Under the Drapes: Unmasking the Mechanisms and Clinical Diagnosis of Perioperative Hypersensitivity

Purpose of the review Perioperative hypersensitivity reactions are uncommon but potentially life-threatening complications of anaesthesia and remain a major concern in clinical practice. This review provides an updated overview of the mechanisms and aetiologies underlying perioperative hypersensitivity and examines contemporary diagnostic strategies for identifying the responsible agent. Emphasis is placed on the integration of clinical assessment with laboratory and functional testing to establish an accurate diagnosis and guide the selection of safe alternatives for subsequent anaesthetic procedures. Current evidence is complemented by the authors' extensive clinical experience in the field.New findings Recent advances have highlighted the complexity of perioperative hypersensitivity, encompassing both antigen-dependent and non-antigen-dependent mechanisms. Neuromuscular blocking agents, antibiotics, latex, and chlorhexidine remain among the most frequently implicated triggers, underscoring the importance of a systematic and comprehensive evaluation. A stepwise diagnostic strategy integrating in vitro assays, skin testing, basophil and mast cell activation tests, and, in selected cases, drug provocation testing can improve identification of the culprit agent and assessment of alternative drugs. The complementary use of these approaches, interpreted within the clinical context, is particularly important when conventional testing yields inconclusive results. Accurate identification of the cause of perioperative hypersensitivity is critical to preventing recurrent, potentially fatal reactions and ensuring safe future anaesthetic care. A structured diagnostic approach that combines detailed clinical evaluation with targeted immunological and functional testing enables individualised risk assessment and informed selection of alternative agents. Incorporating current evidence with clinical expertise can therefore optimise diagnostic accuracy and strengthen strategies for the prevention of recurrent perioperative hypersensitivity.