MIDDLE EAST JOURNAL of ANESTHESIOLOGY Department of Anesthesiology American University of Beirut Medical Center P.O

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MIDDLE EAST JOURNAL OF ANESTHESIOLOGY Department of Anesthesiology American University of Beirut Medical Center P.O. Box 11-0236. Beirut 1107-2020, Lebanon

Editorial Executive Board Consultant Editors Editor-In-Chief: Bikhazi George Assem Abdel-Razik (Egypt) Executive Editors Mohamad El-Khatib Bassam Barzangi (Iraq) Editors Chakib Ayoub Marie Aouad Izdiyad Bedran (Jordan) Ghassan Kanazi Dhafir Al-Khudhairi (Saudi Arabia) Sahar Siddik-Sayyid Mohammad Seraj (Saudi Arabia) Managing Editor Mohamad El-Khatib [email protected] Abdul-Hamid Samarkandi (Saudi Arabia) Founding Editor Bernard Brandstater Mohamad Takrouri (Saudi Arabia) Emeritus Editor-In-Chief Anis Baraka Bourhan E. Abed (Syria) Honorary Editors Nicholas Greene Musa Muallem Mohamed Salah Ben Ammar (Tunis) Managing Editor Assistant Aurélie Mailhac M. Ramez Salem (USA) Webmaster Rabi Moukalled Elizabeth A.M. Frost (USA) Secretary Alice Demirdjian Halim Habr (USA) [email protected] The Middle East Journal of Anesthesiology is a All accepted articles will be subject to a US $ 100.00 publication of the Department of Anesthesiology of (net) fee that should be paid prior to publishing the the American University of Beirut, founded in 1966 by accepted manuscript Dr. Bernard Brandstater who coined its famous motto: “For some must watch, while some must sleep” Please send dues via: (Hamlet-Act. III, Sc. ii). WESTERN UNION and gave it the symbol of the poppy flower (Papaver To Mrs. Alice Artin Demirjian somniferum), it being the first cultivated flower in Secretary, Middle East Journal of Anesthesiology the Middle East which has given unique service to OR TO the suffering humanity for thousands of years. The Credit Libanaise SAL Journal’s cover design depicts The Lebanese Cedar Tree, with’s Lebanon unique geographical location AG: Gefinor.Ras.Beyrouth between East and West. Graphic designer Rabi Swift: CLIBLBBX Moukalled Name of Beneficent The Journal is published three times a year (February, Middle East Journal of Anesthesiology June and October) The volume consists of a two year Acc. No. 017.001.190 0005320 00 2 indexed six issues. The Journal has also an electronic (Please inform Mrs. Demirjian [email protected] issue accessed at www.aub.edu.lb/meja - Name and Code of article The Journal is indexed in the Index Medicus and - Transfer No. and date (WESTERN UNION) MEDLARS SYSTEM. - Receipt of transfer to (Credit Libanaise SAL) E-mail: [email protected] Personal checks, credit cards and cash, are not Fax: +961 - (0)1-754249 acceptable “For some must watch, while some must sleep” (Hamlet-Act. III, Sc. ii) 134

Middle East Journal of Anesthesiology Vol. 22, No. 6, October 2014

CONTENTS

editorial

Somatic And Autonomic Upregulation In The Quadriplegic Patient �� Anis Baraka 535 review article

Differential Diagnosis Of Delayed Awakening From General Anesthesia: A Review ��Elizabeth A. M. Frost 537 scientific articles

Dexmeditomidine Versus Fentanyl As Coadjuvants Of Balanced Anaesthesia Technique In Renal Transplant Recipients ��Sunder Negi, Indu Sen, Virender Arya, Ashish Sharma 549

Short Beveled Sharp Cutting Needle Is Superior To Facet Tip Needle For Ultrasound- Guided Rectus Sheath Block In Children With Umbilical Hernia: A Case Series �� A. Alsaeed, A. Thallaj, T. Alzahrani, N. Khalil and A. Aljazaeri 559

Breast Cancer Recurrence In Patients Receiving Epidural And Paravertebral Anesthesia: A Retrospective, Case-Control Study ��Stephanie L. Koonce, Sarah A. McLaughlin, Dustin L. Eck, Steven Porter, Sanjay Bagaria, Steven R. Clendenen, Christopher B. Robards 567 Effect Of Pressure Support Level, Patient’s Effort, And Lung Mechanics On Phase Synchrony During Pressure Support Ventilation ��Ghazi A. Alotaibi 573

The Incidence Of Postoperative Residual Curarization Following The Use Of Intermediate- Acting Muscle Relaxants And Related Factors �� Ozlem Kocaturk, Nil Kaan, Nurten Kayacan, Fatma Ertugrul 583

Is Unilateral Spinal Anesthesia Superior To Bilateral Spinal Anesthesia In Unilateral Inguinal Regional Surgery ��Faruk Cicekci, Huseyin Yilmaz, Mehmet Balasar, Mustafa Sahin, Fatih Kara 591 The Effects Of Provision Of Anesthesia On One-Year Mortality In Patients With Severe Complications �� Junko Ushiroda, Satoki Inoue, Yu Tanaka, Masahiko Kawaguchi 597 Teaching Ultrasound Procedural Skills-Low Cost Phantoms And Animal Models �� Jacek A. Wojtczak, Sonia Pyne 603

531 M.E.J. ANESTH 22 (6), 2014 case reports

Awake Tracheal Intubation With Combined Use Of King Vision™ Videolaryngoscope And A Fiberoptic Bronchoscope In A Patient With Giant Lymphocele �� Mohamed R. El-Tahan, D. John Doyle, Alaa M. Khidr, Mohamed A. Regal, Ayman B. El Morsy, Mohamed El Mahdy 609 Anesthesia For Arthroscopic Shoulder Surgery In The Beach Chair Position: Monitoring Of Cerebral Oxygenation Using Combined Bispectral Index And Near-Infrared Spectroscopy ��Hiroaki Kawano, Tomomi Matsumoto 613

Impossible Mask Ventilation After An Unusually Low Dose Fentanyl-Induced Muscle Rigidity In A Patient With Essential Tremor: A Case Report And Review Of The Literature ��Vassilios Dimitriou, Ioannis Zogogiannis, Despoina Liotiri, Freddie Wambi, Nasser Tawfeeq, Adnan Koumi, Georges Geldhof 619 Hypotension On Induction: Anaphylaxis Or Cardiac Failure? �� Himani V. Bhatt, Elizabeth A. M. Frost 623 letter to the editor

Anesthetic Management Of A Patient After Functional Hemispherectomy Using Bilateral Bispectral Index Monitoring ��Shinichiro Kira, Kentaro Okuda 627

532 Welcome our new Editor-in-Chief

The Editorial Board of the Middle East Journal of Anesthesiology is pleased to announce that Dr. George B. Bikhazi is the new Editor-in-Chief of the Middle East Journal of Anesthesiology. This comes in line with the appointment of Dr. Bikhazi as the new Chairman of Anesthesiology at the American University of Beirut - School of Medicine and Medical Center as of July 1st, 2014. Dr. Bikhazi received his MD degree from the American University of Beirut in 1971. Following graduation he pursued his residency and fellowship at AUB and in the USA. In 1976, he was appointed assistant professor of anesthesiology at University of Miami School of Medicine and the Director of Pediatric Anesthesia until 2001. During his stay at Miami, he was promoted to associate professor (1979) and professor (1991). Dr. Bikhazi joined the Department of Anesthesiology at St. Jude Children’s Research Hospital in Memphis, Tennessee in 2002 and later on became the Chief of the Division of Anesthesia until he returned to AUB as the Chairman of the Department of Anesthesiology in 2014. Dr. Bikhazi is a member and has served on boards/committees of several professional organizations and societies (ASA, AMA, ASA Committee on Pediatric Anesthesia) and throughout his career has received numerous prestigious awards and recognitions (Fellow, American College of Anesthesiologists and Diplomat, American Board of Anesthesiologists). Furthermore, Dr. Bikhazi has published around 113 original articles, abstracts, and book chapters throughout his academic career. He delivered numerous lectures at major national and international scientific meetings. The Editorial Board extends a warm welcome to Dr. Bikhazi and looks forward for fruitful years and bright future of the journal under his leadership.

533 M.E.J. ANESTH 22 (6), 2014

EDITORIAL

SOMATIC AND AUTONOMIC UPREGULATION IN THE QUADRIPLEGIC PATIENT

Patients with chronic spinal cord transection develop both somatic and autonomic denervation below the level of denervation. This can result in “up-regulation” of both the somatic and adrenergic receptors below the level of the cord transection, with a subsequent increased sensitivity to the chemical transmitter at both the neuromuscular junctions and the adrenergic receptors. The number of postjunctional receptors can be influenced by the ambient concentration of the chemical transmitter. As a rule, there is an inverse relationship between the concentration of the transmitter and the number of its receptors. Alteration in the number of the receptors is referred to as either “up-regulation” or “down-regulation”. Patients with chronic spinal cord transection will develop both somatic and autonomic denervation, which can result in “up-regulation”, and hence a supersensitivity response at both the neuromuscular junction and the adrenergic vascular receptors. Somatic denervation will be followed by extrajunctional spread of the receptors beyond the motor endplate into the whole muscle membrane, with a subsequent increased sensitivity to the chemical transmitter acetylcholine. A similar response will follow sympathetic denervation, resulting in extrajunctional spread of the adrenergic receptors, with a subsequent adrenergic supersensitivity to the chemical transmitter norepinephrine which can trigger the so-called “autonomic hyperreflexia”. The “autonomic hyperreflexia” is not secondary to an increased secretion of the chemical transmitter norepinephrine, but rather to an increased sympathetic response of the expanding adrenergic receptors, resulting in severe hypertension, associated with reflex slowing of heart rate via the innervated carotid sinus baroreceptors. It has been shown that plasma catecholamines (epinephrine and norepinephrine) are subnormal in patients with cord transaction. During autonomic hyperreflexia, the level of norepinephrine increases, but still does not exceed the resting level of the control normal patients. These findings demonstrate that patients with chronic spinal cord transection have a subnormal sympathetic tone, even during an attack of autonomic hyperreflexia. These findings suggest the excessive reflex elevation of the blood pressure in patients with spinal cord transaction is not secondary to autonomic hyperreflexia, but is rather due to a denervation supersensitivity response of the adrenergic receptors to the released norepinephrine. The somatic “up-regulation” will explain the marked hyperkalemia following the administration of succinylcholine to the quadriplegic patient. That is why, succinylcholine is contraindicated in the quadriplegic patient, while the nondepolarising relaxants may be safely administered whenever indicated.

535 M.E.J. ANESTH 22 (6), 2014 536 baraka a.

The autonomic “up-regulation” will explain the the use of epidural meperidine or intrathecal morphine marked vasopressor response to stimulation below which act on the substantia gelatinosa in the spinal the level of cord transection. The autonomic response card, blocking the response to nociceptive stimulation. consisting of severe hypertension associated with The technique has been used to block the autonomic reflex bradycardia can follow bladder distension, hyperreflexia in the quadriplegic patient undergoing uterine contractions during pregnancy and labor, as delivery or surgery below the level of cord transection. well as surgical stimulation. About 85 percent of patient with cord transection above T6 will exhibit the Anis Baraka, MD, FRCA (Hon) reflex, since vasodilation in the neurologically intact Emeritus Professor of Anesthesiology portion of the body is insufficient to offset the effects of vasoconstriction below the level of transection. American University of Beirut The vasopressor response can be decreased by

References

1. Baraka A, Noueihid R, Hajj S: Intrathecal injection of morphine for supersensitivity? Editorial. M E J Anesth; 1989, 10:95-97. obstetric anesthesia. Anesthesiology; 1981, 54:136-140. 5. Baraka A, Noueihid R, Sibai AN, et al: Epidural meperidine for 2. Baraka A: Antagonism of succinylcholine-induced contracture of control of autonomic hyperreflexia. M E J Anesth; 1989, 10:185- denervated muscles by d-tubocurarine. Anesth Analg; 1981, 60:605- 188. 607. 6. Erickson RP: Autonomic hyperreflexia: Pathophysiology and 3. Baraka A: Epidural meperidine for control of autonomic medical management. Arch Phys Med Rehabil; 1980, 61:431-440. hyperreflexia in a paraplegic parturient. Anesthesiology; 1985, 7. Karnick NB: Autonomic hyperreflexia and its control in patients 62:688-690. with spinal cord lesions. Ann Intern Med; 1956, 44:678-686. 4. Baraka A: Is it autonomic hyperreflexia or denervation REVIEW ARTICLE

Differential Diagnosis of Delayed Awakening from General Anesthesia: A Review

Elizabeth A. M. Frost*

Abstract

With the general use of fast acting anesthetic agents, patients usually awaken quickly in the post operative period. However, sometimes recovery is protracted and the list of possible causes in long. Accurate diagnosis is key to institution of appropriate therapy. Key Words: Anesthetic agents, delayed recovery, overdose, risk factors.

Definition

There is no single definition of what might constitute delayed awakening or emergence after general anesthesia. With the almost universal use of evanescent agents such as propofol and desflurane, patients generally awaken in a few minutes. Even after prolonged surgery and anesthesia a response to stimulation within 60-90 minutes should occur1. Consciousness implies “awake and aware of surroundings and identity” according to the Oxford English Dictionary. But consciousness is a continuum with varying depths. Coma, from the Greek, means a state of sleep and is defined medically as “a state of unresponsiveness from which the patient cannot be aroused”. Although the Glasgow Coma Scale (Table 1) was originally developed as a means to assess prognosis after head trauma, it has also been used to trend the level of consciousness although inconsistencies may occur2. Other scores have been developed including the Aldrete Score (Table 2)3 and the Postoperative Quality Recovery Scale (PQRS)3. Recognizing that recovery from anesthesia and possible long term effects of the perioperative experience are complex issues, this latter scale tracks multiple domains of recovery from immediate to long-term periods in patients of different ages, languages and cultures. In consists of 6 domains; physiologic, nociceptive, emotive, activities of daily living, cognitive and patient perspective4. Physiologic recovery was complete in 40% of patients by 40 minutes. In only 11% of patients was recovery complete in all domains by day 3. Thus the concept of awakening would seem to be more involved with far greater dimensions than assessing a patient as being “recovered” or “awakened” and judging the anesthetic effect as terminated. These added factors have been assessed in several studies by patient reported surveys addressing functional quality of recovery5-9. Patient reports are an important approach in assessing recovery, but other crucial aspects are in areas perhaps influenced by anesthesia that may not rise to the patient’s consciousness. For example the topic of cognitive recovery especially after cardiac and even non cardiac surgery is rarely assessed. This questions as to whether recovery as a measure

* MD, Professor of anesthesia. Affiliation: Icahn Medical Center at Mount Sinai, New York. Corresponding author: Elizabeth A. M. Frost, MD, Professor of anesthesia, Icahn Medical Center at Mount Sinai, New York. E-mail: [email protected]

537 M.E.J. ANESTH 22 (6), 2014 538 frost e. A. M.

Table 1 Glasgow Coma Scale. A score of >12 indicates return of consciousness in most patients and <8 indicates coma. The scale is also used as a trend monitor.

of the quality of anesthesia care should be targeted for Causes not only identification but also for improvement10-16. Drug effect: Too much drug may have been given Incidence or the patient is very susceptible or drug interaction has occurred. In otherwise healthy patients who have Duration and type of anesthetic. Speed of undergone relatively short operative procedures the emergence is inversely related to blood gas solubility incidence of delayed awakening is practically zero and and directly related to alveolar ventilation. Other its occurrence usually relates to some underlying but factors include total tissue uptake of the drug (depends undiagnosed condition or medical error. on solubility), duration of anesthesia and average

Table 2 The commonly used Aldrete score is broad based. A value of 9 is required for discharge from the postanesthetic care unit (PACU). Delayed Awakening from General Anesthesia 539 concentration. undergoing brief urologic procedures and found that Potentiation by other drugs: Premedication with midazolam irrespective of the dose given significantly other sedatives such as benzodiazepines or alcohol increased depressed mental function and delayed 21 increases central nervous system depression. PACU discharge . Anticholinergic agents (atropine, scopolamine) also add to postoperative somnolence, Neuromuscular blockade: Although these attributed to decreased brain cholinergic activity patients may not be unconscious, prolonged muscle caused by anesthetics22. Muscle relaxants if given on paralysis may be almost indistinguishable from a weight controlled basis both delay onset of action delayed awakening. and prolonged duration of drug effects and must be considered with increasing age as these effects lead Risk Factors to respiratory depression and continued sedation20. Pharmacodynamic involvement appears to be nearly Risk factors for slower than normal return to absent if neuromuscular agents are given in the reduced consciousness are shown in Table 3. dosages required for this group of patients19. Close monitoring of depth of anesthesia and neuromuscular Patient Factors blockade and avoidance of benzodiazepines and substitution of non steroidal analgesic agents and Extremes of Age peripheral blocks for opiates should all be considered Geriatric Patient: as preventive of prolonged sedation in geriatric patients. Older patients have an exaggerated response to central nervous system (CNS)-active drugs due to an underlying age-related decline in CNS function as well Neonates: as increased pharmacodynamic sensitivity towards the Several studies have demonstrated the adverse benzodiazepines, general anesthetics and opioids18. consequences of untreated pan and stress on brain However, for opioids and local anesthetics used for development in preterm infants. Controversy still CNS blockade, the pharmacodynamic involvement is exists over the safety of benzodiazepines and opiates23. not always clear19. However, other studies have shown Predictive pharmacokinetic/pharmacodynamic that the demand for opioids is reduced by almost 50% models have been developed for fentanyl24. Because and with total intravenous anesthesia the dosages of awareness has been raised that anesthesia is essential propofol and remifentanil and recovery times are more for newborns, the risk of overdose and hence over determined by patient age than by body weight20. A sedation becomes considerable. Recent information report by Fredman et al assessed the effect of different suggests that there may be an association between doses of midazolam (0.5mg-2mg) in geriatric patients anesthetic exposure on a depth and time level to later

Table 3 Many factors may result in delayed awakening, roughly divided into 4 factors although clearly there is considerable overlap Patient Factors Drug Factors Surgical Factors Metabolic factors Extremes of age Dosage/hypoxia/hypotension Long surgery and anesthesia Hypo/hyper glycemia Genetic variation Absorption/distribution Muscle relaxant use Hypo/hyper natremia Body habitus Metabolism Regional techniques with sedation Hypothermia Co-morbidities Excretion Decreased pain and stimulation Hypothyroidism Obstructive sleep apnea Drug interactions Intracranial surgery Hepatic/renal failure Cognitive dysfunction Local anesthetic toxicity Central anticholinergic syndrome Seizures Fluid overload Acidosis Stroke Embolism Coagulation defects

M.E.J. ANESTH 22 (6), 2014 540 frost e. A. M. cognitive dysfunction25,26 Two large-scale clinical contain developmental and behavioral components as studies are currently underway to explore these issues. well as altered sensitivity to analgesics and variation The PANDA study is a large-scale, multisite, ambi- in gene-expression patterns. While the entire science directional sibling-matched cohort study in the USA. of pharmacogenetics is still in its infancy, it is The GAS study will compare the neurodevelopment growing rapidly. Undoubtedly in the not too distant outcome between sevoflurane anaesthesia and regional future, it will be possible to plan a precise, tailored anaesthesia, in infants undergoing inguinal hernia anesthetic. repair. Results from these studies may not be known 27 for 1-2 decades . Body Habitus A common cause of delayed return to consciousness in children is hypothermia. Because Males with a higher percentage of fat have of their relatively large body area compared to a tendency to delayed awakening after propofol weight, heat loss is greater than in adults. Hence drug anesthesia, an effect that is not seen in women31 With metabolism is delayed28. the exception of neuromuscular antagonists, lean body weight is the optimal dosing scale for most drugs Genetic factors used in anaesthesia especially opioids and anaesthetic induction agents32. A diagnosis of obstructive sleep Unexpected responses such as prolonged apnea with an increased incidence of fat deposits in the somnolence following the administration of specific pharynx and chest wall coupled with increased oxygen anaesthetics are most commonly associated with utilization and carbon dioxide production places the a genetic defect of the metabolic pathway either of morbidly obese patient at risk for adverse respiratory a given agent or its receptor. Most anesthetic agents events secondary to anesthetic agents, thus altering are metabolized in the liver by the cytochrome P450 the pharmacodynamic properties of these drugs. superfamily enzymes (CYPs) and phase II drug- Cardiac output increases with obesity and thus metabolizing enzymes (glutathione S-transferases these individuals require administration of higher drug (GSTs), sulphotransferases (SULTs), UDP- doses to attain the same peak-plasma concentration glucuronosyltransferases (UGTs) and NAD (P) H: than would be required for a standard-size person. quinone oxidoreductase (NQO1))28. Polymorphic Lean body weight (LBW) correlates highly with changes in GABRG 2 receptor can adversely affect increased cardiac output, more so than fat mass33. the expected rapid reversal of propofol anesthesia28. Clearance for most drugs increases nonlinearly with Unanticipated drug reactions are a common and total body weight but linearly with LBW. Thus morbid important complication of drug therapy both in obesity, which implies mainly increased fat mass, has adults and in children. It is becoming increasingly no clinically significant impact on the uptake of the apparent that genetically controlled variations in drug inhalation anesthetics isoflurane, sevoflurane, and disposition and response are important determinants of desflurane in routine clinical practice. Total body unexpected events for many important adverse events weight dosing of neuromuscular blocking agents may associated with drug therapy29. result in a prolonged effect although other studies 32,33 Pharmacogenetic differences appear to play have found different results . However, in a study major roles in predicting adverse effects, especially of 56 obese patients undergoing craniotomy Bilotta et of opioids30. A subset of genes appears to modulate al found desflurane-based anesthesia allowed earlier the proteins involved in pain perception pathways, postoperative cognitive recovery and reversal to 34 metabolism of analgesics (pharmacokinetics), and normocapnia and normal pH . transport and receptor signaling (pharmacodynamic). Propofol and remifentanil infusions have been Adult genetic studies have limited direct applicability, used for spinal fusion, especially in obese individuals, as children’s genetic predispositions to analgesic when evoked potential monitoring was required. response are influenced by different factors and However, this combination has been shown to delay Delayed Awakening from General Anesthesia 541 awakening. Addition of dexmedetomidine reduces compromise. Obesity, body mass index (BMI) ≥ 30 the dose requirements of propofol and remifentanil kg/m2, with enlarged neck circumference (males allowing faster wake up35. ≥ 17inches; females ≥ 16 inches) are often present. Other anatomical abnormalities include nasal polyps, Co-morbidities septal deviation, lingual tonsils, large adenoids, retrognathia, or tumors of the naso-oro-hypo-pharynx. Preexisting cardiac and pulmonary disease require adjustments in anesthetic dosages to prevent overdose Following anesthesia and surgery and for several and postoperative somnolence. Significant lung days thereafter, sleep architecture is largely disturbed disease decreases the ability to wash out inhaled agents in most patients but more so in patients with OSA as the speed of emergence relates directly to alveolar who already have altered architecture sleep patterns 37,38 ventilation. Similarly, congestive cardiac failure and as a consequence of the disease . Most patients do decreased cardiac output prolong somnolence. not experience the deeper planes of non rapid eye movement (NREM) sleep or REM sleep for the first Both hyper and hypo glycemia may induce three postoperative days. “REM rebound” then follows coma36. Patients with hyperglycemia have usually been as a “catch-up” on missed REM sleep phase. During diagnosed as type ll diabetics. A sugar infusion may REM rebound, nightmares may trigger a sympathetic have been inadvertently given or the patient may have surge, causing dysrhythmias, and myocardial ischemia. recently eaten a carbohydrate meal. Dexamethasone Also, during REM sleep, the increase in upper airway and long duration of surgery (stress response) can also resistance, coupled with generalized atonia and airway significantly increase hyperglycemia. Hypoglycemic obstruction, may lead to severe hypoxemia. The patients are more likely to be juvenile or insulin residual effects of anesthetic agents and neuromuscular dependent diabetics. Postoperative hypoglycemia blocking agents that tend to have a more profound most frequently results from starvation, or excessive insulin, especially in patients with end stage renal effect on the upper airway muscles than on ventilatory disease. Causes of hyper/hypoglycemia are shown in muscles, further contribute to respiratory obstruction. Table 4. Benzodiazepines as well as opioids (especially methadone) may cause central followed by obstructive Table 4 apneic events. Thus, profound/prolonged upper airway Several causes of either hyperglycemia or hypoglycemia may muscle weakness may be present despite adequate be identified spontaneous ventilation by the patient. Thus patients as contributing to delayed return to consciousness in the PACU with OSA are at considerable risk of cardiorespiratory (Adapted from ref 36, RCF Sinclair and RJ Faleiro) complications after surgery and during a period HYPERGLYCEMIA HYPOGLYCEMIA when analgesia may be maintained principally with 37,38 Ketoacidosis/pancreatitis Starvation opiates . Hyperosmolar non ketotic coma Sepsis Gestational diabetes Liver failure Cognitive Dysfunction Failure to take antiglycemic Children Structural disorders of cerebral nervous system medications such as increase in intracranial pressure, brain ischemia, Steroids Hypoadrenalism and psychological disorders may all cause postoperative Insulin resistance (Cushing, Endocrine tumors somnolence For example, patients with Parkinson’s acromegaly) disease are more prone to postoperative confusion and hallucinations39. Inhalational anaesthetic agents have Obstructive sleep apnea (OSA) complex effects on brain dopamine concentrations, inhibiting synaptic reuptake of dopamine, thereby Patients with OSA have several anatomical increasing the extracellular concentration and and functional factors that contribute to airway affecting both spontaneous and depolarization‐evoked

M.E.J. ANESTH 22 (6), 2014 542 frost e. A. M. dopamine release40-2, changes that occur at clinically Stroke relevant concentrations. Hypotension is a concern due to hypovolemia, norepinephrine depletion, Stroke is not common after anesthesia although autonomic dysfunction and the co‐administration of several risk factors such as hypertension, smoking, other medications. Patients taking bromocriptine or diabetes, obesity among others increase susceptibility. pergolide are prone to excessive vasodilation further Stroke may occur following carotid endarterectomy exacerbating hypotension. when an atheromatous plaque has been dislodged Patients who are depressed and taking monoamine of after cardiac surgery due to the embolization of oxidase inhibitors (MAO) or selective serotonin small clots or air. Occasionally this complication can reuptake inhibitors (SSRI) may experience severe be detected intraoperatively by cerebral oximetry. drug interactions with intravenous agents that can However, usually the first sign is a delayed return result in hyper/hypotension and postoperative coma, to cognitive function. Diagnosis depends on signs up to a full blown serotinergic syndrome. Other agents and radiologic studies. Neurologic consult should be that can result in drug interactions include St John’s sought immediately and an interventionalist consulted Wort, ginseng, lithium, ondansetron, metoclopramide, if time allows for intravenous administration of codeine, fentanyl, oxycodone among many others. recombinant tissue plasminogen activator (usually Severe symptoms include tachycardia and shock. within 4-6 hours of the event). Occasionally in patients Temperature may rise to above 41.1 °C (106.0 °F) in who have had a stroke in the past but recovered, life-threatening cases. Other abnormalities include paralysis of the previously affected limb may appear. metabolic acidosis, rhabdomyolysis, seizures, renal This complication usually reverses within a few hours. failure, and disseminated intravascular coagulation; these effects usually arising as a consequence of Drug Factors hyperthermia43. Patients with Down syndrome or mental The most common cause of delayed return to retardation may be particularly susceptible to delayed consciousness relates to residual drug effects Due awakening. Risk factors included age <21 years, to the many patient variables as noted above, it is males and those given > 0.032mg/kg midazolam not surprising that a drug given at one dose may be especially when administered together with propofol44. satisfactory for one patient but not for another. Intravenous sedation for dental patients with disabilities, particularly those with cerebral palsy Overdose increases the risk of hypoxia and delayed recovery of > 60 minutes is expected. The dose may have been excessive or the patient elderly or of small size. If vaporizers are not calibrated Seizures correctly, higher dose than believed of inhaled agents may be delivered, especially if end tidal drug Seizures are not uncommon after brain injury, concentrations are not measured. Drug metabolism is including after surgical intervention. A post ictal state delayed by renal or hepatic failure and in hypothermic may well mimic unconsciousness. Anti epileptic drugs patients. Sensitivity to some drugs is recognized, are well known to reduce neuromuscular blocking for example in patients with myasthenia gravis non- agent responsiveness when given chronically but not depolarizing muscle relaxants have a long duration acutely45-47. Sahoo et al reported on a case of a patient of action. Preoperative oral midazolam while it may with a long term seizure history who was not currently cause delayed awakening in geriatric patients was not taking any antiseizure medication and was paralyzed predictive of delayed emergence in adolescents or for over 3 hours following rocuronium 40mg and a preadolescents unless there was detectable preoperative loading dose of phenytoin 20mg.kg47. sedation48. Delayed Awakening from General Anesthesia 543

Inhaled Agents Table 4 Several factors may contribute to prolonged apnea after The speed of emergence from inhaled agents directly succinylcholine administration. Genetic Acquired relates to alveolar ventilation and hypoventilation may Plasma cholinesterase Hepatorenal disease delay emergence. The less soluble the agent, the deficiency more rapid the elimination. Thus awakening Myotonic dystrophy Pregnancy is fastest with desflurane and nitrous oxide. (Malignant hyperthermia) Thyrotoxicosis After prolonged surgery and anesthetic administration, Mitochondrial myopathies Cardiac failure Drug interactions( tissue uptake, which relates to drug solubility becomes ecothiopate, neostigmine, 49 a factor . fertilizers)

Intravenous Agents Potentiation by other drugs

Recovery is determined chiefly by redistribution Prior ingestion of sedative premedication such as benzodiazepines, monoamine oxidase inhibitors, from blood and brain into muscle and fat. Awakening selective serotonin reuptake inhibitors and some after propofol is fast because of rapid hepatic herbal preparations like St Johns Wort or alcohol metabolism and no accumulation. Pentothal is potentiates the central nervous system depressant redistributed quickly but elimination by oxidative effects of anesthetic and analgesic drugs and may metabolism in the liver is slow and the drug has a long delay emergence from anesthesia. The effects of non elimination half life of 3.4 to 22 hours. Up to 30% of depolarizing muscle relaxants may be increased by the dose may remain in the body for up to 24 hours drugs such as amino glycosides, lithium, calcium if repeat doses have been given or it is administered channel antagonists, and diuretics36. as an infusion49. Advanced age or renal or hepatic disease can prolong drug action of agents dependent Local Anesthetic Toxicity on hepatic metabolism or renal excretion. One report notes miscalculation combined with advanced age and Repeated dose of local anesthetic agents especially cardiac disease as a cause of continued somnolence into very vascular areas may result in toxicity that may in an 86 year old patient receiving an intravenous manifest from somnolence to seizures to cardiac arrest. lidocaine infusion for dysrythmia50. Management requires cardiopulmonary support and lipid emulsion infusion52-4. Neuromuscular Blocking Agents Fluid Overload Residual paralysis is not delayed awakening but Crystalloids migrate from the vascular space unresponsiveness may be perceived as such. quickly after infusion to dependent and soft tissue Causes include, overdose, incomplete reversal, spaces such as the airway, gut wall and lungs. syringe swap when additional dosing may have been Pulmonary edema after lung surgery correlates with given rather than the reversal agents, infiltration large fluid administration (12-15% incidence)55. of the intravenous cannula or in patients following Ten% of patients receiving >6l fluid over 24 hours succinylcholine administration who may have had respiratory failure. Hypoxia and hypercarbia are plasma cholinesterase deficiency51. Repeated doses of common due to cardiac failure. succinylcholine may result in dual block. Causes of succinylcholine apnea are listed in table 4. Mivacurium Surgical Factors is also metabolized by plasma cholinesterase and can have prolonged effects in susceptible individuals. As noted above long surgery is associated with

M.E.J. ANESTH 22 (6), 2014 544 frost e. A. M. delayed return to consciousness. Rare Causes of delayed return to consciousness

Procedures most likely to be associated Hypokalemia with postoperative somnolence are neurosurgical interventions. Comparison of patients undergoing Rayazi et al reported 2 cases of delayed spinal or intracranial surgery indicated that those awakening associated with low potassium levels due who underwent craniotomy for removal of large mass perhaps to hyperventilation. They recommended lesions awoke more slowly than patients who had serum potassium evaluation as part of determining the 62 spinal procedures or only small lesion56. Incidental differential diagnosis . rupture of an arteriovenous malformation may cause intracerebral hemorrhage and delay awakening57. Child Abuse Acute intracranial hemorrhage has also been described after ventriculo-peritoneal shunt placement58. Ott et al reported a case of a child who underwent meatoplasty in what appeared to be a Patients with dystonia undergoing deep brain straight forward anesthetic. The child was very slow stimulation may have an almost 70% incidence of to recover and eventually died. Autopsy showed delayed emergence, related to excessive anesthetic very high chlorpromazine levels, the drug apparently potentiation of the low output pallidal state in dystonia administered by her mother during the hospitalization63. which may depress the pallido-thalamo-cortical- circuitry or depression of the ventral pallidal inputs to Dandy Walker Malformation the septo-hippocampal system59. De Santis et al described an incidental diagnosis The beach chair position has been associated with of Dandy Walker malformation (DWM) in a 73 year old decreased cerebral perfusion and cerebral ischemia60. adult following coronary artery surgery complicated Recommendations are that blood pressure should be by delayed awakening. DWM is a rare posterior fossa measured at the level of the auricle and some form of malformation defined by hypoplasia and upward cerebral monitoring be used such as entropy or cerebral rotation of the cerebellar vermis. The patient remained oximetry. intubated for 6 days64.

