Opioid drugs are commonly administered to patients to relieve moderate and severe pain. Because of their potent analgesic properties, opioids are commonly coadministered with inhalation anesthetic agents to reduce the concentration of the inhaled agent necessary for anesthesia, and as a result they decrease anesthesia-related cardiovascular depression. Fentanyl is a potent, short-acting member of the opioid drug class, and its ability to reduce inhalation anesthetic requirement, as defined by the MAC, in a variety of species is well known.1–3 Thus, use of fentanyl for clinical anesthetic management of these species is common.
It is also broadly accepted that morbidity and mortality rates associated with general anesthesia are much greater in horses,4 compared with the other species commonly anesthetized under clinical conditions. Similar to other species, inhalation anesthetics are commonly administered to equine patients, and depression of cardiovascular function accompanies their use.5 Accordingly, it is logical to consider coadministration of opioids with inhalation anesthetics for management of horses with the goal of improving anesthetic outcome. However, objective evidence supporting such clinical practice in horses is limited. For example, Steffey et al6 determined that IV administration of 2 mg of morphine/kg caused a 50% reduction in isoflurane MAC in dogs, but under similar laboratory conditions, the same dose of morphine, at a similar time after administration, caused a much smaller reduction in isoflurane MAC in some horses, an increase in others, and no change in still others.7 Similarly, alfentanil reduced the MAC of isoflurane in human patients8 and cats9 but did not change MAC in horses.10 However, most recently, Thomasy et al11 reported a small (18%) decrease in isoflurane MAC when fentanyl was administered, supporting further investigation of opioid use as an adjunct to inhalation anesthesia in equine patients.
In 1 study,11 3 targeted plasma concentrations of fentanyl (1, 8, and 16 ng/mL) were studied in 8 horses during anesthesia with only isoflurane in O2 (no other anesthetic or adjuvant drugs were administered). Mean measured plasma concentrations of fentanyl of 0.7 and 8.5 ng/mL did not cause a change in isoflurane MAC in those horses, but at 13.3 ng/mL, isoflurane MAC decreased by a mean of 18%. These results suggest a dose-dependent favorable response to fentanyl coadministered with isoflurane. Accordingly, the study reported here was designed to verify the isoflurane MAC-sparing effect of a target plasma fentanyl concentration of 16 ng/mL and characterize an anticipated further sparing in isoflurane MAC associated with target plasma fentanyl concentrations of 24 and 32 ng/mL.
Constant rate infusion
Diastolic arterial pressure
Intermittent positive pressure ventilation
Minimum alveolar concentration
Mean arterial pressure
N-(1-phenyl-4-piperidyl) malonanilinic acid
Systolic arterial pressure
Volume of distribution at steady state
LB-2 CO2 and anesthetic analyzer, Sensormedics Corp, Anaheim, Calif.
Model P23D, Division of Mark IV Industries, Oxnard, Calif.
Model 7 polygraph, Grass Instruments, Quincy, Mass.
Model AB330, Radiometer America, Cleveland, Ohio.
YSI-Tele-thermometer, model 43, Yellow Springs Instrument Co, Yellow Springs, Ohio.
Modified Mark 14, Bird Corp, Palm Springs, Calif.
SAS Institute Inc, Cary, NC.
McEwan AI, Smith C, Dyar O, et al. Isoflurane minimum alveolar concentration reduction by fentanyl. Anesthesiology 1993;78:864–869.
Murphy MR, Hug CC. The anesthetic potency of fentanyl in terms of its reduction of enflurane MAC. Anesthesiology 1982;57:485–488.
Ilkiw JE, Pascoe PJ, Haskins SC, et al. The cardiovascular sparing effect of fentanyl and atropine, administered to enflurane anesthetized dogs. Can J Vet Res 1994;58:248–253.
Johnston GM, Taylor PM, Holmas MA, et al. Confidential enquiry of perioperative equine fatalities (CEPEF-1): preliminary results. Equine Vet J 1995;27:193–200.
Steffey EP, Baggot JD, Eisele JH, et al. Morphine-isoflurane in dogs, swine and rhesus monkeys. J Vet Pharmacol Ther 1994;17:202–210.
Steffey EP, Eisele JH, Baggot JD. Interactions of morphine and isoflurane in horses. Am J Vet Res 2003;64:166–175.
Westmoreland CL, Sebel PS, Gropper A. Fentanyl or alfentanil decreases the minimum alveolar anesthetic concentration of isoflurane in surgical patients. Anesth Analg 1994;78:23–28.
Ilkiw JE, Pascoe PJ, Fisher LD. Effect of alfentanil on the minimum alveolar concentration of isoflurane in cats. Am J Vet Res 1997;58:1274–1279.
Pascoe PJ, Steffey EP, Black WD, et al. Evaluation of the effect of alfentanil on the minimum alveolar concentration of halothane in horses. Am J Vet Res 1993;54:1327–1332.
Thomasy SM, Steffey EP, Mama KR, et al. The effects of i.v. fentanyl on the minimum alveolar concentration of isoflurane in horses. Br J Anaesth 2006;97:232–237.
Steffey EP, Howland D Jr, Giri S, et al. Enflurane, halothane, and isoflurane potency in horses. Am J Vet Res 1977;38:1037–1039.
Thomasy SM, Mama KR, Whitley K, et al. The influence of general anesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses. Equine Vet J 2007;39:54–58.
Mama KR, Steffey EP, Pascoe PJ. Evaluation of propofol as a general anesthetic for horses. Vet Surg 1995;24:188–194.
Mama KR, Steffey EP, Pascoe PJ. Evaluation of propofol for general anesthesia in premedicated horses. Am J Vet Res 1996;57:512–516.
Thomasy SM, Mama KR, Stanley SD. Comparison of liquid chromatography-mass spectrometry and radioimmunoassay for measurement of fentanyl and determination of pharmacokinetics in equine plasma. J Anal Toxicol 2008;39:754–759.
Steffey EP, Zinkl J, Howland D Jr. Minimal changes in blood cell counts and biochemical values associated with prolonged isoflurane anesthesia of horses. Am J Vet Res 1979;40:1646–1648.