What is the annual death rate associated with nitrous oxide (N2O) abuse?

Annual Death Rate Associated with Nitrous Oxide Abuse

There is currently no established annual death rate specifically for nitrous oxide (N2O) abuse, but mortality is primarily associated with asphyxiation during acute use and thrombotic events in heavy users.

Mortality Mechanisms from N2O Abuse

Acute Mortality Causes

• Asphyxiation: The primary acute cause of death from recreational N2O use is asphyxiation
  • N2O displaces oxygen in closed spaces, leading to hypoxia 1
  • Fatal accidents have been reported due to asphyxia when using N2O in confined spaces 2
  • Laboratory simulations confirm that N2O displaces oxygen in closed spaces, which likely leads to asphyxia 1

Long-term Mortality Causes

• Thrombotic events: A concerning emerging risk in heavy users
  • A 2023 study found 5% of patients who used N2O recreationally presented with severe thrombotic events 3
  • These included arterial thrombosis (acute coronary syndrome, femoral artery thrombosis, cerebral artery thrombus) and venous thromboembolisms (pulmonary embolisms, portal vein thrombosis, cerebral vein thrombosis) 3
  • Associated with extremely high homocysteine levels (median 125 μmol/L; reference <15 μmol/L) 3
  • Affected patients reported using 400-6000g (50-750 balloons) of N2O in a single day 3

Vitamin B12 Deficiency Complications

• Heavy or sustained use of N2O inactivates vitamin B12, resulting in:
  • Functional vitamin B12 deficiency
  • Peripheral neuropathy
  • Megaloblastic anemia 2
  • Neurological symptoms often precede thrombotic events in heavy users 3

Prevalence and Usage Patterns

• N2O is the second most popular recreational drug after cannabis in the UK 2
• Last month prevalence among clubbers and ravers ranges between 40-80% 2
• Most users take less than 10 balloons per episode 2
• About 80% of users have fewer than 10 episodes per year 2
• Usage is generally moderate and infrequent for most users 4

Clinical Considerations

Risk Factors for Mortality

• Heavy usage patterns (hundreds of balloons in a single session)
• Use in confined spaces without adequate ventilation
• Concomitant use with other substances
• Pre-existing vitamin B12 deficiency

Warning Signs

• Persistent numbness (reported by 4.3% of last-year users) 4
• Neurological symptoms (often precede thrombotic events) 3
• Confusion and hallucinations (reported by 27.8% and 23.9% of last-year users, respectively) 4

Harm Reduction Approach

While specific annual mortality data is lacking, the evidence suggests that N2O-related deaths are relatively rare but do occur. The primary risks are:

1. Acute asphyxiation during use in confined spaces
2. Thrombotic events in heavy, frequent users due to extreme homocysteine levels
3. Neurological damage from vitamin B12 inactivation

Healthcare providers should be aware of these risks when encountering patients who use N2O recreationally, particularly those reporting heavy use patterns.