Metabolic Factors Brainstem Paralysis

After local perioperative bupivacaine wound Many of these factors are already mentioned infiltration in 2 adolescent patients who underwent above as also being part of patient characteristics. foramen magnum decompression for Arnold Chiari Other causes include: malformation delayed awakening was attributed 1. Epileptic drugs reduce neuroblocking agents to absent brainstem reflexes caused by the local responsiveness when given chronically but not anesthetic65. A similar case of absent brain stem reflexes acutely47. due to a field block with bupivacaine was described by Fuzaylov et al in an infant66. 2. Hypo- hyperglycemia, electrolyte, acid-base disorders and hypothermia may cause delayed emergence from anesthesia. Hypokalemia is Intravenous Infiltration induced by low potassium intake, excessive Infiltration of an intravenous infusion of excretion from gastrointestinal (GI) and kidneys remifentanil was noted shortly after induction in a (diuretics). 30 year old male67. A 2nd vein was cannulated and the 3. Hypothyroidism may be diagnosed for the first anesthetic continued with remifentanil and sevoflurane time by delayed awakening61. for the short duration of the microlaryngoscopy. A Delayed Awakening from General Anesthesia 545 few minutes after extubation, the patient developed 11. CT scan, neurologic/neurosurgical consultation respiratory arrest, responsive to naloxone. He remained is indicated if other causes have been excluded. somnolent for the next 5 hours. No other abnormalities 12. In difficult cases, there should be no delay in were detected and the cause was determined to be requesting help. subcutaneous remifentanil accumulation. Treatment Hunter Syndrome Therapy depends on the cause. Nevertheless Hunter syndrome, one of the mucopolysaccharide in the initial assessment of the patient who is not storage diseases, is known to complicate anesthetic recovering as expected in the PACU, several steps and airway management. Following an apparently must be followed: uneventful intraoperative course including isoflurane, 1. Give oxygen to treat hypoxia. nitrous oxide and fentanyl recovery was delayed in a patient with severe manifestations of the disorder for 2. Give naloxone and/or flumazenil to reverse an almost 2 hours until naloxone was given68. overdose of narcotics or benzodiazepines. 3. Reverse effects of non depolarizing muscle Diagnosis relaxants. 4. Give intravenous aminophylline to antagonize As causes of delayed awakening are multifactorial, the effects of sedative and analgesic drugs, an accurate diagnosis must be made. including propofol69. 1. Past history should be reviewed, especially 5. Correct any airway difficulties including as regards drug ingestion, including herbal jaw life, insertion of an airway, reintubation, therapies such as St Johns Wort. application of continuous positive airway pressure. 2. Ensure all agents are turned off. 6. Establish blood pressure at appropriate levels 3. The anesthetic record should be reviewed as for the patient with vasopressor if necessary. regards concentration and dosages of drugs and duration. 7. Warm the patient to a temperature of 36-37 degrees. 4. Amount of fluid administration should be 8. Measure arterial blood gases, glucose and reviewed as excess fluid may gravitate to the electrolytes and make corrections. Especially of lungs, causing decreased oxygen exchange and acidosis. hypercarbia and hypoxia. 9. Perform a complete blood count and give blood 5. Vital signs should indicate cardiopulmonary if indicated. stability. 10. Obtain a 12 lead electrocardiogram and 6. Temperature should be close to normal. appropriate consults. 7. Hypo and hyperventilation should be excluded 11. Order a CT scan and request a neurological by blood gas analyses. consult. 8. Metabolic acidosis should be excluded. 9. Residual muscular paralysis should be excluded Concluding Statement by train of four monitoring and head lift of >5 seconds. The causes of delayed awakening after anesthesia 10. Neurologic examination should include pupil are often multifactorial and governed by patient, drug, examination, symmetric motor movements, surgical and metabolic factors. Drug overdose and presence of a gag or cough. interactions, especially with neuromuscular blocking

M.E.J. ANESTH 22 (6), 2014 546 frost e. A. M. agents, are among the most common causes. Metabolic sequelae and thus early diagnosis and treatment are abnormalities often do not present with the usual signs imperative. On rare occasions, dissociative states may and symptoms in a patient who is anesthetized. Organic present first as extended periods of unconsciousness cause of unresponsiveness may have long lasting without other identifiable causes. Delayed Awakening from General Anesthesia 547

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DexmeditomidineVersus Fentanyl As Coadjuvants Of Balanced Anaesthesia Technique In Renal Transplant Recipients

Sunder Negi*, Indu Sen**, Virender Arya*** and Ashish Sharma****

Abstract

Background: Ideal anesthetic technique for renal allograft recipients should provide hemodynamic stability, optimum graft reperfusion and adequate analgesia. Balanced anesthesia is preferred because renal nociception is conducted multi-segmentally and chronically ill ESRD patients have labile psychological profile. Present study compared the efficacy of dexmedetomidine with fentanyl administered via intravenous and epidural route before induction of general anesthesia. Methods: Prospective, double blind randomized study, recruited sixty hemo-dynamically stable ESRD adults, 18-55 years, scheduled for elective live related renal transplantation. Patients randomly received intravenous dexmedetomidine 0.5 µg/kg followed by epidural dexmedetomidine 0.5 µg/kg alongwith 5ml;0.25% ropivacaine or intravenous fentanyl 1 µg/kg followed by epiduralfentanyl 1 µg/kg alongwith 5ml;0.25% ropivacaine. All patients received standardized general anaesthesia and continuous epidural ropivacaine 0.25%; 4-8 ml/hr. Preoperative sedation, peri-operative haemodynamics, end tidal anaesthetic agent requirement, peri-operative fluid requirement, need for vasopressors, blood loss and early graft function was assessed. Results: 80% patients receiving intravenous dexmedetomidine did not require rescue midazolam for achieving satisfactory sedation before induction of general anaesthesia. Dexmedetomidine significantly reduced propofol and end tidal inhalational agents requirement and need for rescue analgesics. Early renal graft function (onset time of diuresis after declamping, 24 hours urine output and serum creatinine levels) was comparable. There were no adverse sequelae. Conclusion: Dexmedetomidine-based anaesthetic regimen versus fentanyl-based anaesthesia provided appropriate anxiolysis and analgesia for conducting invasive procedures and subsequent epidural administration of these agents reduced anaesthetic requirement and prolonged postoperative analgesia without compromising hemodynamics and respiratory parameters. Further dose finding studies can be conducted in kidney transplant recipients. Peri-operative management of renal allograft recipient should assure hemodynamic stability,

* MD, Senior Resident, Anesthesia & I. Care. ** MD, Additional Professor, Anesthesia & I. Care. *** MD, Additional Professor, Anesthesia & I. Care. **** MS, Assistant Professor, Transplant Surgery. Affiliation: Department of Anesthesia & Intensive Care and Department of Transplant Surgery. Post Graduate Institute of Medical Education and Research, Chandigarh, India-160012. Corresponding author: Dr. Indu Sen, Additional Professor, Anaesthesia & Intensive Care. House Number 5439, Sector 38-West, Chandigarh 160014, INDIA. Tel: 0091-172-2686677. E-mail: [email protected]

549 M.E.J. ANESTH 22 (6), 2014 550 Negi S. et. al enhance graft reperfusion and provide good post- respiratory parameters in end-stage renal disease operative pain relief1-,3. Every effort is made to choose patients undergoing live-related kidney transplant the right techniques as well as pharmacological agents surgery. which facilitate proper functioning of the newly 4,5 transplanted organ . Combined general and regional Methods anesthesia has been preferred considering that renal nociception is conducted multi-segmentally and This prospective, double blind randomized trial, chronically ill ESRD patients have labile psychological enrolled sixty ASA physical status II or III adults, 6,7 profile . Epidural anesthesia provides dynamic pain either gender, 18-55 years suffering from end stage relief, permits early extubation and a better response renal disease. Research ethics committee approval to the stress of anesthesia and surgery. However, large and informed written consent was taken. Patients with volumes of local anesthetics (LA) administered via drug allergy, compensated/decompensated myocardial neuraxial route can have deleterious hemodynamic insufficiencies, coagulation abnormalities or accidental consequences with associated risk of LA toxicity. dural puncture were excluded. Premedication consisted Although, Ropivacaine has low risk of cardio- of oral alprazolam 0.25 mg and ranitidine 150 mg vascular and central nervous system toxicity and a administered the night before surgery. Preoperative 8 lesser propensity for motor blockade . Traditionally, monitoring included: electrocardiography (ECG), opioids have been used as neuraxial adjuvants to baseline heart rate, respiratory rate, noninvasive reduce the dose of local anesthetics and improve the blood pressure (NIBP), arterial oxygen saturation quality of peri-operative analgesia9. However, there (SpO2), and bispectral index (BIS). The mean of is always a possibility of urinary retention, nausea, first three recordings of hemodynamic parameters vomiting, pruritis and respiratory depression with at 5 min interval taken after the patient was shifted 10 these agents . The incidence of motor blockade after to the operation theatre were considered as the epidural analgesia with amide local anesthetics (LA) baseline values. A 16 G cannula was secured in and opioids is approximately 4-12%, which defeats the a peripheral vein normal and saline infusion was 9 novel purpose of appropriate pain relief . started at 2 ml/kg/hour. The limb with arteriovenous fistula was not used for peripheral venous Dexmedetomidine, an α2-adrenergic agonist has sedative, anxiolytic, and anesthetic sparing access and invasive pressure monitoring. properties. The anti-nociceptive properties of the drug Patients were randomized using computer has been demonstrated in various trials where it was generated permuted block into two groups (randomized administered via systemic, intrathecal, perineural blocks of 6 patients in a 1:1 ratio using sealed or intra-articular routes11-15. Compared to fentanyl, envelopes). Group F patients (n=30) received 1 µg/ dexmedetomidine has been reported to induce sedation kg fentanyl infusion diluted to 20ml intravenous fluid without affecting the respiratory status. However, over 10 minutes before induction of anesthesia and efficacy of dexmedetomidine in renal transplant 1 µg/kg fentanyl in combination with 5ml of 0.25% surgery has not been evaluated. Therefore, the present ropivacaine (total volume 8ml ) via epidural route study was planned to compare dexmedetomidine after insertion of epidural catheter. Group D patients and fentanyl administered via both intravenous and (n = 30) received 0.5 µg/kg dexmedetomidine infusion epidural route prior to induction of anesthesia. diluted to 20 ml intravenous solution over 10 minutes Our hypothesis is that preinduction intravenous before induction of anesthesia, followed by 0.5 µg/kg dexmedetomidine infusion will provide anxiolysis dexmedetomidine in combination with 5ml of 0.25% and analgesia for central venous line and epidural ropivacaine by epidural route (total volume 8 ml). catheter insertions and its subsequent administration A 20 G arterial canula was inserted in the via epidural route alongwith ropivacaine will reduce radial artery under local infiltration for continuous intraoperative anesthetic requirement and prolong blood pressure monitoring. A double lumen central postoperative analgesia without compromising venous catheter was inserted in to internal jugular BALANCED ANESTHESIA FOR KIDNEY RECIPIENTS 551 vein (IJV) under local infiltration. Subsequently, In case of poor graft function (no urine output) under aseptic precaution 18G epidural catheter fluid administration was restricted. The total dose was placed in T12-L1 space with patient in left of vasoconstrictors/ ionotropes used to maintain lateral position. Correct placement of catheter was perioperative hemodynamics were noted. Intra confirmed by injecting epidural test dose (3ml 2% venous ondansetron (0.1 mg/kg) was administered lignocaine with adrenaline 5µg/ml). The epidural half an hour before the expected time of completion study solutions were prepared by an uninvolved of the surgery. At end of surgery patient was anesthesiologist according to written instructions reversed with neostigmine (0.05 mg/kg) and on sealed envelopes. The solution (8ml) was atropine (0.02 mg/kg)/ glycopyrolate (0.01 mg/ infused over 10 minutes via epidural route. This kg) and extubated on meeting the standard criteria was followed by maintenance infusion of 0.2% for extubation. They were shifted to post renal ropivacaine at4ml-8ml/hr administered epidurally. transplant care unit as per the institutional protocol where hourly hemodynamic parameters were recorded Hypotension was defined as systolic blood for 24 hrs. For postoperative pain relief, 4-8 ml/hr pressure (SBP) ˂90 mmHg or a greater than 20% drop of 0.2% ropivacaine infusion was used. If VAS was in mean arterial pressure (MAP) and managed with >4, first rescue analgesic with intravenous tramadol intravenous fluid administration to maintain CVP 12- 50 mg was used. For the patients not relieved with IV 15 mmHg. If MAP remained low despite adequate tramadol morphine 3mg was given. fluid infusion, vasoconstrictor (mephenteramine 3-6 mg intravenous boluses) or ionotropic support The level of sedation was assessed by the was instituted to maintain hemodynamic parameters Modified Observers Assessment of Alertness/ 16 within 20% of the baseline values. Sedation Score (OAA/S) . The intensity of pain (assessed by a linear Visual Analog Scale)17 and BIS General anesthetic technique consisted of values were noted every 5 minutes till the induction intravenous propofol, atracurium and a mixture of of anesthesia. Dose of intravenous propofol needed O N O and isoflurane titrated to BIS value between 2, 2 for loss of conciousness was also noted. 40-60. Endotracheal intubation was facilitated by IV atracurium 0.5 mg/kg when TOF count was zero. After intubation, intermittent positive pressure Statistical Analysis ventilation was commenced with a mixture of 50% nitrous oxide in oxygen and isoflurane, using a ANOVA with post-hoc significance, Chi-square closed circuit with a circle absorber. Ventilation test and Fisher’s exact test were used as appropriate. was adjusted to maintain end-tidal carbon dioxide Value of P<0.05 was considered significant andP <0.001 as highly significant. The sample size was calculated (EtCO2) between 35-40mm Hg. A TOF count of 2 7 or more was an indication for giving atracurium based on previous study employing epidural 0.1mg/kg IV. Total dose of atracurium consumption anesthesia with local anesthetic for renal transplant was noted. In all the patients, CVP was gradually surgery. To detect a 50% decrease in the incidence build up to 15 mmHg by crystalloids up to 50 ml/ of rescue analgesic requirement a minimum of 28 kg and colloids (2-4 ml/kg; 20% albumin) until patients per group were required to ensure adequate revascularization. Intravenous frusemide 2 mg/kg, power of the study with α of 0.05 (confidence interval hydrocortisone 10 mg/kg and 20% mannitol 2 ml/ 95%) and β of 0.1 (power of 90%). kg was given to all patients before reperfusion of grafted kidney. Target hemodynamics of mean Results BP> 85 mmHg, systolic BP> 135 mm of Hg and CVP of 12-15 mm of Hg were maintained during The demographic profile of both groups was and after declamping. Blood transfusion was comparable (Table 1). The baseline hemodynamic considered according to hemodynamic parameters, parameters were comparable in both the groups. estimated blood loss and serum hemoglobin levels. Observers Assessment of Alertness and Sedation

M.E.J. ANESTH 22 (6), 2014 552 Negi S. et. al

Table 1 The demographic profile of all the patients THE DEMOGRAPHIC Data

Patient Parameters GROUP D(n=30) GROUP F (n= 30) P-Value

Age(Yrs) 34.33±9.77 35.80±10.35 0.579 Height (cm) 162.10±7.298 160.93±7.315 0.539

Weight(kg) 55.04±7.55 53.083±9.05 0.366 Gender (M:F)* 25:5 22:8 0.387 Wt Before HD 56.583±7.76 54.58±9.04 0.362 Wt After HD 55.04±7.55 53.083±9.05 0.366

Preoperative Creatinine (mg/dl) 6.13 ± 1.74 6.74 ± 1.16 0.15 Preoperative GFR (ml/min) 11.93 ± 5.51 9.93 ± 1.99 0.14

Table 2 Perioperative characteristics of the patients of both the groups PERIOPERATIVE CHARACTERISTICS

Patient Parameters GROUP D(n=30) GROUP F (n= 30) P-Value

Warm ischemia time (min) 24.50±3.149 23.50±2.991 0.212

Cold ischemia time (min) 82.53±7.026 79.97±9.223 0.230 Time of onset of diuresis declamping (min) 5.44 ± 1.40 5.53 ± 1.53 0.972

Total dose of Propofol for induction (mg) 64.00±12.205 82.50±19.77 0.000* Total dose of Atracurium (mg) 84.00 ±13.15 89.50±11.91 0.095 Total dose of Fentanyl (µg) 60.80 ± 9.54 92.00 ± 21.21 0.01*

Blood loss (ml) 255.00±56.24 263.33±54.03 0.561

Crystalloids (ml/kg) 2500.00±435.494 2513±450.178 0.905 Albumin (ml/kg) 198.33±20.692 186.67±34.575 0.118 Duration of surgery (min) 121.33±10.41 125.33±11.66 0.279 Duration of anesthesia (min) 191.33±13.83 190.67±12.61 0.458 Time to 1st Rescue analgesia 13(10-16) 4(3-5) 0.001* Post op Tramadol (mg) 11.67±21.50 50.00±22.74 0.000* Post op Morphine (mg) 0.30±0.915 5.30±8.991 0.004* Post surgery Urea (mg/dl) 60.07±19.59 72.91±33.34 0.075

Post surgery Creatinine (mg/dl) 3.718±1.38 4.843±2.305 0.060 Post operative Nausea 5 (16%) 4 (13%) 0.784 Postoperative Vomiting 4 (13%) 3 (10%) 0.673 Postsurgergery Shivering 1 (3.3%) 1 (3.3%) 1.000 Postsurgery Headache 1 (3.3%) 0 0.554 BALANCED ANESTHESIA FOR KIDNEY RECIPIENTS 553

Score noted at 5 minutes interval for 30 minutes after of these two study drugs were chosen. For the same giving the intravenous drug in both the groups. OAAS reasons, variable rate local anesthetic epidural of 4 was achieved in 25 patients in Group D after 10 infusion was administered periopeatively ie 0.25% minutes. However, in Group F only 4 patients achieved ropivacaine at 4-8 ml/hour to titrate MAP within 20% OASS of 4. The Rest of the patients required injection of the baseline values. Both the anesthetic regimens of midazolam (1 mg iv). Between groups OAA/S was provided satisfactory anesthesia, but dexmedetomidine significantly better in group D versus group F (p<0.05). group proved to be a better alternative with less Induction dose of propofol for hypnosis and requirement of intraoperative anaethetic agents and achieving BIS value 40 – 60, was significantly lower postoperative rescue analgesics. in Group D as compared to Group F (p<0.05). EtAA ESRD patients frequently have marked swings requirement was significantly lower in Group D as in BP during surgery (±30%) and exaggerated compared to Group F (p<0.05). responses to induction, laryngoscopy, intubation, A total 27 patients in Group F received injection declamping and extubation21. This is because of tramadol as compared to only 8 patients in Group preoperative dialysis induced dehydration, increased D for VAS > 4. In Group F, 18 patients received sensitivity to anesthetics and/or long-term usage injection morphine as second rescue analgesic versus of anti hypertensives. Therefore, a concern about 4 patients in Group D (p<0.05).Time for maintaining haemodynamic instability has been raised when adequate analgesia without the need for tramadol was general anaesthesia is administered alongwith central significantly longer in group D. neuraxial blockade18. In previous studies, prophylactic Early graft function was assessed by onset of low dose dopamine infusion has been used to maintain diuresis after declamping, hourly urine output, serum perfusion pressure of the grafted kidney. Bhosale et 22 creatinine levels and glomerular filteration rate (GFR) al reported 6% incidence of hypotension in their estimation in the first 24 hours.Values were comparable prospective study involving CSEA in renal transplant 23 in both the groups (p > 0.05). Both the groups did not surgery. Dauri et al compared combined general and differ in terms of post operative nausea, vomiting, epidural anaesthesia with general anaesthesia. No case shivering and headache. Patients in both the groups of hypotension was reported though the dopamine received epidural infusion of 0.2% of ropivacaine infusion rate required to maintain perfusion pressure at the rate of 4-8ml/hr in the post operative period. was higher in the combined group. Akpek al5 started The epidural catheter was removed when VAS was dopamine infusion soon after the epidural drug was consistently less than 4 for 12 hours. All the patients administered to maintain adequate perfusion pressures. were discharged from the transplant unit on the 6th This may be the reason that no case of hypotension or 7th postoperative day. There were no readmissions. was reported. Literature reveals that high vasopressor support Discussion required for the maintainenace of perioperative haemodynamics can adversely affect micro In the present study, combination of general circulation of the grafted kidney19,20. Therefore, it has anesthesia alongwith continuous epidural ropivacaine been commented that vasoconstrictors with strong infusion was used for live-related renal transplant α-adrenergic effects, such as phenylephrine, should be surgery. We also used a fixed dose of two different drugs of last resort, Several animal models have also adjuvants ie fentanyl versus dexmedetomidine via demonstrated that vessels in the transplanted organs are intravenous and epidural routes prior to induction of more sensitive to sympathomimetics24,25. Therefore, it general anaethesia. Both these adjuvants alongwith is worthwhile to find out ideal anesthetic regimens. standard anaesthesia, provided stable hemodynamics Low dose epidural ropivacaine is being preferred and optimum intraoperative analgesia. Considering because it is less cardiotoxic, provides better analgesia frequent reports of labile hemodynamic profile of without motor blockade. Addition of neuraxial ESRD patients18-20, fixed and relatively lower doses adjuvants like opioids and alpha-2 receptor agonists

M.E.J. ANESTH 22 (6), 2014 554 Negi S. et. al

Fig. 1 Consort diagram of patients enrolled for the study

further improve the quality of peri-operative analgesia fusion surgery reduced propofol infusion requirements due to sedative, anxiolytic, and local anesthetic sparing with less effect on hemodynamics. We also observed properties9,11,12,13,26 Asano T et al27 observed in an that induction dose of propofol required in Group animal study that anti-nociceptive efficacy of epidural D was significantly lower as compared to Group F. dexmedetomidine is approximately five times more Intraoperative EtAA requirement for maintaining BIS compared to its systemic administration. Salgado P value within 40-60 was also lower in Group D. 28 et al found that epidural dexmedetomidine does All the graft recipients received adequate not affect onset time or upper level of anesthesia (p hydration to maintain CVP of 12-15mm of Hg. Intra > 0.05) moreover it prolongs block duration time (p operative fluid requirements (crystalloid and colloid) < 0.05) and postoperative analgesia (p < 0.05), and to maintain CVP was comparable in both the groups. also results in a more intense analgesia (p < 0.05). Carlier32 and Luciani33 et al. The authors have emphasize Superiority of epidural dexmedetomidine has been upon the importance of maximal hydration and proved in an orthopedic study29. These findings were maintenance of adequate haemodynamic parameters at confirmed in the present study in ESRD patients. the time of reperfusion for the development of early Kasaba et al.30 observed that hypotensive effects of diuresis and prophylaxis of acute tubular necrosis in propofol are additive to epidural anaesthesia, resulting the immediate postoperative period. Kadieva et al34 in significant decrease in MAP. Ngwenyama N et al.31 reported that maintenance of perfusion pressure by has commented that concomitant use of intravenous generous administration of intravenous fluids to permit dexmedetomidine in patients undergoing spinal adequate renal blood flow was more important than BALANCED ANESTHESIA FOR KIDNEY RECIPIENTS 555 perioperative dopamine infusion in achieving graft in Group D.None of the patients had adverse effects function and survival. During declamping there is a related to the study drugs, anaesthetics used or surgery. release of acid metabolites, prostaglandins, activated Opioid related urinary retention, pruritis, or respiratory complements, cold perfusate of grafted kidney and depression did not occur with the dose of fentanyl myocardial depressant factor35. After eclamping the used. Undue bradycardia did not occur with the single MAP decreased in all the patients. However, the fall dose dexmedetomidineadministered via parenteral was not significant in both the groups. Akpek et al36 in and epidural route. None of the patients had any their prospective study comparing general anaesthesia cardiovascular or neurological side effects due to local and epidural anaesthesia for renal transplant recipients anaesthetics. There was no accidental dural puncture, found no difference in the immediate postoperative There was no case of epidural hematoma, neurological graft function as determined by biochemical markers deficits, hyperacute graft rejection, excessive bleeding, and DTPA scan. Early graft function was assessed anuria, injury to bowel or other vascular structures. by onset of diuresis after declamping, post operative Considering the paucity of published data in serum creatinine and urine output estimation at hourly ESRD patients, we preferred to use fixed single dose intervals for first twenty four hours. These parameters of dexmedetomidine and infusion was not continued were comparable in both the study groups. Warm and intraoperatively or postoperatively. Frumento37 et al cold ischaemic time and time of onset of diuresis was found that dexmedetomidine infusion administered as comparable in both the groups. The estimated blood a supplement to epidural analgesia induces diuresis in loss didnot differ amongst groups. Postoperatively post-thoracotomy patients with normal preoperative analgesia as assessed using visual analogue scale renal function and undergoing fluid restriction. In the (VAS) scores revealed longer and better pain relief

Fig. 2 Peri-operative Hemodynamics, Preoperative Sedation Scores Intra-operative Anesthetic Agent Requirement Data

M.E.J. ANESTH 22 (6), 2014 556 Negi S. et. al present study, single dose of dexmedetomine was used provided appropriate anxiolysis and analgesia for and no such beneficial effects were noticed. Further conducting invasive procedures and subsequent studies can be conducted in renal transplant recipients epidural administration of these agents reduced to demonstrate this effect of dexmedetomidine on the anaesthetic requirement and prolonged postoperative grafted kidney. analgesia without compromising hemodynamics and To conclude, dexmedetomidine-based respiratory parameters. Further dose finding studies anaesthetic regimen versus fentanyl-based anaesthesia can be conducted in kidney transplant recipients.

