N2O. A greenhouse gas and an analgesic.
Discovered by Joseph Priestley in 1772, who called it phlogisticated nitrous air it was studied in man by Humphry Davy, at the time a surgical apprentice, whose other accomplishments eclipsed this. He did exhibit addictive behaviour due to inhaling the gas. While he did mention its potential in surgery, it was not until 1844 that the dentist Horace Wells introduced it as an anaesthetic. It rapidly became popular due to its second-gas effect of accelerating induction of anaesthesia and ability to allow reduction in the use of ether, chloroform or halothane. It is now mainly used in mask induction in children. N2O opposes vitamin B12 and thus if used for a prolonged period can produce the confusing signs of B12 deficiency - subacute combined degeneration affecting the brain and spinal cord. In people deficient in B12 this is at least a theoretical risk with relatively short exposures such as anaesthesia. A situation where this is relevant is in repeated use of Entonox (premixed 50% N2O: 50% Oxygen) for dressings to burns or abscesses. Dearlove and Briggs briefly discuss the chemistry and "suggest ... that the oxidation reaction only occurs in fluids such as blood and not in the liver so that oxidation of Vitamin B12 by nitrous oxide only becomes significant where there are no hepatic stores." Cases have been reported of nitrous oxide exposure causing a late motor neuropathy after correction of B12 depletion.
Pragmatically, giving B12 if a lot of nitrous is to be used seems unlikely to cause harm.
It is no longer used as often in anaesthesia due to its tendency to induce post operative nausea and vomiting, as well the development of intravenous and low pressure inhalation techniques. The switch to pure oxygen inhalation is associated in time with decreased post operative mortality and surgical post operative infection but as there is actually no evidence from randomised controlled trials for such an effect this may be artefact). In animal laproscopic models it appears to reduce surgical adhesions.
Its analgesic effects are mediated by short term inhibition of N-methyl-D-aspartate receptors. Davy's and many others subsequent addiction problems are presumably caused by this NMDA antagonist property.
- ↑ Elsworth PW. Dr. Ellsworth on the Modus Operandi of Medicines. The Boston Medical and Surgical Journal 1845; 32:389-400June 18, 1845DOI: 10.1056/NEJM184506180322001
- ↑ Cassidy A, Plekan O, Balog R, Dunger J, Field D, Jones NC. Electric field structures in thin films: formation and properties. The journal of physical chemistry. A. 2014 Aug 21; 118(33):6615-21.(Link to article – subscription may be required.)
- ↑ Davy H. Researches, Chemical and Philosophical; Chiefly Concerning Nitrous Oxide, or Dephlogisticated Nitrous Air, and Its Respiration 1800
- ↑ Letters to the editor: Nitrous oxide and vitamin B12
- ↑ Doran M, Rassam SS, Jones LM, Underhill S. Toxicity after intermittent inhalation of nitrous oxide for analgesia. BMJ. 2004 Jun 5;328(7452):1364-5 Available from bmj.com here.
- ↑ Rapid responses to above paper (Toxicity after intermittent inhalation of nitrous oxide for analgesia.)
- ↑ Morris N, Lynch K, Greenberg SA. Severe motor neuropathy or neuronopathy due to nitrous oxide toxicity after correction of vitamin B12 deficiency. Muscle & nerve. 2014 Oct 9.(Epub ahead of print) (Link to article – subscription may be required.)
- ↑ von Bormann B, Suksompong S, Weiler J, Zander R. Pure oxygen ventilation during general anaesthesia does not result in increased postoperative respiratory morbidity but decreases surgical site infection. An observational clinical study. PeerJ. 2014; 2:e613.(Epub) (Link to article – subscription may be required.)
- ↑ Myles PS, Leslie K, Chan MT, Forbes A, Peyton PJ, Paech MJ, Beattie WS, Sessler DI, Devereaux PJ, Silbert B, Schricker T, Wallace S. 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 Aug 14.(Epub ahead of print) (Link to article – subscription may be required.)
- ↑ Corona R, Binda MM, Mailova K, Verguts J, Koninckx PR. Addition of nitrous oxide to the carbon dioxide pneumoperitoneum strongly decreases adhesion formation and the dose-dependent adhesiogenic effect of blood in a laparoscopic mouse model. Fertility and sterility. 2013 Dec; 100(6):1777-83.(Link to article – subscription may be required.)