Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Inhalation anesthetic agents

Stephen Robert Hays, MD, FAAP
Section Editor
Girish P Joshi, MB, BS, MD, FFARCSI
Deputy Editor
Nancy A Nussmeier, MD, FAHA


This topic will review the mechanisms, pharmacokinetics, pharmacodynamics, advantages, disadvantages, and techniques employed to induce and maintain general anesthesia with inhalation anesthetics, including the potent volatile agents (sevoflurane, desflurane, isoflurane [and in some countries, halothane]) and one gas (nitrous oxide [N2O]). (See "Anesthesia machines: Prevention, diagnosis, and management of malfunctions".)

Intravenous agents used to induce and maintain general anesthesia are reviewed in separate topics. (See "General anesthesia: Intravenous induction agents" and "General anesthesia: Maintenance and emergence", section on 'Total intravenous anesthesia'.)


The precise mechanisms whereby inhalation agents induce general anesthesia are not known, and no single proposed mechanism of action fully explains their clinical effects (see 'Clinical effects' below). Various ion channels including gamma-aminobutyric acidA (GABAA), glycine, and glutamate receptors located in the central nervous system (ie, brain and spinal cord) are affected by the volatile inhalation anesthetics (sevoflurane, desflurane, and isoflurane) [1-4]. Nitrous oxide (N2O) gas is thought to act both by agonism of GABAA receptors and by antagonism of N-methyl-D-aspartate (NMDA) receptors [5,6].

Similarly, the mechanisms by which various intravenous agents are able to induce general anesthesia are not fully understood. (See "General anesthesia: Intravenous induction agents" and "General anesthesia: Maintenance and emergence", section on 'Total intravenous anesthesia'.)


