Effect of clevidipine, an ultra-short acting 1,4-dihydropyridine calcium channel blocking drug, on the potency of isoflurane in rats and dogs

Abstract

Clevidipine is a new lipophilic, ultra-short acting 1,4-dihydropyridine calcium channel antagonist for intraoperative use. Because sarcolemnal calcium currents are involved in the mechanism of action of anaesthetics we questioned whether clevidipine alters the potency of volatile anaesthetics. We studied the effects of clevidipine on minimal alveolar concentration and the time to awaken from isoflurane anaesthesia. Sprague-Dawley rats were anaesthetized with isoflurane, and were allocated to one of four treatments prior to minimal alveolar concentration determination: (a) saline control; (b) clevidipine 20 nmol kg⁻¹ min⁻¹; (c) clevidipine 40 nmol kg⁻¹ min⁻¹; (d) clonidine 1 μg kg⁻¹ – positive control. Ten mongrel dogs were anaesthetized with isoflurane and received a continuous infusion of clevidipine 6 nmol kg⁻¹ min⁻¹ or the solvent (Intralipid 20% – control). After 2 h of steady-state anaesthesia, minimal alveolar concentration awake and the time to awakening were recorded. Clevidipine reduced minimal alveolar concentration to a small but statistically significant extent (from 1.40±0.16 control to 1.23±0.13 vol% with 20 nmol kg⁻¹ min⁻¹ and to 1.27±0.12 vol% with 40 nmol kg⁻¹ min^−1; mean±SD; P < 0.05) in rats. Clonidine reduced minimal alveolar concentration to 0.90±0.17 vol% (mean± SD; P < 0.05). Minimal alveolar concentration awake and the duration of sleep were not affected by clevidipine in dogs. Clevidipine mildly reduces miinimal alveolar concentration of isoflurane but does not prolong the duration of sleep and does not affect minimal alveolar concentration awake after a 2-h steady-state isoflurane anaesthesia.