ToxCard: Chasing the Dragon

Authors: Victoria Serven, MD (Emergency Medicine Resident, Carolinas Medical Center, Charlotte, NC); Kathryn T Kopec, DO (Emergency Medicine Attending; Medical Toxicologist, Carolinas Medical Center, Charlotte, NC)// Edited/Reviewed by: Cynthia Santos, MD (@Cynthia Santos, MD); Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)

Case:

A 28-year-old male presents to the emergency department (ED) via EMS after being found unresponsive by friends. They last saw him the night before at a party where he was “chasing the dragon.” On arrival the patient has a GCS is 3, Temp 99.6, BP 130/80mmHg, HR 112 bpm, RR 16 breaths/minutes, SpO2 96% on RA. Physical exam demonstrates pinpoint pupils and extensor posturing in response to pain with occasional tonic movements in the upper extremities.

Questions:

• What is “Chasing the Dragon”, and why do people do it?
• What are the common side effects of this method of drug use?
• What are the signs and symptoms of Toxic Spongiform Leukoencephalopathy? 
• How is Toxic Spongiform Leukoencephalopathy managed? 

Background: 

Chasing the Dragon refers to the practice of heroin inhalation (1). It is performed by placing heroin in a small square of aluminum foil which is then heated from below. As the heroin melts it turns into a reddish-brown substance that may resemble a dragon’s tail (1). As the smoke forms the user “chases” it with a straw or a pipe inhaling it. Smoking heroin originated in Shanghai in the 1920s and was refined to “Chasing the Dragon” in Hong Kong in the 1950s (2). The practice spread to Southeast Asia in the 1960s, Europe in the 1980s, and to the United States in the 1990s (2).

When comparing inhalation verse injection of heroin there are a couple notable differences. First, there is a marked reduction in disease transmission when heroin in smoked rather than injected (1). Intravenous heroin has nearly 100% drug availability, while much of the drug is lost in the physiologic dead space of the airway with inhalation (3). Interestingly, in a study completed at the Addiction Research Center in Baltimore, volunteers were given controlled doses of intravenous and inhaled heroin and found that the onset of miosis and the sensation of being “high” was similar between the two groups (3). Heroin was detected within the blood within 2 minutes with both practices, though it was in found in lower serum concentrations in those who inhaled compared to those who injected (3). 

Common Side Effects (4):

• Dry mouth
• Pruritus
• Nausea
• Vomiting
• Skin flushing
• Chronic cough
• Bronchospasm 

Major Side Effects:

• Respiratory Depression
• Altered Mental Status
• Toxic Spongiform Leukoencephalopathy
• Death

What is Toxic Spongiform Leukoencephalopathy?

Toxic spongiform leukoencephalopathy is the destruction of white matter in the CNS primarily affecting the cerebellum via multivacuolar degeneration of oligodendrocytes (5). Different forms of leukoencephalopathy can be caused by many different substances. Cases of toxic spongiform leukoencephalopathy have been associated with methylenedioxymethamphetamine, ethanol, cocaine, toluene, and inhaled heroin (6). The mechanism of action is unknown but there are several theories (5):

• Aluminum toxicity 
• Reaction to an impure drug/contaminate (heroin “cut” with other substances)
• Induction of white matter mitochondrial dysfunction 

Signs and Symptoms:

Severity likely depends on the amount of heroin inhaled and the duration of abuse (7).  The disease can be tracked by severity of the syndrome or in stages (8). 

Severity Classification:

• Mild Syndrome:
  • Inattentiveness
  • Confusion
  • Ataxia
  • Psychomotor symptoms
• Moderate Syndrome:
  • Somnolence
  • Clonus  
  • Extrapyramidal symptoms
    • Hyperreflexia 
    • Muscle spasms
    • Myoclonic jerks 
• Severe Syndrome:
  • Generalized motor impairment
  • Aphasia
  • Hyporeflexia
  • Hypotonia 
  • Posturing
  • Altered mental status 
  • Respiratory depression
    • However, this is less significant than with other forms of heroin use

Stage Classification:

• Stage 1: 
  • Cerebellar dysfunction (including motor restlessness, ataxia, pseudobulbar speech) 
• Stage 2:
  • Extrapyramidal Syndrome (myoclonic jerks, choreoathetoid movements, spastic paralysis, and hyperactive reflexes)
• Stage 3:
  • Extensor posturing, akinetic mutism, central pyrexia, autonomic hyperactivity, and death

How To Make the Diagnosis:

• CT scan of the brain without contrast is often unremarkable but occasionally can display signs of hypoxic injury (6). 
• MRI is the gold standard (6): 
  • Areas effected: cerebellum, cerebellar peduncles, cerebral peduncles, and the posterior limb of the internal capsule 
  • Sparing of the anterior limb, dentate nuclei, and the U-fibers can distinguish it from other causes of leukoencephalopathy. 
  • Gray matter is relatively spared in this condition while it is usually affected in hypoxic injury. 

