Africa). • Opioids should only be prescribed by one person. • Patients and their relatives should—before start- Pearls of wisdom ing the opioid medication—receive an education on the pros (nontoxic, long-term use) and cons • Morphine is still the opioid of fi rst choice. (no stopping therapy without consulting the pre- • Th e preferred route of application is oral. scriber, no change of doses without consultation • In patients needing long-term parenteral opioids, of the prescriber) of opioids. subcutaneous administration should be preferred. • When initial pain readings are high, intravenous • Opioids should be used early on and not as the titration of morphine may be used to estimate last resort of therapy. the (additional) daily opioid requirements of the • Th ere is no advantage to using “weak” opioids like patient (this only applies to cancer patients!). Th e codeine or tramadol; therefore—if only morphine cumulative dose of i.v. morphine that is necessary is available—morphine or other “strong” opioids to achieve acute pain control multiplied by 12 will may be used fi rst. roughly give the daily oral dose of morphine the • Opioids should be combined with NSAIDs, dipy- patient will need in the days to come. Th e next rone, or paracetamol (acetaminophen) to reduce consultation should be within the next few days the dose and side eff ects of opioids. to reevaluate the patient. • If neuropathic pain is the leading symptom, co- • When pain readings are high, but pain is not ex- analgesics such as amitriptyline or gabapentin cruciating, a dose increase of roughly 25–50% should be added where available. will be adequate, and the next consultation • All opioid medication should consist of a fi xed- should be within a few days to reevaluate the pa- dose regimen and an on-demand dose. If avail- tient. able, the fi xed dose should be a slow-release • Opioid-naive patients should expect sedation and opioid and the on-demand dose an immediate- nausea. Nausea should be treated prophylactically release opioid. for about one week (e.g., with metoclopramide, • Th e on-demand dose should be calculated from when available). the fi xed-dose regimen (around 10% of the cumu- • Always educate patients about the constipating lative daily dose of opioid). eff ects of opioids and advise them to take laxa- • Th e on-demand dose may be used by patients as tives. often as they need it, with a 30–45 minute mini- • Transdermal opioid patches—if available—are mum wait before the next on-demand dose. only indicated in patients with stable dose re- • If more than four on-demand doses are used quirements of opioids and have to be combined daily on average, the fi xed daily dose should be with on-demand doses. increased by 75% of the cumulative daily on-demand dose. References • If the sedating and nauseating side eff ects of the [1] Agency for Health Care Policy and Research. Clinical practice guideline. fi rst opioid used last longer than 2 weeks and the Management of cancer pain. Available at: http://www.painresearch. daily dose cannot be reduced due to the patient’s utah.edu/cancerpain/guidelineF.html. [2] Klaschik E, Nauck F, Ostgathe C. Constipation—modern laxative thera- analgesic requirement, the opioid should be ro- py. Support Care Cancer 2003;11:679–85. tated to another opioid, which might have a more [3] Kulke MH. Metastatic pancreatic cancer. Curr Treat Options Oncol 2002;3:449–57. favorable individual side-eff ect profi le for the pa- [4] Mercadante S. Opioid rotation for cancer pain: rationale and clinical aspects. Cancer 1999;86:1856–66. tient. [5] Mercadante S, Nicosia F.Celiac plexus block: a reappraisal. Reg Anaesth • Alternative routes of application for opioids (e.g., Pain Med 1998;23:37–48. [6] Müller-Lissner S. Th e diffi cult patient with constipation. Best Pract Res parenteral or intrathecal) are never required in Clin Gastroenterol 2007;21:473–84. the normal course of cancer and are seldom re- [7] Nersesyan H, Slavin KV. Current approach to cancer pain management: availability and implications of diff erent treatment options. Th er Clin quired in patients undergoing sophisticated Risk Manag 2007;3 381–400. Abdominal Cancer, Constipation, and Anorexia 145

[8] Portenoy RK. Pharmacologic management of cancer pain. Semin Oncol 1995;22:112–20. Websites [9] Rao SS. Constipation: evaluation and treatment. Gastroenterol Clin North Am 2003;32:659–83. www.cancercare.ns.ca: a provincial educational cancer program (from Nova [10] Walker VA. Evaluation of WHO analgesic guidelines for cancer Scotia in Canada) with a lot of useful information on diﬀ erent cancer types pain in a hospital-based palliative care unit. J Pain Symptom Manage and their management 1998;3:145–9. http://aspi.wisc.edu (Alliance of State Pain Initiatives with downloadable [11] Wiﬀ en P, Edwards J, Barden J, McQuay H. Oral morphine for cancer educational material on cancer pain) pain. Cochrane Database Syst Rev 2003;4:CD003868.

Appendix

Profi les of laxatives (in alphabetic order) Bisacodyl (phenolphthalein): antiresorptive and hydragogue, 5–10 mg for prophylaxis, 10–20 mg for therapy Gastrographin (dye): propulsive, only in acute danger of ileus, 50–100 cc Lactulose (osmotic sugar): for prophylaxis when oral fl uid intake is not impaired, 10–40 g Macrogol 3350 (polyethylene glycol): osmotic, prophylaxis for cancer patients, 13–40 g Magnesium sulfate and sodium sulfate (saline and osmotic): short term-treatment, 10–20 g Naloxone (opioid antagonist): prophylaxis with chronic sub-ileus, 4 × 3–5 mg orally Sodium-picosulfate (phenolphthalein): antiresorptive and hydragogue, for cancer patients, 5–10 mg Paraffi n: improves “gliding” of stools, short-term therapy without risk of aspiration, daily 10–30 mL Senna (anthraquinone glycoside): antiresorptive und hydragogue for prophylaxis and long-term therapy, 10–20 mL Sorbitol: saline and osmotic for refractory constipation, suppository in the morning (fast-acting)

Guide to Pain Management in Low-Resource Settings

Chapter 19 Osseous Metastasis with Incident Pain

M. Omar Tawﬁ k

What is incident pain? Is it How common is osseous diﬀ erent from breakthrough pain? metastasis?

Incident pain is an episodic increase in pain intensi- Bone metastasis in cancer patients is seen frequently. It ty. Some include incident pain as a subtype of break- is the third most common metastatic site after the lung through pain (BTP), while others defi ne BTP as one and liver. Myeloma is the hematological malignancy of the subtypes of incident pain. BTP is defi ned as “a most frequently associated with lytic bone lesions. Bone transient increase in pain to greater than moderate in- metastases are more often seen with cancer of the lung tensity, which occurred on a baseline pain of moderate and the prostate in males and cancer of the breast in fe- intensity or less.” males; up to 85% of patients dying from breast, prostate, Th e term BTP can only be used when base- or lung cancer demonstrate bone involvement at autopsy. line pain is controlled by analgesics. However, there is Th e most common cancer that produces pain metastasis no general agreement on the defi nition of BTP. In the is breast cancer, and the most common site is vertebral United Kingdom the term is often used synonymous- bodies, as seen in Table 2. Twenty-fi ve percent of patients ly with end-of-dose failure. However, there is a gen- have multiple sites of pain, and 10% of patients with spine eral agreement that BTP in cancer patients may occur pain have been found to have epidural cord compression. spontaneously. When it is precipitated by an event, it can be defi ned as incident pain. Precipitating events Are all osseous metastases similar? may be volitional and related to movements, walking, coughing, sitting, standing, or even touching. BTP Osteolytic bone disease is the major source of pain. It usually occurs at the same site as the background pain, causes diffi culty in ambulation or immobility, neuro- while incident pain may occur at the site or in a diff er- logical defi cits, and pathological fractures. Pathologi- ent place when there is widespread osseous metastasis. cal fractures due to increased bone fragility have been Th e onset, duration, and frequency of BTP dif- reported to occur in 8–30% of patients with bone me- fer. Th e duration may vary from minutes to hours It tastases. Fracture is common in patients with a my- has been estimated to be 15–30 minutes on average, eloma and breast cancer, and long bones are more fre- with a frequency of 4–7 pain episodes per day. quently involved.

Table 1 Diﬀ erences between breakthrough and incident pain Breakthrough Pain Incident Pain Occurs in the same site as background pain Occurs at any site Is spontaneous, without any volitional act Should be related to a volitional act Has a duration and frequency Occurs with an incident and needs a speciﬁ c interventional treatment

Prostate cancer cells produce osteoblast-stimu- How does bone destruction occur? lating factors, probably specifi c growth factors or acid phosphatase. In this case, new bone is laid down di- Bone destruction results from interactions between tu- rectly on the trabecular bone surface before osteoclas- mor cells and bone cells that are normally responsible tic resorption. Th e resulting sclerotic metastases are for the maintenance of skeletal integrity. Th e enhanced less prone to fracture because of the locally increased osteoclastic bone resorption, stimulated by bone-re- bony mass. sorbing factors, is a major factor in the development of bone metastases. Moreover, immobilization and secondary eff ects of osteolysis may be the reasons for de- Table 2 pressed osteoblast function. Bone metastatic lesions and sites Osteoclasts can be activated by tumor products Primary sites in this study: Pain sites of these metastases: or indirectly through an infl uence on other cells. Tumor Breast cancer (24%) Lumbar spine (34%) cells frequently produce factors that can activate im- Prostate cancer (19%) Th oracic spine (33% mune cells, which release powerful osteoclast-stimulat- Unknown primary (22%) Pelvis (27%) ing substances, such as tumor necrosis factor and inter- Renal cancer (13%). Hip (27%) leukins 1 and 6. Tumor products could also act directly Malignant melanoma (7%) Sacrum (17%) on bone cells. In the late stages of a metastatic disease, Lung cancer (6%) Humerus (19%) malignant cells appear to directly cause the destruction Other (8%) Femur (14%) of bone. In bone metastases, reactive osteoblastic activity can occur and is detected by bone scans and serum Breast cancer cell metastasis to bone promotes alkaline phosphatase. Osteoclastic activity leads to col- osteoclastic activity. However, the normal balance of lagen fragments such as pyridinoline and deoxypyr- bone resorption and new formation is upset. It exhib- idinoline that can be measured in urine. Patients have its a mixed picture of both lytic and sclerotic areas, localized sharp pain, often worsened by movement or with fractures usually occurring through the lytic ar- weight bearing. eas. Th ese diff erent mechanisms correspond to typical radiological features showing mixed lytic and sclerotic metastases, osteolytic metastases, or sclerotic metasta- Can all osseous metastases ses (see Table 3). produce pain?

Not all bone metastases are painful. However, a study Table 3 at a multidisciplinary bone metastasis clinic found that Characteristics of skeletal assessment in the most common 57% of patients reported severe (7–10) pain, and 22% tumors associated with bone metastases had experienced intolerable pain. Th e pathophysiologi- Myeloma Breast Prostate cal mechanism of pain in patients with bone metastases Hypercalcemia 30% 30% Rare without fracture is poorly understood. Th e presence of Bone scans - + ++ pain is not correlated with the type of tumor, location, Alkaline phosphatase - + ++ number and size of metastases, or gender or age of pa- Histology Osteoclastic Mixed Osteoblastic tients. While about 80% of patients with breast cancer X-ray Osteolytic Mixed Sclerotic will develop osteolytic or osteoblastic metastases, about Osseous Metastasis with Incident Pain 149 two-thirds of all demonstrated sites of bone metastases characteristically described as dull in character, con- are painless. Many nerves are found in the periosteum, stant in presentation, and gradually progressive in in- and others enter bones via the blood vessels. tensity. Pain increases with pressure on the area of in- Microfractures occur in bony trabeculae at the volvement. Th ese characteristics are fully described by site of metastases, resulting in bone distortion. Th e the patient, so the condition should be investigated as stretching of periosteum by tumor expansion, mechani- probable osseous metastasis with bone pain. cal stress on the weakened bone, nerve entrapment by Th e gnawing pain described by the patient is the tumor, or direct destruction of the bone with a con- characteristic sign suggesting neuropathic elements. It sequent collapse are possible associated mechanisms. is radicular in distribution (L2/3) and unilateral, sug- Th e weakening of bone trabeculate and the release of gesting an origin from the lumbosacral spine. Pain is cytokines, which mediate osteoclastic bone destruction, usually bilateral when originating in the thoracic spine may activate pain receptors. and is exacerbated in certain positions that the patient Th e release of algesic chemicals within the mar- usually tries to avoid. Straight leg raising, coughing, row probably accounts for the observation that pain and local pressure can exaggerate the pain, while pain produced by tumors is often disproportionate to their may be relieved by sitting up or lying absolutely still. size or degree of bone involvement. A secondary pain Weakness, sphincter impairment, and sensory loss are may be caused by reactive muscle spasm. Nerve root in- uncommon at presentation, but they develop when fi ltration and the compression of nerves by the collapse the disease progresses in the compressive phase, and of osteolytic vertebrae are other sources of pain. should be prevented. In osseous metastasis, hypercalcemia, i.e., el- Clinical presentation evated plasma levels of ionized calcium, is inevitable. As half of the calcium is albumin-bound, the total calcium Case study value should be adjusted for the albumin level to cor- A female patient, aged 63 years, came to the pain clinic rectly evaluate the calcemic status. Renal function, in- with vague aching pain in the lower back, which she has cluding urea and electrolytes, should be checked. Symp- had for 3 months, accompanied by gnawing pain in the toms occur with calcium values exceeding 3 mmol/L, middle of her right thigh, particularly on standing up and their severity is correlated with higher values. In or walking. Pain scoring by the patient defi ned the pain elderly and very ill patients, very slight increases of ion- at rest as 4, and pain on walking as 6, on a 10-cm line. ized calcium plasma levels may be symptomatic. Th e back pain has been steadily increasing during this • A shortened QT interval on the electrocardio- time, and now she lies in bed all the time to prevent her gram may be evidenced. Increases in urinary cal- pain from increasing further. Her back pain was great- cium levels are caused by the release of calcium ly reduced by NSAIDs. Th e patient has had radical left into the circulation secondary to an increased breast surgery due to breast cancer, followed up by radio- bone resorption. therapy. On examination, there was clear tenderness on • Urinary excretion of hydroxyproline, a major the lumbar spine, at the second lumbar vertebra, and on constituent of type I collagen, is an indirect mea- the medial part of the lower third of the right thigh. sure of increased bone turnover. Both urinary hy- Pain may be vague or absent because osseous droxyproline/creatinine and calcium/creatinine metastasis may be painless. However, any vague pain ratio have been used to monitor the eff ects of in a patient with a history of treated cancer should be bisphosphonate treatment. taken seriously and thoroughly investigated. Bone pain • Hypercalcemia is associated with pain, nausea, usually results from osteolytic bone metastases. Pain as vomiting, anorexia, constipation, weakness, de- a symptom is present in about 50% of patients. Th e fi ve hydration, polyuria, mental disturbances, and most frequently involved sites are the vertebrae, pelvis, confusion. Symptoms can mimic those associ- ribs, femur, and skull. Pain develops gradually during ated with diseases or conditions. Gastrointestinal a period of weeks or months, becoming progressively symptoms are often mistaken for opioid eff ects or more severe. Th e pain usually is localized in a particular are potentiated by opioid-related symptoms, and area, such as the back and the lower third of the femur, neurological symptoms are often attributed to ce- and is often felt at night or on weight bearing. Pain is rebral metastases. Hypercalcemia complicates the 150 M. Omar Tawfi k clinical course of 10–20% of patients with lung A magnetic resonance scan delineates the whole and breast tumors. spine, identifi es multiple sites of cord and vertebral in- • Serum levels of alkaline phosphatase and osteo- volvement, shows the paravertebral epidural extension calcin refl ect osteoblast activity. Patients with a and integrity of the spinal cord, and allows diff erentia- myeloma presenting low values of serum osteo- tion between traumatic, osteoporotic, or pathological calcin, a sensitive and specifi c marker of osteo- fractures and compression without the need of invasive blastic activity, have advanced disease, extensive techniques, such as myelography. However, MRI is ex- lytic bone lesions, frequent hypercalcemia, and a pensive. All the data deriving from these radiological poor survival rate. studies should be interpreted in the context of the clinical fi ndings. Case study (cont.) In questioning the patient, some specifi c symptoms about How can we make a plan the presence of hypercalcemia should be assessed. Symp- for treatment? toms related to hypercalcemia are nausea, vomiting, anorexia, stomach pain, constipation, excessive thirst, Th e treatment plan should contain: dry mouth or throat, fatigue or lethargy, extreme muscle • Management of osseous metastasis. weakness, moodiness, irritability, confusion, irregular • Management of pain. heartbeat, and frequent urination. Hypercalcemia can • Treatment of hypercalcemia. be a life-threatening condition. Investigations related to • Prevention of incidental fracture or vertebral hypercalcemia should test for free serum calcium level collapse. corrected for albumin level, ECG, urinary hydroxyproline/creatinine, and serum alkaline phosphatase. Radio- Case study (cont.) logical investigations are of course needed, such as ra- Th e investigations reveal osseous metastasis in the lower diography, scintigraphy, CT scan, and MRI, which were medial end of the femur as well as in the lumbar spine, ordered for this patient, particularly for the back and particularly L2, by bone scintigraphy and ordinary radi- right thigh. ography. Some thoracic vertebrae show early signs on single photon emission computed tomography/CT (SPECT/ How can we choose between CT). Hypercalcemia was proven by serum level. radiographic investigations? How is osseous metastasis treated? Bone metastases may be diagnosed by a variety of methods, including radiography, scintigraphy, com- Once bone cancer is discovered, attempts to treat the puted tomography (CT) scan, and magnetic reso- cancer should be the primary concern, as all other com- nance imaging (MRI). With conventional radiography plications including pain and hypercalcemia can then be a change of about 40% in bone density is required be- alleviated. Th e most important is radiation therapy, or fore bone metastases may be identifi ed, and small le- the use of radionuclides. sions may remain undetected. A change of 5–10% is suffi cient when using bone scintigraphy. Bone scintig- Radiation therapy raphy is positive in 14–34% of patients who have no In 60–90% of patients, radiotherapy has been eff ective radiographic evidence of bone metastases. However, using a standard treatment regime delivering 60 Gy in the method is less sensitive for the detection of pure- 30 fractions over 6 weeks with daily treatment sessions. ly osteolytic metastases. Bone scan abnormalities are Radiotherapy should be the fi rst step in the manage- not specifi c, and several benign conditions give rise to ment of metastatic bone pain. Radiotherapy is used as false-positive results. Scans may appear negative when an adjunct to orthopedic surgery to decrease the risk lesions are predominantly osteolytic, after radiother- of skeletal complications. An actual or impending bone apy, and when surrounding bone is diff usely involved fracture may require a short fractioned course of 20–40 with tumor. CT scans allow the identifi cation of the Gy over 1 week. Radiotherapy is used for bone metas- type of metastases and yield more sensitive results tases to relieve pain, prevent impending pathological than the previous methods. fractures, and promote healing of pathological fractures. Osseous Metastasis with Incident Pain 151

Radiotherapy is successful in relieving pain in 60–70% to prevent withdrawal in recovering drug users, is used of patients, but it takes up to 3 weeks for the full eff ect in hospices in the United Kingdom and Canada. It is to be seen. also used in the United States for the treatment of pa- Potential complications of radiation include sys- tients with refractory or neuropathy-associated pain. temic side eff ects not confi ned to the area of irradiation, Numerous opioid preparations are now avail- such as nausea and vomiting, anorexia, and fatigue, as able. Currently, immediate-release forms of morphine, well as eff ects specifi cally related to the irradiation fi eld, oxycodone, and hydromorphone are available for a fairly including skin lesions, gastrointestinal symptoms, my- rapid onset of drug action. Sustained-release (SR) prep- elosuppression, and alopecia. Th e best treatment for arations (morphine, oxycodone, or hydromorphone) are hypercalcemia due to cancer is treatment of the cancer eff ective in dosing every 12 or 24 hours, or sometimes itself. However, since hypercalcemia often occurs in pa- every 8 hours. Th ey are usually used after dose titration tients whose cancer is advanced or has not responded to defi ne the eff ective daily dose for baseline continu- to treatment, management of hypercalcemia is some- ous pain. Fentanyl is now also available in two forms of times necessary. immediate-release preparations—the transmucosal formula and sustained-release transdermal patches. Radionuclides Long-term use of opioids is associated with Radionuclides that are absorbed at areas of high bone physical dependence and (rarely) tolerance. Tolerance turnover have been assessed as potential therapies for is defi ned as a physiological phenomenon of progressive metastatic bone pain. Strontium-89 chloride and samar- decline in the potency of an opioid with continued use, ium-153 are available in the United States. manifested by the requirement of increasing opioid doses to achieve the same therapeutic eff ect. Increased dos- How is osseous pain treated? es can continue to provide adequate analgesia because there appears to be no ceiling eff ect, but escalating dos- Analgesic drugs es can increase side eff ects (nausea, vomiting, constipa- Nonsteroidal anti-infl ammatory drugs (NSAIDs) and tion, abdominal pain, and pruritus) that may limit their COX-2 inhibitors are promising as anticancer drugs use. At this point, opioid rotation is needed. because they inhibit tumor angiogenesis and induce tumor cell apoptosis. NSAIDs play a key role in the fi rst Coanalgesics step of the WHO guidelines for management of cancer Steroids, including corticosteroids, have benefi cial ef- pain. Nearly 90% of patients with bone metastasis pres- fects in reducing metastatic bone pain, due to their an- ent with pain. NSAIDs are the most eff ective agents for ti-infl ammatory properties in blocking the synthesis of treatment of patients with this condition because pros- cytokines, which can contribute to both infl ammation taglandins appear to play an important role. Th ey are and nociception. Th e duration of pain relief is general- comparable in safety profi le and eff ectiveness. Compari- ly short. Special consideration should be given to these son of opioid combination preparations with NSAIDs drugs in cases of spinal cord and brain compression, in alone showed no or at most only a slight diff erence. which their role in reducing peritumoral edema is very Continuous bone pain shows a good response advantageous. Th ey are eff ective and can sometimes to opioids. Most terminally ill patients with incident temporarily stabilize or improve neurological dysfunc- pain found that pain was a major limiting factor to action. Although corticosteroids are part of the treatment tivity. Th e diffi culty with incident pain is not a lack of in advanced cancer patients for their benefi ts regarding response to systemic opioids, but rather that the doses improved appetite, reduced fatigue, and a sensation of required to control the incident pain produce unaccept- well-being, prolonged use should be weighed against able side eff ects when the patient is at rest. Oral mor- the adverse eff ects. Serious complications of prolonged phine is the primary opioid used in the United States administration of corticosteroids include immunosup- for treatment of patients with severe pain in advanced pression, pathological fractures, swelling, and delirium. stages of cancer. In the United Kingdom, diamorphine Calcitonin, a hypocalcemic agent, may be use- (heroin) is used secondarily because of its greater solu- ful as an adjuvant analgesic. Calcitonin inhibits sodium bility, but it has no clinical advantage over morphine. and calcium resorption by the renal tubules and reduces Methadone hydrochloride, a drug commonly prescribed osteoclastic bone resorption. However, despite its rapid 152 M. Omar Tawfi k eff ect, the role of calcitonin appears to be limited by its prevent loss of bone that occurs from metastatic le- short duration of action and poor effi cacy due to the sions, reduce the risk of fractures, and decrease pain. rapid development of tachyphylaxis (a rapid decrease in One of the primary treatments for hypercal- the body’s response to a drug after repeated doses over cemia of malignancy is hydration, which may consist a short period of time). Calcitonin is usually adminis- of increasing oral fl uid intake or intravenous (i.v.) ad- tered subcutaneously and intranasally. Th e initial dose ministration of fl uids. Hydration helps decrease the is 200 IU in one nostril a day, alternating nostrils every calcium level through dilution and causes the body to day. Apart from infrequent hypersensitivity reactions eliminate excess calcium through the urine. For mild- associated with subcutaneous injections, the main side to-moderate elevations of calcium, patients are usu- eff ect is nausea. ally directed to increase oral fl uid intake. For acute Bisphosphonates can delay the onset of skel- hypercalcemia, hydration with saline is immediately etal fractures, reduce the need for radiation therapy administered intravenously. Th e rate of hydration is to treat bone metastasis, reduce hypercalcemia (high based on the severity of the hypercalcemia, the sever- blood levels of calcium), and reduce the need for or- ity of dehydration, and the ability of the patient to tol- thopedic surgery. Bisphosphonates available in the erate rehydration. clinical fi eld are alendronate, etidronate, ibandronate, Sometimes, hypercalcemia related to malignan- pamidronate, risedronate, or tiludronate. Bisphospho- cy is treated with a diuretic. Th e most commonly used nate drugs include zoledronic acid and pamidronate. diuretic is furosemide, which causes loss of calcium, Of these two drugs, the fi rst appears to demonstrate sodium, and potassium. Furosemide is well tolerated, the strongest activity and is more convenient due to but it is not free of side eff ects, which may include de- reduced administration time. hydration and low blood potassium and sodium levels. Antidepressants are by far the most commonly Furosemide is available by i.v. administration, as well as used coanalgesics when neuropathic pain accompanies oral tablets. Th e intravenous method of administration osseous bone pain, such as after radiation damage. Tri- is used to achieve an urgent eff ect. Oral tablets are used cyclic antidepressants, such as amitriptyline, are used for maintenance (once or twice a day). with a daily starting dose of 10–25 mg, which may be titrated to eff ect, to potentiate analgesia and increase central norepinephrine and serotonin, and for their so- Is it possible to prevent incidental dium-channel blocking eff ect (as local analgesics). Th ey fracture or vertebral collapse? can also promote natural sleep. Anticonvulsants such as carbamazepine or Prediction of impending fracture and prophylactic clonazepam are particularly useful in neuralgias, such treatment is very important, although prediction itself as in situations with nerve root compression due to remains controversial, with roles advocated both for malignant vertebral body collapse. Th e dose is between radiographic and functional predictors. Th e Healy and 600–1200 mg daily and 0.5 mg, respectively. Although Brown system of predictions includes: it is successful in trigeminal neuralgia, carbamazepine’s • Painful lesions with involvement of more than eff ect on secondary neuralgias is less convincing. Gaba- 50% of the thickness of the cortex. pentin maybe an alternative for patients with impaired • A lytic lesion greater than the cross-sectional di- liver function or who have intolerable side eff ects with ameter of the bone. carbamazepine. • A cortical lesion more than 2.5 cm long. • A lesion producing functional pain after radiation How is hypercalcemia treated? therapy.

Treatment for hypercalcemia is based on a number of Case study (cont.) factors, including the condition of the patient and the Based on previous data, the plan of treatment included severity of the hypercalcemia. Increasing fl uid intake referring the patient to the radiotherapy unit to start ra- and the use of diuretics have been standard practice. diation therapy. Pain management was started according Most recently, bisphosphonate drugs have become an to the WHO ladder system and included an NSAID, cele- eff ective approach. Bisphosphonates can eff ectively coxib, 200 mg twice daily. When this proved insuffi cient, Osseous Metastasis with Incident Pain 153 sustained-release tramadol was added at a dose of 100 Case study (cont.) mg twice daily. Th e patient was put on patient-controlled analgesia, us- Bisphosphonates (zoledronic acid) at a dose of 4 ing morphine to give her relief from severe pain. She has mg monthly in a drip was prescribed, together with hy- been transferred to an orthopedic unit for fi xation proce- dration and advice for the patient to take lots of fl uids, dures to help relieve her pain and help her to be able to along with furosemide (one tablet daily with a potassium move around. supplement to guard against hypercalcemia). Percutaneous vertebroplasty was done for both L2 and T12, and this procedure was followed by a rapid What can be done by a dedicated relief of back pain. orthopedic specialist? Th e right lower-limb neuropathic pain was treated with gabapentin, starting with 100 mg three About 10–30% of patients with bone metastases de- times daily. Th is dose was gradually increased until a velop fractures of the long bones requiring orthopedic 1200-mg daily dose was achieved and maintained. Af- treatment. Th e femur is the most common site. Exten- ter vertebroplasty, the neuropathic element disappeared, sive bone loss due to the local eff ects of chemotherapy and the gabapentin was gradually withdrawn. and radiation should be supported during recovery. Th e patient was satisfi ed with this treatment for Protection with orthotic devices, such as lightweight 9 months, during which tramadol was changed to sus- functional bracing, may be useful during upper-extrem- tained-release morphine (90 mg daily dose). ity lesions. Th e lower extremities are not very amenable After 9 months, the patient accidentally fell. She to this method because of the high degree of load. As developed severe incidental pain in the right lower third a consequence, conservative treatment for fractures or of the thigh. Plain X-ray demonstrated a fracture at the symptomatic impending fractures of the extremities is site of the previous femur metastasis. rarely successful. Prophylactic pinning is indicated and may pre- What options would we have vent a long period of immobility. Conservative treatment of bone fractures in the axial skeleton is more in this case? likely to be successful because such bones have a bet- Guidelines have been developed using radiographic- ter blood supply and tend to heal more readily. Bracing series criteria, although the reliability of a radiographic in combination with radiotherapy may be a successful evaluation has been questioned because a bone metas- treatment for pathological vertebral fractures. tasis becomes apparent only after major bone loss, and It is important to ensure that pathological frac- some cancers, such as prostate cancer, are not charac- tures are stabilized to prevent pain and to facilitate terized by evident bone destruction. Moreover, bone physiotherapy and radiotherapy. Diff erent surgical solu- pain unresponsive to radiation has not been found to be tions may be proposed according to the kind of fracture, correlated with fracture risk. the clinical situation, and the patient’s life expectancy. Th e approach to treatment for bone pain may Orthopedic management includes internal fi xation and require diff erent modalities depending upon the initial osteosynthesis, resection of joint and joint replacement, assessment. Surgery should be considered if an impend- segmental resection of a large tract of bone and pros- ing fracture is diagnosed, and radiation therapy should thetic replacement, and arthroplasty. Surgical treatment be considered for painful bone metastases. Pharmaco- should be undertaken when a fracture occurs. Th e po- logical therapy with NSAIDs and opioids, along with tential benefi ts of surgical intervention have to be tem- medications for breakthrough pain, form the main pered with patient survival. symptomatic treatment. In addition, many adjuvant ap- Surgical stabilization of the spine and extremi- proaches have been recommended, such as calcitonin, ties may dramatically improve the quality of life, de- bisphosphonates, or radionuclides. In vertebral metas- crease the pain and suff ering of these patients, and pre- tasis with collapse, vertebroplasty may be an important vent complications associated with immobility, allowing procedure, as well as cementoplasty for other bone me- many patients to be cared for at home. Recovery from tastasis, particularly with weight-bearing pain, depend- prophylactic fi xation surgery is quicker and requires less ing on availability. aggressive procedures. 154 M. Omar Tawfi k Pearls of wisdom References

Osseous metastasis should be expected when vague [1] Bruera E. Bone pain due to cancer. In: Refresher course syllabus. Seattle: IASP; 1993. p. 237–44. pain starts to develop in patients with a history of treat- [2] Clavel M. Management of breast cancer with bone metastases. Bone ed or untreated cancer. 1991;12(Suppl 1):S11–2. [3] Demers LM, Costa L, Lipton A. Biochemical markers and skeletal me- Bone scans can detect osseous metastasis earlier tastases. Cancer 2000;88: 2919–26. [4] Koltzenburg M. Neural mechanisms of cutaneous nociceptive pain. than ordinary radiographs. Clin J Pain 2000;16:S131–8. Attempts to detect hypercalcemia should be done [5] Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1–18. in every case. Early effi cient treatment should start, and [5] Mercadante S, Radbruch L, Caraceni A, Cherny N, Kaasa S, Nauck F, Ripamonti C, De Conno F; Steering Committee of the European Asso- bisphosphonates are the best remedy. ciation for Palliative Care (EAPC) Research Network. Episodic (break- A high success rate after surgical intervention has through) pain: consensus conference of an expert working group of the European Association for Palliative Care. Cancer 2002;94:832–9. been reported, leading to improved patient survival. [6] Mundy GR. Mechanisms of osteolytic bone destruction. Bone More than 60% of patients benefi t from surgical decom- 1991;12(Suppl 1):S1–6. [8] Portenoy RK, Hagen NA. Breakthrough pain: defi nition, prevalence and pression and obtain adequate neurological recovery, characteristics. Pain 1990;41:273–81. [9] Tubiana-Hulin, M. Incidence, prevalence and distribution of bone me- although patients with rapid neurological compromise tastases. Bone 1991;12(Suppl 1):S9–10. have a worse prognosis. If only symptomatic treatment is available, NSAIDs and opioids, and in some cases coanalgesics, may im- Websites prove pain at rest, but pain on movement will be hard http://patient.cancerconsultants.com/cancertreatment_bone_cancer. to control suffi ciently without mechanical stabilization. aspx?linkid=53855 Guide to Pain Management in Low-Resource Settings

Chapter 20 Lung Cancer with Plexopathy

Rainer Sabatowski and HansJ. Gerbershagen

Case study such as surgery, radiotherapy, or even chemotherapy. Th erefore, they started morphine therapy with a start- Ruben Perez is a 52-year-old farmer living in the proving dose of 2.5 mg immediate-release morphine every ince of Yucatan in Mexico. He had lost his job at a farm 4 hours. Th ey instructed Mr. Perez to use 2.5 mg addi- some years before and has worked as a laborer ever tionally in case of pain recurrence, such as breakthrough since. He and his wife, his children, and two grandchil- pain episodes. He was advised to increase his daily fl uid dren live in a small hut in the village of Yaxcopil. Mr. intake to a minimum of 1.5 L of water a day to prevent Perez has smoked cigarettes his whole life. During the opioid-induced constipation. Additionally, the physi- last year, he noticed some health problems, feeling ex- cians prescribed gabapentin to improve morphine effi - haustion and noticing his cough getting worse. When he cacy in the presence of neuropathic pain. Mr. Perez was experienced lancinating pain in his left arm associated told to start with a dose of 100 mg and to increase the with continuous weakness of his arm, he and his family dose at day 4 to 100 mg t.i.d. If pain was still not ad- decided to visit the doctor at a large municipal hospital equately alleviated, he was asked to consult his local in Mérida. At the initial presentation, Mr. Perez reported physician again. his lancinating pain, involving predominantly the lower In the following weeks, the pain was alleviated segments of the brachial plexus. Weakness and sensory suffi ciently, even though it was not absent. But with this loss as well as Horner’s syndrome could be confi rmed. improvement and the support of his family, Mr. Perez Th e pain was severe, and pretreatment with acetamino- could cope with his situation. Several weeks later, he had phen, as needed, and codeine, which had been prescribed to go back to the hospital in Mérida because his pain in- by a local doctor, was not able to relieve the pain. Mr. creased dramatically. Even though the morphine dose Perez also reported dramatic weight loss, severe coughing was increased to a daily dose of 120 mg and gabapentin with red spots in the sputum, as well as breathlessness. had been increased to 900 mg, the pain intensity wors- An initial CT scan, which could be performed ened, and Mr. Perez reported a new pain sensation. Light at the hospital, showed a tumorous mass in the apical touch on his left arm led to severe pain. Dr. Rodriguez region of the left lung. Invasion and partial destruction decided to switch from morphine to methadone. Mor- of the upper thoracic and lower cervical vertebral bod- phine treatment was stopped immediately, and metha- ies could be confi rmed. Due to the progress of the disease done was started with a dose of 5 mg every 4 hours. For and the comorbidity, the physicians at the hospital did breakthrough pain episodes or inadequate pain relief not see an indication for further palliative treatment or both, 5 mg methadone could be administered within

included into the treatment algorithms for neuro- the α2δ-subunit of the voltage-dependent calcium chan- pathic pain. nel in the spinal cord. Th e binding to these receptors • Unavailability of opioids. inhibits the release of excitatory neurotransmitters. Ga- • Fear of legal consequences when prescribing “il- bapentin is administered three to four times a day. Th e licit drugs.” starting dose is 3 × 100 mg, and the maximum dose Lung Cancer with Plexopathy 159 around 2400 mg/day. Due to the drug’s common side Among opioids, morphine is the best studied eff ects such as drowsiness and sedation, a slow titra- drug. It is a mu-receptor agonist. Morphine is available tion is necessary. in immediate-release formulations and (in some countries) in sustained-release formulations. As the duration Antidepressants of action of the immediate-release formulation is ap- Among the antidepressants, the tricyclic antidepres- proximately 4 hours, frequent administration is neces- sants (TCAs) such as amitriptyline are most fre- sary. Titration should start with 5–10 mg every 4 hours. quently applied in neuropathic pain. TCAs have been On occurrence of breakthrough pain, an additional 1/6 studied extensively in noncancer pain patients. Th ey to 1/10 of the total daily morphine dose should be ap- enhance the endogenous inhibitory pathways by in- plied as an initial step. Later, the adequate dose to treat hibiting the presynaptic reuptake of serotonin and episodes of breakthrough pain must be adjusted ac- norepinephrine in spinal pain pathways. TCAs also cording to the individual patient’s needs and responses. have agonistic eff ects on histamine and muscarinic In the case of painful procedures, immediate-release receptors, which contributes to side eff ects such as morphine might be administered approximately half sedation and dry mouth. Additionally, there may be an hour before the procedure (such as wound manage- binding to sodium channels as well as inhibition of ment) will be performed. Th e most common side eff ects voltage-dependent calcium channels. Due to its seda- include sedation, constipation, nausea, and vomiting. It tive eff ects, amitriptyline should be administered dur- is essential to take care of side eff ects (for constipation, ing the evening and should be slowly titrated. Par- prescribe laxatives and advise the patient about fl uid in- ticularly in older patients, the initial dose should not take; for nausea, prescribe antiemetics and inform the exceed 25 mg. Th e maximum dose for cancer pain patient that nausea is often self-limiting). In cases of he- is approximately 75–100 mg/day. Contraindications patic dysfunction (e.g., liver cirrhosis), the duration of might arise from preexisting cardiac diseases such as action might be prolonged, so dosing intervals should arrhythmias or conduction defects. Secondary anti- be extended. In renal impairment, dose reduction is rec- depressants such as nortriptyline or desipramine are ommended while maintaining the application intervals. as eff ective as TCAs but are often better tolerated Other opioids to be used include tramadol, due to less side eff ects. Selective serotonin reuptake which is a synthetic opioid not only stimulating mu-re- inhibitors (SSRIs) such as fl uoxetine are better toler- ceptors but also inhibiting the presynaptic reuptake of ated as well, but they are also less eff ective in relieving serotonin and norepinephrine. Dosage is every 4 hours neuropathic pain. New antidepressants with a mixed for immediate-release formulations and three times a mechanism of action such as venlafaxine, paroxetine, day for sustained-release formulations. When switch- or duloxetine seem to be eff ective as well, but for can- ing from tramadol, which is sometimes classifi ed as a cer pain management the evidence is sparse, and they “weak opioid,” to morphine, the conversion ratio has to are not available in many countries. be considered (e.g., 100 mg oral tramadol is equivalent to approximately 10 mg of oral morphine). Th e maxi- Opioids mum dose of tramadol should not exceed 400–600 mg/ Common fallacies about opioids include a lack of effi ca- day. Among the side eff ects, there is a high prevalence cy in neuropathic pain conditions. Th is belief has been of nausea and vomiting. In renal failure, intervals be- proven not to be true. Th ere is abundant evidence dem- tween doses should be increased. Th e recommended onstrating the effi cacy of these drugs. However, neuro- dose in the case of liver cirrhosis amounts to 50 mg ev- pathic pain may be less responsive to opioids compared ery 12 hours. to nociceptive pain. Opioids should be titrated indi- Oxycodone is a semisynthetic opioid that ac- vidually and carefully to fi nd out the optimal balance tivates the mu-receptor as well as the kappa receptor. between benefi t and side eff ects. By combining opioids Duration of action is 4 hours. Due to the better oral with adjuvants such as gabapentin, the dose of each bioavailability the conversion ratio to morphine is 1:2 drug can be reduced and the eff ect on pain relief is usu- (e.g., 5 mg oral oxycodone equals 10 mg oral morphine). ally greater than using only one of those drugs. Th ere- Oxycodone should be used very carefully in situations fore, a combined therapy should be considered in neu- of renal or hepatic dysfunction, due to the increased ropathic pain. elimination half-life. 160 Rainer Sabatowski and Hans J. Gerbershagen

Transdermal fentanyl, a synthetic mu-receptor grapefruit juice are responsible for magnifi ed metha- agonist, delivers fentanyl via a self-adhesive patch with done eff ects, whereas corticosteroids, St. John’s wort, a rate-limiting membrane. Due to the slow delivery, the carbamazepine, and rifampin might lower the eff ect. patches have to be changed every 72 hours (in 20% of Methadone might cause prolongation of the QT-inter- patients a new patch has to be applied every 48 hours val and may cause torsades de pointes ventricular tachy- due to end-of-dose failure). Th e conversion ratio to cardia. Th erefore in patients at risk of hypokalemia, car- morphine is 100:1 (e.g., 120 mg morphine/day equals diac diseases, or cocaine abuse, methadone should be 50 μg fentanyl/hour). Advantages over morphine are used carefully, and an electrocardiogram should be per- the absence of active metabolites. However, in the pres- formed, if available. ence of renal dysfunction, sensitivity to the drug’s eff ect is increased. Liver cirrhosis does not seem to aff ect the Corticosteroids pharmacology of fentanyl, but impaired liver blood fl ow Corticosteroids, especially dexamethasone, are helpful or liver failure does so. Constipation is less pronounced when there is clinical evidence of nerve structure com- as compared to morphine. Disadvantages include adhe- pression or pain due to edema surrounding the metas- sive problems and the slow onset of action (when the tases. In cases of severe pain, doses of 16–24 mg a day patch is applied for the fi rst time, a 12-hour gap before should be prescribed initially. In cases of an emergency the onset of action has to be taken into account). (spinal cord compression) initial intravenous doses of Methadone might be considered an important up to 100 mg, followed by 60 mg in three divided doses alternative and, in cases of severe plexopathy, even as should be used. Steroids should be continued until oth- a fi rst-line opioid. Methadone is a synthetic opioid act- er treatment approaches (radiotherapy, drug therapy) ing as a μ-receptor agonist, an NMDA-receptor block- are initiated, after which dexamethasone can be tapered er, and a presynaptic serotonin reuptake inhibitor. Due off gradually. Dexamethasone has two other “side ef- to its long elimination half-life of 24 hours (up to 130 fects” that might be helpful for palliative treatment. It hours), titration is sometimes diffi cult, but methadone has an antiemetic eff ect and might increase the appetite. can also be regarded as a long-acting opioid, which ne- To increase appetite, dexamethasone can be prescribed cessitates only three to four daily dosages. Th e usual continuously in a daily dose of 2 mg. dose begin with 5 mg q.i.d. for 2–3 days. For inadequate pain relief or breakthrough pain, an additional 5 mg NMDA-receptor antagonists might be administered. Switching to or starting with Excitatory neurotransmitters, such as glutamate, play a methadone might be diffi cult. For this reason an algo- major role in pain transmission at the spinal cord level. rithm is recommended. On day 1 treatment with pre- Glutamate activates the NMDA receptor, which is as- existing opioids should be stopped. Oral methadone sociated with phenomenon such as central sensitiza- 2.5–5 mg should be administered every 4 hours. For tion. Ketamine, an NMDA-receptor antagonist and a breakthrough pain 2.5–5 mg methadone might be used drug used extensively in anesthesia, should be consid- additionally (with a dosage interval of 1 hour). On days ered, especially in situations when opioid analgesia is 2–3, a dose maximal increment of 30% might be neces- not eff ective enough. Th e addition of oral ketamine ap- sary, if pain relief on day 1 was not suffi cient. On day proximately 10–25 mg t.i.d. should be combined with 4, 72 hours after initiating methadone therapy, the dos- diazepam in low doses (e.g., 5 mg) to avoid psychotic ing interval should be changed to t.i.d. (every 8 hours), symptoms associated with the use of ketamine. and the intervals for breakthrough medication should be prolonged to 3 hours as well. If pain relief is still not Cannabinoids adequate or if pain increases due to cancer progression, Newer classes of drugs to treat neuropathic pain are dose adjustments might be performed. Patients on very cannabinoids. Th ere is evidence that oral delta-9-tetra- high oral morphine doses (>1000 mg/day) should start hydrocannabinol (THC) and other cannabinoids might on day 1 with 50 mg methadone q.i.d. Over the follow- provide relief from neuropathic pain, improve appetite, ing days, dose adjustments should be performed as de- and reduce nausea and vomiting. However, these drugs scribed above. Due to its metabolism via cytochrome cannot be recommended in general, due to the lack of P-450, precautions have to be taken to prevent drug in- well-designed studies in the area of cancer-related neu- teractions. Ketoconazole, HIV protease inhibitors, and ropathic pain. Lung Cancer with Plexopathy 161 Nonpharmacological Approaches cold spoon) give strong evidence of a neuropathic Nonpharmacological treatment approaches include epi- pain syndrome. dural opioid application and continuous infusion of lo- • In cases of neuropathic pain, a combination of cal anesthetics via a brachial plexus catheter. However, anticonvulsants, antidepressants, and opioids catheter dislocation and infection might be regarded is usually more eff ective compared to an opioid as a major obstacle in applying this form of therapy, es- monotherapy. pecially in rural areas where anesthesiologists are not • Consider the use of methadone in cases of “in- available. tractable” neuropathic pain syndromes. Cordotomy is a neurodestructive procedure in which the anterolateral spinothalamic tract is destroyed References to produce contralateral analgesia. Th e pain has to be [1] Dworkin RH, O’Connor AB, Backonja M, Farrar JT, Finnerup NB, Jen- strictly unilateral and due to the frequent recurrence of sen TS, Kalso EA, Loeser JD, Miaskowski C, Nurmikko TJ, Portenoy pain, the life expectancy of the patient should be lim- RK, Rice AS, Stacey BR, Treede RD, Turk DC, Wallace MS. Pharmaco- logic management of neuropathic pain: evidence-based recommenda- ited. Important neurological complications include pa- tions. Pain 2007;132:237–51. [2] Jaeckle KA. Neurological manifestations of neoplastic and radiation- resis, ataxia, phrenic nerve paralysis, and in long-term induced plexopathies. Semin Neurol 2004;24:385–93. survivors a delayed onset of dysesthetic pain. [3] Shen KR, Meyers BF, Larner JM, Jones DR. American College of Chest Physicians. Special treatment issues in lung cancer: ACCP evidence- based clinical practice guidelines, 2nd edition. Chest 2007;32(Sup- pl):290–305. Pearls of wisdom [4] Vecht CJ. Cancer pain: a neurological perspective. Curr Opin Neurol 2000;13:649–53. • In the clinical evaluation certain pain descriptors (e.g., burning or lancinating pain) reported Websites by patients in combination with neurological National Cancer Institute: www.cancer.gov signs (e.g., hypoesthesia, allodynia, or pathologi- World Health Organization: www.who.int cal cold/warm thresholds) by bedside testing with European Association for Palliative Care: www.eapcnet.org Non-Small Cell Lung Cancer Treatment (PDQ®): simple tools (e.g., a cotton-wool tip, needle, or www.meb.uni-bonn.de/cancer.gov/CDR0000062932.html

Guide to Pain Management in Low-Resource Settings

Chapter 21 Lung Cancer with Breathing Problems

Th omas Jehser

Why is important to know about (burning pain). Mr. K. sought consultation with his doc- pain in lung cancer? tor, who established a successful medication regimen with a combination of tramadol and carbamazepine. Being Lung cancer is the most common lung tumor and the able to move a lot better, Mr. K. became more aware of most common malignant disease. Th e incidence in his dyspnea and exhaustion following relatively short dis- Europe is estimated by the World Health Organiza- tances of walking. His wife also noticed that he had sig- tion (WHO) to be 38/100,000 inhabitants (in Africa nifi cant weight loss and a constant cough during the last 9/100,000). It causes about 1.2 million deaths per year couple of months. An X-ray of the thorax showed a prom- worldwide. Since 1953 it has been the most common inence of the right hilum of the lung. He was sent to Atba- cause of death by cancer within the male population, ra for further examination. Unfortunately, the CT detect- and since 1985 within the female population. ed a central tumor of the right bronchial system, which by bronchoscopy was histologically classifi ed as a non-small- Case report—part one cell lung cancer. Furthermore, scintigraphic and X-ray examinations reveal scattered bone metastases, such as in Mr. Tarik Al-Khater is a 65-year-old man with an ath- the lumbar spine and the right knee. letic constitution. He used to work as a postman in Bar- bar, Northern Sudan, and remained active doing fi tness What are the causes and risk exercises until a year ago. Twenty years ago, he had quit smoking, having accumulated 10 “pack years” (one “pack factors for lung cancer? year” means smoking 20 cigarettes per day throughout one year). Up to 2 years ago, he had never been ill, though Th ere are endogenous factors for the onset of lung can- he had undergone an appendectomy and osteosynthet- cer (genetic disposition, active HIV infection, pulmo- ic surgery for a tibial fracture. Th en at the age of 63, he nary fi brosis, and scarring following parenchyma injury received a diagnosis of pulmonary emphysema and dia- or tuberculosis). Exogenous conditions considered as betes mellitus. Nine months ago, he suff ered a herniated risk factors are smoking in the fi rst place (partly respon- lumbar disk and underwent surgery because of muscle sible in 90% of lung cancer deaths) as well as exposure weakness of the right thighs. Furthermore, there remained to dust and particles such as asbestos, chromates, and a mixed pain syndrome of the lower back, right hip, and polycyclic aromatics or to radiation from uranium, ra- right knee, with a dominating neuropathic component don, or even medical radiation therapy.

Box 1. Common symptoms of beginning Box 2. Common extrathoracic diseases and lung cancer infections with pulmonary manifestation Persistent cough Breast cancer Hemoptysis Rectal cancer Dyspnea Renal cancer Chest pain Malignant melanoma Hoarseness Sarcomas Fever, mucoid impaction Aspergillosis Other pain locations Tuberculosis Loss of appetite, weight, and strength Helminthiasis Paraneoplastic syndromes Cushing syndrome Herpes zoster Peripheral neuropathy Venous thrombosis Lung Cancer with Breathing Problems 165 Case report—part three and blood vessels. Th e degree of ventilatory restriction depends on the magnitude of resection. Surgical treat- Mr. K. has been ill with lung cancer for 7 months now. ment needs to be conducted in a specialized clinical de- Four weeks ago, he lost his appetite, and he feels sick partment. Postoperative rehabilitation is possible in the quite often. He has lost weight continuously (about 30% outpatient setting and must not be disregarded. Palliative of his initial body weight within one and a half years). surgery is done to remove metastases of extrathoracic Although carbamazepine has been stopped, the blood tumors or local relapse as well as for draining of second- tests show high values for liver transaminases, accompa- ary infection such as empyema. Endoscopic or vascular nied by upper abdominal pain. A physical examination interventions help with the reopening of airways and reveals an upper abdominal mass, and ultrasonography vessels by stenting or by laser or cryoextraction. detects multiple metastases in the liver and also in both Radiotherapy alone cannot be used with a cu- adrenal glands. rative intention. In combination with chemotherapy, it The oncologist recommends chemotherapy, may reduce the size of the tumor (downstaging), which which would have to be conducted in the regional hos- might open the route to successful surgery (neoadjuvant pital. Mr. K. is reluctant to return to the hospital in strategy) and to an extension of survival time. Palliative Atbara, the capital, and asks his friends and relatives radiotherapy intends to reduce the activity of metasta- for information on traditional treatment options they ses, which may result in reduction of pain (bones, liver, might have heard of. CNS, and pleura), blood congestion (superior vena cava syndrome caused by lymph node metastases of the me- What are the treatment options diastinum), or neurological disorders (CNS). in advanced lung cancer? Systemic pharmacological therapies (chemo- therapeutic, antihormone therapy, and others) work Treatment options include: in a palliative way to reduce the bulk mass or the tu- • Surgical therapy (curative or palliative) mor growth rate, allowing prolongation of survival. • Radiotherapy (neoadjuvant, palliative, or symptom- Th eir application usually weakens the general condi- targeted) tion of the patient. It is therefore necessary to consid- • Chemotherapy and other pharmacological therapy er the quality of life of individual patients from their (palliative) personal perspective. • Naturopathy (palliative) • Palliative care (adjuvant) Are there therapeutic alternatives Of course, the very best therapy would be the prevention of risk factors, but primary prevention pro- to surgery, chemotherapy, cedures are not established. Diagnostic evaluation at the and radiotherapy? earliest time is crucial for the course of the illness. Alternative (or complimentary) treatment strategies are Curative surgery needs the diagnosis of a low based on traditional and empirical concepts. Th ey may stage of disease (0–IIIa) in order to make eradication of be looked at as palliative and should not replace sci- the tumor possible by resection. Potential techniques entifi c medical eff orts. Using a palliative perspective, include lobe resection, (pleuro-) pneumonectomy, or these strategies may very well be of great meaning and bronchial reconstruction. Additional options are dissec- eff ectiveness within the individual disease trajectory. It tions of lymph nodes and reconstruction of pericardium

Box 3. Common general disorders in lung cancer patients Neurological: Limb palsy, hemiparesis, paraparesis, pain, delirium, epileptic seizures Metabolic: Diabetes mellitus, SIADH (syndrome of inappropriate antidiuretic hormone hypersecretion), anemia, thrombocytosis, thrombopenia, hypercalcemia Cardiovascular: Hypotension, thrombosis, superior (or inferior) vena cava congestion Gastrointestinal: Nausea, vomiting, bowel obstruction, liver failure 166 Th omas Jehser is often quite astonishing how they help the patient and pain, as well as some dyspnea at rest. Shortly afterwards, their relatives face the illness with more understanding a scleral icterus begins, and Mr. K. shows periods of dis- and to deal better with feelings of helplessness, which orientation and depression. His family takes him again again might help to direct the path of disease to a cer- to the Atbara district hospital for examination. It turns tain extent. out there that he has developed a serious bone marrow According to the WHO, “Palliative care is an insuffi ciency so that no further chemotherapy can be giv- approach that improves the quality of life of patients en. He is now sent home to talk with his family doctor and their families facing the problems associated with about further action that might be taken. life-threatening illness, through the prevention and relief of suff ering by means of early identifi cation and im- What are the consequences of peccable assessment and treatment of pain and other dyspnea, and how is it treated? problems, physical, psychosocial and spiritual.” Th e founder of modern palliative care, Dame Cicely Saun- Dyspnea is defi ned as a subjective experience of breath- ders (1918–2005), developed her fundamental ideas ing discomfort, consisting of diff erent conditions that when she was trying to ease and diminish cancer pain all lead to an increased breathing eff ort, either needing by looking at it from more than a “physical” perspective. more strength or a higher respiratory rate. Th is experi- So she inaugurated treatment strategies for the psycho- ence is also infl uenced by interactions among physical logical, social, and spiritual needs of the patients besides and emotional conditions. Dyspnea may be caused by, taking care of their physical condition, according to the but is not at all identical to, respiratory insuffi ciency. concept of “total pain.” Palliative care, therefore, eases While dyspnea is a subjective sensation of the patient, physical suff ering and provides information and under- respiratory insuffi ciency is a “physiological” phenom- standing within the social context of the patient. In the enon that can be exactly quantifi ed by testing. Th ere are same way, it delivers consolation and assistance to help multiple causes for respiratory insuffi ciency originating with anxiety and emotional pain caused by the threat- in the pulmonary, cardiac, vascular, bony, muscular, and ened loss of one’s relations and life. nervous systems. Th e amount of resulting dyspnea depends heavily on the course of development of respira- Case report—part four tory insuffi ciency and its profoundness. Th erefore, some patients may be able to live with a greatly decreased re- Mr. K. fi nally agrees to have chemotherapy. After fi nding spiratory capacity without feeling any dyspnea at rest, transportation, he visits the district hospital in Atbara while others with minor respiratory insuffi ciency may routinely for the treatments and the necessary examina- suff er intense shortness of breath. Feeling dyspnea eas- tions and feels somehow safe and stabilized, although he ily causes anxiety, and vice versa. Th e diff erentiation of has to take antibiotics for a short term of pyogenic bron- shortness of breath therefore requires the clinician to chitis. He meets other patients—many of them much evaluate not only vital capacity and FEV1, but also the younger than himself—who tell him about side eff ects, general condition of the patient, so as to avoid underes- which he fi nds to be irrelevant to himself at this point. timation of the problem. He gets a lot of relief when he fi nds a group supervised by For therapy for dyspnea to be eff ective, knowl- a health care worker in his home town where they prac- edge of its physiology is helpful. In case of a possible tice breathing and relaxation techniques. With the help treatment of underlying causes, such as bronchospasm of his family and friends he also gets advice from a tradi- or anemia, priority is given to this type of therapy. As tional healer, who recommends an additional composite one symptom of dyspnea deals with some sort of agita- medication consisting of herbal and mineral substances. tion, sedative treatment allows successful symptom con- In personal meetings with his spiritual adviser Sheikh trol, which might even help the breathing system to run Farshi, he learns to talk to his wife and three children more effi ciently. about the possible consequences of a fatal disease for the Besides sedative drugs such as benzodiazepines, family and their fi nancial aff airs. morphine is probably the most important remedy avail- After the next course of chemotherapy, he suff ers able for this important clinical situation. Morphine re- from vomiting and weakness for the fi rst time following duces the subjective “air hunger” signifi cantly, regardless such a treatment. Again he feels abdominal and back of the actual physiological need for O2 and CO2 transport Lung Cancer with Breathing Problems 167 and exchange. Other drugs such as haloperidol, cannabi- Case report—part fi ve nol, and doxepin help to reduce the psychological distress and agitation. Besides pharmacotherapy, the treatment Mr. K. has returned home and is mostly resting in a com- of cutaneous trigger zones by massage, cognitive and be- fortable chair in the living room. His wife and two of the havioral distraction, and even simply directing fresh air three children live with him in the house. Neighbors and toward the face stimulating trigeminal receptors, with a some other family members visit quite regularly so that direct infl uence on breathing frequency, are means that the patient participates in what is going on around him to lead to reproducible relief of suff ering. Th e availability of a certain extent. Mr. K. has started to smoke again (about morphine, oxygen, and a fan may therefore be the most three cigarettes on a good day), which he claims “does not important means and, most of the time, are suffi cient to make any diff erence” at this point and reminds him of the control even advanced stages of dyspnea. “good old days” when he was a young postman in his original home town. Smoking also gets him to walk a few steps, Besides dyspnea, what else should because his family insists that smoking is only allowed be considered in the treatment of outside. Th e family doctor regularly visits the patient twice a week. He has instructed Mrs. K. and one of the sons to lung cancer? administer morphine via a subcutaneous route using ti- Most often lung cancer is a progressive disease accom- tration doses in case of pain or dyspnea, which has been panied by complications caused by tumor metasta- occurring several times during the evenings and nights. ses and general physical exhaustion. Th ese complica- One day Mr. K. stumbles on his way back to his chair tions often go along with pain and dyspnea and lead to and is afraid of falling again after this incident. Th e next enormous psychological suff ering, which needs to be day he does not leave his bed and seems to be more dis- addressed by appropriate treatment and honest infor- oriented than ever. Th e visiting community nurse admin- mation about the therapeutic options. In this way it is isters a sedative drug to the more and more agitated Mr. possible to infl uence the patient’s perspective regarding K. and calls for the family doctor. When the doctor comes his or her personal quality of life. in the next day, the general condition of Mr. K. has wors- • Th e wide range of treatments targeting the diff er- ened. He dreams heavily, is feverish, and shows seizures of ent possible complications include: his right arm and his face. Th e doctor decides to leave Mr. • Medication (e.g., analgetics, antibiotics, broncho- K. in Barbar, since he sees no further options for specifi c dilators, corticosteroids). treatment, as he explains patiently to the anxious family. • Substitution of albumin, erythrocytes, electro- Again a sedative is given subcutaneously, and the patient’s lytes, fl uids, and caloric agents. agitation subsides, which helps the family to remain at his • Radiotherapy (to treat lytic bone lesions, tumor side constantly, though weeping a lot. At the end of this obstruction of central airways, superior vena cava day, Mr. K. dies without regaining consciousness or show- syndrome, or intracranial pressure). ing signs of agitation or suff ering, especially dyspnea. • Surgical, endoscopic, and intravascular interventions. Pearls of wisdom Complementary treatment off ers exercise (physiotherapy), psychological or spiritual support, Understand that: as well as receptive and imaginative therapies (mas- • Lung cancer is a life-threatening disease. sage, musical therapy, and active relaxation tech- • Th e character of breathing problems helps you to niques). A great number of patients carrying progres- decide on their treatment. sive lung cancers die from the complications of their • Lung cancer causes pain problems, which can be illness rather than from the lung cancer itself. During treated. the fi nal period of life, supporting and comforting the • Palliative care can be given to patients with lung patient by lowering anxiety, agitation, weakness, pain, cancer. and dyspnea is most important. When clinicians have • Morphine and a fan may, in most cases, be suffi - provided comprehensive instructions and are available cient to prevent the patient from suff ocating. as a backup if needed, this support may be provided by • Th e necessary dose of morphine is not given family members at home. as milligrams per kilogram of body weight, but 168 Th omas Jehser rather by titration in small repetitive doses until complimentary, alternative, or traditional median eff ective dose is achieved. cine are not justifi ed. • Th e positive eff ects of morphine far outweigh the risk of respiratory depression by opioids, since ti- References tration allows fi nding the balance between reduction of dyspnea and the typical side eff ect of re- [1] Alberg AJ, Samet JM Epidemiology of lung cancer. Chest 2003;123:21. [2] American Th oracic Society. Dyspnea: mechanisms, assessment and spiratory depression. management, a consensus statement. Am J Respir Crit Care Med • Morphine should be given subcutaneously to al- 1999;159:321. [3] Bruera E, MacEachern T, Ripamonti C, Hanson J. Subcutaneous mor- low fast onset of action in acute situations of dys- phine for dyspnea in cancer patients. Ann Intern Med 1993;119:906. [4] Colice GL. Detecting lung cancer as a cause of hemoptysis in pa- pnea, if the intravenous route is not available. tients with a normal chest radiograph: bronchoscopy vs. CT. Chest • Patients with dyspnea in end-stage lung cancer 1997;111:877. [5] Harrington SE, Smith TJ. Th e role of chemotherapy at the end of life: not only need pharmacotherapy, but especially “when is enough, enough?” JAMA 2008;299:2667. require a team of caring family members, health [6] Holty JEC, Gould MK. When in doubt should we cut it out? Th e role of surgery in non-small cell lung cancer. Th orax 2006;61:554. care workers, friends, and spiritual advisors. [7] Silvestri GA, Spiro SG. Carcinoma of the bronchus 60 years later. Th o- rax 2006;61:1023. • Anything that helps the patient should be used, [8] Toloza EM, Harpole L, McCrory DC. Noninvasive stating of non-small because in palliative care, reservations about cell lung cancer: a review of current evidence. Chest 2003;123:137. Guide to Pain Management in Low-Resource Settings

Chapter 22 Hematologic Cancer with Nausea and Vomiting

Justin Baker, Raul Ribeiro, and Javier Kane

Case report treatment or palliative treatment) or complications directly or indirectly related to the disease. More than half Michael is a 23-year-old man with recurrent lympho- of cancer patients who are dying experience signifi cant blastic lymphoma in his bone marrow and central ner- nausea, and nearly one-third experience vomiting. Th e vous system (CNS) who is receiving end-of-life care with clinical picture of N/V is often multifactorial. Regardless palliative chemotherapy. Five days ago, Michael started of the etiology, the symptoms of N/V can interfere with on a course of oral cyclophosphamide (see Table 1 for patients’ nutritional status and their enjoyment of eat- emetogenic properties of chemotherapy) with the inten- ing and drinking and can signifi cantly aff ect their quality tion of prolonging a life of good quality. Michael’s chief of life and the quality of their death. When not properly complaint at this time is severe nausea accompanied by managed, N/V interferes with a patient’s nutritional sta- vomiting 2 or 3 times per day. Th e main concern of Mi- tus, hydroelectrolytic homeostasis, mental status, clinical chael’s parents is his inability to eat or drink anything performance, and compliance with treatment. Clinicians considerable. Michael is currently receiving morphine 30 therefore have an ethical imperative to prevent, screen, mg orally every 4 hours, mostly to control his headaches. assess, treat, and follow up N/V to ensure the best pos- He is on no other medications. Further history reveals sible care for dying cancer patients. that Michael’s nausea and vomiting have been increasing in severity over the past 3 days (he started the cyclophos- What are the main pathways phamide 5 days ago). He has not had a bowel movement involved in the pathophysiology for 7 days. of nausea and vomiting? Why is treatment of nausea Th e pathophysiology of nausea and vomiting is fairly and vomiting so important? well characterized. Th e vomiting center receives aff erent input from four neuronal pathways that carry emeto- Nausea is defi ned as a feeling of sickness in the stomach genic signals: and is characterized by an urge to vomit. Vomiting is the Peripheral pathways from the gastrointestinal forceful expulsion of the contents of the stomach and (GI) tract through the vagus and splanchnic nerves. Th e proximal small intestine. Nausea and vomiting (N/V) are GI tract may elicit nausea through sensations of irrita- common symptoms in dying patients and arise as a re- tion by medications, tumor infi ltration, obstruction, dis- sult of either treatment-related toxicity (disease-specifi c tension, or constipation or fecal impaction.

