【期刊导读】单次剂量的Etomidate对皮质醇水平、病死率及医疗资源应用的影响

对该文的评论转载自黄教授的博客

http://huangwei98.blog.sohu.com/157001898.html

来自《Annals of emergency medicine》刊登了Canada学者有关静推依托咪酯对皮质醇水平、病死率以及医疗资源应用影响的系统综述——The Effect of a Bolus Dose of Etomidate on Cortisol Levels, Mortality, and Health Services Utilization: A Systematic Review：

Study objective:To synthesize the evidence on the effect of a bolus dose of etomidate on adrenal function, mortality, and health services utilization compared with other induction agents used for rapid sequence intubation.
Methods:We developed a systematic search strategy and applied it to 10 electronic bibliographic databases. We hand searched journals; reviewed conference proceedings, gray literature, and bibliographies of relevant literature; and contacted content experts for studies comparing a bolus dose of etomidate with other induction agents. Retrieved articles were reviewed and data were abstracted with standardized forms. Data were pooled with the random-effects model if at least 4 clinically homogenous studies of the same design reported the same outcome measure. All other data were reported qualitatively.
Results:From 3,083 titles reviewed, 20 met our inclusion criteria. Pooled mean cortisol levels were lower in elective surgical patients induced with etomidate compared with those induced with other agents between 1 and 4 hours postinduction. The differences varied from 6.1 μg/dL (95% confidence interval [CI] 2.4 to 9.9 μg/dL; P=.001) to 16.4 μg/dL (95% CI 9.7 to 23.1 μg/dL; P<.001). Two studies in critically ill patients reported significantly different cortisol levels up to 7 hours postinduction. None of the studies reviewed, nor our pooled estimate (odds ratio 1.14; 95% CI 0.81 to 1.60), showed a statistically significant effect on mortality. Only one study reported longer ventilator, ICU, and hospital lengths of stay in patients intubated with etomidate.
Conclusion:The available evidence suggests that etomidate suppresses adrenal function transiently without demonstrating a significant effect on mortality. However, no studies to date have been powered to detect a difference in hospital, ventilator, or ICU length of stay or in mortality.
对危重患者应用依托咪酯持最大反对意见的就是法国的Annane D同志——他2005年就说“ICU physicians should abandon the use of etomidate!（PMID:15750800）”。在2009年完成“The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock（PMID:19652948）”的研究后，他的结论是“We recommend clinicians demonstrate extreme caution in the use of etomidate in critically ill patients with septic shock”。可见他本人对依托咪酯是存在巨大的警惕的。

尽管上述系统综述没有发现依托咪酯对病死率的影响，但是上文对入选病例的病情程度并没有进行分级，因此对于研究结论应该辩证的看待。

这里我想说点题外话——著名学者与医药工业的关系。我们一般看见的都是这些著名学者与厂商的良好互动关系——无论国际和国内，药品或器械的良好的商业运作与推广依赖的都是这些著名学者的抛头露面，这个我不想多说。我想说的是如果某些学者，尤其是著名学者的发现可能导致某些产品严重受挫，甚至退市的话，那么情况就要复杂的很多。一个著名的例子就是心血管病专家Nissen与糖尿病药物罗格列酮的激烈碰撞，可以在我的blog看到相关内容。其实另外两个发生在危重病界的著名例子就是NIH的著名专家Natanson C与血红蛋白代用品的故事，以及AnnaneD与依托咪酯的故事。前者知道的不多，Natanson同志2008年在JAMA发的一篇荟萃“Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a meta-analysis” ,其结论是“Based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI”，也就是说现有证据足以证明这个玩意将导致死亡和心梗的风险显著增加——这直接导致了这个将近数亿元的产业顷刻间就要玩完了（这不是我说的，网上说的）！可惜的是Natanson C“一时大意”，荟萃发表的时候忘记公布自己可能存在的“经济冲突”，于是这个“小小的”纰漏产生的争议要比论文本身更具爆炸性。

另外一个就是Annane D与依托咪酯的纠葛，这个代谢迅速、对循环系统影响甚微的镇静药因为可疑的抑制肾上腺的副作用导致该药物的推广严重受限。

可见，成名立万之余，在坚持真理与增加营收之间还是存在不小的矛盾的，居高位者尤其如此。不过，能观人所未观，道人所未道的真正的“高人”又能有几？

http://www.annemergmed.com/article/S0196-0644(10)00103-4/abstract