Tramèr M R, Moore R A, McQuay H J
Nuffield Department of Anaesthetics, Oxford Radcliffe Hospital, Headington.
Br J Anaesth. 1997 Jun;78(6):642-51. doi: 10.1093/bja/78.6.642.
As part of the development of a model for the study of adverse events, we have investigated the risk of bradycardia with propofol. A systematic search for any type of report, published and unpublished, was made to review the evidence that propofol increases the risk of bradycardia, asystole and death from bradycardic events. Quantitative and qualitative analyses of data with different strengths of evidence were performed. Sixty-five published and 187 spontaneous reports to drug monitoring centres described with different strength of evidence a biological basis for propofol-induced bradycardia, 1444 bradycardias, 86 asystoles and 24 deaths. In controlled clinical trials, propofol significantly increased the risk of bradycardia compared with other anaesthetics (number-needed-to-harm 11.3 (95% confidence interval 7.7-21)). In paediatric strabismus surgery the number-needed-to-harm was 4.1 (3-6.7). One of 660 patients undergoing propofol anaesthesia had an asystole. The risk of bradycardia-related death during propofol anaesthesia was estimated to be 1.4 in 100,000. Data from the phase IV study of propofol did not agree with data from controlled studies. Propofol carries a finite risk for brady-cardia with potential for major harm. Study of adverse events should be made with systematically searched data and, in contrast with study of efficacy, not restricted to randomized, controlled trials.
作为不良事件研究模型开发的一部分，我们调查了丙泊酚导致心动过缓的风险。我们对已发表和未发表的各类报告进行了系统检索，以审查丙泊酚增加心动过缓、心搏停止及因心动过缓事件导致死亡风险的证据。对不同证据强度的数据进行了定量和定性分析。向药物监测中心提交的65篇已发表报告和187篇自发报告以不同证据强度描述了丙泊酚诱发心动过缓的生物学基础、1444例心动过缓、86例心搏停止和24例死亡。在对照临床试验中，与其他麻醉剂相比，丙泊酚显著增加了心动过缓的风险（伤害所需人数为11.3（95%置信区间7.7 - 21））。在小儿斜视手术中，伤害所需人数为4.1（3 - 6.7）。接受丙泊酚麻醉的660例患者中有1例发生心搏停止。丙泊酚麻醉期间与心动过缓相关的死亡风险估计为十万分之1.4。丙泊酚IV期研究的数据与对照研究的数据不一致。丙泊酚存在导致心动过缓的一定风险，且有造成重大伤害的可能性。不良事件研究应使用系统检索的数据进行，与疗效研究不同，不应局限于随机对照试验。