Neuronal pathways from the chemoreceptor cells of the small intestine and activates 5-HT3 re- trigger zone (CTZ). Th e CTZ is located in the oorfl of ceptors on peripheral vagal fibers and central struc- the fourth ventricle and lacks a true blood-brain bar- tures. Delayed emesis occurs after the first 24 hours rier. Th is allows the zone to sense fl uctuations in the of the exposure to the emetogen and persists up to concentration of certain substances in the blood- 4–6 days. In addition to serotonin, substance P, along stream. Th e CTZ may also be stimulated by posterior with other neurotransmitters, appears to have an im- fossa tumors. portant role in the maintenance of acute and delayed Vestibular pathways from the labyrinth. Vestibu- N/V. Anticipatory N/V is defined as a conditioned lar pathways may be stimulated by vestibular disease such “learned” response, usually occurring when episodes as vertigo, middle-ear infections, or motion sickness. of N/V have been inadequately controlled with prior Cortical pathways in response to sensory or psy- exposures. It occurs before, during, or after the expo- chogenic stimuli. Cortical stimulation may come from a sure to the emetogen, but not at the time emetogen- CNS or meningeal tumor, increased intracranial pres- related N/V would be expected to occur. In this situa- sure, anxiety, or uncontrolled pain. tion, a variety of stimuli such as odor, sight, or sound provoke emesis. How are nausea and vomiting classifi ed? What is the diff erential diagnosis

Nausea and vomiting are usually classified as acute, of nausea and vomiting? delayed, refractory, anticipatory, or breakthrough. Michael’s case has helped demonstrate that nausea and Acute emesis, which appears to be mediated by se- vomiting is often multifactorial. Fig. 2 details the diﬀ er- rotonin, occurs within 3 to 4 hours after exposure ential diagnosis and etiologies of nausea and vomiting to an emetogen such as chemotherapy (see Table as well as providing a helpful mnemonic to quickly re- 1). Serotonin is released from the enterochromaffin call the cartoon:

Metabolic abnormalities: Increased Delayed e.g. uremia, liver failure, intracranial pressure chemotherapy-induced hypercalcemia nausea and vomiting

Constipation Anxiety Nausea and vomiting etiology mnemonic A − Anxiety or anticipatory V − Vestibular Opioids O − Obstructive M − Medications and metabolic Radiation A − Infection and inammatory therapy T − Toxins

Other drugs− e.g. antibiotics, NSAIDs Autonomic dysfunction Bowel Fig. 1. Diﬀ erential diagnosis/etiologiesPeptic ulcer of nausea and vomiting (adapted from Dalal et al. [1]) disease obstruction and a quick diﬀ erential diagnosis mnemonic.

Fig. 1. Diﬀ erential diagnosis/etiologies of nausea and vomiting (adapted from Dalal et al. [1]) and a quick diﬀ erential diagnosis mnemonic. Hematologic Cancer with Nausea and Vomiting 171 What chemotherapy agents cause the most problems with nausea and vomiting?

Table 1 Risk for emesis in the absence of prophylactic antiemetic treatment with commonly used chemotherapy drugs [adapted from Perry (2001)] Drug (Dose) High Risk (>90%) Moderate Risk (≥30–90%) Low Risk (<30%) Carmustine (>250 mg/m2) Carboplatin Asparaginase Cisplatin Carmustine (<250 mg/m2) Bleomycin Cyclophosphamide (1500 mg/m2) Cisplatin (<50 mg/m2) Cytarabine (<1 g/m2) Dacarbazine (>500 mg/m2) Cyclophosphamide (<1500 mg/m2) Docetaxel Dactinomycin Cytarabine (>1 g/m2) Doxorubicin (<20 mg/m2) Lomustine (>60 mg/m2) Doxorubicin Etoposide (p.o. or i.v.) Mechlorethamine Epirubicin Fluorouracil (<1 g/m2) Streptozocin Idarubicin Gemcitabine Ifosfamide Interleukin-2 Irinotecan Methotrexate (<100 mg/m2) Melphalan Methotrexate (>100 mg/m2) Mitoxantrone (>12 mg/m2) Mitomycin Procarbazine Mitoxantrone (<12 mg/m2) Paclitaxel Rituximab Temozolomide Teniposide Th iotepa Topotecan Trastuzumab Vinblastine Vincristine

How should I assess for nausea • Anxiety or unrelieved pain (often overlooked as and vomiting? causes of nausea) When performing the physical examination, Th e assessment should include the history and physical watch out for: examination of the patient. When taking the history, ask • Cachexia or malnutrition, muscle wasting, de- about the characteristics of N/V: creased skin fold thickness (indicators for malab- • Onset (to identify a speciﬁ c trigger) sorption) • Relationship to eating (postprandial N/V may be • Abdominal distension, increased bowel sounds, caused by an obstruction) abdominal masses or ascites (indicators for bowel • Medication review (a medication change may obstruction) help) • Abdominal fullness, including rectal examination • Bowel movement history (are there indications (constipation due to hypomotility) for dysfunctional intestines?) • Papilledema (raised intracranial pressure) • Vestibular component (antihistamines might be • Lying and standing blood pressure and Valsalva’s useful) maneuver (autonomic dysfunction) 172 Justin Baker et al. How can nausea and vomiting be Can you treat nausea and vomiting treated pharmacologically? with nonpharmacological options (complementary and alternative Pharmacological treatment of N/V is the mainstay of therapy. Table 2 lists frequently used medications to medicine)? treat N/V. Th e summary table at the end of this chap- Nonpharmacological modalities have not yet been ad- ter also includes useful treatment algorithms, including opted and incorporated into evidence-based practice pharmacological therapy. As with all symptoms, clini- guidelines. However, several acupuncture-point stim- cians need to frequently reassess the eﬃ cacy of treat- ulation techniques have been examined for treating ment and anticipate exacerbating factors. Adequate nausea, vomiting, or both. Th ese techniques include treatment and prevention of recurrent or prolonged methods that involve needles, electrical stimulation, nausea and vomiting are critical. magnets, or acupressure. Evidence supports the use of

Table 2 Common pharmacological agents used to treat nausea and vomiting (adapted from Policzer and Sobel [3]) Class of Drug Dose Comments Prokinetic Agents Metoclopramide 5–15 mg before meals and at For nausea and gastric stasis from various causes. Use bedtime; s.c./i.v. = p.o. metoclopramide with care; may cause dystonia, which is reversible with 1 mg/kg diphenhydramine. Antiemetic dosage is greater than prokinetic dosage by 0.1–0.2 mg/kg/ dose. Well tolerated with s.c. administration. Domperidone 0.3–0.6 mg/kg dose before meals Use domperidone with care; may cause dystonia, which is and at bedtime to a maximum of reversible with 1 mg/kg diphenhydramine. 80 mg/day. Antihistamines (Useful for vestibular and gut receptor nausea and vomiting, but relatively contraindicated by constipation because they slow the bowels further) Diphenhydramine 1 mg/kg/dose p.o. every 4 hours to a maximum of 100 mg/dose; s.c./i.v. = p.o. Hydroxyzine 0.5–1 mg/kg/dose every 4 hours to a maximum of 600 mg/day; s.c./i.v. = p.o. Promethazine 0.25–1 mg/kg every 4 hours; Use promethazine with care; can cause dystonia. Risk of s.c./i.v. = p.o. respiratory arrest in infants Dopamine Antagonists (Useful for medication and metabolic-related nausea and vomiting. Can cause dystonia, reversible with 1 mg/kg diphenhydramine or 0.02–0.05 mg/kg/dose benztropine to a maximum of 4 mg i.v. Intravenous use can cause postural hypotension; therefore i.v. should be given slowly.) Haloperidol 0.5–5 mg/dose every 8 hours up Use with care; only some preparations can be given i.v. to 30 mg/day; s.c./i.v. = ½ p.o. Use dextrose 5% in water to dilute. Well tolerated with s.c. administration. Chlorpromazine 0.5–1 mg/kg every 8 hours; i.v. More sedating. Irritating to tissues with s.c. administra- = p.o. tion. Prochlorperazine 0.15 mg/kg/dose every 4 hours Irritating to tissues with s.c. administration. to a maximum of 10 mg/dose; i.v. = p.o.

Serotonin 5-HT3 Receptor Antagonists (Also useful for postoperative nausea and vomiting and as second- or third-line agents after other types of antiemetics have demonstrated limited utility) Ondansetron 0.15 mg/kg/dose every 6 hours to Particularly helpful in chemotherapy-induced nausea and a maximum of 8 mg; i.v. = p.o. vomiting. High cost may preclude its use. Hematologic Cancer with Nausea and Vomiting 173

Class of Drug Dose Comments Benzodiazepines Helpful for anticipatory nausea and vomiting. Diazepam stings during i.v. administration; use a large vein and dilute solution. For patients younger than 5 years, max. dosage is 0.05–0.2 mg/kg dose every 6 5 mg/dose. For patients older than 5 years, max. dosage is Diazepam hours; i.v. = p.o. 10 mg/dose. 0.03–0.05 mg/kg dose every 5 hours to a maximum 4 mg/dose; Lorazepam i.v. = p.o./s.l. Corticosteroids Helpful for hepatic capsular distention, anorexia, and increased intracranial pressure. Can have long-term side eff ects. If the patient weighs less than 10 kg, 1 mg/kg 6–10 mg loading dose, then 2–4 loading dose, and then 0.1–0.2 mg/kg 2–4 times a day for mg 2–4 times a day for mainte- maintenance. Agonist eff ect when used in combination Dexamethasone nance; i.m./i.v. = p.o. with serotonin antagonists. 1.5 mg dexamethasone = 10 mg Prednisone prednisone Cannabinoids 2.5 mg twice a day (for adults Can cause dysphoria, drowsiness, or hallucinations. Ap- Dronabinol only) to a max of 20 mg/day petite stimulant. Other Anticholinergics Helpful for motion- or movement-related nausea and Transdermal preparation: 0.5 mg vomiting. Well-tolerated by s.c. tissues. Often causes dry changed every 72 hours; i.v./s.c.: mouth and blurred vision, and sometimes causes confu- Scopolamine 0.006 mg/kg every 6 hours sion. electroacupuncture by clinicians competent in its ad- details of all nonpharmacological and complementary ministration for chemotherapy-induced nausea. Other and alternative modalities and gives examples of po- modalities have not been well studied, but details are tential antiemetic benefi ts. provided for a comprehensive analysis. Table 3 provides

Table 3 Nonpharmacologic and complementary and alternative modalities used to treat nausea and vomiting (adapted from the National Comprehensive Cancer Network 2005) Examples with Benefi t in Nausea Modality Defi nition and Vomiting Massage therapy Group of systematic and scientifi c manipulations of Reiki, therapeutic touch body tissues best performed with the hands to aff ect the nervous and muscular systems and general circulation Mind-body, other Methods that emphasize mind-body interactions with Meditation—transcendental and relaxation techniques intended benefi ts that include relaxation and emo- mindfulness, yoga, prayer, guided tional well-being imagery, relaxation training Music therapy Th e use of music to help treat neurological, mental, Eff ective in postoperative nausea/ and behavioral disorders vomiting Acupuncture therapy Treatment of symptoms by inserting needles along Acupuncture or acupressure at the specifi c pathways Nei Guan or P6 point Dietary supplements Products in capsule, tablet, liquid, or dried form, in- Ginger root, huangqi decoctions, cluding vitamins, proteins, herbs, and other over-the- aromatherapy counter substances intended for decreasing nausea and vomiting 174 Justin Baker et al. What are the side eff ects of therapy?

All medications have a primary eff ect and side eff ects. Antiemetics should be chosen mainly on the basis of the etiology of the N/V and the mechanism of the medication. Side eff ects may hinder the ability to use certain drugs, however. Table 4 lists common side eff ects of antiemetics by the category of drug.

Table 4 Side eff ects of medications commonly used to treat nausea and vomiting Medication Adverse Eff ects* Antihistamines Most common: sedation, dry mouth, constipation. Diphenhydramine Less common: confusion, blurred vision, urinary retention. Hydroxyzine Belladonna alkaloid Most common: dry mouth, drowsiness, impaired eye accommodation. Scopolamine Rare: disorientation, memory disturbances, dizziness, hallucinations. Benzamides Most common: sedation, restlessness, diarrhoea (metoclopramide), agitation, Benzquinamide CNS depression. Metoclopramide Less common: extrapyramidal eff ects (more frequent with higher doses), Trimethobenzamide hypotension, neuroleptic syndrome, supraventricular tachycardia (with i.v. administration). Benzodiazepines Most common: sedation, amnesia. Lorazepam Rare: respiratory depression, ataxia, blurred vision, hallucinations, paradoxical reactions (weeping, emotional reactions). Butyrophenones Most common: sedation, hypotension, tachycardia. Droperidol Less common: extrapyramidal eff ects, dizziness, increase in blood pressure, Haloperidol chills, hallucinations. Cannabinoids Most common: drowsiness, euphoria, somnolence, vasodilation, vision dif- Dronabinol fi culties, abnormal thinking, dysphoria. Less common: diarrhea, fl ushing, tremor, myalgia. Corticosteroids Most common: gastrointestinal upset, anxiety, insomnia. Dexamethasone Less common: hyperglycemia, myopathies, osteonecrosis, facial fl ushing, Methylprednisolone mood changes, perineal itching or burning. Phenothiazines Most common: sedation, lethargy, skin sensitization. Prochlorperazine Less common: cardiovascular eff ects, extrapyramidal eff ects, cholestatic jaun- Promethazine dice, hyperprolactinemia. Chlorpromazine Rare: neuroleptic syndrome, hematological abnormalities. Th iethylperazine

5-HT3-receptor antagonists Most common: headache, asymptomatic prolongation of electrocardiographic Granisetron interval. Dolasetron Less common: constipation, asthenia, somnolence, diarrhea, fever, tremor or Ondansetron twitching, ataxia, lightheadedness, dizziness, nervousness, thirst, muscle pain, warm or ﬂ ushing sensation on i.v. administration. Rare: transient elevations in serum transaminases. * Most common; >10%; less common, 1%–10%; rare, <1%. Based on U.S. Food and Drug Administration- approved labeling and generalized to the drug class. Hematologic Cancer with Nausea and Vomiting 175 Pearls of wisdom

Treatment algorithms (adapted from Policzer and Sobel [3]) are shown in Table 5.

Table 5 Treatment algorithms Cause Symptoms Treatment Alternatives Cortical CNS tumor/meningeal irritation Focal neurological signs or mental status Corticosteroids changes Consider palliative radiation Increased intracranial pressure Projectile vomiting and headache Corticosteroids Anxiety or psychogenic symp- Anticipatory nausea, conditioned responses Counseling toms Relaxation techniques Benzodiazepines Uncontrolled pain Pain and nausea Increase pain medications Use adjuvants Vestibular Vestibular disease Vertigo or vomiting after head motion Antihistamines (meclizine) Middle-ear infections Ear pain or bulging tympanic membrane Antibiotic therapy and other supportive care Motion sickness Travel-related nausea Anticholinergics (scopolamine) Chemoreceptor Trigger Zone Medications Nausea worse after medication dosage or exac- Decrease dose or discontinue medication erbated after increasing dose Metabolic (renal or liver failure) Increased blood urea nitrogen (BUN), creati- Dopamine antagonist nine, bilirubin, etc. Hypercalcemia Somnolence, delirium, high calcium Hydration Corticosteroids Bisphosphonates Gastrointestinal Tract Irritation from medications Use of nonsteroidal anti-inﬂ ammatory drugs Discontinue drug if possible

(NSAIDs), iron, alcohol, antibiotics Add histamine (H2) blocker, proton pump inhibitor, or misoprostol Tumor inﬁ ltration or infection Evidence of abdominal tumor, candida esopha- Antihistamines gitis, colitis Treat infection Anticholinergics Constipation or impaction Abdominal distension, no bowel movement for Laxatives many days Manual disimpaction Enema Obstruction by tumor or poor Constipation unrelieved by treatment Prokinetic agents motility Malignant bowel obstruction Severe pain, abdominal distension, visible Analgesics (opioids) peristalsis Anticholinergics Dopamine antagonists Corticosteroids Consider octreotides

[2] Naeim A, Dy SM, Lorenz KA, Sanati H, Walling A, Asch SM. Evidence- References based recommendations for cancer nausea and vomiting. J Clin Oncol 2008;26:3903–10. [1] Dalal S, Palat G, Bruera E. Chronic nausea and vomiting. In: Berger [3] Policzer JS, Sobel J. Management of selected nonpain symptoms of life- AM, Shuster JL, Von Roenn, Jamie H, editors. Principles and practice limiting illness. Hospice and palliative care training for physicians—a of palliative care and supportive oncology, 3rd edition. New York: Lip- self-study program, 3rd edition, vol. 4. Glenview, IL: American Acad- pincott Williams & Wilkins; 2007. emy of Hospice and Palliative Medicine; 2008.

Management of Neuropathic Pain

Guide to Pain Management in Low-Resource Settings

Chapter 23 Painful Diabetic Neuropathy

Gaman Mohammed

Case report 1 (“neuroarthropathy”) insulin that she could also obtain at her local hospital and was given an antibiotic with a good Gram-positive Zipporah, a 54-year-old woman, who has had type 2 di- and -negative eff ect. She was advised to have her daily abetes for 12 years and is on oral hypoglycemic agents, dressing done at her local clinic and not use hydrogen came to the offi ce complaining about a history of leg peroxide solution on her injury. She was started on sim- pains, especially at night. She regularly walks to the lo- ple analgesics (paracetamol/acetaminophen) in combi- cal market where she sells vegetables. She has noticed nation with a weak opioid, tramadol. During follow-up swelling on her legs over the last few months, but has no review, she was started on amitriptyline at a low dose history of pain or trauma to the feet. Her husband Tom of 25 mg after she complained of burning sensations, es- noted blisters on her feet a day after she had worn a new pecially at night. She was also given crutches and was pair of sandals bought at her local market. Zipporah advised to mobilize, with partial weight bearing, for a hadn’t felt any discomfort while wearing these sandals. month as she mentioned she had to attend to her duties Th e blisters had burst, revealing cuts over the feet, and at the market. her husband convinced her to seek medical attention after she unsuccessfully tried using home remedies such as Case report 2 (60-year-old bandaging the wound with an old cloth and cleaning the diabetic male on oral wound with salt solution. hypoglycemic medication) Tests revealed an elevated random blood sugar of 15 mmol with an HbA of 11%. On visual examination Yusuf, a 60-year-old man from a coastal city, has had she had bilateral foot edema with a septic lesion over diabetes for 6 years. He gave a history of severe burn- both feet. Her foot pulses were present but feeble, prob- ing sensations in his feet at night, which was relieved by ably as result of the edema. She had reduced vibration placing his feet in a bucket of water. He didn’t seek medi- perception and pressure sensation in both feet. X-rays cal treatment for his ailment until he noted a painful were suggestive of destruction of the talus and calcaneus swelling of his toes of the right leg, although he did not bones in her feet. remember having had an injury to the foot. Examination On discussion with Zipporah, she was advised revealed that the right foot was infected, and the infec- that in view of her current poor glycemic control and foot tion had spread to the interdigital spaces. He also had infections, insulin therapy had to be recommended to decreased vibration and pressure sensation, as tested by control the blood sugar. She was started on twice-daily using a 10-g monofi lament and a tuning fork.

Pearls of wisdom

• Managing painful diabetic neuropathy continues to be a challenge in developing countries where resources are scarce and access to health care facilities is limited. • Diabetic patients often have poor follow-up or are seeking treatment at a late stage, when com- Advanced testing can be done using a biothesi- plications associated with neuropathy have al- ometer. A probe is applied to a specifi ed part of the foot, ready set in. usually on the big toe. Th e probe can be made to vibrate • On the other hand, primary care physicians may at increasing intensity by turning a dial. Th e person be- lack adequate knowledge and skills to screen for ing tested indicates as soon as he or she can feel the vi- and treat diabetic neuropathy. bration, and the reading on the dial at that point is re- • However, with basic knowledge on diabetic neu- corded. Th e biothesiometer can have a reading from 0 to ropathy and appropriate management of diabetes, 50 volts. It is known that the risk of developing a neuro- and with the help of simple screening tools such pathic ulcer is much higher if a person has a biothesiom- as tuning forks and monofi laments, early diagno- eter reading greater than 30–40 volts, if the high reading sis and improved management of diabetic neu- cannot be explained by age. ropathy are possible. • Since a diverse range of mechanism cause pain in What are the pharmacological diabetic neuropathy, treatment principles should treatment options for painful include a multifaceted approach aiming at improving glucose control, targeting the underlying diabetic neuropathy? pathological factors, and treating the symptoms. See Chapter 20 on Management of Postherpetic Neu- • Painkillers are selected according to the princi- ralgia for pharmacological analgesic treatment options, ples of treating neuropathic pain. since the same principles for treatment of neuropathic • Since pain often has a continuous burning quality, pain apply. gabapentin or amitriptyline—possibly combined with a weak opioid—are typical choices for pharmacological management of pain. What are complimentary • Th e eff ectiveness of nonpharmacological treat- approaches in management of ment options should not be underestimated. painful diabetic neuropathy?

Sometimes the simple things maybe very eff ective; pa- References tients sometimes fi nd out what works for they and may [1] Sorensen L, Wu M, Constantin D, Yue K. Diabetic foot disease: an in- be very inventive. Techniques often reported by patients teractive guide. International Consensus on the Diabetic Foot. [2] Zachary T, Bloomgarden MD. Clinical diabetic neuropathy. Diabetes to be very eff ective are: Care 2005;28:2968–74. • Immersing the feet in a bucket of cold water • Placing the feet on a cold cement fl oor Guide to Pain Management in Low-Resource Settings Chapter 24 Management of Postherpetic Neuralgia

Maged El-Ansary

Case report be called postherpetic neuralgia. Th is has a therapeutic consequence because spontaneous remission of pain be- As a general practitioner, you receive a 75-year-old male comes more unlikely after this period of time. Th erapeu- patient with a history of diabetes mellitus. He has had tic eff orts should be increased if pain lasts longer than a bronchogenic carcinoma and is currently on chemo- couple of weeks. therapy. He has pain in the left side of the chest along the distribution of the 5th, 6th, and 7th intercostal nerves. What is your possible diagnosis? Is acute pain a predictor of an Th e possibilities are myositis, coronary ischemia, outcome of postherpetic neuralgia? left-sided pleurisy, fractured ribs, itching due to skin allergy or drug eruption or other causes, such as the pre- Unfortunately, there are no accepted and validated fac- eruptive stage of acute herpes zoster. tors for predicting the severity and duration of pain after herpes infections. Pain may be almost or completely absent in patients who develop PHN. But for the elderly, Why is postherpetic neuralgia as pain can start before the skin changes, hemorrhagic diffi cult to treat? effl orescence and a location outside the trunk might indicate a high-risk patient. Postherpetic neuralgia (PHN) is known to be one of the most resistant chronic pain problems. It is classifi ed as a neuropathic pain state. Th e signifi cance is that the pain Are pain management and antiviral is coming from nerve lesions due to viral infections at therapy suffi cient to treat a patient the site of spinal nerve roots. with herpes zoster? Not only pain fi bers of the nerve but also sympathetic and tactile fi bers, and in rare occasions motor It is wise to summarize acute herpes zoster as a sign of fi bers, may be involved in the syndrome. Remember: an alarmingly low level of immunity. It should be known you can only make a diagnosis if you undress your pa- that acute herpes zoster and PHN could indicate a wide tient and look at the site of pain. range of underlying diseases. In many regions of the world, the fi rst diseases to consider underlying shin- When is pain after herpes zoster gles are immune-compromised diseases such as HIV/ called postherpetic neuralgia? AIDS and/or malnutrition. Early use of antiviral drugs and pain treatment in the early stages of the acute her- Most experts agree that pain lasting longer than 3 pes zoster will have an impact on the course of an acute months after an acute herpes infection (“shingles”) should attack and the possibility of lowering the incidence of

Chapter 25 Central Neuropathic Pain

Maija Haanpää and Aki Hietaharju

Case report 1 penetrate the spinal canal. Cord contusion was probably the result of the kinetic energy transmitted by the Abdul Shamsuddin, a 35-year-old shopkeeper from bullet. Th e patient’s pain medication included amitrip- Gulshan, Dhaka, was found by his wife lying on the fl oor tyline and gabapentin. Within 4 years, the neuropathic of his apartment. He was brought into the hospital on a pain started gradually to resolve, and gabapentin was makeshift stretcher carried by four relatives, all saying successfully tapered off . diff erent things about what had happened. In the emergency room, he was conscious but not able to move his Case report 2 legs or left arm. He was complaining of severe burning pain in his right hand and deep aching pain in both of Shabana, an Afghan housewife from Jalalabad in her his upper extremities. Th e man explained, incoherently, late thirties, came to a psychiatric outpatient clinic es- that his house had been entered by a gang of robbers, corted by her husband. She had suff ered for more than and the last thing he remembered was a loud gunshot. A 2 years from continuous burning pain in her left hand lacerated wound 1 cm in diameter was revealed on ex- and the right side of her face. She had been referred to amination of his neck. Neurological examination showed the psychiatrist by a general practitioner who, due to total loss of sensation below T2. Th ere was severe hyper- Shabana’s infertility, had assumed a psychogenic basis esthesia, hyperalgesia, and dynamic allodynia as well as as the cause of her pain. History taking revealed that she impaired cold sensation in the 4th and 5th fi ngers and had had a sudden attack of vertigo, slurred speech, and on the ulnar side of his right hand. In the left hand, there motor weakness in her left extremities 3 years earlier. was mild dynamic allodynia, and hyperalgesia was no- She had not consulted her doctor at that time. Most of ticed in the 3rd fi nger. Th e patient was able to fl ex his her symptoms had subsided within 2 days, but the mo- right arm and lift his hand up against gravity. A radio- tor weakness had persisted for weeks. She reported that graph of the cervical spine showed a posterior arch frac- the painful symptoms had appeared about 2 months ture of C7 and a 9-mm bullet lying close to the scapula after this attack. Neurological examination revealed on the right side. MRI of the cervical spine showed spinal slight clumsiness and ataxia in her left arm, but muscle cord contusion extending from the C4 to T2 level. Th e strength was regarded as normal. A conspicuous de- continuity of the spinal cord was intact, and no signs of crease in cold and pain sensibility was noticed on her hematoma were present. right cheek, and in the lower two-thirds of her left arm as Th is case shows that neurological injury and compared to the contralateral side. Cardiac auscultation spinal cord pain can occur even if a projectile does not did not reveal a pathological rhythm or sounds. Due to

Various traumas may result in dislocation and fracture What is syringomyelia? of spinal vertebrae and cause spinal cord injury. In ad- Syringomyelia is a cystic cavitation of the central spinal vanced countries, road traffi c accidents rank highest cord, most commonly in the cervical region. It can be among the etiological factors for traumatic spinal cord developmental, as in Chiari I malformation, or acquired, injury. According to an epidemiological study conduct- usually due to traumatic spinal cord injury. It is clinically ed in Haryana, India, the predominant cause of injury characterized by segmental sensory loss, which is typi- was falling from a height (45%), followed by motor vehi- cally of a dissociated type, in which thermal and pain cle accidents (35%). Other causes of spinal cord trauma sensations are lost but tactile and proprioceptive sensa- include sports injuries and acts of violence, primarily tions are preserved. Pain in cervical syringomyelia can gunshot wounds. In people with asymptomatic cervical be located in the hand, shoulder, neck, and thorax, is spinal stenosis, a fall or a sudden deceleration force can often predominantly unilateral (ipsilateral to the syrinx), cause a contusion in the cervical cord, even without any and can be exacerbated by coughing or straining. Auto- bone or joint trauma. Spinal cord injury can be partial, nomic symptoms such as changes in skin temperature saving some motor or sensory functions or both, or it or sweating in the painful area can also be present. Pain can be complete, causing paralysis and complete senso- may be the fi rst symptom, or it may appear after a long ry loss below the level of the lesion. delay after the original lesion. Motor weakness may appear with the progression of the disease. Neurosurgical What are the characteristics treatment is considered only in cases with recent and of central neuropathic pain in quick progression. spinal cord injury? What is phantom limb pain? Pain following spinal cord injury is divided into below- level pain and at-level pain. Th e latter is located in a After traumatic amputation, at least half of patients segmental or dermatomal pattern, within two segments experience phantom limb pain, which refers to pain above or below the level of spinal cord injury. It may be experienced in the lost part of the body. It is related 192 Maija Haanpää and Aki Hietaharju to central reorganization in the cerebrum, which ex- burning pain, but aching, pricking, and lacerating pain plains the peculiar phenomenon of pain experienced is also common. Central poststroke pain is most often in the missing part of the body. In some patients, phan- constant and spontaneous, but in rare cases it may be tom limb pain is maintained by stump pain (a periph- paroxysmal and allodynic (i.e., evoked by touch, ther- eral pain at the site of amputation). Phantom limb pain mal sensation, or emotions). Hyperesthesia is a com- is more likely to occur if the individual has a history of mon fi nding in sensory examination. In a hemisphere chronic pain before the amputation and is less likely if lesion, there is abnormal sensation on the contralateral the amputation is done in childhood. side of the face, trunk, and limbs, and accompanying Phantom pain is often similar to the pain felt motor paresis if the pyramidal tract is aff ected. In a low before the amputation, and in addition, the patient may brainstem lesion, there is a crossed pattern in the sen- experience nonpainful phantom phenomena, such as a sory changes: they are located ipsilaterally in the face twisted leg. and contralaterally in the trunk and limbs due to dam- Graded motor imagery and mirror therapy age of the ipsilateral trigeminal sensory nucleus and the are novel and inexpensive approaches that have been crossed spinothalamic tract, respectively. shown to reduce pain and disability in patients with phantom limb pain. In graded motor imagery, patients Is all pain neuropathic in patients go through three phases. First, they assess images who have had a stroke? of their limbs in various positions. Th e second phase consists of imagining moving the limbs in a smooth Nociceptive pain is also very common in patients who and painless manner. Finally, patients end up by actu- have had a cerebrovascular lesion. It most often aff ects ally mimicking the movement. In mirror therapy, pa- the shoulder and is related to changed dynamics due to tients are instructed to use the mirror in such a way motor weakness on the aff ected side. Possible causes are that the refl ected image of the intact limb seems to subluxation of the glenohumeral joint, rotator cuff tear, appear in the place of the amputated or aff ected ex- soft tissue injury due to inappropriate handling of the tremity. Th e mirror image produces an illusion of two patient, and spasticity of the shoulder muscles. “healthy” limbs, and movement of the healthy limb may ameliorate the phantom limb pain. Both of these What are the characteristics therapies aim at activation of cortical networks that subserve the aff ected limb. of central pain after traumatic brain injury?

What is the defi nition of central Traumatic brain injury occurs when a sudden, blunt, or poststroke pain? penetrating trauma causes brain damage. Th e prevalence of central pain in patients with traumatic brain All neuropathic pain directly caused by cerebrovascu- injury is not known. Chronic pain in these patients is lar lesion (i.e. infarct or hemorrhage), independent of almost exclusively unilateral, and the most common where the lesion is located, is called central poststroke qualities are pricking, throbbing, and burning. A curi- pain. It was previously called thalamic pain according to ous feature is the manifestation of pain in body regions the typical location of the lesion, but it can also be due that are not associated with local or spinal injury. Th ese to cortical (parietal cortex), subcortical, internal capsule painful regions exhibit very high rates of pathologically (posterior limb), or brainstem lesion. evoked pain (allodynia and hyperpathia). Th e most frequently reported painful body regions are the knee area, What are the clinical features of shoulders, and feet. Neuronal hyperexcitability has been central poststroke pain? suggested as a contributing factor to the chronic pain. Treatment of central pain in patients with traumatic In the majority of patients, central poststroke pain is brain injury is challenging, because most of these pa- a contralateral hemi-pain, not always including the tients are also suff ering from cognitive defi cits and emo- face, but it may also be restricted to part of the upper tional distress, and neuropathic pain may overlap with or lower extremity. Th e most common pain quality is pain of psychogenic origin. Central Neuropathic Pain 193 How can I diagnose central hematomas usually present with headache and progres- neuropathic pain? sive neurological symptoms, but central neuropathic pain is an uncommon symptom in these cases. Th e cornerstones of the diagnosis are a detailed history of development of symptoms and relieving and ag- How should the patient be treated? gravating factors, and a careful neurological examination including sensory testing to touch, pinprick, cold, Treatment consists of: warmth, and vibration. Abnormal sensory fi ndings sug- • Treatment of the causative disease, when possible gest the possibility of neuropathic pain, and other neu- (e.g., medical and surgical treatment of epidural rological fi ndings help to localize the site of the lesion. abscesses causing spinal cord compression). It is important to keep in mind that the region of sen- • Secondary prevention (e.g., commencing ace- sory abnormalities may be larger than the painful region tylsalicylic acid prophylaxis for atherothrom- (Case 2). Diagnosing central neuropathic pain is actu- botic cerebral infarct, or treating endocarditis in ally identifying symptoms and neurological signs com- a patient with embolus from an infected cardiac patible with a lesion in the CNS, and excluding other valve). possible causes of pain. Typical neurological fi ndings • Symptomatic relief of the neuropathic pain. referring to a central neurological lesion are a positive • Treatment of other concomitant sources of pain Babinski sign, accelerated tendon refl exes, and spastic- such as spasticity, which may exacerbate central ity. Other possible causes of pain need to be excluded neuropathic pain. with reasonable certainty. Careful clinical examination Th e fi rst line of therapy, after a thorough assess- is usually suffi cient for this process, such as diagnosing ment, is information and education, for both the patient musculoskeletal pain or pain due to local infection. and the family. For example, phantom limb pain is dif- Diagnostic studies, such as neuroimaging and fi cult to understand for a layman. Th e doctor’s explana- cerebrospinal fl uid analysis, may provide useful infor- tion in this situation may be very helpful (“your father mation in reaching an accurate diagnosis, but they may is not crazy having pain where he has lost a limb”). Th e not be available. In such conditions, recognition of the character of the pain, the disease causing it, and the clinical features of the causative diseases is very useful. possibilities for pain relief need to be explained to the Th e decision as to the use of limited resources and se- patient and the family. As symptomatic treatment of lection of patients for referral is based on the possibili- central neuropathic pain is less successful than treat- ties of treatment of the causative disease, such as with ment of peripheral neuropathic pain, giving thorough neurosurgery. Spinal and cerebral abscesses, spinal trau- information may be the best way to help the patient. mas with partial cord lesion, and spinal tumors are ex- Similarly to peripheral neuropathic pain, antide- amples of conditions with radically improved prognosis pressants and anticonvulsants are used for symptomatic with active surgical treatment. Cerebral abscess should treatment of central neuropathic pain. Amitriptyline be suspected if a patient has fever and progressive neu- is the drug of choice for central poststroke pain. It is rological symptoms (in cerebral abscess contralateral started with 10–25 mg in the evening, and the dose is symptoms, and in spinal abscess sensory and motor de- escalated by 10–25 mg steps to 50–150 mg/day depend- terioration below the level of the abscess). ing on the extent of side eff ects. Diffi culties in urination, History of trauma before the onset of weak- constipation, dry mouth, and dizziness are typical side ness of the limbs and sensory changes, including central eff ects, which may prevent further dose escalation. Ar- pain, is suggestive of partial cord lesion. If there is an rhythmias caused by amitriptyline contraindicate its unstable lesion of the vertebral column, quick stabilizing further use. If amitriptyline is intolerable or ineff ective, surgery may prevent complete paralysis, and the same is carbamazepine can be tried instead. It is started at 100 true with laminectomies in spinal contusion with par- mg b.i.d., and the dose is escalated in 100-mg steps over tial paresis. Slowly progressive paraparesis and sensory several days until 400–800 mg/day is reached. If side ef- changes may be caused by a spinal tumor. Removal of fects (dizziness, headache, ataxia, or nystagmus) appear, the tumor may prevent paralysis. Th e fi nal prognosis the dose should be reduced. depends on the histology of the tumour and the severity Pregabalin has been shown eff ective for spinal of the symptoms before surgery. Treatable intracranial cord injury pain, but it is not available in every country. 194 Maija Haanpää and Aki Hietaharju Gabapentin has the same mechanism of action and can Pearls of wisdom be used instead. It is started with 300 mg in the evening, and the dose is escalated in steps of 300 mg daily or ev- • Central neuropathic pain may be present from ery other day. Th e daily dose is divided into three dos- the start of the neurological symptoms or may es. Th e eff ective dose is 900–3600 mg/day, divided into appear after a delay of days, months, or even three daily doses. Gabapentin has no pharmacokinetic years. interactions. It can be tried also for central poststroke • Th e most common qualities of central pain are pain if amitriptyline and carbamazepine fail. burning, pricking, and pressing. Central neuropathic pain is unfortunately quite • Remember that nearly all patients with central refractory to treatment, and pain relief is usually only neuropathic pain have abnormalities of pain and partial. Based on information from open studies and temperature sensation. clinical experience, transcutaneous electrical nerve • Amitriptyline, carbamazepine, and gabapentin stimulation (TENS) can be helpful for central pain in can be used for symptomatic treatment. cases where there is well-preserved sensibility to vibration and touch. References

[1] Attal N, Cruccu G, Haanpää M, Hansson P, Jensen TS, Nurmikko What is the prognosis of central T, Sampaio C, Sindrup S, Wiﬀ en P. EFNS Task Force. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J Neurol neuropathic pain? 2006;13:1153–69. (Current evidence and practical guidelines on pharmacotherapy of neuropathic pain) [2] Moseley GL, Gallace A, Spence C. Is mirror therapy all it is cracked Th e natural course of central pain is not known exactly. up to be? Current evidence and future directions. Pain 2008;138:7–10. Resolution of pain has been reported in 20% of patients (Current evidence and practical information of mirror therapy) [3] Ofek H, Defrin R. Th e characteristics of chronic central pain after trau- with central poststroke pain, occurring over a period of matic brain injury. Pain 2007;131:330–40. (Describes central neuro- years. It is still not known whether treatment of the pain pathic pain after brain injury) has any modifying eﬀ ect on the duration of central neuropathic pain. Guide to Pain Management in Low-Resource Settings

Chapter 26 Th e Management of Pain in Adults and Children Living with HIV/AIDS

Glenda E. Gray, Fatima Laher, and Erica Lazarus

What is the scope of the problem? 2) Conducting an adequate assessment. 3) Making an appropriate diagnosis. In 2007, UNAIDS estimated that 33.2 million people 4) Implementing treatment. were infected with HIV. Most of the HIV-infected men, 5) Evaluating pain management. women, and children resided in sub-Saharan Africa. Th e best approach to treating pain in HIV/ Globally, 2 million children under the age of 15 are liv- AIDS is multimodal: pharmacological, psychotherapeu- ing with HIV. Even though antiretroviral therapy is be- tic, cognitive-behavioral, anesthetic, neurosurgical, and coming increasingly available in resource-poor settings, rehabilitative. Th erapy should begin according to the many HIV-infected people, including children, do not World Health Organization (WHO) ladder, with a non- know their status and may never have access to treatment opioid such as paracetamol (acetaminophen). Opioids and care. Although huge strides have been made to make should be the fi rst-line therapy for moderate to severe HIV/AIDS a chronic manageable condition, little is done pain. Nonsteroidal anti-infl ammatory drugs (NSAIDs), to address the issues of pain caused by HIV disease, by adjuvants (tricyclic antidepressants and anticonvul- concomitant opportunistic infections, or by HIV-associ- sants), and nonpharmacological modalities may be im- ated cancers or as a result of side eff ects of antiretroviral portant supplements to eff ective analgesia. NSAIDs use therapy. Pain in HIV/AIDS is highly prevalent, has var- in HIV infection could exacerbate bone marrow dis- ied syndromal presentation, can result from two to three ease and worsen gastrointestinal eff ects seen with HIV sources at a time, is underestimated by doctors, and has or with antiretrovirals. Continuous use of long-acting the potential to be poorly managed. In South Africa, the opioids is the treatment of choice in chronic pain. Th e prevalence of neuropathic pain in AIDS patients prior to WHO analgesic ladder is a stepwise approach to pain antiretroviral treatment was 62.1%, with men signifi cant- management that was developed to manage pain (par- ly more likely to experience pain than women. ticularly cancer pain) in a consistent manner and can be applied to all cases of pain management. What are the principles for successful management of pain? Case report 1 (“pain in infants”)

Five principles are fundamental to the successful man- Flavia is a 4-month-old HIV-infected female who is re- agement of pain symptoms: ferred by the local hospital with a CD4 of 15% (absolute 1) Taking the symptom seriously. value 489) for enrolment into an antiretroviral treatment

Table 1 Causes of pain in HIV-infected children Pain in the oral cavity If the pain is bad, the child may stop eating and drinking. In babies, there may be Oropharyngeal candidiasis, dental caries, gingivitis, drooling. aphthous ulcers, herpetic stomatitis Pain related to infections in the esophagus Th e cause and diagnosis of pain in the esophagus may be very hard to determine. Im- Candida, cytomegalovirus, herpes simplex, and munosuppressed children with oral candidiasis may have esophageal candidiasis as mycobacterial esophagitis well. Older children may complain of heartburn or pain during swallowing.

Pain in the abdomen Pain in the abdomen could be constant or intermittent, dull or sharp. Th e pain may Infectious gastroenteritis, pancreatitis, hepatitis, or occur after eating or when the stomach is empty. Th ere may be associated diarrhea infrequently, gastrointestinal lymphoma and vomiting along with the pain Pain in the nerves and/or muscles HIV can cause muscle pain or joint pain. HIV encephalopathy can be accompanied Hypertonicity/spasticity, peripheral neuropathies, by hypertonicity or spasticity. Certain antiretroviral medications such as D4T can headache, myelopathy, myopathy, herpes zoster, cause peripheral neuropathy. and postherpetic neuralgia Pain due to procedures Much of the pain from procedures can be minimized. Venipuncture, tuberculin skin testing, lumbar puncture, bone marrow aspirates, intravenous infusions, nasogastric tube insertions, immunizations

Pain due to side eﬀ ects of treatment Peripheral neuropathies, pancreatitis, renal stones, myopathy, headache *Adapted from Children’s Hope Foundation. Pain assessment and management of pediatric HIV infection. Pediatric HIV/AIDS Training Module; 1997.

How can we manage procedural pain Do children experience pain from antiretroviral in HIV-infected children? medications? Establishing a diagnosis is critical. Th e underlying cause Many of the antiretrovirals, especially the protease in- should be treated in addition to the administration of hibitors, cause abdominal discomfort, nausea, and diar- analgesia. For procedural pain a multicomponent inter- rhea. Headaches, pancreatitis, and peripheral neuropa- vention is recommended (see Table 2). thies are other common side eﬀ ects of treatment. It is

Table 2 Multicomponent intervention for procedural pain management Intervention Procedure Provide detailed information on the events that will follow. Rehearse what is going to happen. Tailor 1) Preparation the level of information depending on the developmental level of the child. Promote relaxation through the use of breathing exercises. Could use aids like blowing bubbles. 2) Relaxation and Children who are taught a specifi c technique such as breathing exercises believe they have more distraction control over a painful situation, which improves pain tolerance. Mostly in the form of verbal praise, stickers, badges, sweets, or small toys that reward and encourage children to attempt to comply, e.g., by sitting still. Such reinforcement provides an incentive for 3) Reinforcement engaging in coping behaviors. Applying EMLA (eutectic mixture of local anesthetics) cream and increasing the role of parents during procedures can reduce distress and pain. Apply EMLA 1 hour before the procedure and 4) Pharmacological cover with an airtight bandage. Parents play an important role in eff orts to promote children’s coping approach during painful procedures. *Adapted from Schiff et al. 2001. 198 Glenda E. Gray et al. important to look at the package inserts of the antiret- be an NSAID, for example diclofenac suppositories, but roviral drugs that are being prescribed to assess side ef- children who are in this amount of pain will most likely fects and drug interactions. need admission for intravenous (i.v.) fl uids and parenteral analgesia in addition to i.v. fl uconazole. What is the most likely cause of swallowing One week later, the mother reports that that her disorder, and how can you manage it? child shows weakness, but the oral sores have resolved Esophageal candidiasis is the most likely diagnosis and and there are no new complaints. Th e child’s baseline should be suspected on the basis of a history of diffi cul- blood work reveals no contraindications to antiretroviral ty in feeding and the presence of extensive thrush into therapy, so she is started on stavudine, lamivudine, and the oropharynx. lopinavir/ritonavir. While mild oral candidiasis may respond well to topical therapy, the effi cacy of Mycostatin drops is large- Case report 1 (cont.) ly dependent on the length of time that the medication remains in contact with the lesions. It is important to Four weeks after initiating HAART, the mother com- explain to mothers that they need to try and remove plains that her baby has developed a lump under her the thick plaques that form and then apply the drops di- right arm but is otherwise well. Examination reveals a rectly to the lesions (giving the drops as one would give 4-cm mobile mass in her right axilla. Th e baby is clearly a syrup). Allowing the baby to swallow it quickly will miserable and cries on examination of the lesion. A new prove ineff ective. Th is procedure should be repeated at workup to exclude TB is started, but a working diagno- least 4 times per day. Alternatively, one could prescribe sis of BCG-related immune reconstitution infl ammatory a gel formulation like Daktarin oral gel, which will ad- syndrome (IRIS) is made. here to the aff ected areas. Th e TB workup proves negative, so a decision is Severe oral candidiasis and esophageal candi- made to await the results of specimen culture before con- diasis will not respond to topical therapy. Th is is often a sidering TB treatment. Th e node continues to enlarge, severely painful condition, and it is often present in in- causing further discomfort to the baby, and eventually it fants and toddlers, causing loss of appetite or diffi culty becomes red, hot, and fl uctuant. Th e child is referred to in feeding. Systemic therapy is required, and the fi rst- the pediatric surgery department for incision and drain- line drug of choice is fl uconazole. Th e decision needs age of the node, and a course of oral prednisone is started. to be made whether the child will need to receive fl uco Th e surgeons then duly perform an incision and drain- needs to nazole intravenously, thus requiring hospital age (I&D) in the outpatient department. Th e baby is se- admission and possible separation from her mother, or dated with valerian syrup and is also given a dose of whether the child can tolerate it orally. A child who is paracetamol (acetaminophen) prior to the procedure. Six- still taking in some oral feeds will often be able to tol- hourly paracetamol is prescribed for analgesia at home. erate treatment orally. Of course, esophageal candidiasis Th e node improves, somewhat, following I&D is a CDC (Centers for Disease Control and Prevention) and prednisone, but two new areas of fl uctuation develop category C (“severely symptomatic”) diagnosis, and later on. Th e lesions are aspirated in the consulting rooms highly active antiretroviral therapy (HAART) is also an under the same sedation and analgesia as before. Th e re- important part of the treatment. sults of the sputum test and fi ne needle aspiration (FNA) As mentioned above, this condition can be ex- fi nally show that the sputum is negative for TB, and the tremely painful, and analgesia should also be prescribed FNA reveals Mycobacterium bovis as the causative agent. for this patient. According to the WHO analgesic ladder, No TB treatment is started, HAART is continued, and one could begin with oral paracetamol (acetaminophen) the baby receives a total of 6 weeks of prednisone. No syrup if the patient is able to take oral medication or else further procedures are required, and the node improves paracetamol suppositories. Th is drug can be safely and slowly over time, with resolution after 1 year of HAART. easily administered 6-hourly in children. It is often useful to advise the mothers to try to give the dose 30 minutes What other options were available for before a scheduled feed so that the maximum effi cacy is manag the initial axillary abscess? reached at the feed time, reducing pain on swallowing. 1) Conservative. Th is is not an advisable option If this therapy proves inadequate, the next step would as the pus will need to be drained, and if a controlled Management of Pain in HIV/AIDS 199 drainage procedure is not undertaken, a poorly healing and brings up her breakfast all over the clinic fl oor, making sinus or fi stula may develop. Also not addressed, is that the procedure exceedingly challenging for the staff . the abscesses are extremely painful, particularly in an area such as the axilla, which will be manipulated during What are some possible things that could have been done to have prevented this state dressing, transportation, and so on. Relief of the pressure of aff airs? is in itself an eff ective pain management procedure. 2) Aspiration. Small abscesses can be aspirated with While it is often traumatic for parents to watch blood ease with minimal pain to the child. Th is process allows being drawn from their child, it is more often more the pus to be drained to the surface and prevents sinus traumatic for the child to face the procedure alone feel- formation as well as relieving the pain of the abscess iting abandoned by their mother, whom they trust to pro- self. Unfortunately, inadequately aspirated abscesses of- tect them from pain. It is therefore advisable to encour- ten recur with resultant recurrence of pain. It is diffi cult age parents to remain in the room and speak words of to adequately aspirate large abscesses, particularly those comfort to their child during the procedure (they do not which have been present long enough to begin develop necessarily need to watch the procedure). Also, parents into separate locations. or caregivers should be encouraged to explain why the 3) Incision and drainage (I&D) under general an- blood has to be taken as far as the child can understand. esthesia. In some cases this method is preferable to the Th ey should also be encouraged not to mislead their outpatient procedures for children as the pain of the children and promise that no blood will be taken. Par- procedure is completely dealt with by the anesthetic. It ents should be discouraged from “villainizing” the staff allows the abscess to be completely drained and to en- performing the procedure. It is often the natural instinct sure that all septae are broken for good drainage. On the of mothers in particular to vindicate their child’s pain by other hand, general anesthesia requires that the child be promising them that they will hit the doctor or, as one separated from her mother, admitted to hospital, and patient’s mother promised, report them to the police! exposed to an unfamiliar and scary operating room. Th is behavior serves to increase the child’s fear of the And, of course, the postoperative pain still has to be staff and makes the child begin to doubt their mother’s managed, just as for the outpatient procedure. word or ability to off er the protection promised. What can be done in future to alleviate Case report 2 (“psychological pain the situation? due to recurrent procedures”) Th e multicomponent approach described in Table 2 Edith is a 2½-year-old girl who has been attending the should be introduced. EMLA should be used in an at- antiretroviral clinic since she was 6 weeks of age. She tempt to reduce pain. As soon as the child is old enough was started on HAART at 12 weeks of age and was seen to make brachial vein blood sampling as easy as exter- monthly for the fi rst year of her life. Blood samples were nal jugular vein sampling, this option should be ad- taken every 3 months. Since she was 6 months old, the opted. Th e child will be able to remain on her mother’s necessary blood samples have been taken from her exter- lap with her mother’s loving arms as her unforced renal jugular vein, which involved her being held supine on straints. Off ering some form of comforting compensa- an examination bed with her neck slightly extended over tion like a chewy sweet or lollipop will often stop the the edge of the bed while her hands were held by a nurse to tears or at least attenuate the trauma of the procedure prevent her from trying to pull the needle out. Her mother with some positive association. has a fear of needles and couldn’t bear the sight of the doctors inserting a needle into her baby’s neck, so she would al- Case report 3 (“pain due to ways place the baby on the examination bed in the care of opportunistic infection with the nurse ready for the blood drawing and then leave the exacerbating psychosocial factors”) room until the procedure was complete, when she would be called back in. Two years later, it now takes two nurses to Abigail is a 12-year-old girl who is brought to the clinic hold her down fi rmly enough to make phlebotomy safe for having just been diagnosed with HIV. Her parents died her, with the doctor performing the procedure. As soon as 2 years ago from AIDS-related illnesses, and her mater- she is supine, she begins to gag until she induces vomiting nal aunts have been caring for her since then. When they 200 Glenda E. Gray et al. saw that she was losing weight rapidly over a period of Th ree days later, her temperature has settled, her consti- a few months, they decided she needed to be tested for tutional symptoms have improved, her abdominal pain HIV as well. At the local clinic Abigail and her aunt had is much better, and she is back to her usual self and able pre-test counseling together as it was felt she was mature to be discharged home. enough to understand the implications of the test and to give consent herself. When the results were available they What are some possible contributing factors were given to Abigail alone without her aunt present. No to her pain? post-test counseling was done, and Abigail was simply 1) Intra-abdominal pathology: splenic tuberculosis. told that she needed to go to the clinic as she was HIV It is also likely that with splenic involvement, there was positive and needed treatment. also further lymphatic involvement. Tuberculosis of At the fi rst visit, Abigail, is clearly disturbed by the mesenteric lymph nodes could cause partial bowel the diagnosis. She is a bright child who obviously under- obstruction, resulting in the signs of peritonitis found stands the meaning of the diagnosis and is hence some- on examination. what reserved and noticeably scared—worried about 2) “Referred” pain. After 4 weeks of coughing and in her future, scared of rejection, her whole life upturned. the face of disease-induced malnutrition, the patient’s She has had a chronic cough for more than 4 weeks and diaphragm and accessory respiratory muscles have been is wasted, listless, and in respiratory distress, with a sorely overexerted. Her abdomen may be tender due to temperature of 40°C. A chest X-ray reveals a bilateral the prolonged muscular strain. patchy infi ltrate. She clearly requires hospital admis- 3) “Psychological” pain. Children, particularly sion but is reluctant as she is afraid of leaving the care younger children, often present with generalized or of her aunts and of being abandoned in the hospital. Her nonspecifi c abdominal pain without any apparent pa- aunts reassure her of their love, and the doctor assures thology. Th e pain may often simply be a sign of emo- her that it is necessary and in her best interest, and she tional distress (although, of course, physical pathology fi nally agrees. must fi rst be excluded). Caution must be exercised to She is admitted with a diagnosis of community- diff erentiate real pain and peritonism from psychologi- acquired pneumonia and is started on intravenous an- cal pain. Often by distracting the patient with conver- tibiotics. Her CD4 count is 4. On admission it is also sation and questions or, for younger children, toys or noted that she has severe abdominal pain. Th e ward doc- mobiles, you will be able to elicit whether or not the tors note that the pain is generalized, with some appar- pain is real. Real pain will cause a grimace and even an ent rebound tenderness, and order an abdominal X-ray interruption in the conversation. Peritonism will result and serum lipase level. Th ey start her on tilidine drops in obvious rebound tenderness in spite of the distrac- (an oral opioid analgesic) to be given 6-hourly. Investiga- tion. Purely psychological pain (or even feigned pain) tions prove normal, but her tenderness does not seem to will result in no obvious signs of tenderness during the improve. In the meantime, her condition appears to be examination while the child is distracted. worsening. She appears weaker and more tired than ever. Due to her deteriorating condition, Abigail is What are some possible reasons for the seen by a palliative care specialist. She recommends deterioration in the patient’s condition? that the tilidine be changed to paracetamol (acetamino- 1) Incorrect diagnosis with worsening of her oppor- phen) and codeine (a weak opioid with much less seda- tunistic infection. Th is child had several symptoms that tive eff ect.) She also arranges for Abigail to be seen by her should have alerted the clinicians to the strong possibil- team’s psychologist when she is more lucid. In the mean- ity of tuberculosis. She had a chronic productive cough, time her temperature and symptoms are still not con- an unresponsive fever, and signifi cant weight loss with trolled, despite various diff erent intravenous antibiotics suspicious chest radiograph changes. With a CD4 count including tazobactam, amikacin, and even imipenem. of 4, the likelihood of TB and especially disseminated Sputum results are delayed due to a backlog at the labo- TB was very strong. ratory, and the cause for abdominal tenderness still has 2) New nosocomial (i.e., hospital-acquired) infec- not been found. An abdominal ultrasound is ordered, tion. While this is often the cause of deterioration in which shows splenic microabscesses. She is diagnosed severely immunocompromised in-hospital patients, it with disseminated TB and started on TB treatment. was unlikely in view of the lack of positive specimen Management of Pain in HIV/AIDS 201 cultures and lack of response to potent intravenous an- pain, abdominal pain, chest pain, arthralgias and myal- tibiotic therapy. gias, and painful dermatological conditions. 3) Psychological pain. Loss of the will to continue fi ghting and resignation to the possibility of death. Th e Are the principles of pain management diff erent in HIV? loss of both parents, the tragic way she received her diagnosis, and the lateness of her presentation, together Th e principles of pain management in HIV are similar with her severe ill health and opportunistic infection, to those in other medically ill patients. At each visit, comprise a daunting load for a young psyche. Th e temp- both in the outpatient and inpatient facility, it is useful tation to give up hope must certainly be strong. Th e to take “pain vital signs” to assess the degree of pain and need for a strong, loving family support system with ex- the response to the current analgesic program (also see ternal psychosocial intervention is crucial. Fortunately, the Brief Pain Inventory). Abigail has very loving aunts who visited her daily and • Ask patients if they have experienced pain in the caring school friends who sent cards and gifts during last week. her hospital stay. Th e palliative care psychologist was • Ask them to describe the intensity of pain: mild, also able to counsel and encourage her and her family moderate, or severe. and provide them with the extra care they needed at • Ask them to tell you what it feels like: burning, this diffi cult time. shooting, dull, or sharp. 4) Drug side eff ects. Tilidine is a strong opioid. • Find out what makes it better or worse. Opioid analgesics are known to cause sedation and • Ask them to rate the pain (at its worst and at its mood changes (euphoria or dysphoria.) Tilidine itself best) on a 0–10 numerical scale. can also cause dizziness, drowsiness, and confusion. • Ask them to rate their quality of life on a 0–10 scale. According to the WHO analgesic ladder, strong opi- • Ask about sadness, fatigue, and depression. oids should be reserved for pain that does not respond After obtaining the history, a careful medical to less strong analgesia. Th ey should not be used as a examination will help elucidate the causative factors. fi rst-line analgesic, except postoperatively or where Th e baseline assessment can be used as an indicator as clear pathology requiring strong analgesia is required, to whether the analgesia is eff ective or not. such as pancreatitis. Do women with HIV infection have more pain? How to manage pain in HIV-infected adults Women experience pain diff erently from men due to Th e pain syndromes seen in HIV-infected adults may be biological, psychological, and social factors. Men and directly related to HIV infection, immunosuppression, women respond diff erently to pharmacological and or HIV therapy. Pain can be divided into two categories: nonpharmacological treatments. Women with pain are nociceptive or neuropathic. Th e most common syn- often underdiagnosed and undertreated. Th ey may not dromes reported in HIV-positive adults include painful have the information or education to understand that peripheral neuropathies, as well as pain caused by ex- their painful conditions may be part of HIV disease. tensive Kaposi’s sarcoma, headache, oral and pharyngeal Culture also infl uences pain experience.

Table 3 Common sources of pain in HIV/AIDS Cutaneous/Oral Visceral Deep Somatic Neurological/Headache Kaposi’s sarcoma Tumors Rheumatological Headaches: HIV-related (encephalitis, meningitis, etc.) Oral cavity pain Gastritis disease Headaches: HIV-unrelated (tension, migraine) Herpes zoster Pancreatitis Back pain Iatrogenic (zidovudine-related) Oral/esophageal Infection Myopathies Peripheral neuropathy candidiasis Biliary tract Herpes neuritis disorders Neuropathies associated with ddI, D4T toxicities, alcohol, nutritional defi ciencies. *Modifi ed from Carr DB. Pain in HIV/AIDS: a major health problem. IASP/EFIC (press release). Available at www.iasp-pain-org. 202 Glenda E. Gray et al. Case report 4 (“postherpetic What complications of zoster are more neuralgia”) common in immune-compromised individuals? Extensive skin involvement, disseminated disease, A 44-year-old HIV-positive man, compliant and stable pneumonitis, ocular involvement, meningoencepha- on antiretroviral therapy for 3 years, complains of sud- litis, myelitis, and involvement of cranial nerves have den-onset fatigue and severe pain in his left shoulder. been described. He describes the pain as the worst pain he has ever felt, with a burning quality, waking him up from his sleep, worse with movement of the left shoulder, causing him to Case report 5 (“cryptococcal break out into a sweat and incapacitating him. He has meningitis”) no history of trauma. He recalls experiencing a mild fl u- An 18-year-old, pregnant, HIV-infected woman with like illness 1 week ago. His daughter was ill recently with baseline CD4 count of 38 × 106/L and viral load chicken pox. On examination of the skin, two vesicles are >500,000 copies/mL has been receiving stavudine/la- found at the tip of the left shoulder, and the pain extends mivudine/nevirapine for 3 weeks. She now presents unilaterally in a dermatomal distribution. Oral valacy- with a 7-day history of headache, described as mild, clovir, a combination paracetamol (acetaminophen)-co- initially, but worsening with time, persistent, stabbing, deine tablet, and ibuprofen, were initiated. no longer responsive to paracetamol, exacerbated by What treatments may be used to alleviate the movement and associated with photophobia and vom- pain and itchiness of zoster rash? iting. On examination, she is mildly pyrexial, fully awake, alert and oriented but restless. Five papular Th is condition is extremely painful, and analgesic use skin lesions measuring 2 mm in diameter have been should be liberal. Topical calamine lotion and water noted below the lower right eyelid since prior to antiret- dressings may help relieve the itchiness. Paracetamol, roviral induction, which were thought to be molluscum ibuprofen, and dihydrocodeine will be necessary as well. contagiosum. She displays neither focal neurological Secondary infection of the blisters may occur and may defi cits nor papilledema. Serum cryptococcal antigen exacerbate pain, and so should be treated with antibiot- is positive, and cerebrospinal fl uid results are as fol- ics and a topical agent such as chloramphenicol, tetra- lows: opening pressure 20 cm H2O, slightly turbid fl uid, cycline, or gentian violet. Th ere is some evidence that CSF-protein 0.5 g/L, CSF: serum glucose 40%, chloride corticosteroid use with acyclovir decreases acute pain, 125 mmol/L, acellular, Gram stain negative, CSF- but steroids should be used with caution, especially in cryptococcal latex agglutination test positive, India ink immune-compromised patients. positive. Skin biopsy results culture Cryptococcus neo- How can one manage the pain formans. Intravenous amphotericin B and oral dihy- of postherpetic neuralgia? drocodeine were given, and the patient reports complete pain relief by the third day of treatment. Amitryptiline and carbamazepine should be considered for postherpetic neuralgia. Carbamazepine has drug in- Which signs will alert the clinician to raised teractions with antiretrovirals and should be used with intracranial pressure in a patient with caution. Consider the use of pregabalin, a new drug in cryptococcal meningitis? the anticonvulsant class, for postherpetic neuralgia pa- Focal neurological defi cits. Transient loss in visual acu- tients who are not responding to tricyclic antidepres- ity, diplopia, hearing loss, confusion, and papilledema. sants, gabapentin, and other analgesics. Th e initial dose of pregabalin is 75 mg b.i.d., but the dose may be How should one manage and treat patients with increased to 150 mg b.i.d. after three days. Pregabalin raised intracranial pressure >25 cm H2O? would require dose adjustment if creatinine clearance To avoid herniation, prior to lumbar puncture, a CT is below 60 mL/min. Dizziness and somnolence has or MRI scan of the brain should exclude mass eff ect. been reported frequently with pregabalin, and we sug- Drainage of small amounts of cerebrospinal fl uid daily gest care when coadministering the drug with efavi- for a maximum of 2 weeks, with monitoring of pres- renz, which has similar side eff ects in the initial weeks sure, usually improves headache and other symptoms of treatment. associated with cryptococcal meningitis. After 2 weeks, Management of Pain in HIV/AIDS 203 consider surgical placement of a ventriculoperitoneal or Name all the contributory factors of the lumbar-peritoneal shunt if increased pressure persists. peripheral neuropathy! HIV itself, possible vitamin B defi ciencies, and isoniazid Which analgesics are contraindicated for use with raised intracranial pressure? prophylaxis or treatment. Morphine sulfate, pethidine (meperidine). Which NRTI agents should be avoided, if possible, in such a case? Case report 6 (“peripheral Stavudine and didanosine, as both can cause peripher- neuropathy”) al neuropathy with long-term use owing to mitochondrial toxicity. A young woman, 23 years old, is referred to the antiretroviral (ARV) clinic with a recent positive HIV-ELISA Which nutritional defi ciencies can cause test and absolute CD4 of 19 × 106/L. She is ARV-naive. peripheral neuropathy?

