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

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.

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Faculty Opinions recommendation of Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and meta-analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725315390.793536965 ◽

2017 ◽

Author(s):

Peter Kahrilas

Keyword(s):

Systematic Review ◽

Vitamin B12 ◽

Meta Analysis ◽

Vitamin B12 Deficiency ◽

B12 Deficiency

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Systematic Review and Pragmatic Clinical Approach to Oral and Nasal Vitamin B12 (Cobalamin) Treatment in Patients with Vitamin B12 Deficiency Related to Gastrointestinal Disorders

Journal of Clinical Medicine ◽

10.3390/jcm7100304 ◽

2018 ◽

Vol 7 (10) ◽

pp. 304 ◽

Cited By ~ 2

Author(s):

Emmanuel Andrès ◽

Abrar-Ahmad Zulfiqar ◽

Khalid Serraj ◽

Thomas Vogel ◽

Georges Kaltenbach

Keyword(s):

Vitamin B12 ◽

Prospective Studies ◽

Clinical Manifestations ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Cochrane Library ◽

Clinical Approach ◽

Oral Vitamin ◽

Hand Search ◽

B12 Deficiency

The objective of this review is to provide an update on the effectiveness of oral and nasal vitamin B12 (cobalamin) treatment in gastrointestinal (GI) disorders. Relevant articles were identified by PubMed and Google Scholar systematic search, from January 2010 and June 2018, and through hand search of relevant reference articles. Additional studies were obtained from references of identified studies, the Cochrane Library and the ISI Web of Knowledge. Data gleaned from reference textbooks and international meetings were also used, as was information gleaned from commercial sites on the web and data from CARE B12 research group. For oral vitamin B12 treatment, 4 randomized controlled trials (vs. intramuscular), 4 narrative and 4 systematic reviews, and 13 prospective studies fulfilled our inclusion criteria. These studies concerned patients with vitamin B12 deficiency related to: food-cobalamin malabsorption (n = 6), Biermer’s disease (n = 3), veganism or vegetarianism (n = 1), total gastrectomy after Roux-en-Y gastric bypass (n = 2) and Crohn’s disease (n = 1). Four prospective studies include patients with vitamin B12 deficiency related to the aforementioned etiologies, except veganism or vegetarianism. The systematic present review documents that oral vitamin B12 replacement, at a daily dose of 1000 μg (1 mg), was adequate to normalize serum vitamin B12 levels and cure main clinical manifestations related to vitamin B12 deficiency, in GI disorders, and thus, with safety profile. For nasal vitamin B12 treatment, only one preliminary study was available. We conclude that oral vitamin B12 is an effective alternative to intramuscular vitamin B12 (except in patients presenting with severe neurological manifestations). Oral vitamin B12 treatment avoids the discomfort, contraindication (in patients with anticoagulation), and cost of monthly injections.

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Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review

Nutrients ◽

10.3390/nu11112557 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2557 ◽

Cited By ~ 8

Author(s):

Martín-Masot ◽

Nestares ◽

Diaz-Castro ◽

López-Aliaga ◽

Alférez ◽

...

Keyword(s):

Celiac Disease ◽

Iron Deficiency ◽

Vitamin B12 ◽

Clinical Manifestations ◽

Vitamin B12 Deficiency ◽

Deficiency Anemia ◽

Intestinal Biopsy ◽

B12 Deficiency ◽

Endomysial Antibodies ◽

Inflammatory Bowel

Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.

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Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B12 deficiency

Journal of Oral and Maxillofacial Surgery ◽

10.1016/0278-2391(94)90259-3 ◽

1994 ◽

Vol 52 (8) ◽

pp. 891-892

Author(s):

K.N. Chow

Keyword(s):

Nitrous Oxide ◽

Vitamin B12 ◽

Vitamin B12 Deficiency ◽

B12 Deficiency ◽

Oxide Anesthesia

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Subacute Combined Degeneration of the Spinal Cord due to Different Etiologies and Improvement of MRI Findings

Case Reports in Neurological Medicine ◽

10.1155/2013/159649 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Azize Esra Gürsoy ◽

