A surge in recreational nitrous oxide misuse has prompted new guidelines to be published and adopted with the aim of helping clinicians recognise cases and prevent spinal cord damage.
Nitrous oxide (N2O) is an anaesthetic gas with pain-relieving and anti-anxiety properties. It is commonly known as laughing gas and is widely and easily available for recreational use, as it can be "legally bought and sold for the purpose of making whipped cream". For recreational use, the gas is usually transferred from its canister to a balloon and then inhaled.
In addition to the risks of oxygen starvation, frostbite from exposure to extreme cold when gas is released from the highly pressurised canister, and injury from falling, with regular heavy recreational use of the drug comes the risk of nitrous oxide-induced subacute combined degeneration of the spinal cord (N2O-SACD).This condition can cause "serious and permanent disability" in young people, highlighted the authors of the new guidance, published in Practical Neurology.
The mechanism by which nitrous oxide causes subacute combined degeneration involves nitrous oxide-induced inactivation of vitamin B12 and inhibition of methionine synthetase, disrupting methylation and DNA synthesis, and leading to injury of the neuronal axons. Demonstrating a "pattern of myeloneuropathy usually associated with severe vitamin B12 deficiency", it commonly presents with sensory deficits, distal paraesthesia, weakness, ataxia, and gait disturbance. Other symptoms include bladder or bowel urgency or incontinence.
"The initial presenting complaint is often distal paraesthesia involving the lower and/or upper limbs. If the patient ignores this, or if N2O-SACD is not diagnosed at presentation, patients may then develop gait ataxia, falls, or inability to walk independently," the authors described.
Commonly Misdiagnosed and Inappropriately Treated
Awareness and recognition of the disease were crucial to preventing long-term harm, explained the authors, who emphasised that this could be helped by considering the local availability of N2O, the clinical features of the case, enquiring carefully about N2O use, and maintaining a high index of suspicion.
Professor Tom Warner, President of the Association of British Neurologists,explained that recreational use of nitrous oxide carries a "significant risk of damage to the nervous system, particularly the spinal cord, which is treatable if picked up".
While it may be treated effectively if recognised early with high doses of vitamin B12, it is "commonly misdiagnosed and inappropriately treated", the authors said. "All neurologists should be aware of N2O-SACD and its treatment," they added, but "no agreed treatment guidelines had previously existed".
The new research was based on a project to improve recognition, diagnosis, and treatment of N2O-SACD at the Royal London Hospital, where a new case presented, on average, once a week, revealed the authors.
"Patients often do not mention nitrous oxide use, possibly because they do not connect it with their symptoms or because they feel there is stigma associated with disclosing its use," highlighted the authors. They suggested that clinicians shouldbe aware of the prevalence of nitrous oxide abuse in their local area and make "careful enquiries" to determine whether nitrous oxide abuse might be causing the symptoms.
No Delay in Commencing Treatment Promptly
In the guidance, the authors afforded a pathway for patients with suspected N2O-SACD and emphasised that in the emergency department the focus should be on "immediate treatment with intramuscular hydroxocobalamin, time-critical investigations, and patient education".
Investigations in suspected N2O-SACD may support the clinical diagnosis, they said, but there should be "no delay in starting treatment promptly", with intramuscular B12 injections, while awaiting results. Intramuscular B12 injection is a "low-risk, high-impact" treatment they reassured, and should continue until improvement reaches a "plateau".
"On first suspecting N2O-SACD, we take blood for serum B12 and methylmalonic acid (MMA). Homocysteine is an alternative to MMA, but it must be transported to the laboratory on ice, which in practice places a barrier to its use," they explained.
The authors said they requested MRI of the cervical and thoracic cord on most patients with suspected N2O-SACD - the exception being for patients with a very clear history of recently heavy N2O use and mild symptoms that resolve with B12 therapy and who have stopped N2O, as for these cases "imaging may not be necessary".
Patient education was the most important aspect of N2O-SACD management, they said, and stressed that all patients should be warned that "N2O has caused their symptoms and that treatment with B12 will not work if they continue to use N2O, since this would inactivate the B12 supplements".
However, relapse following return to N2O use was relatively common, the authors said. Therefore, they "encourage all patients to contact their local drug and alcohol service to support their abstinence".
Speed of Guideline Adoption Unprecedented
In parallel with the publication of the new guidance, the recommendations from the research on the diagnosis and treatment of spinal cord damage caused by nitrous oxide misuse have been "simultaneously adopted" as official clinical practice guidelines by the Association of British Neurologists.
"We developed these practical guidelines to try to standardise care for patients who have come to harm from recreational nitrous oxide use,"Professor Alastair Noyce, consultant neurologist at Queen Mary, and senior author, pointed out. He expressed hope that "if implemented correctly" the guidelines will ensure patients get the treatment they need, and by improving efficiency in the emergency department, and reducing unnecessary admissions, pressure on hospitals will be alleviated.
The authors emphasised that the "unprecedented speed" in translating research into practice was necessary as medical cases of nitrous oxide abuse surged in parallel with increased use of what is now the second most popular recreational drug among young people in the UK.
Yesterday, during the first oral evidence to the Commons Health and Social Care Committee in its inquiry into prevention in health and social care in England, Chief Medical Officer Professor Sir Chris Whitty responded to concerns raised by Committee members about the growing appeal of nitrous oxide by promising a review of evidence on its health implications.
The newly published and adopted clinical practice guidelines set out how to "recognise, diagnose and, most importantly, treat" those people attending emergency departments with symptoms of subacute combined degeneration of the spinal cord, and "prevent long-term neurological disability", said Professor Warner.
The Preventive Neurology Unit is funded by Barts Charity. The authors declared no competing interests.