Fig. 3 Postoperative Pain VAS scores BALANCED ANESTHESIA FOR KIDNEY RECIPIENTS 557

References

1. James Baker, Spencer Yost, Claus Niemann U: Kidney renal transplantation. Anesth Analg; 1993, 76:362-65. transplantation. In: Miller RD eds. Miller’s anaesthesia 7th ed. 20. Morita K, Seki T, Nonumura K: Changes in renal blood flow in Elsevier Churchill Livingstone; 2010, 2161-66. response to sympathomimetics in the rat transplanted and denervated 2. Kazimirov VG, Pisariauk SN, Perlin DV: Advantages of epidural kidney. Int J Urol; 1999, 6:24-32. anaesthesia in patients with end stage chronic renal failure. 21. Cronnelly R, Kremer PF, Beaupre P, et al: Haemodynamic Anesteziol Reanimatol; 1995, 4:63-66. response to anaesthesia in patients with end stage renal disease. 3. Rockemann G, Seeling W, Pressler S, Steffen P, Georgiff M: Anesthesiology; 1983, 59:47-52. Reduced postoperative analgesic demand after inhaled anaesthesia 22. Bhosale G, Shah V: Combined spinal-epidural anaesthesia for renal in comparison to combined epidural-inhaled anaesthesia in patients transplantation. Transplant Proc; 2008, 40:1122-4. undergoing abdominal surgery. Anesth Analg; 1997, 84:600-5. 23. Dauri M, Costa F, Servetti S, Sidirupoulou T, Fabbi E, Sabota AF: 4. Linke CL, Merin RG: A regional anaesthetic approach for renal Combined general and epidural anaesthesia with ropivacaine for transplantation. AnesthAnalg; 1976, 55:69-73. renal transplantation. Minerva Anesthesiol; 2003, 69:873-84. 5. Akpek E, Kayhan Z, Kaya H, Candan S, Haberal M: Epiural 24. Morita K, Seki T, Nonumura K: Changes in renal blood flow in anaesthesia for renal transplant. Transplant Proc; 1999, 31:3149-50. response to sympathomimetics in the rat transplanted and denervated 6. Hadimioglu N, Ertug Z, Bigat Z, Yilmaz M, Yegin A: A randomized kidney. Int J Urol; 1999, 6:24-32. study comparing combined spinal epidural or general anaesthesia 25. Gabriels G, August C, Grisk O: Impact of renal transplantation on for renal transplant. Transplant Proc; 2005, 37:2020-22. small vessel reactivity. Transplantation; 2003, 75:689-97. 26. Katarzyna R, Piotr K and Hanna M: The effect of dexmedetomidine 7. Davies J, Silbert S, Mooney J, Dysart H, Meads C: Combined epidural and general anaesthesia versus general anaesthesia for sedation on brachial plexus block in patients with end-stage renal abdominal aortic surgery. Anaesth Int Care; 1993, 21:790-94. disease. Eur J Anaesthesiol; 2009, 26:851-55. 27. Asano T, Dohi S, Shimonaka H, Lida H: Antinociception by epidural 8. McClure JH: Ropivacaine. Br J Anaesth; 1996, 76:300. and systemic alpha 2-adrenoceptor agonists and their binding 9. Axelsson K, Gupta A: Local anaesthetic adjuvants: neuraxial versus affinity in rat spinal cord and brain.Anesth Analg; 2000, 90:400-7. peripheral nerve block. Curr Opin Anaesthesiol; 2009, 22:649-54. 28. Salgado PF, Sabbag AT, Silva PC: Synergistic effect between 10. Rawal N, Schott U, Dahlstrom B: Influence of naloxone infusion dexmedetomidine and 0.75% ropivacaine in epidural anaesthesia. on analgesia and respiratory depression following epidural Rev Assoc Med Bras; 2008, 54:110-5. morphine. Anesthesiology; 1986, 64:194-201. 29. Sukhminder JB, Vikramjit A, Jasbir K: Comparative evaluation of 11. Katarzyna R, Piotr K and Hanna M: The effect of dexmedetomidine dexmedetomidine and fentanyl for epidural analgesia in lower limb sedation on brachial plexus block in patients with end-stage renal orthopedic surgeries. Saudi J Anaesth; 2011, 5:365-370. disease. Eur J Anaesthesiol; 2009, 26:851-55. 30. Kasaba T, Kondero O, Yoshimuri Y, Watanbe Y, Takasaki M: 12. Asano T, Dohi S, Shimonaka H, Lida H: Antinociception by epidural Haemodynamic effects of induction of general anaesthesia with and systemic alpha 2-adrenoceptor agonists and their binding propofol during epidural anaesthesia. Can J Anaesth; 1998, 11:1061- affinity in rat spinal cord and brain.AnesthAnalg ; 2000, 90:400-7. 5. 13. Elhakim M, Abdelhamid D, Abdelfattach H, Magdy H, Elsayed 31. Ngwenyama NE, Anderson J, Tobias JD: Effects of dexmedetomidine A: Effect of epidural dexmedetomidine on intraoperative awareness on propofol and remifentanil infusion rates during total intravenous and postoperative pain after one lung ventilation. Acta Anaesthesiol anesthesia for spinal surgery in adolescents. PaediatricAnaesth; Scand; 2010, 18:703-9. 2008, 18:1190-5. 14. Chad B, Mary N, John M, Ralph L: Perineural administration 32. Carlier M, Squffle JP, Pirson Y, et al: Maximal hydration during of dexmedetomidine in combination with bupivacaine enhances anaesthesia increases pulmonary arterial pressures and improves sensory and motor blockade in sciatic nerve block without inducing early function in human renal transplant. Transplantation; 1982, neurotoxicity in rat. Anesthesiology; 2008, 109:502-511. 34:201-7. l etwalli owafi smail 15. A -M R, M H, I H: Effect of intra-articular 33. Luciani J, Frantz P, Thibault P: Early anuria prevention in human dexmedetomidine on postoperative analgesia after arthroscopic kidney transplantation. Advantage of fluid load under pulmonary knee surgery. Br J Anaesth; 2008, 101:395-99. artery pressure monitoring during surgical period. Transplantation; 16. Chernik DA, Gillugs D, Laine H, et al: Validity and reliability of 1979, 28:308-12. the observation and alterness/sedation score: study with intravenous 34. Kadieva VS, Friedman L, Margolius LP, Jackson SA, Morell DF: midazolam. J clinpsychopharmacol; 1990, 10:244-51. The effects of dopamine on graft function in patients undergoing 17. Chapman CR, Case KL, Dubner R: Pain measurement overview. renal transplantation. AnesthAnalg; 1993, 76:362-65. Pain; 1985, 22:1-31. 35. Akpek EA, Kayhan Z, Donmez A, Moray G and Arslan G: Early 18. Hadimioglu N, Ertug Z, Bigat Z, Yilmaz M, Yegin A: A randomized postoperative following renal transplantation surgery: Effect of study comparing combined spinal epidural or general anaesthesia anaesthetic technique. J Anesth; 2002, 16:114-18. for renal transplant. Transplant Proc; 2005, 37:2020-22. 36. Frumento RJ, Logginidou HG, Wahlander S: Dexmedetomidine 19. Kadieva VS, Friedman L, Margolius LP, Jackson SA, Morell DF: infusion is associated with enhanced renal function after thoracic The effects of dopamine on graft function in patients undergoing surgery. J ClinAnesth; 2006, 18:422-6.

M.E.J. ANESTH 22 (6), 2014

SHORT BEVELED SHARP CUTTING NEEDLE IS SUPERIOR TO FACET TIP NEEDLE FOR ULTRASOUND-GUIDED RECTUS SHEATH BLOCK IN CHILDREN WITH UMBILICAL HERNIA: A CASE SERIES

A. Alsaeed*, A. Thallaj**, T. Alzahrani**, N. Khalil*** and A. Aljazaeri****

Summary

Background: The most common peripheral nerve blocks used in umbilical hernia repair are rectus sheath block and regional block (caudal block). Ultrasound guidance of peripheral nerve blocks has reduced the number of complications and improved the quality of blocks. The aim of this study is to assess the post rectus sheath block pain relief in pediatric patients coming for umbilical surgery, and to evaluate the easiness of soft tissue puncture and ultrasonic appearance of two different needle types. Methods: Twenty two (22) pediatric patients (age range: 1.5–8 years) scheduled for umbilical hernia repair were included in the study. Following the induction of general anesthesia, the ultrasonographic anatomy of the umbilical region was studied with a 5-16 MHz linear probe. An ultrasound-guided rectus sheath block in the lateral edge of both rectus abdominis muscles (RMs) was performed (total of 44 punctures). A 22 gauge short beveled sharp cutting needle 1.1x 30 mm needle A (BD Insyte – W, Vialon material. Spain) was used in one side, and a Stimuplex A insulated Needle 22G 50mm (needle B) was used on the other side. Surgical conditions, intraoperative hemodynamic parameters, and postoperative analgesia were evaluated. Results: Ultrasonograghic visualization of the posterior sheath was possible in all patients. Needle A scored 72.7% of excellent needle tip and shaft view (16 out of 22) compared to 63.63% for needle B (14 out of 22). None of the needles scored poor view. The ultrasound guided rectus sheath blockade provided sufficient analgesia in all children with no need for additional analgesia except for one child who postoperatively requested morphine 0.1 mg/kg intravenously in recovery room. There were no complications. Conclusions: Ultrasound guidance enables performances of an effective rectus sheath block for umbilical hernia in the lateral edge of the rectus muscle. Use of the sharp short beveled needle of 22 gauge intravenous (IV) cannula stylet provides easy, less traumatic skin and rectus muscle penetration and better needle visualization by the ultrasound. Keywords: surgery: umbilical hernia; ultrasonography; umbilical peripheral nerve block, anesthesia; analgesia, postoperative; anesthetic techniques, regional, rectus sheath block.

* Professor, Department of Anesthesia. ** Associate Professor, Department of Anesthesia. *** Senior Registrar, Department of Anesthesia. **** Associate Professor, Department of Surgery, Pediatric Surgery Division. Affiliation: College of Medicine, King Saud University, Riyadh, KSA. Corresponding author: Abdulhamid H. Alasaeed, (Samarkandi) MD, Professor of Anaesthesia, College of Medicine, King Saud University, P.O. Box: 7805, Riyadh 11472, KSA. Tel: +966505428205. E-mail:[email protected] Accepted as presentation at Euroanthesia2014 congress (Stockholm, Sweden, 31 May-3 June 2014).

559 M.E.J. ANESTH 22 (6), 2014 560 Alsaeed A. et. al

Introduction After general anesthesia was induced and venous access established, fentanyl 2mic/kg was given and an Umbilical hernia repair is a common operation appropriate size laryngeal mask airway was placed. in pediatric surgery. It is carried out in children over 2 Spontaneous ventilation with 1 MAC sevoflurane in a years old, usually under general anesthesia combined mixture of 50% air and oxygen was maintained in all with a regional block (caudal block). It is done as cases throughout the procedure. a day case procedure; a peripheral nerve block is The ultrasonographic anatomy of the umbilical usually the choice. The rectus sheath block was region was studied in each case, with 5-16MHz 1 described in adults , has been used for laparoscopic US linear probe (Sonosite M TURBO). The probe 2 surgery in gynecology , and is one of the currently was positioned 1 cm above the umbilicus, and the 3 used techniques in pediatric umbilical surgery . adjustments in depth and gain were made in order to However, it may be associated with complications achieve the optimal sonographic view of both rectus such as retroperitoneal hematoma 4 and possibility abdominis muscle (RMs), their sheaths, and adjacent 5 of peritoneal puncture . The paraumbilical block structures. was described in 11 pediatric patients to avoid these The sheath and lateral edge of the RM were complications and to improve the success rate of the localized, and the peritoneum and the aponeurosis block6. Recently, direct ultrasonographic visualization of ipsilateral transverse abdominis (TM), internal of the brachial plexus7, of the sciatic nerve in the and external oblique muscles (EOM&IOM) were popliteal fossa8, the ilioinguinal/iliohypogastric identified (Figure 1). After aseptic preparation of nerves9, and of rectus sheath10 has been done the puncture site, the ultrasound probe was covered successfully in children. with sterile TEGADERM film (3M Health Care St. The aim of this case series was to investigate the Paul, MN.USA) and sterile ultrasound gel was used ultrasound visualization of the anatomy in the umbilical (Ultra/Phonic Pharmceutical Innovations, Inc, New region in children and to describe an ultrasound-guided Jersey.USA). The block was performed with 22G new needle type needle A (22G short beveled sharp short beveled sharp cutting stylet needle 1.1x 30 cutting stylet needle 1.1x 30 mm BD insyte -W) that mm (BD Insyte – W, Vialon material, Spain) needle might improve the quality of the blocks and reduce A (Figure 2, 7), assembled with extension set with T the risk of complications compared with conventional adaptor (VEINSYSTEM, Sigo, Ireland). The needle needle B (Stimuplex A insulated facet tip Needle 22G was introduced in-long axis parallel to the ultrasound 50 mm B Braun). probe (Figure 4) to reach the lateral border of the rectus muscle, and advanced slowly and carefully Methods until the tip of the needle was seen just between the posterior aspect of the rectus abdominis and its sheat Approval of the IRB ethical committee (King (Figure 1). A single injection of plain bupivacaine Khalid University hospital, King Saud University, 0.25%, 0.25 ml/kg-1 was injected under the real-time Saudi Arabia) was obtained (No14/3999/IRB), and ultrasound control. The procedure was repeated on informed consent from the parents was obtained in the other side of the rectus sheath with the same drug all cases. Twenty two children, age range 1.5–8 years, volume and concentration, using a facet tip needle ASA physical status I or II, scheduled for umbilical (Stimuplex A insulated Needle 22G 50mm) needle hernia repair on an outpatient basis, were included B (Figure 3, 5, 6). All blocks were done by the same in this case series. None had a history of convulsion, operator (AHS). A blinded observer with reasonable neuromuscular disease or hematological disorders ultrasounguided regional block experience, and and local anesthesia allergy. No premedication was unaware of the study design was asked to assess the given. Intraoperative monitoring included, ECG, pulse quality of the sonographic visualization of the needle oximetry, non-invasive blood pressure, and end tidal tip and shaft and to rate the view as: +: poor, ++: good, carbon dioxide concentration. +++: excellent. ULTRASOUND-GUIDED RECTUS SHEATH BLOCK IN CHILDREN 561

Fig. 1 Short axis sonographic view of the periumibilical region shows: the rectus muscle surrounded by the rectus sheath (RS), Internal oblique muscle (I.O), External oblique muscle (E.O), Transversus abodominis muscle(T.A)

Fig. 2 Needle A, 22G short beveled sharp cutting stylet and needle tubing assembly

Fig. 3 Needle B: a facet tip insulated needle Stimuplex A

M.E.J. ANESTH 22 (6), 2014 562 Alsaeed A. et. al

Fig. 4 Needle position; in plane technique lateral to the ultrasound probe

Fig. 5 Tip of Needle A; short beveled sharp tip, Needle B: facet tip

Fig. 6 Needle B tip and shaft visualization within the posterior rectus sheath fascial split by ultrasound during rectus sheath block and injection of local anaesthesia, the rectus sheath (RS), Internal oblique muscle (I.O), External oblique muscle (E.O), Transversus abodominis muscle (T.A), Local anaesthesia (LA)

Fig. 7 Needle A tip and shaft visualization within the posterior rectus sheath fascial split by ultrasound during rectus sheath block and injection of local anaesthesia, the rectus sheath (RS), Internal oblique muscle (I.O), External oblique muscle (E.O), Transversus abodominis muscle(T.A), Local naesthesia(LA) ULTRASOUND-GUIDED RECTUS SHEATH BLOCK IN CHILDREN 563

Fig. 8 Heart rate in different time

Fig. 9 Blood pressure in different time

Surgery was then started and hemodynamic morphine 0.1 mg/kg IV. parameters were recorded throughout the surgery. In the surgical wards, trained nurses recorded the Fentanyl 1mic/kg was administered in the event time when the child first required additional paracetamol of an increase in heart rate or blood pressure of more 15 mg/kg suppository, supplement analgesia during the than10% from baseline or an increase in respiratory first day at home was with paracetamol 15 mg/kg PO rate of more than 20% from baseline following the every 6-8 h, and analgesia requirement were recorded skin incision or at any time during the procedure and during the day after telephone call. was defined as insufficient analgesia. At the endof the procedure, the laryngeal mask was removed and Results general anesthesia was discontinued. Children were taken to the post anesthesia care unit (PACU). A total of 14 females and 8 males children were Postoperative analgesia was evaluated by a blind included in the study. Table 1 shows demographic investigator using the modified CHEOPS pain scale 11 data. Each patient received two punctures one on each in the PACU every 10 min until discharge. Children side of the umbilicus, for a total of 44 punctures in 22 who scored 5 at any of the evaluated times were given patients. No increases in the heart rate or blood pressure

M.E.J. ANESTH 22 (6), 2014 564 Alsaeed A. et. al were recorded intraopertively (Figure 8, 9) also no Peritoneum and the lateral edge of the rectus increase on respiratory rate and no patient was given muscles was easily identified in all the cases and the additional fentanyl. Different surgeons performed the punctures were performed without complication. cases and assessed the surgical conditions as good in Only one child scored >5 in the modified all the patients. Needle A scored 72.7% of excellent CHEOPS Scale and was given morphine 0.1 mg/ needle tip and shaft view (16 out of 22) compared kg intravenous in the PACU. The nurses reported no to 63.63% for needle B (14 out of 22). There was supplement of analgesia. statistical difference between the two groups with All patients were discharged and no child more visibility of the needle in group A compared to received more than two doses of paracetamol 15 mg/ group B needles (P<0.05) by using Fisher exact test kg -1 P.O at home. as statistical analysis. None of the needles scored poor view (Table 2). Table 1 Discussion Patient demographic data The rectus sheath block was first used in pediatric Total number :22 Mean age(years) Mean weight(kg) surgery by Ferguson et al. in 19963. The authors Female 16, Male 8 3.7 (1.5-8 years) 16 (10-27) described that the tendinous intersections of the rectus sheath are only anterior and do not extend through the Table 2 thickness of the muscle, so a potential space would Visualization score in needle A & needle B exist between the posterior aspect of the muscle and +: Poor visualization (needle tip & shaft) its sheath. This potential space would allow dispersion ++: Good visualization (needle tip & shaft) of LA at several levels, enabling an effect on several +++: Excellent visualization (needle tip & shaft) intercostal nerves. The puncture was performed on Case No. Needle A Needle B each side of the abdomen, just above and lateral to the 1 +++ ++ umbilicus, half-to-1 cm medial to the linea semilunaris. 2 +++ +++ The block proved to be effective and safe both for 3 ++ +++ umbilical and paraumbilical hernia repair3. 4 +++ ++ In recent years, ultrasound is of increasing 5 ++ +++ interest in regional anesthesia, as direct visualization 6 +++ +++ of the anatomic structures allows optimal placement of 7 ++ ++ the needle and thereby reduces the risk of inadvertent 8 +++ +++ interneural, intravascular or adjacent structures injury 9 ++ +++ (e.g. peritoneum)7. 10 +++ ++ In our case series, we described an ultrasound 11 +++ +++ guided technique of the 10th intercostal nerve block 12 +++ ++ using a 22G short beveled sharp cutting needle (Needle 13 +++ +++ A) in order to achieve smooth and easy puncture of the 14 ++ +++ skin, subcutaneous tissue, rectus sheath and muscle 15 +++ +++ penetration. When performing rectus sheath block in 16 +++ +++ children with the facet tip needle (Needle B), the needle 17 +++ ++ tip faces a highly compliant tissue compared to adults, 18 +++ +++ and tends to push rather than penetrate the tissue, thus 19 ++ ++ the operator’s hand need to apply more pressure on the 20 +++ +++ needle with a hazard of inadvertent peritoneal injury. 21 +++ +++ In contrast to peripheral nerve block, where facet 22 +++ ++ tip needle is considered as a safety measure, rectus ULTRASOUND-GUIDED RECTUS SHEATH BLOCK IN CHILDREN 565 sheath block does not approach specific nerve. The the use of short sharp beveled needle for rectus sheath use facet tip needles in this block have no justification. block in children In conclusion. Ultrasound guided Sonoghraphic visualization of needle A was superior to rectus sheath block is effective and safe intra and needle B. However, other cannula stylets of different postoperative analgesic approach in children and can brands need to be investigated. Economic wise, the be alternative to caudal block in day case surgery. cost of facet tip needle is five times that of stylet The use of the short beveled sharp cutting needle needle, which might influence needle type selection overcomes technical difficulty while penetrating the for the block. Before considering using stylet needle soft tissue, have easy penetration and good needle tip for rectus sheath block, further study with larger and shaft visualization compare the facet tip needle. numbers of patients is required before implementing

M.E.J. ANESTH 22 (6), 2014 566 Alsaeed A. et. al

References

1. Dolan J, Lucie P, Geary T, Smith M and Kenny G: The Rectus 7. Marhoferp, Sitzwohlc and Greher M, et al: Ultrasound guidance Sheath Block Accuracy of Local Anesthetic Placement by Trainee for infraclavicular brachial plexus anaesthesia in children. Anesthesiologists Using Loss of Resistance or Ultrasound Guidance. Anaesthesia; 2004, 59:642-646. Regional Anesthesia and Pain Medicine; 2009, 34:3:247-250. 8. Schwemmer U, Markus CK and Greim CA, et al: Sonographic 2. Smith BE, Suchak M, Siggin D and et al: Rectus sheath block for imaging of the sciatic nerve and its division in the popliteal fossa in diagnostic laparoscopy. Anaesthesia; 1988, 43:947-948. children. Pediatr Anesth; 2004, 14:1005-1008. 3. Ferrguson S, Thomas V and Lewis I: The rectus sheath block in 9. Willschke H, Marhoferp and Bosenberg A, et al: Ultrasonography paediatric anaesthesia: new indications for an old technique? for ilioinguinal/iliohypogastric nerve blocks in children. Br J Paediatric Anaesth; 1996, 6:463-466. Anaesth; 2005, 95:226-230. 4. Yuen PM and Ng PS: Retroperitoneal hematoma after rectus sheath 10. Willschke H, Bosenberg and Marhoferp, et al: Ultrasonography- block. J Am Assoc Gynecol Laparosc; 2004, 11:448, 5. guided rectus sheath block in pediatric anaesthesia - a new approach 5. Courreges P and Poddevin F: Rectus sheath block in infants:what to an old technique. Br J Anaesth; 2006, 97:244-249. suitability? (Letter). Paediatr Anaesth; 1998, 8:181-182. 11. Splinter WM, Reid CW and robert DJ, et al: Modified Children’s 6. Courreges P, Poddevin F and Lecoutre D: Para-umbilical block: a Hospital of Eastern Ontario Pain Scale in reducing pain after new concept for regional anaesthesia in children. Paediatr Anaesth; inguinal hernia repair in children. Anesthesiology; 1997, 87:542- 1997, 7:211-214. 546. BREAST CANCER RECURRENCE IN PATIENTS RECEIVING EPIDURAL AND PARAVERTEBRAL ANESTHESIA: A RETROSPECTIVE, CASE-CONTROL STUDY

Stephanie L. Koonce*, Sarah A. McLaughlin*, Dustin L. Eck*, Steven Porter*, Sanjay Bagaria*, Steven R. Clendenen* and Christopher B. Robards*

Abstract

Purpose: Studies have suggested an association between the use of regional paravertebral or epidural anesthesia and a reduction in tumor recurrence following breast cancer surgery. To examine this relationship we performed a retrospective case-control study of patients undergoing breast cancer surgery receiving regional, regional and general, or general anesthesia. Methods: A retrospective chart review was performed of patients undergoing surgery for stage 0 to III breast cancer. Patients identified as receiving regional anesthesia were then matched for age, stage, estrogen receptor (ER) status, progesterone receptor status, and HER-2 expression with patients who received no regional anesthesia. Univariate (Pearson’s χ2 test and odds ratio) and multivariate logistic analyses with backward stepwise regression were performed to determine factors associated with cancer recurrence. Results: Between 1998 and 2007, 816 women underwent surgery for stage 0-III breast cancer at our institution. Forty-five patients developed tumors. Univariate analysis showed the use of regional anesthesia trended towards reduced cancer recurrence, but it did not achieve statistical significance (p=0.06). Higher recurrence rates were associated with ER positive status (p=0.003) and higher tumor stage (p <0.0001). Age and HER-2 status were not associated with increased cancer recurrence (both p>0.11). Multivariate analysis confirmed ER status and stage as independently influential p( = 0.002 and p<0.0001 respectively). Conclusion: Although we found a trend towards reduced breast cancer recurrence with the use of regional anesthesia, univariate analysis did not reach statistical significance. Key words: Epidural anesthesia; Paravertebral Block; Regional Anesthesia; Recurrence.

* MD. Affiliation: Department of Anesthesiology, Mayo Clinic, Jacksonville, FL. Corresponding author: Christopher B. Robards, MD. Department of Anesthesiology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida, 32224. Tel: 904-956-3327, Fax: 904-956 3332. E-mail: [email protected]

567 M.E.J. ANESTH 22 (6), 2014 568 Koonce S. L. et. al

Introduction were performed using SAS (version 9.2, Cary, North Carolina) to determine factors associated with cancer Breast cancer is the most common cancer in recurrence. Age, cancer stage, ER, PR, HER-2, and women in the United States with an overall incidence anesthesia type were all evaluated. End points for the of 118.7 per 100,000 females in the year 20101. study were first local, regional, or distant metastatic Surgery remains the primary and most definitive recurrence. treatment for breast cancer. Despite optimal surgical technique, tumor recurrence occurs in 10 to 20 percent Results of patients. The mechanism by which recurrence following surgery occurs is multifactorial and likely A total of 619 patients were included in the study. includes release of tumor cells into the bloodstream Two hundred and thirteen patients (213/619; 34.4%) during surgery from tumor manipulation, increase of received regional anesthesia and were matched with systemic and local growth factors during surgery, and 406/619 (65.6%) controls who received only general 2,3 perioperative immunomodulation . Recent studies anesthesia. Median age was 64.7 (range 25-95 years), suggest that paravertebral and epidural anesthesia may and tumor size was 1.5 cm (range 0.1-10 cm). Five reduce breast cancer recurrence following surgery hundred (500/619; 80.8%) were ER+ tumors, and by decreasing surgical stress, minimizing the use of 50/619 (8.1%) were HER-2 positive tumors. The 4 opioids, and avoiding certain inhalational agents . majority of patients were Caucasian (569/619). Thirty- In order to explore the relationship between regional seven were African American; the remainders were anesthesia and tumor recurrence we performed reported as Hispanic, Native American, or other. a retrospective case-control analysis comparing Mean follow-up was nine years (range 5-13 years). oncologic outcomes in patients receiving regional, Two hundred and eighty-eight patients had breast regional and general, and general anesthesia for breast conserving surgery. Three hundred and thirty-one cancer surgery. had total mastectomy. Diagnoses included ductal carcinoma in situ (DCIS), lobular carcinoma in situ Methods (LCIS), invasive ductal carcinoma, tubular carcinoma, invasive lobular carcinoma, mucinous carcinoma, and Between 1998 and 2007, 858 patients underwent other. The majority of cancers were located in the upper surgical intervention for breast cancer at our institution. outer quadrant (208/619; 33.6%). All patients who A retrospective chart review was conducted of these underwent breast conservation surgery also received patients. Study exclusion criteria were male gender, adjuvant radiation therapy. A total of six surgeons stage IV disease at presentation, and use of local performed the operations. anesthesia alone. Eight hundred and sixteen (816/858) Two hundred and thirteen (34.4%) patients women underwent surgery for stage 0-III breast cancer. received paravertebral or epidural anesthesia. Of those, Of these, 213/816 (26.1%) patients received regional 123 (57.7%) received solely regional anesthesia (Figure anesthesia with or without general anesthesia. Patients 1). Overall, 45/619 (7.3%) patients developed local, receiving any regional anesthesia were then matched at regional, or distant metastases at a mean follow-up of a ratio of 1:2 for age (less than 40, 41-50, 51-70, and 71 nine years (range 5-13 years). Recurrence occurred in and older), cancer TNM stage, estrogen receptor (ER) seven patients who had regional anesthesia (5.7%), three status, progesterone receptor (PR) status, and HER-2 patients who received regional and general anesthesia expression with those patients receiving no regional (3.3%), and 35 general anesthesia patients (8.6%). anesthesia. Twenty regional anesthesia patients could Univariate analysis (Pearson χ2 and simple logistic only be matched with one control. A total of 619 patients regression) revealed statistically significant greater were, therefore, available for analysis. Univariate recurrence rates in patients who were ER positive (Pearson’s χ2 test and odds ratio) and multivariate and higher TNM stage. PR status, HER-2 status, and logistic regression analyses with backward stepwise age were not found to be statistically significant. BREAST CANCER AND REGIONAL ANESTHESIA 569

Table 1 Breast cancer recurrence rates univariate analysis Recurrence No Recurrence χ2 p value OR (95% CI)

ER positive 33 467 8.9 0.003 3.79 (0.20-0.73) PR positive 31 419 3.8 0.051 0.54 (0.29-1.01) HER-2 positive 6 43 2.5 0.111 2.11 (0.83-5.37) Age (<50) 13 74 0.09 0.767 1.14 (0.49-2.64) TMN stage 32 554 29.7 <0.001 3.31 (1.03-3.23) Regional Anesthesia 7 116 3.19 0.073 0.52 (0.25-1.08) Pearson χ2; OR, odds ratio; CI, confidence interval; ER, estrogen receptor; PR, progesterone receptor; TNM, tumor/node/metastasis.

Having a form of regional anesthesia, with or without The results of this retrospective chart review indicate general anesthesia trended toward lower recurrence that while there is a trend towards lower chance of rates, but did not reach statistical significance. When metastatic recurrence in breast cancer patients that the anesthesia type was further divided into regional, receive regional anesthesia, it is not a statistically regional plus general, and general, there was no significant benefit. Only estrogen receptor status and significant difference in recurrence rate. See Table 1 cancer stage were independently influential factors for details. Multivariate analysis confirmed ER status on whether or not a recurrence was likely. However, and stage as independently influential (p = 0.002 and a previously published report on this subject found p<0.0001, respectively). that metastatic recurrence was significantly reduced in patients receiving regional anesthesia10. Our results are disappointing, as we had hoped to find a definitive Discussion benefit. Other previous in vitro data on this subject are mixed in that some cytokines associated with The role that anesthesia plays in the recurrence breast cancer are attenuated while others are not7-9. of disease following cancer surgery is complex and The benefits of regional anesthesia for breast cancer poorly defined. There are conflicting data at this point surgery have been shown to include decreased nausea as to whether anesthetic technique can influence and vomiting, lower pain scores, and decrease length serological markers of cancer recurrence or the of stay12. The fact that our data had a trend towards recurrence of clinically relevant metastatic disease5-11. lower recurrence in the regional anesthesia group is

Fig. 1 Number of Patients Receiving Each Type of Anesthesia. Between 1998 and 2007, 619 patients underwent surgical intervention for breast cancer at our institution under one of three types of anesthesia. Exclusion criteria were male gender, stage IV disease at presentation, and use of local anesthesia alone.

M.E.J. ANESTH 22 (6), 2014 570 Koonce S. L. et. al encouraging, but not compelling. Although our data anesthetic technique irrelevant in regards to breast lack statistical significance, complications of regional cancer recurrence is unknown at this time. There is one anesthesia are rare, and because of the aforementioned prospective trial in the literature that addressed the use benefits to using this technique, we advocate regional of epidural anesthesia and cancer recurrence in major anesthesia for breast cancer surgery when possible. abdominal surgery14. Unfortunately this trial failed to Whether or not a definitive benefit can be gained demonstrate any difference in cancer free survival. A through the use of regional anesthesia is a question yet large randomized multicenter trial comparing regional to be answered. The oncology literature has suggested and standard anesthetic techniques is currently being that perhaps utilizing specific chemotherapeutic performed and the results of that study may help answer medications can mimic any benefit gained through the question of whether or not anesthetic technique can anesthetic technique13. Whether or not that would make influence recurrence in breast cancer15. BREAST CANCER AND REGIONAL ANESTHESIA 571

References

1. Group USCSW: United States Cancer Statistics: 1999-2007 serum vascular endothelial growth factor C and transforming growth Incidence and Mortality Web-based Report. 2012, http://apps.nccd. factor beta in women undergoing anesthesia and surgery for breast cdc.gov/uscs/. cancer. Anesthesiology; Nov. 2010, 113(5):1118-1125. 2. Denis MG, Lipart C, Leborgne J, et al: Detection of disseminated 10. Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI: tumor cells in peripheral blood of colorectal cancer patients. Int J Can anesthetic technique for primary breast cancer surgery affect Cancer; Oct. 21, 1997, 74(5):540-544. recurrence or metastasis? Anesthesiology; Oct. 2006, 105(4):660- 3. Crisan D, Ruark DS, Decker DA, Drevon AM, Dicarlo RG: 664. Detection of circulating epithelial cells after surgery for benign 11. Fleischmann E, Marschalek C, Schlemitz K, et al: Nitrous oxide breast disease. Mol Diagn; Mar 2000, 5(1):33-38. may not increase the risk of cancer recurrence after colorectal 4. Gottschalk A, Sharma S, Ford J, Durieux ME, Tiouririne M: surgery: a follow-up of a randomized controlled trial. BMC Review article: the role of the perioperative period in recurrence Anesthesiol; 2009, 9:1. after cancer surgery. Anesth Analg; Jun 1, 2010, 110(6):1636-1643. 12. Coveney E, Weltz CR, Greengrass R, et al: Use of paravertebral 5. Biki B, Mascha E, Moriarty DC, Fitzpatrick JM, Sessler DI, block anesthesia in the surgical management of breast cancer: Buggy DJ: Anesthetic technique for radical prostatectomy surgery experience in 156 cases. Ann Surg; Apr. 1998, 227(4):496-501. affects cancer recurrence: a retrospective analysis. Anesthesiology; 13. Munoz M, Rosso M, Casinello F, Covenas R: Paravertebral Aug. 2008, 109(2):180-187. anesthesia: how substance P and the NK-1 receptor could be 6. Bovill JG: Surgery for cancer: does anesthesia matter? Anesth involved in regional block and breast cancer recurrence. Breast Analg; Jun 1, 2010, 110(6):1524-1526. Cancer Res Treat; Jul. 2010, 122(2):601-603. 7. Deegan CA, Murray D, Doran P, et al: Anesthetic technique and 14. Myles PS, Peyton P, Silbert B, Hunt J, Rigg JR, Sessler DI: the cytokine and matrix metalloproteinase response to primary breast Perioperative epidural analgesia for major abdominal surgery for cancer surgery. Reg Anesth Pain Med; Nov-Dec, 2010, 35(6):490- cancer and recurrence-free survival: randomised trial. BMJ; 2011, 495. 342:d1491. 8. Deegan CA, Murray D, Doran P, Ecimovic P, Moriarty DC, Buggy 15. Sessler DI, Ben-Eliyahu S, Mascha EJ, Parat MO, Buggy DJ: Can DJ: Effect of anaesthetic technique on oestrogen receptor-negative regional analgesia reduce the risk of recurrence after breast cancer? breast cancer cell function in vitro. Br J Anaesth; Nov. 2009, Methodology of a multicenter randomized trial. Contemp Clin 103(5):685-690. Trials; Jul. 2008, 29(4):517-526. 9. Looney M, Doran P, Buggy DJ: Effect of anesthetic technique on

M.E.J. ANESTH 22 (6), 2014

Effect of Pressure Support Level, Patient’s Effort, and Lung Mechanics on Phase Synchrony during Pressure Support Ventilation

Ghazi A. Alotaibi*

Abstract

Background: Pressure support ventilation (PSV) is used to encourage spontaneous breathing and facilitate weaning. During PSV, duration of the breath is not set, but controlled by the patient, and influenced by some ventilator settings. There is no guarantee that the PS breathe will match start and end of patient’s breathe. Indeed, patient-ventilator breath mismatching during PSV is the rule, not the exception. Objective: This bench study was conducted to investigate effects of varying PSV, patient’s effort, and lung mechanics on trigger response time (TRT), and expiratory delay time (EDT). Methods: We used an electromechanical lung simulator (ASL 5000) to create different clinical scenarios. The simulator was set at 15 b/min and inspiratory time of 1 sec. In experiment

I, we used 5, 10, 15, and 20 cm H2O of PS at each level of patient effort (Pmus) of 3, 6, and 10 cm

H2O. In the second experiment, we set airway resistance (R) at 5, 10, and 20 cm H2O/L/s at each compliance (C) level of 30, 60, and 90 ml/cm H2O. For each combination of setting, we analyzed 5 consecutive breaths and calculated TRT and EDT. Mean values of TRT and EDT for each scenario were reported and compared for trends and statistical significance. Results: At each given Pmus, increasing PS produced shorter TRT. This effect seems to plateau at higher PS levels. Significant change (p<0.01) in EDT was noticed with increase in PS setting. Pmus alone did not affect trigger or cycle delay times. Increasing airway resistance caused an increase in TRT, expect when R5 was increased to R10 at compliance levels of 30 and 60 ml/ cm H2O. Similarly, increasing compliance significantly lengthened TRT. Higher R and C produced extended EDT, casing major expiratory asynchrony. Conclusion: This study delineates direction of effect for certain individual variables on patient-ventilator synchrony. Results of this study should help clinicians understand the complexity of synchrony issue. Keywords: Ventilator synchrony, lung model, trigger synchrony, expiratory synchrony, lung mechanics.