Treatment:

• There is no known antidote or proven treatments for this condition. 
• The standard of care is supportive care including IVF and benzodiazepines for muscles spasms and seizure activity (7). 
• It has been theorized that antioxidants may help reduce inflammation secondary to removal of free radicals (8). Unfortunately, no clinical trials have examined this treatment. 
• Empiric antioxidant therapy (8) that have been proposed but not validated for efficacy:
  • Coenzyme Q10 (300 mg QID)
  • Vitamin C (2000 mg daily)
  • Vitamin E (2000 mg daily)
• In a case series publication Dantrolene was used to treat the muscle rigidity and hyperthermia in 2 cases. The authors noted improvement of symptoms, however the evidence is lacking and also not validated (9). 
• Patients have the potential to regain significant neurologic function, however, recovery is often prolonged taking weeks to months. Radiologic resolution of white matter abnormalities has been documented after multiple months (10). 

Key Points:

• Inhaling heroin may induce toxic leukoencephalopathy. 
• Initial symptoms include confusion, ataxia and psychomotor symptoms.
• Symptoms may progress to include extrapyramidal signs.
• Severe disease is characterized by hyperpyrexia, mutism, spasms, hypotonia, and areflexia.
• Brain MRI is the imaging modality of choice. 
  • Diffuse, symmetrical white matter hyperintensities on T2 
  • Posterior to anterior gradient of involvement on FLAIR
  • Relative sparing of frontal lobes
• There is no proven treatment, current suggested therapy includes supportive care and antioxidant therapy with Coenzyme Q10, Vitamin C, and Vitamin E.
• Recovery, if any, is prolonged.

References:

1. Alambyan V, Pace J, Miller B, et al. The Emerging Role of Inhaled Heroin in the Opioid Epidemic: A Review. JAMA Neurol. 2018;75(11):1423–1434. doi:10.1001/jamaneurol.2018.1693
2. Strang J, Griffiths P, and Gossop M. (1997), Heroin smoking by ‘chasing the dragon’: origins and history. Addiction, 92: 673-683. doi:10.1111/j.1360-0443.1997.tb02927.
3. Jenkins AJ, Keenan  RM, Henningfield JE, and Cone EJ. Pharmacokinetics and pharmacodynamics of smoked heroin. Journal of Analytical Toxicology 18:317-330, 1994.
4. NIDA. What are the immediate (short-term) effects of heroin use?. National Institute on Drug Abuse website. https://www.drugabuse.gov/publications/research-reports/heroin/what-are-immediate-short-term-effects-heroin-use. May 28, 2020 Accessed July 30, 2020.
5. Keogh C, Andrews G, Spacey SD, Forkein KE, and Graeb D. Neuroimaging Features of Heroin Inhalation Toxicity: “Chasing the Dragon.” American Journal of Roentgenology 2003 180:3, 847-850
6. Buxton JA, Sebastian R, Clearsky L, et al. Chasing the dragon – characterizing cases of leukoencephalopathy associated with heroin inhalation in British Columbia. Harm Reduct J 8, 3 (2011). https://doi.org/10.1186/1477-7517-8-3
7. Singh R, Saini M. (2015). Toxic leucoencephalopathy after ‘chasing the dragon’. Singapore medical journal, 56(6), e102–e104. https://doi.org/10.11622/smedj.2015094
8. Molloy S, Soh C, Williams TL. Reversible delayed posthypoxic leukoencephalopathy. AJNR Am J Neuroradiol. 2006;27:1763–5. 
9. Achamallah N, Wright RS, Fried J. Chasing the wrong dragon: A new presentation of heroin-induced toxic leukoencephalopathy mimicking anoxic brain injury. J Intensive Care Soc. 2019;20(1):80-85. doi:10.1177/1751143718774714
10. Sanaei-Zadeh H. Toxic leukoencephalopathy. MOJ Toxicol. 2016;2(2):44. DOI: 10.15406/mojt.2016.02.00033