Hypersensitivity Reactions to Benzodiazepines Used for Perioperative Premedication: A Narrative Review

Background: Hypersensitivity reactions to benzodiazepines, although uncommon, represent a clinically relevant issue in perioperative practice. Benzodiazepines are widely used medications with anxiolytic, sedative, and anticonvulsant properties. The objective of this review is to synthesize current knowledge on benzodiazepine hypersensitivity, focusing on underlying mechanisms, clinical manifestations, diagnostic considerations, and strategies for management and prevention in the perioperative setting. Methodology: A narrative synthesis of the current literature on hypersensitivity reactions to benzodiazepines was performed. The review included published case reports, case series, and clinical studies describing hypersensitivity reactions, their clinical presentation, and diagnostic approaches. Particular attention was given to both immunological and non-immunological mechanisms, reported clinical phenotypes, and issues relevant to perioperative patient safety. Results: The extant evidence suggests that benzodiazepine hypersensitivity may involve both immunological and non-immunological pathways. The spectrum of reported reactions encompasses mild cutaneous manifestations and severe systemic responses, although the incidence remains low. This review highlights diagnostic challenges related to variable clinical presentation and the limited availability of standardized testing methods. Conclusions: Although cases of benzodiazepine hypersensitivity are uncommon, awareness of potential reactions is critical for ensuring safe clinical practice. This review emphasizes the necessity for additional research to elucidate the underlying mechanisms, standardize the diagnostic criteria, and formulate management protocols.