General concepts — Inhalation agents are unique in their method of delivery via the lungs as a volume percent of inspired gas, rather than as a dose by weight with intravenous (IV) or oral medications. Inhalation agents are delivered via specialized airway circuits that are connected to an anesthesia machine, with scavenging of exhaled anesthetic gases to prevent environmental contamination of the operating room or interventional suite. Bottled volatile anesthetic liquids (sevoflurane, desflurane, isoflurane, halothane) are delivered via vaporizers on the anesthesia machine. Nitrous oxide (N2O) gas is supplied as a pressurized gas in equilibrium with its liquid phase in a cylinder, then delivered via a flow meter on the anesthesia machine (similar to delivery of other gases such as medical air or oxygen). (See "Anesthesia machines: Prevention, diagnosis, and management of malfunctions".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Aug 2017. | This topic last updated: Sep 08, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Franks NP, Lieb WR. Molecular and cellular mechanisms of general anaesthesia. Nature 1994; 367:607.
  2. Franks NP, Lieb WR. Do general anaesthetics act by competitive binding to specific receptors? Nature 1984; 310:599.
  3. Franks NP, Lieb WR. Where do general anaesthetics act? Nature 1978; 274:339.
  4. Franks NP. General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci 2008; 9:370.
  5. Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children. Anesth Analg 2007; 104:509.
  6. Zarate CA Jr, Machado-Vieira R. Potential Pathways Involved in the Rapid Antidepressant Effects of Nitrous Oxide. Biol Psychiatry 2015; 78:2.
  7. Tanner GE, Angers DG, Barash PG, et al. Effect of left-to-right, mixed left-to-right, and right-to-left shunts on inhalational anesthetic induction in children: a computer model. Anesth Analg 1985; 64:101.
  8. Hasija S, Chauhan S, Jain P, et al. Comparison of speed of inhalational induction in children with and without congenital heart disease. Ann Card Anaesth 2016; 19:468.
  9. Boonmak P, Boonmak S, Pattanittum P. High initial concentration versus low initial concentration sevoflurane for inhalational induction of anaesthesia. Cochrane Database Syst Rev 2016; :CD006837.
  10. de Oliveira GS Jr, Girao W, Fitzgerald PC, McCarthy RJ. The effect of sevoflurane versus desflurane on the incidence of upper respiratory morbidity in patients undergoing general anesthesia with a Laryngeal Mask Airway: a meta-analysis of randomized controlled trials. J Clin Anesth 2013; 25:452.
  11. Nyktari V, Papaioannou A, Volakakis N, et al. Respiratory resistance during anaesthesia with isoflurane, sevoflurane, and desflurane: a randomized clinical trial. Br J Anaesth 2011; 107:454.
  12. Lejus C, Bazin V, Fernandez M, et al. Inhalation induction using sevoflurane in children: the single-breath vital capacity technique compared to the tidal volume technique*. Anaesthesia 2006; 61:535.
  13. Joo HS, Perks WJ. Sevoflurane versus propofol for anesthetic induction: a meta-analysis. Anesth Analg 2000; 91:213.
  14. Peyton PJ, Chao I, Weinberg L, et al. Nitrous oxide diffusion and the second gas effect on emergence from anesthesia. Anesthesiology 2011; 114:596.
  15. Eger EI 2nd, Saidman LJ, Brandstater B. Minimum alveolar anesthetic concentration: a standard of anesthetic potency. Anesthesiology 1965; 26:756.
  16. Torri G. Inhalation anesthetics: a review. Minerva Anestesiol 2010; 76:215.
  17. Hendrickx JF, Eger EI 2nd, Sonner JM, Shafer SL. Is synergy the rule? A review of anesthetic interactions producing hypnosis and immobility. Anesth Analg 2008; 107:494.
  18. Aranake A, Mashour GA, Avidan MS. Minimum alveolar concentration: ongoing relevance and clinical utility. Anaesthesia 2013; 68:512.
  19. LeDez KM, Lerman J. The minimum alveolar concentration (MAC) of isoflurane in preterm neonates. Anesthesiology 1987; 67:301.
  20. Kanazawa S, Oda Y, Maeda C, Okutani R. Age-dependent decrease in desflurane concentration for maintaining bispectral index below 50. Acta Anaesthesiol Scand 2016; 60:177.
  21. Rooke GA, Choi JH, Bishop MJ. The effect of isoflurane, halothane, sevoflurane, and thiopental/nitrous oxide on respiratory system resistance after tracheal intubation. Anesthesiology 1997; 86:1294.
  22. Sun R, Jia WQ, Zhang P, et al. Nitrous oxide-based techniques versus nitrous oxide-free techniques for general anaesthesia. Cochrane Database Syst Rev 2015; :CD008984.
  23. Imberger G, Orr A, Thorlund K, et al. Does anaesthesia with nitrous oxide affect mortality or cardiovascular morbidity? A systematic review with meta-analysis and trial sequential analysis. Br J Anaesth 2014; 112:410.
  24. Leslie K, Myles PS, Kasza J, et al. Nitrous Oxide and Serious Long-term Morbidity and Mortality in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II Trial. Anesthesiology 2015; 123:1267.
  25. Myles PS, Leslie K, Chan MT, et al. The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial. Lancet 2014; 384:1446.
