Propofol and bradycardia: causation, frequency and severity.

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 A systematic search for any type of report, published and unpublished, was made to review the evidence that propofol increases the risk of bradycardia, asystole and death from bradycardic events.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.