She complains of a burning sensation on the soles of both Vitamin B1 (Th iamine), vitamin B3, vitamin B6, vitamin B12. feet. Positive fi ndings on examination include marked muscle wasting, malnourishment, a weight of 50 kg, pal- Why did the neuropathy progress to grade 2? lor, a right-sided 5-cm supraclavicular lymphadenopa- Th e initial presenting neuropathy was most likely sec- thy, and a grade 1 sensorimotor peripheral neuropa- ondary to HIV. Th e pain was exacerbated by the addi- thy. Of note in the blood results is HIV-1 viral load by tion of isoniazid, a component of TB treatment and a branched DNA, 238,810 copies/mL, and normocytic cause of peripheral neuropathy via vitamin B6 (pyridox- normochromic anemia. Chest X-ray reveals hilar ad- ine) depletion. Peripheral neuropathy has also been re- enopathy. A fi ne needle aspirate is undertaken of the ported as a side eff ect of cotrimoxazole (used in higher lymph node and is consistent with TB. She is commenced doses for treatment and lower doses in prophylaxis of on cotrimoxazole prophylaxis, TB treatment, pyridoxine Pneumocystis jirovecii pneumonia treatment). 25 mg daily, and vitamin B complex. Ten days after starting TB treatment, she calls What drug used to treat peripheral neuropathy may be unsuitable for this patient? the doctor at 3 am to complain of worsening foot pain, and is advised to present herself to the clinic at 8 am Carbamazepine may be unsuitable because it induces that day. She does so, in a wheelchair and wearing slip- the metabolism of efavirenz and nevirapine via the cyto- pers, and complains that she cannot bear to walk on her chrome P450 3A4 system. own because of the pain in her feet, so she sleeps all day. At the consultation, the causes and course of her periph- Remember the WHO analgesic eral neuropathy, now grade 2 sensory and grade 3 mo- ladder for pain management tor, are explained to her. Amitryptiline 25 mg at night, ibuprofen and paracetamol, are started, and pyridoxine Step 1: MILD PAIN dosage is increased to 50 mg daily. Vitamin B12 and fo- Paracetamol (acetaminophen), nonsteroidal anti-in- late levels are normal, and iron studies suggest anemia fl ammatory drugs) (NSAIDS) (and adjuvants if needed) of chronic disorders. Adjuvants include (if there is neuropathic pain): tri- Th ree days later she calls the doctor at 1 am cyclic antidepressants (TCAs), anticonvulsants, steroids and complains of the nonresolution of her foot pain. She Step 2: MILD TO MODERATE PAIN is asked once more to come in, and is assessed again as Mild-acting opioids + step 1 nonopioids (and adju- having grade 2 peripheral neuropathy. Pyridoxine is in- vants if needed) creased to 75 mg daily, amitryptiline to 50 mg at night, Mild-acting opioids: codeine, dihydrocodeine, dex- and a highly active antiretroviral therapy (HAART) regi- tropropoxyphene men of nucleoside analog reverse transcriptase inhibitors Step 3: MODERATE TO SEVERE PAIN (NRTIs) and non-nucleoside reverse transcriptase inhibi- Stronger opioids + Step 1 nonopioids (and adjuvants tors (NNRTIs) is started. After 3 months, the neuropathy if needed) regresses to grade 1, and after 6 months the neuropathy Stronger opioids: morphine, diamorphine, fentanyl, has resolved completely. hydromorphone 204 Glenda E. Gray et al.

[3] Foley MK, Wagner JL, Joranson DE, Gelband H. Pain control for people References with cancer and AIDS. Disease control priorities in developing countries, 2nd edition. New York: Oxford University Press. 2006. p. 981–94. [1] Breitbart W. Pain. In: A clinical guide to supportive and palliative care [4] Gray G, Berger P. Pain in women with HIV/AIDS. Pain 2007;132: S13– for HIV/AIDS. U.S. Department of Health and Human Services: Health 21. Resources and Services Administration; 2003. Available at: http://hab. [5] Hitchcock SA, Meyer HP, Gwyther E. Neuropathic pain in AIDS pa- hrsa.gov/tools/palliative/chap4.html. tients prior to antiretroviral therapy. S Afr Med J 2008;98: 889–92. [2] D’Urso De, Cruz E, Dworkin RH, Stacey B, Siﬀ ert J, Emir B. Treatment of neuropathic pain (NeP) associated with diabetic peripheral neuropathy (DPN) and postherpetic neuralgia (PHN) in treatment-refractory patients: ﬁ ndings from a long-term open-label trial of pregabalin. Arch Phys Med Rehabil 2005;86:E34, Poster 165. Management of Chronic Noncancer Pain

Guide to Pain Management in Low-Resource Settings

Chapter 27 Chronic Nonspeciﬁ c Back Pain

Mathew O.B. Olaogun and Andreas Kopf

Case report 1 raising in supine position) is negative. He can perform an abdominal curl (sitting up from the supine position) A 27-year-old chemical engineer who has had back without pain. With the patient prone, Ely’s test (hip ex- pain for about the past 10 years was referred for phys- tension with a straight knee) is negative, and back ex- iotherapy. He reported with a recent radiograph, which tension does not elicit pain. Th us, there is no evidence showed no serious pathology aside from straightening of of disk herniation, facet-joint osteoarthritis, or lumbar the lumbar lordosis. Pain is constant but is relieved with spinal stenosis. rest; it radiates in a nonradicular pattern into the upper Th e patient is rather disappointed that the limb. Th e patient has taken a series of periodic medica- doctor does not prescribe a strong pain killer or pro- tions, particularly analgesics, with no lasting modulation pose a surgical intervention. He is not really taken of pain. Th e back pain is often exacerbated in attempts with the extensive explanations on the structure and to get up from a lying position to a sitting position, and pathomechanics of the spine. Th e education of the pa- often the patient has experienced pain around the waist. tient involves using a plastic model to demonstrate On questioning, the patient complains that carrying correct lifting techniques (not exceeding 70% of body heavy loads has damaged his spine. He had the ﬁ rst epi- weight) and correct sitting posture, while at the same sode of acute pain at the age of about 16, when he car- time explaining the extraordinary functional reserves ried a 50-kg keg of water (about 100% or more of his of the spinal column. Th e patient is advised to use a body weight at that time). Th e pain subsided after taking portable back support for his car and for chairs with medication, but he has not been completely free of the poor ergonomic design, but to avoid extended rest and pain since then. Th e pain has been undulating in intensi- not look after himself too much. When leaving the con- ty, and he has continued to live with it, but he has seen a sultation room, the patient—as could be seen—was doctor occasionally for medication. Now he explains that not fully convinced, and nobody expected to see him he has come to the teaching hospital in Ile-Ife, Lagos, Ni- again. Interestingly, he came back a few days later for geria, to have his pain treated “once and for all,” and, he his scheduled “education consultation” and was now says, “even it requires surgery.” less demanding about invasive procedures but was ask- On examination, the pain is axial around L3– ing for more advice on the etiology and the prevention L5, not referred and nonradicular. Th e X-ray shows of back pain. He seemed to have a high motivation for no degenerative disk disease. When he lies supine on a changing his attitudes and behavior, with an overall table there is no pain, and Lasègue’s sign (straight leg positive approach to the future. He was satisﬁ ed after

Chapter 28 Headache

Arnaud Fumal and Jean Schoenen

How is headache classifi ed? (i.e., familial hemiplegic migraine) are based on headache features and the exclusion of other disorders, not Headache is a leading reason for medical consultation etiology. In contrast, secondary headache are classifi ed and particularly for neurological consultation. A tre- based on etiology and are attributed to another disorder. mendous range of disorders can present with headache. Because primary headaches are the most common, this A systematic approach to classifi cation and diagnosis discussion focuses on the diagnosis and management is therefore essential both for clinical management and of those syndromes. Th e epidemiology and experiences research. Headache disorders were poorly classifi ed and of patients with headache disorders in the developing defi ned until 1988. At that time, the International Head- world are uncertain, because the majority of research ache Society (IHS) published its International Clas- on headache disorders comes from a limited number of sifi cation of Headache Disorders (ICHD-1), in which high-income countries. Where sought, regional varia- headaches were classifi ed into 13 major groups. Th is tion in the incidence, prevalence, and economic burden headache classifi cation with operational diagnostic cri- of headache disorders has been found. Social, fi nancial, teria was an important milestone for clinical diagnosis and cultural factors can all infl uence the experience and is accepted worldwide. Its second edition (ICHD- of the individual headache suff erer, and patients in re- 2) has fi ne-tuned the classifi cation of diff erent specifi c source-poor settings could presumably experience an headaches and expanded the number of groups to 14 even greater impact of these infl uences. (Table 1). For each disorder, explicit diagnostic criteria are provided. Th ese diagnostic criteria are very use- What are important issues for ful for the clinician because they contain exactly what non-headache specialists? needs to be obtained from the patient while taking the history. Nevertheless, it is surprising and disappointing Caring for a patient complaining of headaches requires that headache patients remain poorly diagnosed and above all a thorough history taking and physical exami- treated in most countries. nation that includes a neurological examination. First, Th ere are four groups of primary headache one needs to distinguish primary from secondary head- disorder: (1) migraine, (2) tension-type headache, (3) aches. To evaluate the likelihood of a secondary, symp- trigeminal autonomic cephalalgias, and (4) other pri- tomatic headache, the most crucial feature, besides mary headache. Th e criteria for the primary headaches clinical examination, is the duration of the headache are clinical and descriptive and, with a few exceptions history. Patients with a short history require prompt at-

Table 1 • Is the pain on one or both sides? Tension-type headache (episodic form): • Is it aggravated by physical activity? general diagnostic criteria (ICHD-2) • Th e presence of trigger zones and lancinating General Diagnostic Criteria quality suggest a neuralgia. A. Headache lasting from 30 minutes to 7 days • Is a migraine aura present? B. At least 2 of the following pain characteristics: • Very importantly, are there accompanying symp- Bilateral location Pressing/tightening (non-pulsating) quality toms such as nausea, hypersensitivity to light and Mild or moderate intensity sound, or autonomic symptoms such as tearing, Not aggravated by routine physical activity such as walking or stuff y nose, sweating, ptosis, or miosis? climbing stairs Th e next question is whether the patient has one C. Both of the following: 1. No nausea or vomiting (anorexia may occur) or more diff erent kinds of headache. Th is must be eluci- 2. No more than one of photophobia or phonophobia dated skillfully. Th e reason for the consultation must be D. Not attributed to another disorder made clear. Is it because the usual headache is getting worse, or is it because of a new kind of headache? We tention and may need quick complimentary investiga- have to keep in mind that if headache is the fi fth most tions, while those with a longer headache history gen- common complaint seen in United States emergency de- erally require time and patience rather than speed and partment, the minority of these patients have a second- imaging. Patients with a headache history of more than ary cause for headache, and an even smaller number have 2 years defi nitely have a primary headache disorder. Red a grave and potentially catastrophic cause for headache, fl ags (see Table 2) that should alert to the possibility of a such as meningitidis or subarachnoid hemorrhage. secondary headache include pain of sudden onset, fever, In clinical practice, it is known that patients marked change in pain character or timing, neck stiff - may not easily identify and recall certain features of ness, pain associated with neurological disturbances, their headaches, such as the presence and type of aura such as cognitive dysfunction or weakness, and pain symptoms, specifi c associated symptoms, and the coex- associated with local tenderness, for example of the su- istence of several types of headache. Th erefore, the use perfi cial temporal artery. of monitoring instruments becomes crucial in the diagnosis of these disorders. Using headache diaries and Table 2 calendars, the characteristics of every attack can be re- Migraine with aura diagnostic criteria (ICHD-2) corded prospectively, increasing the accuracy of the de- Diagnostic Criteria for Migraine without Aura scription and making it possible to distinguish between A. At least 5 attacks fulfi lling criteria B–D coexisting headache types. B. Headache attacks lasting 4–72 hours (untreated or unsuccess- Moreover, headache diaries provide the phy- fully treated) sician with information concerning other important C. At least 2 of the following pain characteristics: Unilateral location features, such as the frequency and temporal pattern Pulsating quality of attacks, drug intake, and the presence of trigger fac- Moderate or severe intensity tors. Use of acute drugs can be checked for optimal dos- Aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) ing. Frequent use (10 days or more per month) of acute D. During headache at least one of the following: medication is an alert for medication overuse headache. 1. Nausea and/or vomiting Th e diary could even be sent to headache patients before 2. Photophobia and phonophobia their fi rst consultation at the headache center as it can E. Not attributed to another disorder improve the clinical diagnosis from the fi rst interview.

Patients with recent onset headache or with What is essential to know neurological signs require at the least brain imaging about migraine? with computed tomography (CT) or magnetic resonance imaging (MRI). To classify primary headaches, Migraine is the commonest cause of severe episodic re- the following questions are crucial: current headache. Migraine aff ects approximately 12% • Frequency and duration of attacks. of Western populations, and prevalence is higher in fe- • Headache severity. males (18%) than males (6%). Migraine is a recurrent Headache 215 headache manifesting in attacks lasting between 4 and disability and reduced quality of life, even between at- 72 hours. Typical features of this headache are unilateral tacks. Although migraine is one of the most common location, pulsating quality, moderate or severe intensity, reasons for patients to consult their doctor, and despite aggravation by routine physical activity, and association its enormous impact, it is still under-recognized and with nausea and/or photophobia and phonophobia (see undertreated. Th is lack of recognition has various rea- Table 3 for diagnostic criteria of migraine without aura sons. On the one hand, there are no biological markers from the ICHD-2). to confi rm the diagnosis, and many doctors lack knowl- Th e headache may be preceded in 15–20% of pa- edge, time, interest, or all three, to manage migraineurs. tients by an aura, so-called migraine with aura. Th e aura On the other hand, there is no cure for migraine, and, may last between 5 and 60 minutes. Th e most common although eff ective therapies do exist, they have only par- type is visual aura, causing scotomas, teichopsia, forti- tial effi ciency or are not accessible to all. Finally, percep- fi cation spectra, and photopsias. It can also comprise tion of migraine may vary between cultures, some of other neurological symptoms such as focal paresthe- which tend to negate or trivialize its existence. As a re- sias, speech disturbances and, in hemiplegic migraine, a sult, a proportion of aff ected individuals do not seek (or unilateral motor defi cit. Th e heterogeneity of the clini- have given up on) medical help. cal phenotype of migraine is underestimated. Despite a Migraine is a neurovascular disorder (i.e., both common diagnostic denominator, some clinical features neuronal and vascular factors are involved) in which ge- such as type of aura symptoms, pain intensity, presence netic susceptibility renders the brain hyperresponsive to of prodromes, coexistence of migraine with and without stimuli and probably metabolically vulnerable, setting a aura, or associated symptoms such as vertigo, may char- “migraine threshold” on which trigger factors may act acterize subgroups of patients bearing diff erent underly- to precipitate an attack. Th e consensus is now that the ing pathophysiological and genetic mechanisms. migraine aura is caused by the neuron-glial phenome- In migraine, premonitory symptoms and trig- non of so-called “cortical spreading depression,” where ger factors are manyfold, and they may vary between a brief front of neuronal depolarization (“scintillations”) patients and during the disease course. Th e most is followed by a wave of arrest of neuronal activity due frequently reported premonitory symptoms are fa- to hyperpolarization; both spread over the cortex with a tigue, phonophobia, and yawning. Concerning trig- velocity of 3–5 mm/minute. ger factors, the most common ones are stress, the Th e migraine headache probably results from perimenstrual period, and alcohol. Overuse of acute activation of the trigeminovascular system, the major antimigraine drugs, in particular of combination anal- pain-signaling system of the visceral brain composed of gesics and ergotamine, is another underestimated fac- nociceptive aff erents belonging to the visceral portion of tor leading to chronifi cation. the ophthalmic nerve (V1) and surrounding meningeal If the migraine is a benign condition, the se- blood vessels. Th e precise pathogenic relationship be- verity and frequency of attacks can result in signifi cant tween aura and migraine headache is not fully clarifi ed.

Table 3 Typical symptoms of migraine and tension-type headache Migraine Tension-Type Headache Sex ratio (F:M) 2 to 3:1 5:4 Pain Type Pulsating Pressing/tightening (non-pulsating) quality Severity Moderate to severe Mild or moderate intensity Site Unilateral Bilateral Aggravated by routine physical activity Yes No Duration of attack 4 to 72 h 30 minutes to 7 days Autonomic features No No Nausea and/or vomiting Yes No Photophobia and/or phonophobia Yes, both No more than one of photophobia or phonophobia 216 Arnaud Fumal and Jean Schoenen What are the options for acute proven cost-eff ective. In severely disabled migraineurs, migraine treatment? the effi cacy rate of injectable sumatriptan for a pain-free outcome at 2 hours is twice that of ergot derivatives or During the last decade, the advent of highly eff ective NSAIDs taken at high oral doses and of i.v. acetylsalicylic acid lysinate. Th e therapeutic gain tends to be clearly 5-HT1B/1D agonists, the triptans, has been a major breakthrough in treatment. Triptans are able to act as vaso- lower for simple analgesics or NSAIDs, such as acetaminophen (1000 mg p.o.), eff ervescent aspirin (1000 constrictors via vascular 5-HT1B receptors and to inhibit neurotransmitter release at the peripheral as well as at mg), or ibuprofen (600 mg), than for oral triptans, when severe attacks are considered. central terminal of trigeminal nociceptors via 5-HT1D/B receptors. Th e site of action relevant for their effi ca- For mild and moderate attacks, however, it has cy in migraine is still a matter of controversy; possibly proven diffi cult to show superiority of oral triptans in their high effi cacy rate is due to their capacity of acting randomized controlled trials. Combining analgesics at all three sites, contrary to other antimigraine drugs. or NSAIDs with an antiemetic and/or with caff eine or Sumatriptan, the fi rst triptan, was followed by several- administering them as suppositories clearly increas- second generation triptans (zolmi-, nara-, riza-, ele-, es their effi cacy, often up to that of oral triptans. Re- almo-, and frovatriptan), which were thought to correct cently, combining a triptan plus an NSAID as a single some of the shortcomings of sumatriptan. A large me- tablet for acute treatment of migraine resulted in more ta-analysis of a number of randomized controlled trials favorable clinical benefi ts compared with either ther- performed with triptans confi rms that the subcutane- apy used alone, with an acceptable and well-tolerated ous auto-injectable form of sumatriptan (6 mg) has the adverse-eff ect profi le. best effi cacy, whatever outcome measure is considered. As expected, the triptans have not solved pa- Diff erences between oral triptans do exist for some out- tients’ problems. Th ere is room for more effi cient and come measures, but in practice each patient has to fi nd safer oral acute migraine treatments. As triptans are con- the triptan that gives the best satisfaction. traindicated in patients with cardiovascular disorders, At present, the major reason for not considering non-vasoconstricting agents are the holy grail in acute triptans as fi rst-choice treatments for migraine attacks therapy research. Serotonin 5-HT1F-receptor agonists is their high cost, and in some patients their cardiovas- and a novel calcitonin gene-related peptide (CGRP) an- cular side eff ects. However, stratifying care by prescrib- tagonist are currently being investigated, with promising a triptan to the most disabled patients has been ing results. Treatment algorithms should be inspired by

Table 4 Red fl ags in the diagnosis of headache Red Flags To Consider Possible Investigation(s) Sudden-onset headache Subarachnoid hemorrhage, brain bleeding, Neuroimaging, lumbar puncture (after neuro- mass lesion (especially posterior fossa) imaging) Worsening-pattern headache Mass lesion, subdural hematoma, medica- Neuroimaging tion overuse Headache with systemic illness (fever, Meningitidis, encephalitis, Lyme disease, Neuroimaging, lumbar puncture, biopsy, blood neck stiff ness, cutaneous rash) systemic infection, collagen vascular disease, tests arteritis Focal neurologic signs, or symptoms Mass lesion, arteriovenous malformation, Neuroimaging, collagen vascular evaluation other than typical visual or sensory aura collagen vascular disease Papilledema Mass lesion, pseudotumor, encephalitis, Neuroimaging, lumbar puncture (after neuro- meningitidis imaging) Headache triggered by cough, exertion Subarachnoid hemorrhage, mass lesion Neuroimaging, consider lumbar puncture or Valsalva Headache during pregnancy or post- Cortical vein/cranial sinus thrombosis, Neuroimaging partum carotid dissection, pituitary apoplexy New headache type in a patient with Metastasis, meningoencephalitis, opportu- For all neuroimaging and lumbar puncture cancer, Lyme disease or HIV nistic infection Source: Bigal ME, Lipton RB. Headache Pain 2007;8:263–72. Headache 217 personal experience, by the local pharmacoeconomic subject to controlled studies, and some, like butterbur situation, as well as by the available literature. (Petasites), were found clearly more eff ective than placebo. Several nondrug therapies (such as biofeedback What prophylactic therapy and psychologically based interventions) have proven is available in migraine? effi cacy in migraine prophylaxis. Prophylactic antimigraine treatment must be individ- How is the pharmacological ually tailored to each patient, taking into account the migraine subtype, the ensuing disability, the patient’s prophylaxis therapy in history and demands, and the associated disorders. A migraine selected? prophylactic treatment is also useful to prevent the Interestingly, the recommendations for prophylac- transformation of episodic migraine into chronic dai- tic treatment of migraine diff er around the world. ly headache with analgesic overuse (medication over- Beta-blockers and valproate are usually among the use headache). fi rst choices. Th e choice of drug should neverthe- A major drawback of most classical prophylac- less be individualized according to the drug’s side-ef- tics (beta-blockers devoid of intrinsic sympathomimetic fect profi le. For example, older patients might benefi t activity, valproic acid, Ca2+ antagonists, antiserotonin- from the antihypertensive properties of beta-blockers, ergics, and tricyclics), which have all on average a 50% while younger ones may suff er considerably from beta- effi cacy score, is the occurrence of side eff ects. If the blocker-induced sedation. initial trial is successful in reducing frequency of attacks Apart from the drugs in the list, there are other without causing signifi cant chronic side eff ects, then pharmacological options with weaker evidence, including the preventive therapy may be continued for 6 months. magnesium (24 mmol daily, especially for migraine asso- After 6 months, the dose is gradually decreased before ciated with the menstrual period), Petasites (butterbur), stopping the treatment. If the treatment is not success- Tanacetum parthenium (feverfew), candesartan (16 mg ful, dosing of the medication should be increased up to daily), coenzyme Q (100 mg t.i.d.) and ribofl avin (400 the maximum allowed, or a new preventive treatment 10 mg daily). should be initiated. In recent years, some new prophylactics with less side eff ects have been studied. Well-tolerated, but Table 5 Selection criteria for prophylactic pharmacological treatment in poorly eff ective in comparison to the classical prophylac- migraine tics, are high-dose magnesium or cyclandelate. A novel Drug and Dose Selected Adverse Eff ects preventive treatment for migraine is high-dose (400 Valproic acid, 500–1000 Liver toxicity, sedation, nausea, mg/d) ribofl avin, which has an excellent effi cacy/side- mg nightly (sustained weight gain, tremor, teratogenic- eff ect ratio and probably acts by improving the mito- release) ity, possible drug toxicity, hair loss, drowsiness chondrial phosphorylation potential. Coenzyme Q (100 10 Beta-blockers Reduced energy, tiredness, postural t.i.d.), another actor in the mitochondrial respiratory Propranolol, 40–240 mg symptoms, contraindicated in asthma chain, is also eff ective in migraine prophylaxis. Lisinopril Bisoprolol, 2.5–10 mg (10 mg b.i.d.), an inhibitor of angiotensin-converting en- Metoprolol, 50–200 mg zyme, and even more so, candesartan (16 mg b.i.d.), an Flunarizine, 5–10 mg daily Drowsiness, weight gain, depression, parkinsonism angiotensin II inhibitor, well-known for the treatment of Topiramate, 25–100 mg Paresthesias, fatigue, nausea, cogni- hypertension, were found useful in migraine. twice daily tive dysfunction Recent preliminary but encouraging results Amitriptyline, 25–75 mg Weight gain, dry mouth, sedation, with novel antiepileptic compounds such as gabapentin nightly drowsiness need to be confi rmed in large randomized controlled Methysergide, 1–4 mg daily Drowsiness, leg cramps, hair loss, ret- trials, whereas topiramate was found eff ective in several roperitoneal fi brosis (1-month drug “holiday” required every 6 months) placebo-controlled trials. Lamotrigine is up to now the Gabapentin, 900–3600 mg Dizziness, sedation only preventive drug that has been shown eff ective for daily migraine auras, but not for migraine without aura. Non- Lisinopril, 10–20 mg daily Cough pharmacological and herbal treatments are increasingly 218 Arnaud Fumal and Jean Schoenen What is essential to know about of amitriptyline at bedtime. Many patients will be satis- tension-type headache? fi ed by such a low dose. Th e average dose of amitriptyline in chronic TTH, however, is 75–100 mg per day. If Tension-type headache (TTH) is an ill-defi ned and a patient is insuffi ciently improved on this dose, a trial of heterogeneous syndrome, of which diagnosis is mainly higher doses of amitriptyline is warranted. If the head- based on the absence of features found in other headache has improved by at least 80% after 4 months, it is ache types such as migraine (see Tables 4 and 5 for diag- reasonable to attempt discontinuation of the medication. nostic criteria). It is thus above all a “featureless” head- Decreasing the daily dose by 20–25% over 2–3 days may ache, characterized by nothing but pain in the head. avoid rebound headache. Th e best results are obtained Th e diagnostic problem most often encountered is to by combining tricyclics with relaxation therapy. discriminate between TTH and mild migraines. TTH is the most common form of headache, but it receives What is essential to know about much less attention from health authorities, clinical re- cluster headache and other searchers, or industrial pharmacologists than migraine. trigeminal autonomic cephalalgias? Th at is because most persons with infrequent or frequent TTH never consult a doctor; treat themselves, if Trigeminal autonomic cephalalgias (TACs) are a group necessary, with over-the-counter analgesics. Howev- of rare primary headache syndromes that include clus- er, chronic TTH, which causes headache ≥15 days per ter headache, paroxysmal hemicrania, SUNCT (short- month represents a major health problem with an enor- lasting unilateral neuralgiform headache attacks with mous socioeconomic impact. In a population-based conjunctival injection and tearing), and SUNA (short- study, the lifetime prevalence of tension-type headache lasting unilateral neuralgiform headache attacks with was 79%, with 3% suff ering from chronic TTH, i.e., cranial autonomic symptoms). Although rare, they are headache ≥15 days per month. important to recognize because of their excellent but It still is a matter of debate whether the pain in highly selective response to treatment. Th ey share the TTH originates from myofascial tissues or from central same features in their phenotype of headache attacks, mechanisms in the brain. Research progress is ham- which is a severe unilateral orbital, periorbital, or tem- pered by the diffi culty in obtaining homogeneous pop- poral pain, with associated ipsilateral cranial autonomic ulations of patients because of the lack of specifi city symptoms, such as conjunctival injection, lacrimation, of clinical features and diagnostic criteria. Th e present nasal blockage, rhinorrhea, eyelid edema, and ptosis. consensus, nonetheless, is that peripheral pain mecha- Th e distinction between the syndromes is made on du- nisms are most likely to play a role in infrequent epi- ration and frequency of attacks. sodic TTH and frequent episodic TTH, whereas central As cluster headache (CH) is the commonest of dysnociception becomes predominant in chronic TTH. the TACs, we will describe only this kind of headache in Simple analgesics (i.e., ibuprofen 600 to 1200 the present chapter. CH has a prevalence of about 0.3%, mg/d) are the mainstay of treatment of episodic TTH. and male-female ratio of 3.5–7:1. Th e attacks of CH Combination analgesics, triptans, muscle relaxants, are stereotypical, being severe or excruciating, lasting and opioids should not be used, and it is crucial to even 15–180 minutes, occurring once every other day up to avoid frequent and excessive use of simple analgesics to eight times per day, and associated with ipsilateral au- prevent the development of medication overuse head- tonomic symptoms. In most patients, CH has a striking ache. Prophylactic pharmacotherapy should be consid- circannual and circadian periodicity. Diagnosis is based ered in patients with headaches for more than 15 days on IHS criteria for the phenotype of attacks, but an MRI per month (chronic TTH). A prophylactic treatment is of the brain with contrast should be performed in order useful to prevent the transformation of episodic TTH to rule out a secondary/symptomatic CH. into medication overuse headache. Th e tricyclic antide- Cluster headache patients should be advised to pressant amitriptyline is the drug of fi rst choice for the abstain from taking alcohol during the cluster period. prophylactic treatment of chronic TTH, but nonphar- Because the pain of CH builds up so rapidly, abortive macological management strategies (relaxation, bio- agents have to act quickly to be useful. By far the most feedback, physical therapy) are equally eff ective. Th e effi cient one is a subcutaneous injection of sumatriptan initial dosage of tricyclics should be low: 10–25 mg 6 mg. Inhalation of 100% oxygen, at 10 to 12 L/minute Headache 219 via a nonrebreathing facial mask for 15 to 20 minutes, • Although headache is one of the most common can be eff ective in up to 60–70% of attacks, but pain reasons for patients to consult their doctor, and frequently recurs. Th e aim of the preventive therapy despite its enormous impact, it is still under-rec- is to produce a rapid remission of the disorder and to ognized and undertreated. maintain that remission with minimal side eff ects un- • Inaccurate diagnosis is probably the most com- til the cluster bout is over according to its natural his- mon reason for treatment failure. A systematic tory, or for a longer period in patients with chronic CH. approach to classifi cation and diagnosis is there- Steroids are very eff ective in interrupting a bout. Sub- fore essential both for clinical management and occipital injections of long-acting steroids should be research. preferred to oral treatment, to lessen the risk of “corti- • Improvements in treatment have been less dra- co-dependence.” Verapamil is the next preventive drug matic than remarkable revelations from basic and of choice, but lithium, topiramate, methysergide, or cor- clinical research on headaches. ticosteroids can also be used. Functional imaging data • Finally, while the eff ective newer treatments are suggest the hypothalamus to be the origin for CH. quite expensive, e.g., newer antiepileptics and triptans, older drugs are still available everywhere Can headache medication with a good benefi t-cost ratio: NSAIDs (for acute cause headache? treatment) and beta-blockers and/or ribofl avin (for prophylactic treatment) in migraine, and oxy- Overuse of acute medication is the most frequent factor gen (for acute treatment) and verapamil (for pro- associated with the transformation of episodic migraine phylactic treatment) in cluster headache. into chronic daily headache. Th e latter is called “medication overuse headache” (MOH) in the 2nd edition of the References International Classifi cation of Headache Disorders (ICHD- II, 2004). It is classifi ed as a secondary headache disorder, [1] Cohen AS, Matharu MS, Goadsby PJ. Trigeminal autonomic cephalalgias: current and future treatments. Headache 2008;47:969–80. which may evolve from any type of primary headache, but [2] Colas R, Munoz P, Temprano R, Gomez C, Pascual J. Chronic daily mainly from episodic migraine, and in a lower proportion headache with analgesic overuse: epidemiology and impact on quality of life. Neurology 2004;62:1338–42. in tension-type headache. MOH is a disabling health prob- [3] Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT agonists) in acute migraine treatment: a meta-analysis of 53 lem, which may aff ect 1–2% of the general population. 1B/1D trials. Lancet 2001;358:1668–75. Th e most effi cient treatment for MOH is abrupt [4] Fumal A, Schoenen J. Current migraine management—patient acceptability and future approaches. Neuropsychiatr Dis Treat 2008;4:1043– drug withdrawal and immediate prescription of a pre- 57. ventive drug (an antimigraine agent if the primary head- [5] Fumal A, Schoenen J. Tension-type headache. Where are we? Where do we go? Lancet Neurol 2008;7:70–83. ache is a migraine, or tricyclics in case of TTH), but [6] Goadsby P. Recent advances in the diagnosis and management of mi- there are no studies comparing diff erent strategies. Th ere graine. BMJ 2006;332:25–9. [7] International Headache Society. Th e International Classifi cation of are thus no clear, worldwide accepted guidelines regard- Headache Disorders. 2nd edition (ICHD-II). Cephalalgia 2004;24(Suppl 1):1–160. ing modality of withdrawal or treatment of withdrawal [8] Mateen FJ, Dua T, Steiner T, Saxena S. Headache disorders in de- symptoms. Oral prednisone, acamprosate, tizanidine, veloping countries: research over the past decade. Cephalalgia 2008;28:1107–14. clomipramine, and intravenous dihydroergotamine were found useful for withdrawal headaches, but results are confl icting, for example, prednisone shows both posi- Websites tive and negative results. It seems clear that after the fi rst International Headache Society (IHS): http://www.i-h-s.org/ 2-week physical withdrawal period, comprehensive long- Following the listing by the World Health Organization of the world’s 100 term management of the biopsychosocial problem of poorest countries (British Medical Journal 2002;324:380), IHS off ers Associ- ate Membership free to individuals living in those countries who qualify for these patients is necessary to minimize relapse. Ordinary Membership. Associate Membership carries the responsibilities to the Society of Ordinary Membership (other than payment of the membership fee), but off ers limited benefi ts. Th ese include on-line access to the Pearls of wisdom Society’s journal Cephalalgia. American Headache Society (AHS): www.americanheadachesociety.org/ • Recurrent headache disorders impose a substan- World Headache Alliance (WHA): http://www.w-h-a.org/ tial burden on individual headache suff erers, on their families, and on society.

Guide to Pain Management in Low-Resource Settings

Chapter 29 Rheumatic Pain

Fereydoun Davatchi

What is rheumatology? tenosynovitis, bursitis, etc.). Bone diseases are divided into metabolic (osteoporosis, osteomalacia), infec- Rheumatology is a subspecialty of internal medicine tious, tumoral (benign, malignant, metastatic), and ge- dealing with bone and joint diseases (connective tis- notypic malformations. sue and related tissue disorders of bone, cartilage, tendons, ligaments, tendon sheets, bursae, muscles, etc.). What is the connection between Although modern rheumatology is based on advanced molecular biology, immunology, and immunogenetics, rheumatology and pain? the daily practice and routine diagnosis is mainly clini- The most important symptom in rheumatology is cal and based on symptoms and signs. In the majority pain. The pain can be inflammatory, mechanical, or of cases, laboratory tests and imaging have a confi rma- continuous. Inflammatory pain occurs during rest tory role, instead of being mandatory. Simple tests, such and disappears or improves gradually with activity. as complete blood count (CBC), erythrocyte sedimen- It is accompanied by some degree of stiffness, espe- tation rate (ESR), C-reactive protein (CRP), rheumatoid cially in the morning when the patient wakes up. Me- factor (RF), uric acid, and urinalysis, are suffi cient in chanical pain appears with activity, increases gradu- many cases. Sophisticated investigations are rarely man- ally, and disappears with rest. It can be accompanied datory in routine practice. Th e same is true regarding by gelling pain, which resembles inflammatory pain, elaborate imaging technics. but is of very short duration (a few minutes or less). Pure continuous pain is rare; usually one can find an How are rheumatological inflammatory or mechanical feature. Joint swelling is diseases classifi ed? the second most important symptom in rheumatology. It can be due to either effusion or synovial hy- They are divided in three groups: articular, extra-ar- pertrophy. Bony enlargement of the joint (bone hy- ticular, and bone diseases. Articular manifestations pertrophy) is the differential diagnosis. Limitation of can be divided into six categories: inflammatory, joint movement is an indicator of joint involvement. mechanical, metabolic, neurological, infectious, and Abnormal movement is an indicator of joint disloca- tumoral disorders. Extra-articular manifestations tion (cartilage destruction, ligament tear, and epiphy- are also called soft tissue rheumatism (tendonitis, seal collapse).

Fig. 1. Decision tree for rheumatic pain. OA, osteoarthritis; STR, soft-tissue rheumatism.

[4] Dayo RA, Diehl AK, Rosenthal M. How many days of bed rest for References acute low back pain? A randomized clinical trial. N Engl J Med 1986;315:1064–70. [1] Davatchi F. Rheumatic diseases in the APLAR region. APLAR J Rheu- [5] Medscape. Back schools for nonspeciﬁ c low back pain. Available at: matol 2006;9:5–10. www.medscape.com/viewarticle/485199. [2] Davatchi F, Akbarian M, Shahram F, et al. DMARD combination ther- [6] Medscape. Low-intensity back rehab programs promote quicker return apy in rheumatoid arthritis: 5-year follow-up results in a daily practice to work. Available at: www.medscape.com/viewarticle/531807. setting. APLAR J Rheumatol 2006; 9: 60–63. [7] Medscape. New guidelines to diagnose hand osteoarthritis. Available at: [3] Davatchi F, Jamshidi AR, Banihashemi AT, Gholami J, Forouzanfar MH, www.medscape.com/viewarticle/569860. Akhlaghi M, Barghamdi M, Noorolahzadeh E, Khabazi AR, Salesi M, [8] Peul WC, van Houwelingen HC, van den Hout WB, Brand R, Eekhof Salari AH, Karimifar M, Essalat-Manesh K, Hajialiloo M, Soroosh M, JA, Tans JT, Th omeer RT, Koes BW; Leiden-Th e Hague Spine Interven- Farzad F, Moussavi HR, Samadi F, Ghaznavi K, Asgharifard H, Zan- tion Prognostic Study Group. Surgery versus prolonged conservative giabadi AH, Shahram F, Nadji A, Akbarian M, Gharibdoost F. WHO- treatment for sciatica. N Engl J Med 2007; 356: 2245–2256. ILAR COPCORD study (stage 1, urban study) in Iran. J Rheumatol [9] Wikipedia. World population. Available at: http://en.wikipedia.org/ 2008;35:1384. wiki/World_population.

Diﬃ cult Th erapeutic Situations and Techniques

Guide to Pain Management in Low-Resource Settings

Chapter 30 Dysmenorrhea, Pelvic Pain, and Endometriosis

Susan Evans

Case report • Regular daily gentle exercise should be encouraged to help reduce pain levels. A 25-year-old married woman presents with pelvic pain • Her headaches should be managed. on most days each month, especially during the time of • Th e decision to refer her to a surgeon will depend her period. She suff ers crampy period pain before and on whether her period pain becomes unmanage- during her period, sharp stabbing pains that come at able or she has diffi culty becoming pregnant. It any time and wake her at night, bladder symptoms (uri- will also depend on the surgical skills available. nary frequency, urgency, and nocturia), headaches, and dyspareunia (painful sexual intercourse). How frequent is pelvic pain? What are the treatment options? Pelvic pain is underreported, undertreated, and underestimated throughout the world. It aff ects approximate- Th is woman has chronic pelvic pain, with a combina- ly 15% of all women aged 18–50 years. Although it is tion of diff erent types of pain, and she probably has en- complex to treat, the improvement in quality of life that dometriosis. For pain control she will need treatment can be achieved is very rewarding. Most women have for each type of pain: more than one type of pain. Th eir symptoms include • Th e oral contraceptive pill and a nonsteroidal an- any, or all of: ti-infl ammatory drug (NSAID) are good fi rst-line • Dysmenorrhea options for her period pain. If the pain persists, • Dyspareunia and high-level laparoscopic surgery to remove • Neuropathic pain endometriosis is not available, then continuous • Bowel dysfunction progestogen or a levonorgestrel intrauterine de- • Bladder dysfunction vice are options. • Vulval pain • Amitriptyline starting at 10 mg at early evening, • Bloating daily, and increasing slowly as tolerated up to 25 • Chronic pelvic pain mg daily could be prescribed for her sharp stab- Frequently, their pain symptoms have been present bing pains and the bladder symptoms. for years without diagnosis or management. Th e pain • A careful history should identify dietary triggers aff ects their education, employment, relationships, self- for her bladder symptoms and the cause of her esteem, general wellbeing, sleep and sometimes fertility, dyspareunia (see below). so it is important to realize that patients needs emotional

History How can I treat dysmenorrhea Ask about the date of the last period in case of pregnan- on day 1–2 of the menstrual cycle? cy, and make a list of each pain or symptom the patient Pain at this stage of the cycle is usually uterine pain. has. For each pain, ask her to describe what it feels like, Management options at the primary care level include where it is, when it occurs, how many days she has it monophasic oral contraceptive pills, such as 20–35 μg per cycle, and what aggravates or relieves it. Ask about ethinyl estradiol with 500–1,000 μg norethisterone or bladder symptoms (nocturia, frequency, urine infec- 150 mg levonorgestrel, as well as pain medication. Th e tions, urgency), ask about bowel function (constipation, pain medication of fi rst choice should be an NSAID tak- diarrhea or bloating, pain opening her bowels during en early on in the episode of pain, such as ibuprofen at her period), ask about pain with movement and pain in a dose of 400 mg initially and then 200 mg three times other areas of the body (e.g., migraine or muscle tender daily with food. For moderate or severe pain, opioids points), ask whether intercourse is painful, and ask how should be off ered. Nonpharmacological options include many days a month she feels completely well. hot or cold packs over the lower abdomen, Vitex agnus castus (chasteberry) 1 g daily (avoid if pregnant; ineff ec- Examination tive if on oral contraceptive pills), vitamin E (400–500 Assess the patient’s general well-being (depression, pos- IU natural vitamin E from 2 days before period until day ture, and nutrition), the abdomen (for sites of pain, ten- 3) and zinc 20 mg (as chelate) twice a day. Traditional derness, peritonism, or masses), the vulva (for tender- Chinese Medicine (acupuncture and herbal therapies) ness, skin lesions, or vulval infection), the pelvic fl oor are also popular, but they should only be recommended muscles (for tenderness and spasm), the vagina (for if aff ordable and if the patient has a positive attitude. nodules of endometriosis posterior to the cervix or in Many women with severe dysmenorrhea become the rectovaginal septum, or congenital anomalies), and fearful as their period approaches. Th ey fear pain that the pelvis (for uterine or adnexal masses, pregnancy). they cannot control. By providing them with strong an- Vaginal examination is rarely necessary in virgins. algesics to control severe pain if it occurs, this anticipation of pain can be reduced and they can regain control Investigation of the pain. Th erefore, “on-demand” doses of analgesics Exclude pregnancy, including ectopic pregnancy, screen should be provided. for sexually transmitted diseases if appropriate, and take a cervical smear if available (unnecessary for virgins). How can I treat prolonged dysmenorrhea? Ultrasound may show an endometrioma, but it is often Could the patient have endometriosis? normal, even with severe endometriosis. Dysmenorrhea (painful cramps) for more than 1–2 days is often due to endometriosis, even in teenagers. How can I plan treatment A woman with endometriosis also has a more painful for pelvic pain? uterus than other women. She thus has two causes for her pain. Management options include on the prima- Th e treatment recommended depends on the symp- ry care level all the treatments used for dysmenorrhea toms present. Most women will have more than one above, a levonorgestrel intrauterine device, continuous pain symptom. Plan a treatment for each separate pain progestogen (norethisterone 5–10 mg daily, dydroges- symptom. Remember to treat any coexisting health terone (a synthetic hormone similar to progesterone) Dysmenorrhea, Pelvic Pain, and Endometriosis 231

10 mg daily, or depot medroxyprogesterone acetate to (start with 10 mg at night, increase slowly to 10–50 mg achieve amenorrhea). If referral to a well-equipped hos- at night). pital is an option, surgery, preferably laparoscopy, to di- Many women with bladder symptoms develop sec- agnose and remove endometriosis, if medical treatments ondary pelvic fl oor dysfunction with dyspareunia and have failed, would be indicated. Hysterectomy is only in- severe muscular pelvic pain. If pain persists, consid- dicated if the patient is older and her family is complete. er cystoscopy with hydrodistension. All medications Conserve the ovaries where possible in premenopausal should be avoided in pregnancy, if possible. Also note women. Ovarian endometriomas can usually be treated that hydroxyzine is contraindicated in epileptics. with cystectomy rather than oophorectomy. How can I treat sharp, stabbing pains? How can I treat ovulation pain? Sharp, stabbing pains are usually a form of neuropathic Normal ovulation pain should only last for 1 day, oc- pain. Treatment includes neuropathic pain medications curs 14 days before a period, and changes sides each (e.g., amitriptyline 5–25 mg in the early evening, gaba- month. Management options include an NSAID when pentin 100–1200 mg daily), regular sleep, regular exer- pain occurs, an oral contraceptive pill to prevent ovu- cise (start with regular low-level exercise to avoid initial lation, or continuous norethisterone 5–10 mg daily to worsening of pain), and stress reduction. Start all medi- induce amenorrhea. If more than the primary care lev- cations at a very low dose and increase slowly. Where el is available, and pain is severe or always unilateral, a high-level surgical skills are available, excision of endo- laparoscopy with division of adhesions and removal of metriosis lesions, if present, can sometimes improve the endometriosis is indicated. An ovary should only be pain, although frequently this type of pain continues af- removed if severely diseased, and the patient’s fertility ter surgery. needs have been discussed and carefully considered. How can I diagnose the cause of dyspareunia? How can I treat a woman with pelvic Dyspareunia (painful intercourse) may be the most dis- pain and bladder symptoms? tressing symptom for many women, as it interferes with Many women with pelvic pain describe frequent urina- the relationship they have with their husband. She may tion, nocturia, pain when voiding is delayed, suprapubic feel that she is letting her husband down when she is pain, vaginal pain, dyspareunia, or the feeling of having unable to have intercourse due to pain, and he may feel a urinary tract infection. Th is feeling is often due to in- that she is avoiding intercourse because she no longer terstitial cystitis of the bladder. Th ere may be a history loves him. It is important to identify the cause of the of frequent “urinary tract infections” but with negative problem: urine culture. First, exclude urine infection, chlamydia, • Examine the vulva visually for abnormalities (in- and gonococcal or tuberculous urethritis. Th en ensure fection, dermatitis, lichen sclerosis). suffi cient fl uid intake to avoid concentrated urine. Iden- • Use a cotton-tipped swab to test for tenderness of tify and avoid dietary triggers if present. Common trig- the posterior fourchette, even if it looks normal gers include coff ee, cola drinks, tea (including green (to check for vulvar vestibulitis). tea), vitamins B and C, citrus fruit, cranberries, fi zzy • Use one fi nger in the lower vagina to push back- drinks, chocolate, alcohol, artifi cial sweeteners, spicy wards (to check for pelvic fl oor muscle pain or foods, or tomatoes. Peppermint and camomile teas are vaginismus). Use one fi nger to push anteriorly (to usually acceptable. If food triggers are present, pain usu- check for bladder or urethral pain). ally follows within 3 hours of food intake. Provide in- • Use one or two fi ngers to check the upper vagina structions about how to manage symptom fl ares (drink for nodules of endometriosis, pelvic masses, or 500 mL water mixed with 1 teaspoon of bicarbonate uterine fi xation. Push the cervix to one side to of soda. Take a paracetamol (acetaminophen) and an check for contralateral adnexal pain (to check for NSAID if available. Th en drink 250 mL water every 20 endometriosis, ovarian cysts, pelvic infection, or minutes for the next few hours). For symptom control, adhesions). try amitriptyline 5–25 mg at night, oxybutynin (start • Use a speculum to look for cervicitis, vaginal in- with 2.5 mg at night, increase slowly to 5 mg three times fection, vaginal anomaly, or endometriotic nod- a day), or hydroxyzine, especially for those with allergies ules in the posterior vaginal fornix. 232 Susan Evans If any part of the examination causes pain, ask the • Regular gentle exercise (e.g., walking, stretching, patient if this is the same pain she has with intercourse. gentle yoga), improved posture, sitting square in It is important to examine the lower vagina gently with a comfortable chair with good support, keeping one fi nger before using the speculum, or pelvic fl oor/ both feet fl at on the fl oor when sitting, and taking bladder pain may be missed. Generalized dyspareunia, regular breaks. especially where sharp pains are present, may be neu- • Heat packs to the pelvis and a warm bath 1–2 ropathic. Include in the consultation a discussion about times daily for 3–6 weeks the relationship she has with her husband and whether • Management of anxiety and depression, if present. he is supportive of her. When should I refer my patient How can I help my patient with pelvic pain to a surgeon? with a painful vulva (vulvodynia)? Surgery should be considered where nonsurgical treat- General vulval care is often helpful. Th e patient should ments have failed. Laparoscopy is preferred to laparoto- not use soap and should avoid vulval products such my where it is safe and available. However, laparoscopy as talc or oils. Recommend aqueous cream as a soap, requires advanced surgical equipment and skills, and soother, and daily vulval moisturizer. Recommend cot- major surgical complications do occur. It is therefore ton underwear and loose clothing. Treat any vaginal important to try nonsurgical options fi rst. Endometrio- infection. Prescribe amitriptyline 5–25 mg at night or sis surgery is frequently diffi cult and requires the best an anticonvulsant for vulval pain if present. For vulvar surgical skills available. Situations that suggest severe vestibulitis, prescribe a course of oral ketoconazole (an- disease, possibly requiring a bowel surgeon as well as a tifungal) 200 mg and betamethasone cream (0.5 mg/g) gynecologist, include: applied thinly daily for 3 weeks. For lichen sclerosis, • Th e presence of ovarian endometriomas. prescribe steroid cream applied thinly daily for intermit- • Nodules of endometriosis palpable in the recto- tent courses only when symptoms are present. vaginal septum. • An immobile uterus. How can I help my patient • Pain opening the bowels during the menstrual with painful pelvic muscles? period. Th e muscles are in spasm and do not relax normally. In premenopausal women, if postoperative estro- Th is type of pain can be secondary to painful bladder gen replacement is unavailable, bilateral oophorec- symptoms, any type of pelvic pain, previous sexual as- tomy should be avoided, if possible. Endometriomas sault, or anxiety regarding sexual intercourse. Pain is se- in young women should be managed with cystectomy vere, just as pain from back spasms can be severe. Typi- rather than oophorectomy in most cases. Drainage cal symptoms include dyspareunia (with pain for 1–2 alone of an endometrioma is usually followed by rap- days afterwards), pain on moving, pain with insertion of id recurrence. a fi nger or a speculum, and pain with tampons. Th ere may be pain on prolonged sitting. Pelvic fl oor muscle What are common barriers to spasm is involuntary, and the patient cannot “just relax.” Th e best treatment involves pelvic fl oor physiotherapy, eff ective pain management? instruction in relaxation techniques, and the regular use A long delay between the beginning of symptoms and of vaginal dilators in a relaxed, secure, nonpainful situ- the diagnosis and management of pelvic pain is com- ation. Intercourse should be avoided until the problem mon for many reasons. Th e patient’s family may not has resolved because the problem will worsen with re- believe that her pain is real and severe, she may believe peated painful intercourse. If intercourse continues, that severe pain with periods is normal, or her local a vaginal lubricant and a slow approach to intercourse doctor may believe that she is too young for endome- may help. Other treatments include: triosis or underestimate how severe her pain is. • Resolution of initiating factors, e.g., bladder Other barriers to eff ective pain management include symptoms/pelvic pain. fear of gynecological examination, especially where a • Avoid straining with voiding or trying to stop female doctor is unavailable; fear of surgery, infertility, passing urine in mid-void. and cancer; and fear of the unknown. Dysmenorrhea, Pelvic Pain, and Endometriosis 233 It is therefore important to explain to the patient • Many common causes of pelvic pain cannot be and her family: seen during an operation, including bladder pain, • Th e pain is real, and the pain is not her fault. neuropathic pain, uterine pain, pelvic fl oor mus- • She does not have cancer, and her pain is not life- cle pain, and bowel pain. Some women have en- threatening. dometriosis and all these other pains. Migraine • Although it may not be possible to completely headaches are also common. cure all her pain, she can optimistically look for- • Women with chronic pain who appear “worn ward to less pain and living better with what pain down” emotionally or depressed often have a remains. It is important to be positive. neuropathic component to their pain. Th is will be • Resources she can contact if she needs help. worse if the patient is stressed or overworked. • What extra pain relief she can use if the pain be- • Recognize that many women have had pain for comes more severe; her anxiety will decrease long periods of time, resulting in loss of confi - when she knows that she can manage pain if it dence, employment and education opportunities, occurs. relationships, and sometimes fertility. • To ensure that she is not overworked, because • It is important that the patient’s family value her tiredness will worsen her pain. health and happiness, and that she has activities • To ensure that she has activities in her life that in her life that bring her joy, relaxation, and satis- she enjoys. faction. “Fit, happy people have less pain.” • Recognize that while surgery can be very helpful, What should I ask it does not cure all pain. Th e decision whether to proceed to surgery or use nonsurgical treatment at follow-up visits? will depend on the surgical facilities available. Follow-up assessments are important because the pain • Be careful to explain the pain to the patient and will vary over time, and the patient will need continued make sure she knows that you believe in her pain. support to be well. At each follow-up: Most women with this type of pain have been • Ask about each of the pains she reported at her told that “it is all in their head,” which lowers their fi rst visit to assess progress. Pain that has been self-esteem. resolved is often forgotten. She may feel that no • Make sure that the family knows that the pain is progress has been made if any pains remain. real. Th e patient will need the support of her fam- • Ask about any new pains. Ask about sexual func- ily to access care. tion. Off er treatment for any new pains. • Discuss lifestyle issues again, such as regular ex- References ercise, healthy diet, stress management, relation- [1] Evans S. Endometriosis and pelvic pain. Available from: www.drsusane- ship issues, and activities that she enjoys. vans.com. (An easy-to-read book for patients that explains how to diag- • Make sure she understands that her pain may nose and treat many types of pelvic pain.) [2] Howard FM. Pelvic pain: diagnosis and management. Lippincott Wil- change over time but that help is available if she liams and Wilkins; 2000. (A textbook for doctors describing all aspects needs it. of pelvic pain in detail.) [3] Stein A. Heal pelvic pain. Available from: www.healpelvicpain.com. (A book for patients with all types of musculoskeletal pelvic pain.) Pearls of wisdom Websites • Most women with chronic pelvic pain have several diff erent pain symptoms. Each pain needs to be www.endometriosis.org (world forum for patients and doctors) assessed, and a treatment plan made. Pelvic pain www.endometriosisnz.org.nz (for teenagers with endometriosis) cannot be considered as a single entity. www.ic-network.com (for bladder symptom information)

Guide to Pain Management in Low-Resource Settings

Chapter 31 Pain Management Considerations in Pregnancy and Breastfeeding

Michael Paech

Case report 1 (analgesics in (30–60 mg every 6 hours as required, but only once or pregnancy) two days each fortnight).

You are visited by a woman, Shillah, and her partner, Should you be concerned about prescribing pain killers in a pregnant or lactating woman? Alusine, from a large rural town. Th ey have recently married, and they plan to move to the regional city and We should be cautious about prescribing any drug to stay with relatives because they are hoping to start a a pregnant woman! Nevertheless, almost 90% of wom- family. Alusine says: “Doctor, my wife has bad back and en take prescribed drugs during pregnancy. Although leg pain, and every day she takes medication prescribed the incidence of analgesic use during pregnancy varies by the local doctor. We are trying to have a baby, so I am across diff erent countries, it is probably 5–10% during worried about how those drugs might aff ect the baby. Is it the fi rst trimester and is likely to be much higher in later okay for her to keep taking them?” pregnancy. Th e incidence of perinatal use of illicit drugs You ask Shillah about her pain, and learn that (including opioids) also varies widely, but it ranges from she has had it for over a year since a motor vehicle ac- 10% to 50%. Th us, it is extremely common for preg- cident in which she broke some lumbar vertebrae. Th e nant women and their fetuses to be exposed to drugs pain has persisted and is a burning sensation that radi- relevant to pain management during pregnancy and ates from the low back down through the buttock past lactation. Th e incidence of fetal abnormalities among the back of her knee, often occurring at night when she is live births is approximately 2%, so this background lying quietly. She also has an area near her spine in the rate should be considered when comparing rates in the lower back that tingles and feels sore, even when it is only whole pregnant population with those among women touched lightly. He doctor has tried her on several diff er- taking specifi c drugs. ent analgesic drugs, and the only one that helps a little is Despite the prevalence of their use, there is very a tablet she takes at night before bed, although she is also little information about the eff ects of analgesic drugs taking an anti-infl ammatory drug, and she takes some being taken prior to conception on fertility. Th ere are codeine when the pain is bad—but it makes her consti- limited human epidemiological or observational data pated, so she doesn’t like to use it much. On examination on the eff ects of pain-relieving drugs during early preg- she has no obvious spinal abnormality. You later learn nancy. With the exception of aspirin and the nonsteroi- she is taking a low dose of amitriptyline (10 mg) at night, dal anti-infl ammatory drugs (NSAIDs), the embryo ap- regular diclofenac (100 mg twice a day), and codeine pears protected in the fi rst 2 weeks. Th e fetus is most

Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. All rights reserved. Th is material may be used for educational and training purposes with proper citation of the source. Not for sale or commercial use. No responsibility is assumed by IASP for any injury and/or damage to persons or property 235 as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends that there should be independent verifi cation of diagnoses and drug dosages. Th e mention of specifi c pharmaceutical products and any medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text. 236 Author(s) at risk during the period of organogenesis, between 17 anesthetist or pain specialist, a physiotherapist, a chi- and 70 days postconception; however, the use of some ropractor, a psychologist, a pharmacist, and/or a com- drugs during the second and third trimesters of preg- munity nurse. Th is multidisciplinary team approach nancy can also cause organ abnormalities, especially will optimize her care, and regular review of her pain in the central nervous and cardiovascular systems. It is management can be organized. Shillah may well have thus important to know, in detail, the potential risks as- physical and psychological factors contributing to sociated with analgesic drug administration at any stage her pain that can be treated in various ways, includ- of pregnancy. ing physical therapies and even invasive pain therapy Fortunately, we know it is likely that millions procedures or surgery, such that her reliance on drugs of women have taken some of the commonly used might be reduced or even eliminated. Th e latter would, pain killers, both at the time of conception and dur- of course, solve all the issues related to the potential ing early pregnancy. For a number of analgesic drugs, pharmacological toxicities of drugs administered dur- extensive clinical experience indicates a very low risk ing pregnancy. Even if drug treatment remains the only of problems, which is reassuring. When clinical in- way of controlling her pain, her response to the types formation is combined with analysis of animal data of drugs, their doses, and the regimens prescribed will about potential teratogenic or carcinogenic eff ects, need to be reviewed once she becomes pregnant and or data about how much drug is transferred into the as pregnancy advances. breast milk, the level of concern about a drug can be estimated. Consequently, regulatory bodies and edu- What would your advice be for Shillah and Alusine? cational organizations in many countries have classifi ed drugs into risk categories that are used to guide Shillah has chronic nonmalignant pain with neuro- a risk versus benefi t assessment in the pregnant and pathic features, and you should refer to the chapters lactating woman. For example, there is no evidence on back pain and neuropathic pain for information. that opioids are risky in early pregnancy, but they may You also need to be in a position to advise her about cause depression of the neonate at birth, so most opi- the specifi c risks of the drugs she is currently taking oids are classifi ed as drugs that have harmful but re- and about any risks associated with alternative drugs. versible pharmacological eff ects on the human fetus First, what about a tricyclic antidepressant such as am- or neonate, without causing malformations. itriptyline, an NSAID such as diclofenac, and an opioid It is imperative to relieve maternal suff ering, but such as codeine? at the same time, harm to the fetus should be avoided. It is important to be honest and transpar- Breastfeeding is also a critical imperative for optimizing ent in all communication. Although there can be no the infant’s health, possibly with life-long benefi ts. It is guarantees of complete safety with any drug, and be- important that we know where to look and are able to cause controlling neuropathic pain can be challenging, access information about these topics when specifi c in- it is not necessary for her to abandon all pain killers. formation is required. Indeed, there is no evidence that continuing amitriptyline in early pregnancy signifi cantly increases the What would be the ideal approach to pain risk of malformations. Th is is a drug many pregnant management in pregnancy and lactation? women have used, so the couple can be reassured of its During and immediately prior to pregnancy, nonphar- relative safety, and it could be continued. Th e NSAIDs macological pain management options should be con- such as diclofenac and indomethacin (and a similar sidered and explored before analgesic drugs are used. drug, aspirin) are not eff ective against neuropathic Ideally, if available in the regional city, and prior to pain but may be very helpful for a few days for mus- Shillah becoming pregnant, she should be reviewed by culoskeletal or postoperative wound pain. However, a group of health care providers, particularly those with unless there is active infl ammation, which is unlikely an interest in pain medicine and clinical experience in Shillah’s case, they should not be continued long- dealing with patients with diffi cult pain management term. Although these drugs do not cause fetal mal- problems. In Shillah and Alusine’s case, for example, formations, they adversely infl uence fertility, increase this group might include an orthopedic surgeon, a reha- the risk of miscarriage by interfering with blastocyst bilitation physician, an obstetrician, a family doctor, an implantation, and can cause serious problems in late Chapter Title 237 pregnancy (see below). You should advise Shillah to abnormalities, but experience in early pregnancy is very stop the diclofenac, and if available to try paracetamol limited, so it would be preferable to use an opioid in- (acetaminophen) instead, this being a much safer op- stead for Shillah. After the period of organogenesis, lim- tion. Although it is not ideal, there is no reason why ited data suggest that tramadol is probably of low risk to Shillah should not continue to take codeine when she the fetus, although high dosing near delivery should be needs it (at a maximum dose of 240 mg per day), es- avoided (see case 3 below). pecially if you check her diet and advise her as to how In some countries, transdermal clonidine patch- to reduce her risk of constipation. Codeine has been es (100 μg/day) are available, but clonidine is of ques- used by many pregnant women and is considered safe tionable eff ectiveness, and despite extensive clinical use for the fetus in early pregnancy. Th e main problem during pregnancy without evidence of causing congeni- with codeine is that some people lack the liver enzyme tal abnormalities, data on its safety in the fi rst trimester required to demethylate it to its active metabolite, are very limited. Th erefore, the use of clonidine is not morphine, rendering it completely ineff ective. Other recommended. people are ultrarapid codeine metabolizers and will experience higher plasma concentrations and more side What if Shillah continues to have neuropathic pain later in pregnancy? eff ects (sedation, dysphoria, constipation, and neonatal depression), even after small to modest doses. Good levels of evidence support both the effi cacy and safety of typical doses of amitriptyline (initially 10–25 Are there any other analgesics that mg orally at night). Ketamine, another potent analgesic, might be available when Shillah attends can be eff ective for both acute and neuropathic pain, the large city hospital? although oral tablet or lozenge forms are still being de- Th ere are some other pain killers that might prove more veloped. Ketamine has been used in large numbers of eff ective or cause fewer side eff ects. Instead of codeine, pregnant women without links to malformations, so oxycodone (5–15 mg repeated as required) is an exit is considered safe, making it a valuable option when ample of an oral opioid, eff ective against moderate to patients are admitted to hospital when either acute or severe pain, which causes less constipation. Long-term neuropathic pain is diffi cult to manage(bolus up to 0.25 opioid administration continued until delivery of the mg/kg and initial infusion rate 5–10 mg/h). Because lo- baby has some signifi cant disadvantages, however (see cal anesthetics are safe during pregnancy, lidocaine (lig- case 3 below), so it would be essential to confi rm that nocaine) infusion (1 mg/kg over 20 minutes then 10–30 Shillah’s pain is opioid-sensitive. She could be admitted mg/h, see the chapter on neuropathic pain) is another to hospital, her pain evaluated (pain scores, functional option that is eff ective in a minority of patients with disability, and opioid-related side eff ects) and docu- neuropathic pain. mented, and then the opioid introduced at a low dose, If gabapentin is available, it can be considered. escalating the dose over a few days until the drug is ef- It does not cause major malformations in animal stud- fective with acceptable side eff ects, or until failure (lack ies and has not demonstrated evidence of harm in lim- of eff ect, or benefi t limited by excessive side eff ects). ited human experience to date. Mexiletine also appears Another possibility is tramadol, which has oral to be of low risk to the fetus, but it is less eff ective and and intravenous formulations. Doses of 400–600 mg has more side eff ects. In contrast, carbamazepine, al- per day are eff ective against both acute pain and neu- though still used during pregnancy in some epileptic ropathic pain. Tramadol has several antinociceptive ac- patients because its benefi t is considered to outweigh tions (serotoninergic, noradrenergic, and weak mu-opi- the risk of harm, should be avoided, even after the fi rst oid activity from its principal metabolite), is useful for trimester, because it causes major and minor abnor- moderate to severe pain, and does not cause respiratory malities, including spina bifi da, craniofacial defects, depression. Tramadol should be avoided in women who and coagulation disorders in humans. Th e selective se- are at increased risk for seizures, such as those with rotonin reuptake inhibitors and similar drugs (citalo- preeclampsia or eclampsia, or those taking other drugs pram, paroxetine, venlafaxine), lamotrigine (an anti- that increase central nervous system levels of serotonin. convulsant) and pregabalin (a voltage-gated calcium Common side eff ects are nausea and dizziness. Animal channel blocker) have limited information available studies indicate that tramadol is a low-risk drug for fetal and are best avoided. 238 Author(s) Case report 2 (analgesia baby, while establishing lactation and breastfeeding. when breastfeeding) Eff ective, regular, and early pain relief reduces the risk of moderate or severe pain after the fi rst one to three Agnes is a 28-year-old multigravid woman who has two days such that most women need only paracetamol children and is now 34 weeks pregnant. She comes from (acetaminophen) and/or an NSAID by the third to fi fth a good and sensible family that is well known to you. She postoperative day (and may reduce the risk of chron- has come to you for advice because the obstetrician has ic wound pain later!). Most methods of postcesarean just booked her for an elective repeat cesarean delivery pain relief are based on opioids, the majority of which in 1 month. She has been told that the baby appears to are considered safe for the breastfed baby if used only be much bigger than last time, when she experienced short-term during lactation. failed progress of labor and had to have an urgent cesarean section. Although she has been doing well and un- What should the “district” hospital be able to off er Agnes? derstands why it would be best to have another cesarean, she is very anxious and is not sure whether to have her Th e best approach to acute pain management for Ag- operation at the district mission hospital or whether to nes is a “multimodal” approach, which means combin- ask if she can go to the referral hospital in the nearby city ing diff erent painkillers or analgesic methods to reduce with better facilities. the dose and thus side eff ects of each component. An Agnes is worried for two reasons. First, after her opioid such as morphine should be prescribed, pref- last cesarean she had a lot of pain, especially during the erably using regular doses with extra supplementary fi rst two days, and she is scared about suff ering the same doses if requested, for the fi rst 24–48 hours. If an in- experience. Second, local women elders had told her travenous method (patient-controlled analgesia or that if she had any strong painkillers after the operation, continuous infusion, see below for these referral hos- the baby would not be able to breastfeed—but she can- pital methods) is unavailable, then the oral or subcuta- not aff ord to use milk formula. You listen sympatheti- neous route can be used. Intramuscular injections are cally because you are aware that many women are not more painful than subcutaneous (especially if the latter getting very good pain management after their cesarean are given through a small cannula or ‘butterfl y” nee- at the district hospital. You are planning to talk to the dle); they have a higher risk of deep infection and are doctors there to suggest some simple changes that you no more reliable in their effi cacy. Giving the opioid “as think will improve the situation signifi cantly. You dis- required” leads to undertreatment and poor pain relief cuss with Agnes the options that are likely to be avail- because of inconsistent absorption pharmacokinet- able for her postoperative analgesia at the two hospitals ics and individual response. If a range of doses is pre- and their implications when she starts to breastfeed— scribed, then the smallest can be used fi rst and substi- and then you make some recommendations and prom- tuted with a larger dose subsequently if required. Th e ise to contact the hospital to try and make sure she gets drug of choice is morphine, which may be available as satisfactory treatment. a tablet or oral syrup (30–45 mg every 8 hours) or a parenteral formulation (subcutaneous 10–15 mg every Does pain after cesarean delivery really need to 6 hours). Oral codeine (60 mg every 6 hours) should be treated well? only be used if another oral opioid is not available. Most women experience moderate to severe pain in During lactation, pethidine (meperidine) should be the fi rst 48 hours after abdominal surgery, including ce- avoided unless there is no other alternative. It has an sarean section, and both mother and baby will benefi t active metabolite, norpethidine (normeperidine), that from good pain relief. If the mother is able to move in has a very long elimination half-life in the newborn relative comfort, she can mobilize soon after recover- (approximately 72 hours), and as both accumulate in ing from the anesthetic (within a few hours of surgery the neonate, the baby becomes sleepier and less active, after a spinal anesthetic), which reduces the risk of pul- and its ability to suck on the breast is impaired. Th ese monary infections and venous thromboembolism, an eff ects are prominent when intravenous doses are giv- important cause of sudden death from pulmonary emen after cesarean delivery, but they also occur from bolism. She will be able to eat within hours of the op- lower intramuscular dosing during labor. If the baby eration and continue to care for and interact with her is very premature and has worrisome apneic spells, all Chapter Title 239 opioid doses should be minimized and if possible sub- acceptable for use during lactation, it has been as- stituted with tramadol, which is safe for the baby in the sociated with the rare and serious condition of Reye’s fi rst few days after delivery when breastfeeding is be- syndrome in newborns, so prolonged administration ing established. should be avoided. Every attempt should be made to make sure You should explain to Agnes that she should try that Agnes also gets either an NSAID such as diclofe- to time her feeds to avoid the peak milk concentrations nac (a second choice is indomethacin, which has more of the opioid she is taking, which will usually coincide side eff ects), paracetamol (acetaminophen), or even with 1–2 hours after the last dose. both. Th ese painkillers reduce the dose of morphine needed by 30–40% and 10–20% respectively, and an What other methods might the city referral hospital be able to off er Agnes? NSAID can reduce “cramping” pain from the uterus. Oral paracetamol (1 g every 6 hours) has almost no Th ere may be a number of potentially superior meth- side eff ects and is contraindicated only in patients ods of postoperative pain relief at the referral hospi- with severe liver dysfunction. An NSAID, preferably tal that Agnes can consider and request. Intravenous given at its maximum recommended dose (e.g., diclof- morphine (and in some countries the metabolite-free enac 50 mg t.i.d. [three times daily] or indomethacin but more expensive opioid fentanyl) provides better 100 mg b.i.d. [twice daily]) and with food to avoid gas- quality pain relief than subcutaneous or intramuscular trointestinal upset, is contraindicated in women with morphine and is preferably administered using a pa- hypertensive disease including preeclampsia, renal tient-controlled analgesia (PCA) device (standard set- impairment, peptic ulcer, or symptomatic refl ux dis- ting, e.g., 1 mg bolus on demand, no continuous infu- ease, and in women with a bleeding disorder or cursion, 5-minute lockout interval) to safeguard patients rent bleeding risk. from unintentional overdosing. An additional measure for the surgeon, that is Neuraxial (spinal or epidural) opioid methods not too expensive, is infi ltration of local anesthetic (for of analgesia provide better relief than intravenous, sub- example, 0.25% bupivacaine up to a maximum dose of cutaneous, intramuscular, or oral opioid administration. 2 mg/kg) into the wound. Skin infi ltration alone is not If spinal anesthesia is used, then intrathecal morphine eff ective, but injection beneath the rectus sheath fascia 100–150 μg is a very safe and eff ective means of achiev- and subcutaneously may reduce the amount of opioid ing excellent pain relief. needed, with a low risk of complications. Morphine’s long elimination half-life in cerebrospinal fl uid results in clinically good or excellent What are the eff ects of these drugs pain relief for 4–24 hours (on average 12 hours), es- on the breastfed baby? pecially if an oral NSAID is also given. Sedation, nau- With a couple of exceptions, especially those apply- sea, and vomiting are common side eff ects after opi- ing to pethidine (meperidine), Agnes can be assured oids. In general, sedation will be greater after systemic that all these drugs have been evaluated well and that administration (oral, intramuscular, and intravenous) they are considered safe and acceptable to use in the and itch more severe after neuraxial (spinal or epi- fi rst few days after delivery. At this time, production dural) administration. All patients receiving opioids, of breast milk is increasingly rapidly, but the content is especially neuraxial, should be monitored for overse- still changing from protein-rich colostrum, which is a dation and low respiratory rate, although serious mor- poor transfer medium for most drugs, to fat-rich milk. bidity is rare in the obstetric population. Many hos- Th e transfer of morphine and codeine, paracetamol, and pitals and doctors appear especially concerned about NSAIDs into breast milk is only 2–4% of the weight- spinal or epidural opioids, but when they are used adjusted maternal dose, and none has adverse eff ects in correctly, case series suggest a signifi cantly higher risk the infant. of clinically important respiratory depression associ- Aspirin is not as good a choice as paracetamol/ ated with intravenous opioid. Postoperative epidu- acetaminophen, which has no detectable eff ects de- ral analgesia is less likely to be available but is highly spite immature glucuronide conjugation. Aspirin is eff ective. It can be achieved with single or repeated contraindicated in those at risk of bleeding due to its (8–12 hourly) doses of morphine 3 mg or in technol- eff ect on platelet function, and although considered ogy-rich hospitals, with epidural infusion or patient- 240 Author(s) controlled epidural analgesia (PCEA) using fentanyl of 0.25% bupivacaine or 0.5% ropivacaine on each side. (2 μg bolus, 15 minute lockout time) or pethidine/me- Th e injection is made just above the pelvic brim in the peridine (20 mg bolus, 15 minute lockout time). Th ese posterior section of the triangle of Petit, in the gap be- epidural methods are associated with lower rates of tween latissimus dorsi and the external oblique muscle. opioid consumption (by 20–50%) than intravenous A “two-pop” (or in some countries ultrasound-guided) opioid and although short-term epidural opioid ad- technique (as the blunt-tip needle passes through the ministration after cesarean delivery has not been well external oblique fascial extension, then internal oblique investigated, clinical experience suggests the breast- fascia) allows local anesthetic to be deposited between fed neonate is not aff ected. the internal oblique and transverse abdominis muscles. Immediate-release oxycodone (e.g., 5–10 mg Combined with oral analgesics, an eff ective TAP block regularly 4 hourly for 48 hours, with additional doses on covers the incision for cesarean delivery well (T10 to L1 request) is a more eff ective oral opioid than codeine and dermatomes) and lasts up to 36 hours. also tastes less unpleasant than oral morphine. Trama- dol (50–100 mg intravenous or oral, repeated 2 hourly Case report 3 (analgesics to a maximum of 600 mg per day) is also an excellent in later pregnancy) choice for postoperative pain relief. Agnes can also be reassured that short-term use for a couple of days im- Th e nurse comes to tell you that Martine, a healthy mediately postpartum is associated with low transfer of woman in her fourth pregnancy at 33 weeks gestation drug into breast milk (less than 3%) and that there are who is attending the antenatal clinic, has been com- no apparent eff ects on the baby. In some countries the plaining of severe stabbing pain both at the back of her new generation of NSAIDs, the cyclooxygenase-2-spe- pelvis and low down at the front. Th e pain has been get- cifi c inhibitors (COX-2 inhibitors) such as intravenous ting progressively worse for several weeks, and Martine parecoxib (40 mg daily) and oral celecoxib (400 mg then can no longer care properly for her children. She fi nds it 200 mg 12 hourly) may be available, and because they very painful to rise from a sitting position and is more have no eff ect on platelet function they are the best comfortable crawling around the house on all four limbs choice for women who are bleeding or at high risk of than walking. When you see Martine, she explains that bleeding. However, they have not yet been adequately it took her 2 hours to walk from her house to the clinic, evaluated during human lactation, and although the risk a journey that usually takes her 20 minutes. She is very of aff ecting the breastfeeding baby appears low, safety tender to palpation over both the suprapubic region and cannot be guaranteed. Some countries may also have in- upper buttocks. Th e pain is increased by “springing” the travenous paracetamol/acetaminophen, which provides pelvis. “Please, is there anything that you can do to help higher and more rapid peak plasma concentrations than me?”asks Martine. You explain that she appears to have an equivalent oral dose. symphysial diastasis with signifi cant separation and secondary disruption and infl ammation at the sacroiliac Might any other local anesthetic blocks be joints. You explain the problem and discuss an initial useful in reducing Agnes’s risk of having poorly plan of management with her. You tell her that she can controlled pain? start on some strong medications if she has not improved Wound infusion of local anesthetic (or perhaps even di- within a week. clofenac) is eff ective in reducing the dose of opioid needed, but it requires expensive pumps and wound cath- What sort of painful conditions occur eters, so it is not likely to be available. If there is a doctor during pregnancy? with suitable training, bilateral ilioinguinal and iliohypo- Diastasis of the pubic symphysis is an example of a very gastric blocks into the abdominal wall near the anterior painful and disabling condition that frequently occurs iliac crest, or a rectus sheath block, can achieve similar during and after pregnancy. However, the principles of opioid dose-sparing in the fi rst 12–24 hours. Th e best drug treatment for pain present after the fi rst trimes- peripheral nerve block, if someone has the knowledge ter of pregnancy can be applied to most painful condi- and expertise, would be for Agnes to receive bilateral tions or diseases, including musculoskeletal pain (other transverse abdominis plane (TAP) blocks. Th is regional examples are lumbar vertebral facet pain, disk protru- analgesic block is performed using, for example, 20 mL sion or rupture); visceral pain (cholecystitis, renal Chapter Title 241 colic, degenerating uterine fi broids, or bowel pain); impairment, premature closure of the ductus arterio- neuropathic pain (intercostal neuralgia, meralgia par- sus with subsequent neonatal pulmonary hyperten- esthetica of the lateral cutaneous nerve of the thigh, sion, and neonatal intracranial hemorrhage. Th ere is iliohypogastric and genitofemoral neuralgia, various insuffi cient information about the eff ects of the COX-2 cancer-induced neuralgias, post-traumatic complex inhibitors (e.g., celecoxib), so these agents should also regional pain syndrome, or post-amputation pain); be avoided. migraine; and invasive cancer pain. Would local anesthetics or opioid drugs What initial treatment would you be suitable in this case? suggest for Martine? It is the case with many painful conditions (including Irrespective of the cause of the pain, nonpharmacologi- Martine’s) that the treatment you start with ultimate- cal pain management options should be considered and ly proves insuffi cient. Th e possibility of a neuropathic tried, where possible, before analgesic drugs are used component should be considered in Martine’s case, and for acute pain that appears likely to require prolonged the appropriate drug treatment is discussed in case 1 treatment or a stepwise approach to continued manage- above. However, the two main options to consider next ment. Your plan for Martine should start with physi- for Martine are local anesthetic infi ltration and oral cal therapies (for example referral to a therapist for a opioid analgesia. Infi ltration with local anesthetic pro- sacroiliac pelvic support belt; gentle manipulation and vides temporary (and sometimes prolonged) relief of postural exercises; and local application of heat or ice, joint pain (another example is into the coccyx for coc- transcutaneous electrical nerve stimulation, acupunc- cydynia, or into the facet joint for back pain) and myo- ture or similar treatments), but it would also be reason- fascial pain (for example into trigger points in the ab- able to introduce nonopioid analgesic drugs, bearing in dominal wall, neck, or shoulders or the costochondral mind their safety for the fetus and neonate. Paracetamol and intercostal area). A steroid such as triamcinolone (acetaminophen) has been used in millions of pregnant could be included if infl ammation is suspected, but women and is safe. Aspirin is acceptable, but its pro- steroids are best omitted in the fi rst trimester and in longed use is best avoided (see case 2 above). Tramadol repeated injections. Provided the operator has knowl- has not been evaluated in large trials during pregnancy edge of the relevant anatomy and adequate expertise, but is widely used after the fi rst trimester, so it would be infi ltration is generally a low-risk procedure that can acceptable for short-term use for Martine to reduce the be useful both diagnostically and therapeutically. Th e severe pain until other measures have had a chance to local anesthetic drugs are of no or minimal risk to the become eff ective. It would not be ideal to continue tra- fetus, although maximum dose limits for the individu- madol for several weeks until the time of delivery, be- al drug and the type of block should be applied. Extra cause a neonatal withdrawal syndrome at 24–36 hours care must be taken when injecting near major organs has been reported. or the fetus (for example, when injecting near the blad- NSAIDs have a limited role during pregnancy, der and lower uterine segment or cervix at the pubic and it is very important to understand the implications symphysis). As a fi nal option, if epidural techniques are of prescribing them. Th ese drugs prevent prostaglan- available in a referral hospital, a period of epidural an- din-induced myometrial gap junction formation and algesia with a combined local anesthetic and opioid can transmembrane infl ux and sarcolemmal release of cal- be very benefi cial. cium, making indomethacin an eff ective tocolytic drug If opioid analgesia is commenced during that has been used to prevent preterm labor after the pregnancy, it would be best to arrange inpatient care period of organogenesis. However, they are contrain- for a few days. This strategy allows oral opioid titra- dicated in later pregnancy, certainly after 32 weeks tion and stabilization (see case 1 above) and supple- gestation (as applies to Martine), and some would ar- mentation with intravenous opioid or intravenous gue from the start of fetal viability (23–24 weeks in re- ketamine to establish pain control. Oral or sublingual source-rich countries and hospitals). Th is leaves only a opioids (morphine, methadone, codeine, and in some short period during the second trimester of pregnancy countries oxycodone, buprenorphine, and fentanyl) when these drugs may be useful. Fetal exposure in late can be used safely for short periods during pregnancy pregnancy may result in oligohydramnios due to renal (and in some cases will already be prescribed or are 242 Author(s) being used by patients illicitly). If prolonged admin- a quiet environment, and some will need treatment with istration is expected, drugs without active metabo- sedative drugs such as phenobarbitone (10 mg/day), di- lites are preferable, for example methadone rather azepam, clonidine, or morphine (starting at 0.4–1.0 mg/ than morphine for maintenance therapy in opioid ad- day in divided doses and increasing 10–20% every 2–3 dicts. Although there is a slightly higher rate of low days as needed). Treatment may need to be continued birth weight and stillbirth among women on chronic for 4–20 days and sometimes much longer. opioid therapy, the majority have good neonatal outcomes. It has been suggested that chronic opioid use Pearls of wisdom in pregnancy is associated with addictive behavior in later adult life, but observational evidence does not • Know which common analgesics are considered prove causality, and such findings should be viewed safe in early pregnancy, and know where to fi nd with some scepticism. Women who become opi- an information resource describing drug safety oid tolerant and need escalating doses will provide a in pregnancy and lactation. Be guided by pub- number of challenges in managing pain during labor, lished recommendations and liaise with other as well as during and after cesarean section. Options medical and nursing staff involved in pain man- such as opioid rotation and multiple opioids may agement. need to be considered (see chapter on chronic opioid • Choose a postoperative analgesic regimen af- therapy). These women need more interventions and ter cesarean section that is not only eff ective but increase the staff workload. also minimizes neonatal drug exposure through The neonatal effects of opioid analgesics be- breast milk. Th ere should be a multimodal opi- ing used at the time of childbirth are important, so oid-based approach, preferably using the spinal a number of staff need to be aware of opioid con- (subarachnoid) route of opioid administration. If sumption, including the obstetrician, midwife, pe- a systemic opioid is used it should be combined diatrician, and local doctor. Neonatal respiratory de- with nonopioid analgesics and/or a regional an- pression may be present at birth, so staff skilled in algesic method (e.g., the transversus abdominis neonatal resuscitation may be required; if possible, plane block). naloxone should be available. Also, the baby should • Use of opioids during pregnancy does not cause be observed in a high-dependency care area if possi- fetal malformations but may result in neonatal re- ble, and staff trained to watch for neonatal withdraw- spiratory depression at birth and a neonatal absti- al/neonatal abstinence syndrome. This syndrome nence syndrome starting the fi rst or second day usually commences in the hours or days following after birth. birth (depending on the half-life of the specific opi- • During and immediately after pregnancy, oid, i.e., 6–36 hours for morphine and 24–72 hours paracetamol (acetaminophen) is the safest nono- for methadone and buprenorphine), but it is occa- pioid analgesic, and opioids other than codeine sionally delayed for several days. The risk is greatest and pethidine are preferred. if the mother has become opioid-tolerant and has • Nonsteroidal anti-infl ammatory drugs are valu- needed an escalation dose or high maintenance doses able analgesics but should be reserved for use (30–90% incidence with long-term methadone use during the second trimester of pregnancy and and 50% incidence, but less severe, with buprenor- must be avoided after 32 weeks’ gestation. phine maintenance therapy). Unfortunately, breast- • Use the following table to make an individual feeding does not prevent the syndrome. The signs risk-benefi t-ratio for your patient before starting and symptoms in the baby are due to autonomic analgesia: overactivity (which can manifest as yawning, sneez- ing, or fever) and cerebral irritability (for example tachypnea, tremor, increased tone, poor feeding behavior, and in severe cases, seizures). The severity of the syndrome also correlates partly with the maternal dose, so is most severe in opioid-tolerant or addicted women. The baby should be swaddled and nursed in Chapter Title 243

Drug Recommendation during Pregnancy Recommendation during Breastfeeding Paracetamol (acetaminophen) Compatible throughout Compatible Aspirin Avoid at conception and avoid chronic high doses dur- Potential toxicity ing pregnancy Indomethacin Avoid at conception, during fi rst 10 weeks of gestation, Probably compatible and after 32 weeks of gestation Diclofenac Avoid at conception, during fi rst 10 weeks of gestation, Compatible and after 32 weeks of gestation Ibuprofen As indomethacin Compatible Naproxen As indomethacin Compatible Ketoprofen As indomethacin Compatible Ketorolac As indomethacin Compatible Celecoxib As indomethacin Limited data, potential toxicity Tramadol Probably avoid in the fi rst trimester, but thereafter low risk (neonatal abstinence syndrome is possible) Morphine Compatible, but possible neonatal depression at birth Probably compatible and abstinence syndrome with third-trimester use Codeine As morphine, but less eff ective Probably compatible Pethidine (meperidine) As morphine, but use alternative opioids if possible Compatible, but use alternative opioids Methadone As morphine Probably compatible Oxycodone As morphine Probably compatible Fentanyl As morphine Amitriptyline Low risk throughout Limited data, potential toxicity Carbamazepine Compatible if used for epilepsy, but preferably avoid Compatible (risk of malformations) Gabapentin Limited evidence suggests low risk No data—probably compatible Pregabalin Insuffi cient data No data—probably compatible Ketamine Low risk throughout Clonidine Probably avoid in the fi rst trimester Probably compatible Bupivacaine Low risk throughout Probably compatible Ropivacaine Compatible throughout Probably compatible Lidocaine (lignocaine) Compatible Probably compatible

Prescribing Medicines in Pregnancy, 4th edition 1999, and amendments. References Australian Government. Department of Health and Aging. Th erapeutic Goods Administration. http://www.tga.gov.au/docs/html/medpreg.htm or [1] American Academy of Pediatrics Committee on Drugs. Th e transfer of http://www.tga.gov.au/DOCS/HTML/mip/medicine.htm drugs and other chemicals into human milk. Pediatrics 2001;108:776– Drugs in Pregnancy and Breastfeeding. http://www.perinatology.com/expo- 89. sures/druglist.htm [2] McDonnell NJ, Keating ML, Muchatuta NA, Pavy TJ, Paech MJ. Anal- gesia after caesarean delivery. Anaesth Intensive Care 2009;37:539–51. Th erapeutic Guidelines. http://www.tg.com.au [3] Rathmell JP, Viscomi CM, Ashburn MA. Management of nonobstetric National Institutes of Health. US National Library of Medicine. Drugs pain during pregnancy and lactation. Anesth Analg 1997;85:1074–87. and Lactation Database (LactMed). http://toxnet.nlm.nih.gov/cgi-bin/sis/ [4] Roche S, Hughes EW. Pain problems associated with pregnancy and htmlgen?LACT their management. Pain Reviews 1999;6:239–61. ObFocus. High risk pregnancy directory. http://www.obfocus.com/resources/ medications.htm Websites

Acute Pain Management: Scientiﬁ c Evidence. Chapter 10.2. Th e pregnant patient. Second edition 2005, Dec 2007 update. Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. Approved by Austra- lian Government and National Health and Medical Research Council. http:// www.anzca.edu.au/resources/books-and-publications

Guide to Pain Management in Low-Resource Settings

Chapter 32 Pain in Sickle Cell Disease

Paula Tanabe and Knox H. Todds

Case report Th e severity and frequency of pain crises varies with the speciﬁ c genotype. Patients with SS and SB0 Ruben is a 25-year-old male with sickle cell disease who typically have more severe pain episodes when com- presents for evaluation of moderate, constant right hip pared with patients with SC and SB+. Th is is not to say pain (rated as 6/10) and intermittent episodes of severe that patients with SC and SB+ cannot experience pain- pain, reported as “crisis pain.” Ruben describes these cri- ful episodes—the episodes are just more uncommon ses as severe, occurring monthly, and feeling “as if all my and infrequent. bones are breaking.” Th e pain is most often experienced Both physiological and psychological factors in his legs. can trigger a painful crisis. Common triggers of painful crises include infection, temperature changes, and any How often do individuals with type of physical or emotional stress. Common causes of sickle cell disease have pain? acute pain include: • Hand-foot syndrome in children (dactylitis) Th is case depicts a typical scenario faced by therapists • Painful crises: vasoocclusion around the globe. Often, the pain associated with sickle • Splenic sequestration cell disease (SCD) is poorly understood. Persons with • Acute chest syndrome SCD often experience both acute and chronic pain. It • Cholelithiasis is now clear that more than half of patients with SCD • Priapism report some type of pain on a daily basis. “Crisis pain,” In addition to experiencing acute painful crisis, the most severe pain experienced by persons with SCD, persons with SCD also often experience chronic pain. has been reported on up to 13% of all days. Crisis pain Speciﬁ c causes of chronic pain include: (acute pain) has been described as “if all my bones are • Arthritis breaking” or “being hit with a board.” • Arthropathy Th ese lifelong episodes have an abrupt onset, • Avascular necrosis (often in the hips and shoul- are episodic and unpredictable, and are associated with ders and more common in persons with SC geno- very severe pain. Individuals are usually not able to con- type) duct normal activities during a painful crisis, which may • Leg ulcers last for several hours and up to a week or more. • Vertebral body collapse

Tips from a complementary [1] National Institutes of Health. National Heart, Lung, and Blood Insti- tute. Th e management of sickle cell disease, 4th ed. NIH publication no. medicine specialist 02–2117. Washington, DC: National Institutes of Health; 2002. [2] Smith WR, Penberthy LT, Bonbjerg VE, McClish DK, Roberts JD, Dah- Many complementary alternative medicine strategies man B, Aisiku IP, Levenson JL, Roseﬀ SD. Daily assessment of pain in have been found to both limit the frequency of pain adults with sickle cell disease. Ann Intern Med 2008;15:94–101. crises and improve patients’ quality of life. Careful attention to nutrition, obtaining adequate sleep, the use of heat, and massage have all been reported by persons Websites with SCD who function at a very high level. Use of com- http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_WhatIs.html plementary strategies should therefore be encouraged. http://www.nhlbi.nih.gov/health/prof/blood/sickle/ http://consensus.nih.gov/2008/2008SickleCellDRAFTstatementhtml.htm Pearls of wisdom

• Many persons with SCD experience pain on a daily basis.

Guide to Pain Management in Low-Resource Settings

Chapter 33 Complex Regional Pain Syndrome

Andreas Schwarzer and Christoph Maier

In 1865, the neurologist Silas Weir Mitchell reported single nerve, e.g., the whole hand is aff ected following about soldiers complaining of strong burning pain, pro- fracture of the radius; (3) usually both joints and nerves nounced hyperesthesia, edema, and reduction of motor are aff ected; (4) patients often present with psychological function of the limb following injuries of the upper or disturbances. Th ere are no clinical diff erences between lower extremity. Mitchell named these disturbances “cau- CRPS type I and type II; except for the nerve damage. salgia.” In the following years, these symptoms were described again and again after extremity injuries but were What is the incidence of CRPS, and labeled diff erently (algodystrophy, refl ex sympathetic dys- are there specifi c triggers? trophy, Morbus Sudeck). Currently, this disease pattern is referred to as complex regional pain syndrome (CRPS). CRPS is a rare disease. Approximately 1% of patients de- Two types are recognized: CRPS type I without nerve in- velop CRPS following a fracture or nerve injury. How- jury and CRPS type II associated with major nerve injury. ever, exact data on prevalence do not exist. In a current study from the Netherlands, the incidence was esti- What are the main characteristics mated 26/100,000 persons per year, with females being of patients with CRPS? aff ected at least three times more often than males. In another population-based study from the United States, As a general rule, the symptoms of CRPS manifest the incidence was estimated at 5.5/100,000 persons per themselves in the distal extremity (usually in the upper year. Th e upper extremity is more often aff ected, and a limb, and less often in the lower limb). Almost all pa- fracture is the most common trigger (60%). tients (90–95%) suff er from pain, which is described as burning and drilling and is felt deep in the tissue. Fur- What is the explanation for thermore, an edema of the aff ected extremity, with an development of CRPS? emphasis on the dorsal areas (dorsum of the hand or foot) can be observed in almost all patients. Pain and In almost all of the patients (90–95%) there is an ini- edema increase when the limb is hanging down. Further tiating noxious event (trauma) in the clinical history. essential disease features are the following: (1) patients Th e reason why only some patients develop CRPS is suff er from sensory, motor, and autonomic impairment; still unclear. Th ere is also no comprehensive theory (2) the symptoms spread beyond the area of the primary that can explain the diversity and the heterogeneity damage and cannot be assigned to the supply area of one of the symptoms (edema, central nervous symptoms,

Table 1 Diagnostic criteria for CRPS (according to Harden and Bruehl [3]) 1 Persistent pain, which is disproportionate to any known inciting event 2Th e patient must report at least one symptom in three of the following categories (anamnestic hints): 2.1 Sensory Reports of hyperesthesia and/or allodynia 2.2 Vasomotor Reports of temperature asymmetry and/or skin color changes and/or skin color asymmetry 2.3 Sudomotor/edema Reports of edema and/or sweating changes and/or sweating asymmetry 2.4 Motor/trophic Reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nails, skin) 3Th e patient must display at least one sign in two or more of the following categories during the current physical examination: 3.1 Sensory Evidence of hyperesthesia and/or allodynia 3.2 Vasomotor Evidence of temperature asymmetry and/or skin color changes and/or skin color asymmetry 3.3 Sudomotor/edema Evidence of edema and/or sweating changes and/or sweating asymmetry 3.4 Motor/trophic Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nails, skin) 4Th ere is no other diagnosis that would otherwise account for the signs and symptoms and the degree of pain and dysfunction. Complex Regional Pain Syndrome 253 and opioids (controlled-release) can be prescribed. Th e particular setting and meets the standards of a com- most important adjuvants for the treatment of neuro- munity or primary care level. Th e application of nerve pathic pain are tricyclic antidepressants (amitriptyline) block techniques should be reserved for specialized pain and anticonvulsive drugs (gabapentin). After taking into management centers (“referral hospital level”). Th e ad- consideration their possible contraindications and their vantage of treatment in specialized pain management anticholinergic eff ects, the physician should increase centers is, besides the reliability of making the diagnosis the dose slowly. Furthermore, the dose should be high of CRPS and the use of sympathetic blocks, the greater enough before its effi cacy is evaluated. Th e dose of ami- experience in dosing the physical and the occupational triptyline should be initially 25 mg in the evening (alter- treatment—fi nally, it is perhaps the most essential issue natively 10 mg). Th e dose can be increased every seven for the function recovery of the aff ected extremity. days in 25-mg steps up to a maximal dose of 75 mg. Th e starting dose of gabapentin is 3 × 100 mg, and the dose What are today’s insights about should be increased in 300-mg steps every three days. the pathophysiology of CRPS? A dose of at least 1800 mg/d should be achieved. Espe- cially in cases of arthrogenic pain (particularly during Currently, there is no global pathophysiological concept physical examination), oral glucocorticoids are indicat- that explains all the symptoms in CRPS. Th ere are sev- ed (prednisolone in decreasing doses of 90/60/30/10/5 eral possible explanations. Next to hints for a genetic mg for 14 days). predisposition, infl ammation seems to play an impor- Invasive therapies: Th e sympathetic nervous tant role. In the context of a neurogenic infl ammation, system can be blocked either by unilateral anesthetic C fi bers and some receptors may release neuropeptides, blockades of the lower cervical sympathetic ganglion inducing clinical signs such as vasodilatation and ede- (stellate ganglion) (10–15 mL bupivacaine 0,5%) or by ma. Additionally, experts are discussing the concept of a blocks of the lumbar or thoracic sympathetic chain (5 disease of the central nervous system, in which changes mL bupivacaine 0.5%). Intravenous regional anesthe- of the aff erent neurons, such as pathological connec- sia blocks are seldom performed because of poor eff ect tions with the sympathetic nervous system, may cause and painful procedures. Th e indication for a sympa- spontaneous and evoked pain. Th e pattern of symptom thetic block is pain at rest despite immobilization and/ spread resembles that of diseases of the central nervous or pronounced allodynia. Sympathetic blocks not only system. Th e central nervous dysregulation is assumed reduce the pain, but can often also improve the motor to result in maladaptation, for example a change in the and autonomic impairment. However, it is important to ambient temperature induces an inadequate reaction of prove that the sympatholysis was technically successful skin blood fl ow and sudomotor function. Furthermore, by noting a signifi cant skin temperature increase in the cortical reorganization processes seem to play an im- supplying area. portant role, wherein the degree of the reorganization Nonpharmacological options: As long as pain correlates positively with the spread of the mechanical at rest prevails, therapy should be restricted to consis- hyperalgesia and the pain, which in turn is reversible us- tent immobilization of the aff ected extremity in a po- ing the appropriate treatment. sition higher than the heart, supported by a splint and by lymphatic drainage. After a distinct decrease of the Pearls of wisdom pain, physical and occupational therapy come to the fore. Initially, the proximal joints of the aff ected and the • Th ree important aspects account for the diag- contralateral extremity should be treated. Especially in nosis of CRPS: pain or functional impairment, cases of sensory impairment and allodynia, desensitiza- which is disproportionate to the inciting event; tion exercises are indicated. Th e main treatment prin- hints of sensory, vasomotor, sudomotor, or motor ciple should start with stimulus adaptation, followed by impairment in the past; and current fi ndings of exercises aiming at pain-free mobility and improvement sensory, vasomotor, sudomotor, or motor impair- of fi ne motor skills, and ultimately movements against ment in the clinical examination strong resistance. • Th e treatment must not induce pain. If a treat- Th erapy for CRPS, with regard to the use of medi- ment procedure leads to escalation of pain, this cal and nonmedical treatment, does not require any procedure must be given up. Th e following three 254 Andreas Schwarzer and Christoph Maier

therapeutic steps should be followed: ﬁ rst, treat- [4] Maihöfner C, Handwerker HO, Neundörfer B, Birklein F. Patterns of cortical reorganisation in complex regional pain syndrome. Neurology ment of the pain and edema; second, treatment 2003;61:1707–15. of the pain, allowing movement; and third, treat- [5] Moseley GL. Graded motor imagery for pathologic pain: a randomized controlled trial. Neurology 2006;67: 2129–34. ment of the functional orthopedic impairment. [6] Nelson DV, Brett RS. Interventional therapies in the management of complex regional pain syndrome. Clin J Pain 2006;22:438–42. • Th e intensity of physiotherapy must be reduced if [7] Pleger B, Ragert P, Schwenkreis P, Förster AF, Wilimzig C, Dinse H, pain increases again or after a new physical trau- Nicolas V, Maier C, Tegenthoﬀ M. Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex ma. regional pain syndrome. Neuroimage 2006;32:503–10. [8] Rowbotham MC. Pharmacological management of complex regional pain syndrome. Clin J Pain 2006;22:425–9. References

[1] Baron R, Schattschneider J, Binder A, Siebrecht D, Wasner G. Relation Websites between sympathetic vasoconstrictor activity and pain and hyperalgesia in complex regional pain syndromes: a case-control study. Lancet http://www.mayoclinic.com/health/complex-regional-pain-syndrome/ 2002;359:1655–60. DS00265 [2] Birklein F, Schmelz M. Neuropeptide, neurogenic inﬂ ammation and http://www.iasp-pain.org/AM/Template.cfm?Section=WHO2&Template=/ complex regional pain syndrome (CRPS). Neurosci Lett 2008;437:199– CM/ContentDisplay.cfm&ContentID=4174 202. [3] Harden RN, Bruehl S. Diagnostic criteria: the statistical derivation of the four criterion factors. In: Wilson PR, Stanton-Hicks M, Harden RN, editors. CRPS: current diagnosis and therapy, Progress in pain research and management, vol. 32. Seattle: IASP Press; 2005. Guide to Pain Management in Low-Resource Settings

Chapter 34 Pain Management in Children

Dilip Pawar and Lars Garten

Th is chapter will cover the diffi culties in treating pain in quantitatively compared to adults. Th e pain response is children and provide you with an overview of pharma- more intense at the beginning, but wears off much ear- cological and nonpharmacological interventions for ef- lier than in adults. Hence, no single formula is going to fective pain control in acute pain (injury/trauma-related work for everyone, and customized pain relief measures and postoperative pain) and chronic pain (cancer and are required. HIV-related pain) in children. Parental understanding and support is helpful because of their emotional attachment. As children may Do children feel pain? not ask for analgesia as adults can or do, an eff ort has to be made to anticipate pain, especially in infants and Until recently, many believed that children do not feel children who cannot express themselves verbally. pain, a belief based on lack of understanding, and on Most of the general principles of analgesia can be fear of using narcotics with potential respiratory depres- applied to children, but there are some signifi cant physi- sion and addiction in children, rather than on any sci- ological diff erences between adults and children that entifi c rationale. Today it is well known that the sensory can cause problems, especially in neonates and small in- nervous system and pain pathways develop around mid- fants. Just look at the case reports and imagine you have gestation, with connections and function maturing over to deal with these clinical situations. the fi rst 3 months after birth. Th ere is no evidence to support the view that pain is Case reports less intense in neonates and young children due to their developing nervous system. However, pain is subjec- You are in a small rural hospital with limited drugs. tive, and the pain response is individual and is modifi ed Consider the following real-life cases. How might you through social learning and experience. Early pain expe- manage them? rience plays an important role in shaping an individual’s Case report 1 (“acute trauma”) later pain response by alternation in the stress-axis and antinociceptive circuitry. Ahmed, a 3-year-old boy, with acute burns over a large part (more than 20%) of his body, has been admitted. Aren’t children just “little adults”? He is in severe pain. How will you manage analgesia in this child? Th e pediatric age group is heterogeneous, ranging from Th e boy suff ers from severe post-traumatic pain, the newborn to the adolescent. Children’s pain percep- so he needs fast analgesia. Use morphine as an intra- tion and responses are diff erent both qualitatively and venous (i.v.) bolus (if not possible, substitute enteral

Fig. 1. Medication instructions (from: World Health Organization. Palliative care: symptom management and end-of-life care. Interim guidelines for ﬁ rst-level health workers. World Health Organization; 2004. Reprinted with permission.) Pain Management in Children 259

Fig. 2. Adapted pain intensity scales (left: pain ladder, right: modiﬁ ed VAS-scale).

3) Respiratory rate cultural beliefs, experience nightmares related to pain, 4) Body movements and crying (AIIMS, FLACC, exhibit stalling behaviors (e.g., “Wait a minute” or “I’m OPS) not ready”), have muscular rigidity such as clenched 5) Crying is also the ultimate expression of the fi sts, white knuckles, gritted teeth, contracted limbs, non-pain-related needs of a child such as hunger, body stiff ness, closed eyes, or wrinkled forehead, en- thirst, anxiety, or parental attention. Th ese factors gage in the same behaviors listed for preschoolers/ should be carefully excluded before considering crying young children, or be unable to sleep. as a sign of pain. 5) Adolescents may localize and verbalize pain, deny pain in the presence of peers, have changes in Do children express their pain sleep patterns or appetite, be infl uenced by cultural be- in the same manner as adults? liefs, exhibit muscle tension and body control, display No, they do not. Due to developmental diff erences, pain regressive behavior in the presence of the family, or be expression varies among diff erent pediatric age groups. unable to sleep. 1) Infants may exhibit body rigidity or thrashing, may include arching, exhibit facial expression of Can you assess pain intensity in children pain (brows lowered and drawn together, eyes tightly by just looking at their behavior? closed, mouth open and squarish), cry intensely/loudly, As every child has individual strategies of coping with be inconsolable, draw knees to chest, exhibit hypersen- pain, behavior can be very nonspecifi c for estimation sitivity or irritability, have poor oral intake, or be un- of pain levels. For example, a school-age girl may spend able to sleep. hours playing normally with a toy. At fi rst sight, you 2) Toddlers may be verbally aggressive, cry in- may think she is happy and not in pain. But this could tensely, exhibit regressive behavior or withdraw, exhibit be her behavioral expression for coping with pain (by physical resistance by pushing painful stimulus away af- distracting her attention from pain and attempting to ter it is applied, guard painful area of body or be unable enjoy a favorite activity). Th ough a child’s behavior can to sleep. be useful, it can also be misleading. Using a pain rat- 3) Preschoolers/young children may verbalize inten- ing scale and looking at physiological indicators of pain sity of pain, see pain as punishment, exhibit thrashing of (changes in blood pressure, heart rate, and respiratory arms and legs, attempt to push a stimulus away before rate) in addition is recommended. it is applied, be uncooperative, need physical restraint, cling to a parent, nurse, or signifi cant other, request Are children able to tell you emotional support (e.g., hugs, kisses), understand that if and where they hurt? there can be secondary gains associated with pain, or be Studies have shown that children as young as 3 years of unable to sleep. age are able to express and identify pain with the help of 4) School-age children may verbalize pain, use pain assessment scales, accurately. Children are able to an objective measurement of pain, be influenced by point to the body area where they are experiencing pain 260 Dilip Pawar and Lars Garten or draw a picture illustrating their perception of pain. A pain, a combination of (1) questioning the child and widely used and appropriate pain assessment scale is the parents, (2) using a pain rating scale, and (3) evaluating Faces pain rating scale (recommended for children age 3 behavioral and physiological changes is recommended. years and older) (Fig. 3). How can you assess pain Do children always tell you in infants and toddlers? when they are in pain? Parents, caregivers, and health professionals are con- Even when they have adequate communication skills, stantly challenged to interpret whether the distressed there are some reasons children may not report pain. behaviors of infants and children, who cannot self- Children may be frightened of (1) talking to doctors, report, represent pain, fear, hunger, or a range of other (2) fi nding out they are sick, (3) disappointing or both- perceptions or emotions. A range of behavioral distress ering their parents or others, (4) receiving an injection scales for infants and young children have been devised. or medication, (5) returning to hospital or delaying dis- Facial expression measures appear to be the most useful charge from hospital, (6) having more invasive diagnos- and specifi c in neonates. Typical facial signs of pain and tic procedures, or (7) having medication side eff ects. physical distress in infants are: (1) eyebrows lowered And after all, children just may not think it is necessary and drawn together; (2) a bulge between the eyebrows to tell health professionals about their pain. Th us, par- and vertical furrows on the forehead; (3) eyes sightly ents should always be asked for their observations re- closed; (4) cheeks raised, nose broadened and bulging, garding the child’s situation. So even in children whose deepened nasolabial fold; and (5) open and squarish cognitive development should allow them to report mouth (Fig. 4).

Fig. 4. Facial expression of physical distress and pain in the infant. Fig. 3. Faces Pain Rating Scale. Original instructions: Explain to the (From: Wong DL, Hess CS. Wong and Whaley’s clinical manual person that each face is for a person who feels happy because he has of pediatric nursing, 5th ed. St Louis: Mosby; 2000. Reprinted no pain (hurt), or sad because he has some or a lot of pain. Face 0 with permission.) is very happy because he doesn’t hurt at all. Face 1 hurts just a little bit. Face 2 hurts a little more. Face 3 hurts even more. Face 4 hurts a whole lot. Face 5 hurts as much as you can imagine, although you Th e FLACC Scale (Fig. 6) is a behavioral pain don’t have to be crying to feel this bad. Ask the person to choose the face that best describes how he is feeling. Brief word instruc- assessment scale for use in nonverbal patients unable to tions: Point to each face using the words to describe the pain inten- provide reports of pain. It is used for toddlers from 1 to sity. Ask the child to choose face that best describes their own pain and record the appropriate number. Continuous use of a pain assess- 3–4 years of age and for cognitively impaired children of ment scale for monitoring the eﬀ ectiveness of pain therapy is recom- any age). Each of the ﬁ ve categories is scored from 0–2, mended. (From: Whaley LF, Wong DL. Nursing care of infants and children, 3rd ed. St Louis: Mosby; 1987. Reprinted with permission.) which results in a total score between 0 and 10. Pain Management in Children 261

Neonatal/Infant Pain Scale (NIPS) Pain Assessment Score Facial Expression 0—Relaxed muscles Restful face, neutral expression. 1. Grimace Tight facial muscles, furrowed brow/chin/jaw (negative facial expression— nose, mouth, and brow). Cry 0. No Cry Quiet, not crying. 1. Whimper Mild moaning, intermittent. 2. Vigorous Cry Loud scream; rising, shrill, continuous (note: silent cry may be scored if baby is intubated, as evidenced by obvious mouth and facial movements). Breathing Patterns 0. Relaxed Usual pattern for this infant. 1. Change in Breathing Indrawing, irregular, faster than usual; gagging; breath holding. Arms 0. Relaxed/Restrained No muscular rigidity; occasional random movements of arms. 1. Flexed/Extended Tense, straight arms; rigid and/or rapid extension/ﬂ exion. Legs 0. Relaxed/Restrained No muscular rigidity; occasional random movements of legs. 1. Flexed/Extended Tense, straight legs; rigid and/or rapid extension/ﬂ exion. State of Arousal 0. Sleeping/Awake Quiet, peaceful sleeping or alert. 1. Fussy Alert, restless and thrashing. Fig. 5. Neonatal/Infant Pain Scale (NIPS). An example of an evaluated pain rating scale for neonates and infants. Th e maximum score is 6; a score greater than 3 indicates pain. (From: Lawrence J, et al. Th e development of a tool to assess neonatal pain. Neonatal Nets 1993;12:59–66.)

Pain Assessment Score Facial Expression 0– No particular expression or smile. 1– Occasional grimace or frown, withdrawn, disinterested. 2– Frequent to constant quivering chin, clenched jaw. Legs 0– Normal position or relaxed. 1– Uneasy, restless, tense. 2– Kicking, legs drawn up. Activity 0– Lying quietly, normal position, moves easily. 1– Squirming, shifting back and forth, tense. 2– Arched, rigid or jerking. Cry 0– No cry (awake or asleep). 1– Moans or whimpers, occasional complaint. 2– Crying steadily, screams or sobs, frequent complaints. Consolability 0– Content, relaxed. 1– Reassured by occasional touching, hugging or being talked to, distractible. 2– Diﬃ cult to console or comfort. Fig. 6. Th e FLACC scale. (From: Merkel S, et al. Th e FLACC: a behavioral scale for scoring postoperative pain in young children. Pediatr Nurse 1997;23:293–7. Copyright 1997 by Jannetti Co. University of Michigan Medi- cal Center.) 262 Dilip Pawar and Lars Garten

Table 1 Clinical bedside pain assessment scale No pain Child can cough eﬀ ectively Mild pain Child can breathe deeply but cannot cough without distress Moderate pain Child can breathe normally but cannot cough or take a deep breath without distress Severe pain Child is distressed even during normal breathing

Table 2 Parental assessment scale No pain Playful, comfortable in bed, no discomfort in turning over, calm face, when crying easily comforted by parents Mild Complains of discomfort at the site of surgery on movement Moderate Facial grimace present, pain and discomfort at site of surgery on movement Severe Persistent crying and restlessness, pain even without movement

Are simple bedside assessment tools available? for treatment of moderate to severe pain. For mild to In the clinical practice of the All India Institute of Medi- moderate pain therapy, use nonpharmacological meth- cal Sciences (AIIMS) in New Delhi, a clinical bedside ods, and a formula of 30% sucrose with a pacifi er. Local pain assessment scale and a parental assessment scale anesthetics can be used for wound care (see Table 7 for have been developed (Tables 1 and 2), which have prov- frequently used drugs and their dosage regimes.) en helpful even with illiterate parents. What do the pain management terms “by the ladder,” “by the clock,” “by mouth,” and “by the Pain management child” mean? Pain management in children should follow the WHO What drugs can be used for eff ective analgesic stepladder (“by the ladder”), be administered pain control in children? on a scheduled basis (“by the clock,” because “on de- Local anesthetics for painful lesions in the skin or mu- mand” often means “not given”), be given by the least cosa or during painful procedures, e.g., lidocaine, TAC invasive route (“by mouth”; whenever possible give pain (tetracaine, adrenaline [epinephrine], cocaine) or LET medication orally and not by i.v. or i.m. injection), and (lidocaine, epinephrine, and tetracaine). be tailored to the individual child’s circumstance and Analgesics for mild to moderate pain (such as needs (“by the child”). post-traumatic pain and pain from spasticity), e.g., paracetamol (acetaminophen) or nonsteroidal anti-in- What nonpharmacological methods can fl ammatory drugs (e.g., ibuprofen or indomethacin). be used to relieve pain, fear, and anxiety Opiates for moderate to severe pain not respond- in children? ing to treatment with analgesics, e.g., codeine (moderate If the child and parents agree and if it helps, the follow- pain, alternatives are dihydrocodeine, hydrocodone, and ing additional methods (for local adaption) can be com- tramadol) and morphine (moderate to severe pain; al- bined with pain medications. ternatives are methadone, hydromorphone, oxycodone, • Emotional support (whenever possible allow par- buprenorphine, and fentanyl). ents to stay with their child during any painful Note: aspirin is not recommended as a fi rst-line an- procedures). algesic because it has been linked with Reye’s syndrome, • Physical methods (touch, including stroking, a rare but serious condition aff ecting the liver and brain. massage, rocking, and vibration; local application Especially avoid giving aspirin to children with chicken of cold or warm; controlled deep breathing). pox, dengue fever, and other hemorrhagic disorders. • Cognitive methods (distraction, such as singing In neonates and infants up to 3 kg body weight, or reading to the child, listening to the radio, play opioids alone have been shown to be eff ective drugs activities, or imagining a pleasant place). Pain Management in Children 263

• Prayer (the family’s practice must be respected). for opioids. NSAIDs can aff ect bleeding time and should • Traditional practices that are helpful and not be used with caution in adenotonsillectomy. harmful. (Health professionals should get to Tramadol hydrochloride, a mild opioid (with only know what can help in the local setting.) partial opioid receptor agonist activity), is available for Another important point is to give children and oral and rectal administration in children. It is absorbed family members proper information about the mecha- rapidly (within less than 30 minutes), and the concen- nisms and appropriate treatment of pain, to help them tration profi le supports an eff ective clinical duration in better cope with the situation and encourage better the region of 7 hours. Transmucosal, intraoral, or intra- compliance with recommended care. For neonates and nasal opioids might become an interesting alternative infants up to 3 months old, oral glucose/sucrose (e.g., for breakthrough pain in children, since they generally 0.5–1 mL glucose 30%) given orally 1–2 minutes be- accept this form of application well. fore the painful procedure, in combination with paci- Parenteral route fi ers off ered to the baby during the painful procedure, Th e traditional route of parenteral administration used are eff ective for reducing procedure-related pain from to be intramuscular, which should be avoided nowadays injections or blood sampling. All these methods are “ad- because of the fear, anxiety, and distress it produces in ditionals” and should not be used in place of analgesic children. A subcutaneous route might be an alternative medications when they are necessary. in those cases where venous access is diffi cult. What routes of administration are used What is the role of opioids? for pharmacotherapy? Opioids are the fi rst line of systemic therapy in moder- Non-parenteral route ate to severe pain, with morphine being the most fre- Th e most commonly used nonopioid analgesic in chil- quently used. Morphine has been intensively studied in dren is paracetamol (acetaminophen). Th e traditionally children. Serum levels of 10–25 μg/kg have been found recommended dose is the antipyretic dose, which is too to be analgesic after major surgery in children. A steady conservative for pain relief. Th e current recommenda- static serum level of 10 μg/mL can be achieved in chil- tion is an oral dose of 20 mg/kg followed by 15–20 mg/ dren for moderate perioperative pain with a morphine kg every 6–8 hours, or a rectal dose of 30–40 mg/kg hydrochloride infusion of 5 μg/kg/h in term neonates followed by 15–20 mg/kg every 6 hours. Th e total dai- (8.5 μg/kg/hr at 1 month, 13.5 μg/kg/hr at 3 months, ly dose for either route should not exceed 90–100 mg/ 18.0 μg/kg/hr at 1 year, and 16.0 μg/kg/hr at 1–3 years kg/day in children and 60 mg/kg/day in neonates. Th is of age). For the use of morphine and fentanyl in the pe- maximum daily dose should not be given longer than 48 diatric patient, and especially in neonates and infants, hours in infants under 3 months, and not longer than no strong correlation between dose/serum plasma levels 72 hours in children over 3 months old. If a suppository and analgesic eff ects has been shown, due to the high is used, it should not be cut, because drug distribution variability in individual opioid metabolism. For that might be uneven. Multiple suppositories can be used reason it is advisable not to rely on specifi c dose recom- to obtain the desired dose. Th e use of paracetamol sup- mendations, but use the “WYNIWYG” concept: “what positories given for analgesia has to be seen very criti- you need is what you get.” Titration of the medication is cally, because in studies rectal absorption was shown recommended to identify the patient’s individual opioid to be slow and erratic with substantial variability, es- dose for proper pain relief. pecially in neonates and infants. Often, rectally applied Total body morphine clearance is 80% of adult val- paracetamol does not provide therapeutic drug serum ue at 6 months of age. Morphine clearance is higher in levels. If paracetamol is used, the oral route should be infants than adults, primarily because of higher hepatic the fi rst choice. blood fl ow and the active alternative sulfation pathway. Nonsteroidal anti-infl ammatory drugs (NSAIDs) Fentanyl can be used as a substitute for morphine such as ibuprofen and ketorolac can be used. Ibuprofen in children who have hemodynamic instability and who (10–20 mg/kg orally) provides eff ective relief for mild cannot tolerate histamine release. In neonates, fentanyl pain. Ketorolac rectal suppositories have been found to has a prolonged elimination half-life compared to mor- be useful in children with a narrow therapeutic margin phine. In children older than 1 year, clearance is similar 264 Dilip Pawar and Lars Garten to adults, but in neonates it is almost twice as long as No evidence for the eff ectiveness and safety of these in adults. An infusion rate of 1–4 μg/kg/hr usually pro- drugs in neonates and infants has been published. vides adequate analgesia in children. For remifentanil, which may only be used intraop- Is it possible to use patient-controlled analgesia (PCA)? eratively, adequate analgesia is achieved with a loading dose of 1 μg/kg/hr followed by maintenance infusion of A PCA device is an infusion pump with the facility to 0.25 μg/kg/min. Alfentanil is eff ective at a dose of 50 μg/ deliver a top-up dose whenever the patient feels the kg followed by an infusion of 1 μg/kg/min. While pethi- need of it. In the pediatric patient, PCA use is pos- dine (meperidine) has been used clinically for many sible at beginning school age (over 5 years). In children years, it should not be used in continuous infusions any less than 5 years old, a “parent-controlled” or “nurse- longer, as it can produce seizures in children. controlled” analgesia could be an alternative to PCA. Th e pump can be programmed to prevent delivery of What are some ways to reduce opioid toxic doses by using a lockout interval and a maximum side eff ects? hourly dose. Morphine is the usual drug of choice. Th e Th e following methods can be tried by “trial and er- patient bolus delivers 10–25 μg/kg. A basal rate of con- ror” to reduce opioid side eff ects: (1) dose reduction, (2) tinuous infusion of 10–20 μg/kg maximum might be ad- change of opioid (e.g., from codeine to morphine), (3) ministered with a lockout interval of 6–12 minutes. In change of route of administration (e.g., from oral to i.v.), children, a background infusion might be helpful dur- and (4) symptomatic therapy (e.g., preventive remedies ing sleep and it does not seem to increase the total dose. or a laxative for constipation). Patient-controlled regional analgesia is also possible. It has been found to be eff ective in popliteal and fascia ili- What is the maximum dose of morphine per day? aca blocks as well as in epidural blocks. One should remember, though, that the lockout interval in these cas- Th ere is no maximum dose of morphine. If an addition- es should be longer than 30 minutes because the time al reduction in pain without dangerous medication side needed for the bolus dose to be eff ective is longer. eff ects is possible with an increased dose, it is indicated. Titration of the medication is recommended to identify the patient’s individual opioid dose for proper pain re- Regional and local anesthesia lief. If tolerance develops after some time, the dose will What is the therapeutic value of regional blocks need to be increased to maintain the same degree of in children? pain relief. In recent years, there has been a resurgence in the pop- What are parenteral nonopioid analgesics ularity of regional blocks in children because of their to consider? effi cacy in providing good pain relief. Regional blocks Th ere has been a resurgence of interest in ketamine, an hold the key to provision of good pain relief in diffi cult NMDA-receptor antagonist, for its analgesic properties. situations as they are simple to use, easy to learn, and A dose of 0.1–0.5 mg kg i.v. has been found to provide cost-eff ective. Th ey provide profound analgesia, and lo- eff ective intraoperative pain relief. Ketorolac has suf- cal anesthetics, such as lidocaine (lignocaine) and bupi- fi cient analgesic potency for most day care cases and vacaine, are available even in the least affl uent countries. maybe supplemented initially by parenteral tramadol. Commonly used blocks in children are given in Table 3.

Table 3 Common regional blocks practiced in children Caudal epidural Hernia repair, orchidopexy, urethro plasty, circumcision Lumbar epidural All upper and lower abdominal surgery, thoracotomy Ilioinguinal/iliohypogastric Hernia repair Dorsal nerve of penis Circumcision, advancement of prepuce Axillary Surgery of hand and forearm Femoral/iliac Th igh and femur surgery Pain Management in Children 265 Note: wound infi ltration can be as good for a hernia, anatomical diff erences, and much easier than in adults. or caudal block with bilateral drug administration pro- Th e catheters may even be advanced—always without viding complete blockade. Epinephrine-containing local resistance—up to the thoracic segments in infants be- anesthetics should not be used because the penile artery cause their more compact and globular fat makes it easy is an end-artery. to pass the catheter. Subcutaneous tunneling of the caudal catheter reduces the rate of bacterial contamination. Is there a maximum dose of local anesthetics that is safe when the drug is used for local anesthesia? Planning an analgesic strategy Yes. No more than 4 mg/kg of lidocaine without epi- It is important to have a plan for pain relief from the nephrine, or 7 mg/kg with epinephrine, should be beginning of the perioperative period until such time used when infi ltrating for local anesthesia. Bupivacaine as the pediatric patient is pain free (see Fig. 7). Factors should not exceed 2 mg/kg or 8 mg/day; it is commonly that need to be considered for eff ective planning are used in concentrations of 0.125–0.25% for caudal epi- as follows. dural block (interestingly, 0.5 mg/kg ketamine by the same route prolongs the action of bupivacaine for up to Developmental age 12 hours). Maximum doses are generally an issue when Th e chronologic and neurodevelopmental age of the suturing large wounds or when using higher concentra- patient should be considered. A premature or young tions of local anesthetics. infant who may have problems with central respiratory Helpful tips drive may benefi t from techniques that minimize the use of opioids, which have central respiratory depres- 1) For painful mouth ulcers, apply lidocaine on sant drug eff ects. In older infants and toddlers, play gauze before feeds (apply with gloves, unless the family therapy and the presence of parents have an important member or health worker is HIV-positive and does not role in pain relief. Older children may understand the need protection from infection; acts in 2–5 minutes). concept of a PCA. 2) For suturing, apply TAC (tetracaine, adrenalin, cocaine)/LET (lidocaine, epinephrine, and tetracaine) to Surgical considerations a gauze pad and place over open wounds. 3) Morphine, when administered through the cau- Th e degree of pain is often associated with the type of dal route, is eff ective even for upper abdominal and tho- surgery. Th e type of surgery often is the deciding fac- racic surgery, and can be eff ective and safe at a dose of tor in choosing a particular pain relief measure. For 10 mg/kg through the epidural route. surgeries in areas that are moved regularly, such as the chest and upper abdomen, the pain relief measure re- What regional techniques may be used quired would be intense. Th e patient’s ability to take oral for continuous analgesia? medications after surgery is another important factor in Compared to neuraxial blocks, peripheral nerve blocks planning of care. with or without catheters have the least complications Educating nurses and parents and are popular, especially the axillary, the femoral, and the three-in-one-block. Lumbar epidurals can be A nurse is the fi rst person who faces a child with pain. used for a single dose administration, especially when She also is the one who takes care of epidural infu- caudal block is contraindicated or when the volume sions, i.v. infusions, and PCA devices. It is her respon- needed for the caudal block would be close to toxic sibility to monitor and coordinate with the surgical levels. A catheter placed in the epidural space can pro- and the anesthetic team. Her education in pain man- vide continuous analgesia for a long period of time (if agement is important. If trained nursing personnel is tunneled for periods of more than 1 week). Th e cath- not available or a high-dependency area is not avail- eter can be placed at the lumbar, caudal, or thoracic able, more aggressive methods of pain relief may not level. Th e thoracic level should be used by experienced be safe. Parents provide emotional support to the and skilled clinicians only. In children, often the caudal child, and it is important to discuss the plan with the route is preferred because it is safest technically due to parents to elicit their support. 266 Dilip Pawar and Lars Garten Availability of resources induction of anesthesia a caudal or ilioinguinal and ilio- Limited resources can be defi ned as non-availability of a hypogastric block, followed by wound infi ltration at the potent analgesic such as morphine or fentanyl, or equip- end of surgery. Two hours after surgery, oral paracetamol ment for drug delivery such as an infusion pump or a 300 mg or a combination of paracetamol and ibuprofen PCA pump or skilled personnel to perform the proce- (300 mg) is given 8-hourly until the pain score allows re- dure and monitor the patient postoperatively. In such duction or stopping of the medication. situations, the strategy should be to devise simple tech- Plan 2 niques, which do not require precision equipment and A newborn baby with an anorectal anomaly is scheduled intensive monitoring in the postoperative period. Th ese for an emergency colostomy. No oral medication is pos- could be as follows: sible. Th e baby can be managed with a spinal subarach- • Eff ective use of commonly available oral medi- noidal block with bupivacaine alone. In that case no cations such as paracetamol, NSAIDs, and ket- other intraoperative analgesic is needed. In case the baby amine. Paracetamol and ketamine have been ex- is administered general anesthesia, ketamine (0.5 mg/ tensively used in developing countries. kg) and morphine (50 μg/kg) may be administered. For • Optimum utilization of local anesthetics. Local premature babies, opioids should be avoided due to im- anesthetics can be applied by wound infi ltration, mature respiratory function. Although ketamine is used prior to incision, before closure, or continuously in many places, there is no good evidence for the eff ec- in the postoperative period. tiveness and safety of this drug in neonates. At the end of • Th e extremely low incidence of complications surgery, wound infi ltration is also used. In the postopera- after peripheral nerve blocks should encour- tive period, the baby can be given oral paracetamol. age using them more often when appropriate. In single-injection regional nerve blocks, postopera- Plan 3 tive analgesia is limited to 12 hours or less. Con- A 5-year-old boy is admitted to the emergency ward tinuous peripheral nerve blocks provide an eff ec- with acute burns and severe pain. A child with acute tive, safe, and prolonged postoperative pain relief. pain should be managed with available i.v. medication Th ey have been used even in day-care cases up such as morphine, ketamine, or tramadol or a combi- to the age of 8 years. If all patients received a re- nation of these drugs, along with low-dose midazolam gional block intraoperatively, that would obviate to avoid post-traumatic stress, but not for analgesia. the need for potent parenteral opioids. Th e dura- Once acute pain subsides, oral medication may be initi- tion of analgesia provided by a caudal block can ated with paracetamol 20 mg/kg. Th is child will require be prolonged by addition of other adjuvants. pain medication for physiotherapy, change of dressings, • Alternative therapies such as acupuncture analge- or even simple bedsheet changes subsequently. Th e child sia might prove to be simple, safe, and economi- and his parents should be prepared with an explanation cal. of what is being done. Th e pain can be managed with • If infusion pumps are not available, a simple pe- oral paracetamol and ketamine (8–10 mg/kg) and i.v. diatric burette can be used for infusion. Th e au- ketamine (1 mg/kg). If it comes to surgery, local infi ltra- thor’s many years of experience have seen it to be tion with local anesthetics of the donor area or a regional safe, if only 2 hours’ worth of the dose is fi lled up block would be benefi cial. at any time (even with potent opioids like morphine and fentanyl). What monitoring would be Practical treatment plans necessary for analgesia in the for a district hospital postoperative period? Resuscitation measures should be available at the bed- Plan 1 side for all patients who are receiving opioid infusions. A 2 year old child weighing 15 kg is scheduled for her- Routine monitoring and recording of pain score, se- nia repair as a day care procedure. Premedication with dation score, and respiratory rate is important in all paracetamol 300 mg orally or 600 mg rectally, and after moderately to severely painful conditions, and for all Pain Management in Children 267 patients on infusion. All children on opioid medica- neuropathic pain. Pharmacological management must tion should be monitored carefully for at least the fi rst be combined with supportive measures and integrative, 24 hours, including children on PCA without back- nonpharmacological treatment modalities such as mas- ground infusion. Sedation always precedes respiratory sage, acupuncture, relaxation, and physiotherapy. Physical depression in opioid overdose. Th erefore, observation methods include a cuddle or hug from the family, mas- of the patient’s alertness is the key to safety monitoring. sage, transcutaneous electrical nerve stimulation, com- A monitoring frequency of check-ups every 4 hours is fortable positioning, physical or occupational therapy, as considered to be safe to detect increasing sedation. A well as rehabilitation. Cognitive-behavioral techniques decrease of respiratory rate below 30% of basal resting include guided imagery, hypnosis, abdominal breathing, value may also be used as an alarm parameter. Oxygen distraction, and storytelling. Th e treatment plan should saturation is a better monitor than apnea/respiratory include passive, and if possible, active coping skills, to be rate monitors as it would detect airway obstruction ear- implemented considering the child’s wishes and those of lier, but for the average situation and patient outside the his or her family. intensive care ward, there is no indication that regular sedation control would be inferior to pulse oximetry. Pearls of wisdom A diff erent story: do children • For eff ective pain management in children, it is also experience chronic pain? very important to know how to assess pain in dif- ferent age groups. Yes they do, but little is known about the epidemiology • For perioperative pain management it is neces- of chronic pain in children, even in the affl uent coun- sary to have basic knowledge of the specifi c phar- tries. Chronic pain is commonly observed in adoles- macokinetics and pharmacodynamics in this spe- cents. Common conditions are headache, abdominal cial age group. pain, musculoskeletal pain, pain of sickle cell disease, • Th ere should be an analgesia plan or algorithm complex regional pain syndrome, and post-traumatic or available on the ward for typical therapeutic situ- postoperative neuropathic pain. Children with cancer or ations. Nonpharmacological treatment options AIDS suff er from varying degrees of pain as the disease should be integrated into the analgesia plan. progresses. Recurrent pain becomes chronic because of • Apart from perioperative pain management, a ba- failed attempts to adjust and cope with an uncontrol- sic ability to diagnose and manage simple chronic lable, frightening, and adverse experience. Over time it pain syndromes should be available. Th e majority is the weight of this experience that leads the patient to of patients, almost 80–90%, may be managed by develop concomitant symptoms of chronic physical dis- simple means, which should be available even in ability, anxiety, sleep disturbance, school absence, and remote or very low-resource environments. Only social withdrawal. Parents report severe parenting stress a small percentage of patients need invasive tech- and dysfunctional family roles. Th ere is a greater psy- niques like epidural analgesia, which might be chological element in chronic pain as compared to acute limited to referral centers. pain as in adults. • With regard to monitoring of analgesia side effects, nothing can substitute for vigilance and fre- How is chronic pain quent clinical assessment. in children treated? • No child should be withheld adequate and safe analgesia because of insuffi cient knowledge. Assessment of chronic pain should establish not only the site, severity, and other characteristics of pain, but also the physical, emotional, and social impact of pain. Table 4 Dose of caudal bupivacaine (0.125–0.25%) Treatment should include specifi c therapy directed 0.5 mL/kg for penile and anal surgery to the cause of pain and associated symptoms such as 0.75 mL/kg up to lumbar spine muscle spasms, sleep disturbance, anxiety, or depression. 1.00 mL/kg up to T10 Standard analgesics such as NSAIDs and opioids may be 1.25 mL/kg upper abdominal up to T6 used, along with antidepressants and anticonvulsants in 268 Dilip Pawar and Lars Garten

Table 5 Table 6 Duration of action of caudal bupivacaine with adjuvants Dosage of epidural infusions Drug Duration of Action (hours) Bupivacaine 0.1% with fentanyl 1–2 μg/mL Bupivacaine 0.25% 4–6 Infants under 6 months 0.1 mL/kg/h Bupivacaine 0.25% with ketamine 0.5 mg/kg 8–12 Children over 6 months 0.1–0.3 mL/kg/h Bupivacaine 0.25% with clonidine 1–2 μg/kg 8–12 Bupivacaine 0.25% with tramadol 1.5 mg/kg 12 Bupivacaine 0.25% with morphine 30–50 μg/kg 12–24 Bupivacaine 0.25% with ketamine 0.5 mg/kg and morphine 30 μg/kg 24

Table 7 Frequently used drugs and their dosage regimes Drug Dosages and Regimens Dose According to Body Weight Drug Dosage Form 3–6 kg 6–10 kg 10–15 kg 15– 20 kg 20– 29 kg Paracetamol 10–15 mg/kg, up to 4 times a 100-mg tablet - 1 1 2 3 (acetaminophen) day 500-mg tablet - ¼ ¼ ½ ½ Ibuprofen 5–10 mg/kg orally 6–8 hourly 200-mg tablet - ¼ ¼ ½ ¾ to a maximum of 500 mg/day 400-mg tablet - - - ¼ ½ Codeine 0.5–1 mg/kg orally 6–12 hourly 15-mg tablet ¼ ¼ ½ 1 1½ Morphine Calculate EXACT dose based on weight of child! Oral: 0.2–0.4 mg/kg 4–6 hourly; increase if necessary for severe pain. Intramuscular: 0.1–0.2 mg/kg 4–6-hourly. Intravenous bolus: 0.05–0.1 mg/kg 4–6-hourly (give slowly!). Intravenous infusion: 0.005–0.01 mg/kg/hour (in neonates only 0.002–0.003!). Ketamine 0.04 mg/kg/hr–0.15 mg/kg/hr i.v./s.c. (titrated to eﬀ ect: usually maximum 0.3 mg/kg/h–0.6 mg/kg/h) OR 0.2 mg/kg/dose–0.4 mg/kg/dose orally t.i.d., q.i.d., and p.r.n. Tramadol 1 mg/kg–2 mg/kg 4–6 hourly (max. of 8 mg/kg/day) Adapted from: World Health Organization. Pocket book of hospital care for children—guidelines for the management of common illness with limited resources. World Health Organization; 2005.

