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

PLoS One. 2018 Jan 9;13(1):e0190167. doi: 10.1371/journal.pone.0190167. eCollection 2018.

Abstract

Introduction: Nitrous oxide (N2O) is an anesthetic gas with antinociceptive properties and reduces the minimum alveolar concentration (MAC) for volatile anesthetic agents, potentially through mechanisms involving central alpha2-adrenoceptors. We hypothesized that 70% N2O in the inspired gas will significantly reduce the MAC of sevoflurane (MACSEVO) in sheep, and that this effect can be reversed by systemic atipamezole.

Materials and methods: Animals were initially anesthetized with SEVO in oxygen (O2) and exposed to an electrical current as supramaximal noxious stimulus in order to determine MACSEVO (in duplicates). Thereafter, 70% N2O was added to the inspired gas and the MAC re-determined in the presence of N2O (MACSN). A subgroup of sheep were anesthetized a second time with SEVO/N2O for re-determination of MACSN, after which atipamezole (0.2 mg kg-1, IV) was administered for MACSNA determinations. Sheep were anesthetized a third time, initially with only SEVO/O2 to re-determine MACSEVO, after which atipamezole (0.2 mg kg-1, IV) was administered for determination of MACSA.

Results: MACSEVO was 2.7 (0.3)% [mean (standard deviation)]. Addition of N2O resulted in a 37% reduction of MACSEVO to MACSN of 1.7 (0.2)% (p <0.0001). Atipamezole reversed this effect, producing a MACSNA of 3.1 (0.7)%, which did not differ from MACSEVO (p = 0.12). MACSEVO did not differ from MACSA (p = 0.69). Cardiorespiratory variables were not different among experimental groups except a lower ETCO2 in animals exposed to SEVO/N2O.

Conclusions: N2O produces significant MACSEVO-reduction in sheep; this effect is completely reversed by IV atipamezole confirming the involvement of alpha2-adrenoreceptors in the MAC-sparing action of N2O.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / administration & dosage*
  • Animals
  • Imidazoles / administration & dosage*
  • Methyl Ethers / administration & dosage*
  • Nitrous Oxide / adverse effects*
  • Sevoflurane
  • Sheep

Substances

  • Anesthetics, Inhalation
  • Imidazoles
  • Methyl Ethers
  • atipamezole
  • Sevoflurane
  • Nitrous Oxide

Grants and funding

This work was supported by the Centro di Ricerca di Chirurgia Comparata (CRCC), Università degli Studi di Sassari and a contribution of the Fondazione Banco di Sardegna as well as the Regione Autonoma della Sardegna. Some essential equipment was acquired through unrestricted funds of the Section of Anesthesia in the Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania. Lauren Duffee received a travel grant from the Department of Clinical Studies-VHUP, School of Veterinary Medicine, University of Pennsylvania. Prof. B. Driessen was awarded a competitive, 14-day all inclusive Visiting Professorship grant from the Central Administration of the University of Sassari, Italy. The funder provided support in the form of salaries for authors N.C., A.S., V.M., and G.M.C., but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Dr. Bernd Driessen is the founder and current managing partner of Narkovet Consultung®, LLC., however the company had neither funded the study nor had any other interest (i.e. financial, patent, or other commercial interest) in the study.