ICU physicians should abandon the use of etomidate!

Excerpt

Etomidate is an imidazole derivative and a potent short-acting hypnotic that was introduced as an anesthetic drug about 30 years ago [1]. Because induction of anesthesia with etomidate had very few adverse effects on the cardiopulmonary system in either animals [2] or patients [3], this drug was considered the first-line agent for rapid sequence intubation [4]. Experiments with transgenic mice suggested that the favorable hemodynamic profile of etomidate is mediated by activation of α_2b-adrenoreceptors [5]. The stimulation of the vascular α-adrenoreceptors would result in a vasoconstriction that would counteract the hypotensive effects of the concomitant anesthetic agents. This α-agonist effect of etomidate may also explain the cardiovascular tolerance to etomidate in hypovolemic conditions [6]. Thus this drug has became very popular among intensive care physicians. They became alarmed almost 20 years ago, however, that prolonged sedation with etomidate caused excessively high death rates among critically ill patients similar to those with multiple trauma [7]. Subsequent investigations that have demonstrated marked suppression of adrenal function for several hours to 4 days following etomidate infusion [8] suggest that this drug-induced adrenal insufficiency accounts for the increased risk of dying from critical illness. Experiments using human adrenal cells provided some insights into the underlying mechanisms. Indeed, this drug exerts a dual effect, at low concentration it inhibits the 11 β-hydroxylase while at higher concentration 11-desoxycortisol concentrations are decreased, suggesting an inhibition of side-chain cleavage enzyme system [9]. Administration of etomidate is now well recognized as a cause of primary adrenal insufficiency and is no more used for prolonged sedation. However, intensive care physicians still believe that when this anesthetic agent is given as a single bolus for intubation the hormonal changes are very transient and clinically not relevant. In fact, in unstressed subjects or patients under stable condition the administration of about 0.3 mg/kg etomidate as a single intravenous injection inhibits the synthesis of major corticosteroid hormones for at least 5 h [10]. By contrast, the data about the duration and the clinical consequences of adrenal function suppression induced by a single dose of etomidate in critically ill patients are scarce. …