Whippit, whippit bad: Why nitrous oxide abuse is no laughing matter

Doctors baffled by a patient’s unexplained symptoms of vitamin B12 deficiency and other compatible neurologic abnormalities might want to ask about chronic use of nitrous oxide, also known as laughing gas, according to the authors of a new study published in the Canadian Medical Association Journal. The sedative agent that’s been administered for years by dentists has also become an increasingly popular recreational drug, thanks to its relatively low cost and easy availability—a pack of 120 canisters costs less than $85 on Amazon—as well as the general perception that it’s safe compared to other drugs. “Its recreational use is now recognized as a growing problem in many jurisdictions, including Australia and several European countries, particularly the United Kingdom,” wrote the study authors. While the prevalence of recreational nitrous oxide use in Canada is unknown, a 2021 Global Drug survey found that 15% of Canadian respondents had used nitrous oxide in the preceding year. “Although no Canadian agencies track nitrous oxide use, evidence of substantial recreational use is apparent in Toronto and Montréal,” wrote the authors. Read: Anesthesia can cause disturbing sexual hallucinations, leading to lasting psychological trauma Acute, heavy use of nitrous oxide can occasionally cause death by asphyxiation, according to the study. Regular inhalation can have serious and even devastating neurologic consequences. “The main concern is the chronic complications,” study co-author Dr. Cyrille De Halleux told the Medical Post. “These are harder to diagnose or to attribute to nitrous oxide because when a patient is poisoned, usually they get exposed to the poison—for example, fentanyl or some opioid—and they get very sick, and it's obvious that they got sick because they used the substance just right before.” Chronic toxicity from nitrous oxide—also referred to by recreational users as “whippet” or “whippit” because it’s the same gas in those metal canisters used to whip cream— will typically present in people who inhale the gas dozens of times a day over several months. Some case reports have documented users who inhale more than 500 cartridges’ worth in a day. The three most common presentations of toxicity are damage to the spinal cord (myelopathy), nerve damage affecting strength and sensation (neuropathy) and behavioural abnormalities (encephalopathy), according to the study. “Over time, they may start presenting with weakness or numbness even if they haven’t consumed nitrous oxide in the past 24 hours,” explained Dr. De Halleux, a specialist in internal medicine, critical care and resident at Toronto’s Hospital for Sick Children and chief fellow in the Division of Clinical Pharmacology and Toxicology at the University of Toronto. “So it may not be obvious that neurological symptoms that can lead to paralysis and paraplegia are related to nitrous oxide.” Instead, doctors may arrive at a diagnosis of vitamin B12 deficiency and provide inappropriate treatment, “then the patient can get worse,” he added. Read: Waste not, why not? From anesthetic gases to circular-use resource, hospitals need to green up their acts Dr. De Halleux and his co-author Dr. David N. Juurlink—a staff internist and head of the division of Clinical Pharmacology and Toxicology at Sunnybrook Health Sciences Centre in Toronto—suggested a diagnostic approach that considers nitrous oxide toxicity “in the differential for all patients with signs and symptoms of peripheral neuropathy, myelopathy or encephalopathy, especially those who are younger.” Because a diagnosis of nitrous oxide toxicity needs to be supported by evidence of heavy use of the drug, it’s important for physicians to take a comprehensive history of drug and substance use, noted the authors. “When consistent clinical features and a history of heavy nitrous oxide exposure are both present, biochemical testing for functional vitamin B12 deficiency (homocysteine, methylmalonic acid) can confirm the diagnosis,” wrote the authors. “Nervous system involvement should be further characterized with magnetic resonance imaging and nerve conduction studies.” In their study, Dr. De Halleux and Dr. Juurlink noted that treatment includes stopping use of the substance, vitamin B12 supplementation and methionine. “Consider addiction medicine expertise and psychiatric, psychologic and social support,” wrote the study authors. “Vitamin B12 supplementation should also be given, sometimes in combination with methionine, although the evidence supporting efficacy is limited. Given its favourable safety profile, we suggest intramuscular or subcutaneous injection of 1000 micrograms vitamin B12 daily for one to two weeks, followed by weekly doses of 1000 micrograms parentally or daily doses of 2000 micrograms by mouth, until resolution of symptoms.” The authors also suggested supplemental oral methionine at a dosage of three grams three times a day for at least four to six weeks, or until symptoms improve significantly. “Folate supplementation is unlikely to benefit the patient and should not be given before vitamin B12 repletion because of the potential for exacerbation of symptoms and delayed recovery,” wrote the authors. “Physical rehabilitation and psychological and social supports may be required in selected cases.” Read: Laughing gas for depression?

Whippit, whippit bad: Why nitrous oxide abuse is no laughing matter

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