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Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials
Institution:1. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy;2. School of Medicine, Vita-Salute San Raffaele University, Milan, Italy;3. Department of Intensive Care Medicine, Kameda Medical Center, Kamogawa, Japan;4. Division of Infectious Diseases, Department of Medicine, McGill University, Montreal, Quebec, Canada;1. Guy''s and St Thomas'' NHS Foundation Trust, St Thomas'' Hospital, London SE1 7EH, UK;2. Centre of Human Applied Physiological Sciences, King''s College London, London, UK;3. Department of Anesthesiology, University Medical Center of Göttingen, Germany;4. Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King''s College London, London, UK;5. Department of Anesthesiology and Intensive Care, ASST Santi e Paolo Hospital, University of Milan, Italy;1. Hôpital Béclère, Clamart, France;2. Hospices civils de Lyon, Lyon, France;3. Hospices civils de Strasbourg, Strasbourg, France;4. CHU de Lille, Lille, France;5. CHU de Caen, Caen, France;6. Hôpital Cochin, APHP, Paris, France;7. CH de Perpignan, Perpignan, France;8. CHU de Tours, Tours, France;9. CHU de Nantes, Nantes, France;10. CH de Narbonne, Narbonne, France;11. CHU de Dijon, Dijon, France;12. CHU de Saint Etienne, Saint-Etienne, France;13. CH de la Cote Basque, Bayonne, France;14. CHU de Nantes, Nantes, France;15. Hôpital Saint Joseph, Paris, France;16. Hôpital Saint Joseph, Paris, France;17. CH de Versailles, Versailles, France;18. CH de Saint Brieuc, Saint Brieuc, France;19. CHU de Nantes, Nantes, France;20. Hôpital Cochin, APHP, Paris, France;21. Ch de Libourne, Libourne, France;22. CH de Périgueux, Périgueux, France;23. CHU de Bordeaux, Bordeaux, France;24. CHU de Saint Etienne, Saint-Etienne, France;25. CHU de Dijon, Dijon, France;26. CHU de Besançon, Besançon, France;27. CH Alpes Léman, Annemasse, France;28. CHU de Nice, Nice, France;29. CH Delafontaine, Saint-Denis (93), France;30. CH Delafontaine, Saint-Denis (93), France;31. CHU de Caen, Caen, France;32. CH Delafontaine, Saint-Denis (93), France;33. CHU de Limoges, Limoges, France;34. CHU de Nantes, Nantes, France;35. CHU Raymond Poincarré, Garches, France;36. CHU de Grenoble, France;37. CH de Saint Brieuc, Saint Brieuc, France;38. CH de Chambéry, Chambéry, France;39. CH d''Alès, Alès, France;40. CHU de Nantes, Nantes, France;41. CHU de Saint Etienne, Saint-Etienne, France;42. CHU de Montpellier, Montpellier, France;43. CH de Quncy sous Sénart, Quincy sous Sénart, France;44. Hôpital Bichat, Paris, France;45. CHU de Nancy, Nancy, France;46. CHU de Caen, Caen, France;47. CH de Colmar, Colmar, France;48. CH de Colmar, Colmar, France;49. CHU de Rouen, Rouen, France;50. CH de Vendée, La Roche sur Yon, France;51. CH Delafontaine, Saint-Denis (93), France;52. CHJU de Reims, Reims, France;53. Hôpital Cochin, APHP, Paris, France;54. Hôpital Saint Joseph, Paris, France;55. CH de Perpignan, Perpignan, France;56. CHU Cochin, Paris, France;57. CHU de Nantes, Nantes, France;58. CHU de Grenoble, Grenoble, France;59. CHU de Poitiers, Poitiers, France;60. CHU de Nantes, Nantes, France;61. CHU de Nantes, Nantes, France;62. CHU de Nantes, Nantes, France;63. CH d''Annecy-Genevois, Annecy, France;64. CHU Bichat, Paris, France;65. CH de la Rochelle, La Rochelle, France;66. Hôpital Foch, Suresnes, France;67. CH de Metz, Metz, France;68. CHU d''Angers, Angers, France;69. CHU de Montpellier, Montpellier, France;70. CH de Saint-Nazaire, Saint-Nazaire, France;71. CHU de Montpellier, Montpellier, France;72. CHU Cochin, Paris, France;73. CHU de Toulouse, Toulouse, France;74. CH de Colmar, Colmar, France;75. CHU de Montpellier, Montpellier, France;76. CH Manchester, Charleville-Mézières, France;77. CHU Raymond Poincarré, Garches, France;78. CH