The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–3, 2016 Ó 2016 Elsevier Inc. All rights reserved. 0736-4679/$ - see front matter
Selected Topics: Toxicology
SYNTHETIC CANNABINOID ABUSE RESULTING IN ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION REQUIRING PERCUTANEOUS CORONARY INTERVENTION Richard J. Hamilton, MD,* Vadim Keyfes, MD,* and Sahil S. Banka, MD† *Department of Emergency Medicine and †Department of Cardiology, Drexel University College of Medicine, Philadelphia, Pennsylvania Reprint Address: Richard J. Hamilton, MD, Department of Emergency Medicine, Drexel University College of Medicine, 245 North 15th Street, Mailstop 1011, Philadelphia, PA 19102
, Abstract—Background: Synthetic cannabinoids (SC) are recreational designer drugs intended to mimic delta-9tetrahydrocannabinol while surreptitiously circumventing classification by the Drug Enforcement Administration. Case Report: A 50-year-old black male arrived in the Emergency Department transported by Emergency Medical Services (EMS) for altered mental status after complaining of chest pain associated with smoking SCs. EMS found the patient with an empty foil pack labeled ‘‘Scooby Snax Limited Edition Blueberry Potpourri.’’ The patient was somnolent, but became agitated when stimulated and complained of chest pain. Vital signs were blood pressure 87/52 mm Hg and pulse 52 beats/min. The electrocardiogram demonstrated an inferior wall myocardial infarction. Coronary angiography identified an occluded obtuse marginal second branch that was successfully opened with a drug-eluting stent. The patient recovered uneventfully. Urine drug screen was negative for cocaine, and gas chromatography/mass spectrometry testing of the smoked material identified PB-22 and AMBFUBINACA as the active ingredients. Why Should an Emergency Physician Be Aware of This?: Emergency physicians and cardiologists need to be aware that the mechanism of action of synthetic cannabinoids on the endocannabinoid system may result in acute ST-segment elevation myocardial infarction requiring percutaneous coronary intervention. Ó 2016 Elsevier Inc. All rights reserved.
INTRODUCTION Synthetic cannabinoids (SC) are recreational designer drugs intended to mimic delta-9-tetrahydrocannabinol while surreptitiously circumventing classification by the Drug Enforcement Administration (DEA). They are sprayed on plant material and packaged as potpourri and labeled not for human consumption. Urine drug screens do not detect SCs, nor do they cross-react with the tetrahydrocannabinol (THC) component of existing assays. This is the first reported case of an SC requiring percutaneous coronary intervention (PCI). Prior reports of myocardial ischemia in mostly younger patients have demonstrated low troponin peaks and normal coronary arteries on cardiac catheterization (1,2). CASE REPORT A 50-year-old black male arrived in the Emergency Department (ED) transported by EMS for altered mental status after complaining of chest pain associated with smoking SC. EMS found the patient with an empty foil pack labeled ‘‘Scooby Snax Limited Edition Blueberry Potpourri.’’ The patient was somnolent but became agitated when stimulated, and complained of chest pain. The patient could not provide an adequate past
, Keywords—synthetic cannabinoids; myocardial infarction; percutaneous coronary intervention; endocannabinoid system
RECEIVED: 8 September 2016; ACCEPTED: 12 September 2016 1
medical history, nor could the patient appropriately identify the onset, character, or degree of chest pain. Vital signs obtained on arrival were blood pressure 87/52 mm Hg, pulse 52 beats/min, respiratory rate 16 breaths/min, oral temperature 36.7 C, and pulse oximetry 100% on 2 L nasal cannula. Physical examination revealed a somnolent patient without focal neurologic deficit who awakened to voice and would answer yes/no questions slowly. Lungs were clear to auscultation, respirations were nonlabored, and breath sounds were equal. Cardiovascular examination revealed normal capillary refill and a regular rate and rhythm without murmurs. Pupils were 3 mm, reactive, equal, and round. The head was normocephalic and atraumatic. The skin was warm, dry, and pink. The neck was supple and the trachea midline. Intravenous access was obtained and the patient was started on a 1-L bolus of normal saline. The patient’s electrocardiogram (ECG) demonstrated an inferior wall myocardial infarction (Figure 1). The patient became more combative and was intubated with first-pass success using succinylcholine and etomidate. The patient was immediately brought to the cardiac catheterization laboratory and an occluded obtuse marginal second branch was identified and opened with a drug-eluting stent (Figure 2). Initial troponin was 0.048 ng/mL (normal < 0.03 ng/mL) and creatine kinase was 96 IU/L. Urine drug screen was negative for cocaine, 3,4-methylenedioxymethamphetamine (‘‘Ecstasy’’), methadone, oxycodone, phencyclidine, THC, and tricy-
Figure 1. Electrocardiogram on presentation.
