Sex-based differences in perioperative hypersensitivity: A systematic review and meta-analysis

Perioperative hypersensitivity (POH) is a rare, immediate hypersensitivity reaction. Its more severe form, perioperative anaphylaxis, has a 2% mortality rate. Sex is a biological variable that can affect the immune response, but its role in POH remains unclear. We aimed to assess sex-based differences in POH and explore potential differences by age, culprit drugs, and reaction severity.

To systematically assess sex-based differences in the proportion of POH and assess variations by age group, suspected culprit drugs, and reaction severity.

A systematic search was conducted in MEDLINE, EMBASE, Scopus, and Web of Science. Cohort, retrospective, prospective, and cross-sectional studies reporting the female-to-male ratio of POH patients were included. A proportional meta-analysis using an inverse-variance method with logit transformation was performed to calculate pooled sex proportions. Subgroup analyses were conducted based on age, culprit drugs, and severity grading.

A total of 62 studies comprising 19,944 patients (63% female) were included. The pooled proportion of female-to-male patients with POH was 0.60 (95% CI: 0.57-0.63; 95% prediction interval: 0.40-0.78). Subgroup analysis revealed a higher female predominance in adults, 0.59 (95% CI: 0.55-0.62), whereas males predominated in pediatric studies (0.41; 95% CI: 0.36-0.47).

We found a female predominance of POH overall, though males had a higher proportion in pediatric studies, possibly due to chromosomal factors influencing POH rates before adolescence. In adulthood, hormonal changes may contribute to the observed female predominance. Further research is needed to explore the mechanisms behind the observed differences.