MAKERERE UNIVERSITY COLLEGE OF HEALTH SCIENCES SCHOOL OF MEDICINE DEPARTMENT OF ANAESTHESIA AND CRITICAL CARE KETAMINE-MIDAZOLAM VERSUS MORPHINE-MIDAZOLAM FOR CONTINOUS PATIENT SEDATION IN INTENSIVE CARE UNITS IN UGANDA. A RANDOMISED CONTROLLED TRIAL. (#NCT03407404) NAMATA CHRISTINE MBChB (Mak) A DISSERTATION SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE AWARD OF THE DEGREE OF MASTER OF MEDICINE-ANAESTHESIOLOGY AND CRITICAL CARE- MAKERERE UNIVERSITY. TABLE OF CONTENTS DECLARATION ............................................................................................................................. i TABLE OF CONTENTS.................................................................................................................. ii DEDICATION ............................................................................................................................... v ACKNOWLEDGEMENTS. ............................................................................................................ vi LIST OF TABLES ........................................................................................................................ viii LIST OF FIGURES ........................................................................................................................ ix ACRONYMS AND ABBREVIATIONS ............................................................................................. x DEFINITIONS .............................................................................................................................. xi ABSTRACT ................................................................................................................................. xii CHAPTER ONE: INTRODUCTION ................................................................................................. 1 BACKGROUND ........................................................................................................................ 1 PROBLEM STATEMENT ........................................................................................................... 1 JUSTIFICATION ........................................................................................................................ 2 GENERAL OBJECTIVE .............................................................................................................. 2 SPECIFIC OBJECTIVES .............................................................................................................. 2 RESEARCH QUESTION ............................................................................................................. 3 CHAPTER TWO: LITERATURE REVIEW ........................................................................................ 4 Critical care illness and sedation ............................................................................................ 4 Sedation options, recommendations and usual care ............................................................ 4 About Ketamine ..................................................................................................................... 5 Ketamine use for continuous sedation in the ICU ................................................................. 6 Effects on vasopressor requirements, ICP, LOS ..................................................................... 7 CHAPTER THREE: RESEARCH METHODS .................................................................................... 8 Study design ........................................................................................................................... 8 Study setting and sites ........................................................................................................... 8 ii Target population ................................................................................................................... 8 Study population .................................................................................................................... 8 Selection criteria..................................................................................................................... 8 Randomization ....................................................................................................................... 9 Blinding ................................................................................................................................... 9 Allocation concealment .......................................................................................................... 9 Drug Preparation and Use. ..................................................................................................... 9 Participant follow up. ........................................................................................................... 10 Study Outcomes ................................................................................................................... 10 Primary outcomes ................................................................................................................ 10 Secondary outcomes ............................................................................................................ 10 Sample size ........................................................................................................................... 10 Distribution in the study sites .............................................................................................. 12 DATA MANAGEMENT ............................................................................................................... 12 Data collection...................................................................................................................... 12 Quality control ...................................................................................................................... 12 Data analysis ......................................................................................................................... 13 Data Safety and Monitoring Board. ..................................................................................... 13 Adverse event monitoring .................................................................................................... 13 Data dissemination ............................................................................................................... 14 ETHICAL CONSIDERATIONS ...................................................................................................... 15 LIMITATIONS ............................................................................................................................ 15 CHAPTER FOUR: STUDY RESULTS ............................................................................................. 17 Baseline characteristics. ....................................................................................................... 17 CHAPTER FIVE: DISCUSSION ..................................................................................................... 23 CONCLUSION ........................................................................................................................ 26 iii RECOMMENDATION ............................................................................................................. 26 REFERENCES ............................................................................................................................. 27 APPENDICES ............................................................................................................................. 30 APPENDIX I: STUDY COLLECTION TOOL................................................................................ 30 APPENDIX II: RICHMOND AGITATION-SEDATION SCORE ..................................................... 34 APPENDIX III: CONFUSION ASSESSMENT METHOD-INTENSIVE CARE UNIT (CAM-ICU) ...... 35 APPENDIX IV: THE MODIFIED EARLY WARNING SIGN SCORE .............................................. 36 APPENDIX IX: TIME FRAME .................................................................................................. 37 APPENDIX V: LETTER OF CONSENT....................................................................................... 38 TITLE: KETAMINE-MIDAZOLAM VERSUS MORPHINE-MIDAZOLAM FOR CONTINOUS PATIENT SEDATION IN INTENSIVE CARE UNITS IN UGANDA. A RANDOMISED CONTROLLED TRIAL. ......................................................................................................... 38 APPENDIX VI: ASSENT FORM 12 TO 14YRS ....................................................................... 40 APPENDIX VII: ASSENT FORM: 15 TO 17YRS ..................................................................... 43 APPENDIX VIII: TRANSLATED CONSENT FORMS ............................................................... 46 EKIWANDIIKO KYABAANA ABALI WAKATI WEMYAKA 15-17 EKYOKUKKIRIZA OKWETABA MU KUNOONYEREZA ........................................................................................................ 49 EKIWANDIIKO KYABAANA ABALI WAKATI WEMYAKA 12-14 EKYOKUKKIRIZA OKWETABA MU KUNOONYEREZA ........................................................................................................ 52 APPENDIX V: RUNYANKOLE CONSENT FORMS. ................................................................... 54 APPENDIX VI: ASSENT FORM 12 TO 14YRS ....................................................................... 57 ASSENT FORM: 15 TO 17YRS ...........................................................................................