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Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: An Individual Patient Data Meta-Analysis

40 Pages Posted: 6 Jan 2019

See all articles by Abderrahim Oussalah

Abderrahim Oussalah

University of Lorraine

Mélissa Julien

University of Lorraine - Nancy-Université

Julien Levy

University of Lorraine - Nancy-Université

Olivia Hajjar

University of Lorraine - Nancy-Université

Claire Franczak

University of Lorraine - Nancy-Université

Charlotte Stephan

University of Lorraine - Nancy-Université

Elodie Laugel

University of Lorraine - Nancy-Université

Marion Wandzel

University of Lorraine - Nancy-Université

Pierre Filhine-Tresarrieu

University of Lorraine - Nancy-Université

Ralph Green

University of California, Davis

Jean-Louis Gueant

University of Lorraine - Nutrition, Genetics, and Environmental Risk Exposure (NGERE); University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics; University of Lorraine - Reference Centre for Inborn Errors of Metabolism (ORPHA67872)

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Abstract

Background: The risk of adverse effects of nitrous oxide (N2O) exposure is insufficiently recognised despite its widespread use. These effects are mainly reported through case reports.

Methods: We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic resonance findings in association with N2O exposure in medical and recreational settings. We calculated the pooled estimates for the studied outcomes and assessed the potential bias related to population stratification using principal component analysis.

Findings: Eighty-five publications met the inclusion criteria and reported on 100 patients with a median age of 27 years and 57% of recreational users. The most frequent outcomes were subacute combined degeneration (28%), myelopathy (26%), and generalised demyelinating polyneuropathy (23%). A T2 signal hyperintensity in the spinal cord was reported in 68% (57·2%-78·8%) of patients. The most frequent clinical manifestations included paraesthesia (80%; 72·0%-88·0%), unsteady gait (58%; 48·2%-67·8%), and weakness (43%; 33·1%-52·9%). At least one haematological abnormality was retrieved in 71·7% (59·9%-83·4%) of patients. Most patients had vitamin B12 deficiency: vitamin B12 <150 pmol/L (70·7%; 60·7%-80·8%), homocysteine >15 µmol/L (90·3%; 79·3%-100%), and methylmalonic acid >0·4 µmol/L (93·8%; 80·4%-100%).

Interpretation: N2O can produce severe outcomes, with neurological or haematological disorders in almost all published cases. More than half of them are reported in the setting of recreational use. The N2O-related burden is dominated by vitamin B12 deficiency. This highlights the need to evaluate whether correcting B12 deficiency would prevent N2O-related toxicity, particularly in countries with a high prevalence of B12 deficiency.

Funding Statement: INSERM UMR_S 1256.

Declaration of Interest: Authors declare no conflict of interest

Keywords: Nitrous Oxide Exposure; Individual Patient Data Meta-Analysis; Medical and Recreational Settings; N2O-related toxicity; Vitamin B12 deficiency.

Suggested Citation

Oussalah, Abderrahim and Julien, Mélissa and Levy, Julien and Hajjar, Olivia and Franczak, Claire and Stephan, Charlotte and Laugel, Elodie and Wandzel, Marion and Filhine-Tresarrieu, Pierre and Green, Ralph and Gueant, Jean-Louis, Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: An Individual Patient Data Meta-Analysis (December 29, 2018). Available at SSRN: https://ssrn.com/abstract=3309400 or http://dx.doi.org/10.2139/ssrn.3309400

Abderrahim Oussalah

University of Lorraine

Lorraine
France

Mélissa Julien

University of Lorraine - Nancy-Université

France

Julien Levy

University of Lorraine - Nancy-Université

France

Olivia Hajjar

University of Lorraine - Nancy-Université

France

Claire Franczak

University of Lorraine - Nancy-Université

France

Charlotte Stephan

University of Lorraine - Nancy-Université

France

Elodie Laugel

University of Lorraine - Nancy-Université

France

Marion Wandzel

University of Lorraine - Nancy-Université

France

Pierre Filhine-Tresarrieu

University of Lorraine - Nancy-Université

France

Ralph Green

University of California, Davis

One Shields Avenue
Apt 153
Davis, CA 95616
United States

Jean-Louis Gueant (Contact Author)

University of Lorraine - Nutrition, Genetics, and Environmental Risk Exposure (NGERE) ( email )

Nancy
France

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics ( email )

Nancy, F-54000
France

University of Lorraine - Reference Centre for Inborn Errors of Metabolism (ORPHA67872) ( email )

Nancy, F-54000
France