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

OBJECTIVES

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.

METHODS

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.

RESULTS

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).

CONCLUSION

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.