* PhD, RRT, Assistant Professor of Respiratory Care. Affiliation: College of Applied Medical Sciences, University of Dammam, Saudi Arabia. Corresponding author: Ghazi A. Alotaibi, PhD, RRT, Assistant Professor of Respiratory Care, King Fahad University Hospital, P.O. Box: 40269, Dammam 31952, Saudi Arabia. Tel: 00966500558006. E-mail: [email protected]

573 M.E.J. ANESTH 22 (6), 2014 574 Alotaibi G. A.

Introduction of total work of breathing10. Breath termination, or cycle, is modulated in most commercially available There has been a trend in in mechanical ventilation ventilators by setting a flow threshold so that the practice to allow early spontaneous breathing to share breath is terminated when a threshold value is reached. work of breathing between patient and ventilator. Studies Improperly set cycle criteria results in a mechanical have shown that maintaining spontaneous breathing breath that is either precedes (early cycle) or comes during ventilatory support preserves diaphragmatic after patient’s neural timing (delayed cycle). In function, improves respiratory mechanics, and speeds both situations, workload on patient increases, and 1-3 up liberation from mechanical ventilation . Applying discomfort ensues11,12. Breath termination is affected spontaneous breathing during mechanical ventilation by set expiratory threshold, flow profile, patient’s requires a high degree of synchrony between patient effort, and lung mechanics. and ventilator. The ventilator is synchronous with Based on available research work, timing the patient when it delivers inflation in a timely manner with patients’ neural time, and provides flow mechanical breath to coincide with start and end of and pressure sufficient to unload work of breathing. patient’s neural inspiratory time (Ti) is crucial for Literature indicates that level of synchrony in majority optimal patient-ventilator interaction. This interaction of ventilated patients may not be optimal. In a study of is affected by a delicate balance of several patient- 60 ventilated patients on pressure support ventilation and ventilator-related factors. Many investigators (PSV), significant asynchrony was reported in 27% the have studied effects of some ventilator settings and patients4. Mismatch between patient’s ventilatory needs lung mechanics on patient-ventilator synchrony7,11-16. and the ventilator settings can lead to many deleterious However, effects of individual factor on phase effects, such as discomfort, increased patient’s work synchrony during trigger and cycle have not been of breathing, longer duration of ventilation, and longer addressed clearly in these studies. Therefore, we hospital and intensive care unit (ICU) length of stay4-8. conducted this bench research to study influences on Pressure support is a commonly used mode of varying PSV level, patient’s effort, airway resistance gradual ventilatory support. PSV allows patient to and lung compliance on trigger response and expiratory control breathing profile. Breaths are triggered and delay times. terminated based on patient’s efforts, lung mechanics, and certain ventilator settings. Patient-ventilator Methods interaction during PSV has been investigated by numerous research studies. Starting and ending the mechanical breath in relation to patients’ neural Lung Simulator inspiratory time have been a major concern during PSV. Phase synchrony refers to the extent at which To simulate different clinical scenarios, we used ventilator breaths start and end with the patient’s. Active Servo Lung 5000 (ASL5000) (Ingmar Medical, Optimal matching of mechanical inflation to patient’s breath seems to be the exception not the rule. Pittsburgh, USA). The ASL5000 is an electro- Ventilator triggering is controlled by setting pressure mechanical simulator, composed of a piston moving or flow threshold that the patient must achieve in inside a cylinder. The simulator was connected to a order to trigger the ventilator. Trigger sensitivity, software that allows variety of waveform depictions ventilator sensor performance, patient’s effort, flow and calculated variables. Patients’ breathing profile rise, and presence of dynamic hyperinflation are can be configured and controlled by the application among factors that could interfere with triggering software, which uses Equation of Motion to achieve function. Dyssynchrony during trigger phase has simulated settings. ASL5000 is classified as a been reported in 26-82% of patients receiving high fidelity simulator with capability of initiating assisted ventilatory support9. Work excreted during spontaneous breathing, varying breathing effort, and asynchronous trigger phase could be as high as 50% modulating resistance (R) and compliance (C). EFFECT OF PSV AND LUNG MECHANICS ON VENTILATOR SYNCHRONY 575

Fig. 1 Experimental Setup

Experimental Protocol Experiment I: Changing PS and Patient’s effort. Using the baseline settings for the ventilator and Puritan Bennet 840 ventilator (Galaway, Ireland) lung simulator as above, we programmed a script file was connected the ASL5000 simulator via adult on the simulator to produce 3 levels of breathing efforts ventilator circuit with heated humidifier. Experimental simulating low, medium, and high efforts. Pmus of -3, setup is shown in Figure 1. The ventilator was set on 5 -6, and -10 cm H2O were programmed in the script file cm H O of pressure support (PS), 4 cm H O of positive to last for 300 breaths. For each Pmus setting, PS level 2 2 was manually adjusted on the ventilator to achieve 5, end expiratory pressure (PEEP), 21% of oxygen, 2 L/ 10, 15, and 20 cm H O every 20 breaths. min of flow trigger, and expiratory sensitivity (Esens) 2 Experiment II: Changing Pulmonary Mechanics. of 20%. Breathing rate on lung simulator was set at 15 b/min, inspiratory time (Ti) of 1 sec, rise time of 50%, Using the baseline settings for the ventilator breathing effort (reflected by muscle pressure, Pmus) and lung simulator as above, we programmed another script file on ASL5000 simulator to produce 3 levels of -3 cm H O with sine wave pattern, compliance (C) 2 of lung compliance, simulating stiff, normal, and high of 60 ml/cm H O, and resistance (R) of 5 cm H O/L/s. 2 2 compliance. Compliance settings of 30, 60, and 90 ml/ To study effects of changing PS level, patient’s efforts, cm H2O were programed in the script file to last for and changes in lung mechanics on trigger and cycle 200 breaths. For each compliance level, Resistance of functions, we conducted 2 experiments. See Table 1 5, 10, and 15 cm H2O/L/s were programmed so that for protocol settings. each resistance setting lasts for 20 breaths.

Fig. 2 Representative Tracings of Muscle Pressure (Pmus), Airway Presser, and Flow to illustrate definitions of studied variables.

M.E.J. ANESTH 22 (6), 2014 576 Alotaibi G. A.

Table 1 Protocol for Pressure Support (PS), Muscle Pressure (Pmus), Resistance, and Compliance during Experiments I and II Experiment I PS 5 10 15 20 5 10 15 20 5 10 15 20 (cm H2O) Pmus 3 3 3 3 6 6 6 6 10 10 10 10 (cm H2O) Experiment II

Resistance (cm H2O/L/s) 5 10 20 5 10 20 5 10 20

Compliance (ml/ cm H2O) 30 30 30 60 60 60 90 90 90

Table 2 Mean Measured Parameters during Experiment I

Pmus (cm H2O) 3 6 10

PS (cm H2O) 5 10 15 20 5 10 15 20 5 10 15 20 TRT (ms) 165 136 127 119 161 136 127 122 146 131 125 119 PFR (l/min) 56 90 124 148 56 90 124 150 61 93 127 150

PIP (cm H2O) 9.8 14.9 20 25 9.8 12 20 25 9.8 15 20 25

VT (ml) 357 659 952 1255 378 660 956 1283 406 687 982 128 EDT (ms) 0 54 88 145 0 56 101 162 0 63 106 166

Pmus = muscle pressure, PS = pressure support, TRT = trigger response time, PFR = peak flow rate, PIP = peak inspiratory pressure, VT = tidal volume, EDT = expiratory delay time.

Table 3 Mean Measured Parameters during Experiment II Compliance 30 60 90 (ml/cm H2O) Resistance 5 10 20 5 10 20 5 10 20 (cm H2O/L/s) TRT (ms) 142 160 169 166 167 186 169 189 219 PFR (l/min) 59 38 24 72 47 26 82 50 27

PIP (cm H2O) 9.7 9.4 9.2 9.9 9.5 9.3 10 9.6 9.3

VT (ml) 349 279 204 560 427 258 720 494 287 EDT (ms) -150 -41 55 -10 68 174 80 158 186 TRT = trigger response time, PFR = peak flow rate, PIP = peak inspiratory pressure, VT = tidal volume, EDT = expiratory delay time. EFFECT OF PSV AND LUNG MECHANICS ON VENTILATOR SYNCHRONY 577

Data Collection and Measurement was performed using Bonferroni’s correction method. Significance level was considered asp value < 0.01. Measurements were taken for each level of PS during the 3 settings of patient’s effort (12 Results combinations), and for each level of Resistance during the 3 settings of compliance (9 combinations). Trigger Mean values of measured parameters are shown response time, expiratory delay time, peak flow rate, in Tables 2 and 3. Because of high precision of the lung peak inspiratory pressure, and exhaled tidal volume simulator used in this study, standard deviation for were recorded. For each combination of set parameters, each set of measurements was very small. Therefore, it measurement were recorded from 5 consecutive breaths was not shown in the tables. after one-minute of stabilization period. As depicted in Figure 2, trigger response time (TRT) was measured as the time from the start of patient effort (drop in Experiment I Pmus) to the point where airway pressure returns back to baseline (ie. PEEP). Expiratory delay time (EDT) Effect of changes in PS and Pmus on TRT are was defined as the time from the end of patient’s shown in Table 2 and Figure 3. As PS increases, TRT effort (Pmus returns back to zero) to the time when decreases at all levels of Pmus. Within each Pmus level, ventilator’s flow reaches zero. Referring to Figure 2, all reductions in TRT were statistically significant (p< EDT is positive when the ventilator ceases flow after 0.01), expect when PS10 was increased to PS20 at all end of patient’s effort (late termination), or negative Pmus levels. Table 2 shows effect of increased effort on when the ventilator ends inflation while patient’s effort TRT. Increasing Pmus did not significantly affect TRT still in action (early termination). at the same PS level, expect comparison between Pmus 3 and Pmus 10 at PS of 5, and comparison between Data Analysis Pmus 6 and Pmus 10 at PS of 5. As shown in Figure 3, it is notable that the effect of increased effort on TRT is Data was analyzed using SPSS version 16.0. The mitigated by the increase in PS. Figure 4 depicts effect variables were described using means and standard of PS and Pmus on EDT. At each given Pmus level, deviations. All comparisons were tested for statistical increases in PS increased EDT significantly (p<0.01). significance using one-way ANOVA. Post hoc analysis Increased Pmus alone did not change EDT at all PS

Fig. 3 Effects of Pressure Support (PS) Settings and Level of Effort (Pmus) on Trigger Response Time (TRT)

M.E.J. ANESTH 22 (6), 2014 578 Alotaibi G. A.

Fig. 4 Effects of Pressure Support (PS) Settings and Level of Effort (Pmus) on Expiratory Delay Time (EDT)

levels, expect when Pmus was increased from 3 to expect when R5 was increased to R10 at C30 and C60. Similarly, increases in lung compliance increased 10 cm H2O at PS of 15 and 20 cm H2O. This finding suggests that the effect of increased patient’s effort on TRT at every given resistance. Effects of compliance EDT becomes more apparent at higher PS settings. on TRT were statistically significant (p<0.01) for all comparisons except when C30 was increased to C60 at R10, and C60 was increased to C90 at R5. In Figure Experiment II 6, EDT is plotted as a positive bar when ventilator ends inspiration after the patient, and a negative bar Changes in pulmonary mechanics and their when ventilator terminates inspiration prematurely. effects on TRT and EDT are shown in Table 2 and At any given compliance level, increases in resistance Figures 5-6. Figure 5 plotted effect of changes in made the breath to terminate later, leading to delayed compliance and resistance on TRT. At each given termination. All changes on EDT as a result of increased compliance level, there was a trend towards increase resistance were statistically significant (p<0.01), in TRT as resistance increases. That trend was except when resistance was increased from 10 to 20 at statistically significant (p<0.01) in all comparisons higher lung compliance (C90). Similarly, increases in

Fig. 5 Effect of Changes in Resistance (R), and Compliance (C) on Trigger Response Time (TRT) EFFECT OF PSV AND LUNG MECHANICS ON VENTILATOR SYNCHRONY 579

Fig. 6 Effect of Changes in Resistance (R), and Compliance (C) on Expiratory Delay Time (EDT)

lung compliance at any given resistance led to delayed that the rate at which negative airway pressure decays breath termination. All comparisons were statistically to baseline has reached its maximum at PS of 15 cm significant (p<0.01). H2O. Therefore, further increase in PS would not significantly affect TRT. Murata et17 al studied the Discussion effect of different levels of inspiratory rise time and reported that faster rise time reduced duration of post- trigger phase (the time from maximum drop in airway The main findings of the present bench study pressure during trigger to the return to baseline). This can be summarized as follow; (1) As level of set finding support our explanation of TRT reduction as a PS increases, time required to trigger the ventilator result of increased PS. In real clinical situations, effect becomes shorter but expiratory delay time increases; of increasing PS on TRT is extenuated by reduction (2) patient’s effort seems to have little effect on trigger in patient’s effort as a response to PSV unloading. In and cycle delay times; (3) higher pulmonary resistance such case, less trigger effort will be exerted by patient, was found to be associated with longer trigger time extending TRT or even causing missed trigger. The and delayed breath termination; (4) as lungs become net effect may be unappreciable change in TRT, but stiffer, trigger time becomes shorter and mechanical depends on level of trigger work unloading by PS. This breaths tend to terminate earlier. relationship between PS level and TRT has clinical Pressure support is a very common mode of implications. In clinical practice, it is common to wean partial ventilation and waning. Pressure support level PS level as patient recovers to allow more spontaneous is adjusted to achieve optimal work of breathing and breathing and muscle reconditioning. When PS patient’s comfort. In our study, we report inverse reaches an under-assist level, effect on TRT becomes relationship between PS level and TRT when other more exaggerated, prolonging trigger delay time and factors are unchanged. Speed of pressurization was worsening patient-ventilator synchrony. Contrary to set at a medium value (50%) throughout this study. our finding, Thille et al7 found that patient-ventilator Reduction in TRT as a consequence of increased PS synchrony was improved with lower PS. As explained level can be explained by the sharp rise of flow that by the authors, improvement in synchrony reported in accompanied higher PS. Increasing PS level involves their study was attributed to lower VT, shorter inflation time, and reduction in intrinsic PEEP associated higher VT and flow, pushing the negative airway pressure to return to baseline faster as compared to with lower PS. As a result, ineffective triggers were lower PS level. As a result, TRT becomes shorter. eliminated. In our study, intrinsic PEEP and ineffective Reduction in TRT was attenuated when PS increases triggers were not part of the protocol. from 15 to 20 cm H2O at all Pmus levels. We speculate Manipulation of PS does not only affect trigger

M.E.J. ANESTH 22 (6), 2014 580 Alotaibi G. A. phase, it extends to influence breath termination. for all levels of efforts in our experiment could be the

Higher levels of PS produce larger VT and longer reason for the non-significant effect of changing effort inflation times. If patient’s neural Ti does not change on TRT. However, our protocol revealed an important considerably, mechanical breath continues beyond finding about effect of purely increase in Pmus on patient’s neural timing. Because expiratory trigger trigger delay time. It will be interesting to study effect point is set as a percent threshold (20% in our of more vigorous efforts with different waveform protocol), higher VT and flow will cause cycle point pattern and inspiratory times on TRT. to be reached late, causing delayed breath termination. In their mathematical modeling, Yamada and Du Delayed breath termination is uncomfortable to patient suggested that expiratory cycle of a breath is affected and could recruit active expiratory muscles, increasing by the ratio of applied PS and patient’s generated work of breathing. In patients with airflow limitation pressure (PS/Pmus). According to this model, when diseases, such as asthma and COPD, late termination Pmus becomes the main generator of flow and VT, of the breath could be very harmful. Less time will expiratory synchrony improves. In our study, we found be available for expiration, leading to dynamic that all 3 levels of Pmus did not significantly affect hyperinflation and worse patient-ventilator synchrony. EDT, except at higher PS levels (15 and 20 cm H2O). According to our study, lowering PS led to In line with the mathematical proposition, we can shorter EDT. This could be clinically important during speculate that Pmus did not affect EDT because flow weaning process of PSV mode. Clinical experience and VT were predominantly controlled by PS. supported by literature findings indicate that higher PS Our study also provides insight into effect of is associated with poor patient-ventilator synchrony. changes in pulmonary mechanics on both trigger and When PS is reduced, cycle synchrony is expected to cycle phases of the breath. Increases in pulmonary improve. It should be noted that as PS is further reduced, resistance or compliance shifted synchrony window to shorter mechanical breaths and early termination could the left. In such case, the mechanical breath will lag occur. Our observations about PS and EDT support after neural breath and end well after patient finishes 18 the mathematical analysis by Yamada and Du , who his breath. Reduction in resistance and compliance suggested that expiratory synchrony improves when will produce the opposite effect. Both scenarios disrupt PS is reduced. patient-ventilator synchrony. For a given PS setting, as

We simulated 3 different levels of muscle resistance increases, required VT and flow necessary pressure (Pmus) to reflect low, medium, and high to maintain the target PS level are reduced. Lower patients’ efforts. Our findings indicated that the inspiratory flow, in particular at the onset of the breath, degree of effort did not significantly affect TRT or may explain longer TRT observed with high resistance.

EDT. However, there was a trend towards reduction On the other hand, larger VT and faster flow observed in TRT and increase in EDT as Pmus increases. With when ventilating high compliant lungs contribute to higher patient’s efforts, trigger threshold is expected long TRT. Effect of resistance and compliance on EDT to be reached sooner, decreasing TRT. The fact that can be explained by the concept of time constant (Tc). the observed reduction in TRT did not reach statistical Time constant is the time needed to empty about two significance can be attributed to the pattern chosen thirds of exhaled volume19. It is the product of resistance for Pmus. At all Pmus levels used in this study, we and compliance. At longer Tc (as the case of increased configured the drop in pressure to simulate sine wave resistance and/or compliance), expiratory flow decays pattern. We chose to use this pattern of Pmus to study at a slower rate. Therefore, it takes longer time to reach the effect of merely drop in Pmus when other factors expiratory trigger point. This is the underlying cause are unchanged. We realize that in a real patient with for longer EDT that is associated with higher resistance increased effort, Pmus may decrease sharply reaching and compliance. Our findings corroborate results of maximum drop at early stage of the trigger phase. We Tassaux et al12 who reported improvement in ventilator also used a neural timing of 1 sec at all 3 levels of synchrony in COPD patients when expiratory trigger Pmus. Using the same pattern of Pmus and fixed Ti was increased to 70%. Longer Tc in these patients was EFFECT OF PSV AND LUNG MECHANICS ON VENTILATOR SYNCHRONY 581 curtailed by setting expiratory trigger so that EDT is cautiously. Secondly, we did not use active exhalation shortened. In patients with acute lung injury (short feature of the lung model, which could have produced Tc), synchrony and work of breathing improved when different results. The use of active exhalation seems expiratory trigger was decreased from 45% to 1%, more realistic clinically, but our aim was to investigate preventing early cycle of the breath20. According to effect of some single variables on breath start and the mathematical model mentioned above, expiratory end. Thirdly, although we used clinically plausible synchrony is not affected by Tc alone, rather it is the settings, interpretation of our data should be limited effect of time constant divided by neural inspiratory to the range of settings used in this study. Finally, time (Tc/Ti). In the present study, we tested different statistical differences reported in this study cannot levels of Tc (as reflected by resistance and compliance) be directly translated into clinical relevance. Because at a fixed Ti of 1 sec. Further research is needed to of high precision produced by the lung simulator, investigate effect of different Tc/Ti ratios on cycle small changes in parameters could reach statistical synchrony. significant. We used a stricter p values (< 0.01) to Patient-ventilator interaction has been the signify statistical significance. In one study, 15% subject of study for many research works that aimed increase in work of breathing was reported when 24 to understand factors influencing synchrony. Of trigger delay time increased from 89 to 115 ms . particular interest, two technical developments have In conclusion, using a high fidelity lung simulator, been introduced recently to improve phase synchrony. we created several scenarios resembling clinical Neurally adjusted ventilatory support (NAVA) is a conditions and studied “pure” effects of changes in PS, mode of ventilation that uses electrical activity signals breathing effort, resistance and compliance on trigger of the diaphragm to trigger and cycle the breath. and cycle delay times. Higher PS was associated with Research studies indicated that this mode of ventilation shorter trigger time but lengthened time to cycle the produced better synchrony and imposed less work breath. Patient’s effort alone did not affect time to of breathing when compared to PSV21,22. Special trigger or cycle the breath. Increased airway resistance algorithm to automatically select breath termination and/or lung compliance disrupt phase synchrony by criteria was incorporated in Newport ventilator. A delaying time to trigger and extending mechanical preliminary study compared automated vs. fixed breath beyond neural time. expiratory criteria reported improvement in synchrony and patient’s comfort with the automated algorithm23. Financial Support This study has some limitations. First, we None. used an electromechanical lung model to simulate Conflict of Interest breathing. In a laboratory environment, we were able None. to test specific parameters while controlling possible confounding factors. This may not reflect clinical Acknowledgment reality where outcomes are influenced by many inter- I would like to thank Mr. Ahmed Mansi for his related variables. Therefore, direct extrapolation of assistance in setting up the lung simulator. this study findings to clinical practice should be done

M.E.J. ANESTH 22 (6), 2014 582 Alotaibi G. A.

References

1. Guldner A, Braune A, Carvalho N, Beda A, et al: Higher levels 13. Chao DC, Scheinhorn DJ, Stearn-Hassenpflug M: Patient- of spontaneous breathing induce lung recruitment and reduce global ventilator trigger asynchrony in prolonged mechanical ventilation. stress/strain in experimental lung injury. Anesthesiology; 2014, Chest; 1997, 112(6):1592-9. 120(3):673-82. 14. Chiumello D, Pelosi P, Taccone P, Slutsky A, Gattinoni L: Effect 2. Jaber S, Petrof BJ, Jung B, Chanques G, et al: Rapidly progressive of different inspiratory rise time and cycling off criteria during diaphragmatic weakness and injury during mechanical ventilation in pressure support ventilation in patients recovering from acute lung humans. Am J Respir Crit Care Med; 2011, 183(3):364-71. injury. Crit Care Med; 2003, 31(11):2604-10. 3. Putensen C, Zech S, Wrigge H, Zinserling J, et al: Long-term 15. Laghi F, Segal J, Choe WK, Tobin MJ: Effect of imposed inflation effects of spontaneous breathing during ventilatory support in time on respiratory frequency and hyperinflation in patients with patients with acute lung injury. Am J Respir Crit Care Med; 2001, chronic obstructive pulmonary disease. Am J Respir Crit Care Med; 164(1):43-9. 2001, 163(6):1365-70. 4. de Wit M, Miller KB, Green DA, Ostman HE, Gennings C, Epstein 16. Tassaux D, Michotte JB, Gainnier M, Gratadour P, Fonseca S, SK: Ineffective triggering predicts increased duration of mechanical Jolliet P: Expiratory trigger setting in pressure support ventilation: ventilation. Crit Care Med; 2009, 37(10):2740-5. from mathematical model to bedside. Crit Care Med; 2004, 5. Bosma K, Ferreyra G, Ambrogio C, Pasero D, et al: Patient- 32(9):1844-50. ventilator interaction and sleep in mechanically ventilated patients: 17. Murata S, Yokoyama K, Sakamoto Y, Yamashita K, et al: Effects of pressure support versus proportional assist ventilation. Crit Care inspiratory rise time on triggering work load during pressure-support Med; 2007, 35(4):1048-54. ventilation: a lung model study. Respir Care; 2010, 55(7):878-84. 6. Pohlman MC, McCallister KE, Schweickert WD, Pohlman AS, 18. Yamada Y, Du HL: Analysis of the mechanisms of expiratory et al: Excessive tidal volume from breath stacking during lung- asynchrony in pressure support ventilation: a mathematical protective ventilation for acute lung injury. Crit Care Med; 2008, approach. J Appl Physiol (1985); 2000, 88(6):2143-50. 36(11):3019-23. 19. Sassoon C: Triggering of the ventilator in patient-ventilator 7. Thille AW, Cabello B, Galia F, Lyazidi A, Brochard L. Reduction interactions. Respir Care; 2011, 56(1):39-51. of patient-ventilator asynchrony by reducing tidal volume during 20. Tokioka H, Tanaka T, Ishizu T, Fukushima T, et al: The effect of pressure-support ventilation. Intensive Care Med; 2008, 34(8):1477- breath termination criterion on breathing patterns and the work of 86. breathing during pressure support ventilation. Anesth Analg; 2001, 8. Thille AW, Rodriguez P, Cabello B, Lellouche F, Brochard 92(1):161-5. L: Patient-ventilator asynchrony during assisted mechanical 21. Meric H, Calabrese P, Pradon D, Lejaille M, Lofaso F, Terzi ventilation. Intensive Care Med; 2006, 32(10):1515-22. N: Physiological comparison of breathing patterns with neurally 9. Epstein SK: How often does patient-ventilator asynchrony occur adjusted ventilatory assist (NAVA) and pressure-support ventilation and what are the consequences? Respir Care; 2011, 56(1):25-38. to improve NAVA settings. Respir Physiol Neurobiol; 2014, 195:11- 10. Leung P, Jubran A, Tobin MJ: Comparison of assisted ventilator 8. modes on triggering, patient effort, and dyspnea. Am J Respir Crit 22. Vagheggini G, Mazzoleni S, Vlad Panait E, Navalesi P, Ambrosino Care Med; 1997, 155(6):1940-8. N: Physiologic response to various levels of pressure support and 11. Chiumello D, Polli F, Tallarini F, Chierichetti M, et al: Effect NAVA in prolonged weaning. Respir Med; 2013, 107(11):1748-54. of different cycling-off criteria and positive end-expiratory pressure 23. Hoff FC, Tucci MR, Amato MB, Santos LJ, Victorino JA: Cycling- during pressure support ventilation in patients with chronic off modes during pressure support ventilation: effects on breathing obstructive pulmonary disease. Crit Care Med; 2007, 35(11):2547- pattern, patient effort, and comfort. J Crit Care; 2014, 29(3):380-5. 52. 24. Aslanian P, El Atrous S, Isabey D, Valente E, et al: Effects of flow 12. Tassaux D, Gainnier M, Battisti A, Jolliet P. Impact of expiratory triggering on breathing effort during partial ventilatory support. Am trigger setting on delayed cycling and inspiratory muscle workload. J Respir Crit Care Med; 1998, 157(1):135-43. Am J Respir Crit Care Med; 2005, 172(10):1283-9. THE INCIDENCE OF POSTOPERATIVE RESIDUAL CURARIZATION FOLLOWING THE USE OF INTERMEDIATE-ACTING MUSCLE RELAXANTS AND RELATED FACTORS

Ozlem Kocaturk*, Nil Kaan**, Nurten Kayacan*** and Fatma Ertugrul****

Abstract

Purpose: To evaluate the incidence of residual curarization (RC) and related risk factors in the early and late postoperative periods in patients receiving general anesthesia with intermediate- acting muscle relaxants. Methods: Two-hundred and eight American Society of Anesthesiologists class I and II patients, aged 18-70 years, who underwent general anesthesia with intermediate-acting muscle relaxants, were included. Heart rate, blood pressure, oxygen saturation, tympanic temperature were recorded for each patient who was transported to the recovery room, every 10 minutes by a trained nurse. To define the efficacy of residual muscle relaxants, neuromuscular monitoring was performed, and Train of Four (TOF) ratios <90% were regarded as RC whereas ratios ≥90% were considered as adequate neuromuscular recovery in early and late recovery periods. Age, duration of anesthesia, repeated doses, reversal and types of intermediate-acting neuromuscular blockers were evaluated as risk factors for RC. Logistic Regression Analysis was performed to define the risk factors for RC in early and late periods. Results: The RC rate was 10.6% in the early recovery period, and short duration of anesthesia, repeated doses and lack of reversal use were the risk factors for RC. However, RC rate was 2.9% in the late recovery period, and the only risk factor was repeated doses. Conclusion: Reversal use was shown to reduce residual effects of intermediate-acting muscle relaxants in early recovery period, whereas risk of RC in 30 min in PACU was shown to increase with repeated doses of muscle relaxants. Keywords: Residual curarization, train-of-four, intermediate-acting muscle relaxants, postanesthesia care unit.