[10] World Health Organization. Pocket book of hospital care for children: References guidelines for the management of common illnesses with limited resources. Geneva: World Health Organization; 2005. Available at: www. [1] Bouwmeester NJ, Anderson BJ, Tibboel D, Holford NH. Developmental who.int/publications. pharmacokinetics of morphine and its metabolites in neonates, infants [11] World Health Organization. Integrated management of childhood ill- and young children. B J Anaesth 2004;92:208–17. ness: complementary course on HIV/AIDS. Geneva: World Health Or- [2] Duhn LJ, Medves JM. A systematic integrative review of infant pain as- ganization; 2006. sessment tools. Adv Neonatal Care 2004;4:126–40. [12] World Health Organization. Palliative care: symptom management and [3] Elia N, Tramer MR. Ketamine and postoperative pain—a quantitative end-of-life care. Geneva: World Health Organization; 2004. systematic review of randomised trials. Pain 2005;113:61–70. [13] World Health Organization. Symptom management and end-of-life [4] Gaughan DM, Hughes MD, Seage GR 3rd, Selwyn PA, Carey VJ, Gort- care. Geneva: World Health Organization; 2005. maker SL, Oleske JM. Th e prevalence of pain in pediatric human immunodefi ciency virus/acquired immunodefi ciency syndrome as reported by participants in the Pediatric Late Outcomes Study (PACTG 219). Pediatrics 2002;109:1144–52. Websites [5] Pawar D, Robinson S, Brown TCK. In: Brown TCK, Fisk GC, editors. Pain management in anaesthesia for children, 2nd edition. Melbourne: www.whocancerpain.wisc.edu Blackwell Scientifi c; 1992. p. 127–37. Up-to-date information about pain and palliative care published by the [6] Pain control and sedation. Semin Fetal Neonatal Med 2006;11(4). WHO Pain & Palliative Care Communications Program [7] Stoddard FJ, Sheridan RL, Saxe GN, King BS, King BH, Chedekel DS, Schnitzer JJ, Martyn JA. Treatment of pain in acutely burned children. J www.whocancerpain.wisc.edu/related.html Burn Care Rehabil 2002;23:135–56. Lists of numerous websites related to pain and palliative care [8] Wong DL, Baker CM. Pain in children: comparison of assessment www.ippcweb.org scales. Pediatr Nurs 1988;14:9–17. Online education program for health care professionals by the “Initiative for [9] Zeltzer LK, Anderson CT, Schechter NL. Pediatric pain: current status Pediatric Palliative Care” and new directions. Curr Probl Pediatr 1990;20:409–86. Guide to Pain Management in Low-Resource Settings

Chapter 35 Pain in Old Age and Dementia

Andreas Kopf

What is a geriatric patient? the geriatric patient will be a special challenge, since the percentage of patients with chronic pain (pain lasting A geriatric patient is a person of advanced biological age more than 6 months) increases continuously from 11% (the age in years being less important), with multiple to 47% between the ages of 40 to 75 years. Health care morbidity, possibly multiple medications, psychosocial workers have to be aware that geriatric patients not only deprivation, and an indication for (general) rehabilita- expect the general respect of society but—with increas- tion. Th e treatment of geriatric patients is complicated ing life-expectancy—deserve adequate medical treat- when dementia is present, because of the patient’s im- ment, including pain management. Societies have to paired communication abilities. discuss how they want to cope with this demand. Pain management What do elderly patients expect in geriatric patients from their doctor? In surveys, the older generation has deﬁ ned a “wish list”: Why is pain management for the geriatric being active until death, individual treatment, no pain, patient a medical challenge for tomorrow? autonomous decision making, being able to die “early An important demographic phenomenon of the last few enough” before needless suﬀ ering starts, and addressing decades in highly industrialized countries is the con- reduced social context and contacts. tinuous increase of the higher age groups in relation to the younger generation. Within a few decades, the same Why do elderly patients not receive the care demographic change will take place in countries outside they need and deserve? the Organization for Economic Co-operation and De- From the patient’s perspective: velopment (OECD) as well. For example, in Germany • Th e incidence of dementia increases with age, the number of inhabitants in the age group of above 80 resulting in impaired communication. years increased from 1.2 million in 1960 to 2.9 million • Elderly patients tend to behave like “good pa- today, and will further increase to 5.3 million by 2020. tients”. Th erefore, the health care system and health care work- • Th ey have a traditional “trusting” view of the ers will need to be prepared to be able to cope with this doctor “who will take care of everything that is special patient group. With regard to pain problems, necessary.”

Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. All rights reserved. Th is material may be used for educational and training purposes with proper citation of the source. Not for sale or commercial use. No responsibility is assumed by IASP for any injury and/or damage to persons or property 269 as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends that there should be independent verifi cation of diagnoses and drug dosages. Th e mention of specifi c pharmaceutical products and any medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text. 270 Andreas Kopf • Th ey tend to not insist on certain medical inter- If adequate pain medication is provided for ventions. elderly patients, why might they still not receive From the patient’s and doctor’s perspective: suffi cient pain control? • Pain in old age is “part of life” and “fate.” Communication problems and misconceptions of pain From society’s perspective: are relevant causes of this situation. A number of par- • Inadequate resources in the health care system ticularities must be considered in the geriatric patient: restrict adequate treatment. • Compliance: Geriatric patients will have predict- From the doctor’s perspective: able practical problems with their pain medica- • Elderly patients do not feel pain as intensely as tion. Impaired vision and motor skills, combined younger patients. with xerostomia (dry mouth) and disturbances • Th ey cope better with pain and therefore need of memory, may make an adequate treatment a less analgesia. complete failure. It has to be noted that the average geriatric patient in industrialized countries What are the opinions and statements has a prescription for seven diff erent drugs, and of scientifi c medical organizations? only a minority of patients have been prescribed A wealth of literature shows that geriatric patients are fewer than fi ve daily drugs, making noncompli- not provided with adequate pain management. Medi- ance and drug interactions highly likely. Noncom- cal societies have made the elderly patient a medical pliance rates are estimated to be as high as 20%. priority. Since pain is frequent, meaningful, underdi- Apart from that, intellectual, cognitive, and sim- agnosed, and undertreated, and since research on this ple manual impairments may interfere with treat- topic is scarce, pain in the elderly has to be declared a ment. More than a fi fth of geriatric patients fail medical priority. Consequently, the IASP in September at the task of opening drug packages and blister 2006 proclaimed “pain in old age” the main target of the packs. Another patient-related compliance factor, “Global Day of Pain.” compared to younger patients, is reduced “positive thinking”: only 20% of geriatric patients ex- Is it true that pain is frequent pect recovery and healing. in elderly patients? • Availability of opioids and the risks of prescrip- A number of studies document that the incidence of tion. pain is high. In old people’s homes, up to three-quarters • Comorbidity: Comorbidity may impair physical of interviewed residents reported pain. Half of these had performance, thereby possibly reducing the ef- daily pain, but less than one-fi fth were taking an anal- fects of rehabilitation eff orts. gesic medication. Studies show that unrelieved pain is • Pharmacokinetic changes: One of the main one of the most important predictive factors for physi- physiological changes in geriatric patients is the cal disability. reduction of cytochrome P450-dependent metabolization. Also, due to reduced hepatic func- What are the typical pain locations tion, plasma protein levels are generally lower in elderly patients? in elderly patients. Both altered mechanisms Th e number one cause of pain in elderly patients is may cause potential dangerous drug interac- degenerative spine disease, followed by osteoarthro- tions and unpredictable plasma levels. Th is ef- sis and osteoarthritis. Other important pain etiolo- fect may be most pronounced for drugs that are gies include polyneuropathy and postherpetic neural- eliminated through the kidneys, since glomeru- gia. Cancer pain is also a very relevant pain etiology. lar fi ltration rate is generally reduced, too, and In highly industrialized countries cancer pain in the for drugs with high plasma protein binding, elderly is often—at least partially—adequately con- where unpredictable serum levels of free sub- trolled. But in other countries, management of cancer stance may result. pain often is not a top priority, although good cancer • Vegetative state: Sympathetic reactions are re- pain management could be accomplished fairly easy duced, causing misunderstanding and underesti- with simple treatment algorithms based mainly on an mation of pain, since the elderly patient appears adequate opioid supply. to be less strained by pain. Pain in Old Age and Dementia 271 With regard to the opioid-receptor population and Case report: Mr. Ramiz Shehu subjective sensitivity to painful stimuli, there is confl ict- (prostate cancer) ing evidence. Th erefore the conclusion has to be that pain perception and analgesic interactions are unpre- Mr. Shehu is a 72-year-old farmer from the north- dictable. ern part of Albania, living in the village of Filipoje. He was diagnosed with prostate cancer 3 years ago when Do patients with impaired communication, he presented himself to the local doctor, Dr. Frasheri, such as those with Alzheimer disease, receive with diffi culties with urination. As disease of the pros- insuffi cient analgesia? tate was suspected, blood was drawn and send to the Unfortunately, a number of studies show that patients district hospital for the prostate-specifi c antigen (PSA) with Alzheimer disease, and diffi cult or impossible test. Unfortunately, the PSA was highly positive. After communication, receive insuffi cient analgesia. Th is has careful evaluation of the individual situation, espe- been shown both for acute situations such as fractures cially regarding the comorbidity with hypertension and of the neck of the femur and for chronic pain. Th is ob- heart insuffi ciency as well as the patient’s advanced servation is alarming since there is evidence showing age, Dr. Frasheri concluded that there would not be that the pain perception of Alzheimer patients is undis- an indication to send Mr. Shehu to the capital Tirana turbed. for surgery, chemotherapy, or radiotherapy. Now, after 3 years, Mr. Shehu was still in relatively good general What is likely to be the most important reason for inadequate pain management? condition, being an important and active member of St. Bartholomew’s church in his home village. But in the Much of the problem of inadequate pain management recent weeks he had developed increasing pain in his of the geriatric patient is the lack of appropriate assess- left chest and left hip. He described his pain as “drill- ment. Especially in patients with dementia, failure to ing,” increasing with activity, especially when walking assess pain properly results in insuffi cient analgesia, be- and taking a deep breath. Visitors from Italy had fi rst cause less than 3% of these patients will communicate suspected coronary disease and hip arthritis, since the that they need analgesics themselves. high PSA had been forgotten by that time. But the local How is pain in the geriatric patient doctor drew the correct conclusions. assessed eff ectively? 1) Th e options in Filipoje Th e main rule for the geriatric patient is: “ask for pain.” Local therapy: Use a walking stick, apply a home-made Th e patient may not ask for analgesia spontaneously. All elastic bandage around the chest. reported pain should be taken seriously; it is the patient Systemic therapy: Th e only pain killers available were di- who has the pain, and the pain is what the patient tells clofenac and morphine. you it is. Conventional instruments may be used for pain assessment, such as analogue scales or verbal rat- 2) Th e options in the capital, Tirana ing scales, if the patient is able to communicate prop- At Mother Th eresa Hospital, a tertiary care center, the erly. But rating and analogue scales will fail in the non- options are: communicating patient. Th erefore, it will be necessary Local therapy: X-ray or CT for confi rmation to use more sophisticated techniques. All these tech- of bone metastasis, eventually local radiation therapy: niques are based on careful observation and interpre- fractioned radiation (multiple) for analgesia and bone tation of the patient’s behavior. Several scoring systems stabilization, unfractioned radiation (single) for analge- have been developed for this task. Typical items for ob- sia only. servation include facial impression, daily activity, emo- Systemic therapy: Bisphosphonates (for bone sta- tional reactions, body position, the chance of consola- bilization), radionucleotides such as samarium, or action, and vegetative reactions. Some scores also include tivated phosphates (for patients with multiple painful the subjective impression of the therapist. Recent clini- bone metastasis where radiation is not an option), alter- cal research has tried to interpret various therapeutic nating opioids (for continuing side eff ects of the fi rst or interventions to fi nd out more about the patient’s pain, second opioid, because opioid rotation is the therapy of with trials called “sequential intervention trials.” choice if sedation and/or nausea persists beyond 1 week), 272 Andreas Kopf intrathecal catheters (for vertebral metastases where Shehu had been instructed carefully, so that he was pa- pain at rest is well controlled with opioids but pain on tient enough to wait for nausea (and sedation) to wean weight bearing is unbearable or only bearable with opi- off after a week’s time. In the educational part of the of- oid doses that cause intolerable side eff ects). fi ce visits, family members were included to discuss the patient’s wish to stay in Filipoje and his personal attitude Mr. Shehu’s treatment toward coping with the disease and its symptoms, fi nding Due to transportation problems and a long waiting list personal strength in the words of his savior at St. Bar- for treatment in Tirana, Dr. Frasheri decided to treat Mr. tholomew’s church. Shehu symptomatically at home. In Filipoje, he found a used walking stick and an elastic bandage, which How did Dr. Frasheri and Mr. Shehu fi nd the helped with ambulation. Diclofenac was available in lo- optimum dose of morphine? cal pharmacies, but Dr. Frasheri decided to advise Mr. Since Mr. Shehu was opioid-naive, meaning he had Shehu to use paracetamol (acetaminophen) instead, no prior experience with opioids, of advanced age, and since he was not sure about kidney function and it was with unpredictable cancer pain intensity, the method of foreseeable that the need for analgesic therapy would be choice is titration by the patient. Th is means that after long-lasting. When Mr. Shehu received piroxicam from careful explanation of the pros and cons of morphine, the Catholic mission, he also started taking it orally. It Mr. Shehu was provided with morphine solution (2%), was pure luck that Dr. Frasheri found out about the pa- which could be locally produced by the pharmacist. Mr. tient taking piroxicam. He stopped this medication and Shehu was told, with the help of his oldest son Sali, to explained to Mr. Shehu that the drug had a number of take 10 drops (ca. 10 mg) of morphine as needed, always negative prognostic factors for renal and gastrointestinal waiting for at least 30 minutes after the previous dose, side eff ects: old age, prolonged medication, accumula- and was told to always write down the time he took ex- tion of piroxicam because of a long half-life, among other tra medication. After two days, Mr. Shehu and his son problems. Mr. Shehu was not satisfi ed with the pain re- were told to come back to Dr. Frasheri, and together duction from the paracetamol, since he needed to make they looked over the list. It came out that on average ev- his way to and from the church daily, although when sit- ery second hour a dose was required, more in the day- ting or lying down the pain intensity was acceptable. So time and less in the night. To accomplish stable—and he insisted at Dr. Frasheri’s offi ce that he needed some- more tolerable—blood levels of morphine, Dr. Frash- thing else. eri then advised Mr. Shehu to take 30 mg of morphine At fi rst, Dr. Frasheri was reluctant to prescribe regularly every 4 hours, since no slow-release version opioids, because they are not easy available in Albania. of morphine was available. Of course, Dr. Frasheri did Th e per-capita amount of morphine and pethidine has not forget to allow Mr. Shehu to take—as needed—ex- been almost unchanged since the time of Enver Hoxha’s tra doses of 10 mg (roughly 10% of the daily cumulative dictatorship (1970–1980s), and Albania had never dose). If Mr. Shehu did not need extra doses, the basic signed the Single Convention from 1961. Only recently q.i.d. (four times daily) dose would be slightly reduced, have prescriptions of fentanyl (mainly for surgery) and e.g., to 20 mg q.i.d.; if he needed 1–4 extra doses the methadone (mainly for opioid substitution) increased. prescription would stay unchanged; and if the extra dos- Nevertheless, morphine could be obtained—with dif- es would exceed 4 per day, the basic q.i.d. dose would fi culty. After a lot of education on the pros and cons of be increased (e.g., with 6 extra doses per day equal to 60 morphine (Mr. Shehu was quite sceptical about taking mg, the regular dose of 30 mg q.i.d. would be increased it), Mr. Shehu was started on morphine, starting with 10 to 40 mg q.i.d.). Th e same procedure of titration was mg b.i.d. and gradually increasing the dose over several used for the time so that the balance between analgesia days. When he found out about the positive eff ects (es- and side eff ects was to the benefi t of Mr. Shehu. pecially on walking and standing), Mr. Shehu no longer raised any objections. His steady-state dose was 30 mg In conclusion, what should be done? morphine sulfate q.i.d. Activity, drinking an extra liter 1) General: of water, the healthy Mediterranean diet, and milk sug- i) Patients should not be deprived of the benefi ts ar helped against constipation, but nausea could not be of analgesia just because they are elderly. avoided due to the lack of metoclopramide. However, Mr. ii) Include relatives. Pain in Old Age and Dementia 273 iii) Write down your orders in big letters for pa- all dose increases should be done slowly and in small tients with impaired vision. stepwise increments. iv) Always provide patients with written information on what to take, when to take it, and Pharmacotherapy in older patients eventually, what side eff ects to expect. v) Avoid mentally overloading the patient; gen- What special considerations are erally not more than one major topic should there for analgesic pharmacotherapy be discussed per consultation, and directions in the elderly patient? should be repeated several times. NSAIDs have a variety of pharmacological interac- vi) Anticipate pain, and treat accordingly. tions. One of the most relevant is the potential increase vii) Use nonpharmacological techniques where of gastrointestinal side eff ects with the comedication of applicable, such as positioning, counterirrita- steroids. Also, blood sugar reduction is increased if the tion (using ice, external alcoholic herbal lo- patient is taking oral antidiabetics. Other interactions tions, etc.). are the reduction of the comedication’s eff ect, e.g., with viii) Use reassurance for anxiety-associated be- diuretics (reduced urine output) or ACE (angiotensin- havior. converting enzyme) inhibitors (less blood pressure re- ix) Don’t use “cookbook dosing schemes,” but induction). Other interactions with unexpected serum lev- stead titrate doses individually from very low el changes might result from concomitant therapy with initial doses. NSAIDs and alcohol, beta blockers, methotrexate, selec- x) For general assessment of the patient, fi tness is tive serotonin reuptake inhibitors (SSRIs), or quinine. a better guideline than chronological age. xi) Pain management in general may be accom- Why are NSAIDs of special importance plished in the outpatient setting; inpatient regarding unwanted eff ects? treatment for the sole reason of pain control is Elderly patients may experience a typical complication indicated only in selected patients. spiral with the prescription of long-term NSAID medi- 2) Assessment cation. For example, painful arthritis is often the prima- i) Ask the patient, who might not reveal infor- ry cause for prescribing a NSAID. Longer intake (more mation spontaneously for certain reasons. than 5 days of regular intake), higher doses, and con- ii) For patients with impaired communication, comitant steroid medication may cause gastrointestinal one of the suggested scores is the BESD (Beur- ulcers. Repetitive ulcer bleeding then may be the cause teilung von Schmerz bei Demenz [Assess- for anemia. In an older patient with reduced cardiac ment of pain in dementia]). For fi ve observa- function, anemia may cause cardiac insuffi ciency, which tions, 0–2 points may be allocated depending is then followed by diuretics as therapy. Although that on their nonexistence, medium presence, or medication is reasonable in normal instances, the di- strong presence. Th e observations are: uretics might cause renal dysfunction and consequently a) Breathing rate (normal/high/hectic) renal failure! b) Vocalizations (none/moaning/crying) c) Facial expression (smiling, anxious, gri- Can opioids have unwanted eff ects, too? macing) Opioids may also interact with other medications. d) Body position (relaxed/agitated/tonic) Watch out especially for all drugs that have a CYP2D6- e) Consolation (not necessary, possible, im- inhibiting eff ect, and expect higher than usual plasma possible) levels, for example cimetidine, quinidine, paroxetine, iii) Starting with a total of 5 points, this scoring fl uoxetine, methadone, antihistaminic drugs, and halo- system forces the therapist to start analgesic peridol. Other important direct interactions for mor- therapy. phine with other pharmacotherapies are ranitidine and 3) Pharmacotherapy. Th e basic principle of phar- rifampicin; for fentanyl ketoconazole and clarithromy- macotherapy in the elderly patient is “start low and go cin; for methadone cimetidine, quinidine, paroxetine, slow,” meaning that initial doses of all analgesics should fl uoxetine, antihistamines, and haloperidol; and for tra- be reduced compared with normal adult doses and that madol quinine and SSRIs. 274 Andreas Kopf If organ dysfunction is present, choose—if avail- buprenorphine (40%, 80%, or 95%, respectively), since able—buprenorphine for renal insuffi ciency and meth- a high rate of plasma-protein binding might provoke adone for liver insuffi ciency. But all other opioids may drug interactions. also be chosen, as long as doses are titrated individually, and dose reductions are made accordingly. Should coanalgesics be considered in the elderly patient? What are some considerations Th e indication for coanalgesics should be determined if opioids are chosen? very carefully to avoid drug interactions and unwanted Opioids have an unbeatable advantage over almost side eff ects. For example, the use of tricyclic antidepres- all other drugs available, especially in the elderly pa- sants, used often for constant burning pain such as in tient, since there is no known potential for organ diabetic polyneuropathy or postherpetic neuralgia, in- toxicity, even with long-term use. Th erefore, all ad- creases the risk of falling down and the incidence of vanced destructive diseases that present with pain fractures of the neck of the femur. Th erefore, in clinical (HIV-neuropathy, cancer pain, postherpetic neuralgia, practice, the use of coanalgesics should be restricted to and major degenerative spine disease with vertebral well-tolerated drugs, such as external capsaicin or sys- body destruction) are an indication for an opioid trial. temic gabapentin, if available. Some opioids, like morphine, are cheap (less than the cost of a loaf of bread for a week’s dose of morphine) Is there anything in addition to analgesics for my elderly patient? and available in most countries, though local government regulations might prohibit morphine prescrip- Th e incidence of depressive disorders is higher com- tion. Morphine and other “simple” opioids like hydro- pared to younger patients, and older citizens tend to morphone or oxycodone would be fi ne. Pentazocine, have fewer coping strategies regarding stress. If they tramadol and pethidine (meperidine) are not the fi rst have lived through wartime, it is sometimes old age that choice in the older patient because of their specifi c brings back unpleasant memories. Th ere is evidence pharmacodynamics and pharmacokinetics. Although that symptoms similar to post-traumatic stress disorder opioids are safe and eff ective analgesics, some points may surface in advanced age. Even if no adequate treat- should be considered when starting an elderly patient ment for this problem is available, asking for such mem- on opioids. Because of changes in plasma clearance ories and symptoms and an understanding approach and fl uid distribution, plasma concentrations of opi- may relieve some of the hardships of your elderly pa- oids may be higher than expected. Especially in long- tient. Also, religious coping strategies should be used for term treatment, dose adjustments will be necessary. In their healing properties. At times older patients do not general, opioid doses have an inverse correlation with dare to mention their beliefs, and the younger medical age, but the indication for an opioid has a positive (lin- professional may have separated himself from spiritual ear) correlation with age, and men on the average need thinking. Although spiritual healing may not be used in- more opioids than women. Elderly female patients tentionally, if these needs are not already present in the need opioids more often, but at a lower dose. As with patient, they may be integrated into a holistic approach other age groups, certain rules for opioid therapy must if careful questioning reveals the patient’s disposition. In be obeyed, especially structured information about the advanced age, pain may be integrated into life’s reality if advantages (no organ toxicity, long-term treatment) other factors of general life quality are taken care of. If and disadvantages (dependency with the need for dose asked about their “wish-list to the doctor,” older patients tapering, initial nausea and sedation, and more likely would appreciate conversations about their biography, than not continuous constipation). encouragement to have hope, integration of religion and family into their treatment, as well as a tender lov- Is there a “best opioid” for the elderly patient? ing environment in the medical setting. Th e health care In general: “all opioids are equal,” but as in the animal system should try to relieve some of the sorrows and farm of George Orwell, “some are more equal”: the anxiousness in the end-of-life situation, so that the pa- low plasma-protein-binding of hydromorphone and tient does not need to quote the famous movie director morphine (8% and 30%, respectively) might be an ad- Woody Allen: “I am not afraid of dying, I just don’t want vantage over others such as oxycodone, fentanyl, or to be around when it happens.” Pain in Old Age and Dementia 275 Pearls of wisdom • Opioids are the analgesics of choice for strong cancer pain unresponsive to NSAIDs. Keep in • Th ere is no evidence that older patients have less mind that around four half-lives (for morphine pain and need less pain medication than younger the total time would be about one day) will be patients. Also, the belief that opioid receptor den- necessary before a steady-state situation will be sity is reduced has not been confi rmed by recent reached in the patient and that women usually research. Th erefore, withholding opioids because need less opioids than men. In most older pa- the patient is old is not correct. tients, a longer dosing interval might be a good • Pain is underdiagnosed in the elderly patient. Al- solution (morphine t.i.d.). If available, combine ways ask about pain, and do not rely on analogue slow-acting morphine for basic analgesia with scales (e.g., NRS or VAS); instead, use careful ob- fast-acting morphine for on-demand doses. servation of the noncommunicating patient for • Coanalgesics should be used only in individually diagnosing unrelieved pain. selected patients. If coanalgesics are unavoidable, • Elderly patients tend to act in a “socially accept- calcium-channel-blocking anticonvulsants (gaba- able” manner, meaning that they try to be a good pentin or pregabalin) should be preferred. patient (“if I am no burden to anyone, everybody • Nonpharmacological treatment strategies should will value me higher” and “the doctor knows what always be implemented if possible and feasible: is best for me and will ask me if necessary”), and education, activity, cognitive techniques, and they tend to suff er through things, especially counterirritation (e.g., acupuncture). Do not for- pain, deprivation, and isolation (“nobody can help get integration of spiritual beliefs into the treat- me,” “it is the destiny of the older person to suff er,” ment plan. “there is no hope for me”). • End-of-life decisions should respect the wishes of • NSAIDs or paracetamol (acetaminophen) or di- the elderly patient to die at home, in dignity, and pyrone are drugs of fi rst choice for metastatic appreciated, with their pain under control. (bone) pain, depending on the risk profi le of the • Rule of thumb: Start low, go slow. patient (NSAIDs may be used nevertheless in the short term for pain exacerbations). Use the lowest References possible dose of NSAIDs, and avoid long-acting [1] AGS Panel on Persistent Pain in Older Persons. Th e management of NSAIDs that might accumulate (piroxicam and persistent pain in older persons. J Am Geriatr Soc 2002;50:S205–24. others). Avoid NSAIDs with a history of steroid [2] Hadjistavropoulos T. International expert consensus statement. Clin J Pain 2007;23:S1. medication, gastrointestinal bleeding, and kidney [3] Manfredi PL, Breuer B, Meier DE, Libow L. Pain assessment in elderly dysfunction. patients with severe dementia. J Pain Symptom Manage 2003;25:48–52. • If no infl ammatory pain component is suspected, and the anti-infl ammatory activities of NSAIDs Websites are not relevant, than always choose an antipyret- www.merck.com (the Merck manual on geriatrics) ic analgesic such as paracetamol or dipyrone. www.canceradvocacy.org (pain in the elderly)

Guide to Pain Management in Low-Resource Settings

Chapter 36 Breakthrough Pain, the Pain Emergency, and Incident Pain

Gona Ali and Andreas Kopf

Th e concept of “breakthrough pain” is a relatively new At rest, the pain was now controlled well, such one, and it receives much less attention than “back- as when she was in bed or watching television. But Mrs. ground” pain. As a result, breakthrough pain is much Nadhari was very disappointed that she was no longer less well understood and managed than background able to do the cooking for her family since longer peri- pain. Indeed, breakthrough pain has a number of “un- ods of standing or bending down at the oven had be- met needs.” come impossible.

Case report Case report discussion

Tabitha Nadhari, a 66-year-old woman from Basra, Th is patient with breast cancer and auxiliary lymph Iraq, has a history of breast cancer. Seven years ago, node involvement complains of severe pain due to she had a mastectomy with auxiliary clearance, fol- multiple bone metastasis. As it is typical in these cas- lowed by radiotherapy and chemotherapy. She was free es, pain at rest is well controlled by analgesics (accord- of pain up to a year ago, when she started to complain ing to the World Health Organization [WHO] ladder), about low back pain, which was mild and misdiag- but pain on movement is not controlled at all. Since nosed fi rst as “functional.” MRI showed, unfortunately, all pain exacerbations did occur in conjunction with metastasis to cervical, thoracic, and lumbar vertebrae. physical activity, such pain is called incident pain (as At that time, Mrs. Nadhari took nonopioid analgesics opposed to breakthrough pain, which would appear as needed, such as paracetamol (acetaminophen) or di- also spontaneously). Th e best thing for Dr. Foud to do clofenac. Due to the social problems after the war, nei- would be to prescribe 10-mg tablets of morphine for ther chemotherapy or radiotherapy was available in the Mrs. Nadhari and to instruct her to use them when health system. physical activity is planned. For example, before start- Recently, her pain became more severe and intol- ing cooking, Mrs. Nadhari should take a 10-mg tablet erable. Th e pain was no longer responding to diclofenac. (a titration dose), wait approximately 30 minutes, and She found a very caring physician, Dr. Foud, who started then start to go to the kitchen. Of course, she should her fi rst on the weak opioid tramadol in addition to the be warned that the extra morphine, especially if she diclofenac. After a few days, when it was evident that the needs more than one titration dose, might produce se- tramadol was ineff ective, Dr. Foud changed the opioid dation and nausea, or both. If it is available, metoclo- medication of Mrs. Nadhari to morphine (30 mg q.i.d.). pramide should therefore be provided if necessary, and

show that the majority of patients have suﬃ cient [2] Mercadante S, Radbruch L, Caraceni A, Cherny N, Kaasa S, Nauck F, Ripamonti C, De Conno F; Steering Committee of the European Asso- breakthrough pain control with this approach. ciation for Palliative Care (EAPC) Research Network. Episodic (break- • As patients learn that certain actions cause breakthrough) pain. Consensus conference of an Expert Working Group of the European Association for Palliative Care. Cancer 2002;94:832–9. through pain, these episodes can be anticipated, [3] Mercadante S, Villari P, Ferrera P, Casuccio A. Optimization of opioid therapy for preventing incident pain associated with bone metastases. J which may allow patients and physicians to either Pain Symptom Manage 2004;28:505–10. prepare a treatment response or to treat prophy- [4] Portenoy RK, Bennett DS, Rauck R, Simon S, Taylor D, Brennan M, Shoemaker S. Prevalence and characteristics of breakthrough pain in lactically. opioid-treated patients with chronic noncancer pain. J Pain 2006;7:583– 91. • Raising the continuous “background” analgesia [5] Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics dose moderately may reduce the frequency and and impact in patients with cancer pain. Pain 1999;81:129–34. [6] Zeppetella G, O’Doherty CA, Collins S. Prevalence and characteristics intensity of breakthrough pain episodes. of breakthrough pain in cancer patients admitted to a hospice. J Pain • Th e management of breakthrough pain is the art Symptom Manage 2000;20:87–92. of assessment, treatment, and reassessment. Websites

References www.pain.com www.breakthroughpain.eu [1] Fallon M, Zeppetella G, Poulain P, Stein C. Realising unmet needs in breakthrough pain. Eur J Palliat Care 2007;14: 29–31. Guide to Pain Management in Low-Resource Settings

Chapter 37 Pain Management in the Intensive Care Unit

Josephine M. Th orp and Sabu James

Case report pain relief, disadvantages of excessive analgesics or sedatives) A 52-year-old man, Joe Blogg, was admitted to the in- • Assessment of pain and sedation tensive care unit (ICU) from the operating room, after • Aims of therapy undergoing a long surgical procedure. He had been the • Techniques of pain management (routes for phar- driver of a car that was involved in a head-on collision, macological agents, analgesics, anxiolytics, and and he was trapped in the car (no seat belt or air bag) local anesthetic techniques) for about 30 minutes. When fi rst assessed in the receiv- • Adjuncts to pharmacological agents (managing ing accident and emergency care unit, he was rousable the ICU environment, reducing other sources of but confused and in considerable pain. His injuries discomfort, alternative measures, psychological were as follows: measures) Bilateral pneumothoraces (intercostal drains Th e majority of patients requiring intensive care were inserted in the accident and emergency unit by the will suff er pain, of varying intensity, during their stay. resuscitation team). Fractures of the third, fourth, and Despite knowledge since the early 1970s that pain is offi fth ribs on the left side. Deep wounds to right knee and ten the worst memory for patients surviving intensive right elbow, extending to the joint. An extensive mesen- care, in recent multicenter studies up to 64% of patients teric tear, for which he underwent a 5-hour laparotomy. still said they were often in moderate to severe pain Estimated blood loss of about 5 L, coagulopathic, with a while in the ICU. Th e experiences of patients who did platelet count of 50,000 postoperatively. He had several not survive their ICU stay remain unknown. Patients units of blood and blood components in the operating who were in ICU for longer periods reported greater in- room. He is anuric and hypothermic (with a core tem- tensity of pain. perature of 34°C). He was transferred to the intensive care unit for What are the sources of pain? elective ventilation and management. • Primary pathology, such as burns, traumatic injuries, fractures, wounds (surgical or traumatic) What issues must be considered in this case for • Complications of the original condition or new intensive care and afterwards? problems, such as bowel perforation or break- • Sources of pain (exacerbating factors) down of bowel anastomosis causing peritonitis, • Eff ects of untreated pain (advantages of adequate ischemic bowel, pancreatitis

• Other symptoms, such as abscesses, skin infl am- • Pain in itself will result in poor-quality sleep. mation, wound infection, rashes, itches • Support systems and monitoring—peripheral and What are the advantages of adequate pain relief? central intravenous line insertions and sites, catheters, drains, regular suctioning, physiotherapy, • Improved tolerance of endotracheal tube, me- dressing changes chanical ventilation, tracheal suctioning, and oth- • Tissue hypoxia as a result of low cardiac output, er distressing maneuvers. low oxygen saturation, or a sharp fall in hemoglo- • During weaning and after extubation, if chest ex- bin may result in myocardial ischemia cursion is limited by pain, adequate analgesia will • Painful joints, pressure points, pain on changing result in larger tidal volumes, better gas exchange, position in bed improved sputum clearance, and cooperation with physiotherapy. What exacerbating factors may increase pain • Reduction in the stress response. perception? • Less disturbing memories of therapy in the ICU. • Fear in strange surroundings associated with helplessness and lack of control What is the compromise between too much analgesia and too little? • Inability to remember or understand the situation resulting in intensive care Th e middle ground, to gain the benefi ts without the dis- • Anxiety and uncertainty about oneself, one’s fam- advantages can only be achieved by regular assessment ily, and about the present and the future of pain along with a “sedation vacation” (a break from • Background aggravations—noise, machine sedation) and adjustment of the regime on a daily basis. alarms, phones ringing How can you assess pain and sedation? • Ongoing activity through the night, other patients being admitted or resuscitated Even under normal circumstances, assessment and • Inability to communicate, to move, to change po- quantifi cation of pain are diffi cult. Th ese diffi culties are sition obviously far greater in the patient in the ICU, with an • Lack of sleep, disturbed sleep patterns endotracheal tube often present, preventing speech and • Other sensations:—thirst, hunger, hot, cold, empathic discussion. A state of paralysis in an aware pa- cramps, itching, nausea tient should be avoided in the ICU just as in the operat- • Fatigue after surgery; even after uncomplicated ing room, as this is a terrifying experience for a patient. surgery, fatigue is normal If the patient is paralysed, it is important to ensure that • Boredom and lack of distraction adequate sedation and analgesics are given to avoid a Addressing these aspects will make the pain it- patient who is awake but unable to move! self more tolerable and manageable. If the patient is able to speak, a routine history about the pain and its severity can be taken. A patient What are the eff ects of untreated pain? who is able to understand, but unable to speak, may • Pain induces increased sympathetic drive, result- be able to gesture or to indicate severity on a simple ing in cardiovascular changes (increased cardiac evaluation tool such as a visual analogue scale (VAS) work and oxygen consumption). or numeric rating scale (NRS). Th e NRS is a 10-point • An increased stress hormone response results in scale: the patient chooses a number from 0 to 10, with catabolism, with sodium and water retention and 10 being the worst pain imaginable. Where no com- hyperglycemia, which in turn leads to immuno- munication is possible, signs of sympathetic drive can suppression and delayed wound healing. be noted—tachycardia, hypertension, and lacrimation. • Ineff ective cough and retention of secretions, re- Clinical practice guidelines state: “Patients who cannot sulting in reduced oxygenation, infection. communicate should be assessed through subjective • Chest wounds and abdominal incisions decrease observation of pain related behaviors (movement, facial chest wall and abdominal movements, which may expression and posturing) and physiological indicators delay weaning from ventilation, increase the risk (heart rate, blood pressure and respiratory rate) and the of chest infection, and prolong ICU stay. change in these variables following analgesic therapy.” Pain Management in the Intensive Care Unit 285

Pain is exacerbated by movement, which may care. evoke pain of a quite diff erent character. Moving, turn- 3) Patients should be calm, cooperative, and able to ing the patient, and the eff ects of endotracheal tube suc- sleep when undisturbed. Th is does not mean that they tion and physiotherapy give valuable information about must be asleep at all times. the eff ectiveness of analgesia. 4) Patients must be able to tolerate appropriate or- For children, scales have been developed spe- gan system support. Th us, patients with very poor gas cifi cally for neonatal and pediatric use, e.g., the Riley In- exchange, particularly those requiring inverse I:E ra- fant Pain Scale: tios or the initial stages of permissive hypercapnia, may

Score Facial Expression Sleep Movements Cry Touch 0 - Neutral - Sleeping quietly - Moves easily - None - - Smiling, calm 1 - Frowning - Restless - Restless body - Whimpering - Winces with touch - Grimaces movements 2 - Clenched teeth - Intermittent - Moderate agita- - Crying - Cries with touch tion - Diﬃ cult to console 3 - Crying expression - Prolonged, with - Th rashing, - Screaming, - Screams when touched periods of jerking ﬂ ailing high-pitched - Inconsolable or no sleep

Whatever method of assessment is selected, it need neuromuscular blockade. Th e use of a nerve stim- should be regular. Both the patient and the response to ulator to monitor the extent of neuromuscular blockade drugs are constantly changing, so drugs and doses need may be useful in some situations. regular adjustment. 5) Patients must never be paralysed and awake.

What are the main problems for Joe in the intensive care unit? Pain management in the intensive care unit • Being heavily sedated and ventilated, and thus unable to communicate What techniques of pain management • Being critically ill, with multiple injuries includ- are available? ing lung contusions and possible head injury Most intensive care patients will require analgesia. In • Experiencing massive blood loss, massive trans- 1995, the Society of Critical Care Medicine published fusion, and coagulopathy practice parameters for intravenous analgesia and seda- • Having hypothermia tion in the ICU. Morphine and fentanyl were the pre- • Having anuria ferred analgesic agents, and midazolam or propofol were • Experiencing multiple sources of pain: intercostal recommended for short-term sedation, with propofol drains, fractured ribs, elbow and knee wounds, being the agent of choice for rapid awakening. More re- and a laparotomy wound cently, sedative and analgesic practice in ICUs in Europe has been surveyed; opioids are the drugs most common- What are the aims of therapy? ly used for pain relief, usually by infusion, with morphine Th e objective should be a cooperative, pain-free patient, being the most widely used. Shorter-acting fentanyl and which implies that the patient is not unduly sedated. alfentanil, as well as ultra-short-acting remifentanil, are Th e United Kingdom Intensive Care Society also used, but they are more expensive. Propofol and guidelines on sedation state the following: benzodiazepines are used for sedation, with diazepam, 1) All patients must be comfortable and pain free: lorazepam, and midazolam all being widely used. Analgesia is thus the fi rst aim. 2) Anxiety should be minimized. Th is is diffi cult as What are the available application routes for anxiety is an appropriate emotion. Th e most important pharmacological agents? way to reduce anxiety is to provide compassionate and Th e ideal route is intravenous, which is more reliable considerate care; communication is an essential part of than the alternatives. Small frequent intravenous bolus 286 Josephine M. Th orp and Sabu James doses or an intravenous infusion are the best routes for wake up. This contraindication also applies to dia- analgesics. Th e latter avoids peaks and troughs but may morphine and papaveretum. In renal impairment, if result in accumulation. Bolus doses should be regular there is no alternative, the dose and dosing interval without waiting until another dose is obviously essen- should be reduced. tial. In all situations, it is important to review the re- Systemic eff ects of opioids within the context of quirement regularly, for example daily, by discontinuing intensive care are: the infusion or stopping the boluses. In this way, pain • Central nervous system: morphine, diamorphine, can be assessed, accumulation can be avoided, and the and papaveretum have sedative properties, but dose can be adjusted accordingly. Another important excessive doses would be required to achieve se- reason for discontinuing drugs and allowing the patient dation. to recover from the eff ects is the great variations in drug • Respiratory system: all opiates depress respira- handling in the critically ill patient. Th ere are a vari- tion in a manner proportionate to the pain relief ety of explanations for this variation, but discontinuing obtained. Th is is not a major issue in a ventilated drugs allows the eff ect to wear off and reduces the ten- patient. Some cough-suppressant eff ect can be an dency to accumulation. advantage in the intubated patient. Gastrointestinal absorption can be unpre- • Cardiovascular system: given in small doses, dictable, and absorption of opioids is poor. Rectal ad- there is usually little eff ect on blood pressure. ministration, for drugs that are available in supposi- • Gastrointestinal system: opiates have a gut an- tory form, may give better absorption, although the timotility eff ect and so may exacerbate paralytic side eff ects of the enteral route remain. Some classes ileus and constipation. Nausea and vomiting are of analgesics have only become available in parenteral well-known side eff ects of morphine. form relatively recently. Intravenous nonsteroidal an- • Other side eff ects: pruritis can be a distress- ti-infl ammatory agents (NSAIDs) and, more recently, ing side eff ect for the patient. Addiction is not paracetamol (acetaminophen) are available as intrave- a problem with the use of opiates in severe pain nous formulations. and is not a concern in patients who have sur- vived intensive care. However, withdrawal symp- What would be a good choice toms and signs are possible after several days of of analgesia for Joe? continuous therapy or if therapy is stopped sud- • Paracetamol/acetaminophen (intravenous, if denly. An initial reduction of 30% followed by available, or via nasogastric tube regularly) a 10% reduction every 12–24 hours thereafter • Nonsteroidal analgesics (via nasogastric tube) should help to avoid withdrawal phenomena. given regularly (after coagulopathy has resolved), Th e systemic eff ects of other opiates are similar combined with gastric protection agents to those described above. Diamorphine or papaveretum • Opioids (preferably as a continuous intravenous could be used instead of morphine if more readily avail- infusion) able. Fentanyl is a synthetic opioid that was introduced • Nerve blocks (single-shot nerve blocks or epidu- as a short-acting agent, but it can accumulate when giv- ral analgesia) en as an infusion in intensive care. It may be useful for short painful procedures. Alfentanil has the advantages What to bear in mind when using opioid of fentanyl quoted above. Its onset is faster than that of analgesics in the intensive care unit fentanyl, and even as a prolonged infusion, it is less cu- Morphine and fentanyl are the most commonly used mulative; it would be the drug of choice in renal impair- analgesics in Europe according to a survey in 2001; ment. Like fentanyl, it is particularly useful for addition- morphine has the advantage of being cheap. It is al short-term analgesia, lasting around 10–15 minutes. longer acting than synthetic opioids but also more Unfortunately, it is much more expensive. inclined to accumulate. Elderly patients are more Remifentanil, although quite expensive, is cur- sensitive, as are those with renal or hepatic impair- rently used in the intensive care arena, especially for ment. The potent active metabolite, morphine-6- weaning and tube tolerance. It is rapidly metabolized glucuronide, can accumulate in renal failure, resulting and does not accumulate regardless of time or in renal in continued sedation, failure to breathe, or failure to or hepatic dysfunction. Pain Management in the Intensive Care Unit 287 For less severe pain, pethidine and tramadol What nonopioid analgesics are options could be used. Pethidine/meperidine could be given by for analgesia in the intensive care unit? bolus doses for procedural pain relief, but not as an in- Nonopioid analgesics used in combination with an fusion, because its metabolite can accumulate and is as- opioid achieve better-quality pain relief. Although sociated with twitching and seizures. Tramadol has the some intravenous and intramuscular preparations are advantage of two mechanisms of action for pain relief— available, these agents are mostly given by the enteral opiate-like activity by binding to opiate receptors and route if gastrointestinal function permits adequate ab- inhibition of serotonin and norepinephrine reuptake by sorption. Some are available in suppository form or as nerves, mainly in the spinal cord. It is relatively expen- a liquid suspension, which can be given down a naso- sive but avoids the problems of respiratory depression gastric tube. and gastrointestinal stasis. Rapid intravenous injection Paracetamol/acetaminophen is a non-narcotic may cause seizures, and it is not advised in pregnancy analgesic with useful antipyretic action as well. It is or breastfeeding. useful in mild to moderate pain and has an additive ef- Buprenorphine and pentazocine are unsuited fect if given with an opiate. It is available as dispersible for analgesia in intensive care. If given in a suffi cient tablets, as an oral suspension, and in suppository form. dose to cause respiratory depression, they are not reli- It has no anti-infl ammatory activity and so avoids the ably reversible with naloxone. In addition, these agents side eff ects of nonsteroidal anti-infl ammatory drugs antagonize other opioids because of powerful receptor (NSAIDs). Clonidine, an alpha-2-adrenergic agonist, binding, reversing the analgesic eff ect of other opioids can be used to augment both the sedative and analge- by displacing them from receptors. Th us, they may sic eff ects of opioids. A dramatic reduction in opioid precipitate opioid withdrawal symptoms and signs. requirements and the attendant side eff ects has been Pentazocine can be associated with bizarre thoughts reported with low-dose clonidine. Diclofenac, ketopro- and hallucinations. fen, ibuprofen, and other NSAIDS are good for bone Other opioids include meptazinol and codeine. pain and for soft-tissue pain in young patients without Meptazinol is claimed to cause less respiratory depres- asthma or renal impairment and can reduce opioid re- sion, but it can cause nausea. Intravenous injection quirements. Oral, nasogastric, intravenous, and rec- needs to be slow. Codeine is used in mild to moderate tal routes can be used. Regardless of route, they cause pain and might have some eff ect as a cough suppres- gastric irritation. Hence, prophylactic treatment for sant. It is usually given orally, though linctus could be gastric ulceration should be given. However, the signif- given down a nasogastric tube. Actually, codeine is me- icant side eff ects of NSAIDs in intensive care have to tabolized in the liver into morphine and other products be considered: they can cause bronchospasm, may pre- that cause relatively severe side eff ects. cipitate or exacerbate a bleeding tendency, cause gastrointestinal bleeding from mucosal ulceration (exac- How to reverse the eff ects of opioids if necessary erbated by platelet inhibition), or lead to development of renal impairment or worsening of renal failure, Naloxone reverses all opioid eff ects, so both respira- particularly when other risk factors are present, such tory depression and pain relief are reversed (for bu- as hypotension, hypertension, or diabetes. NSAIDs prenorphine and pentazocine, see above). Too much should be used with caution in older patients due to naloxone given too quickly and reversing analgesia a higher incidence of gastric complications and renal may result in restlessness, hypertension, and arrhyth- impairment. Aspirin, indomethacin, and cyclooxygen- mias and has been known to precipitate cardiac ar- ase (COX)-2 inhibitors are not recommended for use rest in a sensitive patient. If possible, dilute naloxone in the ICU due to a plethora of side eff ects. to 0.1 mg/mL and titrate, giving 0.5 mL of the diluted solution at a time to achieve the required degree of re- What about using ketamine versal, so that respiration becomes adequate and some in the intensive care unit? analgesia continues. Naloxone has a shorter duration Good analgesia can be achieved with low-dose ket- of action than many opiates, and the patient may be- amine. It tends not to be used for background analgesia come renarcotized. Repeat doses of naloxone or an in- in intensive care in the United Kingdom, though it may fusion may be required. be used for short procedures. Some studies have shown 288 Josephine M. Th orp and Sabu James that ketamine reduces opioid requirements in surgical In a survey in 2001 in Western Europe, midazolam intensive care patients. Th e dose range for avoiding psy- was most frequently used for sedation in the inten- chomimetic side eff ects is 0.2 to 0.5 mg/kg body weight. sive care situation because it has a shorter duration If using S-ketamine, the dose range has to be divided by of action than diazepam and is less prone to accumu- two. Long-term use is possible. Ketamine could perhaps lation. Lorazepam is a cost-effective drug that is lon- be the analgesic of choice in patients with a history of ger acting and can have useful anxiolytic effects for bronchospasm to have the benefi t of bronchodilator prolonged treatment of anxiety; however, it can result activity without contributing to arrhythmias, if amino- in oversedation. In the American Society of Critical phylline is also required. Where expensive analgesics Care Medicine Guidelines, lorazepam was the drug are not available, ketamine may have a slightly greater recommended for longer-term sedation. Propofol role as an adjunct in pain relief in intensive care. Also, infusion is also frequently used in many countries predominantly neuropathic pain might be an indication, in Europe; the advantage being that it can be titrat- since the “normal” coanalgesics for neuropathic pain, ed easily and the effect will usually diminish quickly e.g., amitriptyline, carbamazepine, and gabapentin, are once the infusion is stopped, allowing for a “seda- not available for parenteral use and have a delayed onset tion vacation” in the ICU. In addition to benzodiaz- of action. epines and propofol, other drugs with sedative properties have been used in the past and are considered Can local-anesthetic techniques be used obsolete for sedation: phenothiazines, barbiturates, in the intensive care unit? and butyrophenones. Opioids should not be used to Intercostal nerve blocks, paravertebral blocks, epidural achieve sedation, and some of their side effects can be analgesia, transversus abdominis plane (TAP) blocks, disturbing in themselves. femoral nerve blocks, and interscalene/brachial plexus Excessive sedation has negative eff ects—re- blocks can be used as single shots or with catheters duced mobility results in increased risk of deep vein (not for intercostal blocks) for continuous infusion. To thrombosis and pulmonary thromboembolism. Overse- avoid nerve damage, nerve stimulators or ultrasound dation may slow the weaning process or delay extuba- guidance should be used, if the patient is sedated and tion, when the patient is otherwise ready, and so can paresthesias cannot be communicated. Regular co- prolong ICU stay, with its attendant risks, and increase agulation profi le, full blood count, and platelet num- the cost of care. After several days of continuous ther- bers should be noted before these procedures as re- apy with propofol or benzodiazepines, withdrawal phe- gional techniques are contraindicated in patients with nomena may be precipitated, and reduction in dose a bleeding tendency such as anticoagulation, coagu- should be gradual to avoid them. lopathy, and thrombocytopenia. If a continuous technique with an indwelling catheter is used, this should What adjuncts to pharmacological agents should be considered in the intensive care unit? be clearly labeled. A fi lter should be used to minimize or prevent infections. Th e ICU can be a noisy place with regular monitor alarms, telephones, and pager calls. Much of the mon- What to discuss regarding appropriate itor alarm noise is avoidable by setting alarm limits analgesia for Joe around the expected variables of a particular patient • Availability of analgesics (both type and form). at that time. Th is means that the alarm will still sound • Appropriate analgesic for this situation, since this if there is a change beyond the expected. Although pa- patient has renal failure and coagulopathy. tients may appear asleep or sedated, their hearing may • Opioids (preferably as a continuous infusion). remain, so discussions about the patient may be bet- • Nerve block and/or epidural may be appropri- ter held out of earshot as the patient may misinterpret ate once his renal function improves and he is no limited information. Th is applies perhaps even more longer coagulopathic. to discussion about other patients, because a listening patient may mistakenly believe that the conversation How and when to use anxiolytics and sedatives applies to himself. Although these drugs have no analgesic proper- Adjustment of the lighting to provide night- ties, they may reduce the dose of analgesia required. time/daytime levels may help. Even if the patient is Pain Management in the Intensive Care Unit 289 tired, it is diffi cult to sustain sleep with full daytime abstract art as opposed to words (reassurance that this lighting, and the ICU patient does not have the option is very common is needed). Alternatively, pictures dis- of hiding beneath the bedclothes. Feeling thirsty, hun- playing the most common complaints and requests can gry, hot, or cold is a driving force that normally results be used. in remedial action, but this is beyond the power of the For planned admissions to the ICU, such as af- ICU patient. ter major surgery, an explanation of tubes, lines, moni- Good nursing care helps to avoid pressure ar- toring and procedures can be made in advance. In this eas and prevents the patient from lying on a rumpled way, common interventions that are not expected by the sheet or tubing, ventilator tubing from dragging on the patient will not interpreted by the patient as “something endotracheal tube, ECG leads pulling across the skin on has gone wrong.” the chest, drip tubing pulling on cannulae (in addition, While pain perception may be exaggerated by dislodgement usually means re-insertion, which may be additional factors, and ameliorating these factors may diffi cult). Awareness of all such details helps to reduce make pain considerably more tolerable, they will not unnecessary discomfort. take pain away. Th erefore, appropriate doses of analge- Supportive modes of ventilation such as pres- sics will still be required. sure support and other modes on modern ventilators are associated with greater patient comfort and require Case report (cont.) less analgesia and sedation compared with full ventila- Still heavily sedated and ventilated, Joe is started on tion. Maintaining muscle activity will reduce respiratory an intravenous infusion of morphine at a rate of 10 mg muscle wasting. per hour. He starts struggling, and the ventilator alarm Other symptoms such as nausea, vomiting, keeps buzzing. He also becomes very tachycardic and itch, significant pyrexia, and cramps require their hypertensive, causing concern for the staff . A review of own management. Fractures need to be stabilized sedation and analgesia is necessary in the unit. (Th ink either surgically, when appropriate, or immobilized. of infection, fat emboli, inadequate sedation/analgesia, Causes of agitation such as a full bladder or rectum respiratory distress due to pulmonary contusions, etc.). should be excluded. Joe’s white cell count is slightly elevated, temperature is on the higher side, platelets are increasing, and coagu- Are there alternative and psychological lation results are encouraging. Th ere is no clinical evi- measures from which my patient could benefi t? dence of fat embolization. Th ere is a concern that Joe’s Relaxation techniques require a cooperative patient sedation/analgesia might be inadequate. He is started preferably breathing spontaneously to coordinate deep on regular nasogastric paracetamol, his sedation with breathing with sequential relaxation of muscle groups midazolam is increased, and his morphine dose is from head to toe. Music can be benefi cial, particularly raised to 15 mg per hour, after a bolus dose of 5 mg. if it is of the patient’s choice and appreciated through He settles down, eventually, and there are no immedi- headphones, rather than being added to background ate concerns. noise of ICU. Speaking to the patient by name, even though What should be considered for weaning and the patient appears sedated, and explaining what is preparation for extubation? about to happen is always helpful, both for the patient Th e fi rst rule is to outline your strategies for a success- and for visiting relatives or friends. It helps patients to ful weaning and extubation, from a pain control point reconnect with who they are and with their family. Tell- of view: ing patients who understand and are recovering that • Continue paracetamol they are making good progress assists positive thinking • Reduce morphine and midazolam and can enhance recovery. • Review full blood count, coagulation parameters, Giving patients the opportunity to express their and renal function pain or discomforts by some means is helpful so that • Does the patient still need the intercostal drains? they know staff are sympathetic and will explain the • Plan to achieve better analgesic control, such possible remedies. If the patient can write, the fi rst op- as with nerve blocks, or by adding an NSAID portunity will invariably produce squiggles resembling if renal function has improved and platelets are 290 Josephine M. Th orp and Sabu James within normal limits (remember gastric muco- • Stabilize fractures with a splint, plaster, or surgi- sal protection) cal fi xation as soon as possible. • As elsewhere, pain on movement is greater than Case report (cont.) pain at rest. Respiratory parameters support adequate weaning, mor- • Anticipate painful procedures or maneuvers by phine infusion is ongoing, no epidural or paravertebral giving extra analgesia beforehand. block has been inserted, and the patient is extubated. He • Bolus doses of opiate are required before an infu- manages to survive off the ventilator for about 2 hours. sion is started. He complains of severe pain in his chest (from the frac- • An infusion rate increase takes time to become tured ribs) and in the laparotomy wound. Progressively eff ective; give a bolus fi rst. he becomes unable to breathe, his saturation drops, and • Multimodal therapy can reduce opioid require- he needs to be re-intubated soon afterward. ments and side eff ects, but beware the hazards of Once Joe is settled and stable, inadequate pain nonopioid analgesics in this group of patients. control is seen to have been a major factor in the failed • Older persons have lower analgesic requirements; extubation, and he gets a thoracic epidural and a left- young adults have higher ones. sided paravertebral block. A bolus dose of local anes- • Addiction to opioids is not a problem in patients thetic is given into the epidural, and a continuous infu- surviving critical care. sion is set up. • Underprovision of analgesia in general is a greater What should be done next? Review his analge- problem than overdosing. sia and slowly wind down the morphine infusion, hoping that the epidural and paravertebral blocks are working. References Joe is reviewed next day; sedation and morphine are minimal, and he is wide awake and wants the endo- [1] Cardno N, Kapur D. Measuring pain. BJA CEPD Reviews 2002;2(1):7–10. [2] Chong CA, Burchett KR. Pain management in critical care. BJA CEPD tracheal tube out. When queried about pain, he signals Reviews 2003;3(6):183–6. that he has none, and is quite comfortable. He is extu- [3] Dasta JF, Fuhrman TM, McCandles C. Patterns of prescribing and administering drugs for agitation and pain in a surgical intensive care unit. bated successfully and remains well. Crit Care Med 1994;22:974–80. [4] Hayden WR. Life and near-death in the intensive care unit. A personal experience. Crit Care Clin 1994;10:651–7. [5] Intensive Care Society, United Kingdom. Clinical guideline for sedation Pearls of wisdom in intensive care units. Available at: www.ics.ac.uk/downloads/sedation. pdf. [6] Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, In general: Chalfi n DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, • Talk to the patient by name. Lumb PD; Task Force of the American College of Critical Care Medi- • Encourage visitors to talk to the patient. cine (ACCM) of the Society of Critical Care Medicine (SCCM), Ameri- can Society of Health-System Pharmacists (ASHP), American College • Tell recovering patients they are doing well; tell of Chest Physicians. Clinical practice guidelines for the use sustained those who are less well about some positive as- use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002;30:119–41. pects. [7] Kehlet H. Multimodal approach to control of postoperative physiology and rehabilitation. Br J Anaesth 1997;78:606–17. • Much can be achieved by reducing additional [8] Park GR. Sedation and analgesia—which way is best? Br J Anaesth sources of discomfort. 2001;87:183–5. [9] Park GR, Ward B. Sedation and analgesia in the critically ill. In: Warrell • An adverse ICU experience can be reduced by DA, Cox TM, Firth JD, Benz EJ, editors. Oxford textbook of medicine, better communication with patients. 4th edition, vol. 2. Oxford University Press; 2003. p. 1250–3. [10] Puntillo KA. Pain experiences of intensive care patients. Heart Lung • As ever, “it’s not what you say, but how you say 1990;19(5 Pt 1):526–33. [11] Shapiro BA, Warren J, Egol AB, Greenbaum DM, Jacobi J, Nasraway it”—use an empathetic tone of voice. SA, Schein RM, Spevetz A, Stone JR. Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: Regarding pain: an executive summary. Society of Critical Care Medicine. Crit Care Med 1995;23:1596–600. • Ask about pain and irritations at regular intervals. [12] Smith CM, Colvin JR. Control of acute pain in postoperative and post- traumatic situations. Anaesth Intensive Care Med 2005;6:2–6. • Regular assessment of pain and discontinuing bo- [13] Soliman HM, Mélot C, Vincent JL. Sedative and analgesic practice in the intensive care unit: the results of a European survey. Br J Anaesth luses or infusions avoids underdosing and over- 2001;87:186–92. dosing and improves outcome and costs [14] Tonner PH, Weiler N, Paris A, Scholz J. Sedation and analgesia in the intensive care unit. Curr Opin Anaesthesiol 2003;16:113–21. Pain Management in the Intensive Care Unit 291

