Case files of the Medical Toxicology Fellowship at the Toxikon Consortium in Chicago: Cocaine-associated wide-complex dysrhythmias and cardiac arrest— treatment nuances and controversies

Abstract

A 19-year-old woman was brought by ambulance to the emergency department (ED) from a police holding cell. Less than 3 hours earlier, the patient had been a passenger in a car stopped for a traffic violation. As the police officer approached the car, the patient was noted to hurriedly stuff 2 plastic bags containing a white powdery substance into her mouth. On questioning, it was reported that the packets contained cocaine. Less than an hour after being taken to the police station, the patient was witnessed to have a generalized seizure. Emergency medical services (EMS) were immediately summoned.Upon EMS arrival, the seizure activity had ceased. The patient was reportedly unresponsive and noted to have a narrow-complex supraventricular tachycardia. The paramedics provided oxygen by a non-rebreather mask, established intravenous (IV) access, and prepared the patient for rapid transport to the ED. En route to the ED, the patient's rhythm evolved into a wide-complex tachycardia. Due to suspected ventricular tachycardia (VT) and ongoing hemodynamic instability, the patient underwent synchronized cardioversion at 100 J with immediate conversion to sinus tachycardia just minutes prior to ED arrival. What is the pharmacological basis of acute cocaine intoxication?Cocaine intoxication typically produces a sympathomimetic toxidrome marked by tachycardia, hypertension, hyperthermia, diaphoresis, and increased psychomotor activity [1]. The pathophysiology of cocaine is driven by its sympathetic nervous system effects, central nervous system (CNS) stimulation, and local anesthetic effects. In addition to its effects on the vasomotor center, cocaine produces tachycardia and hypertension by inhibiting the reuptake of both norepinephrine and epinephrine. Catecholamine stimulation of peripheral postsynaptic ␣ 1 -adrenergic receptors helps mediate the hypertensive response, while binding at postsynaptic ␤ 1 -receptors is implicated in producing tachycardia. In the CNS, the enhanced release of excitatory amino acids plays a key role in mediating the seizures, agitation, and hyperthermia noted in severe cocaine poisoning. In addition, reuptake blockade of the biogenic amines norepinephrine, epinephrine, dopamine, and serotonin are also involved in producing the CNS and neuropsychiatric effects of cocaine [1][2][3].The dysrhythmogenic properties of cocaine, as well as its electrocardiographic manifestations, derive in part from cocaine's effects on cardiac sodium and potassium channels. Similar to other local anesthetics, cocaine blocks neuronal sodium channels, impeding sodium conductance during phase 0 of the cardiac action potential. This produces QRS widening in a manner analogous to Vaughn-Williams type IA and IC antidysrhythmic agents. Cocaine can also cause QTc prolongation via blockade of cardiac potassium efflux channels [1][2].

Outcomes in Cardiac Arrest Patients due to Toxic Exposure Treated with Therapeutic Hypothermia

“…In some cases, consideration of a toxic exposure might modify typical resuscitation measures. For example, lidocaine may be a better antidysrhythmic for sodium channel antagonist-induced ventricular dysrhythmia than amiodarone [15]. Vasopressor doses may be considerably higher for druginduced shock than ischemic shock [16].…”

A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening

“…There are multiple case reports as well as animal studies showing the effectiveness of sodium bicarbonate as a treatment for cocaine-induced sodium channel blockade [6,7,42,[55][56][57]. Wang describes two cases of cocaine intoxicated patients with QRS widening being successfully treated with sodium bicarbonate.…”

“…The QRS was reported in one patient at 120 msec [56]. In addition, Kalimullah and Bryant as well as Kerns et al describe cases of severe cocaine overdose resulting in cardiac arrest being effectively treated with sodium bicarbonate [6,55]. Dayan et al describe three fatal cases of dibucaine poisoning in children where bicarbonate was used in two of the three cases [82].…”

“…Case reports [1,3,53,54] Cocaine Case reports [6,7,55,56] C a n i n e [ 42,57] Cyclic antidepressants Case reports, retrospective series [19,50,58,59] Canine, rat, swine [41,[60][61][62][63] Canine Purkinje fibers, human atrial myocytes [64] Diphenhydramine Case report [2,65] Flecainide Case reports [8,66] …”

“…It is most widely known for its use in tricyclic antidepressant (TCA) toxicity. However, there are case reports of sodium bicarbonate therapy being used to treat QRS widening on the electrocardiogram (ECG) after a wide range of exposures including citalopram, cocaine, flecainide, diphenhydramine, propoxyphene, and lamotrigine [1][2][3][4][5][6][7][8]. The mechanism for its efficacy has not been fully elucidated, and it may differ depending on the drug responsible for toxicity.…”