S5E7: Nitrous Oxide Toxicity
Welcome back to another episode of The Case.Report! This month Leah and Liam take on a case of nitrous oxide (N2O) toxicity at the TCR ED, a presentation which unfortunately seems to be on the rise both nationally and around the globe. Our adult in the room is Dr Deirdre McElwee, an EM Consultant based in Tullamore with discretionary training in toxicology completed at The Royal Prince Alfred Hospital, Sydney. Who better to help us tackle our toxicology case?!
Before we dive in, be sure to check out last month’s episode where Callum, Rachel and Stephen tackled 3 very common paediatric urology. High yield and bursting with clinical pearls, it's not one to miss!
Listen now on Spotify, Apple Podcasts or wherever you get your podcasts, and as always check out our Bluesky, Instagram, Facebook and X to keep updated with all things TCR.
Without further ado, let's get stuck in.
A 21-year-old man has presented to the TCR ED with pins and needles to his feet. He’s vitally stable and has been marked as a cat 3 from triage. He stumbles into the room when called and it's subtly noted that it looks like he’s ‘walking on the moon’. He looks anxious and you note a smell of marjuana.
Immediately Liam is concerned. This is a young ataxic patient, with vague sensory symptoms who’s waited all night to be seen.
Diving a bit deeper into the history we learn that he has been experiencing tingling in his lower limbs the last few weeks. He noticed it while out walking at night and felt a bit unsteady. He initially put it down to feeling a bit cold in the winter months but it seems to have persisted and now he’s beginning to feel off balance.
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What was he doing at the time?
Has it worsened or spread to any areas?
Any other neurological symptoms?
Visual changes?
Recent infections/illness?
Ascending?
Lower back pain/saddle paraesthesia/ faecal incontinence/ urinary retention?
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Social Hx:
Alcohol
Drug use
Sexual hx
Occupational hx
Fam Hx: DM, neurological or autoimmune.
The plot thickens..
The paraesthesia is limited to his feet. It was initially intermittent but now seems a bit more constant. He smokes 5-10 cigarettes/day and occasionally uses nitrous oxide but his demeanour makes us think that he’s underestimating this…
At this point, are worried about paraesthesia in the presence of nitrous oxide use. Particularly in the absence of other red flags.
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We want to know the frequency
We want to know the quantity
Most people use balloons
Best way to quantify is by the canisters/cylinders.
Patients may start using medical cylinders. These contain between 50 - 100 canister equivalents.
Its crucial to be as accurate as possible as nitrous oxide is a dose dependent toxicity!
Exam findings:
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Exam findings: 〰️
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Tone, power, relfexes and sensation intact.
Hoffman’s sign +ve
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Tone and power normal save dorsiflexion is 4/5 bilaterally.
Light and pinprick touch is normal.
Loss of vibration sense to the level of the medial malleolus and symmetrical loss of proprioception at the feet.
Ankle jerks are absent.
Rhomberg’s +ve.
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No abnormalities.
Quick summary so far:
21-year-old man with a history of intermittent N2O use. Significant abnormalities of power, proprioception and reflexes. Bringing it all together we are worried about subacute degeneration of the cord secondary to N2O toxicity.
You can download this infographic here.
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Bloods:
Routine: U&E, FBC, LFTs, TFTs +/- HIV & syphilis.
Case specific:
B12 and folate.
Methylmalonic acid (MMA).
Homocysteine
± HIV & syphilis if suspected
Ideally obtain an MRI spine: Usually changes are seen in the dorsal column of cervical and thoracic spine. Sometimes you can see the classic “B sign” of SCD.
Nerve Conduction Studies may be considered if there is suspicion for a peripheral neuropathy - don’t be afraid to link in with your friendly neurology colleagues for advice if you aren’t sure!
Note: Nitrous oxide leads to a functional deficit in B12. B12 levels may be normal.
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B12, folate, MMA and homocysteine should be checked BEFORE starting treatment. If we give the B12 injection before ordering these tests it may give falsely reassuring results.
Dr McElwee advises to notify the lab in advance of sending the samples to ensure no mix ups.
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N2O can cause different forms of neuropathy - Subacute combined degeneration of the cord / peripheral neuropathy / myelopathy / mixed neuropathy. Nerve conduction studies may be considered in addition to an MRI based on symptoms.
Management
There is much debate is on how long to continue B12 and folate for and this is not discussed a huge amount in the literature. It is crucial however, that B12 and folate should be started on the day to prevent disease progression.
Daily 1mg B12 injections x1/52, weekly B12 thereafter until the follow up appointment. Long term B12 based on symptom resolution.
Treatment dose 5mg folic acid daily
Average time of improvement: Big range from weeks to months.
