Sex differences in propofol-induced loss of consciousness: a clinical study on effect-site concentration and...

Sex differences in propofol sensitivity have been reported, but their characterization remains inconsistent, particularly regarding their electroencephalographic (EEG) correlates. This study aims to elucidate sex-specific responses to propofol-induced loss of consciousness and to identify associated pharmacodynamic and EEG biomarkers for informing individualized clinical dosing.

Fifty-four surgical patients (28 males/26 females) undergoing elective procedures were enrolled in this prospective cohort study. Using the Schnider pharmacokinetic model, we administered target-controlled infusion of propofol with precise effector compartment targeting. Synchronized recordings of effect-site concentration (Ce) and prefrontal EEG activity were obtained at loss of consciousness (LOC) thresholds.

Pharmacodynamic analysis revealed a significant reduction in Ce of propofol at LOC in females compared with males (3.1 vs 4.0 μg·ml^-1). EEG analyses revealed sex-specific differences in neural oscillatory dynamics. Female participants exhibited enhanced alpha and delta oscillations. Sex-dependent coherence patterns were observed: male-predominant focal synchronization in the δ-θ band contrasting with female-biased distributed coherence across the θ-γ range. Both sexes exhibited comparable burst suppression indices (P > 0.05).

Our findings demonstrate that females exhibit greater sensitivity to propofol-induced unconsciousness, as evidenced by a lower effect-site concentration, distinct enhancements in alpha and delta oscillations, and modified high-frequency coherence. These biomarkers offer robust evidence for sex-specific propofol dosing strategies, improving precision in anesthesia depth management and potentially mitigating overdose and awareness risks in female populations.