Impact of female sex on anaesthetic awareness, depth, and emergence: a systematic review and meta-analysis

Background: Suggested anaesthetic dose ranges do not differ by sex, likely because of limited studies comparing sexes. Our objective was to systematically synthesise studies with outcomes of unintended anaesthesia awareness under anaesthesia, intraoperative connected consciousness, time to emergence from anaesthesia, and dosing to achieve adequate depth of anaesthesia, and to compare between females and males.Methods: Studies were identified from MEDLINE, Embase, and the Cochrane library databases until August 2, 2022. Controlled clinical trials (randomised/non-randomised) and prospective cohort studies that reported outcomes by sex were included. Results were synthesised by random effects meta-analysis where possible, or narrative form.Results: Of the 19 749 studies identified, 64 (98 243 participants; 53 143 females and 45 100 males) were eligible for in-clusion, and 44 citations contributed to meta-analysis. Females had a higher incidence of awareness with postoperative recall (33 studies, odds ratio 1.38, 95% confidence interval [CI] 1.09-1.75) and connected consciousness during anaes-thesia (three studies, OR 2.09, 95% CI 1.04-4.23) than males. Time to emergence was faster in females, including time to eye-opening (10 studies, mean difference -2.28 min, 95% CI -3.58 to -0.98), and time to response to command (six studies, mean difference -2.84 min, 95% CI -4.07 to -1.62). Data on depth of anaesthesia were heterogenous, limiting synthesis to a qualitative review which did not identify sex differences. Conclusions: Female sex was associated with a greater incidence of awareness under general anaesthesia, and faster emergence from anaesthesia. These data suggest reappraisal of anaesthetic care, including whether similar drug dosing for females and males represents best care. Systematic review registration: PROSPERO CRD42022336087.

Automated summary

This study systematically reviewed the literature on the dose ranges and intraoperative consciousness in females and males. It found that females had a higher incidence of postoperative awareness and intraoperative connected consciousness, as well as a faster emergence from anaesthesia compared to males. These findings suggest the need for reevaluation of drug dosing for females and males in anaesthetic care.