Influence of naloxone on the increased sensitivity to propofol during hypovolemia in the rat

Objective: Hypovolemia has been shown to decrease the dose requirement for propofol, This increased effect has been explained partially by an increase d end organ sensitivity to the anesthetic effect of propofol, We used the o pioid blocking agent naloxone to test the hypothesis that endogenous opioid s may be involved in this increased sensitivity, Subjects: Thirty-two chronically instrumented rats were assigned randomly t o either the hypovolemia (n = 16) or the control (n = 16) group. Interventions: After pretreatment of each rat in the two groups with either intravenous saline (n = 8) or naloxone (3 mg/kg; n = 8), an intravenous in fusion of propofol (150 mg.kg(-1).hr(-1)) was given until 5 secs of electri cal suppression of the electroencephalographic signal was observed. Return of righting reflex was used to assess depth of anesthesia, and the propofol blood concentration was determined simultaneously with high-performance li quid chromatography, Measurements and Main Results: The mean propofol blood concentrations at th e return of righting reflex were significantly lower in the hypovolemic ani mals compared with the controls within both naloxone-treated (2.1 +/- 0.2 m ug/mL vs, 2.9 +/- 0.2 mug/mL; p <.01) and saline-treated (2.2 <plus/minus> 0.1 vs, 3.0 +/- 0.2 mug/mL; p <.01) rats, The mean concentrations were not different between the saline- and naloxone-treated rats either within the h ypovolemic group or within the control group. Conclusions: The results of our study indicate that it is unlikely that the increased end organ sensitivity to propofol during hypovolemia is mediated by endogenous opioids, because it was not reversed by naloxone.