* MD, Ataturk State Hospital, Department of Anesthesiology and Reanimation, Aydin, Turkey. ** MD, Professor, Adnan Menderes University Faculty of Medicine, Department of Anesthesiology and Reanimation, Aydin, Turkey. *** MD, Professor, Akdeniz University Faculty of Medecine, Department of Anesthesiology and Reanimation, Antalya, Turkey. **** MD, Assistant Professor, Akdeniz University Faculty of Medecine, Department of Anesthesiology and Reanimation, Antalya, Turkey. Corresponding author: Ozlem Kocaturk, MD, Ataturk State Hospital, Department of Anesthesiology and Reanimation, Aydin, Turkey. Tel: +90 536 7730400, Fax: +90 256 2135003. E-mail: [email protected]

583 M.E.J. ANESTH 22 (6), 2014 584 Kocaturk o. et. al

Introduction mass index >30%; 3) use of drugs known to interfere with neuromuscular transmission; 4) pregnancy; 5) Postoperative residual curarization (RC) in the refusal to participate the study; 6) craniotomies, cardio- recovery unit is a very important clinical problem and thoracic and vascular surgeries, emergency operations, is described as the relationship of the train-of-four surgeries requiring longer than 6 hours of anesthesia (TOF) fade ratio to signs and symptoms of muscle and operations requiring blood and fluid replacement. weakness1-3. Even when the effects of a muscle A dose of 0.05 mg/kg midazolam was given relaxant clinically disappear, some receptors in the intramuscularly as a premedication 30 min before nerve muscle junction are still blocked by the muscle surgery. The selection of anesthetic induction relaxant agents4,5. (intravenous propofol 2-3 mg/kg, fentanyl 1-2μg/kg, Residual curarization was a problem due to lidocaine 1 mg/kg) and maintenance drugs (1-1.5% the use of long-acting muscle relaxants in the past; isoflurane and 1.5-2% sevoflurane), muscle relaxants however, it is also seen frequently with the use of (vecuronium, rocuronium, atracurium), intraoperative intermediate-acting muscle relaxants6-11. High RC additional muscle relaxant use, the decision of rates were reported by the use of both intermediate and extubation, reversal use and transfer to the recovery long-acting muscle relaxants12-16. room was at the discretion of the anesthesiologist. Generally, a single TOF measurement in the Induction and maintenance doses of muscle recovery room is used to determine the incidence of relaxants are: vecuronium 0.1 mg/kg and 2 mg, RC. In some studies, TOF was measured immediately rocuronium 0.5 mg/kg and 10 mg, atracurium 0.5 mg/ after extubation, while in others10,16-20 the measurement kg and 10 mg, respectively. In the event of inadequate was made upon arrival of the patient to the recovery spontaneous respiration after surgery or if the last dose room. However, there are few studies on the early of muscle relaxant was in the last 40 minutes of the and late residual effects of intermediate-acting muscle surgery or if weak motor responses to verbal stimuli relaxants12. were present after extubation, neostigmine at a dose of 0.05 mg/kg and atropine were given to the patients. The purpose of this study was to detect the After extubation, the patients breathed 100% oxygen incidence of RC and to investigate the related factors, by mask, and kept in the operating room. Patients, by neuromuscular monitoring in early and late periods who had verbal and motor responses to verbal stimuli of recovery in patients in the recovery room after (take their tongue out, open their eyes, hold their hands general anesthesia with either vecuronium, rocuronium up above their heads), and had adequate spontaneous or atracurium. respiration were transferred to the recovery room as per the decision of the anesthesiologist. Materials and Methods Neuromuscular monitoring was performed at the arrival and 30 minutes later in the recovery room. The study was a prospective, observational TOF fade ratios were measured by using investigation performed in the Department of acceleromyography (TOF-Watch©-SX; Organon Anesthesiology and Reanimation. After local ethic Teknika, Dublin, Ireland). The arm where the committee approval, written informed consents were measurements were taken was immobilized with a obtained from all patients. Patients between 18 and 70 splint and was positioned to assure free movement of years of age in American Society of Anesthesiologists the thumb during nerve stimulation. An acceleration (ASA) physical status I or II were randomly assigned transducer was taped to the distal interphalangeal joint to receive an intermediate-acting neuromuscular of the thumb. Supramaximal TOF stimulation was blocking (NMB) agent (vecuronium, atracurium or delivered to the ulnar nerve via surface electrodes. Two rocuronium) during general anesthesia. consecutive responses to TOF stimulation (separated The exclusion criteria were: 1) the presence of by 15 s) were obtained, and the average of the two a renal, hepatic or a neuromuscular disease; 2) body values was recorded. If the measurements differed by RESIDUAL CURARIZATION ASSOCIATED WITH INTERMEDIATE-ACTING MUSCLE RELAXANTS 585 more than 10%, additional TOF ratios were obtained normal distribution of data. Descriptive statistics were (up to four TOF values), and the closest two ratios presented as mean±standard deviation and median were averaged. (25%-75% percentile). The Wilcoxon T-test was The first measurement, taken as the patient arrives used for changing values of HR, mean arterial blood to the recovery room and the measurement taken 30 pressures (MAP) and SpO2 in recovery room over the minutes after arrival were defined as “early recovery time (mean ± SD). A p <0.05 was considered to be period” and “late recovery period”, respectively. TOF statistically significant. ratios <90% were considered as “the presence of RC” while TOF ratios ≥90% were considered as “the Results absence of RC”. In the recovery room, routine hemodynamic Two hundred and eighteen patients were enrolled monitoring of heart rate (HR), peripheral oxygen in the study. Ten patients were excluded because of saturation (SpO2), noninvasive blood pressure, and lack of data. Statistical analysis was performed on tympanic temperature was maintained. Patients’ age, 208 patients. Patient characteristics, the duration of gender, body weight, type of surgery, drugs used for anesthesia, the duration of surgery and types of surgery anesthesia induction and maintenance, type of muscle are presented in Table 1. relaxants and time of administration of additional doses during the intraoperative period, reversal usage, Table 1 duration of surgery and anesthesia were recorded Patients characteristics, clinical parameters and surgical from the anesthesia sheet. Patients were monitored procedures for at least 30 minutes in the recovery room by trained Patient Characteristics nurses. Age, type of muscle relaxant used, number of additional doses of muscle relaxants during the Gender (Female/Male) 110/98 operation, use of reversals after surgery, duration of Age (year) 43.2±14.2 anesthesia and tympanic temperature changes were analyzed as the risk factors that may affect RC in the Weight (kg) 73.1±12.9 logistic regression model. The variables were grouped ASA according to age (18–39 years, 40–59 years and 60– 70 years), the type of muscle relaxants (vecuronium, I 158 rocuronium, atracurium), number of additional doses of muscle relaxant used during the operation (only for II 50 induction, 1 time, 2 times, 3 times and 4 times), reversal Duration of anesthesia (min) 123.6±58.9 use after operation (yes/no), duration of anesthesia (0- 90 min, 91-180 min, 181-270 min and 271-360 min) Duration of operation (min) 92.9±52.7 and tympanic temperature (34.4-35.4°C, 35.5-36.4°C Surgery and 36.5-37.6°C). Head and neck surgery 94 Statistical analysis Laparoscopic abdominal surgery 34 Non-laparoscopic abdominal 53 Statistical Program for Social Sciences (SPSS, surgery Inc., Chicago, IL, USA) version 10.0 was used for Extremity surgery 6 statistical analysis. Logistic regression analysis was Others (breast, plastic, performed to define the risk factors for RC in early perineal surgery) 21 (0 min) and late (30 min) recovery periods. The Chi- Data are presented as mean±standard deviation or number, square test was used for comparison of the frequency. where appropriate. The Kolmogorov-Smirnov test was used to test the ASA: American Society of Anesthesiologists.

M.E.J. ANESTH 22 (6), 2014 586 Kocaturk o. et. al

Table 2 The induction of anesthesia was similar in all Distribution of patients according to risk factors affecting patients. Anesthesia was maintained with isoflurane residual curarization during early recovery period in 147 patients, and sevoflurane in 61 patients. Residual curarization Rocuronium, atracurium and vecuronium was given to Risk factors Yes No 51, 63 and 94 patients, respectively. p value (n=22) (n=186) Residual curarization (TOF<90%) occurred in 22 18-39 10 73 patients (10.6%) in the early period and continued in Age (years) 40-59 10 83 0.42 six patients (2.9%) in the late recovery period. 60-70 2 30 The distribution of patients with RC according Vecuronium 13 81 to risk factors during the early recovery period is Type of presented in Table 2. No significant difference was muscle Atracurium 5 58 0.20 observed in the number of patients with and without relaxants Rocuronium 4 47 RC in terms of risk factor subgroups.

Induction 11 97 Lack of reversal use (Odd’s ratio 0.311, 95% Number of confidence interval (CI) 0.104-0.932), short duration 1 time 5 66 additional of anesthesia (Odd’s ratio 0.363, 95% CI 0.146 to doses of 2 times 4 20 0.40 0.898) and increased number of additional doses of muscle 3 times 0 3 muscle relaxants (Odd’s ratio 2.762, 95% CI 1.420 to relaxant 5.373) were shown to increase the incidence of RC in 4 times 2 0 the early postoperative recovery period (Table 3). Reversal yes 6 86 use after 0.09 The distribution of patients with RC according operation no 16 100 to risk factors in the late recovery period is shown in 0-90 8 54 Table 4. A significant difference was observed between Duration of 91-180 12 109 the patients with and without RC regarding the number anesthesia 0.46 of additional doses of muscle relaxants (p <0.05) (min) 181-270 1 18 (Table 4). 271-360 1 5 The increase in the number of additional doses of 34.4-35.4 2 32 Tympanic muscle relaxants was the only factor that increased the temperature 35.5-36.4 11 92 0.32 risk of RC (Odd’s ratio 4.241, 95% CI 1.378 to 13.054) (°C) in the late recovery period. The effects of other risk 36.5-37.6 9 62 factors were not significant (Table 5).

Table 3 Effects of risk factors to residual curarization for the early recovery period (0 min) Residual curarization (0 min) Beta Wald p Odds Ratio 95% CI

Age -0.259 0.499 0.480 0.772 0.376-1.583

Type of muscle relaxants 0.561 3.403 0.065 1.752 0.966-3.180 Number of additional doses of muscle 1.016 8.956 0.003 2.762 1.420-5.373 relaxant Reversal use after operation -1.169 4.352 0.037 0.311 0.104-0.932

Duration of anesthesia -1.015 4.807 0.028 0.363 0.146-0.898

Tympanic temperature 0.116 0.084 0.772 1.123 0.514-2.455 CI: Confidence interval RESIDUAL CURARIZATION ASSOCIATED WITH INTERMEDIATE-ACTING MUSCLE RELAXANTS 587

Table 4 The average central body temperatures of Distribution of patients according to risk factors affecting the patients were 36.1±0.6 °C (with a range of residual curarization during the late recovery period 34.4°C-37.4°C) and 36.2±0.5 °C (with a range of Residual curarization 34.6°C-37.4°C) in early and late recovery period, Risk factors Yes No p value respectively. (n=6) (n=202) SpO of 21 patients fell below 94% in the 18-39 2 81 2 early recovery period. In these patients, oxygen was Age (years) 40-59 3 90 0.76 delivered at a rate of 4 L/min via facemasks and 60-70 1 31 additional reversals were given in three of them. Respiratory distress was not observed in any patient in Vecuronium 5 89 Type of the late recovery period. muscle Atracurium 1 62 0.11 relaxants Rocuronium 0 51 Discussion Induction 1 107 Number of In this study, we showed that 10.6% of the 1 time 2 69 additional patients who underwent general anesthesia with doses of 2 times 2 22 0.02 intermediate-acting muscle relaxants (vecuronium, muscle 3 times 0 3 rocuronium, atracurium) had RC upon arrival to the relaxant recovery room. It was found that shorter duration of 4 times 1 1 anesthesia, lack of reversals use and repeated doses of Reversal Yes 4 112 muscle relaxants increased the risk of RC during early use after 0.58 recovery period. In 2.9% of patients, TOF ratio was operation No 2 90 below 90% and RC continued up to 30 minutes after 0-90 1 61 arrival to the recovery room. The intraoperative use of Duration of 91-180 4 117 repeated doses of intermediate acting muscle relaxants anesthesia 0.42 was found to be a factor increasing the risk of RC in (min) 181-270 0 19 the late recovery period. 271-360 1 5 Baillard et al.1 investigated the frequency and 34.4-35.4 1 24 Tympanic risk factors of RC upon arrival to the recovery room. temperature 35.5-36.4 4 91 0.48 Short duration of surgery, lack of reversal use, no (°C) intraoperative monitoring and excess doses of muscle 36.5-37.6 1 87 relaxants were found to increase the risk of RC. In

Table 5 Effects of risk factors to residual curarization for the late recovery period (30 min) Residual curarization (30 min) Beta Wald p Odds Ratio 95% CI Age -0.173 0.062 0.804 0.841 0.215-3.289

Type of muscle relaxants 1.189 2.517 0.113 3.283 0.756-14.264 Number of additional doses of muscle 1.445 6.344 0.012 4.241 1.378-13.054 relaxant Reversal use after operation -1.827 2.182 0.140 0.161 0.014-1.817

Duration of anesthesia -0.847 1.199 0.274 0.429 0.094-1.953

Tympanic temperature -0.960 1.318 0.251 0.383 0.074-1.971 CI: Confidence interval

M.E.J. ANESTH 22 (6), 2014 588 Kocaturk o. et. al this study, the reduction in the incidence of RC over confirmed the role of reversals and intraoperative time was related to the physicians’ clinical practice. neuromuscular monitoring in reducing the risk of RC, Residual curarization usually regarded as a concern others16-18 claimed that these two factors had no effect with the use of long-acting muscle relaxants5, can be on RC. Furthermore, it was emphasized18 that even high frequently encountered with the use of intermediate- doses of reversals could not eliminate RC. In our study, acting muscle relaxants2-7. Naguib et al.11 in a meta- reversals were administered according to the clinical analysis, reported that the incidence of postoperative findings of patients after the surgery. Reversals were RC was significantly decreased by using intermediate- given to 44% of patients. No significant difference was acting muscle relaxants. The decrease in the incidence found in the incidence of RC between patients using was attributed to better clinical evaluation, widespread reversals or not in the late recovery period. However, performance of intraoperative neuromuscular in the regression analysis, the use of reversals was monitoring and increased use of intermediate-acting found to be a factor for reducing RC in the early muscle relaxants in recent years1,11. recovery period. The effect of neostigmine starts in 2-5 19 Residual curarization (TOF<90%) rates with min and lasts until 30 to 45 min . Therefore the use rocuronium in healthy adult patients undergoing of reversal not being an effective factor for reducing elective orthopedic surgery were reported as 29% and RC in the late recovery period may be attributed 2.9% upon arrival to the recovery room and after 30 to a reduction in its effect over time. It is almost minutes, respectively9. Debane et al.6 reported that TOF impossible to eliminate RC completely with routine in 45% of the patients (who were given vecuronium, clinical evaluation, neuromuscular monitoring or use rocuronium or atracurium) were below 90% in the of a reversal agent. However, it has been reported that early recovery period. In our study, the RC incidence objective neuromuscular monitoring may be useful 20 after the use of intermediate-acting muscle relaxants when the reversals are not used . was 10.6% and 2.9%, in the early and late recovery Some studies reported that RC incidence was periods, respectively. The lower RC incidence in our not related to the type of the intermediate-acting study was attributed to the monitoring of patients in neuromuscular relaxant11-14. In Hayes et al. study, RC the operating room until the patients showed verbal (TOF <80%) incidence in patients using vecuronium, or motor responses to verbal stimuli and had adequate atracurium and rocuronium were found to be 64%, tidal volumes. In addition, considering the duration 52% and 39%, respectively upon arrival to the of surgeries, the number of additional doses used for recovery room. No statistical difference was observed maintenance of muscle relaxation was very low. This in RC rates by using different intermediate-acting may also explain the low incidence of postoperative muscle relaxants12. However, in Khan et al study, the RC. patients using rocuronium had higher RC incidence 15 In Baillard et al.3 study, 42% of the patients who (37%) than in patients using vecuronium (17%) . In received vecuronium with no reversals were found our study, no significant difference was observed in to have RC. The cumulative doses of vecuronium RC incidences between patients using atracurium, were 7.7±3.6 mg and 6.2±2.7 mg in patients with and vecuronium or rocuronium in early and late recovery without RC, respectively. RC was shown to increase periods. However, the RC incidences we observed significantly with the increase in the cumulative dose. were much lower compared to other studies. Similarly, we found that the increase in the number of Duration of anesthesia is a factor increasing the additional doses of muscle relaxants was an important risk of RC in surgeries with short duration, in which a factor affecting RC both in early and late recovery single-dose of intermediate-acting muscle relaxant is periods. In addition, “number of additional doses of used7. On the other hand, duration of anesthesia does muscle relaxants” was the only factor affecting RC in not affect the risk of RC in long duration surgeries6. the late recovery period. We thought that the cumulative It is postulated that the risk of RC may increase in effect of additional doses might be the most probable surgeries with long duration with increased frequency cause of this finding. Although, some studies1,2 of muscle relaxant use7. Similarly, risk of RC was RESIDUAL CURARIZATION ASSOCIATED WITH INTERMEDIATE-ACTING MUSCLE RELAXANTS 589 found to increase with shorter duration of anesthesia in normal ranges and as such the “body temperature” early recovery period, whereas duration of anesthesia could not be a risk factor for RC. had no effects on RC in the late recovery period in our In conclusion, dose adjustment of intraoperative study. muscle relaxants in accordance with the duration of Hypothermia is known to prolong the effect of surgery and the use of reversals may reduce the risk muscle relaxants19. The elimination of muscle relaxants of RC. from the liver is related to body temperature, and hypothermia has been found to decrease the clearance Conflict of interest of muscle relaxants19. Although exact hypothermia None. limit leading to prolongation of the effects of muscle Acknowledgments relaxants is not known, there are some studies We would like to thank to Mevlut Ture, MD showing increased incidence of RC when the central Assoc. Prof. of Medical Statistics in Adnan Menderes temperature is below 34°C18,21,22. In the current study University Medical School for helpful advice and the central body temperatures of patients were within suggestions about statistical issues.

M.E.J. ANESTH 22 (6), 2014 590 Kocaturk o. et. al

References

1. Baillard C, Clec’h C, Catineau J, Salhi F, Gehan G, Cupa M, 2007, 98:302-316. et al: Postoperative residual neuromuscular block: a survey of 12. Hayes AH, Mirakhur RK, Breslin DS, Reid JE, Mccourt KC, management. Br J Anaesth; 2005, 95:622-666. et al: Postoperative residual block after intermediate-acting 2. Claudius C, Karacan H, Viby-Mogensen J: Prolonged residual neuromuscular blocking drugs. Anaesthesia; 2001, 56:312-318. paralysis after a single intubating dose of rocuronium. Br J Anaesth; 13. Baurain MJ, Hoton F, D’hollander AA, Cantraine FR, et al: 2007, 99:514-517. Is recovery of neuromuscular transmission complete after the 3. Baillard C, Gehan G, Marty Rj, Larmigrant P, Samama Cm, Cupa use of neostigmine to antagonize block produced by rocuronium, M: Residual curarization in the recovery room after vecuronium. Br vecuronium, atracurium and pancuronium?. Br J Anaesth; 1996, J Anaesth; 2000, 84:394-395. 77:496-499. 4. Viby-Mogensen J, Ostergaard D, Donati F, Fisher D, Hunter J, 14. Kopman AF, Zank LM, Ng J, Neuman GG: Antagonism of Kampmann Jp, et al: Pharmacokinetic studies of neuromuscular cisatracurium and rocuronium block at a tactile train-of-four count blocking agents: good clinical research practice (GCRP). Acta of 2: should quantitative assessment of neuromuscular function be Anaesthesiol Scand; 2000, 44:1169-1190. mandatory?. Anesth Analg; 2004, 98:102-106. 5. Gatke MR, Viby-Mogensen J, Rosenstock C, Jensen FS, Skovgaard 15. Khan S, Divatia JV, Sareen R: Comparison of residual neuromuscular LT, et al: Postoperative muscle paralysis after rocuronium: less blockade between two intermediate acting nondepolarizing residual block when acceleromyography is used. Acta Anaesthesiol neuromuscular blocking agents rocuronium and vecuronium. Indian Scand; 2002, 46:207-213. J Anaesth; 2006, 50:115-117. 6. Debaene B, Plaud B, Dilly MP, Donati F: Residual paralysis in 16. Murphy GS: Residual neuromuscular blockade: incidence, the PACU after a single intubating dose of nondepolarizing muscle assessment, and relevance in the postoperative period. Minerva relaxant with an intermediate duration of action. Anesthesiology; Anestesiol; 2006, 72:97-109. 2003, 98:1042-1048. 17. Kopman AF: Measurement and monitoring of neuromuscular 7. Mccaul C, TOBİN E, BOYLAN JF, Mcshane AJ: Atracurium is blockade. Curr Opin Anaesthesiol; 2002, 15:415-420. associated with postoperative residual curarization. Br J Anaesth; 18. Kim KS, Lew SH, Cho HY, Cheong MA: Residual paralysis 2002, 89:766-769. induced by either vecuronium or rocuronium after antidote with 8. Pino MR: Residual neuromuscular blockade: a persistent clinical pyridostigmine. Anesth Analg; 2002, 95:1656-1660. problem. Int Anesthesiol Clin; 2006, 44:77-90. 19. Kayhan Z: Sinir Kas İletimi ve Kas Gevşeticiler, In: Kayhan Z (ed) - 9. Murphy GS, Szokol JW, Franklin M, Marymont JH, Avram Klinik Anestezi. 3rd ed. Istanbul: Logos Publishers; 2004, 151-180. MJ, Vender JS: Postanesthesia care unit recovery times and 20. Viby-Mogensen J: Postoperative residual curarization and evidence neuromuscular blocking drugs: a prospective study of orthopedic based anaesthesia. Br J Anaesth; 2000, 84:301-303. surgical patients randomized to receive pancuronium or rocuronium. 21. Suzuki T, Kitajima O, Watanabe A, Nonaka H, Saeki S, Ogawa S, Anesth Analg; 2004, 98:193-200. et al: Duration of vecuronium-induced neuromuscular block can be 10. Mcewin L, MERRİCK PM, BEVAN DR: Residual neuromuscular predicted by change of skin temperature over the thenar muscles. J blockade after cardiac surgery: pancuronium vs rocuronium. Can J Anesth; 2004, 18:172-176. Anaesth; 1997, 44:891-895. 22. Heier T, Caldwell JE: Impact of hypothermia on the response to 11. Naugib M, Kopman AF, Ensor JE: Neuromuscular monitoring and neuromuscular blocking drugs. Anesthesiology; 2006, 104;1070- postoperative residual curarisation: a meta-analysis. Br J Anaesth; 1080. IS UNILATERAL SPINAL ANESTHESIA SUPERIOR TO BILATERAL SPINAL ANESTHESIA IN UNILATERAL INGUINAL REGIONAL SURGERY?

Faruk Cicekci*, Huseyin Yilmaz**, Mehmet Balasar***, Mustafa Sahin**** and Fatih Kara*****

Abstract

Background: Unilateral spinal anesthesia is performed to provide restriction of sensory and motor block. Objective: The aim of this study was to compare unilateral and bilateral spinal anesthesia, with regard to limiting the nerve block exclusively to the area of surgery. Methods: This was a prospective, randomised, double-blind study, conducted in 40 consecutive outpatients scheduled for unilateral inguinal regional surgery. Patients in both groups received 0.5 % hyperbaric bupivacaine 15 mg + morphine 0.1 mg. Patients in the unilateral group (Group U) were placed in the lateral decubitus position for 10 minutes (min) on their side to be operated, while patients in the bilateral group (Group B) were placed in the supine position. The pin-prick test was used to assess the times to reach L1, T12 and T10 sensory blocks and the times to reach motor block. In addition, the sensory and motor block recovery times were recorded using a modified Bromage scale. Furthermore, the duration of the operation and the times to first analgesic requirement were noted. Results: There were significant differences between Group U and Group B in the times to reach L1, T12 and T10 dermatome levels of sensory block, and the times to reach motor block using the modified Bromage scale on three levels. However, there was no difference in the time to ambulation, the time to complete sensory regression and the time to first analgesic requirement. Conclusion: The time to reach sensory and motor blocks for unilateral spinal anesthesia could provide an advantage over bilateral spinal anesthesia in inguinal region operations. Key words: Unilateral spinal anesthesia, bilateral spinal anesthesia, inguinal surgery.

* MD, Specialist, Department of Anesthesiology, Konya Numune Hospital, Konya, Turkey. ** Associate Professor, Department of General Surgery, Univercity of Selcuk, Selcuklu Medical Faculty, Konya, Turkey. *** Assistant Professor, Department of Urology, Univercity of Necmettin Erbakan, Meram Medical Faculty, Konya, Turkey. **** Professor, Department of General Surgery, Univercity of Selcuk, Selcuklu Medical Faculty, Konya, Turkey. ***** Assistant Professor, Department of Public Health, Univercity of Selcuk, Selcuklu Medical Faculty, Konya, Turkey. Corresponding author: Faruk Cicekci, M.D. Specialist. Department of Anesthesiology, Konya Numune Hospital, Konya/ Turkey, Konya Numune Hospital Yazir Mah. Turgut Ozal Cad. No:3/999 42090 Selcuklu Konya/Turkey. Tel: +90-332- 2631001, Fax: +90-332-2631050. E-mail: [email protected]

591 M.E.J. ANESTH 22 (6), 2014 592 Cicekci F. et. al

Introduction decubitus position on the side to be operated on for 10 minutes, and then in the supine position, while Unilateral anesthesia is a specific regional patients in Group B were placed in a supine position anesthesiology technique. It was first described by immediately after the intrathecal injection. The pin- Tanasichuk et al. in 1961 as ‘spinal hemianalgesia’ in prick test was used to assess the sensory block level patients who were to undergo extremity surgery1. The of the patients, starting from the administration of the basic objective of unilateral spinal anesthesia is to limit intrathecal injection. The times to reach L1, T12 and the nerve block exclusively to the area of the surgery T10 sensory blocks and the times to reach motor block, and for the duration of the operation2,3. Therefore, as well as the sensory and motor block recovery times it is also often recommended for use in short-term were recorded. Blocks were assessed by the modified surgical interventions that involve only one side of the Bromage scale (Table 1). Furthermore, the duration of body. The advantage of unilateral spinal anesthesia the operation and the times to first analgesic requirement over bilateral spinal anesthesia is the lower incidence were determined. Patients characteristics as well as of hypotension and maintenance of cardiovascular noninvasive systolic and diastolic blood pressure, stability, in addition to providing a stronger block on heart rate and peripheral oxygen saturation (SpO2) the side of surgery and accelerating the recovery of the measurements preoperatively, and then at min 5, 10, nerve block4,5. 30, 45 and 60 of the operation were recorded. Any side In the present study, we aimed to investigate the effects and complications (cardiovascular findings, effects of unilateral spinal anesthesia and bilateral urinary retention, nausea/vomiting and itching) that spinal anesthesia on sensory and motor blocks in male occurred up until end of PACU (post operative care patients undergoing short-term unilateral inguinal unit) were noted. Management of postoperative regional surgery. complications included 4 mg IV ondansetron for nausea/vomiting, 5 mg IV ephedrine for hypotension (mean arterial pressure <70 mmHg) and 0.08 mg IV Method and Materials naloxone for itching, in addition to performing urinary catheterization for urinary retention. Oral ketoprofen We conducted this study as a prospective, (50 mg) were administered at 8-hour intervals to randomised, clinical trial. After gaining approval provide additional postoperative analgesia. from the Ethics Committee (Ref. no. 2009/207) of the Medical Faculty of the University of Necmettin Table 1 Erbakan, Turkey, we included 40 ASA (American Modified Bromage Scale Society of Anesthesiologists) I-II males between the 0 = No motor block. ages of 18-65, who were due to undergo elective 1 = Can flex knee, move foot, but cannot raise leg. inguinal regional surgery and spinal anesthesia. 2 = Can move foot only. All patients were premedicated with 0.1 mg.kg-1 3 = Cannot move foot or knee. intramuscular midazolam prior to their operations. Sample size calculation was done by power Patients were randomized by sealed envelope analysis. This analysis was based on two samples assignment to receive either group U or group B, with statistical significance of 0.05 and 89% power. and administered both groups with a standard 0.5 % The sample size required was 20 in each group. Data hyperbaric bupivacaine 3 ml (15 mg) + morphine 0.2 was analyzed using SPSS for Windows 15.0 software. ml (0.1 mg), using a Quincke 25G spinal needle. We The Bonferroni-corrected Mann-Whitney U-test administered the injection intrathecally, via a median was used to compare the independent variables, and approach through the L4-5 vertebral interspace, in the Chi-square test was used to compare the within- approximately 20 seconds, using a 5 cc syringe, by group data. Categorical data was analyzed using the guiding the tip of the spinal needle to the side to be Chi-square test. Contiuous variables were described as operated on in Group U, and caudaly in Group B. mean±standard deviation (SD). P<0.05 was considered The patients in Group U were placed in the lateral statistically significant. UNILATERAL OR BILATERAL SPINAL ANESTHESIA 593

Results was 223±83.4 min for Group U, and 271.2±78 min for Group B. The difference was not statistically There were no significant differences in age, significant. The time to complete sensory regression weight, height, duration of surgery and type of surgery was 332.4±108 min for Group U, and 351.6±79.8 min between both groups (Table 2). for Group B and the difference was not statistically The times to reach L1, T12 and T10 dermatome significant. The time to the first analgesic requirement levels of sensory block [mean±SD (standard deviation)] was 462.6±213.6 min for Group U, and 355.2±142.8 were 2±1.17 min, 3.34±1.54 min and 4.76±2.11 min for Group B. There was no significant difference min, respectively, for Group U, and 4.19±1.54 min, between the two groups (Table 4). There was no 5.98±2.04 min and 8.06±3.3 min, respectively, for significant difference between the groups in terms of Group B. The difference between the two groups was the preoperative and postoperative systolic arterial statistically significant (p<0.05). The time to reach pressure, diastolic arterial pressure, heart rate and motor block, 0-3 on the modified Bromage scale, was peripheral oxygen saturation values (Table 5). 3.75±1.54 min, for Group U and 6.57±2.34 min, for The comparison of postoperative complications Group B. The difference between the two groups was (nausea/vomiting, hypotension, bradycardia, itching statistically significant (p<0.05), as shown in Table 3. and urinary retention) did not reveal a significant The time to ambulation (Bromage scale 0) difference between the two groups (Table 6).

