title: Cardiovascular, respiratory, and analgesic effects of fentanyl in unanesthetized rhesus monkeys.
abstract: To determine the suitability of the rhesus monkey as a model for investigation of opioids, we examined the analgesic, respiratory, and cardiovascular effects of fentanyl in six adult male rhesus monkeys. Fentanyl was administered in sequential bolus injections of 2, 4, 16, 64, and 128 micrograms/kg, with 10 min between each dose. Arterial plasma fentanyl concentrations and blood gas tensions were measured 3 and 9 min after each dose and 1, 2, 5, 20, 60, and 120 min after the final dose. At the same time periods, mean systemic arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, cardiac output, heart rate, and respiratory rate were measured. Analgesia was quantified as the time required for tail withdrawal from a standardized noxious stimulus. Tail latency response time increased significantly after the 4-microgram/kg dose (plasma fentanyl concentration = 2.7 +/- 0.9 ng/mL). Maximum tail latency response time was attained after the 64-micrograms/kg dose (43.4 +/- 26.0 ng/mL). Respiratory rate decreased significantly after the 2-microgram/kg dose, and PaCO2 increased significantly after the 4-microgram/kg dose. All animals became apneic, requiring tracheal intubation and controlled ventilation, after the 64-micrograms/kg dose. Also, mean arterial pressure and cardiac output decreased significantly after the 64-micrograms/kg dose. There were no other significant cardiovascular changes. Peak plasma fentanyl concentration after the 128-micrograms/kg dose was 117.0 +/- 49.6 ng/mL. It appears that plasma concentrations of approximately 40 ng/mL are sufficient to reach the full cardiovascular, respiratory, and analgesic effects of fentanyl in the rhesus monkey. Significant respiratory and analgesic effects are evident at concentrations as low as 3 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesia, University of California, Davis.
authors.forename: N A
authors.initials: NA
authors.lastname: Nussmeier
authors.forename: J L
authors.initials: JL
authors.lastname: Benthuysen
authors.forename: E P
authors.initials: EP
authors.lastname: Steffey
authors.forename: J H
authors.initials: JH
authors.lastname: Anderson
authors.forename: E E
authors.initials: EE
authors.lastname: Carstens
authors.forename: J H
authors.initials: JH
authors.lastname: Eisele
authors.forename: T H
authors.initials: TH
authors.lastname: Stanley
mesh_terms: D000698:Analgesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D005283:Fentanyl / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D008954:Models, Biological; D009294:Narcotics / Q000633:toxicity; D012119:Respiration / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects*
chemical_list: D009294:Narcotics; D002245:Carbon Dioxide; D005283:Fentanyl