Nitrous oxide‐induced neurotoxicity: A case report and literature review

Abstract

Nitrous oxide is an increasingly popular recreational drug. However, recurrent or prolonged use can be associated with nitrous oxide toxicity, with numerous reports of harm documented in the literature. Nitrous oxide irreversibly binds and inactivates vitamin B12, which is an important co-factor in metabolic pathways involved in DNA and myelin synthesis. Toxicity is therefore associated with vitamin B12 deficiencyrelated syndromes, primarily involving haematological and neurological systems. As a "legal high", nitrous oxide use has attracted repeated health warnings from experts.An awareness and understanding of the pathophysiology and management of nitrous oxide toxicity is therefore important for clinicians. We discuss the case of a 29-yearold man presenting with nitrous oxide-induced sensorimotor neuropathy and review the existing literature surrounding toxicity.

Vitamin B12 inactivation may not be the only cause of acquired peripheral neuropathy in chronic nitrous oxide users

“…The authors suggest that mechanisms other than vitamin B12 deficiency are involved in nitrous oxide-induced peripheral neurological complications, such as inhibition of N-methyl-D-aspartate (NMDA) receptors. 1 We fully agree with them, but another important mechanism that should be taken into account is repeated hypoxia. In the…”

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We read with interest the review by Thayabaran and Burrage "Nitrous oxide-induced neurotoxicity: A case report and literature review" recently published in the journal. 1 We would like to add some elements on neurological complications and discuss the management of these patients.The authors suggest that mechanisms other than vitamin B12 deficiency are involved in nitrous oxide-induced peripheral neurological complications, such as inhibition of N-methyl-D-aspartate (NMDA) receptors. 1 We fully agree with them, but another important mechanism that should be taken into account is repeated hypoxia.

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“…1 We would like to add some elements on neurological complications and discuss the management of these patients.The authors suggest that mechanisms other than vitamin B12 deficiency are involved in nitrous oxide-induced peripheral neurological complications, such as inhibition of N-methyl-D-aspartate (NMDA) receptors. 1 We fully agree with them, but another important mechanism that should be taken into account is repeated hypoxia. In the context of nitrous oxide use, repeated hypoxias arise from (1) the use of pure (oxygen-free) nitrous oxide in large amounts, and (2) the unique characteristics of nitrous oxide.…”

“…We read with interest the review by Thayabaran and Burrage "Nitrous oxide-induced neurotoxicity: A case report and literature review" recently published in the journal. 1 We would like to add some elements on neurological complications and discuss the management of these patients.…”

“…5,6 The hypothesized mechanism is an increase in plasma homocysteine related to nitrous oxide-induced vitamin B12 inactivation, which leads to endothelial dysfunction and promotes thrombosis. 1 Other sites of thrombosis have also been described. 7 However, these complications are often incompletely described (no assessment of plasma vitamins or methylmalonic acid levels and no study of the methylenetetrahydrofolate reductase [MTHFR] gene mutations), and the sole involvement of nitrous oxide remains to be clearly demonstrated.…”