Contemporary local anaesthetic-associated adverse events and mortality: a pharmacovigilance analysis of a US reporting system.

Abstract

One hundred years after the American Medical Association's report on death from local anaesthetics, their contemporary lethality is not well characterised. We investigated local anaesthetic-associated deaths reported to the US Food and Drug Administration Adverse Event Reporting System from 1968 to 2023, comparing adverse events from local anaesthetics with adverse events from other drugs using the reporting odds ratio (ROR). We assessed the impact of professional society practice advisories about systemic toxicity on reporting of mortality from long-acting local anaesthetics and lidocaine. Finally, we extracted individual citations and conducted an exploratory analysis on cases of death. There were 22 050 total adverse events from local anaesthetics and 1473 reports of death. Compared with other agents, reports of death were lower for amide (ROR, 0.4; 95% confidence interval [CI], 0.37-0.42) and ester (ROR, 0.12; 95% CI, 0.09-0.16) local anaesthetics. Death from lidocaine was reported most frequently. After practice advisories, reporting of death from long-acting local anaesthetics decreased (ROR, 0.61; 95% CI, 0.46-0.83) compared with the previous 10 yr, whereas reporting of death from lidocaine remained unchanged (ROR, 0.95; 95% CI, 0.78-1.16). Reporting of death from lidocaine was similar to other agents over the past 5 yr (ROR, 0.95; 95% CI, 0.83-1.1). Citations identified high-dose lidocaine, nerve catheters, and high neuraxial anaesthesia as the primary contributors to death since 2010. Reporting of mortality from long-acting local anaesthetics decreased in the past decade but remained unchanged for lidocaine. The potential lethality of this ubiquitous local anaesthetic deserves further study.