Gaseous Anesthetics

Article Author:
Aneitra Hoggard
Ryan Shienbaum
Miriam Mokhtar

Article Editor:
Paramvir Singh

Editors In Chief:
Bipin Shah
Matthew Ellison
Jorge Palacios

Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi

6/24/2019 9:16:32 AM


The history of anesthesia is a relatively recent one; if one begins with the analgesia dentist, Horace Wells, who discovered the used nitrous oxide during a dental extraction in the early 1800s. The first public showing of anesthesia occurred in October 1846, when ether was used to prevent pain during surgery at Massachusetts General Hospital. The following year, in 1847, Scottish obstetrician James Y. Simpson began using chloroform to treat childbirth pain.

In 1956, halothane came into clinical practice, but it caused fulminant hepatic necrosis, which promoted the development of new inhaled agents. Methoxyflurane came into clinical use in 1960 but was found to metabolize to nephrotoxic inorganic fluoride.  Enflurane in 1972, was an improvement as it was not hepatotoxic nor did it cause myocardial sensitivity to catecholamines like halothane. However, enflurane also metabolized to inorganic fluoride linked to increased seizure activity.[1]

Today, anesthesiologists have several tools for diminishing pain, awareness, movement, and the hemodynamic derangements of stress in the surgical patient.  Gaseous anesthetics, used most commonly today, are a single gas nitrous oxide and volatile fluorinated liquids (isoflurane, desflurane, sevoflurane) that are administered via specific vaporizers that transform the liquids into gases that diminish and, at higher doses, eradicate patient awareness. 


The gaseous anesthetic with the longest history is nitrous oxide. It noncompetitively inhibits N-methyl-d-aspartate (NMDA) receptors.[2] The hypothesis is that nitrous oxide in rodents inhibits nociceptive inputs in the dorsal horn of the spinal cord by activating descending noradrenergic pathways coming from the periaqueductal gray matter in the brainstem. Nitrous oxide is unique among the inhaled anesthetics in that it exists in its gaseous form at ambient room temperatures.

There is not an agreed-upon mechanism of action for gaseous anesthetics, but measurements to characterize them have been used to guide their clinical use. The potency of an anesthetic is determined by its lipid solubility and is described by the minimum alveolar concentration, or MAC, which is the concentration at the end of a breath needed to preclude movement in response to a surgical incision in fifty percent of patients. It is proposed that the cerebral cortex, amygdala, and hippocampus are target areas for gaseous anesthetics to cause amnesia and the activation of descending pathways originating in the periaqueductal gray matter of the brainstem are the target areas for immobility.[3]

Issues of Concern

Nitrous oxide can cause expansion of gas and therefore increased pressure, in closed air-filled spaces like in cases of bowel obstruction and pneumothorax. Air contains 78% nitrogen, which is significantly less soluble in blood than nitrous oxide. The nitrous oxide in the blood diffuses into the air-filled cavities faster than the air can be absorbed into the blood. Nitrous oxide also oxidizes vitamin B12, rendering it ineffective as a coenzyme, which can manifest as megaloblastic anemia, and in rare cases, neuropathy as seen in subacute combined degeneration.[4][5]

Strong bases in desiccated carbon dioxide absorbent can combine with metabolized desflurane to produce carbon monoxide. Sevoflurane also is the only fluorinated gaseous anesthetic whose metabolic products do not create carbon monoxide with desiccated carbon dioxide absorbent. Instead, degraded sevoflurane can produce Compound A in the presence of desiccated carbon dioxide absorbent, leading to proximal tubular necrosis in animal studies. Clinically significant nephrotoxicity in humans has not yet been established.[6]

Malignant hyperthermia (MH) is a relatively rare, but life-threatening hypermetabolic syndrome that can result from the use of gaseous anesthetics (most famously halothane) and succinylcholine. Tachycardia, rigid musculature, diaphoresis, rapid elevations in end-tidal carbon dioxide concentrations, and elevated temperature are all considered signs of malignant hyperthermia.[7] The signs can present very subtly. Dantrolene is the mainstay pharmacologic treatment of MH, administered as a rapid IV infusion (2.5 mg/kg every 5 to 10 minutes until end-tidal CO2 and muscle rigidity start to decline). Dantrolene inhibits calcium release from the muscular sarcoplasmic reticulum and blocks the coupling of muscular excitation and contraction.  Early recognition and diagnosis have led to an improvement in mortality rates from MH, but its treatment is an arduous event that requires rapid and complete cooperation of all healthcare workers in the presence of a surgical patient experiencing this disorder. 

