Weakness and Incontinence in a 24-Year-Old Hiker With Multiple Sex Partners Who Uses Whippets

Hassan Khuram, MS; Scott Goldstein, DO, EMT-PHP


May 18, 2023

Over the past decade, nitrous oxide, also known as whippets or whip-its, has emerged as a popular substance of abuse among adolescents and young adults. According to the National Survey on Drug Use and Health, the lifetime prevalence of nitrous oxide use in the United States was 4.6% in 2015.[2] Nitrous oxide is traditionally used in dental procedures but has become an increasingly popular party drug, especially at music festivals.[2,3] Nitrous oxide is found in whipped cream canisters as a propellant and also in automobiles as a power booster.[4]

A popular route of administration is inhalation through a balloon, resulting in analgesic, anesthetic, and anxiolytic effects that lead to the potential for abuse and/or addiction.[2,4] Inhalation produces an initial "high" followed by feelings of euphoria and numbness. Because the effects last only 30 seconds, users often inhale multiple rounds of whippets in a row to sustain the feelings of euphoria.[5] Owing to the ease of accessibility, low cost, and euphoric effects of nitrous oxide and an inaccurate perception that its adverse effects are limited, recreational use is predicted to rise.[2]

Persons with acute intoxication can present with dizziness, confusion, nystagmus, and gait instability. These symptoms are thought to result from the higher water solubility of nitrous oxide, compared with oxygen, which allows it to enter the bloodstream through the alveoli at a faster rate than oxygen. This results in decreased oxygen delivery to the brain. Although healthy persons may be able to tolerate this form of hypoxia in a well-ventilated room, those with a history of heart disease, epilepsy, or other comorbidities may have arrhythmias, seizures, or even cardiac or respiratory distress.[2] In addition, cases have been reported of spontaneous pneumothorax in persons who inhale directly through a pressurized tank.[6] Long-term use of nitrous oxide can cause damage to the nervous system due to vitamin B12 deficiency,[2,5,7,8] resulting in the classic signs seen in the patient in this case.

The exact mechanism of how nitrous oxide use leads to vitamin B12 deficiency remains unknown, but multiple mechanisms of action have been proposed. Vitamin B12 is a water-soluble cofactor for multiple enzymatic reactions responsible for DNA synthesis and odd-chain fatty acid metabolism.[9] One of the leading theories is that long-term use of nitrous oxide causes permanent oxidation of cobalt ions in vitamin B12, leading to dysfunction of methylmalonyl-CoA mutase. This ultimately results in impaired myelination of the central and peripheral nervous system.[7]

Clinically, the impaired myelination can manifest as myeloneuropathy, subacute combined degeneration, peripheral neuropathy, and myelopathy.[2,5,8] Of all these manifestations, subacute combined degeneration is most commonly found.[2] The pathogenesis involves demyelination of the dorsal columns, spinocerebellar tract, and lateral corticospinal tract.[10] Paresthesias and loss of vibratory sensation and proprioception are due to demyelination of the dorsal columns. Spastic paresis can result from demyelination of the lateral corticospinal tract. Gait abnormalities are caused by damage to the spinocerebellar tract and dorsal columns.[10]

When nitrous oxide abuse is suspected, laboratory testing explicitly for nitrous oxide levels is insufficient, as it is rapidly cleared.[10] A complete blood cell count can provide multiple clues that point toward nitrous oxide abuse, such as megaloblastic anemia. However, studies have found that vitamin B12 levels are normal in more than 70% of persons with a history of nitrous oxide abuse.[5,8,10] Therefore, levels of methylmalonic acid and homocysteine should be evaluated, as they are more sensitive markers for assessing vitamin B12 status in persons who use nitrous oxide.[2]


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