N2O Laughing Matter

NO Laughing Matter St.Emlyn's

Everyone likes balloons, right?  Some people really like balloons, and more specifically the contents of them.  Having recently moved to East London, I can’t cycle to work and back (only about 15 minutes or so) without passing 4 or 5 of these canisters:


Now I use something similar to this when I find myself in a pinch on a long cycle, however I use carbon dioxide.  These contain nitrous oxide and are commonly sold to refill professional whipped cream dispensers…mainly to Janos (for his post-workout carb-fix).  They are ridiculously easy to buy over the internet, and a box of 24 will cost little over £6, yet can be sold in balloons on the street for around £3 a pop (no pun intended). Quick maths, and it’s easy to see the appeal, with around a 12-fold profit per canister.  They otherwise go by the name of ‘Whippets’.

I must admit that I had been, maybe naively, relatively unaware of the issue whilst in Virchester, despite the heavy use of lots of other substances.  A quick google of nitrous oxide balloons is quite the eye-opener.  The Notting Hill Carnival, which was only 1 week ago, saw over £2k worth of the stuff seized (although sources vary on the exact amount), and you can imagine how much of the stuff went around that wasn’t seized.

It is mainly used for it’s euphoria-inducing effects, which are short-lived, lasting 1-5 minutes126.  It is also a great analgesic, as we well know from the use of Entonox in acute pain.  Due to its short-acting nature, recreational users frequently binge and will often see off a large number of the canisters.  In the UK, it is estimated that around 7.6% of individuals aged between 16 and 24 have used nitrous oxide, and it has been responsible for 17 deaths between 2006 and 2012.  These deaths, whilst publicised, have perhaps not gained the same recognition as the fatalities caused by other recreational drugs such as MDMA.  I suspect that due to the short effects it is probably perceived as less dangerous by those who choose to use it.  The deaths caused by nitrous oxide are predominantly due to asphyxiation, as the nitrous oxide dilutes the amount of available oxygen in the lungs thus causing fatally hypoxic sequelae.

It is evidently an emergency when someone presents with acute hypoxia as a result of nitrous oxide use, but that is not where the problem with the drug ends for emergency physicians.  My ultimate take home point from this post is the following:

  • In young patients who present with any peculiar neurology or a new or unexplained B12 deficiency or macrocytic anaemia, have nitrous oxide use on your radar.

Nitrous oxide interferes with Vitamin B12 metabolism and this can really mess an individual up3.  Chronic use, and even acute use in those with existing B12 deficiency, can manifest with a spectrum of disease from uncomplicated macrocyctic anaemia to subacute combined degeneration of the cord (‘combined’ as it affects the central and peripheral nervous tissues)4.  I am reminded of a case I saw of the latter in a young male who had been triaged as ‘knee pain’, who perhaps unsurprisingly had a normal X-ray but a very abnormal ataxic gait!  Nitrous oxide is cleaved to form free nitrogen which then irreversibly inactivates vitamin B12.  It is poorly understood how B12 deficiency leads to subacute combined degeneration of the cord, but it is theorised that demyelination make play an important role.  It is important to note that it can be foetotoxic and teratogenic, so be mindful in pregnancy!

Subacute Cord

The good news it that is treatable and reversible with regular B12 injections and cessation of nitrous oxide use!

What I want you to think about:

  • Users of nitrous oxide may not think of it as a conventional drug in the same way they do with cocaine, cannabis, MDMA etc. so make sure you elicit it from the history
  • Keep it as a differential for young people with new macrocytic anaemia or weird neurology
  • A lot more people use it recreationally than we probably realise
  • It can kill




Further Reading

  • Medscape summary of neurological manifestations of B12 deficiency
  • A nice (free) article on nitrous oxide-induced B12 deficiency5

Before you go…

FRANK U. N2O. Talk to FRANK. http://www.talktofrank.com/drug/nitrous-oxide. Published September 3, 2016. Accessed August 2016.
van Amsterdam J, Nabben T, van den Brink W. Recreational nitrous oxide use: Prevalence and risks. Regulatory Toxicology and Pharmacology. 2015;73(3):790-796. doi:10.1016/j.yrtph.2015.10.017.
Lin R, Chen H, Chang Y, Su J. Subacute combined degeneration caused by nitrous oxide intoxication: case reports. Acta Neurol Taiwan. 2011;20(2):129-137.[PubMed]
Morris N, Lynch K, Greenberg SA. Severe motor neuropathy or neuronopathy due to nitrous oxide toxicity after correction of vitamin B12 deficiency. Muscle & Nerve. 2015;51(4):614-616. doi:10.1002/mus.24482.
Chiang T-T, Hung C-T, Wang W-M, Lee J-T, Yang F-C. Recreational Nitrous OxideAbuse-Induced Vitamin B12 Deficiency in a Patient Presenting with Hyperpigmentation of the Skin. Case Rep Dermatol. 2013;5(2):186-191. doi:10.1159/000353623.
Kaar S, Ferris J, Waldron J, Devaney M, Ramsey J, Winstock A. Up: The rise of nitrous oxide abuse. An international survey of contemporary nitrous oxide use. J Psychopharmacol. 2016;30(4):395-401.[PubMed]

Cite this article as: Richard Carden, "N2O Laughing Matter," in St.Emlyn's, September 4, 2016, https://www.stemlynsblog.org/n2o-laughing-matter/.

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