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The Increasing Recreational Use of Nitrous Oxide: History Revisited
The Increasing Recreational Use of Nitrous Oxide: History Revisited
23. Chen DL, Liess C, Poljak A, et al. Phenotypic characterization 30. Tsukada K, Miyazaki T, Kato H, et al. Body fat accumulation
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Nitrous oxide (N2O) is used in the food industry as a mixing and Crime Survey for England and Wales reporting nitrous oxide
foaming agent (E942) in the production of whipped cream,1 2 and use in the preceding year.2 This is a greater proportion than
as a fuel booster in the motor industry.3 It is also a familiar agent had used cocaine, ecstasy, or ketamine.4 Despite this, it is our im-
in obstetric, dental, emergency, and anaesthetic practice, where pression that many anaesthetists and emergency department
use is made of its analgesic and anaesthetic properties. However, doctors are unaware of the scale of nitrous oxide use in the
nitrous oxide was used recreationally long before its medical community.
potential was realized. Joseph Priestly is accredited with first syn- The product is freely available from catering outlets, street
thesizing the gas in 1772,3 and by the late 18th century inhalation vendors, and even via home-delivery service through the Inter-
of nitrous oxide became a popular public entertainment.4 The net or mobile vans advertising nitrous oxide for sale in UK cities.
gas became a fashionable addition to British high-society parties For recreational use, nitrous oxide is commonly sold in prefilled
in the early 1800s thanks to its euphoric and relaxant properties, balloons (at point of use) or small pressurized metal canisters
which led chemist Humphrey Davy to coin the term ‘laughing (Fig. 1) designed for the food industry. A standard catering canis-
gas’.3 ter containing 8 g of nitrous oxide in a volume of 10 cm3 can be
Although the routine use of nitrous oxide in anaesthesia is de- bought for as little as £2,7 and produces the equivalent of ∼8 litres
clining in both the UK5 and internationally,6 there has been a re- of nitrous oxide gas at standard temperature and pressure.8 The
cent resurgence of recreational use of the gas. Its presence is now pressurized gas is released into balloons using either a punctur-
commonplace at festivals and university parties,4 with a surpris- ing device, called a charger, or equipment designed to produce
ingly high 7.6% of 16- to 24-yr-olds responding to the 2013/14 whipped cream.2 8 Once a user inhales from a balloon, the partial
322 | Editorials
demand valve forms a crucial inherent safety feature in that the processes, and resultant inhaled impurities can cause harm.21
patient must be capable of exerting sufficient inspiratory effort to Deaths have been reported after contamination of nitrous oxide
release any Entonox from the supply, such that no further Ento- balloons with butane,7 and older anaesthetists will have learnt
nox can be released to a patient obtunded by hypoxia. In this about patient fatalities in the UK in 1966 reported in a special
scenario, the rapid offset of action of the gas means that con- BJA editorial.22
sciousness is rapidly restored, and breathing room air reverses Improper storage of the gas also creates the potential for
the hypoxia. harm. Nitrous oxide for medical use is stored in cylinders below
In recreational use of nitrous oxide, inhaling the gas from a its critical temperature, so it exists as a vapour above a volume of
balloon has similar safety features. Air, and therefore oxygen, nitrous oxide in its liquid phase.12 These cylinders are intention-
may be entrained alongside the gas on inhalation, and if the ally under-filled to accommodate increases in pressure as the va-
user is rendered hypoxic and loses consciousness, manual grip pour phase expands. Overfilling of the cylinders and storage
on the balloon will fail, propelling the balloon away. Assuming above the critical temperature carries an explosion risk.11
the airway remains patent, hypoxic drive will cause the user to
start to breathe room air again, reversing the hypoxia. Permanent
Regulation of nitrous oxide
harm could occur if the user is obtunded with other drugs, or as-
pirates vomit, or is prone to seizures or cardiac dysrhythmias in Nitrous oxide is not a controlled drug and therefore not subject to
the presence of hypoxia. the Misuse of Drugs Act 1971.2 The large cylinders of nitrous
More dangerous effects have been recorded when alternative oxide seen in hospitals are classed as medicinal products, and
methods of nitrous oxide administration have been used. Some supplying or administering these without MHRA (Medicines
users dispense the nitrous oxide canisters into whipped cream and Healthcare products Regulatory Agency) authorization is a
dispensers (‘whippets’) and inhale the gas directly from the noz- criminal offence under the Human Medicines Regulations 2012.