Clinical Significance

Sevoflurane, isoflurane, and desflurane cause a decrease in systemic vascular resistance typically seen as a decrease in mean arterial pressure (MAP). Nitrous oxide tends to have no effect on or at most causes a small increase in MAP. Gaseous anesthetics cause myocardial depression, with isoflurane being the least associated with arrhythmogenicity in patients. Sevoflurane, isoflurane, and desflurane increase respiratory rate and decrease tidal volumes. All gaseous anesthetics dilate the pulmonary vascular bed, inhibiting the mechanism of vasoconstriction of the pulmonary vascular bed when hypoxia occurs.[8]  All gaseous anesthetics cause relaxation of the skeletal muscles and also enhance the effect of neuromuscular blocking drugs. Desflurane provides the most significant enhancement of neuromuscular blockade by rocuronium.[9] 

Due to the specific impacts of gaseous anesthetics on various organ systems, their use is limited in certain types of surgical procedures. Hypoxic pulmonary vasoconstriction is a physiologic mechanism to aid in ventilation-perfusion matching, and gaseous anesthetics can clinically inhibit this mechanism.[10]  During surgeries requiring one-lung ventilation, the administration of greater than 1 MAC of gaseous anesthetics is generally avoided to prevent the attenuation of hypoxic pulmonary vasoconstriction.[11]

The clinical effects of gaseous anesthetics are determined by the alveolar partial pressure of the gaseous anesthetics, which govern the partial pressures in all other tissues of the patient's body. The effects on alveolar partial pressure are primarily the result of the amount of gaseous anesthetic delivered to the patient in the inspired gas and the amount of alveolar ventilation. As blood passes through the lungs, it takes some for the gaseous anesthetic to move into the alveoli, depending on the blood/gas solubility coefficient of that anesthetic and the patient's cardiac output; this is what is known as uptake. Increased uptake may slow the time to induction with a gaseous anesthetic. Furthermore, emergence from anesthesia is quicker with gaseous anesthetics with low blood/gas solubility.[12]

Enhancing Healthcare Team Outcomes

When gaseous anesthetics are in use, it is of paramount importance that everyone in the operating room and/or procedural site communicates well in preparation for the onset of its use and possible adverse effects. During all inductions of general anesthesia, the operating room nurse, anesthesiologist/nurse anesthetist, and surgeon should all be paying attention and be ready to assist in securing the patient's airway. Ideally, the operating room nurse is at the patient's side to assist the anesthesiologist and/or anesthetist, and in cases of an anticipated difficult airway, the surgeon should be in the room ready to establish an invasive airway.

Studies overall have been inconsistent to show other adverse effects to healthcare workers occupationally exposed to modern gaseous anesthetics. None have been shown to be teratogenic; however, nitrous oxide in large amounts can cause megaloblastic anemia due to a functional vitamin B12 deficiency.  Since the 1970s, studies have investigated the effects of waste anesthetic gases on healthcare workers exposed to them regularly. There is a suspected associated with an increased relative risk for spontaneous abortions in women who are occupationally exposed to waste gaseous anesthetics. However, there are no official standards by the Occupational Safety and Health Administration (OSHA) regarding the limits of acceptable exposure.[13][14]  The occupational safety and health of everyone in the operating room are aided when anesthesiologists, anesthetists, and anesthesia technicians ensure that scavenging systems are in place and working. Operating room nurses can confirm that operating room ventilation is active, and anesthesia providers can use low gas flow approaches to delivering general anesthesia to help minimize gaseous anesthetic waste.[15] (Level V)

