The MAC, a standard of inhalational anesthetic potency, was first defined in 1963 by Eger and Merkel.1 When calculated for an individual animal, the MAC is the arithmetic mean of the end-tidal concentrations of an inhalational anesthetic that prevent and allow purposeful movement in response to a supramaximal noxious stimulus.1–3
Although modern inhalational anesthetics allow rapid and precise control of depth of anesthesia and are devoid of cumulative effects even after prolonged anesthesia, these drugs do not provide a specific antinociceptive action and may cause dose-related cardiorespiratory depression.4 Relatively high end-tidal concentrations of inhalational anesthetics are necessary to inhibit the cardiovascular responses to noxious stimuli,5 and when these drugs are used at end-tidal concentrations necessary for surgical anesthesia, hypotension or substantial decreases in cardiac output and tissue oxygen delivery may follow. In small animal species, CRIs of phenylpiperidine opioid derivatives (fentanyl, sufentanil, and remifentanil) have been used with the aim of reducing the end-tidal concentration of inhalational anesthetics for maintenance of anesthesia and with the aim of providing intraoperative antinociception.6,7 Pure μ opioid receptor agonists markedly reduce MAC in dogs and humans.8–13
Remifentanil is an ultrashort-acting pure μ opioid receptor agonist that was introduced into clinical use in the early 1990s.14,15 On the basis of the plasma or blood concentration required to reduce ISOMAC by 50%, remifentanil was estimated to have a relative potency that was similar to that of fentanyl (relative potencies of 1.2 and 1.0 for remifentanil and fentanyl, respectively).15 Remifentanil has a unique pharmacokinetic profile, providing rapid and predictable effects without accumulation in tissues or blood even after prolonged IV infusions in humans.14,15 Because remifentanil is metabolized by nonspecific tissue and plasma esterases to a compound with negligible biological action, it does not accumulate even when used in human patients with liver or renal failure.16,17 Mean elimination half-lives of remifentanil were reported to range from 3 to 6 minutes in dogs, with negligible contribution of the liver to the total clearance of the drug.18,19 This pharmacokinetic profile favors the use of remifentanil CRI as an adjuvant to inhalational anesthetics in animals undergoing prolonged anesthetic procedures or those with liver or renal failure.
Remifentanil causes dose-dependent decreases in the MAC of enflurane, up to a maximum of 63% in dogs11; however, the effect of remifentanil on ISOMAC has not been determined. Enflurane is presently not in use because it may cause seizure-like activity that is more evident during deep anesthesia,20 and it is a more potent cardiac depressant than isoflurane and sevoflurane at equipotent doses.4
The purpose of the study reported here was to evaluate the effects of increasing infusion rates of remifentanil on ISOMAC in dogs and evaluate whether the isoflurane-sparing effect provided by a remifentanil CRI is constant over time. The hypothesis formulated was that remifentanil would induce dose-related decreases in ISOMAC and that these effects would be rapidly reversed after termination of a prolonged infusion.
Constant rate infusion
Diastolic arterial pressure
End-tidal concentration of isoflurane
Isoflurane minimum alveolar concentration
Minimum alveolar concentration
Mean arterial pressure
Systolic arterial pressure
Isoforine, Cristália, Itapira, SP, Brazil.
Inter Linea C, Intermed, São Paulo, SP, Brazil.
Gas analyzer module G-AO, Datex-Ëngstrom, Helsinki, Finland.
Quick Cal Calibration Gas, Datex-Ohmeda, Helsinki, Finland.
ST 550 T2, Samtronic, São Paulo, SP, Brazil.
TruWave − PX260, Edwards Lifesciences, Irvine, Calif.
AS/3 Anaesthesia Monitor, Datex-Ëngstrom, Helsinki, Finland.
pH/Blood gas analyzer, model 348, Chiron Diagnostics, Halstead, Essex, England.
Warmtouch Patient Warming System, Mallinkrodt, Pleasanton, Calif.
S48 Stimulator, Astro-Med Inc, West Warwick, RI.
Ultiva, 5 mg, Glaxo Smith Kline Brasil Ltda, Rio de Janeiro, RJ, Brazil.
ST 680, Samtronic, São Paulo, SP, Brazil.
Martinez EA, Lepiz M. Effect of remifentanil and fentanyl on minimum alveolar concentration and recovery in sevofluraneanesthetized dogs (abstr). Vet Anaesth Analg 2009;36:9.
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Valverde A, Morey TE, Hernández J, et al. Validation of several types of noxious stimuli for use in determining the minimum alveolar concentration for inhalation anesthetics in dogs and rabbits. Am J Vet Res 2003;64:957–962.
Mutoh T, Nishimura R, Kim HY, et al. Cardiopulmonary effects of sevoflurane, compared with halothane, enflurane, and isoflurane, in dogs. Am J Vet Res 1997;58:885–890.
Roizen MF, Horrigan RW, Frazer BM. Anesthetic doses blocking adrenergic (stress) and cardiovascular responses to incision-MAC BAR. Anesthesiology 1981;54:390–398.
Allweiler S, Brodbelt DC, Borer K, et al. The isoflurane-sparing and clinical effects of a constant rate infusion of remifentanil in dogs. Vet Anaesth Analg 2007;34:388–393.
Bufalari A, Di Meo A, Nannarone S, et al. Fentanyl or sufentanil continuous infusion during isoflurane anaesthesia in dogs: clinical experiences. Vet Res Commun 2007;31(suppl 1):277–280.
Murphy MR, Hug CC Jr. The anesthetic potency of fentanyl in terms of its reduction of enflurane MAC. Anesthesiology 1982;57:485–488.
Hall RI, Murphy MR, Hug CC Jr. The enflurane sparing effect of sufentanil in dogs. Anesthesiology 1987;67:518–525.
Michelsen LG, Salmenperä M, Hug CC Jr, et al. Anesthetic potency of remifentanil in dogs. Anesthesiology 1996;84:865–872.
Lang E, Kapila A, Shlugman D, et al. Reduction of isoflurane minimal alveolar concentration by remifentanil. Anesthesiology 1996;85:721–728.
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Glass PS, Gan TJ, Howell S. A review of the pharmacokinetics and pharmacodynamics of remifentanil. Anesth Analg 1999;89:S7–S14.
Dershwitz M, Hoke JF, Rosow CE, et al. Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease. Anesthesiology 1996;84:812–820.
Hoke JF, Shlugman D, Dershwitz M, et al. Pharmacokinetics and pharmacodynamics of remifentanil in persons with renal failure compared with healthy volunteers. Anesthesiology 1997;87:533–541.
Hoke JF, Cunningham F, James MK, et al. Comparative pharmacokinetics and pharmacodynamics of remifentanil, its principle metabolite (GR90291) and alfentanil in dogs. J Pharmacol Exp Ther 1997;281:226–232.
Chism JP, Rickert DE. The pharmacokinetics and extra-hepatic clearance of remifentanil, a short acting opioid agonist, in male beagle dogs during constant rate infusions. Drug Metab Dispos 1996;24:34–40.
Scheller MS, Nakakimura K, Fleischer JE, et al. Cerebral effects of sevoflurane in the dog: comparison with isoflurane and enflurane. Br J Anaesth 1990;65:388–392.
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Solano AM, Pypendop BH, Boscan PL, et al. Effect of intravenous administration of ketamine on the minimum alveolar concentration of isoflurane in anesthetized dogs. Am J Vet Res 2006;67:21–25.
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.