Update in Anaesthesia. An educational journal aimed at providing practi- Websites cal advice for those working in isolated or diﬃ cult environments. Extremely valuable resource; all twenty-ﬁ ve issues accessible on-line. Bandolier—evidence based web site incorporating the Oxford Pain Internet http://www.nda.ox.ac.uk/wfsa/index.htm Site is a free resource AnaesthesiaUK is an educational resource for postgraduate exams. As well as http://www.jr2.ox.ac.uk/Bandolier/booth/painpag/index2.html instructive material, it provides access to a weekly tutorial Lothian Joint Formulary is freely accessible on the internet. Th ere are both http://www.frca.co.uk/default.aspx adult and paediatric formularies. Two choices are provided for each group of drugs. Analgesics are under Central Nervous System section 4.7. Detailed A selection of articles on acute pain topics drug information is not given http://www.frca.co.uk/SectionContents.aspx?sectionid=148 http://www.ljf.scot.nhs.uk/ A selection of articles on chronic pain topics Lothian Joint Formulary can be downloaded and saved http://www.frca.co.uk/SectionContents.aspx?sectionid=183 http://www.ljf.scot.nhs.uk/downloads/ljf_adult_20060524.pdf

Guide to Pain Management in Low-Resource Settings

Chapter 38 Diagnostic and Prognostic Nerve Blocks

Steven D. Waldman

What are the assumptions clinical impression. Laboratory and radiological testing underlying the use of nerve are often the next place the clinician seeks reassurance, although the lack of readily available diagnostic testing in blocks in pain management? the low-resource setting may preclude their use. Th e cornerstone of successful treatment of the patient Fortunately, diagnostic nerve block requires with pain is a correct diagnosis. As straightforward as limited resources, and when done properly, it can pro- this statement is in theory, success may become diffi cult vide the clinician with useful information to aid in in- to achieve in the individual patient. Th e reason for this creasing the comfort level of the patient with a tentative diffi culty is due to four disparate, but interrelated issues: diagnosis. However, it cannot be emphasized enough Pain is a subjective response that is diffi cult if not that overreliance on the results of even a properly per- impossible to quantify; formed diagnostic nerve block can set in motion a se- Th e pain response in humans is made up of a variety ries of events that will, at the very least, provide the pa- of obvious and not-so-obvious factors that may serve to tient with little or no pain relief, and at the very worst, modulate the patient’s clinical expression of pain either result in permanent complications from invasive surger- upward or downward; ies or neurodestructive procedures that were justifi ed Our current understanding of neurophysiological, solely on the basis of a diagnostic nerve block. neuroanatomical, and behavioral components of pain is incomplete and imprecise; and What would be a roadmap for Th ere is ongoing debate by pain management spe- the appropriate use of diagnostic cialists as to whether pain is best treated as a symptom nerve blocks? or as a disease. Th e uncertainty introduced by these factors can It must be said at the outset of this discussion, that even often make accurate diagnosis very problematic and the perfectly performed diagnostic nerve block is not limit the utility of neural blockade as a prognosticator without limitations. Table 1 provides the reader with a of the success or failure of subsequent neurodestructive list of do’s and don’ts when performing and interpreting procedures. Given the diffi culty in establishing a correct diagnostic nerve blocks. diagnosis of a patient’s pain, the clinician often is forced First and foremost, the clinician should use to look for external means to quantify or fi rm up a shaky the information gleaned from diagnostic nerve blocks

Table 1 Th e do’s and don’ts of diagnostic nerve blocks Do analyze the information obtained from diagnostic nerve blocks in the context of the patient’s history, physical, laboratory, neurophysiological, and radiographic testing Don’t over-rely on information obtained from diagnostic nerve blocks Do view contradictory information obtained from diagnostic nerve blocks with skepticism Don’t rely on information obtained from diagnostic nerve block as the sole justifi cation to proceed with invasive treatments Do consider the possibility of technical limitations that limit the ability to perform an accurate diagnostic nerve block Do consider the possibility of patient anatomical variations that may infl uence the results Do consider the presence of incidence pain when analyzing the results of diagnostic nerve blocks Don’t perform diagnostic blocks in patients currently not having the pain you are trying to diagnose Do consider behavioral factors that may infl uence the results of diagnostic nerve blocks Do consider that patients may premedicate themselves prior to diagnostic nerve blocks with caution and only as one piece of the overall di- block, e.g., conjoined nerve roots, the Martin Gruber agnostic workup of the patient in pain. Results of a anastomosis (a median to ulnar nerve connection), etc. diagnostic nerve block that contradicts the clinical Since each pain experience is unique to the in- impression that the pain management specialist has dividual patient and the clinician really has no way to formed, as a result of the performance of a targeted quantify it, special care must be taken to be sure that history and physical examination and consideration of everybody is on the same page regarding what pain the available confi rmatory laboratory radiographic, neu- diagnostic block is intended to diagnose. Many patients rophysiological, and radiographic testing, should be have more than one type of pain. A patient may have viewed with great skepticism. Such disparate results, both radicular pain and the pain of diabetic neuropathy. when the nerve block is used in a prognostic manner, A given diagnostic block may relieve one source of the should never serve as the sole basis for moving ahead patient’s pain while leaving the other untouched. with neurodestructive or invasive surgical procedures, Furthermore, if the patient is having incident which in this situation have little or no hope of helping pain, e.g., pain when walking or sitting, the performance to alleviate a patient’s pain. of a diagnostic block in a setting other than one that will In addition to the above admonitions, it must provoke the incident pain is of little or no value. Th is be recognized that the clinical utility of the diagnostic often means that the clinician must tailor the type of nerve block can be aff ected by technical limitations. In nerve block that he or she is to perform to allow the pa- general, the reliability of data gleaned from a diagnos- tient to be able to safely perform the activity that incites tic nerve block is in direct proportion to the clinician’s the pain. Finally, a diagnostic nerve block should never familiarity with the functional anatomy of the area in be performed if the patient is not having, or is unable to which the nerve block resides and the clinician’s expe- provoke the pain that the pain management specialist is rience in performing the block being attempted. Even trying to diagnosis as there will be nothing to quantify. in the best of hands, some nerve blocks are technically Th e accuracy of diagnostic nerve block can be more demanding than others, which increases the like- enhanced by assessing the duration of nerve relief rela- lihood of a less-than-perfect result. Furthermore, the tive to the expected pharmacological duration of the proximity of other neural structures to the nerve, gan- agent being used to block the pain. If there is discor- glion, or plexus being blocked may lead to the inadver- dance between the duration of pain relief relative to tent and often unrecognized block of adjacent nerves, duration of the local anesthetic or opioid being used, invalidating the results that the clinician sees, e.g., the extreme caution should be exercised before relying proximity of the lower cervical nerve roots, phrenic solely on the results of that diagnostic nerve block. nerve, and brachial plexus to the stellate ganglion. It Such discordance can be due to technical shortcom- should also be remembered that the possibility of un- ings in the performance of the block, anatomical varia- detected anatomical abnormality always exists, which tions, and most commonly, behavioral components of may further confuse the results of the diagnostic nerve the patient’s pain. Diagnostic and Prognostic Nerve Blocks 295 Finally, it must be remembered that the pain Neuroaxial diagnostic nerve blocks and anxiety caused by the diagnostic nerve block it- Diff erential spinal and epidural blocks have gained self may confuse the results of an otherwise technically a modicum of popularity as an aid in the diagnosis of perfect block. Th e clinician should be alert to the fact pain. Popularized by Winnie [9], diff erential spinal and that many pain patients may premedicate themselves epidural blocks have as their basis the varying sensitivity with alcohol or opioids because of the fear of procedur- of sympathetic and somatic sensory and motor fi bers to al pain. Th is situation also has the potential to confuse blockade by local anesthetics. While sound in principle, the observed results. Obviously, the use of sedation or these techniques are subject to some serious technical anxiolysis prior to the performance of diagnostic nerve diffi culties that limit the reliability of the information block will further cloud the very issues the nerve block obtained. Th ey include: is in fact supposed to clarify. 1) Th e inability to precisely measure the extent that each type of nerve fi ber is blocked; What are important and useful 2) Th e possibility that more than one nerve fi ber specifi c diagnostic nerve blocks? type is simultaneously, blocked leading the clinician to attribute the patient’s pain to the wrong neuroanatomi- Early proponents of regional anesthesia such as La- cal structure; bat and Pitkin [3] believed it was possible to block just 3) Th e impossibility of “blinding” the patient to the about any nerve in the body. Despite the many technical sensation of warmth associated with sympathetic block- limitations these pioneers were faced with, these clini- ade as well as the numbness and weakness that accom- cians persevered. Th ey did so, not only because they be- pany blockade of the somatic sensory and motor fi bers; lieved in the clinical utility and safety of regional nerve 4) Th e fact that in clinical practice, the construct block, but because the available alternatives to render of temporal linearity, which holds that the more “sensi- a patient insensible to surgical pain at their time were tive” sympathetic fi bers will become blocked fi rst, fol- much less attractive. Th e introduction of the muscle lowed by the less sensitive somatic sensory fi bers and relaxant curare in 1942 by Dr. Harold Griffi th changed lastly by the more resistant motor fi bers, breaks down. this construct [2], and in a relatively short time, region- As a practical matter, it is not uncommon for the patient al anesthesia was relegated to the history of medicine, to experience some sensory block prior to noticing the with its remaining proponents viewed as eccentric at warmth associated with block of the sympathetic fi bers, best. Just as the Egyptian embalming techniques were rendering the test results suspect; lost to modern man, many regional anesthesia tech- 5) Th e fact that even in the presence of a neuroaxial niques that were in common use were lost to today’s block dense enough to allow a major surgical procedure, pain management specialists. aff erent nociceptive input can still be demonstrated in What we have left are those procedures which the brain; have stood the test of time for surgical anesthesia. For 6) Th e fact that the neurophysiological changes as- the most part, these were the nerve blocks that were not sociated with pain may increase or decrease the nerves’ overly demanding from a technical viewpoint and were fi ring threshold, suggesting that even in the present of reasonably safe to perform. Many of these techniques sub-blocking concentrations, there is the possibility that also have clinical utility as diagnostic nerve blocks. Th ese the sensitized aff erent nerves will stop fi ring; techniques are summarized in Table 2. Th e more com- 7) Th e fact that modulation of pain transmission at monly used diagnostic nerve blocks are discussed below. the spinal cord, brainstem, and higher levels is known to

Table 2 exist and may alter the results of even the most carefully Common diagnostic nerve blocks performed diff erential neural blockade; and Neuroaxial blocks: epidural, subarachnoid 8) Th e fact that there are signifi cant behavioral Peripheral nerve blocks: greater and lesser occipital, trigeminal, components to a patient’s pain, which may infl uence the brachial plexus, median, radial and ulnar, intercostal, selective subjective response the patient reports to the clinician nerve root, sciatic performing diff erential neuroaxial blockade. Intra-articular nerve blocks: facet In spite of these shortcomings, neuroaxial dif- Sympathetic nerve blocks: stellate ganglion, celiac plexus, lumbar, hypogastric plexus and ganglion impar ferential block remains a clinically useful tool to aid in 296 Steven D. Waldman the diagnosis of unexplained pain. Furthermore, there up of the fused portion of the seventh cervical and fi rst are some things that the clinician can do to increase the thoracic sympathetic ganglia. Th e stellate ganglion lies sensitivity of this technique, which include: anteromedial to the vertebral artery and is medial to 1) Using the reverse diff erential spinal or epidural the common carotid artery and jugular vein. Th e stel- block, in which the patient is given a high concentration late ganglion is lateral to the trachea and esophagus. Th e of local anesthetic, which results in a dense motor, sen- proximity of the exiting cervical nerve roots and brachi- sory, and sympathetic block, and the observation of the al plexus to the stellate ganglion makes it easy to inad- patient as the block regresses; vertently block these structures when performing stel- 2) Using opioids instead of local anesthetics, which late ganglion block, making interpretation of the results removes the sensory clues that may infl uence patient re- of the block diffi cult. sponses; Selective blockade of stellate ganglion can pro- 3) Repeating the block on more than one occasion vide the pain management specialist with useful in- using local anesthetics or opioids of varying durations, formation when trying to determine the cause of up- e.g., lidocaine versus bupivacaine or morphine versus per extremity or facial pain without clear diagnosis. By fentanyl, and comparing the results for consistency. blocking the brachial plexus(preferably by the axillary Whether or not this technique stands the test of approach) and stellate ganglion on successive visits, the time, Winnie’s admonition to clinicians that sympatheti- pain management specialist may be able to diff erenti- cally mediated pain is often underdiagnosed most cer- ate the nerves subserving the patient’s upper extremity tainly will. pain. Selective diff erential blockade of the stellate ganglion, trigeminal nerve, and sphenopalatine ganglion on Greater and lesser occipital nerve block successive visits may elucidate the nerves subserving of- Th e greater occipital nerve arises from fi bers of the dor- ten diffi cult-to-diagnose facial pain. sal primary ramus of the second cervical nerve and to a lesser extent from fi bers of the third cervical nerve [4]. Cervical facet block Th e greater occipital nerve pierces the fascia just below Th e cervical facet joints are formed by the articulations the superior nuchal ridge along with the occipital ar- of the superior and inferior articular facets of adjacent tery. It supplies the medial portion of the posterior scalp vertebrae [6]. Except for the atlanto-occipital and atlan- as far anterior as the vertex. Th e lesser occipital nerve toaxial joints, the remaining cervical facet joints are true arises from the ventral primary rami of the second and joints in that they are lined with synovium and possess third cervical nerves. Th e lesser occipital nerve passes a true joint capsule. Th is capsule is richly innervated superiorly along the posterior border of the sterno- and supports the notion of the facet joint as a pain gen- cleidomastoid muscle, dividing into cutaneous branches erator. Th e cervical facet joint is susceptible to arthritic that innervate the lateral portion of the posterior scalp changes and trauma caused by acceleration-deceleration and the cranial surface of the pinna of the ear. injuries. Such damage to the joint results in pain sec- Selective blockade of greater and lesser occipi- ondary to synovial joint infl ammation and adhesions. tal nerves can provide the pain management special- Each facet joint receives innervation from two ist with useful information when trying to determine spinal levels. Each joint receives fi bers from the dorsal the cause of cervicogenic headache. By blocking the at- ramus at the same level as the vertebra as well as fi bers lantoaxial, atlanto-occipital, cervical epidural, cervical from the dorsal ramus of the vertebra above. Th is fact facet, and greater and lesser occipital nerve blocks on has clinical importance in that it provides an explana- successive visits, the pain management specialist may tion for the ill-defi ned nature of facet-mediated pain be able to diff erentiate the nerves subserving the pa- and explains why the branch of the dorsal ramus aris- tient’s headache. ing above the off ending level must often also be blocked to provide complete pain relief. At each level, the dorsal Stellate ganglion block ramus provides a medial branch that wraps around the Th e stellate ganglion is located on the anterior surface convexity of the articular pillar of its respective verte- of the longus colli muscle. Th is muscle lies just anterior bra and provides innervation to the facet joint. Selective to the transverse processes of the seventh cervical and blockade of cervical facet joints can provide the pain fi rst thoracic vertebrae.[5]. Th e stellate ganglion is made management specialist with useful information when Diagnostic and Prognostic Nerve Blocks 297 trying to determine the cause of cervicogenic headache to ultimately synapse on the celiac ganglia. Th e greater, and/or neck pain. By blocking the atlantoaxial, atlanto- lesser, and least splanchnic nerves provide the major occipital, cervical epidural, and greater and lesser occip- preganglionic contribution to the celiac plexus. Th e ital nerve blocks on successive visits, the pain manage- greater splanchnic nerve has its origin from the T5–T10 ment specialist may be able to diff erentiate the nerves spinal roots. Th e nerve travels along the thoracic para- subserving the patient’s headache and/or neck pain. vertebral border through the crus of the diaphragm into the abdominal cavity, ending on the celiac ganglion of Intercostal nerve block its respective side. Th e lesser splanchnic nerve arises Th e intercostal nerves arise from the anterior division from the T10–T11 roots and passes with the greater of the thoracic paravertebral nerve [7]. A typical inter- nerve to end at the celiac ganglion. Th e least splanchnic costal nerve has four major branches. Th e fi rst branch nerve arises from the T11–T12 spinal roots and passes is the unmyelinated postganglionic fi bers of the gray through the diaphragm to the celiac ganglion. rami communicantes, which interface with the sympa- Interpatient anatomical variability of the celiac thetic chain. Th e second branch is the posterior cutane- ganglia is signifi cant, but the following generalizations ous branch, which innervates the muscles and skin of can be drawn from anatomical studies of the celiac gan- the paraspinal area. Th e third branch is the lateral cu- glia. Th e ganglia vary in number from one to vefi and taneous division, which arises in the anterior axillary range in diameter from 0.5 to 4.5 cm. Th e ganglia lie an- line. Th e lateral cutaneous division provides the major- terior and anterolateral to the aorta. Th e ganglia located ity of the cutaneous innervation of the chest and ab- on the left are uniformly more inferior than their right- dominal wall. Th e fourth branch is the anterior cutane- sided counterparts by as much as a vertebral level, but ous branch supplying innervation to the midline of the both groups of ganglia lie below the level of the celiac chest and abdominal wall. Occasionally, the terminal artery. Th e ganglia usually lie approximately at the level branches of a given intercostal nerve may actually cross of the fi rst lumbar vertebra. the midline to provide sensory innervation to the con- Postganglionic fi bers radiate from the celiac tralateral chest and abdominal wall. Th is fact has spe- ganglia to follow the course of the blood vessels to in- cifi c import when utilizing intercostal block as part of nervate the abdominal viscera. Th ese organs include a diagnostic workup for the patient with chest wall and/ much of the distal esophagus, stomach, duodenum, or abdominal pain. Th e 12th nerve is called the subcos- small intestine, ascending and proximal transverse co- tal nerve and is unique in that it gives off a branch to lon, adrenal glands, pancreas, spleen, liver, and biliary the fi rst lumbar nerve, thus contributing to the lumbar system. It is these postganglionic fi bers, the fi bers aris- plexus. ing from the preganglionic splanchnic nerves, and the Selective blockade of intercostal and/or sub- celiac ganglion that make up the celiac plexus. Th e dia- costal nerves thought to be subserving a patient’s pain phragm separates the thorax from the abdominal cav- can provide the pain management specialist with use- ity while still permitting the passage of the thoracoab- ful information when trying to determine the cause of chest wall and/or abdominal pain. By blocking the inter- dominal structures, including the aorta, vena cava, and costal nerves and celiac plexus on successive visits, the splanchnic nerves. Th e diaphragmatic crura are bilateral pain management specialist may be able to diff erenti- structures that arise from the anterolateral surfaces of ate which nerves are subserving the patient’s chest wall the upper two or three lumbar vertebrae and disks. Th e and/or abdominal pain. crura of the diaphragm serve as a barrier to eff ectively separate the splanchnic nerves from the celiac ganglia Celiac plexus block and plexus below. Th e sympathetic innervation of the abdominal viscera Th e celiac plexus is anterior to the crus of the originates in the anterolateral horn of the spinal cord diaphragm. Th e plexus extends in front of and around [8]. Preganglionic fi bers from T5–T12 exit the spinal the aorta, with the greatest concentration of fi bers ante- cord in conjunction with the ventral roots to join the rior to the aorta. With the single-needle transaortic ap- white communicating rami on their way to the sym- proach to celiac plexus block, the needle is placed close pathetic chain. Rather than synapsing with the sympa- to this concentration of plexus fi bers. Th e relationship thetic chain, these preganglionic fi bers pass through it of the celiac plexus to the surrounding structures is as 298 Steven D. Waldman follows: Th e aorta lies anterior and slightly to the left of • Do analyze the information obtained from diag- the anterior margin of the vertebral body. Th e inferior nostic nerve blocks in the context of the patient’s vena cava lies to the right, with the kidneys posterolat- history, physical, laboratory, neurophysiological, eral to the great vessels. Th e pancreas lies anterior to and radiographic testing. the celiac plexus. All of these structures lie within the • Don’t over-rely on information obtained from di- retroperitoneal space. Selective blockade of the celiac agnostic nerve blocks. plexus can provide the pain management specialist with • Do view discordant or contradictory informa- useful information when trying to determine the cause tion obtained from diagnostic nerve blocks with of chest wall, fl ank, and/or abdominal pain. By block- skepticism. ing the intercostal nerves and celiac plexus on succes- • Don’t rely on information obtained from diagnos- sive visits, the pain management specialist may be able tic nerve block as the sole justifi cation to proceed with invasive treatments. to diff erentiate which nerves are subserving the patient’s • Do consider the possibility of technical limita- pain. tions that reduce the ability to perform an accu- Selective nerve root block rate diagnostic nerve block. • Do consider the possibility of patient anatomical Improvements in fl uoroscopy and needle technology variations that may infl uence the results of diag- have led to increased interest in selective nerve root notic nerve blocks. block in the diagnosis of cervical and lumbar radicular • Do consider the presence of incidence pain when pain. Although selective nerve block is technically de- analyzing the results of diagnostic nerve blocks. manding and requires resources that may not be avail- • Don’t perform diagnostic nerve blocks in patients able in many settings, the technique may help identify who are not currently having the pain you are the reason behind the patient’s pain complaint. Th e use trying to diagnose. of selective nerve root block as a diagnostic or prognos- • Do consider behavioral factors that may infl uence tic maneuver must be approached with caution because, the results of diagnostic nerve blocks. due to the proximity of the epidural, subdural, and sub- • Do consider that patients may premedicate them- arachnoid spaces, it is very easy to inadvertently place selves prior to diagnostic nerve blocks. local anesthetic into these spaces when intending to block a single cervical or lumbar nerve root. Th is error is not always readily apparent on fl uoroscopy, given the References small amounts of local anesthetic and contrast medium [1] Dawson DM. Carpal tunnel syndrome. In: Entrapment neuropathies, used. 3rd ed. Philadelphia. Lippincott-Raven; 1990. P. 53. [2] Griffi th HR, Johnson E. Th e use of curare in general anesthesia. Anes- thesiology 1942;3:418–20. [3] Pitkin G. Controllable spinal anesthesia. Am J Surgery 1928;5:537. Pearls [4] Waldman SD. Greater and lesser occipital nerve block. In: Atlas of interventional pain management, 2nd ed. Philadelphia: Saunders; 2004. p. 23. • Th e use of nerve blocks as part of the evaluation [5] Waldman SD. Stellate ganglion block. In: Atlas of interventional pain of the patient in pain represents a reasonable next management, 2nd ed. Philadelphia: Saunders; 2004. p. 104. [6] Waldman SD. Cervical facet block. In: Atlas of interventional pain man- step if a careful targeted history and physical ex- agement, 2nd ed. Philadelphia: Saunders; 2004. p. 125. [7] Waldman SD Intercostal nerve block. In: Atlas of interventional pain amination and available radiographic, neurophys- management, 2nd ed. Philadelphia: Saunders; 2004. p. 241 iological, and laboratory testing fail to provide a [8] Waldman SD. Celiac plexus block. In: In: Atlas of interventional pain management, 2nd ed. Philadelphia: Saunders; 2004. p. 265. clear diagnosis. [9] Winnie AP, Collins VJ. Th e pain clinic. I: Diff erential neural blockade in pain syndromes of questionable etiology. Med Clin North Am • Th e overreliance on a prognostic nerve block as 1968;52:123–9. the sole justifi cation to perform an invasive or neurodestructive procedure can lead to signifi - cant patient morbidity and dissatisfaction. Guide to Pain Management in Low-Resource Settings

Chapter 39 Post-Dural Puncture Headache

Winfried Meissner

Case report Dr. Adewale’s diff erential diagnoses were intracranial hematoma, meningitis, or cerebral malaria. Mr. Lehmann, an expatriate, works for Bilfinger & However, there was no CT available in this hos- Berger, a large construction company in Nigeria. For pital. Mr. Lehmann asked for referral back to Abuja, a knee arthroscopy, he received an uneventful spinal where he was based, but Dr. Adewale recommended anesthesia in the company’s hospital. He recovered referral to the nearest teaching hospital for a CT scan. quickly, so he decided to travel to a business meet- However, there was no ambulance immediately avail- ing the next afternoon, although a light headache oc- able, so the patient was kept under observation and curred at noon. On the way to Kano the headache in- clinically monitored. Finally, while admitting the pa- creased in intensity, and only a reclining position gave tient to the ward, the head nurse Betty Hazika noticed Mr. Lehmann any relief. the dressing on his knee and realized the complete med- When Mr. Lehmann arrived in Kano, the ical history. When she informed Dr. Adewale about her headache was so intense that he felt very unwell. He fi nding, he successfully contacted the anesthesiologist in vomited once and was unable to walk. His driver Abuja, who confi rmed that he “might have nicked the could not contact the doctor at Bilfinger & Berger, so dura a touch.” Th ey diagnosed a post-dural puncture they decided to go to the nearest local hospital. Lehm- headache (PDPH) and decided to monitor the patient ann was seen by the on-call physician, Dr. Adewale; for 2 days. As per guidelines in the hospital, Mr. Lehm- however, as Lehmann did not know about the possible ann was given paracetamol, lots of fl uid (which was association between spinal anesthesia and headache, very annoying to the patient because the headache se- he did not mention it. On the other hand, Dr. Adewale verely restricted walking to the toilet), and Betty added only examined Lehman’s head and neck—so he missed some herbal medicines of her own (the latter not in the the wound dressing (and because Lehmann could not hospital guidelines). walk due to his headache, Dr. Adewale could not no- By evening next day, the headache decreased, tice his limping). and Mr. Lehmann recovered well. As he was very Th e following features were documented: Slightly pleased by the care of the nurse, he associated her increased body temperature, increase of headache when herbal treatment with his recovery, and he recom- bending the neck (imitating meningism), otherwise nor- mended it to all his colleagues as a treatment for mal neurological status. hangover!

Do any risk factors increase the likelihood of PDPH? Th e incidence is higher in young patients, during preg- Fig. 1. (A) Quincke needle, (B) pencil-point needle, (C) ballpoint needle. nancy, or with complicated or repeated punctures, and it also depends on the diameter and type of needles (see below). Incidence is decreased if the puncture is Natural course and management performed in a lateral instead of sitting position, and if saline is used instead of air for the loss-of-resistance What is the natural course of PDPH? technique during the epidural. Th e experience of the In most cases, PDPH is self-terminating. Normally, pa- anesthetist has also been shown to inﬂ uence the inci- tients recover spontaneously after 4–6 days. However, dence of PDPH. some cases might last longer, with severe symptoms.

What are diff erential diagnoses of PDPH? How do you manage a case of PDPH? Although the clinical symptoms, together with the his- As PDPH is usually self-terminating, and in most cas- tory of neuraxial puncture, usually allow a straightfor- es a reclining position, oral rehydration, and plenty of ward diagnosis, there are important diff erential diag- patience constitute the best therapy. Overall, clinical noses such tension headache and migraine, and in the guidelines do not off er much, since a number of diff er- case of postpartum women, eclampsia has to be kept ent approaches to treat PDPH have been suggested and in mind. Other possible, but rare, life-threatening dif- are used in diff erent institutions, but only very few of ferential diagnoses are intracranial venous thrombosis, them may be considered evidence-based. meningitis, and subdural hematoma. Symptoms such Bed rest is the most frequent recommenda- as focal neurological defi cits, headache independent tion; however, duration of headache does not seem Post-Dural Puncture Headache 301 to be decreased by bed rest, which could be consid- When should you perform ered purely a symptomatic treatment. Treatment with an epidural blood patch? nonopioid analgesics such as paracetamol (acetamino- As postdural puncture headache is self-limiting in most phen) or other drugs such as caff eine, sumatriptan, or cases, and as EBP is not without risks (see above), it is fl unarizine is poorly supported by scientifi c evidence. recommended only if headache is very incapacitat- Th e same is true for fl uid “therapy.” A recent study sup- ing and it interferes with the patient’s recovery or as in ported the use intravenous theophylline (200 mg the- the case of postpartum females, it prevents them from ophylline in 100 mL 5% dextrose over 40 minutes). breastfeeding or bonding with their child. Being poorly Th e only treatment that has proved to be at mobile or bedridden also increases the incidence of a least partly eff ective is the epidural injection of blood deep vein thrombosis and fatal pulmonary emboli. known as an “epidural blood patch” (EBP). Th e best results from studies indicate that with the correct in- Are there any dangerous complications of dication, a blood patch might terminate PDPH in one PDPH if unrelieved by an epidural blood patch? out of fi ve patients. After repeated blood patching, A rare complication of an untreated PDPH is a subdural this number might increase to more than a 90% suc- hematoma due to traction on cerebral veins. An infre- cess rate. It is used if symptomatic treatment fails, the quent, indirect complication is a deep vein thrombosis intensity of pain is high, and the patient is severely due to bed rest, as mentioned above. incapacitated. Th is method is especially relevant in postpartum females if they are unable to breastfeed or Pearls of wisdom bond with their babies. However, there is no consent on the optimal time of neither an EBP nor the amount • Diagnostic criteria: postural headache shortly af- of blood that should be used. As EBP may cause even ter neuraxial puncture (spinal or accidental dural more complications (see below) and as a PDPH is un- puncture during an epidural). pleasant but very often self-limiting and rarely life- • Diff erential diagnoses: any other forms of head- threatening, the indication to perform an EBP should ache (tension headache, migraine), intracranial be made with precaution and performed by experi- hematoma and venous thrombosis, meningitis, enced, senior staff . and in case of postpartum females, eclampsia. Al- ways check for focal neurological defi cits, head- How do you perform an epidural blood patch? ache independent of upright position, neck stiff - Basically, an EBP is performed in the same way as an ness, fever, blurred vision, confusion, vomiting, epidural anesthesia. Instead of injecting a local anes- and photophobia. thetic drug, 10–20 mL of the patient’s blood, imme- • With a history of neuraxial puncture with typical diately drawn, is used. You need two persons for the symptoms, no further laboratory work or radiol- procedure itself and, if available, a third person assist- ogy examination is necessary. ing. One person performs the epidural, often one seg- • Treatment: reclining or supine position, oral fl u- ment below or above the former insertion site. Th e sec- ids (but not too much); consider EBP only if the ond person draws the blood immediately after the fi rst headache severely interferes with the patient’s person has identifi ed the epidural space under absolute daily life and an experienced team is available. aseptic conditions (surgical skin disinfection, sterile Balance the risks of EBP and the normal sponta- gloves, gown, mask) from an easily accessible vein and neous relief of postdural puncture headache with- passes the syringe with the blood to the fi rst person for in 3 to 7 days. epidural injection. • PDPH persisting for more than 1 week should be Possible complications include all problems as- an indication for EBP. sociated with an epidural, such as infection, hematoma, and nerve damage, and, of course, another perforation References of the dura and a subsequent CSF leak. Th erefore, and [2] Sprigge JS, Harper SJ. Accidental dural puncture and post dural punc- because the fact that PDPH has occurred might indicate ture headache in obstetric anesthesia: presentation and management: a diffi cult puncture conditions, blood patching should be 23-year survey in a district general hospital. Anaesthesia 2008;63:36–43. [1] Th ew M, Paech MJ. Management of postdural puncture headache in performed only by experienced clinicians! the obstetric patient. Curr Opin Anaesthesiol 2008;21:288–92.

Guide to Pain Management in Low-Resource Settings

Chapter 40 Cytoreductive Radiation Th erapy

Lutz Moser

What is the current status What is the signifi cance of of radiotherapy services radiotherapy in pain? in low- and middle-income Th e effi cacy of radiotherapy applies mostly to cancer-re- countries? lated pain. Palliative care improves the quality of life of External-beam radiotherapy can be delivered by linear patients by providing pain and symptom relief from di- accelerators or cobalt teletherapy units. Cobalt units are agnosis to the end of life (according to the World Health more robust and less prone to external infl uences like Organization). Th e principal aim is to alleviate the pa- unstable electricity supply. Even though radiotherapy tient’s symptoms. is one of the most cost-eff ective forms of cancer treat- Pain control in patients with cancer represents a sig- ment, there is an undersupply of radiotherapy facilities nifi cant aspect of radiation therapy practice worldwide. especially in Africa and Asia. Th is problem is due to the Radiation therapy is one of the most eff ective, and often high initial capital investment in equipment and spe- the only, therapeutic option to relieve pain caused by cially designed buildings and in technical maintenance, nerve compression or infi ltration by malignant tumor equipment replacement, and permanent access to en- or pain from liver and bone metastases, and it provides gineering support. Th erefore, radiotherapy facilities are successful palliation of dysphagia caused by esophageal restricted to metropolitan centers such as the capital carcinoma and of pain due to pancreatic cancer. cities of these countries. Many countries in Africa do not have radiother- What is the effi cacy of radiotherapy apy facilities at all. The availability of radiotherapy in pain due to bone metastasis? services differs in the other countries from 1 machine per 126,000 people (Egypt) to 1 machine per 70 mil- In about 50–80% of patients, symptoms from bone me- lion people (Ethiopia). West Africa has the poorest tastases manifest as skeletal or neuropathic pain, path- supply of radiotherapy equipment, with 1 unit per 24 ological fractures, hypercalcemia, nerve root damage, million people. In Asia the distribution ranges from and spinal cord compression. Th e most common symp- no facility in some states, to 1 machine per 11 mil- tom of skeletal metastases is pain, present in the major- lion people (Bangladesh), to 1 machine per 807,000 ity of patients with metastatic bone lesions. Typically, people (Malaysia). the pain is slowly progressive over days to weeks and

Guide to Pain Management in Low-Resource Settings

Chapter 41 Th e Role of Acupuncture in Pain Management

Natalia Samoilova and Andreas Kopf

Case report Basic concepts Mansur, aged 37, with acute back pain radiating to the Why has acupuncture become left leg, has come to you for medical advice. He has an so popular for pain management? acute radicular pain syndrome, without evidence of Acupuncture, as an alternative treatment for pain any major neurological defi cit (bladder/ bowel incon- management, is becoming popular. Th e main reason tinence, loss of sensitivity, or muscle paralysis). You ex- is growing evidence on the eff ectiveness of acupunc- plain to Mansur that currently there is no indication ture, even though studies on effi cacy (e.g., specifi city for surgery as long as sensation and muscle function of standard acupuncture points compared to needling are not impaired. A conservative treatment is planned. sham points) have shown contradictory results. A low Because of the etiology of the pain, epidural steroids rate of adverse events and a high degree of patient sat- and systemic anticonvulsants would be the fi rst thera- isfaction are other main arguments for the growing use peutic option, but there is no anesthesiologist trained of acupuncture in Western countries. Another reason in epidurals, and anticonvulsants are not available. could be that the framework of traditional Chinese Simple analgesics like diclofenac and tramadol are medicine (TCM) regards the human body as “whole,” tried, initially, but they do not relieve the pain, and rather than a complex of individual symptoms. Th ere Mansur comes back complaining about inability to is a strong tendency toward the biopsychosocial model walk and sit for longer periods of time. You decide to of pain management, an idea that has become an inte- try acupuncture. Certain acupuncture points have to gral part of modern pain management. Another reason be chosen according to the symptoms and the underly- is that in small remote hospitals with a limited supply ing disease: of drugs, acupuncture sometimes remains one of the First, acupuncture points at the site of pain are few possible methods of treatment to provide pain treated: B40 and B60, then Du-mai 26. relief. Also, acupuncture maybe a reasonable alterna- After that painful points are chosen: B2, B24, tive in patients with contraindications to various drugs B52, B54, B36, GB30, and GB34. Th e needles are left in or who are intolerant of side eff ects, or in situations place for 10–20 minutes every day for a week, then ev- where drugs are not aff ordable. When used in a ratio- ery other day for 2 weeks. Luckily, over the 3 weeks of nal way and as part of a comprehensive pain manage- treatment, the symptoms decline, allowing Mansur al- ment program, acupuncture can be eff ective, especially most complete range of motion and mobility. if the patient is receptive toward it. Another advantage

Medical treatment starts with the analysis of the entire Qi of the channels rise close to the surface of the body. system, and then focuses on the correction of patho- Twelve main channels have been described, six of which logical changes through readjusting the functions of are yin and six which are yang, and numerous minor the Zang-Fu organs. Evaluation of a syndrome not only channels, which form a network of energy channels includes the cause, mechanism, location, and nature throughout the body. Each meridian is related to, and of the disease, but also the confrontation between the named after, an organ or function. Th e main meridians pathogenic factor and the body’s resistance. Th erefore, are lung, kidney, gallbladder, stomach, spleen, heart, two people with an identical disease might be treated in small intestine, large intestine, gallbladder, urinary blad- diff erent ways, and on the other hand, diff erent diseases der, san jiao (“triple warmer”) and pericardium. It is be- may result in the same syndrome and be treated in simi- lieved that when Qi fl ows freely through these merid- lar ways. Th is is true for some chronic diseases. Pain can ians, the body is balanced and healthy, but if the energy be simply interpreted as a Qi stagnation and be treated becomes blocked, stagnant, or weakened, it can result in pragmatically, with Chinese orthopedic acupuncture. physical, mental, or emotional ill health. TCM also focuses on the “balance” within the patient. According to this view, an imbalance in a per- What does a meridian look like? son’s body can result from inappropriate emotional re- A meridian does not follow conventional anatomical sponses such as excess anger, overexcitement, self-pity, structures, and the designation of meridians is only un- deep grief, or fear. Environmental factors such as cold, derstandable in the context of TCM. Th e nomenclature damp/humidity, wind, dryness, and heat can also cause follows a certain logic in this context. Th e localization of imbalance, as do factors such as wrong diet, too much meridians (and acupuncture points) may diff er depend- sex, overwork, and too much exercise. To restore the ing on the literature resource (which is also true among balance, the acupuncturist stimulates the acupunc- practitioners in China). ture points that will counteract that imbalance. In this way, acupuncture is believed to rebalance the energy How are the various acupuncture points classifi ed? system and restore health or prevent the development of disease. Th e earliest written account of this system Although locations and functions of acupuncture points is found in the Nei Jing (Th e Yellow Emperor’s Classic may vary according to diff erent authors, the main struc- of Internal Medicine). Th is document is believed to be ture of classifi cation is rather uniform. First of all, acu- from around 200 BCE to 200 CE and is one of the oldest puncture points are situated along 12 “organ-related” comprehensive medical text books. meridians; then there are eight extraordinary meridians in acupuncture that are considered to be reservoirs sup- What is the idea behind the acupuncture points? plying Qi and blood to the 12 regular channels. Dotted As described, the idea of harmony and balance is very along these meridians are more than 400 acupuncture important in acupuncture. Th e concept that underlies points, which have been also classifi ed by the World balance is the opposing principles of yin and yang. Th e Health Organization. Th ese are listed by name, num- principle that each person is governed by opposing, but ber, and the meridian to which they belong. Besides the complementary, forces of yin and yang, is central to all classifi cation, we fi nd by experience that points on the Chinese thought. Yin and yang are the opposites that same meridian may have common eff ects. Another type make the whole. Th ey cannot exist without each other, of acupuncture points are the “extra points.” Th ey have and a situation or person could neither be 100% yin nor specifi c names and defi nite locations, but are not attrib- 100% yang. Life is possible only because of a balanced uted to the meridians. Th ey may be selected in certain interplay between these forces. diseases. Ashi points (“tender spots”) are often used in According to TCM, these complementary forc- patients with acute pain syndromes. Local tenderness es of yin and yang infl uence the life energy or Qi (pro- when manually palpating the patients identifi es an Ashi nounced “she”). Qi is thought to circulate throughout point. Th erefore, these points have no specifi c names the body in invisible channels (other translations of the and defi nite locations. Ashi points are considered to Chinese term jing luo include “conduit” and “meridian”). represent the earliest stage of acupuncture point evolu- Th e acupuncture points (or holes, as the Chinese term tion in China and may be also considered as appropriate xue is more aptly translated) are the locations where the acupuncture points for a physiological pain approach to 310 Natalia Samoilova and Andreas Kopf

Small Intestine

Stomach Bladder

Heart

YANG YANG YIN

Spleen

(Image courtesy of John F. Th ie, DC, from his book entitled Touch for Health) acupuncture. But in the original (Chinese) approach to puncture into a simplifi ed acupuncture point selection acupuncture, the points that the practitioner chooses for practical use. Th is strategy would allow the clinician may not necessarily be at the site of the pain. to use acupuncture without becoming a specialist with extensive training in clinical practice. Th e authors are How is this very diff erent medical philosophy well aware that such an approach will be challenged by on disease incorporated into Western traditional acupuncturists, but scientifi c evidence may medical concepts? allow such a simplifi ed approach to acupuncture. From the frequent use of quotation marks, it should be obvious that acupuncture is not easily transferred How are the eff ects of acupuncture explained or translated into the Western concept of medicine. It with modern (patho)physiological knowledge? should therefore be noted that the oriental defi nitions Historically, acupuncture points were believed to be and terms do not necessarily refl ect a physiological view, “holes that allow entry” into the meridians or chan- but a concept that was developed without the knowledge nels to allow alteration of “energy fl ows.” Th ese holes of modern physiology by observing and describing. A provide, in traditional Chinese acupuncture, a gateway great number of diff erent schools for acupuncture exist, to infl uence, redirect, increase, or decrease the body’s using diff erent point localizations and point selections. vital substance, Qi, thus correcting many of the imbal- Hence it is not possible to interpret acupuncture and re- ances mentioned earlier. Th ese traditional Chinese con- defi ne it into a pragmatic pain approach. cepts may be irrelevant to understand the impact of Recent large-scale studies in Germany have acupuncture, since modern physiological research has added a lot to this discussion by showing that acu- been able to demonstrate that acupuncture does have a puncture per se, but not the strict following of classical neuromodulatory eff ect on parts of the peripheral and traditional Chinese rules for acupuncture point selec- central nervous system and on neurotransmitters. Th ese tion, is eff ective in treating pain. Th erefore, it may be eff ects do not seem to be acupoint-specifi c and are at a pragmatic solution to adapt traditional Chinese acu- least partly a psychophysiological phenomenon. Some Role of Acupuncture in Pain Management 311 important analgesic and other eff ects of acupuncture (VAS) for pain intensity, the duration and character of include central release of endorphins, serotonin, nor- pain, and the patient’s psychological/emotional status epinephrine, GABA, and neurokinin A, among other and motivation for treatment. Various tests and ques- substances. Th ere is some evidence of activation of tionnaires for the defi nition of the pain may be used if the descending inhibitory system and activation of appropriate, as discussed in the respective chapters. segmental and heterosegmental inhibitory systems at the spinal level (diff use noxious inhibitory controls). How do we treat the acupuncture points? Other supraspinal mechanisms involved in acupunc- Acupuncture needles are extremely thin and can of- ture analgesia have been found in the limbic system ten penetrate the skin with no pain at all. Some areas (aff ective processing of pain stimuli), the secondary may be more sensitive and feel like a small pinch as the somatosensory cortex, and the hypothalamus. Local needle in inserted, but that lasts for less than a second. eff ects of acupuncture include release of substance P Once the needles are in place, there should be no pain, and calcitonin gene-related peptide (CGRP), which in- but only a sensation of dull pressure (known as a “De creases local perfusion, and a local twitch response of Qi feeling”) refl ecting activation of A-beta fi bers. Th e the muscles followed by relaxation when trigger points acupuncturist will simultaneously feel that the needle is are used for acupuncture. Interestingly, a high propor- “tightened.” tion of identifi ed muscular trigger points coincide with Acupuncture is an extremely safe medical pro- Chinese acupoints. cedure when performed by a qualifi ed practitioner. Needles are presterilized, stainless steel, single-use, and Acupuncture in pain management disposable. Acupuncture needles are usually 0.3 mm wide (30 Gauge) and 1–2 inches long (3–6 cm). Appli- What is more eff ective in the management cation of the needle may be done with the patient in any of chronic pain? position, as long as the patient feels comfortable and is As always, specialists are convinced that their own relaxed, but it would be clearly advisable to use the su- method is superior, and therefore acupuncturists tend pine position during treatment because a minority of to see acupuncture as a panacea (cure-all). Neverthe- patients might get a feeling of dizziness. Th e acupunc- less, experienced pain therapists who use acupuncture ture needles are held between thumb, index fi nger, and and go through a thorough training would use a more middle fi nger, with the needle parallel to the index fi n- sophisticated view: creating an antagonism between ger. Th e needle should be inserted quickly to minimize these two approaches of acupuncture and conven- painful sensations. Th e angle of insertion is usually be- tional pain management would be counterproductive tween 60 and 90 degrees. Depending on the region, the for acupuncture in the long run, since its eff ects are depth of insertion is usually between 0.5 and 5 cm. Th e considerable but not overwhelming. Th erefore, pain needles are usually left in situ for 15–30 minutes. Dur- specialists are trying to incorporate acupuncture as a ing this time the needles may be manipulated to achieve complementary technique into regular pain manage- the eff ect of toning or sedating the Qi, according to the ment as one module together with manual therapy, situation. Needle manipulations generally involve lifting, therapeutic exercises, and psycho- and pharmacother- thrusting, twisting, and rotating, according to treatment apy within a therapeutic, rehabilitative, and preventive specifi cations for the health problem. Th in needles are management complex. inserted into these acupoints.

What do we use for diagnosing and evaluating What are the complications and side eff ects pain if we want to use acupuncture? of acupuncture? Using acupuncture does not eliminate the need for If the practitioner is adequately qualifi ed, side eff ects thorough history taking, a physical examination of the and complications are rarely observed. Care must be patient, as well as laboratory and functional diagnostics. taken in certain regions in the body where vulnerable Before applying acupuncture, a proper diagnosis should structures are close to the skin, such as the lung in the be established, and it should be decided if acupuncture thoracic area or superfi cial blood vessels and nerves, or another mode of therapy is more promising. Pain is none of which should be needled. Hence, basic knowl- assessed, as always, by using the visual analogue scale edge of anatomy is essential. 312 Natalia Samoilova and Andreas Kopf What about the costs of acupuncture? worth using in a simplifi ed and pragmatic way, since the Due to the increase in popularity of acupuncture, acu- true eff ects of acupuncture may be the result of coun- puncture needles are now widely available. Costs may terirritation and modulation of central nervous sensitiv- vary, but have to be set in relation to the savings from ity and not strictly dependent on the classical concepts using less or shorter-lasting pharmacotherapy. Depend- of acupuncture point selection. However, this concept is ing on the wholesale merchant, a box of hundred nee- not widely recognized, and existing scientifi c literature dles may cost around US$5–10. has not evaluated this pragmatic approach. Since the technique of needle placement is sim- Is it possible to treat pain with acupuncture ple and acupuncture needles are widely available and in all patients? relatively inexpensive, it would be a pity if acupuncture Th eoretically, all patients may benefi t from acupunc- would not be used because of the lack of adequate train- ture, but studies have only been able to show—so far— ing facilities. Nevertheless, at least some practical and evidence for selected syndromes. Acupuncture should theoretical training as well as anatomical knowledge are never be used—after adequate Western medicine di- indispensable to make acupuncture an eff ective and safe agnosis—as the exclusive method of treatment, since it pain management technique. might prevent patients, such as cancer patients, from In situations where even the minimum train- receiving other eff ective treatments. ing is not available, it is advisable to replace the needling Typical syndromes where acupuncture is eff ec- technique by acupressure with superfi cial point stimula- tively used are the following: tion, such as by using small wooden sticks. A recent Co- • Headache (e.g., migraine, tension-type headache chrane review (Furlan et al. [1]) suggests the eff ective- • Low back pain ness of acupuncture point massage. • Neck pain Step one: Other indications with less proven eff ectiveness include: Always start with “distant” points to activate the diff er- • Osteoarthritis ent antinociceptive systems, and choose from the fol- • Visceral pain syndromes lowing empirical locations for analgesia (ipsi- and con- • Vascular ischemic pain tralateral sites): • Post-amputation pain and causalgia • ST 36 (stomach): approx. 4 cm below the patella • Chronic postsurgical and post-traumatic pain in a depression lateral to the patellar ligament, syndromes, e.g., post-thoracotomy-syndrome one fi nger width lateral from the anterior border of the tibia Does acupuncture also work in acute pain, • B 40 (urinary bladder): midpoint of the transverse such as postoperative pain? crease of the popliteal fossa, between the tendons Th ere is strong evidence from studies and meta-analysis of biceps femoris and semitendinosus that acupuncture has a role in reducing opioid-related • ST 44 (stomach): proximal to the web margin side-eff ects like nausea, vomiting and sedation. between the 2nd and 3rd metatarsal bones, in a depression distal and lateral to the 2nd metatarsal How can I perform acupuncture for pain joint without knowing complicated acupuncture • LI 4 (large intestine): middle of the 2nd metacar- point selection using the meridian system? pal bone on the radial side Th is question is diffi cult to answer. On one hand side, the • PC 6 (pericardium): approx. 3 cm above the wrist general view of acupuncture is that it may only be used if crease between the tendons of palmaris longus it is part of TCM. Th erefore, thorough training would be and fl exor carpi radialis (also good for nausea) necessary to be able to understand the fundamentally dif- • LI 11 (large intestine): at the lateral end of the ferent approach to illness and therapy concepts. Th e usu- transverse cubital crease, midway between a line al approved (basic) training courses for acupuncture in- between the radial side of the biceps brachii ten- volve more than 200 hours of theory and case seminars. don and the lateral epicondyle of the humerus On the other hand, recent studies, such as the GERAC • K 6 (kidney): in the depression below the tip of studies in Germany, suggest that acupuncture might be the medial malleolus Role of Acupuncture in Pain Management 313 • SP 6 (spleen/pancreas): approx. 4 cm directly • However, nowadays it may be more rational to above the tip of the medial malleolus on the pos- use acupuncture outside the concept of tradition- terior border of the tibia al Chinese medicine, according to the concept of In headache, use: an integrative pain management approach within • ST 44 (stomach): proximal to the web margin the biopsychosocial concept of pain. between the 2nd and 3rd metatarsal bones, in a • In particular, in pain management it seems to depression distal and lateral to the 2nd metatarsal be a worthwhile concept to combine blockades, joint pharmacotherapy, and acupuncture, as well as • GB 34 (gallbladder): in a depression anterior and physical and psychological therapy. inferior to the head of the fi bula • ST 44 (stomach): proximal to the web margin Acknowledgment between the 2nd and 3rd metatarsal bones, in a depression distal and lateral to the 2nd metatarsal Th e authors would like to thank PD Dr. D. Irnich from joint the Pain Management Center of the Ludwig Maximilian University in Munich, Germany, for his advice on pre- Step two: paring the manuscript. Choose 2–4 spots at the site of the pain (Ashi points) as acupuncture points. References

Step three: [1] Furlan AD, Imamura M, Dryden T, Irvin E. Massage for low-back pain. Cochrane Database Syst Rev 2008: CD001929. Choose 1 segmental spot corresponding with the der- [2] Madsen MV, Gøtzsche PC, Hróbjartsson A. Acupuncture treatment for matomal innervation of the painful region at the cor- pain: systematic review of randomised clinical trials with acupuncture, placebo acupuncture, and no acupuncture groups. BMJ 2009;338:3115. responding vertebral level and place the needle at the [3] Manheimer E, Linde K, Lao L, Bouter LM, Berman BM. Meta-anal- identiﬁ ed vertebral level some centimeters paraverte- ysis: acupuncture for osteoarthritis of the knee. Ann Intern Med 2007;146:868–77. brally on the aﬀ ected site. [4] Manheimer E, White A, Berman B, Forys K, Ernst E. Meta-analysis: acupuncture for low back pain. Ann Intern Med 2005;142:651–63. [5] Trinh KV, Graham N, Gross AR, Goldsmith CH, Wang E, Cameron ID, Step four: Kay T; Cervical Overview Group. Acupuncture for neck disorders. Co- chrane Database Syst Rev 2006;19:3:CD004870. Choose 2–4 mirror-like spots on the contralateral site [5] Sun Y, Gan TJ. Acupuncture for the management of chronic headache: for segmental modulation. a systematic review. Anesth Analg 2008;107:2038–47. [6] Sun Y, Gan TJ, Dubose JW, Habib AS. Acupuncture and related techniques for postoperative pain: a systematic review of randomized controlled trials. Br J Anaesth 2008;101:151–60. Pearls of wisdom

• Although there is a centuries-long history of Recommended websites acupuncture, its eﬃ cacy has to be proven in evi- www.acupuncture.com dence-based medicine. www.acupuncture.com.au • According to recent literature, there are a number www.pain-education.com of indications in pain management where acu- http://nccam.nih.gov/health/acupuncture/ puncture can be applied successfully. www.tcmpage.com/index.html www.panafricanacupuncture.org (the Pan-African Acupuncture Project, Allen Magezi, Uganda coordinator)

Planning and Organizing Pain Management

Guide to Pain Management in Low-Resource Settings

Chapter 42 Setting Up a Pain Management Program

M.R. Rajagopal

“I am interested in starting a pain service. But no one not patient- or symptom-oriented. Professionals, hence, seems interested. And there are no resources. What can have a poor concept of the need for pain relief and have I do?” is a question that comes up pretty often in devel- an unnecessary fear of analgesics, particularly of opioids. oping countries. Th e questioner is often a kind-hearted Even if they overcome this fear, often they do not know person who is interested in relieving human suﬀ ering, the fundamentals of pain evaluation and its treatment. but feels at a loss about what the next step should be. Administrators: “Opiophobia” has resulted in Th e absence of a sense of direction often results in the stringent narcotic regulations, and this too comes in the enthusiast burning out and giving up the struggle at way of access to pain relief. Besides, chronic pain is not some point. Th is chapter is aimed at providing some a “killer disease,” and so it is pushed aside in statistics useful information to any aspirant who would like to set and receives little attention. up a pain management program without burning out. Th e public: Th e public is not aware that pain relief is possible and tends to accept pain as inevitable. What are major barriers to access Th e public too, is generally afraid of the “addiction” po- to pain relief? tential of opioids. Drug availability: Th e widely prevailing fear of Lack of awareness is a major barrier to access to pain re- opioids has resulted in complicated restrictions on li- lief. It needs to be remembered that any change is likely to censing of opioids and on prescription practices. Unaf- be resisted anywhere in the world. It will need sustained fordability of drugs and other therapeutic measures is eﬀ ort to bring in a new way of thinking. Improving overall also a limiting factor. awareness is essential for overcoming such resistance. Institutional policy: Pain relief services are not Professionals: Due to lack of professional educa- often seen as lucrative, and hospitals are often reluctant tion on pain and its treatment, unfortunately, medical to invest in them. and nursing professionals often form the biggest barriers to access to pain relief. Th e explosion of knowledge What are essential components in pain physiology and management, at the present time, of service development? remains limited to developed countries. Medical education is oriented to diagnosis and cure, and pain relief is Th e following suggested scheme of action takes the not taught in most medical and nursing schools. In gen- above common barriers into consideration. It is impor- eral, the approach is disease- or syndrome-oriented and tant to remember that all three sides of the following

Education Drug Availability

Institutional Policy Setting up a Pain Management Program 319 • First, an introductory advocacy program for the Setting realistic goals: It may be prudent to start general public and professionals is needed. All with something easily achievable. If the service is part professionals in the hospital and in the neighbor- of a large department of anesthesiology that already hood should be off ered the opportunity to attend has a considerable role in postoperative management, such a program. Th e more people are sensitized, it may be easiest to start a postoperative pain manage- the better the response to your pain management program. A cancer hospital may fi nd it easiest to ment service. All the professionals involved in start with an outpatient facility for cancer pain manage- some way with the pain management program, ment. A stand-alone service may fi nd it easiest to start a including nurses, should be able to evaluate pain chronic pain service. and should understand the fundamentals of pain Multidisciplinary approach: Ideally, pain man- management. agement should be a multidisciplinary eff ort. Volun- • Second, the professionals who deliver pain care teers, social workers, nurses, general practitioners, should all have at least a few weeks’ “hands-on” anesthetists, oncologists, neurologists, psychiatrists, training such as the certifi cate course described and other specialists all have their roles to play. Howev- above. er, all these people sitting around a table to care for one • Th ird (and ideally), at least one or two members patient is an ideal that can never be achieved. It would of the team should, at the earliest opportunity, make better sense to have a system for consultations gain the level of expertise that can be obtained when necessary. At the same time, the better the inter- with a fellowship or diploma program. action is between the social worker, the nurse, and the pain therapist, the better the outcome is likely to be. What are the challenges regarding drug availability? What are the challenges regarding the goal of pain management? Matters related to opioid availability, particularly regulatory issues, have been dealt with in detail in a sepa- Quality of life as the objective: Th e goal of management rate chapter. Aff ordability of drugs is a matter of par- should be improved quality of life rather than just treat- ticular concern in developing countries. Sadly, very ment of pain as a sensation. All the symptoms of the pa- often, the most expensive medication would be avail- tient must be treated. Given that anxiety and depression able in developing countries, while the inexpensive form part of the pain problem, there should be routine drugs tend to slowly fade away and go off the market. screening of patients for psychosocial problems. Organizations such as regional chapters of Interna- Partnership with the patient and family: Suc- tional Association for Study of Pain (IASP) have a big cessful pain management would mean an essential part- role to play in infl uencing national or regional drug nership between the patient, the family, and the thera- policy so that aff ordable essential drugs are available. pist. Th e nature of the problem and treatment options Such an eff ort, for example, has resulted in availability must be discussed with the patient and family and a of a week’s supply of oral morphine for the price of a joint plan arrived at. In developing countries, lack of lit- loaf of bread in Uganda. eracy is often pointed out as the reason for not giving enough explanations to the patient. Professionals need What are the challenges regarding to remember that formal education and intelligence are institutional policy? not synonymous. Th e illiterate villager, with his experience of a hard life, is usually able to understand prob- Whether the pain service is part of a hospital or a lems very well if we remember to avoid jargon and stand-alone service, some clear policy decisions are speak in his language. And often he will be more capa- needed. If the service is successful, the demand is likely ble of making diffi cult decisions than a more sophisti- to be enormous, and soon the service will be fl ooded cated, educated patient. with patients and the service may fi nd it impossible to Aff ordability of treatment: Aff ordability of a reach all the needy. Th e following points would be use- treatment modality should be taken into consideration ful as guiding principles. when treatment options are discussed. 320 M.R. Rajagopal Incorporation of principles of palliative care: Treatment at home: Th e majority of people in What is the objective of pain management? If pain is pain in developing countries may have little access to relieved, but other symptoms such as breathlessness transportation. Hospitals seldom have enough space to or intractable vomiting persist and hence quality of take in such patients, even if the patients could aff ord life does not improve, the purpose of treatment fails. to do so, except for short periods of time. Most patients Hence, the objective should be improvement of quality will need to stay in their homes. Th e service will have of life, and not just pain relief. In developed countries, to be geared to care in the home setting. As in devel- two parallel streams of care have evolved—one man- oped countries, patients are opting to stay at home to be aging pain as a symptom and the other providing “to- treated, especially when they are terminally ill. Success- tal care.” But in the absence of such a system, the pain ful models of care using “roadside clinics” and nurse- therapist in the developing country has to play the role based home care services have been developed in coun- of a family physician too; he needs to be ready to off er tries like Uganda and India. general symptom control, and his team should be able to off er psycho-socio-spiritual support. In many occa- Pearls of wisdom sions, the involvement of a spiritual person close to the family would help decision making and make patient In conclusion, three foundation measures are necessary compliance easier. for an eff ective national program.

Governmental policy National or state policy emphasizing the need to alleviate chronic cancer pain through education, drug availability, and governmental support/endorsement. Th e policy can stand alone, be part of an overall national/state cancer control program, be part of an overall policy on care of the terminally ill, or be part of a policy on chronic intractable pain.

