@article{ref1,
title="Global burden related to nitrous oxide exposure in medical and recreational settings: a systematic review and individual patient data meta-analysis",
journal="Journal of clinical medicine",
year="2019",
author="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 Guéant, Jean-Louis",
volume="8",
number="4",
pages="e8040551-e8040551",
abstract="The risk of adverse effects of nitrous oxide (N<sub>2</sub>O) 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 N<sub>2</sub>O 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. N<sub>2</sub>O 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 N<sub>2</sub>O-related burden is dominated by vitamin B12 deficiency. This highlights the need to evaluate whether correcting B12 deficiency would prevent N<sub>2</sub>O-related toxicity, particularly in countries with a high prevalence of B12 deficiency.<p /> <p>Language: en</p>",
language="en",
issn="2077-0383",
doi="10.3390/jcm8040551",
url="http://dx.doi.org/10.3390/jcm8040551"
}