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

1
University of Lorraine, INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy, F-54000 Nancy, France
2
Department of Molecular Medicine and Personalized Therapeutics, Division of Biochemistry, Molecular Biology, Nutrition, and Metabolism, University Hospital of Nancy, F-54000 Nancy, France
3
Reference Centre for Inborn Errors of Metabolism (ORPHA67872), University Hospital of Nancy, F-54000 Nancy, France
4
Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA 95817, USA
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2019, 8(4), 551; https://doi.org/10.3390/jcm8040551
Received: 23 March 2019 / Revised: 12 April 2019 / Accepted: 16 April 2019 / Published: 23 April 2019
(This article belongs to the Section Epidemiology & Public Health)
The risk of adverse effects of nitrous oxide (N2O) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. 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. 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 generalized 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 paresthesia (80%; 72.0–88.0%), unsteady gait (58%; 48.2–67.8%), and weakness (43%; 33.1–52.9%). At least one hematological 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%). Consistently, 85% of patients exhibited a possibly or probably deficient vitamin B12 status according to the cB12 scoring system. N2O can produce severe outcomes, with neurological or hematological 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. View Full-Text
Keywords: global health; global burden related to nitrous oxide exposure; medical and recreational settings; individual patient data meta-analysis; nitrous oxide-related toxicity; vitamin B12 deficiency; one-carbon metabolism; homocysteine; methylmalonic acid global health; global burden related to nitrous oxide exposure; medical and recreational settings; individual patient data meta-analysis; nitrous oxide-related toxicity; vitamin B12 deficiency; one-carbon metabolism; homocysteine; methylmalonic acid
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MDPI and ACS Style

Oussalah, A.; Julien, M.; Levy, J.; Hajjar, O.; Franczak, C.; Stephan, C.; Laugel, E.; Wandzel, M.; Filhine-Tresarrieu, P.; Green, R.; Guéant, J.-L. Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: A Systematic Review and Individual Patient Data Meta-Analysis. J. Clin. Med. 2019, 8, 551. https://doi.org/10.3390/jcm8040551

AMA Style

Oussalah A, Julien M, Levy J, Hajjar O, Franczak C, Stephan C, Laugel E, Wandzel M, Filhine-Tresarrieu P, Green R, Guéant J-L. Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: A Systematic Review and Individual Patient Data Meta-Analysis. Journal of Clinical Medicine. 2019; 8(4):551. https://doi.org/10.3390/jcm8040551

Chicago/Turabian Style

Oussalah, Abderrahim, Mélissa Julien, Julien Levy, Olivia Hajjar, Claire Franczak, Charlotte Stephan, Elodie Laugel, Marion Wandzel, Pierre Filhine-Tresarrieu, Ralph Green, and Jean-Louis Guéant. 2019. "Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: A Systematic Review and Individual Patient Data Meta-Analysis" Journal of Clinical Medicine 8, no. 4: 551. https://doi.org/10.3390/jcm8040551

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