Whippets: The Forgotten Drug of Abuse

Author: Jane Belyavskya, MD

Reviewed by: Sage Wiener, MD

Patient presentation

A 38-year-old male with no significant past medical history presents with bilateral lower extremity weakness and lower extremity swelling for two weeks. The patient sustained a mechanical fall 10 days ago; he “rolled” his right ankle and fell. He denies head trauma or loss of consciousness at that time. Since that injury, the patient has been unable to get out of bed. The patient also complains of urinary incontinence, ataxia, and abdominal distention for two weeks. He had similar ataxia two years ago and self-administered B12 shots which improved his gait. He denies perirectal or saddle anesthesia, fever, and chills. Review of systems is otherwise negative.

Physical exam:

VITAL SIGNS:  BP 124/89 mm Hg HR 84/min RR 18/min Temp 98 F

HEENT: normocephalic and atraumatic, PERRL, conjunctival pallor noted, EOM intact, moist mucous membranes, neck supple, trachea midline

Cardiac: Normal S1 and S2, no murmurs/rubs/gallops

Respiratory: Normal breath sounds, clear to auscultation bilaterally

Abdomen: soft, non-tender, non-distended

Neurological: CN II-XII intact, 5/5 strength in upper extremities, 2/5 strength/reduced sensation/proprioception/vibration sense bilateral lower extremities, normal finger to nose, unable to perform heel to shin, unable to assess gait due to weakness, decreased rectal tone

So what’s in your differential diagnosis?

In the patient with ataxia and lower extremity weakness, our differential diagnosis includes epidural abscess, cauda equina syndrome, Guillain-Barre Syndrome, normal pressure hydrocephalus, CVA, and less often, subacute combined degeneration. The initial evaluation consists of laboratory testing to assess electrolyte abnormalities, complete blood cell count (including MCV to assess for any nutritional deficiencies) with subsequent MR spine given 3/5 strength in bilateral lower extremities and urinary incontinence. Our patient has no history of IV drug abuse and no evidence of skin changes to the back, making epidural abscess less likely. He has no prior history of malignancy or trauma, therefore cauda equina syndrome is also unlikely. So what would cause our patient with lower extremity weakness and swelling, as well as loss of vibration sense and proprioception, to present with possible subacute combined degeneration? The patient eventually discloses that he has heavily used whippets (30-40 per day) for the last 3-4 years – the presentation becomes a little more clear. 

Pertinent laboratory testing:

CBC                              

WBC	7.03
RBC	3.81
HGB	13.0
HCT	39.6
MCV	103.9
MCH	34.1

Vitamin B12 >2000

Methylmalonic acid, serum 707

Homocysteine 245

Note the elevated MCV – causes of macrocytic anemia include B12 or folate deficiency, liver disease, alcoholism, hypothyroidism, and medications

More importantly, what are whippets and who still uses them?

Whippets is a term used to describe the nitrous oxide charger used for whipped cream dispensation. They are easily accessible and historically abused, because nitrous oxide causes euphoria and reduces anxiety. Nitrous oxide is referred to as “laughing gas” and is often used as an anesthetic.

Although not commonly abused by the general population today, whippets and nitrous oxide were abused in the past and currently in some populations (especially adolescents), resulting in significant long term consequences, particularly lower extremity paraparesis due to subacute combined degeneration (1).

Epidemiology

Nitrous oxide was first used as an anesthetic agent, and is still used in OR, ICU, and outpatient clinics (specifically dental procedures). It unfortunately also has a long history of abuse in the form of whippets.

What does nitrous oxide inhalation feel like?

Recreational uses of N2O describe a feeling of derealization, light-headedness and analgesia, as well as occasional visual hallucinations (2). 

How do you actually go about abusing whippets?

This is an art all on its own. Whippets should not be inhaled directly from the pressurized canister that is purchased. There are reports of significant barotrauma when directly inhaled, including but not limited to pneumothorax, pneumomediastinum, and tympanic membrane rupture. 

The most common method of abuse is via a “cracker” device, which is a low-cost device engineered to puncture the canister and dispense nitrous oxide into a balloon, from which it can be inhaled more safely. 

Another (more costly) option  is to insert the cartridges into a whipped cream dispenser and inhale from the dispenser. This has been referred to as “nanging.”(3)

What are the long-term consequences of nitrous oxide abuse?

Chronic abuse of N2O can lead to multiple neurological effects that stem from the inactivation/inhibition of vitamin B12. These include polyneuropathy, ataxia, and psychosis. 

What is the mechanism of action? How does chronic nitrous oxide use result in lower extremity weakness?

Nitrous oxide is a strong oxidizer of the cobalt atom in cobalamin, rendering it inactive. B12-dependent enzymes including methionine synthetase and methylmalonyl coenzyme A mutase therefore cannot act in the creation of myelin protein and DNA. Since methionine synthetase cannot function with methylcobalamin (B12), long-term abuse of nitrous oxide and subsequent chronic inactivation of B12 results in demyelination of the central and peripheral nervous system (ie subacute combined degeneration). Moreover, the inability to utilize homocysteine to produce methionine and subsequently produce myelin protein results in elevated homocysteine levels (4). 

What happened to our patient?

After admission to the neurology floor, the patient was found to have an elevated serum homocysteine concentration (245 Reference range <15), indicating functional B12 deficiency despite B12 level >2000. Symptoms improved within two days of admission with the administration of supplemental B12. 

Management

Since subacute combined degeneration is due to functional B12 deficiency (specifically, the oxidation of B12 in the setting of nitrous oxide abuse), the treatment is (you guessed it) B12 supplementation and abstinence from nitrous oxide abuse. Our patient had been self-administering B12 injections at home without improvement; however, this is likely due to subsequent oxidation of the additional B12 due to persistent nitrous oxide abuse. The patient had a prolonged hospital course due to the necessity for rehabilitation and was discharged 2 months after admission. 

Teaching Points

1. Surprisingly, people still use whippets, so keep subacute combined degeneration/nitrous oxide toxicity on your differential in a patient with lower extremity weakness

2. When concerned for subacute combined degeneration/nitrous oxide toxicity, check homocysteine levels (B12 levels will be normal in the setting of nitric oxide use)

3. In patients with lower extremity weakness and evidence of macrocytic anemia, always consider B12 deficiency or nitrous oxide toxicity. 

References

[1] Flynn SW, Cheema N. N2O Toxicity: A Rising Concern as Street Use Surges. EM Resident. Accessed September 23, 2021. https://www.emra.org/emresident/article/nitrous-oxide-toxicity/

[2] van Amsterdam J, Nabben T, van den Brink W. Recreational nitrous oxide use: Prevalence and risks. Regul Toxicol Pharmacol. 2015;73(3):790-796.

[3] Attaalla K, Santos C. TOXCard: Nitrous Oxide ‘Whippit’ Abuse. emDocs. Accessed September 23, 2021. http://www.emdocs.net/toxcard-nitrous-oxide-whippit-abuse/

[4] Thompson AG, Leite MI, Lunn MP, Bennett DL. Whippits, nitrous oxide and the dangers of legal highs. Pract Neurol. 2015;15(3):207-209.

[5] Dubrey S, Smith R. ‘Whippits’: nitrous oxide gas inhalation as recreational drug use. Br J Hosp Med (Lond). 2016;77(8):492.