Take Home Points
- Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide a supportive bridge to recovery by preserving organ perfusion in select patients with acute poisoning and refractory cardiogenic shock.
- Survival following VA-ECMO for cardiotoxic medication poisoning is generally >50%.
- Risks with ECMO include bleeding, stroke, limb ischemia, and infection.
- Early recognition of high-risk presentation and timely consultation with poison centers and ECMO-capable centers may help prevent delays in escalation for patients at greatest risk of cardiovascular collapse.
Cardiotoxic Poisoning
- Cardiotoxic poisonings represent some of the highest-risk exposures managed by poison centers, as patients may rapidly progress from mild symptoms to refractory shock, dysrhythmias, and cardiac arrest. In these situations, extracorporeal membrane oxygenation (ECMO) may provide temporary circulatory support while toxicologic management continues and recovery becomes possible.1,2
- Across multiple poison center and population-based studies, medications with cardiotoxic potential consistently account for a large share of severe outcomes. Large clinical reviews emphasize that cardiotoxic agents primarily disrupt ion channels and receptors in myocardial and conduction tissue, leading to depressed contractility, conduction abnormalities, hypotension, and impaired end-organ perfusion.1
- The medication classes most frequently implicated in severe cardiotoxic poisoning include calcium channel blockers, beta-blockers, sodium channel–blocking agents, and several antiarrhythmic drugs.1 These exposures have a similar clinical trajectory, with early hypotension or dysrhythmias followed by escalating vasopressor and inotrope requirements, worsening metabolic derangements, and progressive myocardial failure.
Cardiotoxic Medications
Calcium Channel Blockers
- Calcium channel blocker poisoning is particularly dangerous because of its combined effects on myocardial contractility, atrioventricular conduction, and vascular tone. By inhibiting L-type calcium channels in cardiac and vascular smooth muscle, these agents reduce intracellular calcium availability, leading to negative inotropy, slowed atrioventricular conduction, and peripheral vasodilation. At toxic doses, both dihydropyridine and non-dihydropyridine agents may lose their usual tissue selectivity, producing vasoplegia and myocardial depression, often with rapid clinical deterioration. Shock states may also be prolonged due to sustained-release formulations.3
Beta-Blockers
- Beta-blocker toxicity is mostly driven by antagonism of beta-1 adrenergic receptors in cardiac tissue, resulting in reduced cyclic AMP generation, decreased intracellular calcium availability, diminished myocardial contractility, and sinus bradycardia. Toxic ingestions may be severe, particularly with lipophilic agents and drugs with sodium channel–blocking properties, like propranolol. Excessive beta-1 antagonism reduces heart rate and myocardial contractility, lowering cardiac output. In severe overdose, patients may develop profound bradycardia, cardiogenic shock, and cardiac arrest.1
Sodium channel–blockers
- Drugs with sodium channel blocking properties include tricyclic antidepressants, class I antiarrhythmics, several psychoactive medications, and diphenhydramine at high doses.1
- This classification of medications impairs the sodium influx during phase 0 of the cardiac action potential in ventricular myocardium and the His–Purkinje system. This slows intraventricular conduction and produces QRS widening on electrocardiography (ECG), as well as ventricular dysrhythmias and decreased inotropy. Tricyclic antidepressants also antagonize peripheral alpha-1 adrenergic receptors, contributing to vasodilation and hypotension.1
Bupropion
- Bupropion toxicity involves multiple mechanisms. The primary mechanism is to inhibit norepinephrine and dopamine reuptake, but its active metabolites inhibit gap junction communication between cardiomyocytes at high concentrations, leading to QRS prolongation and increased susceptibility to ventricular dysrhythmias. Gap junction inhibition may also impair coordinated myocardial contraction and contribute to cardiogenic shock. Extended-release formulations can delay peak serum concentrations for several hours, and cardiotoxic manifestations sometimes follow an initial phase of delayed, generalized seizures.1,4
What is ECMO?
