The systemic role of illicit drugs and their toxicology

Abstract

Illicit drug use is commonly associated with sudden death attributed to excited delirium syndrome. Many of these deaths occur during or shortly after a physical struggle. Excited delirium syndrome sequentially passes through four stages including hyperthermia (typically), delirium with agitation, respiratory arrest, and death. Illegal street drugs such as cocaine, methamphetamine and phencyclidine (PCP) have long been known to cause episodes of excited delirium due to their ability to interact with certain brain systems resulting in markedly elevated levels of catecholamines. Interactions of such drugs with the central nervous system (CNS) have also been linked to the acute onset of mania and violent behaviors, including aggression, combativeness, hyperactivity, extreme paranoia, hallucinations, superhuman strength, or incoherent shouting. Subjects exhibiting such violent behaviors often encounter a physical struggle with law enforcement or emergency medical personnel attempting to restrain them. In such cases, multiple personnel are often required to restrain the individual by using increased levels of physical force or multiple restraint techniques due to the elevated level of physical strength displayed by the subject as a result of chemical impairment. Following successful restraint, agitation ceases and subjects become tranquil and unresponsive. In addition to being responsible for the initial onset of symptoms associated with excited delirium, illicit substances such as cocaine, methamphetamine and PCP also appear to play a significant role in the sudden death of subjects experiencing this condition. Although the exact mechanism of these sudden deaths is still the topic of some debate, it appears that the physiological effects of the physical struggle combined with the sympathomimetic effects of these drugs causes a toxic catecholamine assault on the cardiovascular system. Compounding these effects even further are the sudden fluctuations in electrolyte concentrations that are possible following strenuous exercise such as a physical struggle. Increased myocardial oxygen demand, combined with poststruggle hypokalemia is thought to lead to prolongation of the QT interval, development of ventricular tachycardia, and fatal arrhythmias causing sudden cardiac death. While sudden fluctuations in electrolyte concentrations are consistent with fatal cardiac arrhythmias, kalemic cardiac arrest does not necessarily explain why almost all of these sudden arrest-related deaths proceed through an initial stage of respiratory arrest. Until the mechanism of this initial period of quiescence is identified, several possible causations including kalemic cardiac arrest remain largely theories rather than proven etiologies as the mechanism of death due to excited delirium syndrome. © 2009 Springer-Verlag US.