The Effects of High-Dose Fentanyl on Cerebral Circulation and Metabolism in Rats

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Abstract
There is considerable controversy with respect to the effects of narcotics on the cerebral blood flow (CBF) and the cerebral metabolic rate for O2 (CMRO2). The present study examined the effects of high doses of i.v. fentanyl (25-400 .mu.g/kg) on the CBF and CMRO2 in rats. Cerebral cortical blood flow and metabolism were measured using the 133Xe modification of the Kety-Schmidt technique. Fentanyl produced a dose-related decrease in both the CBF and the CMRO2. CBF and CMRO2 were maximally depressed by 50 and 35%, respectively, in rats given fentanyl 100 .mu.g/kg compared with N2O-O2 ventilated controls. The values for CBF and CMRO2 were 168 .+-. 15 ml .cntdot. 100 g-1 .cntdot. min-1 and 10.3 .+-. 0.7 ml .cntdot. 100 g-1 .cntdot. min-1, respectively in the N2O controls compared with 85 .+-. 3 ml .cntdot. 100 g-1 .cntdot. min-1 and 7.1 .+-. 0.1 ml .cntdot. 100 g-1 .cntdot. min-1 in animals receiving fentanyl 100 .mu.g/kg. Higher doses of fentanyl did not further decrease either CBF or CMRO2 (108 .+-. 12 ml .cntdot. 100 g-1 .cntdot. min-1 and 7.0 .+-. 0.4 ml .cntdot. 100 g-1 .cntdot. min-1, respectively for fentanyl 400 .mu.g/kg); however, seizure activity was noticed in about 25% of the rats receiving either 200 or 400 .mu.g/kg fentanyl. The seizures seemed to be related to the narcotic in that they could be abolished by injections of naloxone. The seizure activity appeared to increase the CMRO2 relative to animals who received the same dose of fentanyl but did not have seizures. The CBF was not affected. Narcotics in high enough doses evidently depress the CBF and CMRO2.