Table 2 Demographic data, duration of surgery, type of surgery, according to group. Mean±SD Group U (n=20) Group B (n=20) P value

Age (year) 46.2±11.7 41.4±11.2 0.408 Height (cm) 173.5±6.7 173±6.5 0.856 Weight (kg) 73.7±3.5 74.2±8.5 0.466 Duration of surgery (min) 40.4±10.5 38.8±11.2 0.465 Type of surgery (inguinal hernia/varicocele) 12/11 11/10 0.256

Table 3 Sensory and motor blocks characteristics. Mean±SD Group U (n=20) Group B (n=20) P value

The time to reach L1 dermatome levels of sensory block (min) 2±1.17 4.19±1.54 0.029 The time to reach T12 dermatome levels of sensory block (min) 3.34±1.54 5.98±2.04 0.015 The time to reach T10 dermatome levels of sensory block (min) 4.76±2.11 8.06±3.3 0.018 The time to reach motor block Bromage Scale 3 (min) 3.75±1.54 6.57±2.34 0.042

Table 4 Recovery times of sensory and motor block. Mean±SD Group U (n=20) Group B (n=20) P value

The time to complete sensory regression (min) 223±83.4 271.2±78 0.827 The time to ambulation (min) 332.4±108 351.6±79.8 0.690 Time of the first analgesic requirement (min) 462.6±213.6 355.2±142.8 0.637

M.E.J. ANESTH 22 (6), 2014 594 Cicekci F. et. al

Table 5 Systolic blood pressure, diastolic blood pressure, heart rate and peripheral oxygen saturation values. Mean±SD Group U (n=20) Group B (n=20) P value

Pre 143±25.4 131±17.3 0.726 5 130±28.6 124±20.8 0.656 Systolic blood pressure 10 123±16 121±15.4 0.867 (mmHg) 15 124±14 120±15.5 0.948 30 122±12.9 119±12.6 0.876 45 113±9.4 123±12.8 0.655 60 119±9.9 132±18.3 0.428 Pre 71.6±13.5 70±10.5 0.854 5 70±16.5 65±18 0.803 Diastolic blood pressure 10 69±13.5 61±10.5 0.643 (mmHg) 15 64±11.5 63±10.2 0.597 30 63±12.6 63±8.5 0.612 45 55±8.5 73±5.7 0.588 60 58±11.5 72±7.7 0.312 Pre 86±18.4 86±14.7 0.768 5 80±19.5 86.3±19.2 0.433 10 77±17.2 78.1±12.2 0.790 Heart rate (beats.min-1) 15 75±15.2 73.8±11 0.883 30 76±13.2 81±9.7 0.752 45 73±7.5 71.7±7.7 0.655 60 74±7.2 74±1.7 0.823 Pre 97±1.1 97.5±1 0.987 5 97±1.1 97±1 0.945 10 96±1 97±1 0.897 SpO2 (%) 15 97±1.0 97±0.7 0.878 30 97±1.1 97±0.7 0.836 45 98±0.7 97±0.7 0.798 60 97±0.5 97.5±0.7 0.953

Table 6 Postoperative complications. Mean±SD Group U (n=20) Group B (n=20) P value Nausea/vomiting 1 2 1 Hypotension 1 1 1 Bradycardia 0 0 - Itching 3 2 1 Urinary retention 1 3 0.850 Respiratory depression 0 0 - UNILATERAL OR BILATERAL SPINAL ANESTHESIA 595

Discussion to our current recovery time of 346.8 min. The addition of opioids to hyperbaric bupivacaine Small doses of local anesthetics that are used can accelerate the onset time and increases the only for the blockage of the side to be operated on can quality of analgesia in both the intraoperative and provide an efficient block when administered at a slow postoperative periods11. Milligan et al. found that the pace, by guiding the needle tip to the relevant side and time to first analgesic requirement following surgery placing the patient in the lateral decubitus position was significantly longer in a group of patients who for 10-15 min4. Previous studies have suggested that received bupivacaine and morphine, compared to the average waiting period for keeping the patient patients who received bupivacaine alone12,13. In our in the lateral decubitus position for unilateral spinal study, analgesic requirement was needed in 20 of the anesthesia, performed using hyperbaric bupivacaine, 40 patients, and the time to first analgesic requirement is 10-15 min4. In our pilot study, we found that 10 min was 363 min in the unilateral group and 350.4 min in was sufficient for the lateral waiting period. Lateral the bilateral group. position is advantageous in terms of fast surgical Spinal anesthesia is associated with certain adaptation, rapid recovery, low number of side effects cardiovascular and respiratory side effects. However, and complications and ease of administration5,6. in the current study, no deteriorations of hemodynamic Esmaoglu et al. reported the time for the sensory block stability in either the unilateral or the bilateral group level to reach L1 as being 4.19±2.8 min in a unilateral were noted. group of patients who were administered bupivacaine7. However, Pitkänen reported this time as being 5.3±1.1 Furthermore no major postoperative min1. In our study, the time to reach L1 sensory level complications were observed. Whenever these was 1.72 min for L1, 2.87 min for T12 and 4.15 min complications occurred, they were not at such a level that they required an intervention in either group. for T10 in the unilateral group. In the current study, we postulate that the sensory level was reached in a shorter time because of the high dose of hyperbaric Conclusion bupivacaine (15 mg/3 ml). Liu et al. found that the duration of the sensory block was 196±44 min for We conclude that the time to reach sensory and 7.5 mg hyperbaric bupivacaine8 and 177±53 min for motor blocks in inguinal regional surgeries using hyperbaric bupivacaine with opioid, while Casati et al. unilateral spinal anesthesia could provide an advantage found that the duration of the sensory block was 190±51 over bilateral spinal anesthesia, particularly enabling min for a unilateral spinal anesthesia application in a the surgeons to start these surgeries more rapidly. bupivacaine group2, which was consistent with our findings of 240.6 min. We suggested that this could Conflict of Interest be due to the addition of morphine to hyperbaric bupivacaine. The authors declare that the research was In a study using 8 mg 0.5% hyperbaric conducted in the absence of any commercial or bupivacaine, Moller et al. reported the time to motor financial relationships that could be construed asa block Bromage scale 3 as 5.6±1.0 min9. In our study, potential conflict of interest. the short time to reach motor block might have been due to the addition of higher amounts of hyperbaric Acknowledgements bupivacaine and morphine. The duration of the motor block on the same Author Contributions: side is the key factor affecting the time to discharge. Concept/Design: Faruk Cicekci, Huseyin Yilmaz Whiteside et al. reported that patients were mobilised in approximately 331 min in a group of patients Drafting Article: Faruk Cicekci, Mehmet Balasar receiving 15 mg of bupivacaine10, which was similar Data Collection: Faruk Cicekci,

M.E.J. ANESTH 22 (6), 2014 596 Cicekci F. et. al

Data analysis/Interpretation: Fatih Kara, Mustafa Critical revision of Article: Faruk Cicekci, Sahin Mehmet Balasar Statistics: Fatih Kara Approval of Article: Faruk Cicekci

References

1. Pitkänen MT: Body mass and spread of spinal anesthesia with Surg Sports Traumatol Arthrosc; 2004, 12(2):155-8. bupivacaine. 1987, 66(2):127-131. 8. Lui Ss,Ware PD, Allen HW, Neal JM, Pollock JE: Dose- 2. Kuusniemi KS, Pihlajamäki KK, Pitkänen MT: A low dose of plain response characteristics of spinal bupivacain in volunteers: clinical or hyperbaric bupivacaine for unilateral spinal anesthesia. Reg implications for ambulatory anesthesia. Anesthesiology; 1996, Anesth; 2000, 25(6):605-610. 85(4);729-736. 3. Fanelli G, Borghi B, Casati A, Bertini L, Montebugnoli M, Torri 9. H Moller IW, Fernandes A, Edstöm HH: Subarachnoid anesthesia G: Unilateral bupivacaine spinal anesthesia for outpatient knee with 0.5% bupivacaine: effects of density. Br J Anaesth; 1984, arthroscopy. Italian study group on unilateral spinal anesthesia. Can 56(11):1191-1195. J Anesth; 2000, 47(8):746-751. 10. Whiteside JB, Burke D, Wildsmith JAW: Comparison of 4. Casati A, Moizo E, Marchetti C, Vinciquerra F: A prospective, ropivacaine 0.5% (in glucose 5%) with bupivacaine 0.5% (in randomized, double-blind comparison of unilateral spinal anaesthesia glucose 8%) for spinal anaesthesia for elective surgery. Br J Anesth; with hyperbaric bupivacaine, ropivacaine or levobupivacaine for 2003, 90(3):304-308. inguinal herniorrhaphy. Anasth Analg; 2004, 99(5):1387-1392. 11. Ben-David B, Solomon E, Levin H, Admoni H, Goldik Z: Intrathecal 5. Casati A, Fanelli G: Unilateral Spinal Anaesthesia: state of art. fentanyl with small-dose dilute bupivacaine: Better anesthesia Minerva Anestesiol; 2001, 67(12):855-886. witout prolonging recovery. Anesth Analg; 1997, 85(3):650-655. 6. Cappelleri G, Aldegheri G, Danelli G, Marchetti C, Nuzzi 12. Milligan KR, Fogarty DJ: The characteristics of analgesic M, Iannandrea G Casati A: Spinal anaesthesia with hyperbaric requirements following subarachnoid diamorphine in patients levobupivacine and ropivacaine for outpatient knee arthroscopy: a undergoing total hip replacement. Reg Anesth; 1993, 18(2):114-7. prospective, randomized, double-blind stady. Anaesth Analg; 2005, 13. Fogarty DJ, Milligan KR: Postoperative analgesia following 101(1):77-82. total hip replacement: A comparison of intrathecal morphine and 7. Esmaoglu A, Karaoglu S, Mizrak A, Boyaci A: Bilateral vs. diamorphine. J R Soc Med; 1995, 88(2):70-2. unilateral spinal anesthesia for outpatient knee arthroscopies. Knee The effects of provision of anesthesia on one-year mortality in patients with severe complications

Junko Ushiroda*, Satoki Inoue**, Yu Tanaka** and Masahiko Kawaguchi**

Abstract

Background: General anesthesia in patients with comorbid conditions may affect their intermediate or long-term outcomes. In this study, we evaluated the effects of provision of anesthesia on mortality in critical patients with comorbid conditions by retrospectively investigating one-year mortality in patients with ASA physical status more than III who underwent minor surgery for relative indications and nonfatal reasons. Methods: Data were collected during the period between January 2006 and December 2011. Eligible patients were those with ASA physical status more than III who underwent minor surgery under general anesthesia for relative indications and nonfatal reasons. Preoperative clinical information was collected from the patient’s clinical charts. Comorbidity was quantified using the Charlson comorbidity index. All the patients were evaluated for in-hospital mortality and were followed-up for mortality at one-year. Results: During the study period, 14, 979 patients underwent general anesthesia. Thirty six patients satisfied the eligibility for enrollment. Charlson comorbidity index of the patients ranged from one to five. No patients died during their hospital-stay; however, 4 patients were lost to follow up. Therefore, one-year mortality rates for each Charlson index category were 0%. Conclusion: The postoperative one-year mortality in patients with ASA physical status more than III undergoing minor surgery under general anesthesia for relative indications and nonfatal reasons was expected to be considerably small regardless of the Charlson index category. Key words: Comorbidity, Charlson comorbidity index, Anesthesia, Mortality.

Introduction

Modern anesthesia management allows us to provide surgical interventions for considerably critical patients with comorbid conditions although it is still challenging. On the other hand, it has been discussed that deep anesthesia was associated with mortality among middle-aged and elderly surgical patients1-3. Therefore, it is very likely that provision of anesthesia itself for critical patients with comorbid conditions may affect their intermediate or long-term outcomes. However, little is known about the effects of provision of anesthesia on mortality in critical patients with comorbid conditions because it is practically impossible to provide only anesthesia without surgery just for

* DDS. ** MD. Affiliation: Division of Intensive Care and Department of Anesthesiology, Nara Medical University, 840 Shijo-cho Kashihara Nara 634-8522, Japan. Corresponding author: Satoki Inoue, MD. Division of Intensive Care, Nara Medical University, 840 Shijo-cho Kashihara Nara 634-8522, Japan. Tel +81-744-22-3051 (ext3469), Fax +81-744-23-9741. E-mail: [email protected]

597 M.E.J. ANESTH 22 (6), 2014 598 Ushiroda J. et. al the sake of answering this question. The Charlson comorbidity index originally can To answer the above question as much as predict one-year mortality for a patient who may have possible, we arbitrarily assumed that the situations a range of comorbid conditions. Each condition is of patients with ASA physical status more than III assigned a score of 1, 2, 3, or 6, proportional to the relative risk of death (at one-year) associated with undergoing minor surgery for relative indications and that disease (Table 1). The sum of the integers makes nonfatal reasons resemble the situations of providing up the Charlson score, and the Charlson score was only anesthesia without surgery for critical patients prospectively consolidated into four previously defined with comorbid conditions. It is not unreasonable to groups known as the Charlson Index: 0 points (none), suppose that drugs including anesthetics, analgesics 1–2 points (low), 3–4 points (moderate), and ≧5points and muscle relaxants, endotracheal intubation, positive (high) as originally described4. It has been reported that pressure ventilation and fluid infusion associated with the Charlson index at the hospital admission due to a general anesthesia would have more effect on patients’ specific medical condition has a good correlation with outcome than minor surgical procedure. 1-year mortality rates4-6. In addition, illness severity, In this study, we evaluated the effects of provision which was rated as “not to mildly ill”, “moderately of anesthesia on mortality in critical patients with ill”, or “severely ill” as previously described7, within comorbid conditions by retrospectively investigating the same Charlson index category also has a good one-year mortality in patients with ASA physical correlation with 1-year mortality rates4. We assumed status more than III who underwent minor surgery for that the “not to mildly ill” conditions were similar to the relative indications and nonfatal reasons. situations that patients with ASA physical status more than III undergo minor surgery for relative indications Materials and Methods and nonfatal reasons. It is reasonable to suppose that specific illness conditions providing minor surgery for relative indications and nonfatal reasons are not so Approval for review of patient’s clinical charts severe. The original mortality rates from the work of was obtained from the Nara Medical University Charlson and colleagues are presented in the Table 24. Institutional Review Board (Approval No.533). Data Table 1 were collected during the period between January Charlson comorbid conditions 2006 and December 2011. Eligible patients were those Comorbid conditions Weight with ASA physical status more than III who underwent Myocardical infarction 1 minor surgery under general anesthesia for relative Congestive heart failure 1 indications and nonfatal reasons. Therefore, patients Peripheral vascular disease 1 who underwent cardiovascular surgery, neurosurgery, Cerebrovascular disease 1 Dementia 1 oncological surgery, trauma surgery, debridement, Chronic obstructive pulmonary 1 drainage or amputation, and any emergency surgery disease were excluded. Connective tissue disease 1 Preoperative clinical information was collected Ulcer disease 1 Mild liver disease 1 from the patient’s clinical charts. Comorbidity was Diabetes 1 4 quantified using the Charlson Comorbidity Index . Hemiplegia 2 Additional data including type of surgery, anesthesia Renal disease 2 and operation time, intraoperative fluid balance were Any tumor 2 also collected. All the patients were evaluated for in- Diabetes with end-organ damage 2 hospital mortality and were followed-up for mortality Leukemia 2 Lymphoma 2 at one-year using the clinical charts, telephone Moderate/severe liver disease 3 interviews, or postal questionnaires. If the patient had Metastatic solid tumor 6 died in the follow-up period, the date of death was AIDS 6 recorded. ANESTHESIA AND ONE-YEAR MORTALITY IN CRITICAL PATIENTS 599

Table 2 Table 3 One-year mortality rates from the work of Charlson and Descriptive statistics of patient characteristics colleagues Age (y) 65.1±14 Charlson comorbidity index category Sex, n (%) male 19(52.8%) Illness Severity 0 1-2 3-4 >5 female 17(47.2%) Not to mildly In hospital mortality (%) 0% 7% 16% 41% 64% ill Charlson index category 0 0 Moderately ill 6% 17% 39% 76% 1-2 21 Severely ill 12% 30% 50% 100% 3-4 9 Total 7% 21% 43% 78% ≥5 6 The gray zone shows the one-year mortality rates of the “not to mildly ill” conditions in patients with each Charlson comorbidity Performed Operation index category. We referred these values as predicted mortality Ophthalmology 6 in our patients. Gynecology 4 Urology 4 Descriptive statistics were used to summarize Orthopedics 22 the demographics and intraoperative data. Categorical Operation time (min) 175.3±96.8 variables were reported as percentages. The continuous Anaesthesia time (min) 220.5±118.7 variables were described using the mean and standard Intraoperative fluid balance (mL) 1382.7±233.7 deviation. One-year mortality rates with 95% confidence intervals were calculated for each Charlson Index category. If necessary, to determine correlation Table 4 of the Charlson Index category with one-year mortality, Charlson comobid conditions the Spearman’s rank correlation coefficient was Conditions n(%) calculated. In addition, the Kaplan–Meier estimation Myocardical infarction 8（22%) method was used to obtain the survival distribution Congestive heart failure 4(11%) estimates for each Charlson Index category. The Peripheral vascular disease 1(2.7%) statistical difference of survival distributions among Cerebrovascular disease 7(19.4%) the categories was examined using the log-rank test. Dementia 2(5.5%) Statistical significance was defined as P<0.05. Chronic obstructive pulmonary disease 6(16.6%) Connective tissue disease 0 Results Ulcer disease 0 Mild liver disease 1(2.7%) During the study period, 14, 979 patients Diabetes 6(16.6%) underwent general anesthesia. Of those, 36 patients Hemiplegia 2(5.5%) with ASA physical status more than III underwent Renal disease 8(22.2%) minor surgery under general anesthesia for relative Any tumor 2(5.5%) indications and nonfatal reasons (Table 3). Of the Diabetes with end-organ damage 15 (41.6%) eligible 36 patients, no patients died during their hospital stay; however, 4 patients were lost to follow Leukemia 0 up after discharge. Lymphoma 0 Moderate/severe liver disease 0 Metastatic solid tumor 0 Patients characteristics are presented in the Table AIDS 0 3. The majority of the performed operations was

M.E.J. ANESTH 22 (6), 2014 600 Ushiroda J. et. al orthopedics. There was no patient with Charlson Index patient8. According to these concepts of “comorbidity”, of 0. There were 6 patients with Carlson Index point development of another medical condition is required =5, who were categorized in Charlson index category whenever the term “comorbidity” is intended to use. ≥5; however, there was no patient with Carlson index Otherwise, the term “comorbidity” could not be used point ≥6. Charlson comorbid conditions are presented if development of another medical condition were not in the Table 4. All 32 patients survived one-year observed in patients with specific medical conditions. postoperatively. The one-year mortality rates with 95% Nevertheless, another medical condition indicates confidence intervals for each Charlson Index category significant events including acute injuries and illness. It were 0% (95% confidence interval = 0% to 0%). has been recognized that the Charlson Index is strongly Because all patients in any Charlson Index categories associated with mortality rates in emergency patients survived one-year, correlation of the Charlson Index as well as in medical inpatients4-7,9,10. We could not category with one-year mortality and the survival simply apply the absolute mortality rates observed in distribution could not be determined from our data. In the specific medical conditions to the others even with this regard, looking at the one-year mortality rates of the identical Charlson index; however, it is safe to say illness severity at “not to mildly ill” conditions from that the patients with higher Charlson Index category the original work of Carlson’s4, which we referred, the will have higher mortality rates after sustaining one-year mortality rate increased as Charlson Index any significant events including acute injuries and severity increased (See the gray zone in Table 2). illness. On the contrary, the Charlson index in our patients who underwent minor surgery under general anesthesia showed no association with one-year Discussion mortality. As mentioned before, we need to consider comorbid medical conditions when significant medical Our results revealed that the postoperative one- events occur. Therefore, it may be concluded that no year mortality in patients with ASA physical status significant medical events consequently occurred in more than III undergoing minor surgery under general our patients. In other words, it can be said that minor anesthesia for relative indications and nonfatal reasons surgery under general anesthesia is not a condition was expected to be considerably small regardless of that can deteriorate comorbid diseases. The effects of the Charlson Index category. As mentioned before, provision of anesthesia itself on comorbid conditions we assumed that the situations that patients with ASA should be less significant than the combined effects physical status more than III undergo minor surgery of anesthetic and minor surgical procedures. Thus, it for relative indications and nonfatal reasons resemble is reasonable to suppose that provision of anesthesia the situations that we provide only anesthesia without itself does not fulfill the medical events that can surgery for critical patients with comorbid conditions. threaten comorbid conditions. Therefore, it might be postulated that the effects of In clinical settings, there seems to be no provision of anesthesia on mortality in critical patients objection that the effects of surgical reason with with comorbid conditions are not significant. However, absolute indication or major surgical procedures on a prerequisite may be necessary that the comorbid mortality exceeds provision of anesthesia in most condition should be stable because the scheduled cases. Therefore, the effects of provision of anesthesia surgery should be canceled if the comorbid condition itself on comorbid conditions can be negligible in such itself is life-threatening. cases. However, anesthesiologists frequently encounter There is a lack of definition of “comorbidity”, but situations where they need to consider the effects of it seems that the following concept is widely accepted; provision of anesthesia on mortality in critical patients a medical condition existing simultaneously but with comorbid conditions. As mentioned above, it independently with another condition in a patient. In is when critical patients with comorbid conditions addition, a newer concept has been also proposed that a undergo a minor surgery for relative indication and medical condition in a patient that causes, is caused by, nonfatal reasons. With our results, we could come or is otherwise related to another condition in the same to the postulation that there is no need to refuse to ANESTHESIA AND ONE-YEAR MORTALITY IN CRITICAL PATIENTS 601 provide anesthesia management, for the concern about on the obtained results in this study. Third, 4 patients significant effects of anesthesia on patient’s outcome. were lost to follow up (10%). It has been suggested that However, as mentioned before, this proposal may be plausible assumptions regarding outcomes of patients rejected when the comorbid condition is unstable and lost to follow-up could change the interpretation of life-threatening in itself. results even with the median percentage of participants lost to follow-up is 6%12. Therefore, we might need to There are several limitations in this study. First, be careful to interpret our study results while taking it we did not see the effects of provision of anesthesia into consideration that 10% patients were lost to follow itself on mortality in critical patients with comorbid up. Lastly, we extracted only 36 eligible patients from conditions in the true meaning. It is difficult to make our study population. In addition, no patient died a real answer; however, there is a laboratory report within one year after anesthesia possibly due to the giving a clue to this question. Culley and colleagues small population. The conclusion drawn from this investigated whether general anesthesia with study might exceed the capability of the present data. isoflurane-nitrous oxide shortens life expectancy in Accordingly, much larger data base would be required aged rats. They reported that general anesthesia does to confirm our results. not reduce life expectancy in aged rats11. We need to consider a discrepancy of human and animal studies In conclusion, the postoperative one-year and the hypothesis regarding old age as a comorbid mortality in patients with ASA physical status more than III undergoing minor surgery under general condition; however, it is not unreasonable to think anesthesia for relative indications and nonfatal reasons that this study supports our opinion. Second, we is considerably small regardless of the Charlson Index recruited for our study surgical patients who had category. With this finding, we might postulate that actually undergone scheduled operations. However, the effects of provision of anesthesia on mortality critical patients with comorbid conditions, should in critical patients with comorbid conditions are not have existed, would most likely have their scheduled significant. However, to derive this conclusion, we surgeries canceled after considering their comorbid need at least a prerequisite that the comorbid condition conditions, relative indications, and nonfatal reasons. should be stable. The mortality rates might have been affected if these patients had undergone scheduled operations. One of Study funding the reasons for this concern might be on account of Departmental financial source only supported the retrospective nature of this study design. However, this study. such a selection bias is thought to be difficult to avoid in clinical settings even in a prospective study because Conflicts of Interest there must be cases where patient selection is completed None. before anesthesia consultation. Therefore, a necessary prerequisite might be that the comorbid condition Acknowledgement should be stable when deriving any conclusion based None.

M.E.J. ANESTH 22 (6), 2014 602 Ushiroda J. et. al

References

1. Kertai MD, Palanca BJ, Pal N, Burnside BA, Zhang L, Sadiq F, Douglas RG Jr: Assessing illness severity: does clinical judgment Finkel KJ, Avidan MS: B-Unaware Study Group: Bispectral index work? J Chronic Dis; 1986, 39:439-52. monitoring, duration of bispectral index below 45, patient risk 8. Valderas JM, Starfield B, Sibbald B, Salisbury C, Roland M: factors, and intermediate-term mortality after noncardiac surgery in Defining comorbidity: implications for understanding health and the B-Unaware Trial. Anesthesiology; 2011, 114:545-56. health services. Ann Fam Med; 2009, 7:357-63. 2. Leslie K, Myles PS, Forbes A, Chan MT: The effect of bispectral 9. Gabbe BJ, Magtengaard K, Hannaford AP, Cameron PA: Is the index monitoring on long-term survival in the B-aware trial. Anesth Charlson Index useful for predicting trauma outcomes? Acad Emerg Analg; 2010, 110:816-22. Med; 2005, 12:318-21. 3. Monk TG, Saini V, Weldon BC, Sigl JC: Anesthetic management 10. Murray SB, Bates DW, Ngo L, Ufberg JW, Shapiro NI: Charlson and one-year mortality after noncardiac surgery. Anesth Analg; Index is associated with one-year mortality in emergency department 2005, 100:4-10. patients with suspected infection. Acad Emerg Med; 2006, 13:530-6. 4. Charlson ME, Pompei P, Ales KL, MacKenzie CR: A new method 11. Culley DJ, Loguinov A, Yukhananov R, Crosby G: General of classifying prognostic comorbidity in longitudinal studies anesthesia does not reduce life expectancy in aged rats. Anesth development and validation. J Chron Dis; 1987, 40:373-83. Analg; 2006, 102:956-9. 5. Murray SB, Bates DW, Ngo L, Ufberg JW, Shapiro NI: Charlson 12. Akl EA, Briel M, You JJ, Sun X, Johnston BC, Busse JW, Mulla Index is associated with one-year mortality in emergency department S, Lamontagne F, Bassler D, Vera C, Alshurafa M, Katsios CM, patients with suspected infection. Acad Emerg Med; 2006, 13:530-6. Zhou Q, Cukierman-Yaffe T, Gangji A, Mills EJ, Walter SD, Cook 6. D’Hoore W, Bouckaert A, Tilquin C: Practical considerations on DJ, Schünemann HJ, Altman DG, Guyatt GH: Potential impact the use of the Charlson comorbidity index with administrative data on estimated treatment effects of information lost to follow-up in bases. J Clin Epidemiol; 1996, 49:1429-33. randomised controlled trials (LOST-IT): systematic review. BMJ; 7. Charlson ME, Sax FL, MacKenzie CR, Fields SD, Braham RL, 2012, 344:e2809. Teaching Ultrasound Procedural Skills-Low Cost Phantoms and Animal Models

Jacek A. Wojtczak* And Sonia Pyne**

Abstract

Acquiring the necessary cognitive and psychomotor skills to perform ultrasound guided procedures may require initial training. Growing evidence shows that simulation can help in the acquisition of procedural skills. Commercially available phantoms are expensive, have non-tissue like haptics, are preformed with fixed targets and do not allow for additional targets to be imbedded. In this study we have described several new phantoms and animal models that are inexpensive, easy to assemble and allow a rapid change of targets. Such phantoms can provide an ideal initial learning opportunity in a zero-risk environment. Key words: ultrasound phantoms, ultrasound-guided procedural skills.

Introductıon

Ultrasound (US) guided nerve blocks, cricothyroid punctures and vascular cannulations require, for safety reasons, initial training in animal models or phantoms. In-vitro models can facilitate learning of scanning techniques and hand-eye coordination skills. The elastomeric phantoms that are usually used for training lack tissue feedback, are expensive, rapidly deteriorate and become unusable due to needle tracks. In this study we describe new, improved animal models and phantoms that can be used in teaching ultrasound guided procedural skills.

Methods

We have prepared and evaluated low-cost phantoms (gelatin/agar or tofu bars with immersed tubular structures or plastic spine models), animal models (intact porcine heads, infrahyoid airway) and hybrid models (animal tissues immersed in gelatin or tofu, human hand placed on the foam to model lung with rib cage). US scanning was performed using BK Medical Flex Focus 400 and Sonosite S-Series systems.

* MD, PhD, Professor of Anesthesiology. ** MD, Assistant Professor of Anesthesiology. Affiliation: Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, New York. Corresponding author: Jacek A. Wojtczak, MD, PhD, Professor of Anesthesiology, Department of Anesthesiology, Box 604. University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Rochester, New York 14642. Tel: 585- 275-2141, Fax: 585-244-7271. E-mail: [email protected]

603 M.E.J. ANESTH 22 (6), 2014 604 WOJTCZAK J.A., PYNE S.

Results Cricothyroid membrane punctures were performed in the porcine infrahyoid airway embedded Retrobulbar blocks are usually placed in gelatin (Fig. 2 and 3) which allowed visualization of blindly in awake patients without US guidance1. the posterior wall of the airway. Severe complications of this blind technique have Vascular cannulations2 were performed in tofu been reported. Real-time US guidance provides models. Thin polyethylene tubings filled with saline visualization of the eye and the optic nerve before and were inserted into tofu bars (Fig. 4). Thin walls allowed during insertion of the needle which can improve the easy penetration of the needle and confirmation of the quality and safety of the block. Intact porcine head successful cannulation. models (Fig. 1) obtained in the slaughterhouse allow Ultrasound-guided placement of the spinal for supervised training to avoid ocular perforation and needle was performed in plastic lumbar and sacral injection of local anesthetic into the optic nerve or spine models3 immersed in gelatin or water bath sheath. (Fig. 5).

Fig. 1 A - pig eye axial sonogram (12 MHz linear probe). The lens (L) is intact and the retrobulbar area well visualized. B - injection of 5 ml of saline through the needle (N) fills the orbital canal. Sclera and the needle tip are well visualized.

Fig. 2 A - cross section of a pig trachea (T) and esophagus (E) embedded in gelatin. B - transverse ultrasound scan of the same specimen (18 MHz linear probe). C - longituinal scan of the specimen. The anterior and posterior walls of the trachea (T) are visualized. The needle was inserted through the crico-thyroid membrane. TEACHING ULTRASOUND PROCEDURAL SKILLS 605

Fig. 3 Upper panels - transverse ultrasound scans of the porcine thyroid cartilage immersed in gelatin (left); porcine cricothyroid membrane puncture (right) with needle reverberation artifact. Lower panels – transverse (left) and longitudinal (right) scans of the trachea immersed in gelatin. Needle visible in the trachea.

Fig. 4 Vascular puncture performed in tofu models. Polyethylene tubings filled with saline were inserted into tofu bars to mimic blood vessels.

M.E.J. ANESTH 22 (6), 2014 606 WOJTCZAK J.A., PYNE S.

Fig. 5 Saggital paramedian ultrasound scans of the plastic spine model immersed in gelatin. Spinal needles are placed in the intervertebral space between L3 - L4 (upper panel) and L5 - S1 (lower panel). N - needle; S - sacrum; L3, L4, L5 - spinal procesess and lamina of the L3, L4, L5 vertebra.

Ultrasound-guided thoracentesis was performed the image of the needle with ultrasound beam in the model consisting of the experimenter’s hand alignment and reaching a target inside the phantom or placed on top of the water-filled container with a wet the animal model may require a considerable number foam. Metacarpal bones of the human hand simulated of attempts5,6. The cumulative sum (cusum) charts 7 a rib cage and a wet foam simulated a diseased lung revealed that novice operators acquire such abilities immersed in the pleural fluid (Fig. 6). at variable rate. Appropriately designed models may allow for controlled, supervised learning, including a formative feedback between trials5,8 and construction Discussion of individual learning curves. An important benefit of using animal models is that it also allows teaching of Ultrasound guidance improves safety, success rate the ultrasound anatomy. Imbedding the animal tissue in and efficacy of various procedures provided that the tip gelatin or gelatin/agar mixture for improved durability of the needle is visualized at all times4. This skill can of the phantom enhances the quality of the ultrasound be taught in animal models and phantoms5. Optimizing image while preserving tissue feedback. TEACHING ULTRASOUND PROCEDURAL SKILLS 607

Fig. 6 Hybrid model of the lung. The experimenter’s hand is placed on top of the fluid-filled container with a wet foam (left panel). A sonogram (right panel) of metacarpal bones (M) of the human hand which simulate a rib cage and a wet foam underneath simulates a diseased lung (L) that is immersed in the pleural fluid F( ). N - needle.

