14
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          Nitrous oxide (N 2O) 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 2O 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 2O was added to the inspired gas and the MAC re-determined in the presence of N 2O (MAC SN). A subgroup of sheep were anesthetized a second time with SEVO/N 2O 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 2O 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 2O.

          Conclusions

          N 2O 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 2O.

          Related collections

          Most cited references25

          • Record: found
          • Abstract: found
          • Article: not found

          Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin.

          Extensive research has failed to clarify the mechanism of action of nitrous oxide (N2O, laughing gas), a widely used inhalational anesthetic and drug of abuse. Other general anesthetics are thought to act by one of two mechanisms-blockade of NMDA glutamate receptors or enhancement of GABAergic inhibition. Here we show that N2O, at anesthetically-relevant concentrations, inhibits both ionic currents and excitotoxic neurodegeneration mediated through NMDA receptors and, like other NMDA antagonists, produces neurotoxic side effects which can be prevented by drugs that enhance GABAergic inhibition. The favorable safety record of N2O may be explained by the low concentrations typically used and by the fact that it is usually used in combination with GABAergic anesthetics that counteract its neurotoxic potential.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The minimum alveolar concentration of nitrous oxide in man.

            The potency and anesthetic state produced by nitrous oxide alone were investigated in order to clarify its contribution to the effect of other anesthetic agents. Seven volunteers anesthetized with 1.55 atm absolute N2O in a pressure chamber displayed muscle rigidity with jerking movements, labored and rapid breathing, sweating, and dilated pupils. At 1.1 atm absolute N2O, relaxation and quiescence occurred, sweating ceased, and pupil size decreased. Determination of MAC (using tetanic electrical impulses as the noxious stimulus) produced a mean value of 1.04 +/- 0.10 (SE) atm absolute. All subjects complained of nausea and vomiting after anesthesia.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Reduction in halothane anesthetic requirement by clonidine, an alpha-adrenergic agonist.

              The effects of clonidine, a potent central alpha-adrenergic agonist, and of tolazoline, an alpha-adrenergic antagonist, on the minimal anesthetic concentration (MAC) of halothane were studied in male mongrel dogs. Control halothane MAC was 0.8 +/- 0.04 vol% (determined in each dog by gas chromatography of arterial blood, n = 30). Clonidine, 5 microgram/kg (n = 10) and 20 microgram/kg (n = 10), give slowly intravenously, maximally reduced MAC by 42% (at 2.3 hours after clonidine) and 48% (at 2.6 hours after clonidine) for each dose. In another set of animals (n = 5) an alpha-adrenergic antagonist, tolazoline, 5 mg/kg IV, reversed the clonidine-induced reduction in halothane MAC rapidly and completely. Tolazoline alone, 5 mg/kg, (n = 5) had no significant effect on halothane MAC. Thus, the administration of the central alpha-adrenergic agonist clonidine decreased the required anesthetic concentration of halothane, as defined by MAC, by almost half. This effect, as it is reversed by tolazoline, is likely to be mediated through a central alpha-adrenergic receptor mechanism.
                Bookmark

                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: Investigation
                Role: Investigation
                Role: Funding acquisitionRole: InvestigationRole: Resources
                Role: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                9 January 2018
                2018
                : 13
                : 1
                : e0190167
                Affiliations
                [1 ] Department of Clinical Studies-New Bolton Center, University of Pennsylvania, School of Veterinary Medicine, Kennett Square, Pennsylvania, United States of America
                [2 ] Dipartimento di Medicina Veterinaria, Università degli Studi di Sassari, Sassari, Sardegna, Italy
                [3 ] Centro di Ricerca di Chirurgia Comparata (CRCC), Università degli Studi di Sassari, Sassari, Sardegna, Italy
                [4 ] Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Sardegna, Italy
                [5 ] Narkovet Consulting™ LLC, Chadds Ford, PA, United States of America
                University of Bari, ITALY
                Author notes

                Competing Interests: The authors do not have any competing interests to declare. 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. Therefore, this does not alter our adherence to PLOS ONE policies on sharing data and materials.

                ‡ These authors also contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-3613-3396
                Article
                PONE-D-17-24869
                10.1371/journal.pone.0190167
                5760021
                29315308
                9c1da497-15a7-4bc4-9f90-1fd2416f5a90
                © 2018 Duffee et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 July 2017
                : 8 December 2017
                Page count
                Figures: 0, Tables: 2, Pages: 10
                Funding
                Funded by: Università degli Studi di Sassari (IT)
                Award ID: 15367
                Award Recipient :
                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.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Ruminants
                Sheep
                Medicine and Health Sciences
                Anesthesiology
                Anesthesia
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Anesthesia
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Anesthetics
                Medicine and Health Sciences
                Pain Management
                Anesthetics
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Functional Electrical Stimulation
                Biology and Life Sciences
                Anatomy
                Nervous System
                Neuroanatomy
                Spinal Cord
                Medicine and Health Sciences
                Anatomy
                Nervous System
                Neuroanatomy
                Spinal Cord
                Biology and Life Sciences
                Neuroscience
                Neuroanatomy
                Spinal Cord
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Blood
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Data
                Custom metadata
                All data files are available from figshare (URL: https://figshare.com/articles/MAC_Sevo_N2O_Data_Plos_One_xlsx/5706046/1 DOI: 10.6084/m9.figshare.5706046).

                Uncategorized
                Uncategorized

                Comments

                Comment on this article