Why do women wake up faster than men from propofol anaesthesia?

It has repeatedly been shown that female patients wake up faster from propofol anaesthesia than male patients. The reason for this is not clear. It is possible that female patients have a more rapid decline in plasma propofol concentration after termination of an infusion, or there could be gender differences in the sensitivity to propofol, making women wake up at higher concentrations. We tested the hypothesis that women wake up faster because of a more rapid decline in plasma propofol.

Sixty adult patients (30 female and 30 male; ASA I or II) undergoing lower limb surgery under regional anaesthesia, were enrolled in an open study. Propofol was given as the only hypnotic drug, administered by the plasma target control system (TCI) Diprifusor, titrated to bispectral index (BIS) values of 40-60. Blood samples for propofol measurements were taken just before the propofol infusion was stopped and when the patients woke up.

The female patients woke up faster than the male patients (5.6 vs 8.2 min, P=0.003). The plasma propofol concentration declined more rapidly in the women (P=0.02). An additional significant finding was that the TCI algorithm had a better fit for the women than for the men, with a median prediction error (MDPE) of 2% in the female patients compared with 40% in the male patients (P<0.001). At emergence the men had a significantly higher measured propofol concentration than the women (P=0.05).

The female patients had a more rapid decline in plasma propofol at the end of infusion. Gender differences in pharmacokinetics could explain the faster emergence for female patients after propofol anaesthesia, and gender differences in propofol sensitivity may also be present.