Dynamic aspects on acute tolerance to hexobarbital evaluated with an anesthesia threshold.

Induction of acute tolerance was studied with hexobarbital in male rats. A threshold technique utilizing an EEG-criterion consisting of a burst suppression of 1 second or more (the SS) was used both to induce and maintain anesthesia. Hexobarbital was infused with an optimal dose rate of 15 mg/kg/min. The infusion was stopped at the criterion and restarted when no SS had been seen for 1 min. The doses of hexobarbital needed to maintain anesthesia were fairly constant around 3.5 mg/kg/min up to durations of 120 min which indicates that redistribution of hexobarbital is of minor importance in the present experiments. After different predetermined times of this fairly stable anesthesia, the rats were sacrificed, and concentrations in the cortex of the brain were determined with a HPLC-method. Maximal induction of acute tolerance was seen as a 45 percent increase in cortex concentration after 60 min of anesthesia, but already after 10 min a slight acute tolerance was recorded.