Ketamine May Be Useful for Intubation in Critically Ill Patients

Ketamine is a safe, valuable alternative to conventional etomidate for use as a sedative during intubation in critically ill patients, according to the results of a randomized controlled, single-blind trial reported online in the July 1 issue of The Lancet. "Critically ill patients often require emergency intubation," write Patricia Jabre, MD, and colleagues from the KETASED Collaborative Study Group. "The use of etomidate as the sedative agent in this context has been challenged because it might cause a reversible adrenal insufficiency, potentially associated with increased in-hospital morbidity. We compared early and 28-day morbidity after a single dose of etomidate or ketamine used for emergency endotracheal intubation of critically ill patients." At 12 emergency medical services or emergency departments and 65 intensive care units in France, 655 patients requiring sedation for emergency intubation were prospectively enrolled and randomly assigned by a computerized random-number generator list to receive 0.3 mg/kg of etomidate (n = 328) or 2 mg/kg of ketamine (n = 327) for intubation. Group assignment was known to only the emergency medicine physician enrolling patients. The main outcome measure was the maximal score of the sequential organ failure assessment (SOFA) during the first 3 days in the intensive care unit. Analysis was by modified intent-to-treat, with exclusion from analysis of patients who died before reaching the hospital and those discharged from the intensive care unit earlier than 3 days. Data were analyzed for 234 patients in the etomidate group and 235 in the ketamine group. Both groups had statistically similar mean maximal SOFA scores (10.3 ± 3.7 for etomidate vs 9.6 ± 3.9 for ketamine; mean difference, 0.7; 95% confidence interval [CI], 0.0 - 1.4; P = .056). Both groups had a median intubation difficulty score of 1 (interquartile ratio, 0 - 3; P = .70) suggesting similar intubation conditions. Compared with the ketamine group, the etomidate group had a significantly higher percentage of patients with adrenal insufficiency (odds ratio, 6.7; 95% CI, 3.5 - 12.7). No serious adverse events occurred with either study drug. "Our results show that ketamine is a safe and valuable alternative to etomidate for endotracheal intubation in critically ill patients, and should be considered in those with sepsis," the study authors write. Limitations of this study include possibly insufficient power to show a significant increase in morbidity rates associated with etomidate use in patients with sepsis. In an accompanying comment, Dr. Volker Wenzel and Dr. Karl H. Lindner, from Innsbruck Medical University in Innsbruck, Austria, note that successful emergency intubation of critically ill patients depends on pharmacologic knowledge as well as manual skills and clinical experience. Unfortunately, tightening regulations of the European Union hinder trials of commercially noninteresting pathology such as multiple trauma. "We should be lobbying our parliamentary representatives to help with non-commercial research, otherwise industry lobbyists will continue pushing for rules that only global drug companies can comply with," Drs. Wenzel and Lindner write. "Should that occur, our fate would be similar to physicians in developing countries, who have many questions about optimising health care but cannot do clinical trials to find valid answers." The French Ministry of Health supported this study. The study authors and editorialists have disclosed no relevant financial relationships.  Lancet. Published online July 1, 2009.