LAUSR

The selection of medications to facilitate safe emergency airway management (EAM) in critically ill patients poses a considerable challenge for clinicians. Concomitant shock, exhaustion of respiratory reserves, and aspiration risk conspire alongside anatomic and environmental challenges to introduce significant complexity. An ideal sedative hypnotic induction agent would offer a reliable and rapid onset of unconsciousness with limited hemodynamic trespass. Etomidate was approved for use in Europe in 1972 followed by the United States in 1983, and thus, its track record is considerable. Studies of the National Emergency Airway Registry have demonstrated that etomidate was administered for 91% of adult and 78% of pediatric rapid sequence inductions between 2002 and 2012 in participating emergency departments (1, 2). In a recent single-day multicenter observational study, etomidate was selected by critical care physicians for 55.9% of intubations (3). Clinical experience and investigational evidence suggest that etomidate offers a favorable hemodynamic profile even in hypotensive patients (4). As attention has been drawn to the association between postintubation hypotension and adverse clinical outcomes, hemodynamic stability should be considered an important goal among many competing priorities during EAM (5, 6). Substantial shock begets higher plasma concentrations of all drugs, and clinicians should consider the sage advice of Paracelsus (1493–1541), “all things are poison and nothing is without poison; only the dose makes a thing not a poison.” Considerable clinical acumen can be necessary to select a safe dose of any induction medication. In one study of a bundled airway management intervention, increased use of etomidate and ketamine versus other sedative agents was associated with more favorable hemodynamic outcomes, suggesting that these agents may have a forgiving therapeutic window in critically ill patients (7). This assertion is backed by a body of underappreciated investigations examining the influence of hemorrhagic shock on the clinical pharmacology of opioids and sedative hypnotic drugs. The conceptual model of a blood-brain circuit in hemorrhagic shock has been proposed, wherein perfusion to the viscera and other tissue beds is shunted; however, etomidate demonstrates little need for dose reduction in models of hemorrhagic shock (8). Furthermore, hemorrhagic shock does not appear to modify the brain’s sensitivity to etomidate (9). As an example to the contrary, propofol demonstrates not only increased plasma concentrations but also markedly increased potency through heightened cerebral sensitivity mediated by complex mechanisms such that dose reductions of more than 80% may be necessary (8, 10). These interactions appear to persist even after fluid resuscitation (11). Historical concerns regarding increased mortality in patients sedated with etomidate were first raised in a letter to the editor of The Lancet by Ledingham and Watt (12) in 1983. The authors had noted that mortality in trauma patients had almost doubled from 1969 to 1982 despite patients having insignificant differences in their injury severity scores and a lower median age. On closer examination of the subset of patients cared for between 1979 and 1982, those who were sedated with opiates and benzodiazepines experienced a 25% mortality rate, whereas patients sedated with opiates and etomidate experienced a 69% mortality rate. Subsequent studies evaluating the safety of etomidate in trauma patients have significant weaknesses, and clear guidance is impossible to glean despite impressive claims. For example, one retrospective study of 94 hypotensive blunt trauma patients undergoing field intubation associated etomidate’s use with greater incidence of both acute respiratory distress syndrome (ARDS) and development of multiple organ system failure (MOSF) (13). Although the cohorts of patients in this study are well matched, the examination of etomidate’s potential role in ARDS and MOSF was done through secondary analysis. Additionally, the selection of induction agent was not randomized and left to the provider to choose. Stepwise multivariate regression models of this study reveal Both authors: Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: [email protected] Etomidate Is a First-Line Induction Agent in Critically Ill Patients