Nitrous oxide causes peripheral neuropathy in a dose dependent manner among recreational users

Abstract

Background: Nitrous oxide (N2O) has been used in clinical and recreational settings for over 150 years. Through inactivation of the Vitamin B12 dependent enzyme, methionine synthase, N2O can lead to the development of peripheral neuropathy. This study sought to determine the relationship between the exposure and risk of neurological symptoms in the largest ever sample of users. Design: Data are drawn from the Global Drug Survey (GDS) over three consecutive years (2014–2016). The Global Drug Survey is an online, cross-sectional survey of substance use, translated into multiple languages. Participants: Respondents to the Global Drug Survey who provided details on N2O use and the experience of paraesthesia in the previous 12 months. Measurements: Questions relating to N2O use, peripheral neuropathy, age and gender were explored among last year’s users. Findings: Of 241,566 respondents, 41,181 (17.0%) indicated that they had ever used nitrous oxide; of these, 42.1% had used in the last 12 months. For the final model, data from 16,124 participants who had used N2O in the last 12 months and had provided responses on age, dose, gender and paraesthesia were used. Of these, the number of respondents reporting persistent numbness/tingling (paraesthesia) in their hands or feet was 537 (3.3%). Although the risk was very low among infrequent users, there was a strong dose–response relationship. For people indicating one or two doses per session, the probability of reporting paraesthesia was approximately 0.018 by comparison; for people indicating 100 doses per session the probability was approximately 0.085. The association, between dose and paraesthesia was influenced by gender and age. Conclusion: While infrequent, episodic users are not at risk, a minority of heavy users are at dose-dependent risk of developing serious neurological consequences. Better education and raised awareness of early symptoms are required.

Nitrous Oxide-Induced Vitamin B12 Deficiency Resulting in Myelopathy

“…Nitrous oxide use not only induces a euphoric state on its own, but can also enhance the effects of other illicit drugs [3]. Its effects last only minutes with prompt return to normal function [2][3]. These properties likely contribute to an escalating recreational use.…”

“…In a review of 18 cases of nitrous oxide toxicity, Massey and colleagues reported paresthesia and gait abnormalities as the most common neurologic presentations [7]. Findings from a survey conducted by Winstock and Ferris completed by over 16,000 recreational nitrous oxide users suggest that neurologic symptoms may be dose dependent with a 3.5% increase in reports of paresthesia with every 10% increase in nitrous oxide dose used [3]. Further evidence of this dose-dependent relationship was demonstrated by the study conducted by Hakimoglu and colleagues, which revealed higher postoperative homocysteine levels in patients who received anesthesia with nitrous oxide for greater than three hours versus those who received anesthesia for under three hours [6].…”

“…Because of its ability to cause euphoria and its widespread availability, recreational nitrous oxide use is escalating. Metal canisters filled with nitrous oxide are sold online and at supermarkets and consumers often inhale the canisters' contents to achieve intoxication [3].…”

“…Though recreational use of nitrous oxide is reported to be safe compared to that of other illicit substances, its use has been associated with several adverse effects, including confusion, hallucinations, and falls [3]. Fatalities associated with nitrous oxide use have been attributed to accidental asphyxiation due to oxygen displacement, often resulting in arrhythmias and seizures [3].…”

“…Though recreational use of nitrous oxide is reported to be safe compared to that of other illicit substances, its use has been associated with several adverse effects, including confusion, hallucinations, and falls [3]. Fatalities associated with nitrous oxide use have been attributed to accidental asphyxiation due to oxygen displacement, often resulting in arrhythmias and seizures [3]. One of the most clinically significant adverse effects of nitrous oxide use is its association with vitamin B12 deficiency and resulting paresthesia, myelopathy, and subacute combined degeneration of the spinal cord [1].…”