- Extracorporeal membrane oxygenation (ECMO), also referred to as extracorporeal life support, is a form of temporary mechanical support that can replace or aid in cardiac and/or pulmonary function. Blood is drained from the patient, circulated through an external pump and oxygenator, and returned to the circulation.1,4
- Two principal ECMO modalities are used in clinical settings:
- Veno-venous ECMO (VV-ECMO) provides respiratory support only. Blood is returned to the venous system and does not directly support systemic circulation.1,4
- Veno-arterial ECMO (VA-ECMO) provides both cardiac and respiratory support by returning oxygenated blood directly to the arterial circulation, thereby bypassing the failing heart and maintaining systemic perfusion.1,5
- In cardiotoxic poisoning, VA-ECMO is the most relevant modality because the primary problem is cardiovascular collapse rather than respiratory failure. Toxicology and critical care literature consistently define VA-ECMO as the preferred extracorporeal support method for poisoned patients with severe myocardial depression, refractory shock, or cardiac arrest.1,2,4
- VA-ECMO may also be initiated during ongoing cardiopulmonary resuscitation. In poisoning, this approach has been used when conventional resuscitation fails, and the underlying toxicologic syndrome is potentially reversible.1,5
How ECMO Helps in Poisoning
- In cardiotoxic poisoning, VA-ECMO functions as physiological support rather than definitive treatment. Its primary role is to maintain cardiac output and end-organ perfusion when the heart is unable to do so despite maximal medical therapy.1,5
- This allows time for ongoing antidotal treatment, decontamination strategies and drug clearance.1,4,5
- Since poisoned patients are often younger and without chronic or structural heart disease, the potential for myocardial recovery is higher than in many other patients with cardiogenic shock.1,4
When To Consider ECMO In Cardiotoxic Poisoning
- There are no standardized criteria for initiating ECMO in poisoned patients. Across reviews and case series, decisions are driven by physiological deterioration and lack of response to optimal medical therapy rather than by the identity of the toxin itself.1,5,6
- Since ECMO is a bridge to survival, typical contraindications for ECMO include a pre-existing condition with low expected survival or irreversible heart or lung injury without option for transplant or durable mechanical circulatory support implantation.
- Relative contraindications for ECMO are center-specific but may include contraindications to systemic anticoagulation, medical comorbidities, advanced age, or severe brain injury.7
- Based on a recent narrative review, a group of physicians with expertise in ECMO, medical toxicology, critical care, and emergency medicine recommended that in the absence of contraindications, VA-ECMO should be considered for:
- All patients with acute poisoning with refractory cardiogenic shock (SBP < 90 mm Hg) and end-organ dysfunction despite treatment with established standards of care, including antidotal therapy, high-dose insulin where indicated, vasopressor and inotrope escalation, correction of metabolic derangements, and advanced cardiac life support.7
- Patients with acute poisoning who suffer a witnessed cardiac arrest or for those with refractory cardiac arrest if feasible for the institution.7
- Whether VA-ECMO is useful for treating refractory vasoplegic shock without concurrent cardiogenic shock (e.g., amlodipine overdose) remains unclear.
- Recently, a large single-center cohort provided practical indicators reflecting how clinicians actually select patients for VA-ECMO. In this study of 146 patients with severe cardiotoxic poisoning, three admission variables were independently associated with VA-ECMO use: mean arterial pressure of < 60 mmHg, serum lactate > 4.1 mmol/L, and left ventricular ejection fraction of < 20%.8
Timing Of ECMO And Early Resuscitation
- Across the toxicology and critical care literature, ECMO is most often considered after patients have already developed profound and refractory cardiovascular failure.1,5 Early identification of worsening hypotension, escalating vasopressor requirements, severe left-ventricular dysfunction, or recurrent malignant dysrhythmias should prompt multidisciplinary discussion and activation of ECMO resources before the development of irreversible multiorgan failure.1
- In institutions without ECMO capability, early consultation with and transfer to an ECMO-capable center should be considered once high-risk features of toxicity emerge, or in reported massive ingestions. In national registry data, survivors were more frequently managed at centers with ECMO access, suggesting that timely referral and coordination may influence outcomes.2
Outcomes and Complications
- In a nationwide German cohort of cardiovascular medication poisonings treated with VA-ECMO, overall survival was approximately 64%, with calcium channel blockers and beta blockers being the most common exposures.9
- In the National Poisons Information Service (NPIS) review, VA-ECMO was used in only 12 of 688 cardiotoxic drug and plant poisonings, and 5 patients survived. Several survivors initially presented to ECMO-capable centers, suggesting potential benefits of early referral and interdisciplinary coordination.2
- In the United States Toxicology Investigators Consortium (ToxIC) registry, ECMO was extremely rare but associated with an overall survival rate of 80%.4
- Despite promising outcomes in acute cardiotoxic poisoning, ECMO is not a benign intervention and comes with risks.
