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“COMPARISON OF NALBUPHINE WITH 0.125% BUPIVACAINE AND PLAIN 0.125% BUPIVACAINE IN THORACIC EPIDURAL FOR POST OPERATIVE ANALGESIA IN UPPER ABDOMINAL SURGERY” Dissertation Submitted in Partial fulfilment of the University regulations for M.D. DEGREE EXAMINATION -MAY 2019 MD DEGREE IN ANAESTHESIOLOGY (BRANCH X) GOVERNMENT THENI MEDICAL COLLEGE, THENI THE TAMIL NADU DR. M.G.R. MEDICAL UNIVERSITY CHENNAI, TAMILNADU CERTIFICATE This is to certify that the dissertation titled “Comparison Of Nalbuphine With 0.125% Bupivacaine And Plain 0.125% Bupivacaine In Thoracic Epidural For Post Operative Analgesia In Upper Abdominal Surgery” is a Bonafide original work done by DR.M.SUBHASHINI during May 2016-May 2019 in partial fulfilment of the requirements for M.D. (Anaesthesiology) Branch X- Examination of the Tamilnadu Dr.M.G.R. Medical University to be held in May 2019. Prof. DR.S.VIJAYA, Prof. DR.S.VIJAYARAGAVAN, M.D., M.D., D.A., Professor and Guide, Professor and HOD, Department of Anaesthesiology, Department of Anaesthesiology, Govt. Theni Medical College, Govt. Theni Medical College, Theni. Theni. Prof. DR.K.RAJENDRAN, M.S.,D.Ortho., Dean, Govt. Theni Medical College, Theni. DECLARATION I DR.M.SUBHASHINI solemnly declare that this dissertation, titled “Comparison Of Nalbuphine With 0.125% Bupivacaine And Plain 0.125% Bupivacaine In Thoracic Epidural For Post Operative Analgesia In Upper Abdominal Surgery” is a Bonafide record of work done by me in the Department of Anaesthesiology, Govt. Theni Medical College and Hospital, Theni under the guidance of Prof. DR.S.VIJAYA, M.D., Professor of Anaesthesiology, Govt. Theni Medical College & Hospital, Theni. This dissertation is submitted to the Tamilnadu Dr.M.G.R. Medical University, Chennai in partial fulfilment of the University regulations for the award of degree of M.D. (Anaesthesiology), Branch X- examination to be held in MAY- 2019. Place: Theni Date: DR.M.SUBHASHINI ACKNOWLEDGEMENTS I wish to express my sincere thanks to The Dean, Govt. Theni Medical College, Theni for having kindly permitted me to do my study in this institution. I take great pleasure in expressing my deep sense of gratitude to Prof. DR.S.VIJAYARAGAVAN, M.D., D.A., Professor and Head of the Department of Anaesthesiology, Govt. Theni Medical College, Theni for his motivation, constant supervision and for providing all necessary arrangements for the conduct of the study, without which this dissertation would not have been materialized. I would like to place on record my indebtedness to my guide Prof. DR.S.VIJAYA, M.D., Professor of Anaesthesiology, Govt. Theni Medical College, Theni for her constant encouragement, constructive criticism and suggestions throughout the period of the study. I express my profound thanks to Prof. DR. KANNAN BOJARAAJ, M.D., D.A., and Prof. DR.M. BALASUBRAMANI, M.D., D.A., Associate Professors of Anaesthesiology, Govt. Theni Medical College, Theni for their whole hearted help and support in doing this study. I am extremely thankful to DR.M.SAKUNTALA, M.D., Assistant Professor of Anaesthesiology, Govt. Theni Medical College, Theni for her valuable advice and appropriate guidance to complete this study. I thank all the Assistant Professors and Senior Residents of Department of Anaesthesiology for their keen interest and encouragement during this study. I thank all the Professors, Assistant professors and Senior Residents in the Department of Surgery, Govt. Theni Medical College, Theni for their help and support during the course of the study. I thank the members of the Ethical Committee for permitting me to do the study. I also wish to thank all my colleagues for their constant help during this study. My thanks are due to all the theatre personnel for their willing cooperation and assistance. I am deeply grateful to all the patients included in the study, for their whole hearted co-operation in spite of their illness which made this study possible. CONTENTS SERIAL NO. CHAPTERS PAGE NO. 1. INTRODUCTION 1 2. HISTORY 2 3. EPIDURAL SPACE – ANATOMICAL 5 CONSIDERATION/TECHNIQUES 4. PHARMACOLOGY 38 5. REVIEW OF LITERATURE 47 6. AIM OF THE STUDY 56 7. MATERIALS AND METHODS 56 8. OBSERVATION AND RESULTS 61 9. DISCUSSION 90 10. CONCLUSION 97 11. ANNEXURES: BIBLIOGRAPHY I PLAGIARISM /ETHICAL COMMITTEE II/III CERTIFICATE IV PROFORMA V MASTER CHART 1 INTRODUCTION: Acute uncontrolled post-operative pain and the pathophysiological response to surgery by stimulation of autonomic nervous system leads to stress responses causing significant adverse effects and complications to multi organ systems. The important goal is to reduce the postoperative pain and discomfort .Controlling pain is a multimodal approach with the use of various pharmacological agents (opioids and non-opioids), by different routes (intravenous vs regional techniques) with minimal incidence of adverse effects. In the above setting, Thoracic Epidural Analgesia (TEA) remains the mainstay of treatment in the management of perioperative pain in upper abdominal surgeries. Advantages of epidural analgesia being the ability to provide prolonged duration of analgesia, minimal adverse effects than with systemic opioids, less haemodynamic changes, improved lung function, minimal gastrointestinal complications (paralytic ileus), early mobilisation and better patient satisfaction. Nalbuphine is an agonist antagonist opioid related chemically to oxymorphone and naloxone. Acts as µ(mu) antagonist and kappa agonist with analgesic potency equal to that of morphine. Its rapid onset and longer duration of action and less cardiovascular and respiratory side effects makes it a better choice in postoperative analgesia. 2 In this study, we attempted to define the haemodynamic, analgesic profile and efficacy of Nalbuphine as an additive to Bupivacaine in thoracic epidural for postoperative analgesia in upper abdominal surgeries. HISTORY: The term extradural, peridural and epidural are synonymous, with a greek and latin origin. The epidural space, consisting of fat and blood vessels lies between the dural envelope of the spinal cord and bony walls of spinal canal and is approached either between the two lamina of adjacent vertebral arches - the “spinal” epidural route, or through sacral hiatus – the “caudal” approach. CORNING1 in 1885 was the first to use epidural analgesia. He hypothesised that, “medications injected within the spinal canal will be taken up by the rich plexus of blood vessels around the spinal cord and carried into the substance of spinal cord, allowing direct medication of the cord, that is used for treatment of neurological disease and provide surgical analgesia”. However, from the descriptions of his two experiments, it is evident that he did not achieve a genuine epidural injection. In 1901, JEAN ATHANASE SICARD2-3 and FERNAND CATHELIN of France popularised caudal/ peridural approach. MARIN THÉODORE TUFFIER4in the same year, attempted Epidural analgesia by use of Lumbar approach but lacked success. 3 In 1911, LAWEN5, emphasised caudal route to be the only safe approach to the epidural space, which limited the spread of drug to the area supplied by cauda equina. Only in 1912, FILDES PAGES6 renewed the mid lumbar approach, because of its easy access and wide applicability. He invented the “PAGES method” of identifying epidural space – a “tactile feel” of the needle obtained on piercing ligamentum flavum. In 1913 HEILE7, revived the idea of epidural block by entering the spinal canal laterally through the intervertebral foramina instead of midline puncture. In 1930’s, ARCHILE MARIO DOGLIOTTI8-10, with the evidence from Jansen’s, “discovery of negative pressure in the epidural space”, described a practical technique for administering lumbar segmental anaesthesia. With Dogliotti’s work as foundation, in 1932,GUTIERREZ11 described the “hanging drop technique” to identify the epidural space. All these works were poorly understood and with the advent of neuromuscular blocking agents in 1946, and much satisfactory muscle relaxation with general anaesthesia alone, there was a rapid decline in use of regional techniques for anaesthesia and analgesia. Epidural analgesia managed to escape this crisis by the introduction of Tuohy needles and indwelling epidural catheters. With technical refinements it was 4 made possible to maintain analgesia intermittently or continuously for long periods of time. EUGENE ABUREL12 placed a silk ureteral catheter in the epidural space and used for analgesia for women in labor. During World War II in America in 1941, ROBERT HINGSON13 was assigned to care for the pregnant wives of United States Coast Guard seamen. Hingson used Lemmon’s malleable needle and placed it sacrally, deep to the peridural ligament and administered drugs continuously. This safe and effective method of producing painless childbirth became popularly known as “continuous caudal anaesthesia”. In 1949, MANUEL MARTINEZ CURBELLO14-15, modified a silk catheter for continuous spinal anaesthesia and inserted it into the lumbar epidural space, producing the first continuous epidural block. By 1962, the first polyvinyl catheter16 with a closed tip was introduced, making the continuous epidural block much more accurate and easier to perform. The First use of epidural morphine for analgesia was reported by BEHAR17 in 1979.This technique had given advantage over muscle relaxants in producing analgesia and maintaining voluntary function of the patient. And then the debate between DE-EFFERENTATION (endotracheal intubation with muscle relaxants - artificial ventilation

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