R. J. Hamilton et al.
clics; and positive for benzodiazepines, buprenorphine, and opiates. Post PCI, the troponin peaked at 32.95 ng/ mL, creatine kinase peaked at 1750 IU/L, and both trended down over the next 72 h. Subsequently, the patient was able to provide a 17 pack-year smoking history as a cardiac risk factor. Lipid profile was low risk, with total cholesterol in the normal range. Echocardiography demonstrated normal systolic and diastolic function and an ejection fraction of 60–65%. The patient returned to the ED within a month complaining of chest pain after cocaine use. ECG at that time revealed persistent Twave inversions without ischemia. Serial ECGs and troponins were normal on the follow-up visit. The substance in the foil pack was identified using gas chromatography-mass spectrometry as AMB-FUBINACA and PB-22. AMB-FUBINACA is an SC of the indazole carboxamide class not currently listed in the DEA Schedules of Control Substances. PB-22 is a SC and is a DEA schedule 1 substance. DISCUSSION Endocannabinoids occur endogenously and bind to cannabinoid (CB)1 and CB2 receptors, which are classical G protein-coupled receptors. The endocannabinoid system is involved in a variety of physiologic processes. CB1 receptors are found primarily at the terminals of central and peripheral neurons and inhibit neurotransmitter release through a phenomenon known as depolarization-induced
Synthetic Cannabinoid Abuse Resulting in STEMI Requiring PCI
Figure 2. Pre- and poststenting of second obtuse marginal cardiac catheterization. Arrow in A indicates location of completely obstructed second obtuse marginal and arrow in B demonstrates post stent angiography with restored flow.
suppression of inhibition. CB2 receptors are mainly located on cells in the immune system. Animal models of the cardiovascular responses to the endocannabinoid anandamide are complex and depend on whether the animals are conscious or anesthetized and whether the cannabinoid is administered systemically or into the central nervous system. In anesthetized animals, systemically administered endocannabinoids elicit predominantly hypotension and bradycardia. In conscious animals, it is primarily a pressor response (3). It is speculated that this variable response reflects the role that the endocannabinoid system plays in systemic illnesses such as sepsis by causing a general sympathomimetic response while preserving regional blood flow. SC agonists display potency and toxicity similar to, but orders of magnitude higher than, THC. The SCs in this case, PB22 and AMB-FUBINACA, when injected intraperitoneally in awake rats, cause hypothermia and bradycardia (4,5). How these substances caused myocardial ischemia in this patient can only be speculated. A prior case report of four deaths involved four different SCs— PB-22, 5F-PB-22, AB-FUBINACA, and ADB-PINACA—but did not identify a clear cause of death in three of the cases, and none involved AMB-FUBINACA (6). Young patients with fewer risk factors for atherosclerotic heart disease have experienced myocardial infarction, although none have required PCI (1,2). It is distinctly possible that the cardiovascular toxicity of SCs relates to the patient’s age, presence of coronary artery disease, and the dose and type of SC ingested. Thus, clinicians may have to consider all of those factors when evaluating a case of SC abuse.
WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? From a toxicological perspective, the pharmacologic complexity of SCs and their interaction with the endocannabinoid system lead to the possibility of widely variable presentations. New SCs are being created at a rapid rate and variations in structure are known to dramatically affect potency. Emergency physicians and cardiologists are advised to consider that SCs are potent cardiovascular substances that may lead to myocardial ischemia and may require PCI, particularly in patients with some risk factors for coronary artery disease. REFERENCES 1. Clark BC, Georgekutty J, Berul CI. Myocardial ischemia secondary to synthetic cannabionoid (K2) use in pediatric patients. J Pediatr 2015;167:757–761.e1. 2. McKeever RG, Vearrier D, Jacobs D, LaSala G, Okaneku J, Greenberg MI. K2—not the spice of life; synthetic cannabinoids and ST elevation myocardial infarction: a case report. J Med Toxicol 2015;11:129–31. 3. Ibrahim BM, Abdel-Rahman AA. Cannabinoid receptor 1 signaling in cardiovascular regulating nuclei in the brainstem: a review. J Adv Res 2014;5:137–45. 4. Banister SD, Stuart J, Kevin RC, et al. Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135. ACS Chem Neurosci 2015;6:1445–58. 5. Banister SD, Longworth M, Kevin R, et al. Pharmacology of valinate and tert-leucinate synthetic cannabinoids 5F-AMBICA, 5F-AMB, 5FADB, AMB-FUBINACA, MDMB-FUBINACA, MDMB-CHMICA, and their analogues. ACS Chem Neurosci 2016;7:1241–54. 6. Behonick G, Shanks KG, Firchau DJ, et al. Four postmortem case reports with quantitative detection of the synthetic cannabinoid, 5FPB-22. J Anal Toxicol 2014;38:559–62.