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Arrhythmogenic potential of antiemetics: perspectives on risk-benefits

2003; Springer Science+Business Media; Volume: 50; Issue: 3 Linguagem: Inglês

10.1007/bf03017787

1496-8975

Donald R. Miller,

Anesthesia and Pain Management

ROPERIDOL has been used for the management of postoperative nausea and vomiting (PONV) for over three decades. Relatively low doses of this drug (0.6–1.2 mg iv) have been shown to be efficacious and costeffective as first- line therapy for PONV prophylaxis. 1 However, a recent strengthening of the “black box” warning from the Food and Drug Administration (FDA) and Canadian Therapeutics Products Directorate regarding the arrhythmogenic potential of droperidol have resulted in many hospitals deleting this antiemetic from their drug formularies. The regulatory warnings emphasize that rare but significant cardiac morbidity and mortality are associated with droperidol, and that even low doses of the drug should be used only when other “first-line” drugs fail. 2 The warnings that injectable droperidol should only be used in the hospital setting in order to allow for screening and monitoring of echocardiograms (ECG), that a 12-lead ECG must be done prior to drug administration to rule out prolonged QTc interval, and that the drug not be used as first-line therapy, will inevitably result in increased utilization of more expensive alternatives, despite rather limited and circumstantial evidence which led to the droperidol directives. The droperidol warnings arose from reports that this drug causes QT prolongation and polymorphic ventricular tachycardia (Torsade de Pointes). While the cardiovascular effects of high doses of this drug have been recognized for some time, many anesthesiologists have questioned the evidence leading to a decision implicating the low doses used for antiemesis in the practice of anesthesia. Using the Freedom of Information Act, Bailey et al. recently provided a summary of the relevant cases which were reported to the FDA during a four-year time period. 3 Of the 273 cases reporting adverse effects associated with droperidol, 127 serious adverse outcomes were identified in which patients experienced either death, prolonged hospitalization, or a life-threatening condition. However, a number of confounding factors were also identified, including amongst others, alcohol intoxication, suicide attempts, multi-organ dysfunction, and sepsis. Of 89 reported deaths, the dose of droperidol was 2.5 mg or less in just two deaths; whereas the majority of deaths involved droperidol doses between 25–250 mg (ten to 100 times higher than doses generally administered during the course of anesthesia). A total of five patients receiving droperidol 2.5 mg or less experienced either ventricular tachycardia or torsades with prolonged QT. Only one of these five cases was fatal. To date, there have been eight reported cases of sudden death associated with the use of droperidol with other agents in Canada. Interestingly, not a single case has been reported in the anesthesia literature of lowdose droperidol being associated with QTc prolongation, cardiac dysrhythmias or mortality in the perioperative setting. The single most important observation from the currently available droperidol data is not that dysrhythmias occurred (the electrophysiological effects of the drug are well documented), but rather that the frequency of dysrhythmias using “antiemetic doses” is extremely low. The actual frequency is impossible to determine, but one might estimate that if 8% of the Canadian population undergoes an operative procedure each year, and that if 25% of these individuals received droperidol in a dose < 1.25 mg iv, the number of “treatments” per year would be in excess of one half million. The corresponding frequency of ventricular tachycardia or torsades would therefore be extremely low, probably be less than 0.0005%. From the standpoint of patient safety, it is also important to consider that this drug is only administered in the perioperative setting in the presence of continuous electrocardiographic monitoring.