N2O Joke: A Consequence of Nitrous Oxide Inhalation

Introduction:
Nitrous oxide inhalation remains a concerning issue in the United States. In 2018, approximately 12.5 million people over the age of 18 acknowledge lifetime use of nitrous oxide (1). Canisters, also known as "whippits", are widely available and can be purchased without any age limit. Chronic and heavy use can have deleterious effects, including loss of consciousness, anoxic brain injury, cardiac arrest, and even death (2). Previous case reports have also identified concomitant Vitamin B12 deficiency, occasionally severe enough to cause subacute combined degeneration of the spinal cord (3-5). We present a case of a 35 year old male who presented with weakness after a relatively short duration of heavy nitrous oxide use.
Case Presentation
A 35 year old male with a past medical history significant for alcohol, benzodiazepine, cannabis use disorder initially presented to the emergency department (ED) with complaints of numbness and tingling in his fingers and toes. He was discharged from the ED on three occasions before admission to the hospital. On this final ED visit, he was noted to have significant gait ataxia with altered mental status. CBC with differential was significant for macrocytic anemia (Hgb: 11.2, MCV: 101). CT of the head without contrast did not show any acute intracranial hemorrhage. Serum ethanol level was negative, and his urine drug screen was positive for THC. He was admitted under the medicine service for further evaluation and Vitamin B12 level was found to be low at 89 (normal: >180 pg/mL). Addiction medicine was consulted, and after further discussion of his substance use history, the patient reported using whippits for about 1 month. He initially was using 50 cartridges per day and subsequently increased to 100-150 per day. He also admitted to occasional alcohol use with a history of dependence requiring residential treatment 5 months ago.
A neurology consultation was obtained, and the patient underwent an MRI of the cervical and thoracic spine, which showed: “Abnormal hyperintense signal seen on the STIR and T2-weighted images within the posterior columns of the spinal cord. The appearance is highly suggestive of subacute combined degeneration of the spinal cord which can be seen in the setting of vitamin B12 deficiency.” Patient was administered intramuscular Vitamin B12 injections and was discharged to inpatient rehabilitation. He is currently following up with neurology and physical therapy. During his last visit with neurology, the patient is still noticing weakness in his feet as well as continued loss of vibratory sensation, which has not completely resolved almost 3 months later.

Discussion:
Despite a relatively brief period of nitrous oxide use, this patient suffered lasting consequences. In patients who admit to using nitrous oxide, a thorough neurological history and physical examination should be performed. While there is no pharmacological management of the disorder, patients should be referred for behavioral treatment for their inhalant use disorder. Early recognition may prevent permanent neurological injury from occurring, as treatment with Vitamin B12 injections may reverse the course of the disease if identified early.

References: 1. 2018 National Survey on Drug Use. https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHDetailedTabs2018R2/NSDUHDetailedTabs2018.pdf. Accessed November 3, 2020.
2. Al-Sadawi, M et al. Inhaled Nitrous Oxide “Whip-Its!” Causing Subacute Combined Degeneration of Spinal Cord. Am J Med Case Rep. 2018; 6 (12): 237-240. https://dx.doi.org/10.12691%2Fajmcr-6-12-3
3. Kaar SJ et al. Up: The rise of nitrous oxide abuse. An international survey of contemporary nitrous oxide use. J Psychopharmacol. 2016;30(4):395-401. doi:10.1177/0269881116632375
4. Lan SY, Kuo CY, Chou CC, Kong SS, Hung PC, Tsai HY, Chen YC, Lin JJ, Chou IJ, Lin KL; PCHAN Study Group. Recreational nitrous oxide abuse related subacute combined degeneration of the spinal cord in adolescents - A case series and literature review. Brain Dev. 2019 May;41(5):428-435. doi: 10.1016/j.braindev.2018.12.003. Epub 2019 Jan 2. PMID: 30611595.
5. Thompson, AG et al. Whippits, nitrous oxide and the dangers of legal highs. Pract Neurol 2015 Jun; 15 (3): 207-209. https://dx.doi.org/10.1136%2Fpractneurol-2014-001071