The Party Drugs of Summer 2017

The year’s major festivals have seen a surge in dangerous MDMA overdoses and a return to LSD. 

An unresponsive patient rolls in with the local volunteer EMS squad from a nearby music festival after a witnessed generalized tonic-clonic seizure lasting for approximately two minutes with a postictal period. He is tachycardic, warm to the touch, and has dilated, reactive pupils. His friends report he has no known medical problems and has taken eight tabs of ‘acid’ throughout the day. He is slowly returning to his baseline mental status as per his friends. What workup is necessary for this first time seizure and for how long should the patient be monitored?

This decade has brought a notable increase in music festival related deaths. The rising mortality rate may be attributed to increasing popularity of recreational ‘club drugs’; potentially impure compounds composed of cheaper, easier to obtain, synthetic substances with narrower therapeutic indexes and wider toxic windows. Resource management and medical care at certain mass gatherings have responded to the changing needs; advanced, intensive, on-site medical therapies and monitoring are becoming common place to offer emergent treatment promptly and to avoid overburdening local healthcare resources.

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Mass gathering medicine (MGM) is a young and rapidly evolving medical discipline that integrates aspects of emergency medicine, disaster medicine, and public health. The standard of care is shifting from first aid coverage to more comprehensive, multidisciplinary medical teams on-site. To mitigate increasing morbidity and mortality, on-site medical staff often includes paramedics, nurses, physicians, and other staff such as drug awareness and sexual assault counselors. On-site medical teams offer similar capabilities and medications as those available in the emergency department [1].

Party Favors
Music festivals present unique challenges due to the fact that their ever-changing drug profile is not always congruent with local community substance use patterns. For instance, opioid abuse and potential carfentanil exposure is relatively rare at festivals. Festival attendees are favoring lysergic acid diethylamide (LSD) over more deleterious psychostimulants. The 1960s and ’70s saw widespread hallucinogenic use in the form of LSD. LSD, colloquially known as ‘acid’, works as a serotonin receptor agonist with greatest affinity for the 5-HT2A receptor providing users with intense hallucinations [2]. The hallucinations are commonly termed ‘tripping’. Common adverse effects of LSD include anxiety, tachycardia, agitation, and vomiting. Rarely, deaths occur when patients sustain traumatic injuries while hallucinating such as falling from elevated locations or being struck by motor vehicles [3].

In the 2000s, festival mortality increased due to rising popularity of psychostimulants. These entactogens, a class of psychoactive drugs that produce emotional openness and communion, include 3,4-methylenedioxymethamphetamine (MDMA, Ecstacy, Molly), 3,4-methylenedioxyethylamphetamine (MDE, Eve), bath salts such as methylone, and their chemical derivatives [4]. These drugs act via serotonin, norepinephrine, and dopamine release and reuptake inhibition. MDMA has ten times more affinity for serotonin transporters compared to norepinephrine and dopamine transporters [5]. Entactogens cause euphoria, sensory changes, agitation, tachycardia, hypertension, seizures, hyperthermia, and cardiac arrhythmias [6]. The disease pathophysiology is similar to serotonin syndrome. Three previously healthy, young adults died at a festival in Los Angeles in 2015 secondary to MDMA toxicity and hyperthermia [7] and this is not uncommon at festivals nationwide. While LSD can contribute to accidental injuries and frequently users become combative and agitated causing self-harm requiring chemical restraints, psychostimulants cause a sympathomimetic toxidrome resulting in systemic end-organ damage including hyperthermia, acute renal failure, pulmonary edema, and death [8].

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Psychostimulant drug-induced toxicity (PDIT) occurs secondary to entactogen use often taken at mass gatherings while performing intense physical activity, such as dancing, in high ambient temperatures. PDIT is a life-threatening condition with sudden onset and rapid progression. The main clinical characteristics of PDIT include core body temperature ≥ 40.5° C (105° F) and changes in mental status such as agitation, delusions, hallucinations, seizures or coma [9]. Other signs and symptoms often include tachycardia, tachypnea, hyperthermia, rhabdomyolysis, dehydration, acidosis, mydriasis, and hyperkalemia. Additionally, MDMA can independently increase ADH secretion and thus intravascular volume. Hypervolemic hyponatremia is a real concern given that many attendees are encouraged to drink large volumes of free water. Serious complications including hyponatremic seizures, cardiac arrhythmias, coagulation disorders, and multi-organ dysfunction, which may result in long-term sequelae or death [^10].

