Acute Tolerance to Fentanyl during Anesthesia in Dogs

Abstract

The effect of fentanyl on increases in heart rate and mean arterial pressure elicited by electric stimulation of a branch of the radial nerve was studied in anesthetized, paralyzed and artificially ventilated dogs. In 1 group, a bolus of 100 .mu.g/kg of fentanyl depressed the evoked changes in heart rate and arterial pressure by 82 and 75%, respectively, by 5 min; recovery occurred within 90 min. A 2nd grou was given increasing bolus doses of fentanyl from 1.5 to 100 .mu.g/kg every 20 min for 200 min. The doses and interval were chosen to give a logarithmic increase in plasma concentration of fentanyl to include a final bolus dose of 100 .mu.g/kg and were predicted by a 2-compartment pharmacokinetic model derived from data of the 1st group. In the 2nd group, the bolus dose of 100 .mu.g/kg after 5 min had no significant effect on evoked cardiovascular responses. Over the following 2 h, the evoked changes in heart rate and arterial pressure increased above those preceding the 100 .mu./kg dose. An additional bolus dose of 100 .mu.g/kg given 2 h after the 1st did not depress the evoked reflexes below the control values. Tolerance to the effects of fentanyl can occur within 3 h, and for evoked responses to arterial pressure, rebound withdrawal effects can be seen within an additional 90 min.