Based on metabolism, nutritional status.
Repeat B12 and folate levels in the community.
“I can’t emphasise the importance of education enough”
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Most people are unaware of the risk of irreversible spinal cord injury
Factor this into the discussion, especially in ED (resources limited and time limited)
Does this patiet need to be admitted?
Investigations can take a few days to come back. Despite this, most cases can still be managed in the community. The 2 most important things in this regard are taking a social history and giving good information on the administration of B12 injections and folic acid. RCEM has very helpful best practice guidelines on this!
If the patient is relsiable, their symptoms are mild and we can orgnaise neurological or other appropriate follow up within 1-2 weeks they can be discharged safely.
Follow up is really important as we need to make sure that he does not go back on the N2O. The risk of long term, irreversible neurological impairment in the absence of cessation is very high.
Dr McElwee discusses how in Australia some considerations for admission included if they can’t walk independently, if there is significant haematological abnormalities, significant psychiatric involvement, or needs admission for urgent access to MRI.
You can download this infographic here.
Pathophysiology and pharmacology deep(ish) dive!
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NMDA receptor antagonist
Used as an anaesthetic: Quick onset and quick offset analgesic properties.
Very short half life → Quantity of inhalation is really important for dose dependent toxicity.
Easily accessible and not currently a controlled drug in Ireland. Sold legally for catering and industrial processes
Street names: Nangs, whippets, bulbs or balloons.
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In nitrous oxide toxicity, B12 is present in the body in normal amounts but nitrous oxide prevents B12 from doing its job maintaining the myelin sheath.
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B12 converts MMA and homocysteine into substances which maintain the myelin sheath.
In nitrous oxide toxicity, B12 cannot convert these substances and so they build up in the body.
Looking for elevated MMA and homocysteine is a key part of working up these patents.
This is why it is crucial to take the bloods before giving B12 and folate.
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The morbidity & mortality in the acute intoxication phase is generally low. It’s generally related to accidental asphyxiation or trauma.
Frostbite type injuries from direct inhalation from a cold pressurised canister.
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Megaloblastic macrocytic anaemia
Increase risk of VTE
There has been one case report of a 28-year-old lady with a STEMI
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While it’s important to know about the details of subacute combined degeneration of the spinal cord, the presentation of UL / LL findings can be varying including myopathies and peripheral neuropathies.
Sensory loss of the dorsal column will give you the pyramidal pattern of weakness
Peripheral neuropathy is a length dependent large and small fibre sensory change which is generally painful and symmetrical.
There may also be eye presentations
Vision changes due to optic neuropathy
Have a high index of suspicion with eye presenting complaints
And now, why you’re really here… for the EPIDEMIOLOGY!
Prevalence: Not routinely collected in the National Irish alcohol and drug survey. Most recent data to go on is the Irish results of the 2021 European Web survey on drugs.
They looked at how recently people have used N2O
And the number of canisters used on day that they use N2O
Statistics:
76% of participants had never used N2O
1% had used N2O in the last month.
21% used less than one canister in a day
26% used more than 10 canisters in a day
The number of canisters used was higher in the 18-24 year-old group (>30%)
Planet youth survey 2021 looking at post Junior Cert students N2O use.
Around 6% of young males and 5% of young females have used N2O before.
Males in 5th year had a greater prevalence of lifetime use (12%)
Highlights the need for a public health campaign targeting N2O use in this age group.
Increase in prevalence is noted worldwide; one study (Australia spanning ‘03-’20), triangulated data sources (social media posts, poisons centres, hospital admissions) showed that there was:
Increase in presentations of 10% per year
6x increase in terms of calls to the poisons centre
N2O is a cheap, available, highly prevalent drug in the <25yo population so important to be aware of it! It causes short term euphoria and is a fairly poorly controlled drug. Always consider it in your differential in these age groups.
Take home messages
Liam:
Always keep N2O abuse in your differential for a young person with vague neurological symptoms. Diagnosing it can prevent long term neurological damage!
Leah:
Consider other differentials like syphilis and STIs but keep it simple. Young person with neurological symptoms and uses N2O. Check B12, homocysteine, MMA +/- MRI. Start B12 and folate. Have a discussion with the patient. Explain to them the risk of long term neurological damage. We’re at the forefront of public health in the ED!
Dr McElwee:
Remember that N20 is cheap, available and is being used increasingly by young people between the ages of 16-24. Target your history and look for other drugs of abuse. Be familiar with street names of drugs. Ask questions in a non-judgemental manner. Be aware of biases affecting this vulnerable patient group, other differentials often get missed and symptoms & signs can be subtle. Things are rarely textbook - keep your differentials wide!
Referenced in text
Page last updated:
03/03/2025