  27. Guelrud AE. Inhalation anesthesia: A fundamental guide, 2nd ed, The Macmillan Company, New York 1951.
  28. Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004; 350:2441.
  29. Schaefer MS, Kranke P, Weibel S, et al. Total intravenous anaesthesia versus single-drug pharmacological antiemetic prophylaxis in adults: A systematic review and meta-analysis. Eur J Anaesthesiol 2016; 33:750.
  30. Myles PS, Chan MT, Kasza J, et al. Severe Nausea and Vomiting in the Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia II Trial. Anesthesiology 2016; 124:1032.
  31. Fernández-Guisasola J, Gómez-Arnau JI, Cabrera Y, del Valle SG. Association between nitrous oxide and the incidence of postoperative nausea and vomiting in adults: a systematic review and meta-analysis. Anaesthesia 2010; 65:379.
  32. www.asahq.org/resources/clinical-information/2008-asa-recommendations-for-pre-anesthesia-checkout (Accessed on March 19, 2017).
  33. Burm AG. Occupational hazards of inhalational anaesthetics. Best Pract Res Clin Anaesthesiol 2003; 17:147.
  34. Anesthetic Gases: Guidelines for Workplace Exposures. Occupational Safety and Health Administration. https://www.osha.gov/dts/osta/anestheticgases/index.html (Accessed on July 19, 2017).
  35. Sigston PE, Jenkins AM, Jackson EA, et al. Rapid inhalation induction in children: 8% sevoflurane compared with 5% halothane. Br J Anaesth 1997; 78:362.
  36. Thwaites A, Edmends S, Smith I. Inhalation induction with sevoflurane: a double-blind comparison with propofol. Br J Anaesth 1997; 78:356.
  37. Joshi GP. Inhalational techniques in ambulatory anesthesia. Anesthesiol Clin North America 2003; 21:263.
  38. Suzuki KS, Oohata M, Mori N. Multiple-deep-breath inhalation induction with 5% sevoflurane and 67% nitrous oxide: comparison with intravenous injection of propofol. J Anesth 2002; 16:97.
  39. White PF, Tang J, Wender RH, et al. Desflurane versus sevoflurane for maintenance of outpatient anesthesia: the effect on early versus late recovery and perioperative coughing. Anesth Analg 2009; 109:387.
  40. Dagal A, Lam AM. Cerebral autoregulation and anesthesia. Curr Opin Anaesthesiol 2009; 22:547.
  41. Mostafa SM, Atherton AM. Sevoflurane for difficult tracheal intubation. Br J Anaesth 1997; 79:392.
  42. Thomas Ebert and Larry Lindenbaum. Inhaled Anesthetics. In: Clinical Anesthesia, Seventh, Paul G. Barash (Ed), Lippincott Williams Wilkins, Philadelphia 2013. p.447-477.
  43. Becker DE, Rosenberg M. Nitrous oxide and the inhalation anesthetics. Anesth Prog 2008; 55:124.
  44. McKay RE, Malhotra A, Cakmakkaya OS, et al. Effect of increased body mass index and anaesthetic duration on recovery of protective airway reflexes after sevoflurane vs desflurane. Br J Anaesth 2010; 104:175.
  45. Jakobsson J. Desflurane: a clinical update of a third-generation inhaled anaesthetic. Acta Anaesthesiol Scand 2012; 56:420.
  46. Dexter F, Bayman EO, Epstein RH. Statistical modeling of average and variability of time to extubation for meta-analysis comparing desflurane to sevoflurane. Anesth Analg 2010; 110:570.
  47. Dikmen Y, Eminoglu E, Salihoglu Z, Demiroluk S. Pulmonary mechanics during isoflurane, sevoflurane and desflurane anaesthesia. Anaesthesia 2003; 58:745.
  48. Satoh JI, Yamakage M, Kobayashi T, et al. Desflurane but not sevoflurane can increase lung resistance via tachykinin pathways. Br J Anaesth 2009; 102:704.
  49. Goff MJ, Arain SR, Ficke DJ, et al. Absence of bronchodilation during desflurane anesthesia: a comparison to sevoflurane and thiopental. Anesthesiology 2000; 93:404.
  50. Weiskopf RB, Moore MA, Eger EI 2nd, et al. Rapid increase in desflurane concentration is associated with greater transient cardiovascular stimulation than with rapid increase in isoflurane concentration in humans. Anesthesiology 1994; 80:1035.
  51. Strebel S, Lam AM, Matta B, et al. Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia. Anesthesiology 1995; 83:66.
  52. Aladj LJ, Croughwell N, Smith LR, Reves JG. Cerebral blood flow autoregulation is preserved during cardiopulmonary bypass in isoflurane-anesthetized patients. Anesth Analg 1991; 72:48.
  53. Echevarría G, Elgueta F, Fierro C, et al. Nitrous oxide (N(2)O) reduces postoperative opioid-induced hyperalgesia after remifentanil-propofol anaesthesia in humans. Br J Anaesth 2011; 107:959.
  54. Chan MT, Wan AC, Gin T, et al. Chronic postsurgical pain after nitrous oxide anesthesia. Pain 2011; 152:2514.
  55. Sanders RD, Weimann J, Maze M. Biologic effects of nitrous oxide: a mechanistic and toxicologic review. Anesthesiology 2008; 109:707.
  56. Myles PS, Chan MT, Kaye DM, et al. Effect of nitrous oxide anesthesia on plasma homocysteine and endothelial function. Anesthesiology 2008; 109:657.
  57. de Vasconcellos K, Sneyd JR. Nitrous oxide: are we still in equipoise? A qualitative review of current controversies. Br J Anaesth 2013; 111:877.
  58. Shuhaiber S, Koren G. Occupational exposure to inhaled anesthetic. Is it a concern for pregnant women? Can Fam Physician 2000; 46:2391.
Topic Outline