zle. The lack of a reducing valve means that this inhaled gas is However, the small canisters designed for the catering industry
under considerable pressure, and instances of pneumomediasti- are not classed as medicinal products and therefore not subject
num and subcutaneous emphysema have been attributed to to this Act.2
intra-alveolar rupture from this practice.18 Until very recently, it was not illegal to sell or possess nitrous
Through lack of available equipment, or through seeking to oxide, given its legitimate uses. Possession of nitrous oxide with
achieve higher concentrations of inspired gas, users may breathe the intent to inhale is a misdemeanour in most states in the
nitrous oxide directly from canisters. When a compressed gas ex- USA,1 and in the UK the Intoxicating Substances (Supply) Act
pands rapidly, it undergoes significant cooling as a result of adia- 1985 prohibits the sale, to those under the age of 18 yr, of sub-
batic change of state (this is the physical principle underlying the stances which the seller has reason to believe may be inhaled
mechanism of the cryoprobe used in therapeutic rapid freezing of for the purposes of intoxication.23 Similar to glue, petrol, knives,
tissues).19 There is further cooling as a result of loss of latent heat and other legal substances that may cause harm through misuse,
of vaporization.12 The anaesthetic effects of the gas may make regulation of sale of this gas to adults is fraught with difficulty. In
users initially unaware of the tissue damage being caused by in- recognition of the resurgence of the recreational use of nitrous
halation of such cold gas or freezing of metal components of the oxide and the difficulties in restricting its availability, the Advis-
delivery system, and frostbite of the mouth, nose and vocal cords ory Council on the Misuse of Drugs recently issued public health
is a recognized complication.1 8 12 20 safety advice and recommendations to the Government, local
The rapid offset of effects may cause abusers of the gas to ex- councils, and the Department of Health to increase awareness
plore methods of continuous inhalation of higher concentrations of this issue.24 In response to this, in May this year, the Home Of-
to enhance and prolong the effects, such as rebreathing in an en- fice released new legislation, the Psychoactive Substances Bill
closed container, such as a bag over the head, or opening cylin- 2015,25 which makes it an offence to ‘produce or supply any sub-
ders in a small enclosed space, such as a car. This increases the stance intended for human consumption that is capable of pro-
ratio of N2O to oxygen. Once there is significantly less than 20% ducing a psychoactive effect.’ Although medicinal nitrous oxide
oxygen in the inhaled gas, there is potential for irreversible hyp- is exempt from this legislation, it does give the police and local
oxic brain damage or death by asphyxiation.1 8 Simulations have authorities new powers to enforce civil sanctions against the
confirmed the dangerous hypoxic environment that can be cre- supply of nitrous oxide for recreational use. It remains to be
ated inadvertently. When a standard 8 g nitrous oxide canister seen how effective such legislation will be, with the danger that
is punctured in an enclosed bag, such as that which has been resulting covert manufacture may lead to unforeseen conse-
found tied over the head of a fatality from nitrous oxide abuse, quences, such as increased concentrations of dangerous impur-
the percentage of nitrous oxide rapidly increases to 59%, while ities in supplied nitrous oxide gas, while restrictions on supply of
the oxygen concentrations decrease to 13% in 10 s, and only canisters and balloons may shift recreational abuse toward the
10% within a minute.8 Adding the effects of respiration within more hazardous larger cylinders and airtight bags.10
this enclosed environment would reduce the available oxygen
even further as oxygen is used. At 50% inspired nitrous oxide,
Relevance to anaesthetists and other medical
the normal response to hypoxia is blunted, making death from
asphyxia even more likely.8
professionals
Perceptions of relative safety of usage coupled with cheapness
and ease of procurement of this gas make it an increasing public
Problems from unregulated manufacture and storage
health issue.
Industrial manufacture of nitrous oxide involves heating ammo- Patients who suffer complications of acute nitrous oxide
nium nitrate to 250°C and then removing impurities, such as NH3, abuse (e.g. hypoxia, aspiration, cardiac arrthythmias, seizures,
N2, NO, NO2, and HNO3, by passage through a series of washers trauma, pneumomediastinum) may present to the emergency
and scrubbers.11 12 Unregulated manufacturing of the gas for rec- department, and recreational abuse should be considered as a
reational abuse is likely to have less stringent quality-control differential diagnosis in these patients.
324 | Editorials