Assessing the safety of midazolam: A comprehensive analysis of adverse events from FAERS

Abstract

Midazolam, a potent sedative from the benzodiazepine class, is widely used in anesthesia and intensive care, but it has been linked to severe and life-threatening cardiopulmonary adverse events (AEs). This study investigated real-world AEs associated with midazolam using data from the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS) from 2004 to 2024. Disproportionality analysis was performed using four signal detection methods—reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker—to assess midazolam-related AEs. A total of 2952 AE reports were identified, involving seven system organ classes, with 31 specific AEs meeting criteria across all four algorithms. Unexpected AEs not listed in the product label, such as seizure, coma, respiratory failure, anaphylactic shock, and hypothermia, were also observed, with most AEs occurring within the first 10 days of midazolam use. This pharmacovigilance study highlights the need for increased awareness of serious and unexpected AEs, including respiratory failure, anaphylactic shock, hypothermia, and metabolic acidosis, to promote safer use of midazolam in clinical practice.