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

Braithwaite, Hannah E.; Payne, Thomas J.; Duce, Nicholas; McCulloch, Tim; Loadsman, John A; Leslie, Kate; Webster, Angela C; Gaskell, Amy; Sanders, Robert D.

doi:10.1016/j.bja.2023.06.042

Cited by 14 publications

(8 citation statements)

References 85 publications

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“…The existence of sex differences in anesthetic sensitivity has been suggested by some previous clinical ( 23 , 37 ) and animal studies ( 43 , 44 , 46 ). However, a major limitation of the previous work was that the sex differences in anesthetic sensitivity were confounded by differences in drug absorption and elimination.…”

Section: Discussionmentioning

confidence: 82%

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Hormonal basis of sex differences in anesthetic sensitivity

Wasilczuk,

Rinehart,

Aggarwal

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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General anesthesia—a pharmacologically induced reversible state of unconsciousness—enables millions of life-saving procedures. Anesthetics induce unconsciousness in part by impinging upon sexually dimorphic and hormonally sensitive hypothalamic circuits regulating sleep and wakefulness. Thus, we hypothesized that anesthetic sensitivity should be sex-dependent and modulated by sex hormones. Using distinct behavioral measures, we show that at identical brain anesthetic concentrations, female mice are more resistant to volatile anesthetics than males. Anesthetic sensitivity is bidirectionally modulated by testosterone. Castration increases anesthetic resistance. Conversely, testosterone administration acutely increases anesthetic sensitivity. Conversion of testosterone to estradiol by aromatase is partially responsible for this effect. In contrast, oophorectomy has no effect. To identify the neuronal circuits underlying sex differences, we performed whole brain c-Fos activity mapping under anesthesia in male and female mice. Consistent with a key role of the hypothalamus, we found fewer active neurons in the ventral hypothalamic sleep-promoting regions in females than in males. In humans, we demonstrate that females regain consciousness and recover cognition faster than males after identical anesthetic exposures. Remarkably, while behavioral and neurocognitive measures in mice and humans point to increased anesthetic resistance in females, cortical activity fails to show sex differences under anesthesia in either species. Cumulatively, we demonstrate that sex differences in anesthetic sensitivity are evolutionarily conserved and not reflected in conventional electroencephalographic-based measures of anesthetic depth. This covert resistance to anesthesia may explain the higher incidence of unintended awareness under general anesthesia in females.

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Section: Discussionmentioning

confidence: 82%

“…Female sex was found to be a risk factor for awareness associated with postoperative recall in some studies ( 24 – 33 ) but not in others ( 34 – 36 ). A recent meta-analysis concluded that females are at higher risk of awareness with or without recall and emerge from the state of anesthesia faster than males ( 37 ).…”

mentioning

confidence: 99%

Hormonal basis of sex differences in anesthetic sensitivity

Wasilczuk,

Rinehart,

Aggarwal

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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“…However, when analyzing data from both inpatients and outpatients together, there was no observed variance in the occurrence of awareness and recall between patients who received benzodiazepine premedication and those who did not [12]. However, some researchers recommended using benzodiazepine when low doses of anesthetics are administered [3][4][5][6][7][8][9][10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

Incidence, Associated Factors, and Behavioral Consequences of Intraoperative Awareness and Dreams During General Anesthesia Among Adult Patients: A Prospective Cohort Study

