MAC-sparing effect of nitrous oxide in sevoflurane anesthetized sheep and its reversal with systemic atipamezole administration

INTRODUCTION: Nitrous oxide (N(2)O) is an anesthetic gas with antinociceptive properties and reduces the minimum alveolar concentration (MAC) for volatile anesthetic agents, potentially through mechanisms involving central alpha(2)-adrenoceptors. We hypothesized that 70% N(2)O in the inspired gas will significantly reduce the MAC of sevoflurane (MAC(SEVO)) in sheep, and that this effect can be reversed by systemic atipamezole. MATERIALS AND METHODS: Animals were initially anesthetized with SEVO in oxygen (O(2)) and exposed to an electrical current as supramaximal noxious stimulus in order to determine MAC(SEVO) (in duplicates). Thereafter, 70% N(2)O was added to the inspired gas and the MAC re-determined in the presence of N(2)O (MAC(SN)). A subgroup of sheep were anesthetized a second time with SEVO/N(2)O for re-determination of MAC(SN), after which atipamezole (0.2 mg kg(-1), IV) was administered for MAC(SNA) determinations. Sheep were anesthetized a third time, initially with only SEVO/O(2) to re-determine MAC(SEVO), after which atipamezole (0.2 mg kg(-1), IV) was administered for determination of MAC(SA). RESULTS: MAC(SEVO) was 2.7 (0.3)% [mean (standard deviation)]. Addition of N(2)O resulted in a 37% reduction of MAC(SEVO) to MAC(SN) of 1.7 (0.2)% (p <0.0001). Atipamezole reversed this effect, producing a MAC(SNA) of 3.1 (0.7)%, which did not differ from MAC(SEVO) (p = 0.12). MAC(SEVO) did not differ from MAC(SA) (p = 0.69). Cardiorespiratory variables were not different among experimental groups except a lower ETCO(2) in animals exposed to SEVO/N(2)O. CONCLUSIONS: N(2)O produces significant MAC(SEVO)-reduction in sheep; this effect is completely reversed by IV atipamezole confirming the involvement of alpha(2)-adrenoreceptors in the MAC-sparing action of N(2)O.