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

Abstract

Relationships between plasma concentrations of fentanyl and its analgesic, respiratory and cardiovascular effects were determined in unanesthetized dogs. To avoid drug interactions the authors used trained unanesthetized spontaneously breathing dogs. After a control period in the awake state, fentanyl was injected in increasing amounts (2.5, 5, 20, 40, and 100 μg/kg) at 5-min intervals to a cumulative dose of 167.5 μg/kg administered over 20 min and its effects studied on pain responses (heart and blood pressure changes and somatic responses to tail clamping), respiration (respiratory rate, oxygen consumption, blood gas tensions), and circulation (heart rate and blood pressure). Plasma concentration/effect curves were derived by relating the changes in variables from the awake state to the corresponding plasma concentration (range 2-453 ng/ml). Maximum effects occurred at plasma concentrations at and around 30 ng/ml. Oxygen consumption decreased only slightly and remained well above the basal metabolic rate. Cardiac output, heart rate, respiratory rate, and arterial oxygen tension were almost halved during the full action of fentanyl. In dogs, fentanyl's analgesic action cannot be separated from its respiratory and cardiovascular effects. All receptor-mediated effects are maximal at the same plasma concentration, a phenomenon suggesting saturation of the opiate receptors.