Education Drug availability Public health-care professionals Changes in health care (doctors, nurses, pharmacists), regulations/legislation to others (health care improve drug availability policy makers/administrators, (especially opioids) drug regulators) Improvements in the area of prescribing, distributing, dispensing, and administering drugs Guide to Pain Management in Low-Resource Settings

Chapter 43 Resources for Ensuring Opioid Availability

David E. Joranson

Th e purpose of this chapter is to provide perspective Case 1 and tools that you can use to make opioid analgesics A patient was initially given radiotherapy for her pain, more available and accessible for the treatment of your but it was not eﬀ ective as the disease progressed. Next patients’ pain. she was given a weak pain-relieving medication, but her Th e availability of opioid analgesics depends on the pain continued to worsen. Finally, she returned to the system of drug control laws, regulations, and distribu- doctor in excruciating pain requesting medication that tion in your country. Unless this system is able to safely would end her life. She was given another weak pain distribute controlled medicines according to medical medication along with antidepressants and sent home. needs, clinicians will be unable to use opioid analgesics She committed suicide. [Pain & Policy Studies Group] to relieve moderate to severe pain according to international health and regulatory guidelines and standards of Case 2 modern medicine. XX is a referral hospital for cancer management. Th e an- Th is chapter poses a number of questions that are nual requirement of morphine is approximately 10,000 relevant to a better understanding of how the system is tablets of 20 mg. But the Institute has not been able to supposed to function, and to identify and remove impedi- procure a single tablet … primarily due to the stringent ments to availability of opioids and patient access to pain state laws and multiplicity of licenses. After a lot of ef- relief. Th is is of utmost importance, since pain manage- fort, the Institute had been able to obtain the licenses… ment of postoperative, cancer, and HIV/AIDS pain is vir- and had approached a [manufacturer] for a supply tually impossible without the availability of opioids. Th is of tablets … the [manufacturer] did not have tablets in does not imply that opioids are indicated for every type of stock and by the time the tablets could be arranged, the pain. Opioids can be useful to treat patients with chronic licenses had expired. Th e doctors at the Institute and the pain from noncancer conditions, but the choice of thera- associated pain clinic have stopped prescribing morphine pies needs to be made on an individual basis, governed by tablets because they would not be available. [Joranson et a careful consideration of risks and beneﬁ ts of treatment. al. 2002]

Case examples Case 3 [T]here were several occasions when no morphine was Several real cases are oﬀ ered to focus this chapter on the available. Such situations normally arose as a result of critical importance of availability and access to opioid the diﬃ culties encountered when trying to obtain the analgesics for the relief of pain. required licences. At other times, manufacturers of the

Th ese cases demonstrate some of the causes and the hu- Th roughout the world every day, millions of people man impact of unrelieved severe pain when access to including older adults and children experience pain opioid analgesics is blocked. Such situations are tragic from surgery, trauma, cancer, AIDS, sickle cell ane- and never should be allowed to happen, but they do set mia, and a range of other diseases that may include the stage for this chapter that will describe a number of severe pain. Th e incidence of cancer and HIV/AIDS is resources that can be used by health professionals and shifting to low- and middle-income countries. Clini- government in low-resource settings, or anywhere else, cians understand only too well how unrelieved severe to improve availability and patient access to opioid anal- pain can destroy quality of life and sometimes even gesics such as oral morphine. the will to live. Th is chapter is based on the international studies Some—but not all—of the wealthier countries and experience of the University of Wisconsin Pain and have fairly good opioid availability, and therefore pa- Policy Studies Group (PPSG) and many collaborators. tients have access to opioid analgesics. However, the Since 1996, the PPSG has been a World Health Orga- reality is that most of the world’s population lacks ac- nization Collaborating Center (WHOCC) with terms of cess to these indispensable medicines. Lack of access reference to develop methods and resources that can be is especially serious in settings with limited resources used to improve availability and access to essential opi- and an inadequate health care infrastructure. A num- oid pain medicines. ber of organizations with an interest in pain, palliative Th e following questions and responses are intend- care, cancer, and HIV/AIDS are working to address ed to assist clinicians and advocates in their eff orts to these problems. improve patient access to pain relief. Readers are encouraged to consult the resource materials referenced Why are controlled drugs such as in the text and at the end, refer to other chapters in oral morphine important? this book, and seek expert professional guidance on specifi c questions relating to clinical pharmacology, While other chapters address this question in more de- medicine, and law. tail, it is important to note that a variety of drug and nondrug therapies, including surgical procedures, radia- What is the principle of balance? tion, and behavioral techniques, can be useful in treating pain and providing palliative care. Pain is treated Eff orts to improve opioid availability should be guided with a combination of drug and nondrug measures. Th e by the drug regulatory principle of “balance.” Balance is WHO has determined that pharmacological treatment, an internationally accepted medical, ethical, and legal including opioids and nonopioids, is the mainstay for principle stating that opioids are indispensable for relief relieving pain due to cancer and HIV/AIDS. Resources for Ensuring Opioid Availability 323 Opioids block the transmission of pain in the path- national and provincial/state regulations are more re- ways of the nervous system. Some opioids, such as strictive than is necessary and impede or completely fentanyl, morphine, hydromorphone, and oxycodo- block access, hampering the ability of pain and pallia- ne can relieve moderate to severe and escalating pain. tive care clinicians to practice modern medicine. Th ese opioid agonists lack a “ceiling eff ect” so that the Although international agreements recognize that dose can be increased to relieve increasing pain, keep- national governments may be more restrictive, regula- ing in mind side eff ects. International health and regu- tory controls over opioid analgesics are not balanced latory bodies do not recommend a maximum dose for if they interfere in legitimate medical treatment of pa- opioid analgesics. Some other opioids and nonopioid tients. Tools for assessing balance in national laws and analgesics do have a ceiling eff ect and, especially in the regulations and for bringing about change are discussed absence of opioid agonists, may be overused to try to later in this chapter. achieve an eff ect of which they are not capable. Th ere is agreement that several opioid agonists How should prescription opioid in diff erent dosage forms should be available to allow analgesics be handled safely? clinicians to change opioids, doses, and routes of administration to maximize effi cacy and minimize side Safe handling of controlled substances can prevent di- eff ects. Th e goal is to ensure the availability of these version, misuse, and injury. All those who handle con- important pain relief medicines at an aff ordable cost, trolled opioid analgesics, including manufacturers, when and where needed by patients. A number of opi- distributors, physicians, pharmacists, nurses, patients, oids are listed on the WHO and International Associa- and family members, should know and respect that tion for Hospice and Palliative Care (IAHPC) lists of opioids are to be distributed, prescribed and dispensed essential medicines. only for a medical purpose such as relief of pain or medical treatment of opioid dependence/addiction. Do opioids have a potential Controlled medicines should be used only by the perfor abuse? son for whom they are prescribed and according to the physician’s instructions. Yes, opioids do have an abuse potential and therefore It is important to keep prescribed medicines in the are “controlled” under international, national, and state original container because the label has the prescription laws and regulations. Many controlled opioids are also information that establishes in the eyes of the law the designated as essential medicines; they are safe and ef- patient’s right to possess a controlled drug. Th e label on fective—indeed indispensable—for the relief of severe the original container should have the instructions for pain. use, as well safety-related warnings. Controlled medi- Th ere is a legal tradition to classify opioids as “nar- cines should always be stored out of sight to prevent cotic drugs,” “dangerous substances,” and even as “poi- theft, and kept out of reach of children to avoid acciden- sons.” “Controlled substances” is a less stigmatizing tal ingestion. term. Th e movement of controlled substances is subject National requirements vary for returning or dispos- to government regulatory controls such as licensing, se- ing of unused or “leftover” medicines. Additional infor- cure storage, inventory, recordkeeping, and reporting mation about requirements for secure disposal and ways of procurement, storage, distribution, and dispensing. to avoid harm to others and the environment should be A medical prescription is required to provide patients obtained from the relevant government authorities. with lawful access to controlled medicines. Th e manner in which regulatory requirements are What should be done if pain administered diff ers greatly from country to country, medicines are diverted? and even from state to state and among institutions. But it should be understood that the purpose of opi- In some cases, opioid analgesics are unlawfully stolen oid regulations should not only be to prevent unau- or “diverted” from various points along the drug distri- thorized use and diversion from the supply chain. Th e bution system, and then sold for nonmedical purposes, purpose is also to ensure medical and patient access. including to abusers. Abuse of essential medicines, es- However, it has been well documented that some pecially if publicity is sensational and unbalanced, can 324 David E. Joranson lead to overreactions and more restrictions on essen- What are the reasons for tial medicines that can undermine confi dence in their inadequate availability and access? therapeutic use. When diversion occurs, the response should be quick and balanced, i.e., the person or per- Th e lack of opioid analgesics in a country is not a “sup- sons responsible should be held accountable, without ply side” problem. According to the INCB, the United interrupting patient access to pain relief. National lead- Nations’ principal regulatory body for narcotic drugs, ers in pain management and palliative care should dis- there is no insuffi ciency of raw materials for manufac- cuss balanced approaches to diversion with the govern- turing opioid medicines. Instead, the problem is the re- ment before it happens. sult of system barriers within countries that result in a low or sometimes nonexistent demand for opioids. How can I fi nd out about the opioids Th e INCB periodically surveys national govern- that are used in my country? ments, in consultation with the WHO, to explore the status of opioid availability and the reasons why they Th e PPSG has posted on its website extensive infor- are not adequately available. Governments have report- mation about the consumption trends of selected opi- ed that the following barriers contribute to the lack of oids in each country. Governments are required to re- availability of opioids in their countries: port consumption statistics to the U.N. International • Concerns about addiction; Narcotics Control Board (INCB). Th e INCB in turn • Insuffi cient training of health care professionals; provides the data to the PPSG/WHOCC. “Consump- • Regulatory restrictions on opioid manufacture, tion” means the amount of opioids that are distributed distribution, prescribing, or dispensing; by manufacturers or distributors to the retail level in • Health care professionals’ reluctance to stock opi- the country, such as to physicians, pharmacies, hos- oids because of concerns about legal sanctions. pitals, hospices, pain clinics, and palliative care pro- Th ese factors and interaction among them can act as grams. Opioid consumption statistics are an indicator a vicious circle—low national availability can lead to low of the capacity of a country to relieve moderate to se- medical use, resulting in weak demand, which in turn fos- vere pain. ters continued low availability. Insuffi cient medical edu- Th e opioid consumption trend graphs include infor- cation about pain, combined with regulatory restrictions mation for fentanyl, hydromorphone, methadone (also and exaggerated concerns about opioid analgesics and ad- considered essential for the treatment of opioid depen- diction, may conspire to maintain the status quo. Howev- dence), morphine, oxycodone, and pethidine (meperi- er, it is possible to break out of this cycle if there is leader- dine). Th ese data do not tell us which dosage forms of ship both from health professionals and government. the opioid are being consumed in a particular country. If the graphs for a country show no consumption What can the “National Competent of a particular opioid, this is an indicator that the drug Authority” do to improve may not available, or it could be a problem in report- availability and access? ing. Th e consumption statistics are updated annually by the PPSG as new data are received. Th ese statistics can Key to breaking the cycle and improving availability and be used to study the consumption trends for the strong access is the National Competent Authority (NCA). opioids in the world, a region, your country, or any Th is is an agency in every country, often located in the country. Opioid consumption statistics can be used in Ministry of Health. It is intended to be responsible for the evaluation of long-term outcomes of eff orts to im- implementing the government’s international narcot- prove availability. ics treaty obligations to ensure adequate availability of Consumption statistics can be found in the Coun- narcotic drugs for medical and scientifi c purposes. Th e try Profi les on the PPSG website. Users can download Country Profi les on the PPSG website provide contact the graphs and tables of data and use them for presenta- information for the NCA for each country. tions without special permission, with appropriate cita- Th e NCAs have been asked by the INCB to work tion. Examples of slide presentations relevant to inter- with health professionals to determine and anticipate national and national pain policy are available at http:// adequately future medical needs for opioid analgesics www.painpolicy.wisc.edu/internat/conferences.htm. so that the necessary amounts can be imported and Resources for Ensuring Opioid Availability 325 manufactured. Th e “estimates system” administered by drug control laws and regulations, how these are im- the NCA and the INCB is designed to estimate unmet plemented in the distribution system, how they can be needs for opioids and then authorize their acquisition. evaluated, and then working with government to make Each year, the NCA prepares and submits to the INCB necessary changes in policy and administration. the estimated requirements of the quantities of each With support from the National Hospice and Pal- opioid that will be needed in the country. liative Care Organization and the Foundation for Hospices Only when the national estimate is increased or ex- in Sub-Saharan Africa, the PPSG developed an Internet panded to include other opioids can there be a change course titled “Increasing patient access to pain medicines in the overall amounts that are imported, manufactured, around the world: a framework to improve national poli- distributed, and dispensed to patients. However, if there cies that govern drug distribution.” Th e course was de- is little public interest in obtaining pain relief or medical veloped to make available this specialized information to interest in providing it, there may be little justifi cation clinicians, government administrators, drug regulatory for increasing availability. personnel, national health policy advisors, health policy When controlled drugs are needed for humanitarian scholars, and to those who develop clinical guidelines and emergencies, the usual time-consuming regulatory pro- training materials for pain management and palliative care. cedures governing exports and imports can be abbrevi- Th e course has seven lessons, each with required ated to expedite increased availability and access; further readings and extensive citations (see Table 1). Th e information is available from the INCB and the WHO. course explains why patients and clinicians have a right to expect that their national drug regulatory system Are there recommendations should make opioids available, and explains how this for educators and professional goal can be accomplished. organizations to address opioid availability problems? Do health professionals already have skills that can be used to Yes. Th e INCB, in consultation with the WHO, has rec- address opioid availability? ommended a strong role for educational institutions and nongovernmental health care organizations—in- If you have medical training, you already have relevant cluding the International Association for the Study of medical knowledge that can be applied in the drug reg- Pain (IASP)—to teach students in health care profes- ulatory policy and systems arena. For example, you may sions and licensed practitioners about the use of opioid appreciate the need for pain relief among patients with analgesics, their control, and correct use of terms related various diseases and conditions. You may know about to dependence. Furthermore, health care professionals the drugs and their uses. Th e medical model is also a and their organizations have been requested to establish solid problem-solving approach that can be applied to ongoing communication with their governments about the diagnosis of barriers to opioid availability and ac- unmet needs for opioid analgesics and to help identify cess, and to formulating action strategies, or treatments, impediments to availability and access. as if the opioid distribution system in your country is your patient. Using this knowledge and skill, you can become an eff ective leader to work with government to Where can a clinician fi nd examine, diagnose, and then decide on and implement information about how to improve the treatments necessary to correct the problems. opioid availability and access?

Although there are numerous guidelines and educa- What tools are available to help tional curricula that address pain and palliative care, diagnose regulatory problems in clinical training materials often do not describe the drug my country? control system and the steps necessary to obtain and distribute opioid analgesics. Obtaining and sustaining Information about drug control policy and systems access to opioid analgesics in any country depends on barriers is often new to the health professional, so the learning about the context of international and national WHO has published Cancer Pain Relief with a Guide 326 David E. Joranson

Table 1 Lessons in the PPSG Internet Course* Lesson 1: Understanding the Relationship between Pain and Drug Control Policy Lesson 2: Th e Role of International and National Law and Organizations Lesson 3: Barriers to Opioid Availability and Access Lesson 4: WHO Guidelines to Evaluate National Opioids Control Policy Lesson 5: WHO Guidelines to Evaluate National Administrative Systems for Estimating Opioid Requirements and Reporting Consumption Statistics Lesson 6: WHO Guidelines on Procurement and Distribution Systems for Opioid Analgesics Lesson 7: How to Make Change in Your Country * Th is is a self-paced noncredit course that can be taken at any one time or over a period of time. It may take between 10 and 12 hours to complete. Each lesson has a pre-test and post-test; links to background reading and many authoritative resources are provided. A certiﬁ cate is issued upon successful completion. Th e welcome and sign-in page is found at http://www.painpolicy.wisc.edu/ on-line_course/welcome.htm. Th e course is available only in English at present.

to Opioid Availability, which explains basics of pol- that physical dependence is an expected adaptation of icy, as well as Guidelines for Achieving Balance in Na- the body to the presence of an opioid analgesic, and tional Opioids Control Policy. Th e WHO Guidelines for that the withdrawal syndrome can be managed if the Achieving Balance provides a framework for diagnosis opioid is stopped. Th e WHO no longer uses the term of impediments in national drug control laws that has “addiction.” Th e current terminology is “dependence been used extensively around the world. Th ese guide- syndrome,” which is a biopsychosocial condition, the lines and the diagnostic checklist are available in 22 lan- markers of which are maladaptive behavior, compulsive guages on the PPSG website at http://www.painpolicy. use, and continued use despite harm. However, in re- wisc.edu/publicat/00whoabi/00whoabi.htm. ferring to dependence syndrome, use of the term “de- From a practical point of view, what can clinicians pendence” by itself has the possibility of being confused and government regulators do to improve cooperation? with physical dependence. Under these circumstances, Table 2 presents recommendations from the it is important to be clear in clinical and scientifi c com- WHO Guidelines for Achieving Balance about how munications whether one is referring to a diagnosis health professionals and drug regulators can cooper- characterized by maladaptive behavior, or to physiolog- ate through exchange of information and perspectives ical adaptation. and establishment of mechanisms of communications Th e notion that morphine should only be used as a and engagement. last resort is based on an outdated view of opioids and addiction. Indeed, eff orts to prevent dependence/addic- Do health professionals have beliefs tion that were based on this now outdated understand- or attitudes that might interfere ing have led to excessively strict prescribing restrictions with addressing opioid availability? that impede access. Examples include strict limits on patient diagnoses that are eligible for opioid analgesics, Possibly. Misinformation about the addictive potential restrictions on dosing and prescription amount, and of opioids and confusing terminology have led to ex- complex prescription forms that require multiple ap- aggerated concerns about the use of opioid analgesics provals and are diffi cult to obtain. Th ese matters are dis- and overly strict regulations that impede eff orts to im- cussed more fully in the PPSG Internet course; articles prove access to appropriate treatment for moderate to about progress to remove barriers in a number of coun- severe pain. tries appear on the PPSG website. Decades ago, experts said that mere exposure to If I want to assume more of a leadership role in my morphine would inevitably result in “addiction.” At that country, is specialized training available? time, addiction researchers studied the withdrawal syn- Yes. In addition to the Internet course, the PPSG drome that occurs when opioid use is stopped abrupt- sponsors an International Pain Policy Fellowship (IPPF), ly. Today in the fi eld of pain management, we know with support from the International Palliative Care Resources for Ensuring Opioid Availability 327 Initiative of the Open Society Institute and the Lance Pearls of wisdom Armstrong Foundation. Th e purpose of the IPPF is to prepare leaders from low- and middle-income countries • Today’s regulatory requirements for “narcotic to become change agents, and to develop plans to im- drugs” were developed long ago, well before pain prove patient access to opioid pain medicines in their relief became a priority, before opioids were des- countries. Fellows are selected through a competitive ignated essential medicines by the WHO, and at a application process and spend a week in training with time when morphine was thought to cause addic- the PPSG and other international experts. In some cas- tion in anyone exposed to it. es, a representative of the NCA accompanies the Fellow • More recently, the WHO and the INCB have en- to facilitate cooperation with the government drug reg- couraged governments to provide patients with ulators. trouble-free access to oral opioid analgesics, and Th e Fellows study the Internet course, diagram and the WHO has updated its defi nition of depen- diagnose impediments in their country’s drug distribu- dence syndrome. Still, opioid analgesics continue tion system, learn to use WHO tools to assess national to be inaccessible to most of the world’s popula- drug control laws, and develop their own action plans tion. to improve opioid availability and access. During the • Th e U.N. drug regulatory and health authorities 2-year fellowship, the Fellows implement their action have recognized the lack of availability of opioid plans with technical assistance from the PPSG. Please analgesics, have urged governments to examine visit the PPSG website for announcements, or go to national laws and regulations for barriers to opi- http://www.painpolicy.wisc.edu/newslist.htm to sign up oid availability, and have asked health profession- for email announcements from the PPSG. als and the IASP to work together to cooperate to

Table 2 Examples of cooperation between government and health care professionals Government regulatory authorities can: Inform health professionals about trends in drug traffi cking and abuse. Explain the framework of drug control policy and administration in the country including how the estimated requirements for opioid analgesics are prepared. Create mechanisms such as a task force or commission to examine ways that national drug control policy and its administration could help to improve availability and access while maintaining adequate control. Endorse World Health Organization guidelines for management of pain. Support national guidelines for pain management. Inform health professionals about legal requirements and discuss any concerns. Explore ways to provide an adequate number of outlets to maximize patient access. Collaborate with other government organizations, e.g., in cancer and AIDS planning for services, and to support medical education, education of patients and the general public. Health professionals can: Provide the government with information about the needs for various opioids for pain management and palliative care in the country. Identify needs to address any barriers in the regulatory system. Provide information about modern pain management, current knowledge about opioid analgesics in treating pain, and knowledge and attitudinal barriers to their optimal use. Demonstrate understanding of the international narcotic conventions and the obligation of governments to ensure adequate availability of opioid analgesics, while also preventing abuse and diversion. Provide information about WHO guidelines that can be used in self-assessment of the national opioids control policy. Assist in providing information to estimate the amounts of various opioids that are needed to satisfy actual needs. Identify impediments and weaknesses in the distribution system that lead to shortages. Support the government’s eff orts to obtain adequate personnel to administer drug control functions under the Single Convention. Explain health professionals’ concerns about prescription requirements and the possibility of investigation. 328 David E. Joranson educate health workers and to ensure adequate rights advocates understand that working with govern- patient access to pain relief. ment is necessary. Th e work outlined here to evaluate • Pain and palliative care experts report that the and reform outdated drug control policies is an integral absence of a clear statement about the govern- part of making the human right to pain relief a reality. mental obligation under international agreements to ensure adequate opioid availability in national References laws makes it diffi cult to convince regulators. PPSG studies show that the U.N. model drug [1] De Lima L, Krakauer EL, Lorenz K, Praill D, Macdonald N, Doyle D. Ensuring palliative medicine availability: the development of the IAH- control laws that should provide balanced guid- PC list of essential medicines for palliative care. J Pain Symptom Man- ance to governments also lack such language. age 2007;33:521–6. [2] Foley KM, Wagner JL, Joranson DE, Gelband H. Pain control for peo- • Traditionally, most countries have used pethi- ple with cancer and AIDS. In: Jamison DT, Breman JG, Measham AR, Alleyne G, Claeson M, Evans DB, editors. Disease control priorities in dine (meperidine) for pain relief, with the thought developing countries, 2nd edition. New York: Oxford University Press; that such a short-acting opioid would be less ad- 2006. p. 981–93. Available at: http://fi les.dcp2.org/pdf/DCP/DCP52.pdf. [3] Human Rights Watch. Please do not make us suff er anymore. March 3, dictive. But since the regulatory controls for 2009. Available at: http://www.hrw.org. morphine and other strong opioids are the same [4] International Narcotics Control Board. Report of the International Nar- cotics Control Board for 1995. Availability of opiates for medical needs. as for pethidine, it should be possible for health New York: United Nations; 1996. Available at: www.incb.org/pdf/e/ ar/1995/suppl1en.pdf. professionals and the NCA to fi gure out how [5] Joranson DE, Rajagopal MR, Gilson AM. Improving access to opi- to make available other opioids where they are oid analgesics for palliative care in India. J Pain Symptom Man- age 2002;24:152–9. Available at: http://www.painpolicy.wisc.edu/ needed. publicat/02jpsm3/index.htm. [6] Joranson DE, Ryan KM. Ensuring opioid availability: methods and re- • Th e resources provided in this chapter off er a sources. J Pain Symptom Manage 2007;33:527–32. Available at: www. starting point as well as encouragement to work painpolicy.wisc.edu/publicat/07jpsm/07jpsm.pdf. [7] Joranson DE, Ryan KM, Maurer MA. Opioid policy, availability, and with colleagues, professional organizations, and access in developing and nonindustrialized countries. In: Fishman SM, government to correct the conditions that block Ballantyne JC, Rathmell JP, editors. Bonica’s management of pain, 4th edition. Baltimore: Lippincott Williams & Wilkins; 2010. p. 194–208. eff orts to relieve pain and suff ering. [8] Pain and Policy Studies Group. Internet course: Increasing patient access to pain medicines around the world: a framework to improve national policies that govern drug distribution. University of Wisconsin Paul P. Carbone Comprehensive Cancer Center. Available at: www.pain- In closing, here are a few tips: policy.wisc.edu/on-line_course/welcome.htm. [9] Rajagopal MR, Joranson DE, Gilson AM. Medical use, misuse, and di- Be alert to new opportunities and resources. Th ere may version of opioids in India. Lancet. 2001; 358(9276):139–143. [10] World Health Organization. Essential medicines. Geneva: World be opportunities in your country for synergistic part- Health Organization; 2005. Available at: www.who.int/topics/essential_ medicines/en. nerships with government and nongovernment public [11] World Health Organization. Cancer pain relief: with a guide to opioid health organizations that advocate the use of metha- availability, 2nd edition. Geneva: World Health Organization; 1996. Available at: http://whqlibdoc.who.int/publications/9241544821.pdf. done for treatment of intravenous drug users to reduce [12] World Health Organization. Achieving balance in national opioids control policy: guidelines for assessment. Geneva: World the spread of HIV/AIDS. Th e international controls on Health Organization; 2000. Available at: www.painpolicy.wisc.edu/ morphine and methadone are the same, and the regu- publicat/00whoabi/00whoabi.htm. [13] World Health Organization. Access to controlled medications program. latory steps to make them available and accessible in a Geneva: World Health Organization; 2007. Available at: www.who.int/ country should be similar to those for opioid analgesics. medicines/areas/quality_safety/access_to_controlled_medications_ brnote_english.pdf. Th e WHO is developing an Access to Controlled Medicines Program to provide additional support for ef- forts to improve medical access to opioid analgesics as Recommended websites well as other essential medicines that are controlled drugs. Pain & Policy Studies Group: www.painpolicy.wisc.edu/ Pain relief is becoming recognized as a human World Health Organization: www.who.int/medicines/ right. As the right to pain relief becomes more widely International Narcotics Control Board: www.incb.org recognized, there may be additional opportunities for International Association for Hospice and Palliative Care: www.hospicecare. collaboration with human rights advocates. Human com/ Guide to Pain Management in Low-Resource Settings

Chapter 44 Setting up Guidelines for Local Requirements

Uriah Guevara-Lopez and Alfredo Covarrubias-Gomez

Case report What are practice guidelines?

A 65-year-old Mexican woman reported generalized ab- Th e original concept of practice guidelines (PGs) was dominal pain. She went to a rural medical practitioner described as “a recommendation for patient manage- in San Juan de Bautista, who prescribed 30 mg of ketoro- ment that identifi es one or more strategies for treat- lac t.i.d. After 2 days the pain had not stopped, and she ment”. However, in 1990, the Institute of Medicine in the returned for medical assistance; this time, the physician United States defi ned PGs as “systematically developed added to his prescription 90 mg of etoricoxib per day. Af- statements to assist practitioner and patient decisions ter two more days, the pain continued, and the woman about appropriate health care for specifi c clinical cir- went to a regional hospital located 10 miles from her cumstances” (see Table 1). Th is defi nition had been gen- home in Lloredo. In the hospital a uterine cancer with erally accepted. omental and liver metastasis was diagnosed, and ad- Guidelines are not rules or standards; they are equate pain management was provided. helpful, fl exible syntheses of all the available, relevant, Th e prescription from the rural practitioner good-quality information applicable to a particular clin- drew the attention of local health authorities. Th ey ical situation that the clinician and patient need to make asked the clinician about his prescription and about his a good decision. Since medical knowledge, techniques, knowledge about Mexican practice guidelines for cancer and technology are in constant development; PG must pain management. Th e physician responded that he had be actualized and improved in certain time intervals. heard of them but he did not know about their content or recommendations, although he had received education Why do we need on Mexican practice guidelines for pain management: he practice guidelines? had attended a 1-month fellowship in the regional hospital, and was also encouraged to promote education to lo- Medical knowledge is under a continuous evolution. cal organizations about the guidelines and their benefi ts. Assume, that a physician knows everything about a dis- A follow-up program for pain management evaluation ease or its treatment on the basis of training and clini- in his community was established. cal judgement, but continuing medical education was So what went wrong? not available. Since there is a great chance, that medical concepts have changed meanwhile, the physician’s

Table 1 Defi nition of practice guidelines and other terms that are confused with practice guidelines Concept Defi nition Practice guidelines A systematically developed statement to assist practitioner and patient decisions about appropriate health care for specifi c clinical circumstances. “Protocol” is often used interchangeably with “guideline,” although some view “practice protocols” as a more specifi c (procedure- or specialty-specifi c) form of practice guidelines. Clinical pathways An optimal sequencing and timing of interventions for a particular diagnosis or procedure. A “care map” or multidisciplinary action plan extends the concept of a clinical pathway by including an outcome index, which allows for the evaluation of the interventions. Clinical algorithms A more complex set of instructions containing conditional logic, usually expressed in branching trees. Information extracted from: Henning [4]. diagnostic and therapeutic approaches are outdated Additionally, pain has a signifi cant impact on meaning either impaired effi cacy or decreased safety. physical function and activity, return-to-work-quota, Th e speed of medical evolution has complicated social and family relations as well as the general psy- medical decision making; for that reason, PG may be choaff ective state of the aff ected patient. Th is may prove used as an instrument to assist the clinician. Th is objec- to be a burden for the family of the patient, but also to tive is possible because PG summarizes the collective ex- the society as a whole, since insuffi cient pain manage- perience and establishes grades to scientifi c knowledge. ment is a major cause for increased use of health care resources. Th erefore, health care policies need the im- Are there diff erent types plementation of rationalized instruments that can op- of practice guidelines? timize and improve the quality of medical attention for the most relevant diseases including pain syndromes. Attempts to regulate PG had been made since the early 1980s. Nowadays, diff erent types of practice guidelines How are practice guidelines can be identifi ed: (i) for the diagnosis and management developed? of specifi c clinical circumstances, (ii) for risk management, (iii) for the improvement of quality systems, (iv) Th ere is a general agreement, that PG must be submit- for medical regulation, (v) for education, and (vi) for ted to public scrutiny, revised regularly in response to preventive care. medical advances, and derived from high quality scientifi c evidence. PG must be easy to comprehend, inclu- Why do we need practice guidelines sive, and manageable. Th e method for evidence selec- for pain management? tion must be explained and the criteria used to grade each recommendation must be explained. Pain is considered a health problem in few countries, Protocols for developing guidelines have many but the number of countries where pain management common features: (i) Reviews of existing research fi nd- becomes a health care priority is increasing. Th e de- ings are conducted, often with the aid of the National velopment of PG in pain medicine is supported by Library of Medicine. (ii) Studies are selected according the following issues: (i) the number of surgical inter- to predetermined criteria and fi ndings are summarized ventions is increasing in many low-resource countries using techniques such as meta-analysis or systematic without any concept to control postoperative pain; (ii) reviews. (iii) Panels of experts are convened and guide- the demographic change (increase of older population) lines are revised according to feedback received. (iv) worldwide will be associated with a growing preva- Consensus is achieved in some areas; and where dis- lence of cancer pain; (iii) the frequency of chronic non agreement or uncertainty remains and more research is cancer pain is recognized more today, for which it has needed, the developers describe this defi ciency. been estimated, that the annual treatment costs equal Strategies for developing PG have been pro- or exceed exceeds those for coronary disease, cancer posed by diverse groups worldwide, a summary of those and AIDS. is described in Table 2. Setting up Guidelines for Local Requirements 331

Table 2 Strategies used for developing practice guidelines Strategy Description Identifi cation of a A regional health problem is identifi ed. Th e impact of this problem on the population and the usefulness of regional medical practice guidelines is analyzed. If needed, a consensus group for the development of guidelines (for manage- problem ment, care, diagnosis, etc.) is formed. Selection of a group Formed by specialists from areas related to the guideline topic. Selection criteria include experience (more of experts than 5 years) in this particular fi eld, in clinical research, in grading the evidence for recommendations, and/ or an academic profi le. Clinical practitioners recommended from the national medical associations related to this specifi c area are also included. Experts must not have any confl ict of interest. Identifying medical A questionnaire to evaluate the medical tendencies (for diagnosis, management, care, etc.) is developed by the tendencies group of experts. Items on the questionnaire are based on the statements made by other consensus groups, clinical guidelines, clinical pathways, or clinical algorithms. Results from questionnaires are sent to the selected experts. Review of the From the selected guideline topic, a focused review of the literature is made. Th is process is achieved using literature diverse electronic medical databases (PubMed, EMBASE, LILACS, and others). Cross-reference of selected documents is made. Resources to obtain references are provided by the national institutes of health, national medical associations, and nonprofi t organizations. Sending evidence to Results from the review of the literature are send to the group of selected experts. Th e objective is that every the selected experts participant have the opportunity to analyze the literature before the consensus meeting. Elaborating recom- A consensus meeting is held to analyze the results obtained from the questionnaire and to develop specifi c mendations recommendations (for management, diagnosis, education, care, etc.). Every recommendation is considered for further review based on the group’s expertise and the results from the review of the literature. Preliminary results From the consensus meeting a preliminary report is obtained. Each of the recommendations is submitted to a focused review of the scientifi c evidence. Meta-analysis, systematic reviews, randomized controlled trials, randomized uncontrolled trials, and case reports for each specifi c recommendation are analyzed. If there are no studies, the recommendation is “based on consensus group expertise.” Results from this search are sent to the group of experts. Grading recom- Feedback from the group of experts about the evidence to endorse a recommendation is analyzed. Th e mendations method for grading for every recommendation is described in Table 3. Preliminary practice A preliminary document is sent to the consensus group. Final notes from the participants are considered, and guidelines a fi nal document is elaborated. Review of the fi nal Th e fi nal document is sent to the participants for approval (as many times as needed). After this process is document completed, the document is sent for publication in a peer-reviewed journal. Implementation of Extensive education among clinicians, health care administrators, policy makers, benefi t managers, and guidelines patients and their families is performed in every fi liation center from each consensus participant. Conferences at regional congresses or medical meetings are provided. Local eff orts to implement guidelines require the commitment of the participants. Follow-up and A questionnaire designed to evaluate clinicians’ knowledge of the guidelines or their outcome is performed. evaluation of the Evaluation is obtained by the method developed by the AGREE Collaboration Group. guidelines Information extracted from: Frances [ref. 2], Guevara-López et al. [ref. 3]. AGREE Collaboration Group: www.agreecollaboration.org; National Institute for Health and Clinical Excellence (UK): www.nice.org.uk.

How does the scientifi c evidence Grading methods take into account the study grade the recommendations design, benefi ts and harms, and outcome (Canadi- an Task Force, U.S. Preventive Services Task Force, of practice guidelines? GRADE working group, SIGN method, SORT taxon- In 1979, the Canadian Task Force on Periodic Health omy, etc.). A description of a strategy for grading the Examination made the fi rst eff orts to characterize the evidence according to the methodology of the study is level of evidence underlying health care recommenda- described here: tions and their strength. Since then, a wide variety of • Level 1: Evidence is extracted from systematic re- methods have been developed for “grading” the strength views of relevant controlled clinical trials (with of the evidence on which recommendations are made. meta-analysis when possible) 332 Uriah Guevara-Lopez and Alfredo Covarrubias-Gomez • Level 2: Evidence is extracted from one or more patients and their families. Th erefore, PGs must in- well-designed randomized controlled clinical trials troduce a comprehensive and integrative strategy for • Level 3: Evidence is extracted from well-designed their implementation. nonrandomized clinical trials or well-designed An implementation strategy relies on informing cohort studies or analytic case reports (if possible and educating physicians about the content of guide- multicenter or performed at diff erent times) lines. Impersonal approaches that use the dissemina- • Level 4: Evidence is extracted from expert opin- tion of written material alone or presentations to large ions and/or opinion leaders (supported if possible audiences have not been very successful. Education of by the reports from other consensus statements) a specifi c PG must be personalized, involve respected Th e evidence can be converted into recommen- physician leaders and incorporate a high degree of in- dations (type A, B, or C) and the “strength of evidence teraction between the target audience and those pre- and maximum benefi t” (Class A to Class E), depending senting the information. on how advisable the use of a specifi c treatment or in- Comparison of actual performance with the per- tervention is (Class A = highly advisable and Class E = formance that would be expected if the guidelines were insuffi cient evidence). followed may be used as a feedback strategy to achieve PG implementation. Feedback can occur either as the How are practice guidelines service is being provided (concurrent feedback) or after that service has been provided (retrospective feedback). evaluated? A physician’s knowledge of PGs to obtain Th e quality of clinical practice guidelines must be evalu- board recertifi cation has been described as an useful ated and diverse methods to achieve this propose have strategy for guideline implementation. For that reason, been reported. Th ere are three basic stages of evalua- medical associations or medical boards should be part tion: (i) evaluation during the development of guidelines of PG implementation strategies. Th eir role could be and before their full dissemination and implementa- to generate distance learning programs and continu- tion (inception evaluation); (ii) evaluation of health care ing medical education (CME) certifi cation on the PG programs within which guidelines play a central role contents. To add (and receive) the support from health (guidelines-program evaluation); and (iii) evaluation of care administrators and policy makers, it is advisable the eff ects of guidelines within defi ned health care envi- to stress the economical impact of PGs (which usually ronments (scientifi c evaluation). attracts their attention!). Th e evaluation of PGs also includes the identi- Finally, education of patients and their families fi cation of potential biases of guideline development, as well as the public about the potential benefi ts ob- and the assurance that recommendations are valid and tained by PG must be part of the implementation pro- feasible for practice. Th is evaluation process takes into cess. Th ese educational eff orts may be extended to non- account the benefi ts, harms, and costs of the recom- governmental organizations. mendations, as well as the practical issues attached to them. Th erefore, the assessment of PGs includes judg- How do clinicians respond ments about the methods used for its development, the to practice guidelines? content of the fi nal recommendations, and the factors linked to their uptake. Th e impact of guidelines on the behavior of physicians has been poorly documented, although some reports How can practice guidelines be documented a considerable disappointment with PGs. implemented? Other studies show that physicians are generally positive about guidelines but that they do not integrate Th e fact that most PGs have been published and then them into their practices to a large extent. Th e reason forgotten has to do with the lack of eff orts for their for this ambivalent behavior lies in problems associ- implementation. Th e acceptance of PGs requires ex- ated with their production, dissemination, and use. tensive education among clinicians, health care ad- However, little is known about physicians’ (and pa- ministrators, policy makers, benefi t managers, and tients’) attitudes and suspicions toward PGs, as well as Setting up Guidelines for Local Requirements 333 regarding the motives for encouraging their use or as list accordingly. To give an example, the introduction to their credibility. Th is has been recognized as a defi - of basic palliative care in East African Uganda was only cit, since certain motives could cause practitioners and possible when the essential drug list was amended by their patients to resist PGs. adding morphine. Some studies indicate that the physician’s ad- Another fact to be respected when introducing herence to guidelines may be hindered by a variety of PGs in low-resource settings is the disparity regarding barriers. Identifi ed were: (i) awareness, (ii) familiarity, access to medical services depending on geographic (iii) agreement, (iv) self-effi cacy, (v) outcome expec- factors, such as the diff erence between the capital and tancy, (vi) ability to overcome the inertia of previous rural regions or the diff erence between underfunded practice, and (vii) absence of external barriers to per- national health system institutions and high-standard form recommendations. private ones. Another factor that may slow down adherence On the one hand, PGs have to be adapted in a by physicians to PGs may be the dogmatic educational stepwise structure to be used depending on the resourc- background. For example, Canadian family physicians es available, and on the other hand, PGs may be used as show little resistance to guidelines and appear to need an instrument to optimize resources and the quality of less threat of external control to incorporate them into delivery of health care. their practice. On the other hand, American internists Also, certain national diff erences exist, due to are less supportive of PGs. It is possible that informa- cultural, ethnic/genetic, and traditional reasons, regard- tion acquired from medical training may play a role in ing the use of certain drugs and procedures. In Mexico, PG support from practitioners. Th erefore, the develop- for example, 80% of the population use herbal medi- ment of PGs must include lecturers and opinion lead- cine, and 3,500 registered medical plants with medicinal ers at medical schools and respected organizations to properties are available. For that reason, phytotherapy foster dissemination. or other complementary medicine could be considered Th e clarity and readability and the clinical ap- for inclusion in locally adapted PGs. plicability of a guideline are other elements that con- Finally, potentially eff ective dissemination and tribute to the acceptance of guidelines by clinicians. education techniques developed in high-resource set- In conclusion, PGs must be written in a user-friendly tings may also have to undergo some changes to be fea- way, adapted to the practical needs of the clinician’s sible in a specifi c low-resource setting. It is understood daily practice, and advocated thoroughly by medical that such an initiative will mean a considerable eff ort, boards, opinion leaders, and medical societies. If the although the work of local PGs could at least be based implementation of a PG is successful, the results for on international accepted PGs. It will be necessary to patient safety are encouraging. get all stakeholders at one table: rural and academic practitioners, other health providers, patients and their Why must practice guidelines families, local organizations, and academic institutions. consider regional resources? Th is sounds like a lot of work, but the gain in safety and economy following the publication and implementation Developing countries have limited access to expensive of (adapted) PGs will justify the eff ort. drugs or procedures. Th erefore, PGs must consider regional resources for their feasibility and routine ap- Pearls of wisdom plication, often making it impossible to simply copy international PGs. It may be inevitable to make certain • Practice guidelines (PGs) are “a systematically de- evidence-based approaches to diagnosis and treatment veloped statement to assist the practitioner’s and optional, e.g., by including phrases like “if available.” Ex- patient’s decisions about appropriate health care isting PGs have to be adapted if possible according to for specifi c clinical circumstances.” Guidelines are the national “essential drug list.” If no reasonable alter- not rules or standards, but they are a helpful, fl ex- native drug choice is available, no further compromise ible synthesis of all the available, relevant, high- for a national PG is recommended. Instead, the essen- quality information applicable to a particular tial drug list should be targeted. Th e eff ort should be clinical situation, so that the clinician and patient made to encourage all stakeholders to change the drug may make a good decision. 334 Uriah Guevara-Lopez and Alfredo Covarrubias-Gomez • Th e evolution of medicine has complicated must consider regional resources for their feasi- medical decision making; for that reason, PGs bility and routine application. may be used as an instrument to assist the clini- • PGs must take into account local resources and cian in medical decision making. Th is objective traditions and make available the evidence reis possible because PGs summarize the collec- garding the risk-benefi t ratio and the cost-eff ective experience and establish easy access to sci- tiveness. If local resources lack proper evidence entifi c knowledge. or local resources ignore essential evidence, PGs • PGs must be easy to comprehend, inclusive, and may be used as an instrument to draw the atten- manageable. Th e method for evidence selection tion of policy makers and health administrators must be explained, and the criteria used to grade to provide the most benefi cial management or each recommendation must be included. intervention to the aff ected population. • A wide variety of methods for “grading” the strength of the evidence on which recommen- References dations are made have been developed. Grading methods take into account the study design, ben- [1] Carter A. Clinical practice guidelines. CMAJ 1992;147:1649–50. [2] Frances A, Kahn D, Carpenter D, Frances C, Docherty J. A new method efi ts and harms, and outcome. of developing expert consensus practice guidelines. Am J Manag Care • Th e acceptance of PGs requires extensive educa- 1998;4:1023–9. [3] Guevara-López U, Covarrubias-Gómez A, Rodríguez-Cabrera R, tion among clinicians, health care administration, Carrasco-Rojas A, Aragón G, Ayón-Villanueva H. Practice guidelines for pain management in Mexico. Cir Cir 2007;74:385–407. policy makers, benefi t managers, and patients [4] Henning JM. Th e role of clinical practice guidelines in disease manage- and their families. Th erefore, PG must introduce ment. Am J Managed Care 1998;4:1715–22. [5] Palda VA, Davis D, Goldman J. A guide to the Canadian Medical Asso- a comprehensive and integrating strategy for its ciation handbook on clinical practice guidelines. CMAJ 2007;177:1221– implementation. 6. [6] Walker RD, Howard MO, Lambert MD, Suchinsky R. Medical practice • Physician adherence to guidelines may be hin- guidelines. West J Med 1994;161:39–44. dered by a variety of barriers, which include: (i) awareness, (ii) familiarity, (iii) agreement, (iv) Websites self-effi cacy, (v) outcome expectancy, (vi) ability to overcome the inertia of previous practice, and NICE: National Institute for Health and Clinical Excellence (UK). www.nice. org.uk (vii) absence of external barriers to perform rec- AGREE: Appraisal of Guidelines Research and Evaluation Collaboration. ommendations. www.agreecollaboration.org • Developing countries may have limited access to (expensive) drugs or procedures. Th erefore, PGs Pearls of Wisdom

Guide to Pain Management in Low-Resource Settings

Chapter 45 Techniques for Commonly Used Nerve Blocks

Corrie Avenant

Why recommend with regards to anticoagulant and antiplatelet drugs, regional anesthesia? such as the type, dose, and the time when the anticoagulants were taken. • Th e patient remains conscious or mildly sedated. It is necessary to explain to the patient what he/she • Airways and respiration are not aff ected. will experience: • Th e incidence of postoperative thromboembo- • Some paresthesias and involuntary movements lism is reduced. during needle insertion. • Regional anesthesia techniques are less expensive • Intraoperatively, the patient may feel movement, compared to general anesthesia. touch, and pressure while having adequate analgesia, and he or she will have to be reassured that What are the disadvantages if the analgesia is inadequate, there is a strong possibility of being given general anesthesia. of regional anesthesia? • Postoperatively the patient will have to wait for a • Special skills are required to do a nerve block suc- few hours for movement and sensation to return cessfully. completely, but he or she can eat a meal straight • Analgesia may not always be eff ective, so conver- away. sion to general anesthesia might be necessary. • Immediate complications can occur, such as tox- What are the contraindications icity or hypotension. for regional anesthesia? What assessment must be done • Patient refusal before performing a block? • Coagulation disorders • Infections at the site of injection Th ere are no diff erences regarding the assessment of a • Pre-existing neurological defi cits: check previ- patient between a general anesthesia or a regional an- ous documentation and make your own brief ex- esthesia technique. Th e same care and considerations amination before planning regional anesthesia to must be taken into account, with a history and relevant avoid being blamed for any undocumented neu- clinical examination. Special drug history is necessary rological defi cits

How is toxicity avoided Intravenous regional anesthesia (Bier’s block) when using local anesthetics? Bier’s block may be a very eff ective block for upper and lower limb manipulation, such as manipulation of sim- • Always respect maximum doses: for bupivacaine ple fractures and suturing of lacerations. the maximum dose is 2 mg/kg for a single injec- Th e method is as follows: tion technique (daily maximum 8 mg/kg for con- • Secure venous access on both sides. tinuous techniques). • Have a full resuscitation trolley available (in case • In case of toxicity symptoms (slurred speech, of cuff failure). tingling in the ear, loss of consciousness, convul- • The inflatable tourniquet is placed around the sions, or arrhythmias), stop the injection, and ad- upper arm over a wool bandage to protect the minister oxygen and support ventilation to avoid skin. acidosis. • A double cuff may be used for prolonged surgery • Stop seizures with intravenous pentothal, benzo- (>15 minutes). diazepines, or propofol. • Drain venous blood from the aff ected limb. • If cardiac symptoms are present, give circulatory • Infl ate the blood pressure cuff to 100 mm Hg support (antiarrhythmics such as amiodarone or above systolic blood pressure. amrinone); if arrhythmias persist, use direct-cur- • Inject local anesthetic. rent (DC) cardioversion and cardiopulmonary re- • Anesthesia is achieved after 10–15 minutes (the suscitation (CPR) for as long as needed (which may blood pressure cuff should not be defl ated within be much longer than for other causes of arrest). 20 minutes). • If available, use lipid infusion (Intralipid) to “an- • Use 0.5 mL/kg of 0.5% lidocaine (plain) solution tagonize” local anesthetic toxicity (a bolus of 1.5 mL/kg body weight of Intralipid 20%, followed by Intercostal nerve block 0.25 mL/kg body weight/minute for 1 hour). A typical indication would be postoperative pain relief after cholecystectomy or thoracotomy, as well as pain What types of nerve blocks relief from fractured ribs. Remember that the intercos- are easy to perform? tal nerves derive from the ventral ramus of the spinal nerves and that they run along the inferior border of Finger block the ribs. To block the intercostal nerves, use the fol- Indications are fractures and lacerations. Th e two digi- lowing technique: tal nerves run on each side of the fi nger. Th erefore, the • Position the patient in a supine position. Techniques for Commonly Used Nerve Blocks 339 • Have the patient’s arm raised with the hand be- Ankle block hind the head. Indications would be all kinds of foot surgery, includ- • Confi rm the rib by palpation or adequate land- ing amputations. For an eff ective ankle block, proceed marks. as follows: • Identify the midaxillary line. • Position the patient supine. • To avoid pneumothorax, the needle point should • Block the superfi cial peroneal nerve with subcu- be in close proximity to the rib. taneous infi ltration between the anterior edge of • Th e rib is held between the second and third fi n- the tibia and the upper edge of the lateral malleo- gers. lus with 5–10 mL anesthetic solution. • Insert the needle between the second and third • Block the sural nerve by subcutaneous infi ltra- fi nger and advance to make contact with the rib. tion of 5 mL local anesthetic between the Achilles • Direct the needle downward (caudally) and walk tendon and the lateral malleolus. the needle until it slides off . • Infi ltrate the saphenous nerve with of 5 mL of • Advance the needle not more than 5 mm to pre- subcutaneous local anesthetic from the anterior vent pneumothorax. edge of the tibia to the Achilles tendon. • Finally, inject 2–3 mL of 0.5% bupivacaine at each • Block the deep peroneal nerve by inserting the level, after careful aspiration, as the intercostal ar- needle between the tendon of the extensor pol- tery and nerve are very close by. licis muscle and the dorsalis pedis artery on the Wrist block dorsum of the foot. Th e needle is inserted per- pendicularly to the skin and advanced slightly Wrist blocks may be used if a plexus block is incom- under the artery. Following negative aspiration plete, as a diagnostic block, or for pain therapy. Be inject 5 mL local anesthetic. familiar with the anatomy. The median nerve is lo- • Tibial nerve block can be obtained with the nee- cated on the radial site of the palmaris longus tendon dle inserted directly dorsal to the posterior tibial (better visible when flexing the wrist), and the ulnar artery on the medial side of the joint, or alterna- nerve is located on its other (ulnar) side. The radial tively, directly anterior to the Achilles tendon be- nerve is superficially located at the lateral aspect of hind the medial malleolus. the wrist. To block the median nerve: • Insert the needle on the fl exor side between the Pearls of wisdom tendons of the fl exor carpi radialis and palmaris longus tendon. • Some peripheral nerve blocks are very easy to • After eliciting paresthesias, withdraw slightly and perform and very eff ective. inject 3–5 mL. • Th ey can be performed with minimum training. To block the ulnar nerve: • Nevertheless, anatomical details have to be • Have the arm stretched out and the hand supi- known and memorized (see webpage). nated. • Peripheral nerve blocks will work better if there is • Insert the needle approx 3–4 cm proximal to the no local infl ammation. crease between the fl exor carpi ulnaris tendon • Toxicity of local anesthetics can be prevented (al- and the ulnar artery. most always) by respecting maximum doses and • After eliciting a light paresthesia, withdraw the avoiding intravascular injection with careful aspi- needle slightly and inject 3–5 mL of the local an- ration. esthetic. • In case of local anesthetic toxicity have all neces- To block the radial nerve: sary instruments and drugs ready for treatment, • Have the arm stretched out and the hand supi- otherwise refrain from performing blocks. nated. • In case of paresthesias, withdraw the needle to • Infi ltrate subcutaneously on the radial side of the avoid injury to the nerve. wrist 3–5 cm proximal to the radial head point. • Do not use blocks if the patient is not willing. 340 Corrie Avenant References Websites

[1] Enneking FK, Chan V, Greger J, Hadzić A, Lang SA, Horlocker TT. http://www.painclinic.org/treatment-peripheralnerveblocks.htm (including Lower-extremity peripheral nerve blockade: essentials of our current anatomical images for each block) understanding. Reg Anesth Pain Med 2005;30:4–35. http://www.nysora.com/ (including real life photos for all relevant blocks) [2] Klein SM, Evans H, Nielsen KC, Tucker MS, Warner DS, Steele SM. Pe- ripheral nerve block techniques for ambulatory surgery. Anesth Analg http://www.nda.ox.ac.uk/wfsa (World Anaesthesia Online educational mate- 2005;101:1663–76. rial on diﬀ erent relevant blocks to be used in low-resource settings) Guide to Pain Management in Low-Resource Settings

Chapter 46 Psychological Principles in Pain Management

Claudia Schulz-Gibbins

What can we use for acute pain? for cancer pain as well as for pain caused by HIV, there is the same relationship, in the framework of the biopsy- Acute pain occurs mainly in connection with an illness chosocial concept, as with other chronic pain models. or injury or as an eff ect of a treatment of an illness (e.g., Th e prevalence of comorbidities such as anxiety and postsurgical pain). In contrast to chronic pain, acute depression is common, as in other pain syndromes, and pain is an alarm signal to the body. Normally, the cause should be taken into consideration and treated. Often is noticeable, and the treatment is mostly rest and man- these disorders are ignored. Additionally, patients have agement of the cause of pain. Th e psychological eff ect is to cope with pain due to a tumor, as well as pain that the hope that the treatment will be successful and the may arise during the course of the treatment. Overcom- pain will be over soon. It is possible that anxiety and ap- ing the consequences of chronic diseases diff ers signifi - prehension may appear within the period of acute pain, cantly in developed countries in contrast to developing for example, the fear of surgery and anesthesia that countries. Caring for the ill person is often very diffi cult could form part of the treatment. for the family because of fi nancial problems. A diffi cult fi nancial situation and poor access to medical, nursing, Practical consequences or other social services can aff ect the process of healing As part of preparation for surgery, interventions such as negatively. At the time of diagnosis, there is often a loss relaxation techniques, a good explanation of the proce- of control and helplessness in the face of possible physi- dure and possible outcomes, and an optimistic outlook cal disfi gurement, accompanying pain, and possible fi - have been proven to be helpful. It is possible to reduce nancial implications for adequate treatment, not least postoperative pain experience through such knowledge. the fear and uncertainty surrounding the prospect of an Knowledge about the treatment can often reduce one’s untimely death. Additionally, questions of guilt can lead anxiety. Relaxation techniques can minimize psycho- to psychological strain because of trying to own up to logical agitation patterns such as a high heart rate and one’s own responsibility for a disease, for example: “It’s inner restlessness. my own fault that I have a tumor, because I have been smoking too much,” or “Being infected by HIV is be- What can we use for cancer cause of my irresponsible sex life.” and HIV/AIDS pain? Practical consequences In the treatment of chronic pain, it is important to dif- Adequate counseling and emotional support should ferentiate between benign and malignant pain. However, be integrated in the provision of health care for these Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. All rights reserved. Th is material may be used for educational and training purposes with proper citation of the source. Not for sale or commercial use. No responsibility is assumed by IASP for any injury and/or damage to persons or property 341 as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends that there should be independent verifi cation of diagnoses and drug dosages. Th e mention of specifi c pharmaceutical products and any medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text. 342 Claudia Schulz-Gibbins patients. Good communication and explanations What can we use for chronic about the existing possibilities of therapy and about back pain? the prognosis can reduce fears and helplessness, and enable patients to cope better with the disease and its Chronic back pain, in most cases, is musculoskeletal in accompanying challenges. Particularly in Kenya, reli- origin, accompanied by poor coping skills along with gious support has been reported as being helpful. other “yellow fl ags.” A special problem in coping with back pain is the fact that sometimes no suffi cient expla- What are the options in chronic nation can be given to the patient regarding the cause and origin of the pain. For example, a diagnosis of “non- noncancer pain? specifi c back pain” leads to an extreme uncertainty on In the context of chronic abdominal pain, which is quite the part of the patient, often leading to increased fear of often diffi cult for the patient to locate and come to serious pathology and the desire for repeated diagnos- terms with, often together with the threat of incurability tic procedures. Often there is an iatrogenic component and looming death. Commonly, the physician wonders, when repeated investigations are ordered—partly be- “Why is the patient coming now?” Possible reasons for cause the patient insists on it, and partly because the the patient can be a fear of serious diseases after deaths physician may be uncertain: “Is there a tumor or a seri- in the family, psychological comorbidities, emotional ous disk prolapse causing the pain?” Th ere may be a re- distress because of sexual abuse, but also trouble with- luctance “to miss something.” in the actual context of life and poor coping strategies, Practical consequences which may lead to an increase in the pain. A comprehensive compilation of all available fi ndings, Practical consequences as well as discussion with colleagues about previous di- Indicators of stress mentioned above should be looked agnosis and treatment, can be useful to get a complete for, which can aff ect the development and maintenance picture about the patient. Th e patient should be advised of pain. Th erapeutic interventions including a good ex- against unnecessary and often very expensive invasive planation of the disease, continuing psychological sup- diagnostic procedures. port, advice on balanced nutrition, and so on should be After considering all possible factors including added over time. psychiatric comorbidity or risks of chronifi cation, a treatment plan can be developed. Good models on interactions, for example between depression and How can we tackle chronic pain, can help the patient to cope successfully chronic headache? with pain.

Most headaches have no organic cause. Very often we fi nd interactions between headache and dysfunction- References al patterns of the muscles, such as increased tension, [1] American Psychiatric Association. Diagnostic and statistical manual of which can then, by itself, become a trigger for head- mental disorders, 4th ed. Washington, DC: American Psychiatric Asso- ciation; 1994. ache. Social stress factors such as excessive demands at [2] Dersh J, Polatin PB, Gatchel RJ. Chronic pain and psychopathol- ogy: research fi ndings and theoretical considerations. Psychosom Med the workplace or poor coping strategies with stress, can 2002;64:773–86. make headaches intense and chronic. [3] Fishbain D, Cutler R, Rosomoff H. Chronic pain-associated depression: antecedent or consequence of chronic pain? A review. Clin J Pain 1997;13:116–37. Practical consequences [4] Gureje O, von Korff M, Kola L, Demyttenaere K, He Y, Posada-Villa J, Lepine JP, Angermeyer MC, Levinson D, de Girolamo G, Iwata N, Important in the treatment of headache is describing to Karam A, Guimaraes Borges GL, de Graaf R, Browne MA, Stein DJ, Haro JM, Bromet EJ, Kessler RC, Alonso J. Th e relation between mul- the patient that stress can lead to an increase in the in- tiple pains and mental disorders: results from the World Mental Health tensity and frequency of the headache. Th e most impor- Surveys. Pain 2008;135:82–91. [5] Merskey H, Lau CL, Russell ES, Brooke RI, James M, Lappano S, tant psychological interventions are education in coping Neilsen J, Tilsworth RH. Screening for psychiatric morbidity. Th e pat- skills and in the importance of stress management, and tern of psychological illness and premorbid characteristics in four chronic pain populations. Pain 1987;30:141–57. the reduction of hyperactivity with lessons in cognitive [6] Murray SA, Grant E, Grant A, Kendall M. Dying from cancer in developed and developing countries: lessons from two qualitative interview behavioral therapy, relaxation techniques, and so on. studies of patients and their carers. BMJ 2003;326:368. Psychological Pearls in Pain Management 343

[7] Norman SB, Stein MB, Dimsdale JE, Hoyt DB. Pain in the aftermath of trauma is a risk factor for posttraumatic stress disorder. Psychol Med Websites 2008; 38:533–42. [8] Tang NK, Crane C. Suicidality in chronic pain: a review of the preva- www. immpact.org (Initiative on Methods, Measurement, and Pain Assess- lence, risk factors and psychological links. Psychol Med 2006:36:575– ment in Clinical Trials) 86. [9] Tsang A, Von Korﬀ , M, Lee S, Alonso J, Karam E, Angermeyer MC, Borges GL, Bromet EJ, de Girolamo G, de Graaf R, Gureje O, Lepine JP, Haro JM, Levinson D, Oakley Browne MA, Posada-Villa J, Seedat S, Watanabe M. Common chronic pain conditions in developed and developing countries: gender and age diﬀ erences and co morbidity with depression-anxiety disorders. J Pain 2008;9:883–91.

Guide to Pain Management in Low-Resource Settings

Chapter 47 Insights from Clinical Physiology

Rolf-Detlef Treede

Insights on acute pain Practical consequences Ask each patient about movement-evoked pain, and Aside from alleviating suffering, one of the major treat with eff ective, multimodal analgesics. aims of postoperative pain management is to facilitate and speed up recovery, reestablish mobility, and ultimately favor a rapid discharge. One of the funda- Insights on cancer pain mental mechanisms in the nociceptive system is interfering with these aims is called central sensitiza- One of the most painful conditions in a patient with tion. Sensitization is a basic learning mechanism that advanced cancer is bone metastasis. Th is well-known describes an increased neural response when stimuli clinical reality is in confl ict with traditional basic sci- of constant intensity are simply repeated. (Its coun- ence teaching: according to standard textbooks, only terpart, habituation, a decrease in response upon re- the periosteum is innervated, but not the bone itself. petitive stimulation, is less prominent in the nocicep- If this were true, only large bone metastases that ex- tive system). In central sensitization, the increased tend into the periosteum should be painful. But ex- neural response is due to enhanced efficacy of the perience teaches otherwise: fortunately, painful bone synaptic connections within the nociceptive system. metastases usually have not yet destroyed the com- Central sensitization mostly enhances pain to me- pacta. Th us, when they are treated causally by radia- chanical stimuli, whereas peripheral sensitization al- tion or chemotherapy, the stability of the bone is still most exclusively increases heat pain sensitivity. This preserved. It is also well known that aspiration of makes central sensitization highly relevant in the bone marrow is very painful, in spite of local anesthe- postoperative setting. sia of the periosteum. When sensitization occurs in the nociceptive sys- Th us, the bone’s interior structures are densely in- tem, the patient perceives more pain in response to nervated by nociceptive aff erents, probably very similar relatively mild stimuli such as moving around in bed to the innervation of teeth. Only recently have anato- or coughing. As a consequence, the patient will move mists been able to demonstrate nociceptive nerve fi bres less and breathe less deeply, in order to titrate the pain within the bone using the marker CGRP (calcitonin down to a tolerable level. Fortunately, eff ective pain gene-related peptide), where they appear to have con- treatment (e.g., with opioids or local anesthesia) also tacts with both the bone trabecula and the osteoclasts. reduces central sensitization. Physiologically, there is also some recent evidence that

Practical consequences Insights on chronic pain It is diffi cult to judge the level of pain and discomfort Migraine is a frequent headache syndrome that has in infants due to their strong refl ex responses that may a major impact on quality of life. In spite of major re- or may not run parallel to conscious perception. To search, its pathophysiology is still not fully understood. be on the safe side, adequate anesthesia and analgesia Clinical Physiology Pearls 347 are considered the standard of care at all ages. Special special observer-based scales have been developed regimens apply, and most medications are being used and validated to allow assessment of pain and suff er- off -label. ing in this vulnerable group. Th ere is some evidence that the placebo eff ect is less effi cacious in demented Insights on pain in people. Decline in liver and kidney function, on the other hand, makes dosage adjustments necessary for old age and dementia many medications. Pain thresholds and pain-evoked brain potentials have Practical consequences been studied in healthy volunteers up to the age of 100 years. Pain thresholds and evoked potential latencies Many people maintain normal functions of their no- slightly increase and evoked potential amplitudes de- ciceptive system way into old age. When dementia is crease at ages above 80 years. In many cases, however, present, pain assessment relies increasingly on the ob- verbal communication skills may deteriorate in old age, servation of pain-related behavior. It is currently as- with large individual variations. In this situation, pain sumed that the level of pain in demented patients is un- assessment becomes diffi cult. For demented people, derestimated substantially.

Guide to Pain Management in Low-Resource Settings

Chapter 48 Herbal and Other Supplements

Joel Gagnier

What is the defi nition Other activities followed, including international con- of natural health products? ferences and research exchanges. Natural health products include vitamins, minerals, What supplements are herbal medicines, homeopathics and other naturally de- best for acute pain? rived substances (e.g., glucosamine, bee pollen) to prevent or treat various health conditions. Surgical procedures and acute trauma may be ad- In the developing world, it would be advis- dressed by several natural health products. For exam- able to consult local elders or healers to determine lo- ple, the homeopathic remedies Arnica and Hypericum cal plants or foods that may be used. You should get may be useful prior to and after surgery. Arnica is par- instructions on how to use them safely. Traditional ticularly useful for decreasing pain, bruising discolor- knowledge from a respected elder, healer, or tribal chief ation, and discomfort in the patient. Homeopathic Hy- may be reliable information. Always think about the pericum is very useful to heal incisions and eliminate risk/benefi t ratio, since natural health products might pain. Th ese remedies can be given orally at 200C po- contain “unnatural” ingredients, such as heavy metals or tencies every 2–4 hours on the day prior to surgery and other contaminants. Th erefore, the use of natural health after surgery until the incision is healed. For acute trau- products depends on mutual trust between the care- ma to muscles, ligaments, and tendons, topical creams giver and the healer, since there are few evidence-based or ointments containing Harpagophytum procumbens data and standardized products available. (Devil’s claw), Capsicum frutescens (cayenne), homeo- It is advisable to seek cooperation between the pathic Arnica, or methylsulfonylmethane (MSM) may “offi cial” and “unoffi cial” medical sector, both to broad- be applied 3–4 times per day on the aff ected site as en therapeutic options and to avoid counterproduc- long as the skin is intact. tive interactions. Some initiatives have undertaken this task. For example, in 1998 a task force was set up by the What supplements are best Ministry of Health in Ghana to identify the credible Na- for neuropathic pain? tional Healer Associations. Six such healer associations were identifi ed. Th ese associations came together to Peripheral neuralgias, if caused by malnutrition, may form the nucleus of the Ghana Federation of Traditional be treated by supplementation with vitamins. Vitamins

Medicine Practitioners’ Associations (GHAFTRAM). E, B1, B3, B6, and B12 are essential for adequate nerve Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. All rights reserved. Th is material may be used for educational and training purposes with proper citation of the source. Not for sale or commercial use. No responsibility is assumed by IASP for any injury and/or damage to persons or property 349 as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the medical sciences, the publisher recommends that there should be independent verifi cation of diagnoses and drug dosages. Th e mention of specifi c pharmaceutical products and any medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text. 350 Joel Gagnier function. A diet with regular fruit and vegetable intake with oral glucosamine sulfate at 1500 mg per day to- would include these vitamins, or alternatively a simple gether with oral chondroitin sulfate at 1200 mg per day; multivitamin mineral formula would be suffi cient. In oral unsaponifi able fractions of avocado and soybean patients with diabetic neuropathy, besides adequately oils at 300 mg per day; oral Harpagophytum procum- controlling blood sugar, vitamin B6 at 150 mg or vitamin bens (Devil’s claw) 2400 mg per day; and topical creams E at 800 IU per day may be eff ective. Th ese supplements containing a combination of camphor, glucosamine may be used together. A simple dietary intervention to sulfate, and chondroitin sulfate. Mild to moderate OA aid in blood sugar control is the regular consumption of may respond to a treatment starting with glucosamine beans and legumes. sulfate (1500 mg/day) and chondroitin sulfate (1200 mg per day) for 4–6 weeks, and if there is a limited eff ect What supplements are adding oral unsaponifi able fractions of avocado and soybean oils and Devil’s claw. Rheumatoid arthritis may be best for chronic pain? treated with oral borage seed oil at 1–1.5 grams per day, Chronic unspecifi ed back pain may be treated with oral oral fi sh oil providing eicosapentaenoic acid (EPA) and Harpagophytum procumbens (Devil’s claw) at 2000– docosahexanoic acid (DHA) at 2 grams/day, oral vita- 3000 mg per day, delivering 50–100 mg of the active min E at 800 IU per day, or oral Tripterygium wilfordii constituent harpagoside; oral willow bark (Salix alba, (thunder god vine) at 200–600 mg per day. Salix daphnoides, or Salix purpurea) at 1200 mg per day, delivering 120–240 mg of the active constituent What supplements are best for salicin; or topical capsicum cream. Dysmenorrhea may special therapeutic situations? be treated with oral calcium at 1000–1500 mg per day, magnesium at 300–400 mg per day, vitamin B6 at 100 Dementia of the Alzheimer’s type may be eff ectively mg per day, vitamin E at 400–800 IU per day, or Vitex treated with oral Ginkgo biloba (Ginkgo) at 120–240 mg agnus-castus (chaste berry) at 20–40 mg per day. For per day, oral Melissa offi cinalis (lemon balm) at 60 drops migraine headaches the following are eff ective: vitamin of a 45% alcohol extract, oral Salvia offi cinalis (sage) at

B2 400 mg per day, Tanacetum parthenium (feverfew) 1000 mg per day, or oral vitamin E at 2000 IU per day. 100 mg per day, magnesium 500 mg per day, or Petasites Th ese supplements may be used in isolation or in com- hybridus (Butterbur) 150 mg per day. Th ese can be used bination. It may take 3–4 months before any eﬀ ects of individually or in combination. Rheumatic pain in the these interventions are seen. form of osteoarthritis (OA) may be successfully treated Guide to Pain Management in Low-Resource Settings

Chapter 49 Proﬁ les, Doses, and Side Eﬀ ects of Drugs Used in Pain Management

Barbara Schlisio

Th e following drug list is a selection of commonly used of high methodological quality. Th is means that safety drugs for pain management. Th e selection refl ects rec- is an issue to be considered when selecting a drug: the ommendations of the “Essential Drug List for Cancer” possible positive eff ects must always be balanced against from Makarere University and the health ministry in possible side eff ects. A good recommendation would be Uganda for the treatment of cancer patients, which ap- to think, when prescribing a drug, whether you would pear to be a reasonable drug selection for treatment prefer the same drug when in a comparable situation, of the most common pain syndromes encountered by since it is your decision to select pharmacological treat- nonspecialists in a low-resource setting. ment. Th is overview explains the mode of action as Pharmacological treatment should be explained well as typical side eff ects of drugs. “Typical side eff ects” thoroughly to the patient, and “informed consent” means that other side eff ects have been described, but I should be obtained in the same way as for a surgical in- have selected from the lengthy lists of side eff ects men- tervention. A valuable tool to avoid misunderstandings tioned in desk references the ones that are most impor- and “incompliance” by the patient is the use of a simple tant for the therapist and the patient to know about. (makeshift) “information sheet” to be given to patients Pharmacological therapy in pain management is when they leave the offi ce with their prescription. often selected because of positive empirical knowledge, Here is an example of an information sheet to because most of the time there are no controlled studies give to patients:

Name of Drug How to Take It What Is It For ? Important Information Morphine 1 tablet of 20 mg: Strong painkiller for con- Nausea and tiredness are possible 6–12–18–24 o’clock tinuous pain control the fi rst week. Never change the dose on your own! Morphine 1 tablet of 10 mg as needed Strong painkiller to be taken See above. Minimum time between if pain increases extra morphine tablets: 30 minutes. Metoclopramide 40 droplets: Prevents nausea caused by Should be taken for 10 days. After 6–12–18–24 o’clock morphine that, try to go without it. Carbamazepine 1 tablet of 200 mg: Helps against shooting Dizziness and tiredness in the fi rst 8–16–24 o’clock nerve pain few days or weeks. Remember to come to the offi ce to have a blood sample taken in one week.

