Enhanced sedative efficacy and delayed recovery in propofol anesthesia in a rat model of hepatic cirrhosis.

PURPOSE: The sedative efficacy of propofol anesthesia is enhanced in patients with hepatic cirrhosis. Establish a rat model to investigate the efficacy of propofol. METHODS: 100 healthy Sprague-Dawley rats were divided into three groups and administered Phenobarbital sodium, carbon tetrachloride and ethanol solution for 0 (control), 9 (mild cirrhosis, M1), or 12 (severe cirrhosis, M2) weeks to induce hepatic cirrhosis. Propofol was infused via the caudal vein and the ED50 of the sedative effect and the recovery time were assessed according to the loss and recovery of the righting reflex. The effect of propofol on circulating cells and platelets, blood biochemistry and neurotransmitter content of the brain were measured. RESULTS: Cirrhosis was achieved in 25 of 35 M1 and 27 of 45 M2 rats. The propofol ED50 was significantly lower in M1 and M2 (5.8 ± 1.2 and 4.8 ± 1.1 mg/kg, respectively) than in control rats (6.2 ± 1.1 mg/kg, P < 0.05), and the time to recovery of righting reflex was significantly longer in M1 and M2 (370.0 ± 108.2 s and 501.6 ± 100.1 s, respectively) than in control rats (275.0 ± 90.3 s, P < 0.05). In M1 and M2 rats white and red blood cell and platelet counts were reduced, but ALT and AST activity was increased. In M1 and M2 rats the cerebral content of Gly and GABA increased but Glu and Asp were reduced. CONCLUSION: The sedative efficacy of propofol anesthesia is enhanced in rats with hepatic cirrhosis, perhaps due to reduced hepatic functional reserve, enhancement of inhibitory neurotransmitters and reduction of excitatory neurotransmitters.