Mehmet Kolukısa ◽

Gülsen Babacan-Yıldız ◽

Arif Çelebi

Keyword(s):

Spinal Cord ◽

Nitrous Oxide ◽

Vitamin B12 ◽

Neurological Complication ◽

Vitamin B12 Deficiency ◽

Vegetarian Diet ◽

Mri Findings ◽

Subacute Combined Degeneration ◽

B12 Deficiency ◽

Reversible Condition

Subacute combined degeneration (SCD) is a rare neurological complication of vitamin B12 deficiency, characterized by demyelination of the dorsal and lateral spinal cord. Herein, we describe three cases, who presented with SCD, one related to reduced intake of vitamin B12 because of a vegetarian diet and two related to nitrous oxide exposure during surgery. MR images of our patients revealed symmetrical hyperintense signals in dorsal and lateral columns in T2 weighted series. After treatment with intramuscular B12 injections (1 mg daily for 2 weeks, once weekly thereafter for three months) all patients showed improvement of their symptoms. Abnormalities of the spinal cord on MRI resolved in three months. In conclusion, SCD either due to nitrous oxide exposure or due to reduced intake of vitamin B12 is a reversible condition, when detected and treated early.

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Vitamin B12 deficiency in the setting of nitrous oxide abuse: diagnostic challenges and treatment options in patients presenting with subacute neurological complications

Acta Clinica Belgica ◽

10.1080/17843286.2021.2015555 ◽

2021 ◽

pp. 1-7

Author(s):

Sluyts Yasmine ◽

Vanherpe Pieternel ◽

Amir Rizvana ◽

Vanhoenacker Filip ◽

Vermeersch Pieter

Keyword(s):

Nitrous Oxide ◽

Vitamin B12 ◽

Treatment Options ◽

Vitamin B12 Deficiency ◽

Neurological Complications ◽

B12 Deficiency

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Clinical, Laboratory and Imaging Features of COVID-19: A Systematic Review and Meta-analysis

10.20944/preprints202002.0378.v2 ◽

2020 ◽

Author(s):

Alfonso J. Rodriguez-Morales ◽

Jaime A. Cardona-Ospina ◽

Estefanía Gutiérrez-Ocampo ◽

Rhuvi Villamizar-Peña ◽

Yeimer Holguin-Rivera ◽

...

Keyword(s):

Observational Studies ◽

Clinical Laboratory ◽

Case Reports ◽

Meta Analysis ◽

Fatal Outcome ◽

Clinical Manifestations ◽

Clinical Infectious Disease ◽

Imaging Features ◽

Pooled Prevalence ◽

Quantitative Analyses

Introduction: An epidemic of Coronavirus Disease 2019 (COVID-19) begun in December 2019 in China, causing a Public Health Emergency of International Concern. Among raised questions, clinical, laboratory, and imaging features have been partially characterized in some observational studies. No systematic reviews have been published on this matter. Methods: We performed a systematic literature review with meta-analysis, using three databases to assess clinical, laboratory, imaging features, and outcomes of confirmed cases of COVID-19. All the observational studies, and also case reports, were included and analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95%CI). Measures of heterogeneity were estimated and reported. Results: 660 articles were retrieved. After screening by abstract and title, 27 articles were selected for full-text assessment. Of them, 19 were finally included for qualitative and quantitative analyses. Additionally, 39 case report articles were included and analyzed separately. For 656 patients, fever (88.7%, 95%CI 84.5-92.9%), cough (57.6%, 40.8-74.4%) and dyspnea (45.6%, 10.9-80.4%) were the most prevalent clinical manifestations. Among the patients, 20.3% (95%CI 10.0-30.6%) required intensive care unit (ICU), with 32.8% presenting acute respiratory distress syndrome (ARDS) (95%CI 13.7-51.8), 6.2% (95%CI 3.1-9.3) with shock and 13.9% (95%CI 6.2-21.5%) with a fatal outcome. Discussion: COVID-19 is a new clinical infectious disease, causing considerable compromise, especially in patients with comorbidities, requiring ICU in at least a fifth of them and sometimes with fatal outcomes. Additional research is needed to elucidate factors that may mediate the pathogenesis of the severe and fatal associated disease.

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