Management Tips
Treatment delay, even in the time required to transport a critical patient to a local hospital, may lead to significant morbidity. Thus it is of critical importance to offer emergent, advanced therapy on-site. Current treatment includes cooling measures (e.g. ice packs, evaporative cooling, cold crystalloid infusion, cold water immersion), sedative and dissociative agents (e.g. benzodiazepines, ketamine), paralysis, and other supportive measures [^11]. Sedatives and dissociative agents are particularly helpful in the cessation of continuous muscle excitation and contraction coupling resulting from entactogen use. Typically, agitated, combative attendees present from the crowd and are chemically restrained with either ketamine (4-5 mg/kg IM) or midazolam IM. Those patients are then monitored in the medical tent with cardiac monitoring and pulse oximetry. Frequently they need to resedated as the effects of their underlying ingestion outlast their chemical restraint. Patients who present with first-time seizures are typically monitored to ensure that there is no recurrence. If they quickly return to their baseline, they are frequently allowed to return to the event after an extensive monitoring period and after being warned about the perils of recreational drug use. If left untreated or not recognized promptly, hyperthermia which is already complicated by physical activity in environments with high heat indexes, will worsen rapidly and dramatically, resulting in systemic multi-organ dysfunction. The importance of rapid cooling using several different mechanisms cannot be understated; rarely will emergency physicians encounter patients in the emergency department that will need aggressive and rapid cooling such as those PDIT patients who present with sympathomimetic toxidromes and core body temperatures of 40° – 44° C.

Dantrolene is a very controversial therapy that has been proposed to treat PDIT’s associated hyperthermia. Dantrolene inhibits the release of calcium in myocytes preventing muscle contraction resulting in a significant decrease in core body temperature. Limited retrospective case reports suggest dantrolene quickly ameliorates the hyperthermia of PDIT. One meta-analysis analyzed 71 patients with hyperthermia in MDMA intoxication. In the dantrolene cohort, 26 patients had a survival rate of 80% versus 55% survival in the remaining control group. Significant complications were less common in the dantrolene treatment group as well [^12]. This limited study does suggest a place for dantrolene use in the critically hyperthermic patient with PDIT. Further prospective, randomized trials need to be conducted in order to elucidate dantrolene’s specific role in the treatment of PDIT. Most toxicologists recommend against its routine use and suggest that supportive therapy including cooling, sedation, and possible RSI with paralysis should be the focus of management for these patients.

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Music festival attendees are shifting their drug selection from MDMA back to LSD, which may pose less detrimental adverse outcomes, but patient ingestions, pathology, patient volume, and venue logistics still present unique challenges for event medicine specialists. Multidisciplinary teams that are knowledgeable about mass gathering medicine literature can use emergency medicine, disaster medicine, and public health core principles to best handle these challenges and optimize on-site care.

REFERENCES

1. Friedman MS, Plocki A, Likourezos A, et al. A Prospective Analysis of Patients Presenting for Medical Attention at a Large Electronic Dance Music Festival. Prehosp Disaster Med. 2017;32(1):78-82.
2. Nichols DE. Chemistry and Structure-Activity Relationships of Psychedelics. Curr Top Behav Neurosci. 2017;
3. Carvalho M, Carmo H, Costa VM, et al. Toxicity of amphetamines: an update. Arch Toxicol. 2012;86(8):1167-231.
4. Ridpath A, Driver CR, Nolan ML, et al. Illnesses and deaths among persons attending an electronic dance-music festival – New York City, 2013. MMWR Morb Mortal Wkly Rep. 2014;63(50):1195-8.
5. Nelson L, Lewin N, Howland MA et al. Goldfrank’s Toxicologic Emergencies, Ninth Edition. Mcgraw-hill; 2010.
6. Greene SL, Kerr F, Braitberg G. Review article: amphetamines and related drugs of abuse. Emerg Med Australas. 2008;20(5):391-402
7. Rong-Gong Lin II. http://www.latimes.com/local/lanow/la-me-ln-hard-summer-rave-ecstasy-overdose-20161130-story.html. Accessed July 7, 2017.
8. Carvalho M, Carmo H, Costa VM, et al. Toxicity of amphetamines: an update. Arch Toxicol. 2012;86(8):1167-231.
9. Callaway CW, Clark RF. Hyperthermia in psychostimulant overdose. Ann Emerg Med. 1994;24(1):68-76.
10. Gunn J, Singer S, Webb M, Kellum A. Oxford American Handbook of Critical Care. Oxford University Press. 2007; 464.
11. Scaggs TR, Glass DM, Hutchcraft MG, Weir WB. Prehospital Ketamine is a Safe and Effective Treatment for Excited Delirium in a Community Hospital Based EMS System. Prehosp Disaster Med. 2016;31(5):563-9.
12. Grunau BE, Wiens MO, Brubacher JR. Dantrolene in the treatment of MDMA-related hyperpyrexia: a systematic review. CJEM. 2010;12:435–442.