Pharmaceutical Care Department, King Abdulaziz Medical City; and the King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Pharmacotherapy. 2012 May;32(5):475-82. doi: 10.1002/j.1875-9114.2012.01027.x. Epub 2012 Apr 9.
Etomidate is a potent imidazole hypnotic used widely in single doses in the rapid sequence intubation of critically ill patients with sepsis due to its presumed hemodynamic safety, fast onset, and short duration of action. However, the literature is conflicting regarding the hemodynamic advantages of etomidate over other induction agents, and its safety in this population is a matter of strong debate in the critical care community as the drug is associated with suppression of adrenal steroidogenesis, which can last up to 72 hours after a single dose, primarily through potent inhibition of the 11β-hydroxylase enzyme. However, the clinical impact of this adrenal suppressive effect is not certain. The use of continuous-infusion etomidate in critically ill patients was abandoned more than 20 years ago due to reports of increased mortality. Nevertheless, mortality data of single-dose etomidate are still controversial, with no strong evidence of benefit over other agents and a tendency toward harm (keeping in mind the limitations of the available literature). Proponents of single-dose etomidate use in patients with sepsis suggest that the increased mortality associated with etomidate is merely a reflection of the patients' severity of illness and not related to the drug itself, whereas others believe that the drug causes true harm and increases mortality in this population. In view of the lack of a clear clinical advantage of etomidate over other agents used in rapid sequence intubation, it would be prudent to favor other agents until further conclusive evidence of etomidate safety is available in critically ill patients with sepsis.
依托咪酯是一种强效咪唑类催眠药，由于其假定的血液动力学安全性、起效迅速和作用持续时间短，在脓毒症危重症患者的快速序贯插管中广泛应用于单次剂量。然而，关于依托咪酯与其他诱导剂相比在血液动力学方面的优势，文献存在争议，并且该药在该人群中的安全性是重症监护界争论的焦点，因为该药会抑制肾上腺皮质激素的生成，这种抑制作用可持续长达 72 小时，主要是通过对 11β-羟化酶的强烈抑制。然而，这种肾上腺抑制作用的临床影响尚不确定。由于连续输注依托咪酯会增加死亡率的报道，20 多年前就已经停止在危重症患者中使用。尽管如此，单次剂量依托咪酯的死亡率数据仍存在争议，没有强有力的证据表明其优于其他药物，反而有趋向于产生危害的趋势（需要注意现有文献的局限性）。在脓毒症患者中使用单次剂量依托咪酯的支持者认为，依托咪酯相关的死亡率增加仅仅反映了患者疾病的严重程度，与药物本身无关，而其他人则认为该药物确实会造成危害，并增加该人群的死亡率。鉴于依托咪酯在快速序贯插管中与其他药物相比没有明显的临床优势，在有进一步明确的依托咪酯安全性的证据之前，明智的做法是选择其他药物。
