Journal of Medical Toxicology

, Volume 15, Issue 4, pp 299–303 | Cite as

Nitrous Oxide Toxicity: Case Files of the Carolinas Medical Center Medical Toxicology Fellowship

  • Kartik ShahEmail author
  • Christine Murphy
Case File

Case Presentation

A 45-year-old man presented to the emergency department with paresthesias and a history of inhaling 100 canisters of whipped cream chargers per week for approximately 4 weeks. During this time period, he noted progressively worsening numbness and tingling in his distal extremities. These symptoms were worse in his lower extremities compared to his upper extremities. He presented to the emergency department after he was nearly involved in a motor vehicle collision. While driving that day, he could sense neither where his feet were in relation to the car pedals nor the vibration of the pedals. He ate an omnivorous diet, had no history of bariatric surgeries, and did not have any gastrointestinal symptoms.

Vital signs on arrival were temperature 36.8 °C, pulse 58 beats per minute, blood pressure 90/60 mmHg, respiratory rate 18 breaths per minute, and oxygen saturation 98% on room air. Physical examination revealed a middle-aged man appearing older than his stated age....


Nitrous oxide Vitamin B12 deficiency Subacute combined degeneration 


Compliance with ethical standards

Conflicts of Interest



  1. 1.
    Shoults K. Case report: neurological complications of nitrous oxide abuse. B C Med J. 2016;58(4):192–4.Google Scholar
  2. 2.
    Sen A, Chandrasekhar K. Spinal MR imaging in vitamin B12 deficiency: case series; differential diagnosis of symmetrical posterior spinal cord lesions. Ann Indian Acad Neurol. 2013;16(2):255–8.CrossRefGoogle Scholar
  3. 3.
    Green R, Kinsella LJ. Current concepts in the diagnosis of cobalamin deficiency. Neurology. 1995;45(8):1435–40.CrossRefGoogle Scholar
  4. 4.
    Thompson AG, Leite MI, Lunn MP, Bennett DL. Whippits, nitrous oxide and the dangers of legal highs. Pract Neurol. 2015;15(3):207–9.CrossRefGoogle Scholar
  5. 5.
    Patel KK, Mejia munne JC, Gunness VRN, et al. Subacute combined degeneration of the spinal cord following nitrous oxide anesthesia: a systematic review of cases. Clin Neurol Neurosurg. 2018;173:163–8.CrossRefGoogle Scholar
  6. 6.
    Flippo TS, Holder WD. Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B12 deficiency. Arch Surg. 1993;128(12):1391–5.CrossRefGoogle Scholar
  7. 7.
    Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014;349:g5226.CrossRefGoogle Scholar
  8. 8.
    LiPuma JP, Wellman J, Stern HP. Nitrous oxide abuse: a new cause of pneumomediastinum. Radiology. 1982;145(3):602.CrossRefGoogle Scholar
  9. 9.
    Gillman MA. Nitrous oxide, an opioid addictive agent. Review of the evidence Am J Med. 1986;81(1):97–102.CrossRefGoogle Scholar
  10. 10.
    Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149–60.CrossRefGoogle Scholar
  11. 11.
    Kobayashi M, Shimizu S. Cobalt proteins. Eur J Biochem. 1999;261(1):1–9.CrossRefGoogle Scholar
  12. 12.
    Ahn SC, Brown AW. Cobalamin deficiency and subacute combined degeneration after nitrous oxide anesthesia: a case report. Arch Phys Med Rehabil. 2005;86(1):150–3.CrossRefGoogle Scholar
  13. 13.
    Gürsoy AE, Kolukısa M, Babacan-yıldız G, Celebi A. Subacute combined degeneration of the spinal cord due to different etiologies and improvement of MRI findings. Case Rep Neurol Med. 2013;2013:159649.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Jordan JT, Weiser J, Van ness PC. Unrecognized cobalamin deficiency, nitrous oxide, and reversible subacute combined degeneration. Neurol Clin Pract. 2014;4(4):358–61.CrossRefGoogle Scholar
  15. 15.
    Kondo H, Osborne ML, Kolhouse JF, Binder MJ, Podell ER, Utley CS, et al. Nitrous oxide has multiple deleterious effects on cobalamin metabolism and causes decreases in activities of both mammalian cobalamin-dependent enzymes in rats. J Clin Invest. 1981;67(5):1270–83.CrossRefGoogle Scholar
  16. 16.
    Stacy CB, Di rocco A, Gould RJ. Methionine in the treatment of nitrous-oxide-induced neuropathy and myeloneuropathy. J Neurol. 1992;239(7):401–3.CrossRefGoogle Scholar
  17. 17.
    Hathout L, El-saden S. Nitrous oxide-induced B12 deficiency myelopathy: perspectives on the clinical biochemistry of vitamin B12. J Neurol Sci. 2011;301(1–2):1–8.CrossRefGoogle Scholar
  18. 18.
    Scalabrino G, Nicolini G, Buccellato FR, et al. Epidermal growth factor as a local mediator of the neurotrophic action of vitamin B(12) (cobalamin) in the rat central nervous system. FASEB J. 1999;13(14):2083–90.CrossRefGoogle Scholar
  19. 19.
    Scalabrino G, Mutti E, Veber D, Aloe L, Corsi MM, Galbiati S, et al. Increased spinal cord NGF levels in rats with cobalamin (vitamin B12) deficiency. Neurosci Lett. 2006;396(2):153–8.CrossRefGoogle Scholar
  20. 20.
    Scalabrino G, Tredici G, Buccellato FR, Manfridi A. Further evidence for the involvement of epidermal growth factor in the signaling pathway of vitamin B12 (cobalamin) in the rat central nervous system. J Neuropathol Exp Neurol. 2000;59(9):808–14.CrossRefGoogle Scholar
  21. 21.
    Buccellato F, Miloso M, Braga M, et al. Myelinolytic lesions in spinal cord of cobalamin-deficient rats are TNF-alpha-mediated. FASEB J. 1999;13(2):297–304.CrossRefGoogle Scholar
  22. 22.
    Obeid R, Fedosov SN, Nexo E. Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency. Mol Nutr Food Res. 2015;59(7):1364–72.CrossRefGoogle Scholar
  23. 23.
    Kamath A, Pemminati S. Methylcobalamin in vitamin B12 deficiency: to give or not to give? J Pharmacol Pharmacother. 2017;8(1):33–4.CrossRefGoogle Scholar
  24. 24.
    Hvas AM, Nexo E. Diagnosis and treatment of vitamin B12 deficiency--an update. Haematologica. 2006;91(11):1506–12.PubMedGoogle Scholar
  25. 25.
    Butzkueven H, King JO. Nitrous oxide myelopathy in an abuser of whipped cream bulbs. J Clin Neurosci. 2000;7(1):73–5.CrossRefGoogle Scholar
  26. 26.
    Lee CC, Surtees R, Duchen LW. Distal motor axonopathy and central nervous system myelin vacuolation caused by cycloleucine, an inhibitor of methionine adenosyltransferase. Brain. 1992;115(Pt 3):935–55.CrossRefGoogle Scholar
  27. 27.
    Scott JM, Dinn JJ, Wilson P, Weir DG. Pathogenesis of subacute combined degeneration: a result of methyl group deficiency. Lancet. 1981;2(8242):334–7.CrossRefGoogle Scholar

Copyright information

© American College of Medical Toxicology 2019

Authors and Affiliations

  1. 1.Department of Emergency MedicineAtrium Health’s Carolinas Medical CenterCharlotteUSA

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