In light of this, an interprofessional team approach is the most prudent course when gaseous anesthetics are in use; this applies to both the patient and those in the operating theater performing and assisting on the procedure. The surgeon, other physicians, anesthesiologist/nurse anesthetist, and medical/surgical nursing professional working together as a team can ensure the optimal outcome for the patient and all OR personnel involved. [Level V]

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Gaseous Anesthetics - References


Stachnik J, Inhaled anesthetic agents. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2006 Apr 1;     [PubMed]
Eger EI 2nd,Koblin DD,Harris RA,Kendig JJ,Pohorille A,Halsey MJ,Trudell JR, Hypothesis: inhaled anesthetics produce immobility and amnesia by different mechanisms at different sites. Anesthesia and analgesia. 1997 Apr;     [PubMed]
Akata T, General anesthetics and vascular smooth muscle: direct actions of general anesthetics on cellular mechanisms regulating vascular tone. Anesthesiology. 2007 Feb;     [PubMed]
Wulf H,Ledowski T,Linstedt U,Proppe D,Sitzlack D, Neuromuscular blocking effects of rocuronium during desflurane, isoflurane, and sevoflurane anaesthesia. Canadian journal of anaesthesia = Journal canadien d'anesthesie. 1998 Jun;     [PubMed]
Jevtović-Todorović V,Todorović SM,Mennerick S,Powell S,Dikranian K,Benshoff N,Zorumski CF,Olney JW, Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nature medicine. 1998 Apr;     [PubMed]
Kollmann-Camaiora A,Alsina E,Domínguez A,Del Blanco B,Yepes MJ,Guerrero JL,García A, Clinical protocol for the management of malignant hyperthermia. Revista espanola de anestesiologia y reanimacion. 2017 Jan;     [PubMed]
Chanarin I, Cobalamins and nitrous oxide: a review. Journal of clinical pathology. 1980 Oct;     [PubMed]
Lin RJ,Chen HF,Chang YC,Su JJ, Subacute combined degeneration caused by nitrous oxide intoxication: case reports. Acta neurologica Taiwanica. 2011 Jun;     [PubMed]
Boivin JF, Risk of spontaneous abortion in women occupationally exposed to anaesthetic gases: a meta-analysis. Occupational and environmental medicine. 1997 Aug;     [PubMed]
Molina Aragonés JM,Ayora Ayora A,Barbara Ribalta A,Gascó parici A,Medina Lavela JA,Sol Vidiella J,Sol López MH, Occupational exposure to volatile anaesthetics: a systematic review. Occupational medicine (Oxford, England). 2016 Apr;     [PubMed]
Byhahn C,Wilke HJ,Westpphal K, Occupational exposure to volatile anaesthetics: epidemiology and approaches to reducing the problem. CNS drugs. 2001;     [PubMed]
Marshall C,Lindgren L,Marshall BE, Effects of halothane, enflurane, and isoflurane on hypoxic pulmonary vasoconstriction in rat lungs in vitro. Anesthesiology. 1984 Apr;     [PubMed]
Lumb AB,Slinger P, Hypoxic pulmonary vasoconstriction: physiology and anesthetic implications. Anesthesiology. 2015 Apr;     [PubMed]
Ong Sio LCL,Dela Cruz RGC,Bautista AF, Sevoflurane and renal function: a meta-analysis of randomized trials. Medical gas research. 2017 Jul-Sep;     [PubMed]
Hasija S,Chauhan S,Jain P,Choudhury A,Aggarwal N,Pandey RK, Comparison of speed of inhalational induction in children with and without congenital heart disease. Annals of cardiac anaesthesia. 2016 Jul-Sep;     [PubMed]


The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Anesthesiology-Cardiothoracic. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Anesthesiology-Cardiothoracic, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Anesthesiology-Cardiothoracic, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Anesthesiology-Cardiothoracic. When it is time for the Anesthesiology-Cardiothoracic board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Anesthesiology-Cardiothoracic.