Gronert G A, Michenfelder J D, Sharbrough F W, Milde J H
Anesthesiology. 1981 Aug;55(2):110-3. doi: 10.1097/00000542-198108000-00005.
The impact of tolerance on cerebral metabolism during prolonged pentobarbital-induced anesthesia was evaluated in 16 dogs. Cerebral metabolic rate for oxygen was calculated from direct measurements of venous blood flow rate and the difference in blood oxygen content between arterial and venous blood during four periods of continuous and unvarying deep pentobarbital anesthesia-0-3 hours, 3-6 hours, 12-15 hours, and 21-24 hours. During 0-3 h, the metabolic rate was 1.8-2.0 ml 02.100 g brain-1.min-1. This increased to 2.3-2.6 ml.100 g-1.min-1 during 3-6, 12-15, and 21-24 h. In all studies, the electroencephalogram indicated a constant deep burst-suppression level at 2-6 bursts/min, and blood pentobarbital levels were unchanged at 4.9-5.9 mg/dl throughout the entire period of anesthesia. The sustained increase in cerebral metabolism that occurred after 3 h and continued through 24 h of pentobarbital anesthesia is presumably due to tolerance. This was a phenomenon in which metabolism increased during steady deep anesthesia with unchanged blood levels of pentobarbital, rather than one in which greater blood levels were necessary to maintain the same level of anesthesia.