Skip to content
DraconiticResearch
Search Sources API
197,788 studies31 sourcesUpdated 12 min ago
Peer-reviewedCC BY-NC-ND 4.0British Journal of Clinical Pharmacology

Relationships among nitrous oxide exposure, neurological injury and biomarkers

  • Laxna Bhujel1
  • Angela L. Chiew1,2
  • Bhashita Jagarlamudi1,2,3
  • Pramod Chandru4,5,6
  • Naren Gunja4,6
  • Nancy Briggs7
  • Betty S. Chan1,2
7 affiliations
  1. 1Faculty of Medicine and Health, School of Clinical Medicine University of New South Wales Sydney New South Wales Australia
  2. 2Clinical Toxicology Unit and Emergency Department Prince of Wales Hospital Sydney New South Wales Australia
  3. 3Department of Clinical Pharmacology and Toxicology Therapeutics Centre St Vincent's Hospital Darlinghurst New South Wales Australia
  4. 4Department of Clinical Toxicology Westmead Hospital Westmead New South Wales Australia
  5. 5Emergency Department, Clinical Toxicology Unit Nepean Hospital Kingswood New South Wales Australia
  6. 6Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
  7. 7Stats Central, Mark Wainwright Analytical Centre University of New South Wales Sydney New South Wales Australia
Read full textDOICite

Abstract

Aims: Recreational nitrous oxide (N2O) misuse is an increasing public health problem associated with functional cobalamin (B12) deficiency and severe neurological complications. Despite growing recognition of its harms, the dose–response relationship and clinical value of biomarkers remain unclear. This study aimed to characterize the demographics, patterns of use, outcomes, and biomarker utility in patients hospitalized with N2O toxicity, as well as to examine the relationship between exposure and toxicity.

Methods: This retrospective cohort study included hospitalized individuals with N2O toxicity (2020–2025) across six Sydney hospitals. Weekly and cumulative N2O exposure volumes were estimated. Exposure volumes were compared with clinical outcomes and biomarker results to assess correlations and biomarker utility.

Results: Eighty‐one individuals across 100 presentations were included. Higher cumulative N2O exposure was associated with worse neurological impairment, including subacute combined degeneration of the spinal cord (SCD, p = .006) and peripheral neuropathy (PN, p = .036), and correlated with greater neuropathy severity (Spearman's ⍴ = 0.43, p = .001). Median homocysteine was 50 μmol/L (IQR:32–114;normal 5–15) with a median half‐life of 14.59 h. Median methylmalonic acid (MMA) was 0.68 μmol/L (IQR:0.18–3.16;normal<0.27). B12 and holotranscobalamin showed high specificity (87% and 98%) but low sensitivity (22% and 5%) for detecting cases associated with SCD, while homocysteine and MMA showed high sensitivity (95% and 93%) but lower specificity (13% and 45%).

Conclusions: Cumulative N2O exposure is the strongest predictor of severe neurological outcomes, demonstrating a dose‐dependent relationship with neurotoxicity. Homocysteine and MMA were sensitive markers associated with neurological toxicity, making them useful screening biomarkers; however, their limited specificity reduces their utility as confirmatory tests. These findings reinforce the importance of clinical assessment and exposure history in diagnosing toxicity.

