Division of Anaesthesiology, Department of Anaesthesiology, Intensive Care and Clinical Pharmacology, Geneva University Hospitals, Geneva, Switzerland.
Eur J Anaesthesiol. 2012 Nov;29(11):511-4. doi: 10.1097/EJA.0b013e32835819ca.
Etomidate is an imidazole-derived hypnotic agent preferentially used for rapid sequence induction of anaesthesia because of its favourable haemodynamic profile. However, 11β-hydroxylase inhibition causes adrenal insufficiency with potentially fatal consequences in specific populations. We review the arguments against the liberal administration of etomidate in critically ill, and especially septic, patients. This review considered only high-quality and prospective studies with a low risk of bias. Three major effects have been observed with the clinical use of a single dose of etomidate. First, independent of the clinical setting, etomidate causes adrenal dysfunction via 11β-hydroxylase inhibition ranging from 12 to 48 h, making the drug unsuitable for use in elective interventions. Second, in a systematic review with meta-analyses, including 3715 septic patients, the relative risk of death with etomidate was 1.22 (95% confidence interval 1.11 to 1.35). Based on this statistically significant and clinically relevant increase in mortality, a single dose of etomidate has to be avoided in patients with septic shock. Third, in small randomised controlled trials, a single dose of etomidate in trauma patients was associated with an increased incidence of pneumonia (56.7 vs. 25.9% in controls), prolonged intensive care stay (6.3 vs. 1.5 days) and prolonged hospital stay (11.6 vs. 6.4 days). Based on these randomised controlled trials, the use of etomidate should be avoided in unstable trauma patients. Midazolam and ketamine are two valid alternatives with similar intubation and haemodynamic conditions as etomidate but without its adverse effects. Therefore, for safety reasons, etomidate should be avoided in the critical conditions of sepsis and trauma.
依托咪酯是一种咪唑衍生物类催眠药物,由于其血流动力学特性,优先用于快速序贯诱导麻醉。然而,11β-羟化酶抑制可导致肾上腺皮质功能不全,在特定人群中可产生致命后果。我们回顾了反对在危重病患者,特别是脓毒症患者中自由使用依托咪酯的论据。本综述仅考虑了高质量和前瞻性研究,这些研究的偏倚风险较低。单次使用依托咪酯可观察到三大临床效应。首先,独立于临床环境,依托咪酯通过 11β-羟化酶抑制导致肾上腺功能障碍,作用时间为 12-48 小时,使其不适合用于择期干预。其次,在一项纳入 3715 例脓毒症患者的系统评价和荟萃分析中,依托咪酯组的死亡相对风险为 1.22(95%置信区间 1.11 至 1.35)。基于这一统计学显著且具有临床意义的死亡率增加,脓毒性休克患者应避免使用依托咪酯单次剂量。第三,在小型随机对照试验中,创伤患者单次使用依托咪酯与肺炎发生率增加相关(依托咪酯组为 56.7%,对照组为 25.9%),重症监护停留时间延长(6.3 天 vs. 1.5 天),住院时间延长(11.6 天 vs. 6.4 天)。基于这些随机对照试验,依托咪酯不应在不稳定创伤患者中使用。咪达唑仑和氯胺酮是两种有效的替代药物,具有与依托咪酯相似的插管和血液动力学条件,但没有其不良反应。因此,出于安全考虑,依托咪酯应避免用于脓毒症和创伤的危急情况。