An Uncommon Adverse Effect of Synthetic Cannabinoids

Between January 1, 2015 and April 22, 2015, the American Association of Poison Control Centers reported getting 1900 calls related to synthetic cannabinoid exposure, proving that the popularity of this alternative to natural marijuana has been steadily increasing. Synthetic cannabinoids, when smoked or ingested, act on the endocannabinoid receptors, similar to delta-9 tetrahydrocannabinol, the primary psychoactive ingredient in marijuana.  While dyspnea related to synthetic cannabinoid use is common, other pulmonary adverse effects have rarely been reported, specifically inhalation fever which is discussed in a recent case published in the American Journal of Case Reports.

The patient, a 29-year-old male, presented to the emergency department with severe agitation after smoking the synthetic cannabinoid K2. Medical history included a diagnosis of schizoaffective disorder for which he was not receiving treatment. To sedate him, multiple doses of lorazepam and haloperidol were used. Physical examination of the patient showed the following:

* Temperature: 100.2º F

* Blood pressure: 110/50 mmHg

* Heart rate: 109/min

* Respiratory rate: 18/min

* Oxygen saturation: 95%

* Chest exam: No crackles, wheeze, rhonchi on auscultation; chest radiograph: diffuse reticular-nodular and interstitial infiltrates

* Cardiovascular exam: JVP not elevated, S1 and S2 heard, no additional heart sounds, murmurs, rubs; rate/rhythm regular

* Lab tests: Leukocytosis with predominant neutrophilia (83.4%); blood culture samples showed no growth after 5 days

* Urine toxicology: Negative for cannabinoids, benzodiazepine, phenycyclidine, opiates, cocaine, barbiturates

The patient was given ceftriaxone 1g IV, azithromycin 500mg IV, magnesium sulfate 2g IV (for hypomagnesemia), potassium phosphate 22mEq IV (for hypophosphatemia), famotidine 40mg daily for GI prophylaxis and heparin 500 Units SC twice daily for prophylaxis of venous thromboembolism. His mental status improved and his fever dissipated 24 hours after admission; repeat chest radiograph showed resolution of the pulmonary infiltrates. Clinicians were unable to re-evaluate his blood levels, as the patient refused repeat blood draws.

Once in stable condition, he was discharged with a diagnosis of inhalation fever due to synthetic cannabinoid and was told to abstain from use of this substance. For empirical treatment of pneumonia, he was given levofloxacin 750mg daily for seven days; he was also given a prescription for risperidone 1mg twice daily for two weeks for his schizoaffective disorder. Though an outpatient appointment was scheduled, the patient did not follow-up and so his long-term outcome is uncertain.

In the United States, there are over 50 types of synthetic cannabinoids; the substances are typically available in herbal blends, potpourri, and incense.  In this patient, given the fever and transient pulmonary infiltrates, inhalation fever is believed to have developed as a consequence to K2 inhalation. Symptoms associated with inhalation fever may include cough, dyspnea, headache, malaise, myalgia and nausea, however, this patient did not experience any of these, apart from leukocytosis which is a feature of this condition.

Treatment generally includes supportive care and avoidance of the causative agent. Other diagnoses considered for this patient included acute hypersensitivity pneumonitis (which may present in a similar manner), chemical pneumonitis (an inflammatory reaction to a particulate), or bacterial pneumonia (given the fever, tachycardia, leukocytosis, and pulmonary infiltrates). Infection, however, was not considered likely given a repeat chest radiograph 24 hours later showed resolution of the pulmonary infiltrates and blood culture was negative.

Given this is the first case to report on inhalation fever as a side effect of synthetic cannabinoid inhalation, further research is needed to understand the mechanism by which this reaction occurred. In the meantime, the authors warn that “as the Emergency Department visits by synthetic cannabinoid abusers are increasing, the importance of physicians being aware of these adverse effects cannot be overstated.”

Source:   Thiru Chinnadurai, Srijan Shrestha, Raji Ayinla. A Curious Case of Inhalation Fever Caused by Synthetic Cannabinoid. American Journal of Case Reports. 2016, doi: 10.12659   6th July 2016

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