Neurological Manifestations Post Recreational Nitrous Oxide Exposure and its Implications for Rehabilitation: A Systematic Review of the Case Literature

Background: The use of Nitrous Oxide (N2O) in a recreational setting has been documented since the late 18th century as a euphoric agent termed “laughing gas”. There has been resurgence in its use in the recreational setting particular among the youth in the community despite falling into disrepute in anaesthetics due to its associated haematological and neurological complications. The primary aims of this systematic review is to detail the common neurological manifestations associated with the recreational use of N2O, detail its many mobility and functional impairments and identify potential predictors of neurological recovery including a period of rehabilitation prior to discharge.

Methods and findings: A detailed systematic review of the available literature was conducted using six different databases. Key Medical Subject Heading (MESH) terms were identified including “Nitrous Oxide”, “Laughing Gas”, “Vitamin B12”, “Spinal Cord” and “Substance Related Disorders”. Only case reports and case series were included. Patient demographics, presenting neurological impairments, neurological examination findings, laboratory, imaging and neurophysiological results were extracted. Mobility and functional deficits on presentation, treatment instituted including the provision of rehabilitation was also extracted.

66 unique articles met our inclusion criteria which included 88 individual cases. This included 43 males and 32 females with a mean age of 26 (± 7.51) years. The most common presenting neurological impairment was sensory disturbance (72%) and gait disturbance (47%). The most common neurological findings on clinical examination included vibration loss (68%) and proprioceptive loss (59%). 79 cases had some form of mobility and functional impairment on presentation but only 34 cases demonstrated residual neurological deficits on discharge. Of this, 59% had moderate to severe deficits while 41% had mild deficits. Despite most patients receiving supplemental vitamin B12, only 12 patients received a period of rehabilitation prior to discharge who had ongoing deficits.

Conclusion: The recreational use of nitrous oxide is an underreported cause of significant neurological impairments causing significant mobility and functional deficits. However, many of the patients with ongoing deficits are not offered a period of intensive multidisciplinary rehabilitation which could address many of these impairments and improve outcomes.


Tarsha C Bulathsinhala* and Stephen F Wilson

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