The role of ultrasound in central neuraxial and can facilitate the teaching of scanning techniques blockade has been underappreciated due to the and hand-eye coordination skills that are required for perceived difficulty in imaging through the narrow real-time sonographically guided blocks. acoustic window produced by the vertebra. However, Procedural skills in the field of anesthesiology the interlaminar window permits passage of sound are assessed poorly compared with other domains waves. The intervertebral level can be identified and of learning5 as they are often given less importance the depth to the epidural and intrathecal spaces can be than the assessment of knowledge and judgement- 9 estimated . based skills. This is partly because there has been no Practicing on cadavers allows participants to study universally accepted and comprehensive way to assess the sonographic anatomy and practice sonographically procedural skills. It is our goal to further develop and guided blocks with realistic tactile feedback, but they optimize our in-vitro models to enable an objective are often limited by the quality of sonograms and have assessment of procedural skills by our anesthesia to be conducted in credentialed facilities. trainees. In-vitro models as described in this study allow Conflict Of Interest visualization of the osseous and soft tissue anatomy None.

M.E.J. ANESTH 22 (6), 2014 608 WOJTCZAK J.A., PYNE S.

References

1. Luyet C, Eichenberger B, Morriggl L, Remada L, Greig R: Real- time visualization of ultrasound-guided retrobulbar blockade: an curve associated with a simulated ultrasound-guided interventional imaging study. Br J Anaes; 2008, 101:855-59. task by inexperienced anesthesia residents. Reg Anesth Pain Med; 2. Troianos C, Hartman S, Glas K, Skubas N: Guidelines for 2004, 29:544-548. performing ultrasound cannulations. Anesth Analg; 2012, 114:46- 7. De Oliveira Filho G, Helayel D, Garzel P: Learing curves and 72. mathematical models for interventional ultrasound basic skills. 3. Li J, Karmakar M, Li X, Kwok W: Gelatin-agar lumbosacral spine Anesth Analg; 2008, 106:568-573. phantom. J Ultrasound Med; 2011; 30:263-72. 8. Raman M, Donnon T: Procedural skills education-colonoscopy as a 4. Hopkins P: Ultrasound guidance as a gold standard in regional model. Can J Gastroenter; 2008, 22:767-70. anaesthesia. Br J Anaes; 2007, 98:299-301. 9. Chin K, Karmakar M, Peng P: Ultrasonography of the adult thoracic 5. Bould M, Crabtree N, Naik V: Assessment of procedural skills in and lumbar spine for central neuraxial blockade. Anesthesiology; anaesthesia. Br J Anaes; 2009, 103:472-83. 2011, 114:1459-85. 6. Sites B, Gallagher J, Cravero J, Landberg J, Blike G: The learning CASE REPORTS

Awake Tracheal Intubation with Combined Use of King Vision™ Videolaryngoscope and a Fiberoptic Bronchoscope in a Patient with Giant Lymphocele

Mohamed R. El-Tahan*, D. John Doyle**, Alaa M. Khidr*, Mohamed A. Regal***, Ayman B. El Morsy*** and Mohamed El Mahdy*

Introduction

Airway devices such as the GlideScope® videolaryngoscope or the Airtraq® optical laryngoscope can facilitate fibreoptic-guided intubation1-4. In this report we show how a fiberoptic bronchoscope (FOB) guided through a channeled King Vision™ videolaryngoscope can aid awake tracheal intubation, as we illustrate in a patient with a giant lymphocele complicated by airway edema.

Case Presentation

A 33 year-old, 160 cm, 106 kg gentleman with 7 years of progressively enlarged chest and neck swelling presented with orthopnea and dyspnea and was scheduled for lymphocele excision. The patient’s hemogram, electrolytes, creatinine, and liver tests were normal. Pulmonary function tests showed a mild restrictive pattern (FEV1 68%, FVC 78%, and FEV1/FVC 87% of predicted). A left anterior multi-cystic, non-tender chest wall swelling measuring 50 × 35 cm with dilated superficial veins was noted. This extended to surround the anterior neck as a collar and extended beyond the thyroid cartilage (Figures 1a and b). Neck movements were impossible, mouth opening was 3.5 cm, and the Mallampati score was II. Chest radiography showed a huge pedunculated left- sided chest wall mass extending to the neck, and compression of the middle third of the trachea. The trachea was deviated to the right (Figure 2). The lymphocele extended beyond the thyroid cartilage, precluding tracheostomy or suprasternal needle tracheotomy. CT demonstrated a large multiple loculated cystic mass arising from the chest wall superficial to the pectoralis muscles compressing the middle third of the trachea, obstructing approximately 40% of the tracheal lumen and extending beyond the thyroid cartilage. The major neck vessels and superior vena cava were patent (Figures 3a and 3b).

* Anesthesiology Department, King Fahd Hospital of the University of Dammam, Dammam, Saudi Arabia. ** Department of General Anesthesiology, Cleveland Clinic, Cleveland, Ohio, USA. *** MD, Department of Surgery, Cardiothoracic Surgery Unit, King Fahd Hospital of the University of Dammam, Dammam, Saudi Arabia. Corresponding author: Mohamed R. El-Tahan, Anesthesiology Department, King Fahd Hospital of the University of Dammam, Dammam, Saudi Arabia, P.O. Box: 40289 Al Khubar 31952, Saudi Arabia. Tel: +966 (56) 9371849, Fax +966 (13) 8651193. E-mail: [email protected]

609 M.E.J. ANESTH 22 (6), 2014 610 El-Tahan m. r. et. al

Fig. 1 Photographs showing the extension of the huge left anterior chest wall and neck lymphocele. (a) Anterior view (b) Right lateral view.

Fig. 2 Postero-anterior views of the chest x ray showing a huge left anterior chest wall and neck lymphocele with no intra-thoracic extension.

Fig. 3 CT scan showing extension of the multi-cystic septated anterior neck and chest swelling. (a) Coronal view (b) Sagittal view. COMBINED AWAKE INTUBATION 611

A plan for intubation was adopted, with the The use of video laryngoscopes as a FOB primary plan constituting of awake intubation conduit1-4 can be helpful where the use of FOB alone using a FOB in conjunction with a King Vision™ is unsuitable. A channeled laryngoscope like as the videolaryngoscope, and with a back-up plan involving Airtraq® optical laryngoscope facilitates fibreoptic- the use of an airway introducer, a tube exchanger and guided intubation using either a small FOB inserted an intubating laryngeal mask airway, depending on the through the ETT mounted in the guiding channel and difficulties encountered. then directed into the glottis or by using a large FOB A cardiothoracic surgeon was on standby inserted through the guiding channel and directed to aspirate the neck cysts, or to initiate rigid into the glottis, followed with railroading the ETT 3 bronchoscopy and jet ventilation. Cardiopulmonary over its shaft . Additionally, video laryngoscope- bypass was available in the event of a failed airway assisted awake fibreoptic intubation has been shown or cardiovascular collapse. The upper airway was to be a potentially useful technique in difficult airway anesthetized with 2 mL of 10% lidocaine delivered by management7. nebulization. The patient then gargled 1.5 mL of 10% An expected problem in patients with a huge lidocaine, followed by 2% lidocaine gel applied to the cervical partially-obstructing mass is hypopharyngeal back of the tongue. Oxygen was delivered via nasal edema. Awake tracheostomy was precluded in this cannula, with sedation provided with an infusion in case with the extension of the lymphocele beyond the conjunction with 1 mg of midazolam5. thyroid cartilage. Laryngoscopy was performed in a semi-sitting In contrast to the fibreoptic bronchoscope, position using a King Vision™ video laryngoscope, the King Vision™ video laryngoscope has many where moderate hypopharyngeal edema and a grade advantages: it is relatively inexpensive and easy to III view of the glottis were observed. A 5.2-mm FOB handle. It offers a 160 degree field of view, potentially loaded with a 7.5-mm endotracheal tube (ETT) was eliminating the need for extensive manipulation of advanced via the King Vision™ video laryngoscope the bronchoscope, and is better suited for the tracheal channeled blade. The ETT was then advanced into the intubation of patients with pharyngeal swelling as trachea, while the glottis was visualized via the King it displaces the pharyngeal tissue and may provide Vision™ video laryngoscope. conduit for the FOB. After intubation, anesthesia was induced using In conclusion, the combined use of King Vision™ propofol and remifentanil and maintained with video laryngoscope and a fiberoptic bronchoscope can desflurane and remifentanil, with no muscle relaxant be an effective method of awake tracheal intubation, administered. as demonstrated in our patient with giant lymphocele. The surgeon excised the cysts through neck collar and left sub-mammary incisions. Intraoperative vital Consent Statement signs remained stable throughout the 4 hour surgery After the surgery, the patient was extubated, and was The patient’s written consent for publication of observed in the surgical intensive care unit for 24 hours. this report was obtained.

Discussion Conflict of Interest

Experience indicates that awake fiberoptic All authors declare that they receive no support intubation is successful in 88–100% of difficult airway from any commercial organization or company, and patients6. The flexible FOB is the preferred instrument have no conflicts of interest. in such patients, but the presence of restricted neck movement, pharyngeal edema or bleeding can preclude Financial support and sponsorship its use. None.

M.E.J. ANESTH 22 (6), 2014 612 El-Tahan m. r. et. al

References

1. Sharma D, Kim LJ, Ghodke B: Successful airway management intubation: a manikin study. J Anesth; 2011, 25:93. with combined use of Glidescope videolaryngoscope and fiberoptic 5. Song JW, Kwak YL, Lee JW, Chang CH, Kim HS, Shim YH: The bronchoscope in a patient with Cowden syndrome. Anesthesiology; optimal effect site concentration of remifentanil in combination with 2010, 113:253. intravenous midazolam and topical lidocaine for awake fibreoptic 2. Morillas Sendín P, del Olmo Rodríguez C, de Diego Isasa P, nasotracheal intubation in patients undergoing cervical spine Rouco Gil R: Combined use of the Glidescope and a fiberoptic surgery. Minerva Anestesiol; 2012, 78:521. bronchoscope in a case of unexpected difficult intubation. Rev Esp 6. Apfelbaum JL, Hagberg CA, Caplan RA, et al: Practice guidelines Anestesiol Reanim; 2008, 55:454. for management of the difficult airway: an updated report by the 3. Yuan YJ, Xue FS, Liao X, Liu JH, Wang Q: Facilitating combined use American Society of Anesthesiologists Task Force on Management of an Airtraq® optical laryngoscope and a fiberoptic bronchoscope of the Difficult Airway. Anesthesiology; 2013, 118:251. in patients with a difficult airway. Can J Anaesth; 2011, 58:584. 7. Kariya N, Kimura K, Iwasaki R, Ueki R, Tatara T, Tashiro C: 4. Nishikawa K, Hukuoka E, Kawagishi T, Shimodate Y, Yamakage Intraoperative awake tracheal intubation using the Airway Scope™ M: Efficacy of the Airtraq(®) laryngoscope with a fiberoptic in caesarean section. Anaesth Intensive Care; 2013, 41:390. bronchoscope compared with that of Airtraq(®) alone for tracheal ANESTHESIA FOR ARTHROSCOPIC SHOULDER SURGERY IN THE BEACH CHAIR POSITION: MONITORING OF CEREBRAL OXYGENATION USING COMBINED BISPECTRAL INDEX AND NEAR-INFRARED SPECTROSCOPY

Hiroaki Kawano* And Tomomi Matsumoto**

Abstract

Recent research has shown that cerebrovascular complications following shoulder surgery performed in the beach chair position under general anesthesia arise secondary to cerebral ischemia. Appropriate management of cerebral oxygenation is thus one of the primary goals of anesthetic management during such procedures. The present report describes the case of a 65-year-old male patient, in which both bispectral index (BIS) and near-infrared spectroscopy (NIRS) were used to monitor cerebral oxygenation. During the positioning, we observed an increased suppression ratio

(SR) while BIS and regional cerebral oxygen saturation (rSO2) were at adequate level. In view of the difference in blood pressure between the heart and the base of the brain, blood pressure was maintained to ensure adequate cerebral perfusion. Although intraoperative rSO2 was at or around the cut-off point (a 12% relative decrease from baseline), no marked decrease in BIS or further increase in the SR was observed. Monitoring of cerebral perfusion using combined BIS and NIRS optimized anesthetic management during the performance of arthroscopic shoulder surgery in the beach chair position. Key words: General anesthesia, Beach chair position, Cerebral oxygenation, Bispectral index, Near-infrared spectroscopy.

Introduction

Several reports have described serious complications secondary to general anesthesia for shoulder surgery performed in the beach chair position1,2. Recent research has identified a causal relationship between the beach chair position and cerebral hypoperfusion3,4, and it is widely accepted that the beach chair position may be associated with a decrease in cerebral perfusion5,6. The present report describes optimal management of cerebral oxygenation during arthroscopic shoulder surgery performed in the beach chair position. This involved the monitoring of cerebral oxygenation using a combination of bispectral index (BIS) and near-infrared spectroscopy (NIRS).

* MD, PHD. ** MD. Affiliation: Department of Anesthesiology and Clinical Research, National Hospital Organization Zentsuji Hospital, Zentsuji, Japan. Corresponding author: Hiroaki Kawano, MD, PhD, Department of Anesthesiology and Clinical Research, National Hospital Organization Zentsuji Hospital, 2-1-1 Senyu, Zentsuji, Kagawa 765-8507, Japan. Tel: +81-877-62-2211, Fax: +81- 877-63-1601. E-mail: [email protected]

613 M.E.J. ANESTH 22 (6), 2014 614 KAWANO H., MATSUMOTO T.

Case report were treated with intravenous ephedrine (4 mg) or phenylephrine (0.1 mg). Anesthesia was maintained The 65-year-old male patient (166 cm, 67 with oxygen (2 l/min), air (2 l/min), sevoflurane (1.0%), kg) was admitted to our hospital for arthroscopic and remifentanil (0.2-0.3 µg/kg/min). Neuromuscular shoulder surgery. He had undergone arthroscopic blockade was maintained with intermittent rocuronium. rotator cuff repair in the lateral decubitus position 7 As postoperative analgesia, approximately 60 min months before, but his symptoms had not improved. before the end of the procedure, intravenous fentanyl During the initial procedure, intraoperative monitoring (200 µg) was administered, and intravenous patient- included electrocardiography, noninvasive blood controlled analgesia infusion (fentanyl 20 µg/ml; basal pressure monitoring, capnography and pulse oximetry, infusion 1 ml/h, bolus 1 ml, lockout time 10 min) was and the anesthetic management was successful with started. no complications. His medical history included In response to anesthetic induction, MAP insulin-dependent diabetes mellitus, hypertension and decreased from 108 to 59 mmHg, which resulted congestive heart failure. in an increase of the suppression ratio (SR) to 19. No preanesthetic medication was administered At this point, the BIS and rSO2 were stable. With prior to the arthroscopic procedure. On arrival in the intravenous administration of ephedrine (4mg), the operating room, his blood pressure was 161/72 mmHg, MAP increased and the SR returned to 8. After the his heart rate was 68 beats/min, and his arterial oxygen patient was placed in the beach chair position, the saturation was 98% on room air. The patient was SR rapidly increased to 21. BIS and rSO2 were in monitored with electrocardiography, capnography, and the 40-50 and 45-50 ranges, respectively, and signal pulse oximetry. In addition to these routine monitoring quality index was more than 75%. The patient’s MAP procedures, an arterial catheter was inserted into the was 70 mmHg. This was treated with intravenous left radial artery to allow invasive blood pressure administration of ephedrine (8 mg), and the SR monitoring, and BIS monitoring was applied. At the improved (Fig. 1). Thereafter, there was no further increase in the SR. The intraoperative systolic blood same time, regional cerebral oxygen saturation (rSO2) was measured using NIRS (INVOS 5100C; Covidien, pressure was 90-160 mmHg, the MAP was 70-110 Boulder, CO, USA). Throughout the procedure, the mmHg, the heart rate was 50-70 beats/min, and the

end-tidal CO2 was 35-40 mmHg. The total dose of rSO2 was recorded from the left (LrSO2) and the right (RrSO ) hemispheres using two probes, which were ephedrine was 40 mg and that of phenylephrine was 2 0.5 mg. The BIS was stable at between 40 and 60, positioned on the left and right sides of the forehead and there were no episodes of any marked decrease respectively. Prior to induction, the LrSO2 and RrSO2 in BIS. The LrSO was stable at around 52% (range were 59% and 51%, respectively (baseline values). 2 50-54%), and the RrSO was also stable at around General anesthesia was induced with intravenous 2 52% (range 50-53%). Surgery was completed remifentanil (0.5 µg/kg/min), propofol (70 mg), and without complications, and the patient emerged rocuronium (40 mg), and endotracheal intubation was from anesthesia uneventfully. Once the patient had performed. The patient was then placed in the beach regained consciousness and was able to follow chair position. The external auditory meatus, which simple commands, the neuromuscular blockade was represents the base of the brain, was positioned 40 reversed and his trachea was extubated. The duration cm above the atrial level. Thus, it was calculated that of the surgical procedure and anesthesia were 8 h:11 the blood pressure at the base of the brain would be min and 9 h:40 min, respectively. Intraoperative approximately 30 mmHg lower than at the arm. To total blood loss was 250 ml, urine output was maintain the mean arterial pressure (MAP) above 80 1450 ml and total infusion volume was 1750 ml. mmHg, a continuous infusion of intravenous dopamine The patient remained stable during the 1-month (2-5 µg/kg/min) was administered. In addition, all inpatient postoperative period, and no postoperative episodes of hypotension (defined as MAP< 80 mmHg) complications were evident. ANESTHESIA IN THE BEACH CHAIR POSITION 615

Discussion during episodes of acute hypotension within the course of cardiac surgery. In these patients, abrupt decreases in The beach chair position (30-90° above the BIS in their patients associated with an acute slowing horizontal plane) is widely used for orthopedic shoulder of the electroencephalogram (EEG), which is an early arthroscopy procedures as it offers advantages such indication of cerebral hypoperfusion. In the present as excellent intraarticular visualization and reduced case, no marked reduction in BIS, a sign which may brachial plexus strain. Although Tange et al.7 reported suggest cerebral hypoperfusion, was observed during that the use of the beach chair position under general the procedure. anesthesia did not alter cerebral oxygenation, several In the present case, the SR increased to 21 studies have reported a causal relationship between following change of position from supine to beach the beach chair position and cerebral hypoperfusion3,4. chair position, while BIS and rSO2 were in a normal 3 According to a report by Murphy et al. , shoulder range. This is similar to previously reported cases surgery in the beach chair position was associated where an increased SR was observed despite BIS with a significant reduction in cerebral oxygenation values at an adequate anesthetic level and the possible compared with the use of the lateral decubitus position. role of hypoxemia was suggested10,11. SR derived Therefore, maintenance of adequate cerebral perfusion from BIS monitoring estimates the percentage of should be ensured during shoulder surgery performed burst suppression EEG pattern or isoelectric activity. in the beach chair position, even in healthy patients It occurs during deep anesthesia, but several reports who are not at increased risk of ischemic stroke. suggest that SR could be related to hemodynamics12 Strict cerebral oximetry monitoring was necessary or metabolism such as hypothermia13 or hypoxia10. in the present case, as the patient was at high risk of A causal relationship between SR and cerebral cerebrovascular events. hypoxemia has been suggested in animal studies14. The BIS is widely used as an indicator of the Furthermore, it has been shown that the presence level of consciousness during general anesthesia. of SR in critically ill patients was associated with In addition, several reports have suggested that the increased mortality15. Therefore, although it is obvious BIS allows detection of cerebral ischemia8,9, since that BIS monitor is not designed to detect cerebral cerebral hypoperfusion decreases the BIS. Hayashida ischemia, it might be useful for detecting cerebral et al.9 described five children in whom 14 episodes of hypoperfusion. Because MAP decreased from 108 a simultaneous decreases in rSO2 and BIS occurred to 59 mmHg in response to anesthetic induction,

Fig. 1 Changes in regional cerebral oxygen

saturation (rSO2), mean arterial pressure (MAP), bispectral index (BIS), and suppression ratio (SR) during the anesthetic procedure. During the positioning, an increased

SR was observed while BIS and rSO2 were in a normal range.

Although intraoperative rSO2 was at or around the cut-off point, no marked decrease in BIS or further increase in the SR was observed. A, tracheal intubation; B, beach chair position; C, start of operation

M.E.J. ANESTH 22 (6), 2014 616 KAWANO H., MATSUMOTO T.

and because hypoxia, hypocapnia, and anemia, all of available. Therefore relying on rSO2 alone to monitor which might cause cerebral hypoperfusion, were not the adequacy of cerebral perfusion might be dangerous present, the first episode of SR increase was thought and inadequate in terms of avoiding neurological to be due to hypotension. However, the second episode complications. Consequently, both BIS and rSO2 were of SR increase in the present case may have been measured with NIRS. Hayashida et al.18 reported that related to cerebral hypoperfusion associated with the the combination of BIS and NIRS can be a convenient beach chair position. It is well recognized that the method of ischemic/anesthetic monitoring, i.e., that beach chair position may be associated with a decrease by monitoring both BIS and NIRS, it is possible to in cerebral perfusion as mentioned above. In our judge whether cerebral hypoperfusion, as indicated by patient, an elevation of the SR was a useful sign for the a decrease in rSO2, is at the saturation level at which detection of the beach chair position-related cerebral cerebral dysfunction will occur. hypoperfusion. In conclusion, appropriate management of NIRS is a noninvasive technique for the cerebral oxygenation is essential during any surgical continuous monitoring of rSO2, and it has been used procedure performed in the beach chair position. We to detect cerebral ischemia and hypoxia in patients recommend the use of cerebral oximetry monitoring undergoing procedures such as cardiovascular devices. In the present case, monitoring of cerebral surgery and carotid endarterectomy (CEA). Although oxygenation using a combination of BIS and NIRS various studies have investigated the optimal cut-off optimized anesthetic management during the point for a decrease in rSO2 in order to identify the performance of shoulder surgery in the beach chair occurrence of neurological complications in patients position. undergoing CEA16,17 , the rSO2 threshold indicating Conflict of interest cerebral ischemia ranges from a 12-20% relative None. decrease. It may therefore be difficult to judge whether pharmacological or physiological intervention is Funding required when the rSO2 is at or around the cut-off point None. like the present case. Furthermore, it has been shown Acknowledgments that EEG and somatosensory evoked potentials (SEP) correlate directly with changes in cerebral blood flow, Published with the written consent of the patient. whereas no such data related to rSO2 are currently ANESTHESIA IN THE BEACH CHAIR POSITION 617

References

1. Pohl A, Cullen DJ: Cerebral ischemia during shoulder surgery in 11. Declerck A, Liu N, Chazot T, Fischler M: BIS values during the upright position: a case series. J Clin Anesth; 2005, 17:463-469. resuscitation: the role of the suppression ratio (case report). J Clin 2. Bhatti MT, Enneking FK: Visual loss and ophthalmoplegia after Monit Comput; 2009, 23:307-309. shoulder surgery. Anesth Analg; 2003, 96:899-902. 12. Umegaki N, Hirota K, Kitayama M, Yatsu Y, Ishihara H, Mtasuki A: 3. Murphy GS, Szokol JW, Marymont JH, GREENBERG SB, A marked decrease in bispectral index with elevation of suppression AVRAM MJ, VENDER JS, VAUGHN J, NISMAN M: Cerebral ratio by cervical haematoma reducing cerebral perfusion pressure. J oxygen desaturation events assessed by near-infrared spectroscopy Clin Neurosci; 2003, 10:694-696. during shoulder arthroscopy in the beach chair and lateral decubitus 13. Hayashida M, Sekiyama H, Orii R, CHINZEI M, OGAWA M, positions. Anesth Analg; 2010, 111:496-505. ARITA H, HANAOKA K, TAKAMOTO S: Effects of deep 4. Lee JH, Min KT, Chun YM, Kim EJ, Choi SH: Effects of beach-chair hypothermic circulatory arrest with retrograde cerebral perfusion position and induced hypotension on cerebral oxygen saturation in on electroencephalographic bispectral index and suppression ratio. J patients undergoing arthroscopic shoulder surgery. Arthroscopy; Cardiothorac Vasc Anesth; 2007, 21:61-67. 2011, 27:889-894. 14. Feet BA, Brun NC, Hellstrom-Westas L, Svenningsen NW, Greisen 5. Cullen DJ, Kirby RR: Beach chair position may decrease cerebral G, Saugstad OD: Early cerebral metabolic and electrophysiological perfusion: Catastrophic outcomes have occurred. APSF Newsletter; recovery during controlled hypoxemic resuscitation in piglets. J 2007, 22:25-27. Appl Physiol; 1998, 84:1208-1216. 6. Mazzon D, Danelli G, Poole D, Marchini C, Bianchin C: Beach 15. Watson PL, Shintani AK, Tyson R, Pandharipande PP, Pun BT, chair position, general anesthesia and deliberated hypotension Ely EW: Presence of electroencephalogram burst suppression in during shoulder surgery: a dangerous combination! Minerva sedated, critically ill patients is associated with increased mortality. Anestesiol; 2009, 75:281-282. Crit Care Med; 2008, 36:3171-3177. 7. Tange K, Kinoshita H, Minonishi T, HATAKEYAMA N, MATSUDA 16. Mille T, Tachimiri ME, Klersy C, TICOZZELLI G, BELLINZONA N, YAMAZAKI M, HATANO Y: Cerebral oxygenation in the G, BLANGETTI I, PIRRELLI S, LOVOTTI M, ODERO A: Near beach chair position before and during general anesthesia. Minerva infrared spectroscopy monitoring during carotid endarterectomy: Anestesiol; 2010, 76:485-490. which threshold value is critical? Eur J Vasc Endovasc Surg; 2004, 8. England MR: The changes in bispectral index during a hypovolemic 27:646-650. cardiac arrest. Anesthesiology; 1999, 91:1947-1949. 17. Samra SK, Dy EA, Welch K, Dorje P, Zelenock GB, Stanley JC: 9. Hayashida M, Chinzei M, Komatsu K, YAMAMOTO H, TAMAI Evaluation of a cerebral oximeter as a monitor of cerebral ischemia H, ORII R, HANAOKA K, MURAKAMI A: Detection of cerebral during carotid endarterectomy. Anesthesiology; 2000, 93:964-970. hypoperfusion with bispectral index during paediatric cardiac 18. Hayashida M, Kin N, Tomioka T, ORII R, SEKIYAMA H, USUI surgery. Br J Anaesth; 2003, 90:694-698. H, CHINZEI M, HANAOKA K: Cerebral ischaemia during cardiac 10. Liu N, Chazot T, Mutter C, Fischler M: Elevated burst suppression surgery in children detected by combined monitoring of BIS and ratio: the possible role of hypoxemia. Anesth Analg; 2006, 103:1609- near-infrared spectroscopy. Br J Anaesth; 2004, 92:662-669. 1610.

M.E.J. ANESTH 22 (6), 2014

IMPOSSIBLE MASK VENTILATION AFTER AN UNUSUALLY LOW DOSE FENTANYL-INDUCED MUSCLE RIGIDITY IN A PATIENT WITH ESSENTIAL TREMOR: A CASE REPORT AND REVIEW OF THE LITERATURE

Vassilios Dimitriou*, Ioannis Zogogiannis**, Despoina Liotiri***, Freddie Wambi****, Nasser Tawfeeq****, Adnan Koumi**** and Georges Geldhof*****

Abstract

Although opioid-induced muscle rigidity occurs more commonly with large doses and rapid administration of the drugs, there is a number of cases reported, where muscle rigidity was experienced with lower doses of opioids. We present and discuss a case of muscle rigidity induced by an unusually low dose of fentanyl as primary agent during induction of anesthesia. A 79 year old male patient, scheduled for hernia repair, and with a preoperative physical examination of slight hand tremor, received a bolus of 100mcg (1.2mcg/kg) fentanyl as primary agent for induction. About 40sec later he stopped responding, lost consciousness and developed neck and masseter muscle spasm with jaw closure and thoracoabdominal rigidity. Blood pressure was increased significantly. Ventilation was impossible. Rapid oxygen desaturation led us to proceed with IV propofol 150mg and suxamethonium 100mg. Opioid-induced muscle rigidity may cause life-threatening respiratory compromise and should be readily recognized and treated by anesthesiologists. Key words: Anesthesia, opioids, muscle rigidity, essential tremor.

Introduction

Opioid administration produces intense analgesia and decreased sympathetic response to attenuate stress response to painful surgical stimulation. Because of these advantageous clinical properties, opioids have increasingly seen wide-spread use in anesthesia. Unfortunately, the profound analgesia of high-dose opioid administration may be accompanied by prolonged respiratory depression and intense muscle rigidity. Opioid-induced muscle rigidity was first described by Hamilton and Cullen in 19531. At the same time with the introduction of fentanyl in anesthetic practice (1981), fentanyl-induced muscle rigidity started to be reported both in adults and children2,3,4. Thereafter, muscle rigidity after opioid administration became a well documented effect, most commonly with lipophilic synthetic opioids such as fentanyl, alfentanil, remifentanil and sufentanil, although its pathophysiology is not as well clarified5-7. It is not a common adverse effect and its true incidence is unknown.

