When children and adolescents present to the emergency department with agitation or mental status changes, intoxication from synthetic drug use should be in the differential diagnosis. Identifying the responsible compound(s) may be difficult, so asking the patient broad questions and utilizing appropriate diagnostic studies, when indicated, will aid in making the diagnosis and help identify more-serious complications. This issue discusses the challenges presented by the changing chemical formulations of synthetic cannabinoids, cathinones, and phenethylamines; outlines common presentations of intoxication from these substances; and summarizes best practices for evaluating and managing patients who present with intoxication after consumption of these synthetic drugs of abuse.
A 15-year-old girl presents to your ED at 3 am. She is brought in by her mother, who woke up and found the girl staggering around their living room. The patient’s electronic medical record is unremarkable; the girl has no significant past medical history. On examination, she is mildly tachycardic; injected conjunctiva and diaphoresis are noted. The girl laughs intermittently and inappropriately during your encounter. Upon further discussion, she admits smoking marijuana that was purchased on the Internet by an older sibling. Several hours later, her mentation improves, but she now reports 6 out of 10 chest pain. What other substances could have been combined with the “marijuana?” Will blood or urine testing lead to a diagnosis? Is any management beyond supportive care indicated for this patient?
A 17-year-old boy presents to the ED via EMS after his friends called for help while at an electronic dance music festival. The patient’s vital signs are notable for tachycardia (110 beats/min) and hyperthermia (40°C [104°C]). On examination, the boy is agitated, and he admits drinking several alcoholic beverages but denies any co-ingestions. Are this patient’s vital sign abnormalities and altered mental status likely explained solely by his reported alcohol use? What other ingestions may have occurred? How can you anticipate such exposures?
Synthetic cannabinoids, cathinones, and phenethylamines have gained popularity due to a public perception that they were relatively safe to consume and that they were legal. In 2011, a temporary ban was placed by the United States Drug Enforcement Administration on some synthetic cannabinoids, and in 2012, federal legislation was passed that covered all synthetic cannabimimetic agents. Other nations have also worked to close legal loopholes and target synthetic cannabinoids. One study from New Zealand demonstrated that legislation that reduced the availability of synthetic cannabinoids was correlated with a decrease in psychiatric ED visits associated with synthetic cannabinoid use.1 Another study conducted in New Zealand found a 52% reduction in patient utilization of emergency psychiatric services after the enactment of legislation that sought to curb the supply of synthetic cannabinoids.2 Today, however, new formulations have been developed to skirt restrictions, and synthetic cannabinoids remain the second most commonly used drugs of abuse, after conventional marijuana. Moreover, synthetic cannabinoids continue to be available for sale online and in many stores.3-5 Additionally, as Mathai et al found in the city of Houston, Texas, use may continue to increase despite legislative attention given to synthetic cannabinoids.6
Many emergency clinicians remain unfamiliar with terminology regarding synthetic drugs. In a 2013 study that surveyed 83 physicians (88% response rate), most providers reported that they gathered a significant amount of their knowledge on this subject from nonmedical sources. The study found that 80% of respondents admitted to feeling uneasy about managing a patient with synthetic cannabinoid intoxication. Additionally, clinicians appeared less likely to ask about synthetic drug use compared to conventional drug use.7 Vazirian et al surveyed 124 emergency clinicians connected to the Cleveland Clinic health system. While analysis of this study’s results may be scrutinized for low participation (34% completion rate), approximately two-thirds of respondents reported having managed, in the prior 2 years, a patient with suspected synthetic cathinone intoxication. Despite this exposure, 77% of surveyed emergency clinicians did not ask about synthetic cathinone use.8 It is imperative that emergency clinicians include acute intoxication and synthetic drug abuse in their differential diagnosis for a wide variety of presentations. Most commonly, these patients will present with agitation or with changes in mental status; however, maintaining a high index of suspicion for complaints of chest or abdominal pain is necessary to detect some of the more serious sequelae.
