Review article: Clinical manifestations and outcomes of chronic nitrous oxide misuse: A systematic review

Abstract

Recreational nitrous oxide (N2O) use is widespread, and complications associated with its use are increasingly common. We sought to identify risk factors, clinical features and outcomes in individuals presenting with effects of chronic N2O abuse to develop an approach to clinical assessment and management. A systemic literature review was completed with searches conducted across EMBASE, MEDLINE, PSYCINFO and Cochrane databases. Our search strategy identified 612 studies, 105 met inclusion criteria, and 10 were added via hand search. Subjects from 24 case series and 91 case reports were typically in their 20s, using over 100 bulbs daily for several months. Neurological presentations, including sensory change, gait disturbance or weakness, were characteristic. Serum Vitamin B12 was normal or raised in 133 out of 243 case series subjects and 37 out of 84 reports. Serum homocysteine and methylmalonic acid were usually raised. Macrocytosis and anaemia were not commonly seen. MRI findings were abnormal with dorsal column change where specified, typically involving the cervical spine. Nerve conduction studies mostly reported a sensorimotor polyneuropathy. B12 replacement was the treatment of choice and partial recovery was most reported. This review highlights the dose‐dependent nature of chronic N2O toxicity and recognises functional B12 deficiency as the cause. As B12 is often normal, homocysteine and methylmalonic acid are important biomarkers of disease. An approach to diagnosis is offered but requires validation in prospective studies. Research exploring B12 and methionine therapy is required to refine management.

Homocystinuria diagnosis and management: it is not all classical

“…Recreational nitrous oxide misuse is increasingly common and its presentation can mimic that of an intracellular cobalamin disorder with subacute neurological features of functional B 12 deficiency (although on a background of normal neurological development), high tHCy and MMA and normal serum vitamin B 12 concentration. 36 The inherited intracellular disorders of cobalamin metabolism are denoted cblC-G, cblJ and cblX in brackets after the affected enzyme. LMBD1 (cblF) and ABCD4 (cblJ) are transporter proteins, which release stored cobalamin from hepatocyte lysosomes.…”

“…Recreational nitrous oxide misuse is increasingly common and its presentation can mimic that of an intracellular cobalamin disorder with subacute neurological features of functional B 12 deficiency (although on a background of normal neurological development), high tHCy and MMA and normal serum vitamin B 12 concentration 36…”

Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review

“…A correlation was found between the extent of N 2 O use (in whippets or balloons) and the degree of myelopathy and GDP [ 32 ], and most chronic users (mean: 300 balloons/day for 6 months) displayed signs of neuropathy. Cobalamin deficiency in patients with GDP has been a common finding in a number of studies [ 16 , 17 , 27 ], and cobalamin (vitamin B12) supplementation induces substantial neurological improvement or even recovery in most patients [ 27 ]. Nonetheless, some of these patients will only partly recover, with persistent neuropathies, such as paresthesia’s, limb weakness and/or partial paralysis, and are therefore in continuous need of medical devices [ 14 , 33 ].…”

“…Frequent and heavy use (up to 700 whippets per day) has been reported in Australia [ 14 ]. This is of serious concern because repeated exposure to high doses of N 2 O for a prolonged time is known to induce neurological damage, such as (irreversible) neuropathy and paralysis due to N 2 O-induced cobalamin deficiency [ 15 , 16 , 17 , 18 , 19 ]. The increasing trend of recreational users with N 2 O-induced neurological damage at emergency departments confirms the urgency of this development [ 9 , 20 , 21 ].…”

Recreational use of nitrous oxide

“…It produces short lasting euphoria and mild perceptual changes (lasting 0.5-1 minute). Occasional use is considered less harmful than for many other types of recreational substance,5 but there is a risk of cold burns to the lips, larynx, or exposed skin 6. Deaths due to sudden cardiac arrhythmias or asphyxiation through administration practices such as inhaling N 2 O from a plastic bag placed over the head have been reported 5.…”