d''Aix, Aix-en-Provence, France;79. CHU Avicennes, Bobigny, France;80. CHU de Lille, Lille, France;81. CHU de Nantes, Nantes, France;82. CH de Colmar, Colmar, France;83. CHU de Montpellier, Montpellier, France;84. CHU de Rennes, Rennes, France;85. CHU de Grenoble, Grenoble, France;86. CH de Vendée, La Roche sur Yon, France;87. CHU de Martinique, Fort-de-France, France;88. CHU de Grenoble, Grenoble, France;89. CH Annecy-Genevois, Annecy, France;90. Hôpital Saint-Louis, Paris, France;91. Hôpital Salpétrière, Paris, France;92. CHU de Bordeaux, Bordeaux, France;93. CHU de Nantes, Nantes, France;94. CH du Havre, Le Havre, France;95. Hospices civils de Lyon, Lyon, France;96. Hospices civils de Lyon, Lyon, France;97. Hôpital Saint Joseph, Paris, France;98. CHU de Strasbourg, Strasbourg, France;99. CHR d''Orléans, Orléans, France;100. Hôpital Laveran, Marseille, France;101. Hôpital Bichat, Paris, France;102. CHU de Grenoble Alpes, Grenoble, France;103. CHU de Rennes, Rennes, France;104. CHU de Fort de France, Fort de France, France;105. CHU de Nancy, Nancy, France;106. CH de la Cote Basque, Bayonne, France;107. CHU de Clermont-Ferrand, Clermont-Ferrand, France;108. CH Annecy-Genevois, Annecy, France;109. Hôpital Foch, Suresnes, France;110. CH de la Cote Basque, Bayonne, France;111. Hôpital Saint Joseph, Paris, France;112. CH d''Aix en Provence, Aix en Provence, France;113. Hôpital Delafontaine, Saint-Denis (93), France;114. Ch de Versailles, Versailles, France;115. CH de Périgueux, Périgueux, France;116. CHU de Limoges, Limoges, France;117. CHU Grenoble Alpes, Grenoble, France;118. Hôpital Raymond Poincarré, Garches, France;119. Hospices civils de Lyon, Lyon, France;120. Santé publique France, Saint-Maurice, France;121. CHU Grenoble Alpes, Grenoble, France;122. CHU de Poitiers, Poitiers, France;123. CHU Grenoble Alpes, Grenoble, France;124. Hôpital Bichat, Paris, France;125. CHU de Rennes, Rennes, France;1. Intensive care unit, Centre Hospitalier Yves Le Foll, Saint Brieuc, France;2. INSERM, CIC 1414, Rennes, France;3. Santé Publique France, Saint-Maurice, France;4. University Grenoble Alpes, Infectious diseases department, Grenoble, France;5. Infectious diseases department, CHU Ponchaillou, Rennes, France;1. Department of Medicine, McMaster University, Hamilton, Ontario, Canada;2. Farncombe Family Digestive Health Research Institute, McMaster University Hamilton, Ontario, Canada;3. Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada;4. Department of Health Research Methods, Evaluation and Impact, McMaster University, Canada;5. Department of Critical Care Medicine, Universite Laval, Quebec City, Quebec, Canada;6. Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia;7. Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Interdepartmental Division of Critical Care Medicine, University of Toronto, Canada;8. Departments of Critical Care Medicine and Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada;9. Division of Critical Care Medicine and Center for Health Evaluation and Outcome Sciences, St. Paul''s Hospital, University of British Columbia, Vancouver, British Columbia, Canada;10. Department of Surgery, Keenan Research Centre for Biomedical Research, University of Toronto, Toronto, Ontario, Canada;11. Departments of Critical Care Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada;12. Pharmacy Department, Hôpital du Sacré-C?ur de Montréal, Montréal, Quebec, Canada;13. Division of Critical Care Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada;14. Research Centre, Centre intégré universitaire de santé et de services sociaux du Nord-de-l''Île-de-Montréal, Faculté de Pharmacie, Université de Montréal, Canada;1. Department of Intensive Care, Austin Hospital, Melbourne, Australia;2. Department of Intensive Care, Northern Hospital, Melbourne, Australia;3. Department of Critical Care, University of Melbourne, Melbourne, Australia;4. Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia;5. Data Analytics Research & Evaluation (DARE) Center, University of Melbourne and Austin Hospital, Melbourne, Australia;6. Department of Critical Care Medicine, Hospital Israelita Albert Einstein, Sao Paulo, Brazil;1. Medical ICU, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Shuai Fu Yuan, Beijing 100730, China;2. State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, 1 Shuai Fu Yuan, Beijing 100730, China;3. Department of Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People''s Hospital, No. 100 Minjiang Road, Kecheng District, Quzhou, Zhejiang 324000, China;4. Department of Critical Care Medicine, The Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Guiyang, Guizhou 550004, China;5. Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Shinan District, Qingdao, Shandong Province 266003, China;6. Department of Intensive Care Unit, The Fourth Hospital of Hebei Medical University and Hebei Cancer Hospital, 12 Jiankang Road, Shijiazhuang, Hebei Province 050011, China;7. Department of Critical Care Medicine, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning Province 110004, China;8. Department of Critical Care Medicine, Shenzhen Second People’s Hospital, 3002 Sungang West Road, Futian District, Shenzhen, Guangdong Province 518035, China;9. Department of Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Bengbu, Anhui Province 233004, China;10. Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, 119 South Fourth Ring West Road, Fengtai District, Beijing 100070, China;11. Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China;12. Clinical Trial Center, West China hospital of Sichuan University, Chengdu, Sichuan Province, China;13. Clinical Research Center for Innovative Drugs, Tianjin Chasesun Pharmaceutical Co., Ltd., 20 Quan Fa Road, WuQing District, Tianjin 301700, China;1. Department of Anesthesiology and Intensive Care Medicine, Catholic University of The Sacred Heart, Rome, Italy;2. Anesthesia, Emergency and Intensive Care Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;3. Department of Internal medicine, Catholic University of The Sacred Heart, Rome, Italy;4. Respiratory Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy;5. Department of Obstetrics and Gynecology, Catholic University of The Sacred Heart, Rome, Italy;6. Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
Abstract:PurposeWe performed a meta-analysis of randomized controlled trials to evaluate if etomidate impacted mortality in critically ill adults when compared with other induction agents.Materials and methodsWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials which compared etomidate with any other induction agent in critically ill adult patients undergoing endotracheal intubation. The primary outcome was mortality at the main timepoint defined by the study. We conducted a fixed-effects meta-analysis for the risk ratio. Using that risk ratio and 95% confidence interval, we then estimated the probability of any harm (RR > 1) and the number needed to harm ≤100 (RR ≥ 1.05).ResultsWe included 11 randomized trials comprising 2704 patients. We found that etomidate increased mortality (319/1359 23%] vs. 267/1345 20%]; risk ratio (RR) = 1.16; 95% confidence interval (CI), 1.01–1.33; P = 0.03; I2 = 0%; number needed to harm = 31). The probabilities of any increase and a 1% increase (NNH ≤100) in mortality were 98.1% and 92.1%, respectively.ConclusionsThis meta-analysis found a high probability that etomidate increases mortality when used as an induction agent in critically ill patients with a number needed to harm of 31.
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