* Professor of Anesthesia, Consultant, Department of Anesthesia, King Abdulaziz Medical Center, Riyadh, Saudia Arabia. ** Senior Registrar, Department of Anesthesia, ‘G Gennimatas’ General Hospital of Athens, Greece. *** Registrar, Department of Anesthesia, ‘G Gennimatas’ General Hospital of Athens, Greece. **** Consultant, Department of Anesthesia, King Abdulaziz Medical Center, Riyadh, Saudia Arabia. ***** Chairman, Department of Anesthesia, King Abdulaziz Medical Center, Riyadh, Saudia Arabia. Corresponding author: Vassilios Dimitriou, Professor of Anesthesia, Consultant, Department of Anesthesia, King Abdulaziz Medical Center, Riyadh, Saudi Arabia. Tel: +966596508911. E-mail: [email protected]

619 M.E.J. ANESTH 22 (6), 2014 620 Dimitriou v. et. al

The development of muscle rigidity accompanies ventilation and oxygenation were resumed successfully induction of anesthesia with opioids and in most cases with an increase of SpO2 to 100%. Laryngoscopy and has been reported in preterm and term infants or after tracheal intubation were successful. The operation was administration of high doses of opioids8-12. However, completed uneventfully and the patient awakened one a recent case report13 concerning fentanyl-induced hour later. When questioned postoperatively the patient muscle rigidity during sedation for bronchoscopy, had no recall of the event. After neurology consultation increased the concern about the safety of opioid the patient was submitted to a CT and MRI scan which administration in minor interventions requiring were normal. The postoperative complete neurology sedation that is very common in the everyday examination concluded that the patient suffered from anesthetic practice. There are other cases where essential tremor. muscle rigidity has been induced after low doses of opioids but in accordance with other factors14-15. The Discussion usual clinical presentation varies from mild symptoms of muscle spasm, up to severe and potentially life- We reported a case of an unusually low dose threatening symptoms like inability of ventilation and fentanyl-induced muscle rigidity. Since the patient clonus. We report a case of muscle rigidity induced by did not receive any premedication and fentanyl was an unusually low dose of fentanyl as primary agent the sole agent during induction, there is no doubt for during induction of anesthesia. the cause of muscle rigidity. To our knowledge this is the first case of muscle rigidity with such a low Case History dose of fentanyl (1.2mcg/kg) and so early (40sec) at induction. Low dose opioid-induced rigidity have A 79 year old male patient (height 177cm, weight been reported in preterm and term infants, or patients 82kg) with history of arterial hypertension and coronary with risk factors like neurological diseases, metabolic artery disease under treatment, was scheduled for hernia disorders and medications modifying dopamine repair. Preoperative physical examination performed levels8,10,14,15. Our patient was only receiving revealed slight hand tremor and otherwise was normal. antihypertensive therapy including an ACE inhibitor His laboratory results were normal. The patient did and a beta adrenoreceptor antagonist. The essential not receive premedication. In the operating room tremor which was diagnosed postoperatively could standard monitoring was applied and the patient was have been a contributing role. preoxygenated and received a bolus of 100μg fentanyl When used intraoperatively, the administration as primary agent for induction, in order to attenuate of a nondepolarizing neuromuscular blocking agent the response to laryngoscopy. About 40sec later he concurrently with fentanyl prevents rigidity16,17. stopped responding, lost consciousness and developed Although chest wall rigidity occurs more commonly neck and masseter muscle spasm with jaw closure, with large doses and rapid administration, there is thoracoabdominal rigidity, upper limb flexion and lower a number of cases reported, where muscle rigidity limb extension without any sign of lateralization. Blood was experienced with lower doses of opioids13,14. pressure increased significantly (from 125/80mmHg to Although most common with the rapid administration 195/110mmHg). Ventilation was impossible even with of large doses, this rare adverse effect may occur with four-handed bag-mask ventilation. The inability to small doses especially in neonates and infants8-11,14. open the mouth due to masseter muscle spasm made Additionally, this occurred in our case as well as in it impossible to insert an oropharyngeal or laryngeal a patient undergoing bronchoscopy13. Skeletal muscle mask airway. A nasopharyngeal airway was inserted and rigidity has been recognized, most commonly with mask ventilation was initiated with no improvement. lipophilic synthetic opioids such as fentanyl, alfentanil, Rapid oxygen desaturation (SpO2 <85%) led us to remifentanil, and sufentanil. This rigidity can primarily proceed with IV propofol (150mg) and suxamethonium affect the chest and abdominal musculature, resulting (100mg). Subsequently, the muscle spasm subsided and in the “wooden chest syndrome.” Chest wall rigidity UNUSUALLY LOW DOSE FENTANYL-INDUCED MUSCLE RIGIDITY 621 decreases chest wall compliance and may result in case fentanyl 100 mcg was given on a bolus which ineffective spontaneous ventilation and may also make is common practice during induction in anesthesia. assisted ventilation more difficult5,18. Rigidity occurred very early after 40sec, and at an The ventilatory difficulty may be contributed to unusually low dose of 1.2mcg/kg. Additionally, our vocal cords closure, to the jaw closure and the thoraco- patient became hypertensive with muscle rigidity. abdominal rigidity20,21. Although a nasopharyngeal This is in accordance with other studies, since muscle airway can be inserted, airway obstruction caused rigidity does not affect only the respiratory system, primarily by glottis closure, may make it difficult to but additionally induces significant hemodynamic 3,13 ventilate the patient manually. The incidence of glottis changes, accompanied by CO2 retention . closure in patients with opioid induced muscle rigidity The exact mechanism of increased muscle tone ranges from 50-100% depending on the opioid used, after the rapid infusion of an opioid is not known. the dose and the rate at which it is administered21. Experimental animal study28 indicated that stimulation Although Muller and Vogtmann22 reported the adverse of central mu1 - opioid receptors increases efferent effects to be self-limited and brief, all other case reports motor traffic, resulting in muscle contraction and required treatment with naloxone administration, rigidity. Additional data29 demonstrate that whereas neuromuscular blockade, and/or mechanical systemic opiate-induced muscle rigidity is primarily ventilation. Pretreatment with an alpha-2 adrenergic due to the activation of central mu receptors, agonist (clonidine and dexmedetomidine) has been supraspinal delta-1 and kappa-1 receptors may shown to decrease the incidence of opioid-induced attenuate this effect. rigidity, whereas serotonergic agents have been found Experimental studies in rats28,30 based on combined effective in animal studies23,24. physiologic, pharmacologic, histochemical, and In our case the patient lost consciousness immunocytochemical evaluations have demonstrated, simultaneously with opioid-induced rigidity. This that fentanyl may elicit muscular rigidity by activating is in accordance with Streisand et al25 in a study in spinal motoneurons by acting on the locus ceruleus in human volunteers. They reported that all subjects lost the pons. The locus ceruleus is the principal source consciousness simultaneously with opioid-induced of central nervous system norepinephrine. It appears rigidity. Fentanyl was administered at a rate of 150 that the participation of the cerulospinal noradrenergic mcg/min and rigidity occurred at a dose of 15 mcg/ pathway in fentanyl-induced muscular rigidity is kg25. The onset of rigidity and unconsciousness critical28. In addition to the cerulospinal noradrenergic occurred an average of 3 min after peak fentanyl mechanism, the cerulospinal glutamatergic pathway plasma concentrations and was associated with and both NMDA and non-NMDA receptors in the plasma fentanyl concentrations consistent with spinal cord may mediate fentanyl-induced muscular 30 drug action25. In contrast Grell et al26 reported that, rigidity in the rat . Fentanyl-induced muscular rigidity 11 of 12 patients developed rigidity that neither may involve disinhibition of spinal motoneurons via produced unconsciousness nor impaired spontaneous an action of norepinephrine and glutamate on separate 30 ventilation. Waller et al27 reported that patients could neuronal populations in the spinal cord . open their eyes to command and initiate a breath, Our patient was diagnosed postoperatively with despite the presence of chest wall rigidity during essential tremor which is one common neurological induction in anesthesia with fentanyl. However, in the disease. From the pathophysiology of the disease there studies of both Grell et al and Waller et al, fentanyl are altered concentrations of some biochemical markers was administered at slower rates (30 and 50 mcg/min in these patients31. They have reduced cerebrospinal respectively) and chest wall rigidity occurred at doses fluid concentrations of gama-aminobutyric acid of 7.3 and 8 mcg/kg respectively. It appears that a (GABA), glycine, and serine, with a slight increase in mild form of rigidity, associated with decreased chest glutamate. Also there are abnormalities on thalamic wall compliance, can be detected with maintenance GABAa receptors. In specific regions increased of consciousness and spontaneous ventilation. In our concentrations of norepinephrine are also found in

M.E.J. ANESTH 22 (6), 2014 622 Dimitriou v. et. al patients with essential tremor: 5-folds in locus ceruleus induced by an unusually low dose of fentanyl as primary and 2-folds in cerebellar cortex32,33. So it is possible that agent during induction of anesthesia. Opioid-induced these abnormalities made the patient more vulnerable muscle rigidity causing respiratory compromise should to fentanyl-induced rigidity even with an unusually be readily recognized and treated by anesthetists. low dose of opioid. Sources of financial support In summary, we presented and discussed the None. successful management of a case of muscle rigidity

References

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Bennet JA, Abrams JT, Van Riper DF, Horrow JC: Difficult or 4. Waller JL, Hug CC, Nagle DM, Craver JM: Hemodynamic impossible ventilation after sufentanil induced anesthesia is caused changes during fentanyl-oxygen anesthesia for aortocoronary primarily by vocal cord closure. Anesthesiology; 1997, 87:1070-4. bypass operations. Anesthesiology; 1981, 55:212-7. 22. Muller P, Vogtmann C: Three cases with different presentation of 5. Neidhart P, Burgener MC, Schwieger I, Suter PM: Chest wall fentanyl-induced muscle rigidity: a rare problem in intensive care of rigidity during fentanyl and midazolam-fentanyl induction: neonates. Am J Perinatol; 2000, 17:23-6. ventilatory and haemodynamic effects. Acta Anaesthesiol Scand; 23. Weinger MB, Segal IS, Maze M: Dexmedetomidine, acting through 1989, 33:1-5. central alpha-2 adrenoceptors, prevents opiate-induced muscle 6. Prys-Roberts C, Schüttler J, Breivik H, Viby-Mogensen J: rigidity in the rat. Anesthesiology; 1989, 71:242-9. Remifentanil. Anaesthesia; 1998, 53:409. 24. Jaros T, Kolasiewicz W: Attenuation of the fentanyl-induced 7. Viscomi CM, Bailey PL: Opioid induced rigidity after intravenous muscle rigidity by the selective 5HT1A agonist 8-OH-DPAT. Pol J fentanyl. Obstet Gynecol; 1997, 89:822-4. Pharmacol; 1995, 47:19-24. 8. Fahnenstich H, Steffan J, Kau N, Bartmann P: Fentanyl-induced 25. Streisand JB, Bailey PL, LeMaire L, Ashburn MA, Tarver chest wall rigidity and laryngospasm in preterm and term infants. SD, Varvel J, Stanley TH: Fentanyl-induced rigidity and Crit Care Med; 2000, 28:836-9. unconsciousness in human volunteers. Incidence, duration, and 9. Van der Lee R, Ceelie I, de Wildt SN: Morphine-induced muscle plasma concentrations. Anesthesiology; 1993, 78:629-34. rigidity in a term neonate. Ann Pharmacother; 2009, 43:1724-6. 26. Grell FL, Koons DA, Denson J: Fentanyl in anesthesia: A report of 10. Lindemann R: Respiratory muscle rigidity in a preterm infant after 500 cases. Anesth Analg; 1970, 49:523-32. use of fentanyl during Caesarean section. Eur J Pediatr; 1998, 27. Waller JL, Hug CC, Nagle DM, Craver JM: Hemodynamic 157:1012-3. changes during fentanyl-oxygen anesthesia for aortocoronary 11. Pokela ML, Ryhanen PT, Koivisto ME, Olkkola KT, Saukkonen bypass operations. Anesthesiology; 1981, 55:212-7. AL: Alfentanil induced rigidity in newborn infants. Anesth Analg; 28. Lui PW, Lee TY, Chan SH: Involvement of locus ceruleus and 1992, 75:252-7. nonadrenergic neurotransmission in fentanyl-induced muscular 12. Bowdle TA, Rooke GA: Postoperative myoclonus and rigidity after anesthesia with opioids. Anesth Analg; 1994, 78:783-6. rigidity in the rat. Neurosci Lett; 1989, 96:114-9. 29. Vancova ME, Weinger MB, Chen DY, Bronson JB, Motis V, Koob 13. Coruh B, Tonelli MR, Park DR: Fentanyl-induced chest wall rigidity. Chest; 2013, 143:1145-6. GF: Role of central Mu, delta-1 and kappa-1 opioid receptors in 14. Dewhirst E, Naguib A, Tobias J: Chest wall rigidity in two infants opioid-induced muscle rigidity in the rat. Anesthesiology; 1996, after low-dose fentanyl administration. Pediatr Emerg Care; 2012, 85:574-83. 28:465-8. 30. Fu MJ, Tsen LY, Lee TY, Lui PW, Chan SH: Involvement of ‐ 15. Zesiewicz TA, Hauser RA, Freeman A, Sullivan KL, Miller cerulospinal glutamatergic neurotransmission in fentanyl induced AM, Halim T: Fentanyl-induced bradykinesia and rigidity after muscular rigidity in the rat. Anesthesiology; 1997, 87:1450-9. deep brain stimulation in a patient with Parkinson disease. Clin 31. Mally J, Baranyi M, Vizi ES: Change in the concentrations of Neuropharmacol; 2009, 32:48-50. amino acids in CSF and serum of patients with essential tremor. J 16. Hill AB, Nahrwold ML, de Rosayro AM, Knight PR, Jones RM, Neural Transm; 1996, 103:555-60. Bolles RE: Prevention of rigidity during fentanyl-oxygen induction 32. Rajput AH, Hornykiewicz O, Deng Y, et al: Increased noradrenaline of anesthesia. Anesthesiology; 1981, 55:452-4. levels in essential tremor brain. Neurology; 2001, 56:A302. 17. Nakada J, Nishira M, Hosoda R, Funaki K, Takahashi S, Matsura 33. Louis ED, Honig LS, Vonsattel JP, Maraganore DM, Borden S, T. Priming with rocuronium or vecuronium prevents remifentanil- Moskowitz CB: Essential tremor associated with focal nonnigral mediated muscle rigidity and difficult ventilation. J Anesth; 2009, Lewy bodies: a clinicopathologic study. Arch Neurol; 2005, 23:323-8. 62:1004-7. Hypotension on Induction: Anaphylaxis or Cardiac Failure?

Himani V. Bhatt* and Elizabeth A. M. Frost**

Abstract

Identification of the cause of hypotension after induction of anesthesia is critical as treatment differs. We describe a case of anaphylaxis in a patient with severe cardiac disease, diagnosed by echocardiography and successfully treated with immediate cardiovascular resuscitation, epinephrine, vasopressors and antihistamines. Keywords: Cardiogenic shock, anaphylaxis, echocardiography.

Introduction

Hypotension is not uncommon after induction of anesthesia. However, when hypotension is severe, especially in patients with co-morbidities such as coronary artery or valvular disease, identification of the cause may be difficult. We describe a case of cardiovascular collapse after induction in a patient scheduled for triple valve replacement.

Case

A 69 year-old female with severe valvular disease was admitted for valve replacement. She had moderate right ventricular dysfunction, severe tricuspid regurgitation and marked pulmonary hypertension. An arterial cannula and right pulmonary artery catheter were placed. Anesthetic induction included 4mg midazolam, 250 mg fentanyl, 50mg rocuronium and antibiosis. Fifteen minutes post induction, blood pressure declined to 50-60/30-40. We presumed a diagnosis of pulmonary hypertension crisis with right ventricular failure secondary to underlying valvular pathology and right ventricular dysfunction. However, pulmonary artery pressures remained unchanged, central venous pressure dropped to 3 mmHg and peak airway pressures increased to 38-40mmHg. Transesophageal echocardiography revealed a hyperdynamic heart. Suspecting anaphylaxis, treatment was instituted with epinephrine, vasopressin, norepinephrine, H-1 and H-2 blockers and steroids. Hemodynamic stability was reestablished. Serum tryptase levels exceeded 400 ug/L. We concluded that cardiac collapse was secondary to anaphylactic shock, exacerbated by cardiac pathology.

* MD, Assistant Professor in Anesthesiology. ** MD, Professor of Anesthesiology. Affiliation: Department of Anesthesia, Icahn School of Medicine at Mount Sinai, New York, NY. Corresponding author: Dr. Himani V. Bhatt, Assistant Professor in Anesthesiology, Department of Anesthesia, Icahn School of Medicine at Mount Sinai, New York, NY. E-mail: [email protected]

623 M.E.J. ANESTH 22 (6), 2014 624 Bhatt h. v., Frost e. a. m.

Discussion increased airway pressures, pulmonary congestion and cardiovascular collapse are common to both. Anaphylactic reactions are rare intraoperatively However, bronchoconstriction, facial edema, and and even when treated appropriately have a mortality cutaneous manifestations including generalized rate ranging from 3.5-4.7%1. Anaphylaxis is an erythema, urticaria and angioedema are characteristic immediate hypersensitivity reaction mediated by the of anaphylaxis. Hemodynamic consequences and interaction of an antigen with IgE causing activation and changes in LV loading conditions are secondary to degranulation of mast cells and basophils. Vasoactive loss of vasomotor tone as opposed to deterioration mediators such as histamine, prostaglandins, kinins, of myocardial function. Other differences in leukotrienes and tryptase are released causing severe hemodynamic parameters are shown in Table 11,3,4,7,13- hypotension, bronchospasm, laryngeal edema, and 16. cardiovascular collapse1-4. Table 1 Many perioperative agents have been Features of anaphylactic vs. cardiogenic shock implicated. Sixty to 70% of reactions are secondary ANAPHYLACTIC CARDIOGENIC to neuromuscular blocking agents (NMDAs), SIMILARITIES commonly succinylcholine and rocuronium. Latex is also often implicated. Other incriminating agents Mean arterial pressure - ↓↓ Tachycardia include antibiotics, hypnotics (thiopental, propofol Airway pressures - ↑↑ (Anaphylactic>cardiogenic) and midazolam), opioids, local anesthetics, iodinated Pulmonary edema contrast materials, non-steroidal ant-inflammatory Dysrhythmias drugs and colloids1,4-6. DIFFERENCES Tests to identify allergens include serum tryptase levels, plasma histamine, and specific IgE Wheezing/ EKG changes concentrations. Tryptase and histamine levels should bronchoconstriction Cutaneous manifestations be drawn within one hour of the reaction but can take Facial edema/angioedema Systemic vascular resistance up to a week for results. Tryptase levels > 25ug/L Systemic vascular resistance - ↑ or ↔ are strongly suspicious of an anaphylactic etiology - ↓↓ Pulmonary vascular and have a positive predictive value of over ninety Pulmonary vascular resistance - ↑↑ 5,6 percent . Radioallergosorbent tests (RASTs) detect resistance - ↓↓ Pulmonary capillary wedge IgE antibodies to specific anesthetic drugs such as Pulmonary capillary wedge pressure - ↑ muscle relaxants and intravenous anesthetic agents1,4-7. pressure - ↓ Left ventricular end- Cardiogenic shock occurs in up to 7% of patients Left ventricular end- diastolic/end-systolic diastolic/end-systolic pressure/area - ↑ with myocardial infarction. It accounts for over 40- pressure/area - ↓ Cardiac output/Cardiac 60% of in-hospital mortality within the first 30 days8- Cardiac output/Cardiac index - ↓↓ 11. Cardiovascular collapse is due to loss of contractile index - ↑ Ejection fraction - ↓ myocardium causing left ventricular (LV) dysfunction, Ejection fraction - ↑ Regional wall motion further aggravated by a systemic inflammatory abnormalities response with refractory vasodilation and myocardial Valvular abnormalities (i.e depression. ST segment elevation myocardial mitral regurgitation) infarction (STEMI) accounts for most cardiogenic shock; other causes include acute mitral regurgitation, Transesophageal echocardiography (TEE) ventricular septal defect, cardiac rupture/tamponade, distinguishes between anaphylaxis and cardiogenic 12-15 dysrhythmias, and type 1 aortic dissection . shock. Intraoperative assessment of regional wall Differentiation of hypotension secondary motion abnormalities and LV end-diastolic and to anaphylactic versus cardiogenic shock can be end-systolic diameters (LVEDid and LVESid) can difficult intraoperatively. Severe hypotension, differentiate conditions of decreased LV preload and HYPOTENSION ON INDUCTION 625 afterload versus myocardial dysfunction. Also seen are performance. Vasodilators (nitroglycerin and decreased stroke volume (SV) and ejection fraction nitroprusside) alter loading conditions and enhance (EF), increased LV end-diastolic and end-systolic the effects of inotropes. Diuretics improve pulmonary area (LVEDA and LVESA), increased pulmonary edema and oxygenation/ventilation11,13,15. artery pressures, diastolic dysfunction and valvular Non-pharmacologic treatment options include abnormalities such as mitral regurgitation secondary to intra-aortic balloon pump (IABP) and left ventricular ischemia. TEE features of anaphylaxis are increased SV assist device (LVAD) but require residual LV mass. 3,17-19 and EF secondary to hyperdynamic LV function . Newer devices (i.e. Impella®) augment cardiac output, Both conditions require immediate cardio improve circulatory support and attenuate the systemic pulmonary resuscitation. Treatment of anaphylactic inflammatory response. Although these devices shock requires interruption of antigen contact by provide superior hemodynamic support, complications discontinuing causative agents and intravascular such as limb ischemia and bleeding increase13,14,21-23. volume expansion. Epinephrine is the drug of choice. Inhaled β2 agonists reverse bronchoconstriction. Conclusion H1- and H2- blockers and corticosteroids attenuate histamine-related adverse effects and prevent delayed Severe hypotension during anesthesia may be anaphylactic symptoms1,3,4,17,20. due to several causes. Accurate diagnosis is imperative Cardiogenic shock requires improvement of LV as the treatment required for cardiogenic shock function and circulatory support to maintain organ differs significantly from that necessary to reverse perfusion until coronary blood flow is reestablished anaphylaxis. via angioplasty, thrombolytic therapy or surgery. Inotropic drugs (epinephrine, dobutamine, dopamine Conflict of interest and phosphodiesterase inhibitors) improve myocardial None.

M.E.J. ANESTH 22 (6), 2014 626 Bhatt h. v., Frost e. a. m.

References

1. Mertes PM, and Laxenaire MC: Allergic reactions occurring during acute heart failure and cardiogenic shock: role of inotropic therapy. anaesthesia. Eur J Anaesthesiol; 2002, 19:240-62. Chest 1992, 102:626S-632S. 2. Tan A, Shephard B and Green D: Use of sophisticated intra- 14. Windecker S: Percutaneous left ventricular assist devices for operative monitoring in resuscitation of unexpected cardiovascular treatment of patients with cardiogenic shock. Curr Opin Crit Care; collapse during general anaesthesia. Int J Surg Case Rep; 2013, 2007, 13:521-7. 4:246-249. 15. Rude RE: Pharmacologic support in cardiogenic shock. Adv Shock 3. Beaupre PN, Roizen MF, Cahalan MK, Alpert RA, Cassorla L and Res; 1983, 10:35-49. Schiller NB: Hemodynamic and two-dimensional transesophageal 16. Menon V, White H, LeJemtel T, Webb JG, Sleeper LA and Hochman echocardiographic analysis of an anaphylactic reaction in a human. JS: The clinical profile of patients with suspected cardiogenic Anesthesiology; 1984, 60:482-4. shock due to predominant left ventricular failure: a report from 4. Soetens FM: Anaphylaxis during anaesthesia: diagnosis and the SHOCK Trial Registry. SHould we emergently revascularize treatment. Acta Anaesthesiol Belg; 2004, 55:229-37. Occluded Coronaries in cardiogenic shocK? J Am Coll Cardiol; 5. Mertes P and Laxenaire M: Allergy and anaphylaxis in anaesthesia. 2000, 36:1071-6. Minerva Anestesiol; 2004, 70:285-91. 17. Schummer W, Schummer C, Wippermann J and Fuchs J: Anaphylactic 6. Mertes PM, Laxenaire M and Alla F: Anaphylactic and shock: is vasopressin the drug of choice? Anesthesiology; 2004, anaphylactoid reactions occurring during anesthesia in France in 101:1025-7. 1999-2000. Anesthesiology; 2003, 99:536-45. 18. Vitarelli A and Gheorghiade M: Transthoracic and transesophageal 7. Laroche D, Namour F, Lefrançois C, Aimone-Gastin I, Romano A, echocardiography in the hemodynamic assessment of patients with Sainte-Laudy J, Laxenaire MC and Guéant JL: Anaphylactoid and congestive heart failure. Am J Cardiol; 2000, 86:36G-40G. anaphylactic reactions to iodinated contrast material. Allergy; 1999, 19. Vitarelli A, Luzzi MF, Penco M, Ciciarello F, Fedele F and 54 Suppl 58:13-6. Dagianti A: PVF velocity pattern in patients with heart failure: 8. Soetens F, Rose M and Fisher M: Timing of skin testing after transesophageal echocardiographic assessment. Cardiology; 1997, a suspected anaphylactic reaction during anaesthesia. Acta 88:585-94. Anaesthesiol Scand; 2012, 56:1042-6. 20. Schummer C, Wirsing M and Schummer W: The Pivotal Role of 9. Kern KB: ST-Segment Elevated Myocardial Infarction, Cardiac Vasopressin in Refractory Anaphylactic Shock. Anesth Analg; 2008, Arrest, and Cardiogenic Shock. JACC Cardiovasc Interv; 2013, 107:620-624. 6(2):126-7. 21. Cook S and Windecker S: Percutaneous ventricular assist devices 10. Singh M, White J, Hasdai D, Hodgson PK, Berger PB, Topol EJ, for cardiogenic shock. Curr Heart Fail Rep; 2008, 5:163-9. Califf RM and Holmes DR: Long-Term Outcome and its Predictors 22. Bahekar A, Singh M, Singh S, Bhuriya R, Ahmad K, Khosla S and Among Patients With ST-Segment Elevation Myocardial Infarction Arora R: Cardiovascular Outcomes Using Intra-Aortic Balloon Complicated by Shock. J Am Coll Cardiol; 2007, 50:1752-1758. Pump in High-Risk Acute Myocardial Infarction With or Without 11. GUSTO Investigators: Cardiogenic shock complicating acute Cardiogenic Shock: A Meta-Analysis. J Cardiovasc Pharmacol myocardial infarction: predictors of death. Global Utilization of Ther; 2012, 17:44-56. Streptokinase and Tissue-Plasminogen Activator for Occluded 23. Cheng JM, Uil den CA, Hoeks SE, van der Ent M, Jewbali LS, van Coronary Arteries. Am Heart J; 1999, 138:21-31. Domburg RT and Serruys PW: Percutaneous left ventricular assist 12. Rackley CE, Russell RO Jr, Mantle JA, and Rogers WJ: devices vs. intra-aortic balloon pump counterpulsation for treatment Cardiogenic shock. Cardiovasc Clin; 1981, 11:15-24. of cardiogenic shock: a meta-analysis of controlled trials. Eur Heart 13. McGhie AI and Golstein RA.: Pathogenesis and management of J; 2009, 30:2102-8. LETTER TO THE EDITOR

Anesthetic management of a patient after functional hemispherectomy using bilateral bispectral index monitoring

Shinichiri Kira* And Kentaro Okuda**

Keywords: bilateral bispectral index monitoring; epilepsy surgery; medically intractable epilepsy; cerebral blood flow.

Dear Editor,

We report the use of bilateral bispectral index (BIS) monitoring during the maintenance of general anesthesia in a patient who had previously undergone functional hemispherectomy, and propose bilateral BIS monitoring to ensure the safe conduct of general anesthesia in patients who have had epilepsy surgery. A 16-year-old woman with hypomelanosis of Ito (HI) was scheduled for surgical correction of a left wrist contracture and left cavus foot deformity under general anesthesia. She had left hemiplegia and right hemianopia, but otherwise normal cerebral function. At the age of 8 months she had undergone right functional hemispherectomy for medically intractable epilepsy caused by right hemimegalencephaly (HME), a recognized feature of HI. Nonetheless, she continued to take carbamazepine as anticonvulsant therapy. Laboratory tests revealed slight elevations in the serum concentrations of total cholesterol, creatine kinase, alanine transaminase, and γ-glutamyltransferase. Asymmetric BIS values were anticipated in view of the known right hemispheric lesion and asymmetric cerebrovascular anatomy (Figure 1). Thus, bilateral BIS monitoring was established using two BIS sensors and two BIS-VISTATM A-3000 monitors running algorithm version 4.0 (Covidien, Mansfield, MA) to titrate anesthetic depth and monitor intra-operative seizure activity. Bilateral BIS sensors were placed as described by Fudickar and colleagues1. A signal quality index of >50% was considered reliable. A regime of total intravenous anesthesia using propofol, rocuronium and remifentanil was chosen for anesthetic management. Ventilation was controlled to maintain normocapnia. Although a number of transient asymmetries between the right- and left- sided BIS values were observed, there were no significant differences (mean ± standard deviation: 43.8 ± 5.3 versus 44.9 ± 9.2; P = 0.15) during steady-state anesthesia. Surgery and anesthesia were concluded uneventfully, and the patient recovered without incident.

* MD, PhD, Division of Anesthesia, Medical Department, Beppu Developmental Medicine & Rehabilitation Center, Beppu, Japan. ** MD, PhD, Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Yufu, Japan. Corresponding author: Dr. S. Kira, Division of Anesthesia, Medical Department, Beppu Developmental Medicine & Rehabilitation Center, 4075-1 Tsurumi, Beppu, Oita 874-0838, Japan. Tel: +81-977-22-4185, Fax: +81-977-26-4171. E-mail: [email protected]

627 M.E.J. ANESTH 22 (6), 2014 628 Kira s., OKUDA K.

Fig. 1 Brain magnetic resonance imaging and angiography 2 months before scheduled surgery: a) T1-weighted sequence, axial view; b) asymmetric cerebral vasculature.

Epilepsy surgery, such as functional had reduced from baseline levels in the abnormal hemispherectomy, is indicated in children with cerebral hemisphere, but had increased in the normal medically intractable epilepsy caused by HME2. hemisphere4. The results of a SPECT study by Soufflet Cerebrovascular asymmetry may be evident after and colleagues suggest that changes in CBF before and epilepsy surgery and changes in cerebral blood flow after epilepsy surgery cannot easily be predicted5. In (CBF) are known to affect BIS values; however, we their case series, mean CBF in the cerebral hemisphere observed no significant differences between the right- affected by HME was decreased after surgery in 64% and left-sided BIS values during steady-state anesthesia but normal in 36% of cases, whereas the mean CBF in this case. Nevertheless, we have already experienced in the unaffected hemisphere was normal in 82% significant differences in BIS values when recorded and increased in 18% of cases. Consequently, it is on both sides during general anesthesia in a patient advisable to titrate anesthetic depth using bilateral BIS with Sturge-Weber syndrome who had previously monitoring to ensure the safe conduct of anesthesia in undergone hemispherotomy3. Chiron and colleagues patients who have had epilepsy surgery. reported changes in CBF after hemispherectomy in a child with HME: single photon emission computed Conflict of interest tomography (SPECT) showed that after surgery CBF None.

References

1. Fudickar A, Voss D, Serocki G, Jeckström W, Ambrosch P, hemispherotomy patient with Sturge-Weber syndrome. Anaesth Steinfath M, Bein B: Clinically relevant asymmetry of bispectral Intensive Care; 2013, 41:552-3. index during recovery from anaesthesia for ear-nose-throat surgery 4. Chiron C, Raynaud C, Jambaqué I, Dulac O, Zilbovicius M, Syrota in adults and children. Anaesthesia; 2011, 66:936-41. A: A serial study of regional cerebral blood flow before and after 2. Villarejo-Ortega F, García-Fernández M, Fournier-Del Castillo hemispherectomy in a child. Epilepsy Res; 1991, 8;232-40. C, Fabregate-Fuente M, Álvarez-Linera J, De Prada-Vicente 5. Soufflet C, Bulteau C, Delalande O, Pinton F, Jalin C, Plouin I, Budke M, Ruiz-Falcó ML, Pérez-Jiménez MÁ: Seizure and P, Bahi-Buisson N, Dulac O, Chiron C: The nonmalformed developmental outcomes after hemispherectomy in children and hemisphere is secondarily impaired in young children with adolescents with intractable epilepsy. Childs Nerv Syst; 2013, hemimegalencephaly: a pre- and postsurgery study with SPECT and 29:475-88. EEG. Epilepsia; 2004, 45:1375-82. 3. Kira S, Arai C: Bilateral bispectral index monitoring of a post- GUIDELINES FOR AUTHORS

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