ECMO…The Ultimate Antidote?

Extracorporeal membrane oxygenation (ECMO) is a resuscitative technology that has been gaining in popularity in both intensive care units and emergency departments.

The technique, pioneered in the 1950s and adapted in the 1970s by Dr. Solomon Hill, has been applied to the gamut of critically ill patients. There is no shortage of literature supporting the role of ECMO in acute coronary syndrome, sepsis, acute respiratory distress syndrome, cardiac arrest, pulmonary embolism, traumatic pulmonary contusion, and more.

Fortunately, the applications of ECMO extend beyond these somewhat common medical emergencies and into the realm of toxicologic emergencies as well.

Veno-venous (VV) and veno-arterial (VA) ECMO strategies have widespread use in many overdose cases, and as the access to ECMO-capable centers and ED cannulation protocols grows, all emergency physicians should be comfortable knowing when to consider this intervention in medical and toxicologic patients.^1,2

ECMO Mechanics
Numerous papers in EM Resident and other publications have described the components of an ECMO circuit in great detail; however, our toxin-specific review would be remiss without a brief overview. Although externally very complex, the mechanics of ECMO can be reduced to two major modes composed of four major components. Circuits are composed of a venous cannula that drains deoxygenated blood from the body to a membrane oxygenator that strips the blood of carbon dioxide and introduces oxygen. This blood is then fed to a pump and heat exchanger that returns it through a return cannula, either arterial or venous. This final detail is where the distinction between VA and VV ECMO is made.^1,2 Prior to initiating transfer to an ECMO center or performing a bedside cannulation, it is imperative to correct intravascular volume and electrolyte disturbances while continuing treatment for the specific ingestion.³

Who is a Candidate?
The recent North American Congress of Clinical Toxicology provided an expert panel on ECMO in toxicology. In principle, ECMO is a “time-buying measure” for toxicant metabolism and can also be combined with enhanced elimination techniques such as hemodialysis. When assessing who is a candidate for ECMO, there are three major considerations:

1. The patient must have a reversible disease process (e.g., ARDS from hydrocarbon toxicity).
2. The patient’s condition is refractory to conventional treatment or antidotal therapy (e.g., refractory hypotension after beta blocker overdose despite treatment).
3. There is a reasonable quality and quantity of life expected after ECMO treatment.

Once a patient meets these criteria, it is important to assess if there are any physiologic contraindications. For example, ingestion of uncoupling agents (salicylates, 2,3-dinitrophenol, etc.), situations causing distributive shock, and refractory dysrhythmias are not improved with ECMO.³ Further discussion regarding patient suitability for ECMO should be had with the local service that would be managing the patient.

ECMO Use
From 2010-2013, more than 26,000 toxicologic emergencies were reported to the American College of Medical Toxicology (ACMT) Toxicology Consortium, and only 10 patients were placed on ECMO.⁴ Overall, ECMO is used in toxicologic emergencies for cardiotoxic drugs causing refractory symptoms with no improvement to conventional treatment. Patients will usually be in shock and may have had cardiac arrest. These are unstable patients who have exhausted conventional toxicologic treatments.⁵ ECMO should be considered when a patient has ARDS, persistent hypotension, cardiac arrest/cardiac arrhythmia, persistent acidosis, and poor ventilation associated with a toxicologic exposure.⁴

The table below describes multiple toxicologic conditions that may be temporized with ECMO^4,6:

Proof of Concept

As a general rule, toxicologic emergencies requiring ECMO are sparse, but ever present. This makes retrospective data collection tedious and planning for randomized controlled trials even more difficult. Despite this, primary literature still exists, serving as a proof of concept of utilizing ECMO in overdose.

According to studies by Yu et al, ECMO has utility in nitric acid and bromine inhalation overdoses.⁷ There is also evidence to suggest that loperamide overdose, most frequently abused when trying to attenuate opioid withdrawal, can be treated with VA ECMO.⁸ With the opioid epidemic worsening over time, this is an accidental overdose we could see more frequently in the emergency department.

Furthermore, the ACMT Consortium showed use of ECMO for a variety of overdoses, including multi-med overdoses and common medication overdoses such as calcium channel blocker, beta blocker, carbon monoxide, and cardiac glycoside overdoses.⁴ Many of these patients also received aggressive supportive care, including continuous renal replacement therapy (CRRT).⁴ Survival rate for patients receiving ECMO in this study was 80%. Moreover, in a 14-year single-center study, VA-ECMO for drug intoxication-induced refractory cardiogenic shock was found to be a feasible therapeutic option with a satisfactory survival rate and acceptable complication rate.⁹

When these patients present, it has been recommended that ECMO should be started as soon as the patient becomes unresponsive to optimal conventional interventions and no contraindications are present. Although evidence of the power of ECMO is still very much based in retrospective studies, case reports, and case series, ECMO has been shown to be a durable, lifesaving bridge to more definitive management in certain clinical settings.

When to Consider ECMO in a Patient With Toxicologic Exposure

• ARDS
• Persistent hypotension
• Cardiac arrest/cardiac arrhythmia
• Persistent acidosis
• Poor ventilation

Conclusion
ECMO use for toxicologic emergencies is uncommon, and its researched efficacy is based primarily on retrospective case studies. ECMO should be considered when available at your institution for severe cardiopulmonary toxicity refractory to conventional toxicologic interventions. Your institution must have ECMO available, or transfer must be completed quickly, for this to be a viable option. When considered and utilized as a treatment option, ECMO can serve as a bridge to reach definitive medical management or provide enough physiologic support to temporize a patient through an acute ingestion.

References

1. Ghobrial M, Nugent K. A Review of ECMO in the ED. EM Resident. 2019 46.4
2. Felix A, Campbell D. Extracorporeal Cardiopulmonary Resuscitation. EM Resident. 2022 49.3
3. AAPCC Scientific Symposium: Extracorporeal Membrane Oxygenation for the Poisoned Patient. (2022, September). N Am Congress of Clin Toxicol. San Francisco, California. 
4. Wang GS, Levitan R, Wiegand TJ, et al. Extracorporeal Membrane Oxygenation (ECMO) 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
5. Nordt, S., Swadron, S., & Herbert, M. (2019, September). Toxicology sessions: ECMO in poisonings. EM:RAP. Retrieved February 18, 2023, from https://www.emrap.org/episode/emrap20194/toxicology1
6. Gussow, Leon MD. Toxicology Rounds: The Next Big Thing. Emergency Medicine News 37(4):p 1,30-30, April 2015. | DOI: 10.1097/01.EEM.0000464074.34205.00 
7. Yu D, Xiaolin Z, Lei P, Feng L, Lin Z, Jie S. Extracorporeal Membrane Oxygenation for Acute Toxic Inhalations: Case Reports and Literature Review. Front Med (Lausanne). 2021 Sep 29;8:745555. doi: 10.3389/fmed.2021.745555. PMID: 34660650; PMCID: PMC8511675.
8. Wu PE, Juurlink DN. Clinical Review: Loperamide Toxicity. Ann Emerg Med. 2017 Aug;70(2):245-252. doi: 10.1016/j.annemergmed.2017.04.008. Epub 2017 May 13. PMID: 28506439.
9. Pozzi M, Buzzi R, Hayek A, Portran P, Schweizer R, Fellahi JL, Armoiry X, Flagiello M, Grinberg D, Obadia JF. Veno-arterial extracorporeal membrane oxygenation for drug intoxications: A single center, 14-year experience. J Card Surg. 2022 Jun;37(6):1512-1519. doi: 10.1111/jocs.16456. Epub 2022 Mar 30. PMID: 35353389.