Equianalgesic doses of morphine Coanalgesics are drugs that were originally developed for Intravenous (i.v.) 10 mg purposes other than analgesia, but were then found to be Subcutaneous (s.c.) useful in certain pain states. Th eir use is common in neu- Intramuscular (i.m.) ropathic pain, where NSAIDs and antipyretics are ineff ec- Oral 30 mg tive most of the time and opioids often fail to be eff ective. Epidural 2–3 mg Although a number of substances have shown Intraspinal 0.1–0.3 mg to have “coanalgesic” properties (among others: capsaicin, mexiletine, amantadine, ketamine, and cannabis), only antidepressants, anticonvulsants, and steroids are Transdermal opioids used regularly and are most likely to be available in low- Two patches are now available for the delivery of resource settings. Th e use of coanalgesics necessitates opioids—the fentanyl patch and the buprenorphine knowledge of how to balance benefi ts and risks and patch. These drugs are strongly lipophilic, allowing avoid side serious side eff ects. good passage through the skin into the circulation As with opioids the doses of most coanalgesics and avoiding first-pass metabolism in the liver. Con- have to be titrated to the eff ect, meaning, that the dose sider that analgesia and side- effect profile do not recommendations for their original indications cannot change by using the transdermal route. Therefore, be transferred to the indication “pain”. As always when only patients with swallowing problems or recurrent treating pain, use thorough patient education to gain vomiting would benefit from this route of applica- good patient compliance and adjust and readjust doses tion. If transdermal systems are used, remember that and drug selection to gain the best results for your pa- they are indicated only in patients with stable opi- tients. Don´t forget to give a message of hope to your oid requirements and that it takes around half to one patient but be honest with him and set realistic goals: day for the patch to produce a steady state of opioid coanalgesics will not take away the pain, but will only be delivery to the patient (and the same time for blood able to give some relief! levels to decrease if the patch is taken off). In conclusion, the vast majority of patients in cancer and Anticonvulsants palliative care may be treated well with opioids with- Th ey reduce neuronal excitability and suppress par- out the use of transdermal systems (which are also oxysmal discharge of the neurons by stabilizing neu- considerably more expensive!). ral membranes. Anticonvulsants work by interacting with diff erent mechanisms, e.g., the voltage dependent Adjuvant medications for opioid-related sodium channel or by the high voltage calcium chan- side eff ects nels. Anticonvulsants of the sodium channel blocking Nausea, vomiting, and constipation associated with type (carbamazepine, oxcarbazepine or lamotrigine) opioids need a concomitant “adjuvant” medication. show best results in attack like shooting pain, e.g., in Without one, your patients’ compliance will be low! patients, where the cancer has infi ltrated nerve plexus For the fi rst week of opioid therapy, metoclopramide or in trigeminal neuralgia. Anticonvulsants of the cal- 10 to 30 mg q.i.d. should always accompany the opi- cium channel blocking type (gabapentin, pregabalin) oid. As mentioned above, earlier tolerance to the nau- are indicated above all for continuous burning pain, seating side eff ects of opioids will then develop. Seda- e.g., in patients with polyneuropathies or postherpetic tion must to be explained to the patient, since there is neuralgia. Th e latter seem to have a synergistic eff ect no eff ective adjuvant medication to counteract it. For on the calcium channels with opioids. Phenytoin can constipation, a constant prophylactic laxative therapy be used as a “rescue” substance for severe and therapy must be initiated immediately with the start of an opi- resistant neuropathic pain. All anticonvulsants should oid. Milk sugar or bisacodyl are good choices. See the be titrated according to the rule “start low, go slow”. chapter on constipation for further details on this ther- Recommended dose ranges for the most common an- apeutic problem. ticonvulsants in pain management are: 356 Barbara Schlisio

Substance Starting Dose Maximum Dose Remarks Carbamazepine 3 × 100 mg 1600 mg/day A low dose is often eﬀ ective Oxcarbazepine 3 × 150 mg 2250 mg/day Th ere is less dizziness and sedation Gabapentin 3 × 100–300 mg 3600 mg/day A high dose is often required Pregabalin 2 × 25 mg 300 mg/day Has anxiolytic eﬀ ects Phenytoin 1 × 100 mg 400 mg/day Avoid long-term use

All anticonvulsants produce drowsiness and not eff ective, unfortunately. Th e only SNRIs considered dizziness, although this problem can be minimized by to be eff ective in the latest meta-analysis are venlafaxine increasing the dose slowly, every 4 to 8 days depending and duloxetine. on the individual side-eff ect tolerance. In carbamaze- Antidepressants induce analgesia by increasing pine and oxcarbazepine, regular blood tests (e.g., weekly the neurotransmitters serotonin and norepinephrine for 4 weeks, then monthly for 3 months, and then once in the descending inhibitory nervous system (e.g., in every 3 months) are necessary to identify patients with the periaqueductal gray). Additionally, antidepressants elevation of liver enzymes, idiosyncratic drug reactions, modulate the opioid system in the central nervous sys- and hyponatremia. Idiosyncratic drug reactions denote tem. Some side eff ects can be used for the benefi t of the a non-immunological hypersensitivity to a substance, patient, such as the sedating eff ect of amitriptyline for without any connection to pharmacological toxicity. better sleep and the anxiolytic eff ect of clomipramine Th e medication has to be stopped in all cases of idio- for relaxation. If the patient is in an advanced stage of syncratic reaction, if liver transaminases are above ca. disease with impaired general condition or comorbidi- 200 and if sodium is below 125. Th e same applies to ties, nortriptyline and desipramine seem to be safer al- phenytoin (with the exception of the danger of develop- ternatives to use within the class of tricyclic antidepres- ing hyponatremia), for which a normal ECG (look espe- sants. cially for AV-conduction abnormalities) should also be As with anticonvulsants, the eff ective dose has a prerequisite. For gabapentin and pregabalin, no blood to be titrated individually using the rule “start low, go tests or ECG controls are necessary. Contraindications slow” to avoid debilitating side eff ects. All tricyclic an- for all anticonvulsants include porphyria, lactation, my- tidepressants should be started with a dose of 10 mg at asthenia gravis, glaucoma, and chronic renal or hepatic nighttime, and the dose should be increased every 4–8 failure. days by only 10–25 mg daily. Elderly patients should not be medicated with Antidepressants tricyclic antidepressants because of multiple drug inter- Antidepressants were the fi rst coanalgesics used after actions and an increased rate of falls. For all other pa- it was found that they eff ectively reduced pain in poly- tients it has to be remembered that the analgesic eff ect neuropathy, even in patients who were not depressed. often starts after a delay, and therefore the caregiver as Th ey have been found to be eff ective in the treatment of well as the patient have to have some patience before constant burning neuropathic pain of diff erent origins. deciding whether the treatment is eff ective. Furthermore, antidepressants are also useful in treating Th e most frequent side eff ects are due to the tension type headache and as a prophylactic treatment anticholinergic properties of antidepressants (mostly of in migraine headache. Contrary to common belief, there the tricyclic class) via the muscarinic receptors. Such is no “general pain-distancing” eff ect, so antidepressants anticholinergic eff ects include xerostomia (dry mouth), should only be used for the indications named above. constipation, urinary retention, blurred vision and im- As a general rule, the “classical” tricyclic antidepressants paired accommodation, tachycardia, and slowed gastric are the most eff ective in pain management. Although emptying. Explain to patients that they are receiving the the best evidence exists for amitriptyline, all tricyclic medication for pain, since they might read the package antidepressants are considered equally eff ective. Th e explanation, where “depression” is the only indication. newer and more tolerable selective serotonin and nor- Also let the patient know that sedation and most other epinephrine reuptake inhibitors (SNRIs) and selective side eff ects usually wear off over several weeks. Explain serotonin reuptake inhibitors (SSRIs) are less potent or that these medications relieve pain but do not resolve it. Drug Profi les, Doses, and Side Eff ects 357 Because tricyclic antidepressants may impair the problem). Always identify and treat the underlying liver function, it is advisable to check the liver enzymes cause along with giving symptomatic treatment with regularly (e.g., once a month for 3 months and than neuroleptics (titrate in increments of 2.5 mg to eff ect once every 3 months). Before initiating tricyclic antide- with haloperidol with a “normal” daily dose of 2.5 to 5 pressant medication, check the ECG for major AV node mg t.i.d.). In advanced cancer patients, delirium may irregularities and polytope extrasystoles. also be a sign of reaching the terminal stage (“terminal Up to 20% of cancer patients develop episodes disorientation”). Even at the fi nal stage of illness, deliri- of depression, and in this case antidepressants with the um should be treated, to reduce the stress of the patient lowest side eff ects should be used (SNRIs and SSRIs). and family. Neuroleptics (like benzodiazepines) have no an- Steroids algesic effi cacy and therefore should never be used for Steroids are widely used in cancer pain therapy, es- the indication of pain. Pain needs analgesics and not se- pecially in patients with an advanced stage of disease. dation, with the exception of terminal sedation, when all Th ese agents reduce perineural edema and may inhib- available alternatives for pain control fail. it spontaneous activity in excitable, damaged nerves Note also that neuroleptics are potent blockers due to cancerous infi ltration or compression of nerval of D2 receptors in the dopamine pathways of the brain. structures. Because of their anti-infl ammatory eff ects, Th erefore, they have direct eff ects on opioid-induced steroids may be also used in chronic infl ammatory dis- nausea and are very valuable antiemetics (a dose of 0.5 eases, such as rheumatoid arthritis. In cancer patients to 1 mg of haloperidol t.i.d. is suffi cient for that purpose the drug of choice is dexamethasone, which provides and is without psychomimetic eff ects). only glucocorticoid properties, causing less fl uid reten- Other neuroleptics that may be available in- tion and potassium loss as compared to hydrocortisone clude thioridazine (25 to 50 mg daily), chlorpromazine, or prednisolone. Th ere is no evidence-based dosing and levopromazine. Th ey all have a low neuroleptic po- scheme, but in acute pain exacerbation because of mas- tency, but a good sedating eff ect, and therefore may be sive cancer progression, a common approach would be used as sleeping pills in cancer patients. Th e new “atypi- to use a loading dose of approximately 24 mg the fi rst cal” neuroleptics such as olanzapine or risperidone are day and then reduce the dose subsequently over the fol- not the fi rst choice for cancer patients and should be re- lowing days to a maintenance dose of 2 mg daily. served for patients with psychiatric disorders. Side eff ects can prove to be benefi cial for the Antipsychotics are associated with a wide range patient, such as euphoria and an increased appetite in of side eff ects. Extrapyramidal reactions include acute cachectic patients. “Negative” uncommon side eff ects dystonia, tardive dyskinesia, and Parkinson-like symp- may include psychotic episodes and myopathies. Other toms (rigidity and tremor) due to blockage of dopamine typical side eff ects such as osteoporosis, skin thinning, receptors. Tachycardia, prolonged QT interval, hypo- diabetes, and adrenal suppression are of less importance tension, impotence, lethargy, seizures, and nightmares in the target patient with limited life expectancy. To lim- are possible. Another serious side eff ect is neuroleptic it the risk of gastric ulcers, do not combine NSAIDs and malignant syndrome. In this case the temperature regu- steroids, and do not use steroids unless critical in the lation centers fail, resulting in a medical emergency, as noncancer patient. the patient’s temperature suddenly increases to dangerous levels. Most of the above-mentioned side eff ects are Neuroleptics fortunately rare and not of relevance in the period of the Neuroleptics are psychoactive drugs that are commonly end of life. used to treat psychotic episodes and nausea. Patients with advanced cancer often suff er from delirium. Do Benzodiazepines not underestimate the distress for the patient and family Benzodiazepines are a group of drugs with varying in the presence of delirium. Try to identify the reason sedative, anxiolytic, anticonvulsant, and muscle relax- for the delirium. Most of the time it is the fi rst sign of ant properties. Th e main indication for these drugs in infection, renal failure, dehydration, or electrolyte im- pain management and the palliative care management balances. In rare instances, it may also be a side eff ect of is the treatment of anxiety and intractable dyspnea. opioid therapy (in which case, opioid rotation will solve Do not hesitate to prescribe these drugs for terminal 358 Barbara Schlisio ill patients, who suff er from panic attacks, dyspnea and dose is between 2 and 10 mg as a single dose or twice insomnia. Benzodiazepines are highly benefi cial in the daily. Sometimes it is necessary to increase the dose ex- palliative care setting. tensively without negative consequences. Diazepam, in Benzodiazepines bind at the interface of the α combination with morphine, is the drug of fi rst choice and γ subunits on the γ-aminobutyric acid (GABA) re- for palliative sedation. For trait anxiety in terminal ill- ceptor, the most prevalent inhibitory receptor within ness, fl unitrazepam subcutaneously once daily is a very the entire brain. Th e anticonvulsant properties of ben- eff ective choice (normally in a dose range between 0.5 zodiazepines may be in part or entirely due to binding and 5 mg). to voltage-dependent sodium channels. During the course of therapy with benzodiaze- Benzodiazepines are well-tolerated and safe. pines, tolerance to the sedative eff ects usually develops, If you want to treat panic attacks, use benzodiazepines but not to the anxiolytic eff ects. Diazepam does not in- with shorter half-lives, such as lorazepam. Diazepam has crease or decrease hepatic enzyme activity. Th ere is no a long half-life. Diazepam can be administered orally, real contraindication in the palliative setting if used with intravenously, intramuscularly, or as a suppository. Th e care, titrated to eff ect, and used where indicated. Guide to Pain Management in Low-Resource Settings

Appendix: Glossary

Andreas Kopf

Introduction review, these experts agreed to take advantage of the A list of pain terms was fi rst published in 1979 (PAIN publication of the draft collection of syndromes and 1979;6:249–52). Many of the terms were already estab- their system for classifi cation, to issue an updated list of lished in the literature. One, “allodynia,” quickly came terms with defi nitions and notes on usage. Edited by H. into use in the columns of PAIN and other journals. Merskey and N. Bogduk, the updated list was published Th e terms have been translated into Portuguese (Re- in 1994 by IASP as Classifi cation of Chronic Pain, Sec- vista Brasiliera de Anestesiologia 1980;30:349–51), into ond Edition. French (H. Dehen, “Lexique de la douleur,” La Presse Th e usage of individual terms in medicine often Médicale 1983;12:1459–60), and into Turkish (as “Agri varies widely. Th at need not be a cause of distress, pro- Teriml,” translated by T. Aldemir, Journal of the Turkish vided that each author makes it clear precisely how he is Society of Algology 1989;1:45–6). A supplementary note using a word. Nevertheless, it is convenient and helpful was added to these pain terms in PAIN (1982;14:205–6). to others if words can be used that have agreed techni- Th e original list was adopted by the fi rst Sub- cal meanings. Th e defi nitions provided in this Appendix committee on Taxonomy of IASP. Subsequent revisions are intended to be specifi c and explanatory and to serve and additions were prepared by a subgroup of the Com- as an operational framework, not as a constraint on fu- mittee, particularly Drs. U. Lindblom, P.W. Nathan, W. ture development. Th ey represent agreement among Noordenbos, and H. Merskey. In 1984, in particular diverse specialties including anesthesiology, dentistry, response to some observations by Dr. M. Devor, a fur- neurology, neurosurgery, neurophysiology, psychiatry, ther review was undertaken both by correspondence and psychology. and during IASP’s 4th World Congress on Pain. Th ose Th e terms and defi nitions are not meant to pro- taking part in that review included Dr. Devor, the other vide a comprehensive glossary, but rather a minimum colleagues just mentioned, and Dr. J.M. Mumford, Sir standard vocabulary for members of diff erent disci- Sydney Sunderland, and Dr. P.W. Wall. Following that plines who work in the fi eld of pain.

359 360 Andreas Kopf Acupuncture that diverge from the expected. “Odynia” is derived from Acupuncture is a procedure involving the stimulation or the Greek word “odune” or “odyne,” which is used in inhibition of anatomical locations on or in the skin by a “pleurodynia” and “coccydynia” and is similar in mean- variety of techniques. A number of eff ects on pain phys- ing to the root from which we derive words with “algia” iology have been identifi ed, the most important being or “algesia” in them. It is important to recognize that al- the activation of the endogenous opioid system and the lodynia involves a change in the quality of a sensation, spinal modulation of pain signalling through activation whether tactile, thermal, or of any other sort. Th e origi- of touch fi bers (Aβ fi bers). Th ere are a number of dif- nal modality is normally nonpainful, but the response ferent approaches to diagnosis and treatment in modern is painful. Th ere is thus a loss of specifi city of a sensory acupuncture that incorporate medical traditions from modality. By contrast, hyperalgesia represents an aug- China, Japan, Korea, and other countries. Acupuncture mented response in a specifi c mode. With other cuta- was originally part of traditional Chinese medicine. In neous modalities, hyperesthesia is the term that cor- the 1950s, French military physicians from Vietnam responds to hyperalgesia, and as with hyperalgesia, the “exported” the technique to Europe, where it was used quality is not altered. In allodynia the stimulus mode mostly as a complementary treatment to mainstream and the response mode diff er, unlike the situation with medicine. A few indications in pain medicine, such as hyperalgesia. Th is distinction should not be confused by certain types of joint pain, back pain, and headache syn- the fact that allodynia and hyperalgesia can be plotted dromes may benefi t from acupuncture. with overlap along the same continuum of physical intensity in certain circumstances, for example, with pres- Addiction sure or temperature. Allodynia might be provoked by Addiction is a chronic relapsing condition character- the touch of clothes, such as in patients with posther- ized by compulsive drug-seeking and drug abuse and by petic neuralgia. Its management may be diffi cult. Apart long-lasting chemical changes in the brain. Addiction from coanalgesics, local treatment with local anesthetics is the same irrespective of whether the drug is alcohol, and/or capsaicin might be of help. amphetamines, cocaine, heroin, marijuana, or nicotine. Every addictive substance induces pleasant states or re- Anesthesia dolorosa lieves distress. Continued use of the addictive substance Pain in an area or region that is anesthetic. Th erefore, induces adaptive changes in the brain that lead to toler- neurodestructive techniques in pain management ance, physical dependence, uncontrollable craving, and, should be limited to the few indications where anesthe- all too often, relapse. Th e genetic factors predisposing sia dolorosa has not been observed. to addiction are not yet fully understood. Addiction has Analgesia to be separated from dependence. For example, in long- term opioid therapy, dependence is a normal result, and Absence of pain in response to stimulation that would the only clinical implication is that dose reduction has normally be painful. As with allodynia, the stimulus is to be stepwise. Addiction to opioids is very rare in pain defi ned by its usual subjective eff ects. Analgesics are patients without preexisting addiction problems. Th ere- used in both acute and chronic pain. Whereas acute fore, asking the patient about alcohol, opioid, and ben- (e.g., postoperative, post-traumatic) pain is generally zodiazepine consumption is a prerequisite before start- amenable to drug therapy, chronic pain is a complex ing an opioid medication. disease in its own right and needs to be diff erentiated into malignant (cancer-related) and nonmalignant (e.g., Allodynia musculoskeletal, neuropathic, or infl ammatory) pain. Allodynia is pain due to a stimulus that does not nor- Acute and cancer-related pain are commonly treat- mally provoke pain. Th e term “allodynia” was originally able with opioids, NSAIDs, and/or local anesthetic introduced to distinguish such pain from hyperalgesia blocks. Chronic nonmalignant pain requires a multi- and hyperesthesia, the conditions seen in patients with disciplinary approach encompassing various pharma- lesions of the nervous system where touch, light pres- cological and nonpharmacological (e.g., psychological, sure, or moderate cold or warmth evoke pain when ap- physiotherapeutic) treatment strategies. Various routes plied to apparently normal skin. “Allo-” means “other” of drug administration (e.g., oral, intravenous, subcuta- in Greek and is a common prefi x for medical conditions neous, intrathecal, epidural, topical, intra-articular, and Appendix: Glossary 361 transnasal) are used depending on the clinical circum- activity in sensitized nociceptors from regenerating stances and available substances. Local anesthetics are nerve sprouts, recruitment of previously “silent” no- used topically and in regional (e.g., epidural) anesthetic ciceptors and Aβ fi bers, and spontaneous activity in techniques for the treatment of acute pain (e.g., associ- dorsal root ganglion cells. Th e increase of peripheral ated with surgery, childbirth) and some selected chronic neuronal activity is transmitted centrally and results pain syndromes. In general, the oral route of application in sensitization of second- and third-order ascend- is preferred, but in emergency situations and periopera- ing neurons. Among the best studied mechanisms of tively the parenteral route is preferred. Th e use of trans- peripheral and central sensitization are the increased dermal, oral transmucosal, and intranasal applications novel expression of sodium channels, and increased may be benefi cial to selected patients if available, but in activity at glutamate (NMDA) receptor sites. Th e general, high-quality pain management is possible with- mechanisms of action of antiepileptics include neuro- out them. nal membrane stabilization by blockage of pathologically active voltage-sensitive sodium channels (carba- Analgesics mazepine, phenytoin, valproate, lamotrigine), blockage Analgesics interfere with the generation and/or trans- of voltage-dependent calcium channels (gabapentin, mission of impulses following noxious stimulation (no- lamotrigine), inhibition of presynaptic release of excit- ciception) in the nervous system. Th is interference can atory amino acids (lamotrigine), activation of GABA occur at peripheral and/or central levels of the neur- receptors (valproate, gabapentin), opening of KATP chan- axis. Th e therapeutic aim is to diminish the perception nels (gabapentin), potential enhancement of GABA of pain. Analgesics can be roughly discriminated by turnover/synthesis (gabapentin), increased nonvesicular their mechanisms of action: opioids, nonsteroidal anti- GABA release (gabapentin), and inhibition of carbonic infl ammatory drugs (NSAIDs), serotoninergic com- anhydrase in neurons (topiramate). pounds, antiepileptics, and antidepressants. Adrenergic agonists, excitatory amino acid (e.g., N-methyl-D-aspar- Antidepressants tate [NMDA]) receptor antagonists, neurokinin recep- Antidepressants are used—in the same manner as an- tor antagonists, neurotrophin (e.g., nerve growth fac- tiepileptics—in neuropathic pain and migraine pro- tor) antagonists, cannabinoids, and ion channel blockers phylaxis. Tricyclic antidepressants have the highest are currently under intense investigation but are not yet eff ectivity. Th ey are titrated to eff ect. Th e purpose used routinely. Local anesthetics are used for local and of monitoring plasma drug concentrations is not to regional anesthetic techniques. Some drugs (e.g., trama- achieve optimal eff ect, but to avoid toxicity and con- dol) combine various mechanisms. trol patient compliance. In most patients, pain reduction may be achieved with a low dose (e.g., 50 to 75 Antiepileptics (anticonvulsants) mg/day of imipramine or amitriptyline). As with all Various antiepileptics (carbamazepine, phenytoin, val- coanalgesic treatment options for neuropathic pain, proate, gabapentin, lamotrigine, and pregabalin) have patients should be told before the start of therapy that been used for neuropathic pain and more recently for the treatment goal may only be a 50% pain reduction. migraine prophylaxis as well. Together with antidepres- Studies have demonstrated that even with optimized sants, they are the most eff ective coanalgesics. Th e most treatment, only half of all patients with neuropathic common adverse eff ects are impaired mental function pain will achieve this goal. In migraine prophylaxis, the (somnolence, dizziness, cognitive impairment, and fa- numbers are higher. tigue) and motor function (ataxia), which may limit In patients with ischemic heart disease, there clinical use, particularly in elderly patients. Serious side may be increased mortality from sudden arrhythmia, eff ects have been reported, including hepatotoxicity, and in patients with recent myocardial infarction, ar- thrombocytopenia, and life-threatening dermatological rhythmia, or cardiac decompensation, tricyclics should and hematological reactions. Plasma drug concentra- not be used at all. Tricyclics also block histamine, cho- tions should be monitored to avoid toxic blood levels. A linergic, and alpha-adrenergic receptor sites. Adverse number of antiepileptics are used in neuropathic pain. events include fatigue, nausea, dry mouth, constipation, Diff erent neuropathic pain syndromes have been attrib- dizziness, sleep disturbance, blurred vision, irritability/ uted to certain common mechanisms, including ectopic nervousness, sedation, and hepatotoxicity. 362 Andreas Kopf

Several antidepressants are used in the treat- of physical symptoms of arousal. Fears in correlation ment of neuropathic pain. Th ey include the clas- with pain are often understandable, for example, anxi- sic tricyclic compounds—divided into nonselective ety about increasing physical impairment and anxiety norepinephrine/5-HT reuptake inhibitors (e.g., ami- about losing one’s employment. In consequence, dis- triptyline, imipramine, and clomipramine) and pref- orders of anxiety can be the result of chronic pain, but erential norepinephrine reuptake inhibitors (e.g., de- they can also be the cause of physical symptoms. For sipramine and maprotiline), selective 5-HT reuptake example, severe chest and heart pain as well as breath- (serotonergic) inhibitors (e.g., citalopram, paroxetine, lessness are some of the symptoms of a panic attack. and fl uoxetine) and 5-HT2 antagonists (nefazodone). One consequence of chronic pain can be agoraphobia, Th e reuptake inhibition leads to a stimulation of en- for example, if the patient is afraid to leave the house dogenous monoaminergic pain inhibition in the spinal because the pain attack might occur on the street, and cord and brain. In addition, tricyclics have NMDA- nobody would be there to help. In consequence, the pa- receptor antagonist, sodium-channel-blocking, and tient tends more and more to avoid leaving the house. potassium-channel-opening eff ects that can suppress Th e most common screening instruments for anxi- peripheral and central sensitization. Block of cardiac ety disorders are the Hospital Anxiety and Depression potassium and sodium channels by tricyclics can lead Scale (HADS-D), State-Trait-Anxiety Inventory (STAI), to life-threatening arrhythmias. Th e selective 5-HT and Profi le of Mood States (POMS). transporter inhibitors lack postsynaptic receptor block- Anxiolytics ing and membrane stabilization eff ects (and the resulting side eff ects) and therefore have only a limited role in Anxiolytics are medications used to treat anxiety. Short- neuropathic pain treatment. acting anxiolytics, especially from the class of benzodiazepines, maybe benefi cial for panic attacks, while Anxiety long-acting anxiolytics, also mostly from the class of Anxiety is a feeling of apprehension and fear charac- benzodiazepines, play a role in palliative medicine when terized by physical symptoms such as palpitations, trait anxiety is uncontrolled by psychological interven- sweating, and feelings of stress. Anxiety disorders tions. Th e antiepileptic drug pregabalin also has some are serious medical illnesses that aff ect pain patients anxiolytic eff ect without the risk of addiction of ben- more frequently than the average population. Th ese zodiazepines and may be benefi cial, therefore, in pain disorders fi ll people’s lives with overwhelming anxiety patients with a mild anxiety disorder. Although recom- and fear. Unlike the brief anxiety caused by a stressful mended in a number of textbooks, there is no indication event such as a business presentation or waiting for for anxiolytics as pain killers. surgery (state anxiety), anxiety disorders are chronic, relentless, and can grow progressively worse if not Arthritis treated (trait anxiety). Arthritis is the infl ammation of a joint, with typical In the case of chronic pain, both in developing symptoms including stiff ness (especially in the morn- and developed countries there is an increased preva- ing), warmth, swelling, redness, and pain. It can be di- lence of anxiety disorders such as generalized anxiety vided into osteoarthritis (with a degenerative etiology) disorder, panic disorder, social phobia, and post-trau- and rheumatoid arthritis (with an infl ammatory etiol- matic stress disorder (PTSD) in comparison to people ogy). If the cause of arthritis is rheumatic, infl amma- without pain. Th e prevalence increases when pain oc- tion control comes before pain management to avoid curs at multiple sites. It is often not possible to de- ongoing tissue destruction in the joint. NSAIDs and termine the direction of causality between pain and a opioids—sometimes given locally into the joint—are psychiatric disorder. In biopsychosocial models of ex- among the drugs of fi rst choice for severe arthritis. plaining the emotions, anxiety is seen as reaction of the organism to external experience (for example, an Bereavement experience of violence) and to internal stimuli (for ex- Th e act of grieving someone’s death. Bereavement is in- ample increased heart rate). Within the experience of tegrated into palliative care by off ering relatives support anxiety there is an unspecifi c feeling of excitement and after the death of the patient. Th erefore, palliative care tension as well as unpleasantness and the experience does not stop with the death of the patient. Appendix: Glossary 363 Bradykinin schools. While “alternative medicine” often is in con- Bradykinin is generated in the blood by the action of fl ict with mainstream medicine and includes sometimes the plasma kallikrein-kinin system (involving prekalli- rather bizarre methods, complementary medicine is krein activator, prekallikrein, kininogen, and kininases). “extending” the conventional medical approaches to en- It produces infl ammation and activates nociceptors via hance its eff ects. Well-known complementary medicine bradykinin B1 and B2 receptors. modalities include acupuncture, low-level laser therapy, meditation, aromatherapy, dance therapy, music thera- Calcitonin gene-related peptide py, herbalism, osteopathy, and naturopathy. Calcitonin gene-related peptide (CGRP) is a neuropeptide expressed in sensory neurons. It works as a Delirium stimulatory (pronociceptive) neurotransmitter when A disturbance of the brain function that causes confu- it is released centrally, and as a proinfl ammatory me- sion and changes in alertness, attention, thinking and diator when it is released peripherally. Th e central reasoning, memory, emotions, sleeping patterns, and role of CGRP in primary vascular headaches (e.g., mi- coordination. Th ese symptoms may start suddenly, graine) has led to the search for suitable antagonists are due to some type of medical problem, and may get of CGRP receptors. worse or better multiple times. Typical causes for delirium include acute infection or cancer progress (with Causalgia (complex regional pain syndrome liberation of TNF-alpha), sudden renal failure, certain type II) drugs including opioids (the incidence for opioids is Pain, usually burning pain, that is associated with auto- around 1–2%), and electrolyte imbalances. If opioids are nomic changes (changes in the color of the skin, chang- suspected to be the cause of delirium, a switch (rota- es in temperature, changes in sweating, and swelling). tion) to another opioid usually terminates the delirium Causalgia is rare and diffi cult to treat and occurs after a with hours. nerve injury. Th e pathophysiology of causalgia includes local infl ammation and reorganization processes in the Dependence central nervous system. If causalgia is suspected, diag- Physical dependence is a state in which the continuous nosis and treatment should be left to a pain specialist. presence of a drug is required to maintain normal func- Central pain tions of an organism. Discontinuation of the drug results in a withdrawal syndrome. Dependence is a “nor- Pain initiated or caused by a primary lesion or dys- mal” phenomenon occurring with a number of diff erent function in the central nervous system. It occurs in drugs. As a consequence, when opioids have been ad- some patients after stroke and may limit the quality of ministered for a prolonged period of time (> 3 weeks) life considerably. Only tricyclic antidepressants have in a dose of 50–100 mg oral morphine equivalents per been able to show any analgesic eff ectivity in these pa- day or more, they should never be acutely discontinued tients. All other treatment options are supported only but tapered with a daily dose reduction (e.g., a 10% daily by anecdotal evidence. dose reduction). Chronic pain Depression Chronic pain is diagnosed if pain persists longer than 6 Depression is a risk factor for pain chronifi cation. Cer- months. For clinical practice it is probably more help- tain screening questions aid in diagnosis. Common ful to defi ne chronic pain as pain that is complicated fi ndings are sleeping problems, unrest, a lack of ener- by certain risk factors according to the biopsychosocial gy that is pronounced in the fi rst half of the day, and concept of pain chronifi cation: central sensitization to loss of interest. Some common screening instruments painful stimuli, depression or anxiety, or somatoform for depression are the Center for Epidemiologic Studies disorders, as well as confl icts at the workplace or in the Depression Scale (CES-D), the Beck Depression Inven- family. tory for primary care, and the Profi le of Mood States Complementary medicine (POMS). A psychopathological result should howev- Approaches to medical treatment that are outside er always form the basis and include an evaluation of of mainstream medical training received in medical suicidal tendency. In accordance with the fi ndings of 364 Andreas Kopf an investigation by Tang et al. in 2006, the suicide rate is recognized that the borderline may present some dif- among chronic pain patients is increased (prevalence fi culties when it comes to deciding whether a sensation 5–14%) in comparison to the general public. Depression is pleasant or unpleasant. It should always be specifi ed is usually the strongest predictor of desire for death. It whether the sensations are spontaneous or evoked. is important to distinguish between passive thoughts of Dyspnea death or death wishes and active suicidal thoughts that involve an intent to take one’s life. It is helpful and reliev- Dyspnea is diffi culty in breathing and is often mixed ing for the patient when concrete questions are asked: up with respiratory depression. While dyspnea causes For example: “Do you ever think about committing sui- major suff ering by the feeling of suff ocation and may cide?” “Do you have a plan of how you want to commit be successfully relieved by morphine or other opioids suicide?” “Are you obsessed by thoughts of suicide?” Very in most cases, respiratory depression is a state of unre- often, patients have set a time, and so questions regard- sponsiveness of the central breathing regulation, which ing the point in time are important; the patient may may be caused by opioids. Since breathing depression agree to a postponement. Furthermore, previous suicide does not cause the patient to suff er (and therefore the attempts should be noted because they are an increased patient will not complain), personal or electronic moni- risk factor for a renewed suicidal tendency. toring, especially in the immediate postoperative period or after opioid applications, is necessary to avoid possi- Do-not-resuscitate (DNR) orders bly fatal complications. Instructions written, usually in the patient’s chart, by a Epidural space doctor or other health care provider. A rather “imprecise” method to indicate that because of an advanced Th e epidural space surrounds the dura mater of the disease stage the treatment of a patient should be re- spinal cord. It is bounded by the pedicles of the verte- stricted and especially exclude cardiopulmonary rebral arches and by the anterior and posterior ligaments suscitation (CPR) or other related treatments. Usually, connecting the bony vertebral column. Th e epidural DNR orders are written after a discussion between a space contains nerve roots, fat, and blood vessels and doctor and the patient and/or family members. Today is routinely used for perioperative analgesia as a single another concept is slowly replacing DNR called AND analgesia technique or in combination with general an- (“Allow Natural Death”). In this modern concept, the esthesia. Epidural analgesia is specially popular in the limitations in therapy are precisely documented after obstetrics department. discussion between the caregivers, the patient, and the Ethics family. Orders for AND may include specifi c topics such A system of moral principles and rules that are used as as antibiotics, ventilation, intensive care, dialysis, and standards for professional conduct. Many hospitals and catecholamines. other health care facilities have ethics committees that Durable power of attorney for health care can help doctors, other health care providers, patients, (DPOAHC) and family members in making diffi cult decisions re- In some countries a legal document has been intro- garding medical care. Besides helping in diffi cult medi- duced in the last years to allow communication be- cal situations, ethics conferences may also help bringing tween the patient and a caregiver in case the patient is together the diff erent disciplines of health care, allowing unresponsive due to his health situation. Th e document a joint approach for optimal care. Ethics committees are specifi es one or more individuals (called a health care usually not meant to set ethical standards—something proxy) the patient wants to make medical decisions if which mostly develops in society and in religious com- the patient becomes unable to do so. munities—but they help to interpret and transfer society’s standards into specifi c standards or fi nd solutions Dysesthesia for specifi c therapeutic dilemmas. An unpleasant abnormal sensation, whether spontaneous or evoked. Compare with pain and with paresthe- Fatigue sia. Special cases of dysesthesia include hyperalgesia and A feeling of becoming tired easily, being unable to com- allodynia. A dysesthesia should always be unpleasant, plete one’s usual activities, feeling weak, and having dif- and a paresthesia should not be unpleasant, although it fi culty concentrating. Fatigue should not be confused Appendix: Glossary 365 with sedation, which usually is a side eff ect of certain the stimulus and the response are in diff erent modes, medical interventions and therefore maybe infl uenced whereas with hyperalgesia they are in the same mode. by changing the therapeutic regimen. Fatigue is the Current evidence suggests that hyperalgesia is a conse- symptom palliative patients complain about most, and quence of perturbation of the nociceptive system with unfortunately it is diffi cult to infl uence. peripheral or central sensitization, or both, but it is im- Fibromyalgia portant to distinguish between the clinical phenomena, which this defi nition emphasizes, and the interpreta- A pain disorder—mostly aff ecting middle-aged fe- tion, which may well change as knowledge advances. males—in which a person feels widespread pain and Hyperalgesia and hyperpathia are an exaggerated re- stiff ness in the muscles, fatigue, and other symptoms. sponse to something that causes pain, with continued Although the name “fi bromyalgia” suggests a muscular pain after the cause of the pain is no longer present. disorder, recent research makes it more likely that fi - bromyalgia is caused by central nervous system changes Hyperesthesia with central hypersensitivity. Th erefore, current treat- Increased sensitivity to stimulation, excluding the spe- ment concepts aim at the descending inhibitory system cial senses. Th e stimulus and location should be speci- and central sensitization. Probably fi bromyalgia should fi ed. Hyperesthesia may refer to various modes of cuta- be seen in the same context as other hypersensitiv- neous sensibility, including touch and thermal sensation ity syndromes, such as chronic back pain, seronegative without pain, as well as to pain. Th e word is used to in- polyarthritis, or tension headache. dicate both diminished threshold to any stimulus and Hospice an increased response to stimuli that are normally recognized. Allodynia is suggested for pain after stimula- A special way of caring for people with terminal ill- tion that is not normally painful. Hyperesthesia includes nesses and their families by meeting the patient’s physi- both allodynia and hyperalgesia, but the more specifi c cal, emotional, social, and spiritual needs, as well as the terms should be used wherever they are applicable. needs of the family. Th e goals of hospice are to keep the patient as comfortable as possible by relieving pain and Hyperpathia other symptoms; to prepare for a death that follows the A painful syndrome characterized by an abnormally wishes and needs of the patient; and to reassure both painful reaction to a stimulus, especially a repetitive the patient and family members by helping them to un- stimulus, as well as an increased threshold. It may occur derstand and manage what is happening. Hospice care with allodynia, hyperesthesia, hyperalgesia, or dysesthe- especially aims to help patients who are unwilling or un- sia. Faulty identifi cation and localization of the stimulus, able to be taken care of in their homes and have stable delay, radiating sensation, and aftersensation may be or manageable symptoms. Hospice care usually ends present, and the pain is often explosive in character. Th e with the death of the recipient, while palliative ward changes in this note are the specifi cation of allodynia care allows reambulation of the patient in many patients and the inclusion of hyperalgesia explicitly. Previously after stabilization. Pallium India and Hospice Africa hyperalgesia was implied, since hyperesthesia was men- Uganda are remarkable examples of hospice care in low- tioned in the previous note and hyperalgesia is a special resource settings. Currently, in many countries, “home case of hyperesthesia. care” is promoted to avoid as long as possible and as of- Hypoalgesia ten as possible hospice or palliative ward treatment. Diminished pain in response to a normally pain- Hyperalgesia ful stimulus. Hypoalgesia was formerly defi ned as di- An increased response to a stimulus that is normally minished sensitivity to noxious stimulation, making painful. Hyperalgesia refl ects increased pain on supra- it a particular case of hypoesthesia. However, it now threshold stimulation. For pain evoked by stimuli that refers only to the occurrence of relatively less pain in usually are not painful, the term allodynia is preferred, response to stimulation that produces pain. Hypoes- while hyperalgesia is more appropriately used for cases thesia covers the case of diminished sensitivity to stim- with an increased response at a normal threshold, or ulation that is normally painful. Hypoalgesia, as well as at an increased threshold, such as in patients with neu- allodynia, hyperalgesia, and hyperpathia, do not have ropathy. It should also be recognized that with allodynia to be symmetrical and are not symmetrical at present. 366 Andreas Kopf Lowered threshold may occur with allodynia but is not Neuraxis required. Also, there is no category for lowered thresh- Nerve structures within the spinal column. Th erefore old and lowered response—if it ever occurs. epidural, caudal, and spinal anesthesia may be called Hypoesthesia neuraxial anesthesia techniques. Decreased sensitivity to stimulation, excluding the spe- Neuritis cial senses. Infl ammation of a nerve or nerves. Informed consent Neurogenic or neuropathic pain Th e process of making decisions about medical care Pain initiated or caused by a primary lesion, dysfunc- that are based on open, honest communication between tion, or transitory perturbation in the peripheral or cen- the health care provider and the patient and/or the pa- tral nervous system. Neuropathic pain occurs when a tient’s family members. Th e idea behind informed con- lesion or dysfunction aff ects the nervous system. Cen- sent is that the patient may act as a “symmetrical” con- tral pain may be retained as the term when the lesion versation partner. In practice, this idea is often diffi cult or dysfunction aff ects the central nervous system. Th e to fulfi ll, when the specifi c situation of the patient and causative agent may be nerve compression, trauma, the highly specialized knowledge of the caregiver may nerve-invading cancer, herpes zoster, HIV, stroke, dia- have to result in specifi c recommendations to the pa- betes, alcohol, or other toxic substances. tient without alternatives (e.g., in advanced chronifi cation of pain). Neuropathy Intrathecal Any disease or malfunction of the nerves. Th e intrathecal space is located between the arachnoid Nociception and the pia mater of the spinal cord. It contains the ce- Nociception is the sensory component of pain. It en- rebrospinal fl uid and the spinal nerves. For anesthesia compasses the peripheral and central neuronal events the intrathecal space may be reached by needle punc- following the transduction of damaging mechanical, ture, in special situations, such as advanced cancer pain; chemical, or thermal stimulation of sensory neurons catheters also may be placed there. (nociceptors). Local anesthetics Nociceptor Local anesthetics interfere with the generation and A receptor preferentially sensitive to a noxious stimu- propagation of action potentials within neuronal mem- lus or to a stimulus that would become noxious if pro- branes by blocking sodium channels. By use of regional longed. Often called a pain receptor. anesthetic techniques they are injected in close proximity to the spinal cord (the intrathecal or epidural space), Nonsteroidal anti-infl ammatory drugs (NSAIDs) to peripheral nerves or nerve plexuses, or—on rare occasions—intravenously infused. NSAIDs inhibit cyclooxygenases, the enzymes that cat- alyze the transformation of arachidonic acid (a ubiqui- Myofascial pain tous cell component generated from phospholipids) to Myofascial pain is characterized by muscle pain and prostaglandins and thromboxanes. Two isoforms, COX- tenderness. Very often chronic back pain or shoulder- 1 and COX-2, are expressed constitutively in peripheral arm syndromes originate in myofascial pain and not in tissues and in the central nervous system. In response nerve entrapment, instability of the spine or skeletal or to injury and infl ammatory mediators (e.g., cytokines, disk degeneration. Relaxation techniques and specifi c growth factors), both isoforms can be upregulated, re- physiotherapy are therefore more successful than anal- sulting in increased concentrations of prostaglandins. gesics or injection therapies in these pain syndromes. As a result, nociceptors become more responsive to Neuralgia noxious mechanical (e.g., pressure, hollow organ distension), chemical (e.g., acidosis, bradykinin, neurotroph- Pain in the distribution of a nerve or nerves. Neural- ins), or thermal stimuli. gia is often—incorrectly—used to describe paroxysmal pains. Appendix: Glossary 367 Noxious stimulus particular compound is mostly based on economical A noxious stimulus is one that is damaging to normal and pharmacokinetic considerations (route of admin- tissues. istration, desired onset or duration, and lipophilicity) and on side eff ects associated with the respective route Opioids of drug delivery. Dosages can vary widely depending on Opioids act on heptahelical G-protein-coupled recep- patient characteristics, type of pain, and route of admin- tors. Th ree types of opioid receptors have been cloned istration. Systemically as well as spinally administered (mu, kappa, and delta). Additional subtypes have been opioids can produce similar side eff ects, depending on proposed but are not universally accepted. Opioid re- the dosage, with some nuances due to the varying ros- ceptors are localized and can be activated along all lev- tral (to the brain) or systemic redistribution of diff erent els of the neuraxis including peripheral and central pro- compounds. Small, systemically inactive doses are used cesses of primary sensory neurons (nociceptors), spinal in the periphery and are therefore devoid of side eff ects. cord (interneurons, projection neurons), brainstem, Opioids remain the most eff ective drugs for the treat- midbrain, and cortex. All opioid receptors couple to G- ment of severe acute and cancer-related chronic pain, proteins (mainly Gi/Go) and subsequently inhibit adeny- while they are only a second choice in neuropathic pain lyl-cyclase, decrease the conductance of voltage-gated and have only a limited indication in chronic noncancer 2+ + Ca channels and/or open rectifying K channels. Th ese pain that is not neuropathic or infl ammatory. Detrimen- eff ects ultimately result in decreased neuronal activity. tal side eff ects are usually preventable by careful dose ti- Opioid peptides are expressed throughout the central tration and close patient monitoring, or they are treated and peripheral nervous system, in neuroendocrine tis- by comedication (e.g., laxatives) or naloxone. Current sues, and in immune cells. research aims at the development of opioids with re- Th e commonly available opioids (e.g., morphine, stricted access to the brain. codeine, methadone, fentanyl, and their derivatives) are pure mu-agonists. Naloxone is a nonselective antago- Osteomyelitis pain nist at all three receptors. Partial agonists must occupy a Infl ammation of the bone due to infection, for ex- greater fraction of the available pool of functional recep- ample by the bacteria Salmonella or Staphylococcus. tors than full agonists to induce a response (e.g., analge- Osteomyelitis is sometimes a complication of surgery sia) of equivalent magnitude. Mixed agonist/antagonists or injury, although infection can also reach bone tis- (e.g., buprenorphine, butorphanol, nalbuphine, and pen- sue through the bloodstream. Both the bone and the tazocine) may act as agonists at low doses and as antago- bone marrow may be infected. Symptoms include deep nists (at the same or a diff erent receptor) at higher doses. pain and muscle spasms in the area of infl ammation, Such compounds typically exhibit ceiling eff ects for anal- and fever. Especially if the history reveals previous gesia, and they may elicit an acute withdrawal syndrome surgery in the painful area and pain does not decrease when administered together with a pure agonist. All opi- with rest in the night, osteomyelitis—especially spon- oid receptors mediate analgesia but with diff ering side dylodiscitis—should be suspected. Treatment is by bed eff ects. Mu-receptors mediate respiratory depression, rest, antibiotics, and sometimes surgery to remove in- sedation, reward/euphoria, nausea, urinary retention, fected bone tissue. biliary spasm, and constipation. Kappa-receptors mediate dysphoric, aversive, sedative, and diuretic eff ects, but Osteoporosis do not mediate constipation. Tolerance and physical de- Th inning of the bones with reduction in bone mass due pendence occur with prolonged—and eventually short— to depletion of calcium and bone protein. Osteoporosis administration of all pure agonists. Th us, the abrupt dis- predisposes a person to fractures. Osteoporosis is more continuation or antagonist administration can result in a common in older adults, particularly postmenopausal withdrawal syndrome. women, and in patients on steroids. Osteoporosis can Opioids are eff ective in the periphery (e.g., lead to changes in posture (particularly in the form of a topical or intra-articular administration, particularly in hunched back known colloquially as “dowager’s hump”) infl amed tissue), at the spinal cord (intrathecal or epi- and decreased mobility. Often the vertebral body is af- dural administration), and systemically (e.g., intrave- fected. Pain is usually not constant but temporary and a nous or oral administration). Th e clinical choice of a symptom of pathological fractures. 368 Andreas Kopf Pain while dysesthesia be used preferentially for an abnormal Th e International Association for the Study of Pain sensation that is considered to be unpleasant. Dysesthe- (IASP) defi nes pain as “an unpleasant sensory and emo- sia does not include all abnormal sensations, but only tional experience associated with actual or potential tis- those which are unpleasant. sue damage, or described in terms of such damage.” Th is Patient-controlled analgesia (PCA) broad defi nition acknowledges that pain is more than a Pain medication given through an intravenous or epi- sensation subsequent to the electrical activation of no- dural catheter may be either applied continuously or by ciceptors (nociception). It includes cognitive, emotional, the nurse or doctor or self-administered by the patient. and behavioral responses, which are also infl uenced by With PCA, patients control the frequency of medication psychological and social factors. Pain is always subjec- dosing, depending on how much they need to control tive. Each individual learns the application of the word the pain. PCA is usually used for patients recovering through experiences related to injury in early life. Biolo- from intra-abdominal, major orthopedic, or thoracic gists recognize that those stimuli which cause pain are surgery, and for chronic pain states, such as those due liable to damage tissue. Accordingly, pain is that expe- to cancer requiring parenteral administration of opioids. rience we associate with actual or potential tissue dam- Usually PCA uses electronic pumps that allow docu- age. It is unquestionably a sensation in a part or parts of mentation of the patient’s analgesic demand and safety the body, but it is also always unpleasant and therefore by locking the pump function for some time (usually 10 also an emotional experience. Experiences that resem- minutes) after each demand dose self-administered by ble pain but are not unpleasant, e.g., pricking, should the patient. not be called pain. Unpleasant abnormal experiences (dysesthesias) may also be pain but are not necessarily Peripheral neuropathic pain so because, subjectively, they may not have the usual Pain initiated or caused by a primary lesion or dysfunc- sensory qualities of pain. tion in the peripheral nervous system, such as diabetic Many people report pain in the absence of tis- polyneuropathy. sue damage or any likely pathophysiological cause; usu- Phantom pain ally this happens for psychological reasons. Th ere is usually no way to distinguish this experience from that Pain that develops after an amputation in the area of due to tissue damage if we accept the subjective report. the missing limb. Th e diagnosis of phantom pain has If people regard their experience as pain and if they re- to exclude fi rst the presence of stump pain (e.g., due port it in the same ways as pain caused by tissue dam- to insuffi cient surgical coverage of the stump tissues) age, it should be accepted as pain. Th is defi nition avoids and phantom sensations (nonpainful, but nevertheless tying pain to the stimulus. Activity induced in the noci- frightening “feelings” in the lost limb). Since phantom ceptor and nociceptive pathways by a noxious stimulus pain is mostly generated in the central nervous system, is not pain, which is always a psychological state, even mostly in the corresponding sensory-motor region of though we may well appreciate that pain most often has the cortex, therapy is usually not directed peripher- a proximate physical cause. ally but centrally. Patients and their relatives sometimes feel that—since pain in a missing body part should not Pain threshold be possible—something is wrong with them. Th ere- Th e least experience of pain that a subject can recognize. fore, simply educating the patient and family about the causes of the pain may bring considerable relief. Pain tolerance level Th e greatest level of pain that a subject is prepared to Physician-assisted suicide tolerate. As with pain threshold, the pain tolerance level Actions by a doctor that help a patient commit suicide. is the subjective experience of the individual. Th ough the doctor may provide medication, a prescription, or take other steps, the patient takes his or her Paresthesia own life (for instance, by swallowing the pills that are An abnormal sensation, whether spontaneous or expected to bring about death). While physician-assist- evoked. It has been agreed that paresthesia be used to ed suicide is legal in Th e Netherlands, Belgium, Luxem- describe an abnormal sensation that is not unpleasant burg, and Switzerland, it is illegal in all other countries Appendix: Glossary 369 worldwide. Th e expansion of physician-assisted suicide level, avoidance of thought and feeling dominates, along is expected to be harmful and to be in competition with with (partial) amnesia, limited emotional scope, reduc- the development of palliative care. Experiences in the tion in interest levels, and alienation. Physiological reac- countries practicing physician-assisted suicide suggest tions are diffi culties in falling asleep or disturbed sleep, that too many patients not meeting the original require- increased irritability, inability to concentrate, hypervigi- ments for this “last resort” are included. Apart from lance, and exaggerated shock reactions. Chronic pain legal discussions, physician-assisted suicide has to be may also occur after the trauma in connection with in- balanced against the Hippocratic oath of the physicians juries or even later, particularly in the case of headaches. and religious teachings. Psychiatric comorbidity Placebo With regard to the prevalence of psychiatric disorders A “sugar pill” or any dummy medication or treatment such as anxiety, depression, and somatoform disorders that causes the placebo response. A remarkable phe- in chronic pain patients, there are great diff erences in nomenon in which a placebo—a fake treatment—can the results of clinical tests. Statements of prevalence sometimes improve a patient’s condition simply because vary from 18% to 56%; furthermore, the details are de- the person has the expectation that it will be helpful. pendent on the treatment parameters. Th e prevalence Expectation plays a potent role in the placebo eff ect. of chronic pain and comorbidity with the depression- Also, preconditioning eff ects generate a placebo re- anxiety spectrum are nearly consistent across devel- sponse. Th erefore, testing the “adequate reaction” by a oped and developing countries. Th e age-standardized placebo will not be able to prove “inadequate analgesic prevalence of chronic pain conditions in the previous 12 demand.” Th e reason is that expectations and precon- months was 37% in developed countries and 41% in de- ditioning are potent principles that are able to mimic veloping countries, and overall the prevalence of pain is the analgesic response. To be able to truly test an “ad- greater among females and older persons, but the large equate reaction” of a patient to an analgesia procedure, majority do not meet the criteria for depression or anxi- short- and long-acting substances should be tested sub- ety disorder. sequently. An “inadequate response” would be if the pa- Public health tient responds identically to both substances (e.g., short- acting lidocaine and long-acting bupivacaine in a nerve Th e approach to medicine that is concerned with the block). health of the community as a whole. Public health is community health. It has been said that: “Health care is Postherpetic neuralgia (PHN) vital to all of us some of the time, but public health is Neuropathic pain in the aff ected dermatome following vital to all of us all of the time.” a varicella infection with herpes zoster (“shingles”), usually defi ned as pain longer than 6–12 weeks after the Quackery onset of herpes zoster. Allodynia is often present and Deliberate misrepresentation of the ability of a sub- diffi cult to treat. stance or device for the prevention or treatment of disease. We may think that the day of patent medicines is Post-traumatic stress disorder (PTSD) gone, but look around you and you will still see them. Th e reasons for developing PTSD can be manifold. In Th ey appeal to our desire to believe that every disease the fi eld of research, a number of categories have been is curable or at least treatable. Quackery also applies to examined—criminal victimization, partner abuse, sex- persons who pretend to be able to diagnose or heal peo- ual victimization, childhood abuse, political trauma, ple but are unqualifi ed and incompetent. disasters, or a threat to one’s life. Th e prevalence of PTSD in pain patients varies from 0.5% to 9%, in com- Receptor parison to persons without pain, where it ranges from In cell biology, a structure on the surface of a cell (or in- nearly 0.5% to 3%. An extreme experience of pain dur- side a cell) that selectively receives and binds a specifi c ing the trauma increases the likelihood of developing substance. Th ere are many receptors; for example, the the symptoms of PTSD. Th e symptoms of a PTSD are receptor for substance P, a molecule that acts as a mes- intrusions (involuntary and stressing memories), night- senger for the sensation of pain, is a unique harbor on mares, and fl ashbacks. On the cognitive and emotional the cell surface where substance P docks. 370 Andreas Kopf Refl ex sympathetic dystrophy (complex regional dermatomes. Therefore, other pain etiologies than pain syndrome type I) radicular compression have to be taken into account, Pain, usually burning pain, that is associated with “au- such as facet-joint pain, sacroiliacal joint irritation, tonomic changes”—changes in the color of the skin, or myofascial pain. changes in temperature, changes in sweating, and swell- Somatoform disorders ing. Refl ex sympathetic dystrophy is caused by an injury Th e somatoform disorders are a group of psychiat- to the bone, joint, or soft tissues without nerve damage. ric disorders that cause unexplained physical symp- Th e most frequent cause is a radius fracture. Apart from toms (somatoform disorder, hypochondriasis, pain nerve damage, CRPS type I is not distinctive from CRPS disorder,and conversion disorder). Th e pathophysiol- type II. An older term is Sudeck disease, which should ogy of these complaints still remains unclear. A com- not be used, because sympathetic dysfunction may be mon main symptom of these disorders is that physical part of CRPS, but is no prerequisite for diagnosis. Diag- symptoms cannot be completely explained by means nosis and treatment are diffi cult and should be left to a of a physiological process. Somatic disorders can be specialist. Advanced CRPS may leave the patient with a accompanied by defi ned physical illnesses, but they permanently unusable extremity. may not be adequately explained by these illnesses. Rheumatoid arthritis Patients who suff er pain without an organic cause An autoimmune disease that causes chronic infl amma- are often unable to cope with emotional stress; this is tion of the joints and the tissue around the joints, as converted into physical stress factors. Th ese diff use well as other organs in the body. Autoimmune diseases stress factors can no longer be understood as a physi- occur when the body tissues are mistakenly attacked by cal expression of an intrapsychic confl ict, but are non- the body’s own immune system. Th e immune system is specifi c, vegetative stress factors (e.g., with agitation, a complex organization of cells and antibodies designed shaking, and pain) as a result of emotional pressure to “seek and destroy” invaders of the body, particularly experienced primarily physically. Various physical dis- infections. Patients with autoimmune diseases have an- orders can result. Th e standard medical treatment is tibodies in their blood that target their own body tis- often limited. Th ese disorders should be considered sues, where they can be associated with infl ammation. early on in the evaluation of patients with unexplained Because it can aff ect multiple other organs of the body, symptoms to prevent unnecessary interventions and rheumatoid arthritis is referred to as a systemic illness testing. Th e identifi cation of a life event that is impor- and is sometimes called rheumatoid disease. While tant enough to be taken as a cause of this disorder may rheumatoid arthritis is a chronic illness (meaning it can prove helpful to “solve” the stress of this life event with last for years), patients may experience long periods behavioral interventions. Consequently, the somato- without symptoms. Pain management includes NSAIDs form pain may diminish over time. and opioids. Pain control should not be attempted with- Spinal stenosis out controlling the infl ammation, otherwise joint de- Narrowing of the spaces in the spine, resulting in com- struction will continue. pression of the nerve roots or spinal cord by bony spurs Sciatica or soft tissues, such as disks, in the spinal canal. Stenosis Pain resulting from irritation of the sciatic nerve, occurs most often in the lumbar spine (in the low back) typically felt from the low back to behind the thigh in patients older than 60 years, but it also occurs in the and radiating down below the knee. While sciatica cervical spine (in the neck) and less often in the thoracic can result from a herniated disk directly pressing on spine (in the upper back). Th e typical symptoms to ask the nerve, any cause of irritation or inflammation of when suspecting spinal stenosis are claudication (pain this nerve can reproduce the painful symptoms of increases after a certain time of exercise without evi- sciatica. Diagnosis is by observation of symptoms, dence of peripheral artery disease) and pain relief with physical and nerve testing, and sometimes by X-ray bending forward. If surgery is not possible, a few thera- or MRI if a herniated disk is suspected. Very often, peutic options are left for analgesia, including epidural physical examination and careful taking of the history steroids, physiotherapy, opioids and NSAIDs, and fl ex- will reveal that the pain is not radiating along typical ion-orthostasis. Appendix: Glossary 371 Spondylolisthesis in the cerebellar region) or due to pulsatile compres- Forward movement of one of the vertebrae of the spine sion by the cerebellar artery that causes brief attacks in relation to an adjacent vertebra, most often at the of severe pain in the lips, cheeks, gums, or chin on one level of L5/S1. Simple “functional” X-ray (lateral view side of the face. Only a symptom complex including in full extension and full fl exion of the spine) may dem- attack-like pain of less than 2 minutes, no neurological onstrate spondylolisthesis. Only a major forward move- defi cits, absent or minor chronic pain, and typical trig- ment (>25–50% of the vertebral length) is an indication ger factors should be diagnosed as trigeminal neural- for surgery. gia. Carbamazepine is still considered to be the drug of fi rst choice. If drug therapy fails, trigeminal neuralgia Substance P is one of the few pain syndromes where surgery is in- Substance P is a member of the tachykinin family of dicated (Janetta surgery). neuropeptides that is expressed in sensory neurons. World Health Organization It works as a stimulatory neurotransmitter or neuro- modulator when it is released centrally, and as a proin- An agency of the United Nations established in 1948 fl ammatory mediator when it is released peripherally. to further international cooperation in improving It activates the neurokinin-1 receptor, a major factor in health conditions. Although the World Health Or- central sensitization. ganization (WHO) inherited specifi c tasks relating to epidemic control, quarantine measures, and drug Withdrawal syndrome standardization from the Health Organization of the Th e abrupt cessation of a repeatedly or continuously ad- League of Nations (which was set up in 1923) and ministered opioid agonist, or the administration of an from the International Offi ce of Public Health at Par- antagonist, typically results in withdrawal syndrome. is (established in 1909), the WHO was given a broad Signs and symptoms include sweating, tachycardia, hy- mandate under its constitution to promote the attain- pertension, diarrhea, hyperventilation, and hyperrefl ex- ment of “the highest possible level of health” by all ia. See also the entry on “Dependence”. people. WHO defi nes health positively as “a state of complete physical, mental, and social well-being and Tolerance not merely the absence of disease or infi rmity.” Th e Tolerance is the need for progressively increasing doses cancer pain management recommendations of the of an agonist to maintain the same eff ect (e.g., analge- WHO (the analgesic ladder) have had a major eff ect on sia). In chronic pain, the need for increasing doses of the rate of opioid prescriptions to patients with cancer opioids can be due to alterations in receptor functioning and HIV-related pain, mainly in countries belonging to (e.g., coupling to G proteins, second messengers) and/ the Organization for Economic Co-operation and De- or to increasing painful stimulation (e.g., by a growing velopment (OECD). Unfortunately, Eastern European tumor), among other reasons. Tolerance is fortunately countries and many low-resource countries continue not common in patients who have opioid-sensitive pain. to have only very restricted opioid delivery rates to In patients seeking opioid treatment for mood stabiliza- cancer patients, which should be considered a health tion, tolerance is frequent. Th erefore, in patients with emergency. Th e Pain and Policy Study Group of the nonmalignant pain and nonprogressing disease, the re- WHO is investing a lot of eff ort to infl uence this situ- peated need for dose escalation (typically every 4 to 8 ation by advising government authorities and health weeks, when tolerance to the sedating and euphoric care workers on legislative, educational, and treat- eff ects of opioids develops) should be a warning sign ment changes necessary to be able to provide adequate for “inadequate” opioid use, and the opioid medication amounts of opioids to patients in need. For further in- should be gradually discontinued. formation see their website for a lot of relevant facts Trigeminal neuralgia regarding opioids in most countries of the world. A disorder of the trigeminal nerve in its root area (e.g., secondary trigeminal neuralgia due to malignant masses