Determination of the minimum alveolar concentration of sevoflurane that blunts adrenergic responses and the effect of a constant rate infusion of ketamine in sheep.

Abstract

Minimizing sympathetic stimulation under anesthesia prevents activation of the neuroendocrine stress response. The minimum alveolar concentration blunting adrenergic responses in 50% of the population when exposed to a noxious stimulus is defined as MAC-BAR. The purpose of this study was to determine the MAC-BAR of sevoflurane (MAC-BARsevo) in sheep and the MAC-BAR sparing effects of ketamine. Thirteen healthy Dorset-cross adult ewes, 4\xa0±\xa01\xa0year old and weighing 74\xa0±\xa09\xa0kg, were enrolled in a randomized blinded crossover study design. Ewes were anesthetized twice for MAC-BARsevo determination. After face mask induction with sevoflurane, sheep received intravenous ketamine at 1.5\xa0mg/kg and a constant rate infusion of 1.5\xa0mg/kg/h or an equivalent volume of saline (placebo). After 8\xa0day washout, the other treatment was administered. A bracketing technique was used for MAC-BARsevo determination and values were collected in duplicate. The mechanical stimulus (sponge forceps) was applied at the coronary band for 1\xa0min and blood was collected for ketamine plasma concentrations. The MAC-BARsevo values of each treatment were compared using a paired t-test. Mean MAC-BARsevo of the ketamine and placebo were 2.73\xa0±\xa00.23% and 2.77\xa0±\xa00.31%, respectively and no significant difference was found (p\xa0=\xa0.638). Average ketamine plasma concentrations was 1.54\xa0±\xa00.18\xa0μg/mL maintained through the study. Ketamine at 1.5\xa0mg/kg, followed by 1.5\xa0mg/kg/h, did not decrease the MAC-BARsevo in sheep. Further studies to determine the effect of higher doses of ketamine on inhalational anesthetic agents and their potential adverse effects are warranted.