Alfentanil's analgesic, respiratory, and cardiovascular actions in relation to dose and plasma concentration in unanesthetized dogs

Abstract

Relationships between plasma concentrations of alfentanil and its analgesic, respiratory, and cardiovascular effects were determined in dogs. To avoid drug interaction, trained, unanesthetized, spontaneously breathing dogs were used. After a control period in the awake state, alfentanil was injected in increasing amounts (10, 20, 80, 160, and 320 μg/kg) at 5-min intervals to a total dose of 590 μg/kg administered over 20 min. The effects were observed on pain responses (heart rate and blood pressure changes and somatic reactions to tail clamping), respiration (respiratory rate, oxygen consumption [V̇(O2)], blood gas tensions) and circulation (heart rate and blood pressure). The plasma concentration-effect curves, derived by relating the changes in multiple variables from the awake state to the corresponding plasma concentrations (range 8-5079 ng/ml), plateaued at and around 200 ng/ml during the injection period but were displaced in parallel to two-fold higher concentrations during recovery, which resembles acute tolerance. At maximally effective analgesic concentrations, which precipitated profound cardiorespiratory slowing with conspicuous hypoxemia, the V̇(O2) of 4.4 ± 0.3 ml · kg-1 · min-1 corresponded with the calculated metabolic rate but increased to 6.3 ± 1.6 ml · kg-1 during recovery. The analgesic action of alfentanil, which cannot be separated from its depressant cardiorespiratory effects and maximally effective analgesic concentrations (between 200 and 400 ng/ml), apparently does not jeopardize the adequacy of tissue oxygenation in dogs.