Nitrous oxide toxicity title image showing whippet canisters and a red balloon on a hospital stretcher

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What Is Nitrous Oxide?

Nitrous Oxide (N2O) is a colorless, odorless inhaled anesthetic that has been used for centuries, particularly in the surgical world. Mechanistically, it can induce euphoria, anxiolysis, and intoxication via NMDA receptor antagonism.

During the late twentieth century, nitrous oxide was increasingly used recreationally due its accessibility and perceived benign nature.

The modern day slang term for nitrous oxide is “whippets” – which tends to refer to the canisters that contain this agent and are frequently used as whipped cream foaming agents.

Despite the legal nature and benign perception of nitrous, frequent use can lead to lasting and permanent neurologic effects.

How Nitrous Oxide Causes Toxicity

Nitrous oxide toxicity results from its ability to oxidize the cobalt moiety in Vitamin-B12, thus leading to a functional B12 deficiency, despite adequate consumption and absorption.1

Functioning B12 is needed as a cofactor for methionine synthase.2 This enzyme has two critical roles:

The conversion of 5-methyl tetrahydrofolate to tetrahydrofolate; tetrahydrofolate is essential for the synthesis of our DNA.

And the conversion of homocysteine to methionine; methionine is needed to maintain the integrity of the myelin sheath of our axons.

As a result, nitrous toxicity leads to: a megaloblastic anemia and demyelination of both the dorsal columns and the lateral corticospinal tracts (also known as subacute combined degeneration).

Clinical Manifestations of Nitrous Oxide Toxicity

These patients will have a combination of both upper and lower motor neuron symptoms due to demyelination of the dorsal columns, lateral corticospinal tracts, and peripheral nerves. As a result, the following may manifest:

Dorsal Columns: diminished sense of proprioception, vibration, and fine touch.

Lateral Corticospinal Tracts: upgoing plantars, hyperreflexia, weakness of voluntary distal muscle control

Peripheral Nerves: numbness/tingling and weakness in a glove and stocking pattern (symptoms that start initially in the feet and hands that progressively spread proximally to the ankles and wrists)

Taking all of this into account, patients may present with difficulty ambulating, positive Romberg sign, dysmetria (difficulty with finger to nose or heel to shin), upgoing Babinski reflex, and decreased strength and sensation in a glove and stocking pattern.

REBEL Rundown

What Is Nitrous Oxide?

How Nitrous Oxide Causes Toxicity

Clinical Manifestations of Nitrous Oxide Toxicity