Al Jabri,

Burad,

Al Moosa

2024

Cureus

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Background The intraoperative awareness with recall phenomenon involves the memory of intraoperative events. The reported incidence is 0.001%. Awareness is rare intraoperatively but has profound implications. This research aimed to study intraoperative awareness and dream experiences in the Omani population undergoing general anesthesia. Methods This prospective cohort study involving 300 adult patients was conducted at a tertiary-level hospital between July and December 2021. Awareness was assessed in the post-anesthesia care unit and then at home on the seventh day and one month telephonically using a modified Brice questionnaire. The study's primary outcome was the incidence of IOA and dreams in adult Omani patients undergoing GA. The secondary outcome was identifying the factors associated with intraoperative awareness and dreams under GA. Results In this study, the incidence of awareness was 0.3% while 7.6% of patients reported intraoperative dreams. The patient who experienced IOA underwent an endoscopic retrograde cholangiopancreatography under GA with neuromuscular blockade and had a prolonged recovery. A total of 49.33% developed psychological effects postoperatively; anxiety, irritability, fear of surgery, change in memory, and repetitive nightmares were the most common ones. Because of the limited sample size, no factor associated significantly with these outcomes was found. Conclusion This study observed a higher incidence of intraoperative awareness and dreams. Awareness might be due to prolonged recovery and the use of neuromuscular blocking agents, but a focused study is required to confirm this finding. The incidence of intraoperative dreams and postoperative psychological effects of GA was also high. It may be worth exploring these findings with larger population-based research.

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“…The paradigm of digoxin for the treatment of heart failure overall had initially missed the increased risk of mortality documented only for women [ 19 ]. A very recent meta-analysis on anesthesiology concluded on suggestion for potential re-appraisal of anesthetic care guidelines for doses, based on gender [ 20 ]. Early evidence based on publications in the New England Journal of Medicine across the years 1994 and 1999 revealed that only 14% of trials conducted gender-specific analyses, while the picture was not improved conditional on receipt of funding by the National Institutes of Health [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Gender-specific treatment effects and outcomes reported in orthodontic research. A cross-sectional empirical study

Kummer,

Eliades,

Koletsi

2023

European Journal of Orthodontics

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Aim To identify practices of assessment of gender effects in research articles in orthodontics and detect whether there were significant differences in the treatment effects on outcomes according to gender. Materials and Methods Four major orthodontic journals were sought over a 3-year period to identify publications which included assessment of gender effects on outcomes in their reporting. Data were extracted on the following characteristics: journal, year of publication, region of authorship, and study design. For the studies including reporting of gender effects, whether a significant effect existed was further documented. Additionally, for these studies, data were extracted on population, sample size per gender, treatment, comparison, outcome type, and nature and whether gender analysis was based on subgroup testing or included as a main effect. Descriptive statistics, cross-tabulations, univariable, and multivariable regression models were utilized as appropriate. Results A total of 718 research articles were eligible for inclusion out of a pool of 1,132 screened articles. Of those, 95 reported on any type of analysis on gender effects (95/718; 13.2%). In the 95 studies that reported assessment of gender effects, it was clear that the majority did not detect significant gender-related differences across the documented outcomes (range of frequency distribution for significant gender differences across all outcomes: 0–50%). Twenty-two articles overall (22/95; 23.2%) described a significant gender effect classified by outcome, 12 favoring female and 10 favoring male participants. Patterns of efficacy and adverse outcomes were schemed either favoring female (root resorption: 4/10; 40.0%, periodontal outcomes: 3/11; 27.3%) or male (cephalometric/growth changes following orthodontic treatment: 4/17; 23.5%) patients across the 22 studies with significant effects. Appropriately designed and adequately powered statistical analyses, with gender effect assessment as a main effect in a multivariable regression model was associated with 6.53 times higher odds for identifying significant gender effects (OR = 6.53; 95% CI: 2.15, 19.8; P = .001). Conclusions A very small proportion of research studies included gender effect assessment in their analyses. Of those, a quarter described significant effects. Nevertheless, careful analysis planning and strategies should be prioritized to allow for any meaningful interpretation.

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

Cited by 14 publications

References 85 publications

Hormonal basis of sex differences in anesthetic sensitivity

Hormonal basis of sex differences in anesthetic sensitivity

Incidence, Associated Factors, and Behavioral Consequences of Intraoperative Awareness and Dreams During General Anesthesia Among Adult Patients: A Prospective Cohort Study

Gender-specific treatment effects and outcomes reported in orthodontic research. A cross-sectional empirical study

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