Sex effects on behavioral markers of emergence from propofol and isoflurane anesthesia in rats

Clinical studies have demonstrated sex-related differences in recovery from surgical anesthesia. This study aimed to characterize the emergence pattern following two anesthesia regimens in both sexes of rats. We considered six different markers of emergence from anesthesia: sigh, eye blinking, forelimb movement, mastication, neck extension, and recovery of the righting reflex (RORR). Spontaneous motor activity 24 h after the anesthesia induction was also examined. Our results showed that the rank order of the emergence latency after intraperitoneal propofol, PRO, exposure was forelimb movement < sigh < blink < mastication < neck extension < RORR, while after inhaled isoflurane, ISO, anesthesia the sequence was changed as sigh < blink < mastication < forelimb movement < neck extension < RORR in both male and female rats. Moreover, the latency to emergence after PRO in female rats was significantly higher than male rats, although following ISO there was no difference between the sexes (P < 0.001; P > 0.05, respectively). Open-field testing revealed no difference in PRO and ISO spontaneous locomotor activity due to drug administration (P > 0.05). These two anesthetics presented different emergence sequences. Although clinical data suggests that females arouse faster than males from anesthesia with propofol, our intraperitoneal technique in a rodent model had the opposite effect. Pharmacokinetic analysis demonstrated increased absorption of injected propofol for the female rats in our study, emphasizing the role of sexual dimorphism in drug distribution in rodents. Despite these pharmacokinetic differences, the pharmacodynamic effects of the drugs were remarkably consistent among both sexes through emergence.