In recent years, synthetic drugs have made their mark in the United States. While ascertaining the true prevalence of these synthetic drugs has been challenging because of underreporting, experts believe that their use has been on the rise.9 Emergency clinicians must be prepared to identify and manage exposures to synthetic drugs in a diverse range of ages within the pediatric population. This issue of Pediatric Emergency Medicine Practice will guide emergency clinicians through the diagnosis, management, and disposition of children who present with synthetic drug intoxication.
A literature search was performed in PubMed using the search terms synthetic cannabinoids and pediatric, synthetic cannabinoids and emergency medicine, synthetic cathinone and pediatrics, synthetic cathinone and emergency medicine, phenethylamines and pediatrics, and phenethylamines and emergency medicine. A search of the Library of Congress found 2 relevant reports. Background information on this topic was obtained from PubMed using the general search terms synthetic cannabinoids, synthetic cathinones, bath salts, phenethylamine intoxication, and MDMA intoxication.
The vast majority of publications were case reports, case series, or review articles. Higher-grade evidence was sparse for several possible reasons. The most significant reason is that designing randomized controlled trials of a toxic exposure would be clearly unethical. Diagnosis of synthetic cannabinoid and synthetic stimulant intoxication, in particular, is often presumed based on history only, as definitive laboratory testing is difficult to obtain and cost-prohibitive for many EDs. Moreover, many synthetic cannabinoids have a variety of active agents, complicating analysis of the clinical effects of a single substance. Finally, presentation of a patient with an acute intoxication to the ED is often due to polysubstance use. This creates a confounding effect, for which establishing an appropriate control is difficult.10 Because of these factors, significant gaps in knowledge remain. As technology is developed to better assess synthetic compound use, this may change. However, significant ethical considerations and confounding variables from polysubstance ingestion are still likely to limit quality evidence on this subject.
4. “This patient already admitted taking MDMA earlier in the day. She was a bit anxious, but looked fine. It was a hot day, and I wanted to keep her hydrated, so I told her to drink plenty of water and sent her home.”
While this patient may appear to be doing well, MDMA is known to increase antidiuretic hormone release and can lead to hyponatremia. Multiple reports have found significant morbidity and mortality secondary to cerebral edema in patients who consumed MDMA, and this is thought to be secondary to low serum sodium levels. A basic metabolic panel should be ordered for any patient suspected of presenting with acute MDMA intoxication. Having the patient drink fluids containing electrolytes or administering a normal saline bolus would be more appropriate courses of management and can help prevent worsening electrolyte disturbances.
5. “My patient stated she had taken a small pill of ecstasy a few weeks ago; there is no way her current psychosis is related to that small quantity.”
This pitfall highlights 2 points. First, it is effectively impossible for patients to accurately know how much MDMA (or other substance, for that matter) they are ingesting when they take ecstasy. Studies have shown that the amount of psychoactive substances in such pills has increased dramatically compared to the drug’s introduction. The “small” size of the pill is meaningless. Second, cases of delayed psychosis secondary to MDMA use have been reported.107,108
6. “While her parents admitted to the use of marijuana at their home, there is no way that this 18-month-old child could have been exposed to a toxic level.”
Children are adventurous explorers when they become mobile, and continuously place items in their mouths. Synthetic drugs are often packaged in shiny, colorful packaging, and may be especially enticing to young children. Oral ingestion of K2 by a 10-month-old child has been documented,30 and such cases are likely to recur.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of patients. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.
Points and Pearls Excerpt
Most Important References
Rahul Shah, MD; Carl R. Baum, MD, FAAP, FACMT
Michael Levine, MD; Dan Quan, DO
May 2, 2018
June 1, 2021
4 AMA PRA Category 1 Credits™, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2-A or 2-B Credits. Specialty CME Credits: Included as part of the 4 credits, this CME activity is eligible for 3 Pharmacology CME credits
Date of Original Release: May 1, 2018. Date of most recent review: April 15, 2018. Termination date: May 1, 2021.
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