Effect of dexmedetomidine on the minimum alveolar concentration of isoflurane in cats

Abstract

This study reports the effects of dexmedetomidine on the minimum alveolar concentration of isoflurane (MAC(iso) ) in cats. Six healthy adult female cats were used. MAC(iso) and dexmedetomidine pharmacokinetics had previously been determined in each individual. Cats were anesthetized with isoflurane in oxygen. Dexmedetomidine was administered intravenously using target-controlled infusions to maintain plasma concentrations of 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10, and 20 ng/mL. MAC(iso) was determined in triplicate at each target plasma dexmedetomidine concentration. Blood samples were collected and analyzed for dexmedetomidine concentration. The following model was fitted to the concentration-effect data: [Formula in text] where MAC(iso.c) is MAC(iso) at plasma dexmedetomidine concentration C, MAC(iso.0) is MAC(iso) in the absence of dexmedetomidine, I(max) is the maximum possible reduction in MAC(iso), and IC(50) is the plasma dexmedetomidine concentration producing 50% of I(max). Mean ± SE MAC(iso.0), determined in a previous study conducted under conditions identical to those in this study, was 2.07 ± 0.04. Weighted mean ± SE I(max), and IC(50) estimated by the model were 1.76 ± 0.07%, and 1.05 ± 0.08 ng/mL, respectively. Dexmedetomidine decreased MAC(iso) in a concentration-dependent manner. The lowest MAC(iso) predicted by the model was 0.38 ± 0.08%, illustrating that dexmedetomidine alone is not expected to result in immobility in response to noxious stimulation in cats at any plasma concentration.

Hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats

“…The range of plasma dexmedetomidine concentrations was however wide enough for complete characterization of the concentration‐effect relationship for most variables of primary interest. 5) Lastly, while an effort was made to maintain equipotent anesthetic concentrations by adjusting isoflurane concentration in relation to the expected plasma dexmedetomidine concentration based on a previous study conducted in the same cats, and in which the same methods of dexmedetomidine administration were used (Escobar et al. 2010a), plasma dexmedetomidine concentrations in the present study tended to be higher than in the previous study, particularly at the higher plasma concentrations.…”

“…1) The hemodynamic effects of dexmedetomidine were studied in isoflurane‐anesthetized cats. While the results are therefore relevant to the use of dexmedetomidine as an anesthetic adjunct, which is the context addressed by this and our previous two studies on dexmedetomidine in cats (Escobar et al. 2010a,b), the effects reported here should not be extrapolated to the use of dexmedetomidine alone.…”

“…Neither the pharmacokinetics of dexmedetomidine nor its effect on the minimum alveolar concentration of isoflurane had been previously reported in cats, precluding better adjustment of isoflurane concentration. The peak plasma dexmedetomidine concentration in that study was approximately 18 ng mL −1 ; according to our study on the effects of dexmedetomidine on the MAC of isoflurane (Escobar et al. 2010a), that dexmedetomidine concentration in combination with the selected isoflurane concentration represents the equivalent of approximately 3.5 × MAC.…”

“…Six healthy adult female spayed domestic shorthair cats weighing 4.6 ± 0.8 kg (mean ± SD) were used in the study. The pharmacokinetics of dexmedetomidine and the MAC of isoflurane without dexmedetomidine, and with the target plasma dexmedetomidine concentrations used in this study had been determined in each cat in previous studies (Escobar et al. 2010a,b).…”

“…Dexmedetomidine, the active stereoisomer in the racemic medetomidine, is a potent, selective alpha‐2 agonist (Aantaa & Scheinin 1993). We have previously reported that dexmedetomidine reduced the minimum alveolar concentration (MAC) of isoflurane in cats, in a plasma concentration‐dependent manner (Escobar et al. 2010a).…”