The opioid epidemic has brought attention to the fatal outcomes associated with drug overdoses. Between April 2020 and 2021, more than 100,000 Americans died of poisoning/drug overdose, with approximately 75% of these deaths attributed to opioids. It is important to recognize, however, that other substances can also contribute to life-threatening toxicity and/or cardiac arrest.

The American Heart Association (AHA) recently updated it guidelines on the management of cardiac arrest or life-threatening toxicity due to poisoning. As the majority of the treatment strategies involve the administration of a parenteral antidote or supportive measure, these guidelines are discussed.

The guidelines address the management of overdose assessing both the strength of recommendations and the quality of the evidence. The authors warn that the quality of the evidence base for resuscitation science and the management of critical poisoning is low. Only 3% of recommendations were based on high-grade evidence (Level of Evidence A), whereas 77% were based on low-grade evidence (Level of Evidence C), which is derived from limited and dated expert opinion.

Among the poisonings covered in the guidelines are benzodiazepines, beta-blockers (BBs), calcium channel blockers (CCBs), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, opioids, organophosphates and carbamates, sodium channel blockers, sympathomimetics, and methemoglobinemia. They also discuss the use of extracorporeal membrane oxygenation in the management of poisoning.

The guidelines include a table listing commonly used doses of antidotes for resuscitation in critical poisonings.

Key highlights from this document include:

• When IV flumazenil, a competitive antagonist at the benzodiazepine binding site on the GABA-A receptor, is used to reverse CNS and respiratory depression from a benzodiazepine overdose, it may precipitate refractory benzodiazepine withdrawal, seizures, and rarely, dysrhythmias, including supraventricular tachycardia, ventricular dysrhythmias, and asystole. This later effect is due to the removal of benzodiazepine-mediated suppression of sympathetic tone and is more common in patients who are receiving other dysrhythmogenic drugs or who are hypoxic. Flumazenil has no role in cardiac arrest related to benzodiazepine poisoning. Naloxone should also be administered with flumazenil in a suspected benzodiazepine overdose, as benzodiazepines and opioids are commonly used concomitantly
• For BB overdose, the treatment of choice for hypotension includes high-dose insulin, which may be vasopressor-sparing. It can be used in patients who are refractory to vasopressor therapy or in conjunction with the pressor agents. The guidelines recommend against the use of IV lipid–emulsion therapy in life-threatening BB poisoning
• Similarly, the guidelines recommend the use of high-dose insulin and vasopressor therapy for hypotension secondary to CCB poisoning (the strength of the recommendation is slightly weaker for BBs) and against the use of IV lipid emulsion therapy in this poisoning. Calcium may also be administered. Atropine may be used in both BB and CCB poisoning, but the role of glucagon and methylene blue is uncertain in the latter type of poisoning
• In patients presenting with cocaine overdose and wide-complex tachycardia, the use of sodium bicarbonate or lidocaine are recommended; sodium bicarbonate is also useful in cocaine-related cardiac arrest. However, data are based on retrospective, observational studies and/or case reports. Hypertension is managed with the use of CCBs, alpha-adrenergic agents, and nitrates. Benzodiazepines are used for blood pressure elevations associated with agitation. However, the use of rapid external cooling for severe hyperthermia is the most supported recommendation
• Digoxin-specific immune antibody fragments (or digoxin-fragment antigen binding) are indicated in digoxin poisoning. Atropine may be administered for bradycardia, but the use of therapeutic plasma exchange is not recommended
• Local anesthetic toxicity can present with both central nervous system and cardiovascular symptoms, known as Local Anesthetic Systemic Toxicity (LAST). In about one-third to one-half of patients, LAST cardiovascular symptoms can be life-threatening and include asystole, ventricular fibrillation, or ventricular tachycardia. Bupivacaine, which appears to be a more potent cardiotoxin, can cause reentry dysrhythmias, suppress conduction pathways, and block calcium channels. The treatment of choice for local anesthetic toxicity is IV lipid emulsion, although the data supporting this intervention are not robust. Sodium bicarbonate or atropine may also have a role depending on the cardiac presentation
• Sodium channel blockers, which include carbamazepine, cocaine, diphenhydramine, flecainide, lamotrigine lacosamide, propafenone, quinine, thioridazine, topiramate, tricyclic antidepressants, venlafaxine, and zonisamide, block cardiac sodium channels similarly to Vaughan-Williams class IA or IC antiarrhythmics. In overdose, this effect may manifest as QRS prolongation, hypotension, ventricular dysrhythmias, and cardiovascular collapse. The management of life-threatening cardiovascular events is limited to retrospective, observational studies, and case reports. The guidelines recommend the use of sodium bicarbonate for sodium channel blocker poisoning. IV lipid emulsion may be administered in refractory cases
• Sympathomimetic poisoning is managed with the use of rapid cooling for life-threatening hyperthermia, control of severe agitation, mechanical circulatory support, and the use of vasodilators (e.g., phentolamine, nitrates) for the management of sympathomimetic-induced coronary vasospasm.

The paper also addressed knowledge gaps and research priorities in resuscitative effects in critical poisonings.

As drug experts, pharmacists are frequently consulted on poison-related questions. These guidelines are a valuable reference for pharmacists involved in the management of these patients. Pharmacists should also encourage patients and other health professionals to call the national poison control number, which is 1-800-222-1222, should they have any poison/overdose-related questions.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.