- In large adult registry analyses, bleeding complications have been reported in approximately 30% of patients, with ischemic stroke occurring in roughly 4% and hemorrhagic stroke in approximately 2%, each associated with increased mortality.10
- Additional complications include limb ischemia related to peripheral cannulation, infection, and circuit malfunction.
Lipid Emulsion Controversies
- Intravenous lipid emulsion (ILE) is frequently discussed in the management of severe cardiotoxic poisoning, particularly for lipophilic agents. However, the evidence supporting lipid emulsion remains limited.
- ECMO circuits are susceptible to complications related to lipid exposure, including fat emulsion agglutination, clogging of the membrane oxygenator, clot formation within the circuit, and mechanical malfunction of tubing and stopcocks.11
- These effects have been described with parenteral lipid administration and are particularly relevant in patients with hypertriglyceridemia. In patients receiving ECMO, severe hypertriglyceridemia has also been associated with sequestration of triglycerides within the oxygenator, which can impair gas exchange and contribute to circuit dysfunction.11
- For this reason, professional guidance recommends avoiding lipid bolus administration into the ECMO circuit and using a separate central venous line for lipid delivery when needed and closely monitoring triglyceride concentrations during lipid exposure.11
- ILE should still be given if ECMO is not immediately available.
The Utah Poison Control Center is available 24 hours a day, 7 days a week at 1-800-222-1222 if you have questions about the use of ECMO for poisoned patients or the treatment of cardiotoxic poisonings.
References
- Voicu S, M'Rad A, Malissin I, Deye N, Mégarbane B. Extracorporeal life support in cardiotoxicant poisoning: a narrative review. Basic Clin Pharmacol Toxicol. 2023;132(1):5-20. doi:10.1111/bcpt.13804.
- Moyns E, Looms J, Jagpal PS, Day R, Sandilands EA, Gray LA, Thanacoody RHK, Bradberry SM. A review of cardiotoxic agent poisoning and the role of VA-ECMO as reported to the National Poisons Information Service (NPIS) 2018-2023. Toxicol Commun. 2025;9(1):2524302. doi:10.1080/24734306.2025.2524302.
- Finn D, Stevens J, Tolkacz M, et al. Calcium channel blocker overdose: what role does extracorporeal membrane oxygenation have in support? A systematic review of the literature. ASAIO J. 2024;70(5):404-408. doi:10.1097/MAT.0000000000002129.
- Wang GS, Levitan R, Wiegand TJ, et al. Extracorporeal membrane oxygenation for severe toxicological exposures: review of the Toxicology Investigators Consortium (ToxIC). J Med Toxicol. 2016;12(1):95-99. doi:10.1007/s13181-015-0486-8.
- Gupta V, Gupta R, Wander GS. Role of ECMO in life-threatening intoxication. Egypt J Crit Care Med. 2018;6(3):103-109. doi:10.1016/j.ejccm.2018.12.007.
- Torre DE, Mangino D, Pirri C. Veno-arterial extracorporeal membrane oxygenation in cardiotoxic drug-induced cardiogenic shock: a systematic narrative review. Life (Basel). 2025;15(6):925. doi:10.3390/life15060925.
- Upchurch C, Blumenberg A, Brodie D, MacLaren G, Zakhary B, Hendrickson RG. Extracorporeal membrane oxygenation use in poisoning: a narrative review with clinical recommendations. Clin Toxicol (Phila). 2021;59(10):877-887. doi:10.1080/15563650.2021.1945082.
- Compagnon B, Tardif E, Pey V, Marcheix B, Labaste F, Conil JM, Minville V, Vardon-Bounes F. Use of extracorporeal membrane oxygenation in severe cardiotoxic poisoning: analysis of a cohort over 10 years. Sci Prog. 2025;108(4):1-15. doi:10.1177/00368504251358951.
- Friedrichson B, Jasny T, Old O, et al. Extracorporeal membrane oxygenation in cardiovascular medication poisoning: a German-wide retrospective study. Sci Rep. 2024;14:21761. doi:10.1038/s41598-024-72547-0.
- Lorusso R, Gelsomino S, Parise O, et al. Neurologic injury in adults supported with venoarterial extracorporeal membrane oxygenation for cardiogenic shock: an analysis of the Extracorporeal Life Support Organization registry. Crit Care Med. 2017;45(8):1389-1397. doi: 10.1097/CCM.0000000000002502.