Related

  1. Lifespan EEG Reference Charts Reveal Aperiodic Confounds in Beta-Band Biomarkers Across Neurological and Neuropsychiatric Disorders
    V. Paliwal, A. Moiseev, S. M. Doesburg +8
    medRxivPreprintAll rights reservedFull textNeurologymedRxiv
  2. Neurological Recovery Trajectories in Older Patients with Cervical Spinal Cord Injury: A Multicenter Longitudinal Study
    Ryosuke Hirota, Yoshinori Terashima, Makoto Emori +48
    Spine surgery and related researchPeer-reviewedCC BY-NC-NDFull textSurgery & anaesthesiaEurope PMC
  3. Biopsychosocial interplay of personal injury insurance, legal frameworks, and functional neurological disorder: an emerging perspective on recovery and disability determinants
    Edwina Rose Sekine, Sarah Oxford, Shannon Gray +3
    Frontiers in neurologyPeer-reviewedCC BYFull textPsychiatry & mental healthEurope PMCCrossref
  4. Unexplained neurological deterioration after acute brain injury: A structured intensive care framework for targeted continuous electroencephalogram.
    Kazunori Oda, Natsuki Nakatani, Tomo Kinoshita +1
    Surgical neurology internationalPeer-reviewedCC BY-NC-SAFull textNeurologyEurope PMCPMC
  5. Modeling Exposure-Mortality Relationships for Indoor Heat.
    Andrew Ibbetson, Charles Simpson, Giorgos Petrou +5
    Risk analysis : an official publication of the Society for Risk AnalysisPeer-reviewedCC BYFull textPharmacology & toxicologyEurope PMC

Cite

BibTeXRIS
BibTeX
@article{bhujel2026relationships,
  title = {{Relationships among nitrous oxide exposure, neurological injury and biomarkers}},
  author = {Laxna Bhujel and Angela L. Chiew and Bhashita Jagarlamudi and Pramod Chandru and Naren Gunja and Nancy Briggs and Betty S. Chan},
  journal = {British Journal of Clinical Pharmacology},
  year = {2026},
  month = jul,
  doi = {10.1002/bcp.70699},
  url = {https://doi.org/10.1002/bcp.70699},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Relationships among nitrous oxide exposure, neurological injury and biomarkers
AU  - Laxna Bhujel
AU  - Angela L. Chiew
AU  - Bhashita Jagarlamudi
AU  - Pramod Chandru
AU  - Naren Gunja
AU  - Nancy Briggs
AU  - Betty S. Chan
PY  - 2026
DA  - 2026/07/20
JO  - British Journal of Clinical Pharmacology
DO  - 10.1002/bcp.70699
UR  - https://doi.org/10.1002/bcp.70699
AB  - Aims: Recreational nitrous oxide (N2O) misuse is an increasing public health problem associated with functional cobalamin (B12) deficiency and severe neurological complications. Despite growing recognition of its harms, the dose–response relationship and clinical value of biomarkers remain unclear. This study aimed to characterize the demographics, patterns of use, outcomes, and biomarker utility in patients hospitalized with N2O toxicity, as well as to examine the relationship between exposure and toxicity.  Methods: This retrospective cohort study included hospitalized individuals with N2O toxicity (2020–2025) across six Sydney hospitals. Weekly and cumulative N2O exposure volumes were estimated. Exposure volumes were compared with clinical outcomes and biomarker results to assess correlations and biomarker utility.  Results: Eighty‐one individuals across 100 presentations were included. Higher cumulative N2O exposure was associated with worse neurological impairment, including subacute combined degeneration of the spinal cord (SCD, p = .006) and peripheral neuropathy (PN, p = .036), and correlated with greater neuropathy severity (Spearman's ⍴ = 0.43, p = .001). Median homocysteine was 50 μmol/L (IQR:32–114;normal 5–15) with a median half‐life of 14.59 h. Median methylmalonic acid (MMA) was 0.68 μmol/L (IQR:0.18–3.16;normal<0.27). B12 and holotranscobalamin showed high specificity (87% and 98%) but low sensitivity (22% and 5%) for detecting cases associated with SCD, while homocysteine and MMA showed high sensitivity (95% and 93%) but lower specificity (13% and 45%).  Conclusions: Cumulative N2O exposure is the strongest predictor of severe neurological outcomes, demonstrating a dose‐dependent relationship with neurotoxicity. Homocysteine and MMA were sensitive markers associated with neurological toxicity, making them useful screening biomarkers; however, their limited specificity reduces their utility as confirmatory tests. These findings reinforce the importance of clinical assessment and exposure history in diagnosing toxicity.
SN  - 0306-5251
SN  - 1365-2125
ER  -