Critical Care, Cardiology

A Review of ECMO in the ED: History, Mechanics, Common Indications, and Future Implications

As the use of extracorporeal membrane oxygenation becomes more prevalent, emergency physicians should understand the history of ECMO, how it works, when it's indicated, and what role it plays in the emergency department.

The use of extracorporeal membrane oxygenation (ECMO) as a potentially lifesaving intervention is becoming increasingly popular and its application more diverse. Advancements in technology, increased training for intensivists, and its implementation at more health care centers have provided growing opportunities for the use of ECMO in patients with the appropriate indications.1 An EM provider is tasked with diagnosing patients with acute, life-threatening pathologies and implementing the appropriate interventions in a timely manner. Certain presentations of acute respiratory failure, cardiopulmonary failure, or cardiac arrest may be refractory to early, aggressive resuscitation resulting in death or significant morbidity, for which ECMO may be a solution. Thus, it is imperative that professionals in the ED are familiar with ECMO in order to provide optimal care for the appropriate candidates. The purpose of this article is to review the history of ECMO, how it works, common indications for its use, and its role in the ED.

History of ECMO
ECMO has had an extensive history, initially functioning as a support device for patients in cardiopulmonary bypass operations in the 1950s.1 As technology progressed, its use expanded, and in 1971, Dr. Solomon Hill successfully treated a patient with acute respiratory failure utilizing an extracorporeal bypass circuit.2 This finding spurred increased usage of ECMO as a therapeutic option for patients with significant isolated lung injury refractory to optimal medical management, and in that time period, devices similar to ECMO were used in more than 150 patients with approximately 15% surviving the initial insult.2 A few years later, an infamous case report was published detailing the use of ECMO in a neonate. In 1974, a mother emigrating from Mexico birthed a child at a hospital in Orange County, California, who aspirated meconium at the time of delivery. This patient remained hypoxic despite maximal ventilator settings and was anticipated to suffer a fatal outcome. The decision was made to initiate ECMO, and the neonate fully recovered after 3 days.3 

Over the next several years, more anecdotal evidence surfaced reporting increased survival when using ECMO in patients with respiratory failure, but no randomized controlled trials (RCT) had been performed to suggest its efficacy in treating patients with this indication.

In 1979, Zapol et al. published an RCT comparing survival between adult patients with severe acute respiratory failure treated with the medical standard of care including mechanical ventilation (MV) to ECMO. This study found no statistical difference in survival with approximately 90% mortality rate in both groups.4 Additionally, in 1994, Morris et al. published an RCT that compared MV to veno-venous ECMO (VV ECMO) in patients with acute respiratory failure and reported survival rates of 44% and 33%, respectively.5 The data up to this point showed the greatest benefit when ECMO was used in the pediatric population but little improvement when used in the adult setting. 

Among the most important studies regarding the potential benefit of ECMO came from the United Kingdom in 2009. The Conventional Ventilatory Support vs Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) trial compared VV ECMO with conventional medical management in patients with acute respiratory distress syndrome (ARDS). The trial’s primary outcome was death or severe disability at 6 months or before discharge from hospital. While the design of this study invited significant criticism, it found an improved survival in the ECMO group (patient transferred to an ECMO center) when compared to the group treated with conventional management.6 In contrast to this, later that year, Jones et al. published an observational study in which VV ECMO was used in patients admitted to the ICU with H1N1 influenza infection. The group reported that of those treated with VV ECMO, 71% survived to ICU discharge and approximately 47% survived to hospital discharge.7 This finding identified that ECMO can be a viable option in certain patients with consideration to age, gender, medical comorbidities, and etiology of respiratory failure. 

In 2018, the widely publicized multicenter RCT, ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial, comparing standard medical management to VV ECMO in patients with severe ARDS was published. While this study did show a reduction in 60-day mortality in the group treated with ECMO, this finding was not statistically significant (p-value 0.07) and ultimately, the study was terminated for futility.8,9 Though this study did not show significant reduction in mortality, it did highlight that patients not responding to optimal standard-of-care management in the setting of severe lung injury may benefit from early consideration of ECMO and showed evidence of clinical improvement within a few hours of its initiation.10 Since this trial, multiple case studies have continued to document positive outcomes when using ECMO; however, additional RCTs are needed to further illustrate its efficacy and identify optimal candidates for its use. 

What is ECMO and How Does It Work?
ECMO works by draining deoxygenated blood from a vein, pumping this blood through a membrane oxygenator which removes carbon dioxide and supplies oxygen, and reintroducing the newly oxygenated blood to a patient’s vein or artery.11 This is performed through a circuit that consists of a blood pump, membrane oxygenator, internal tubing system, heat exchanger, and drainage and return cannulae.12 ECMO can be divided into two main categories, VV ECMO and veno-arterial (VA) ECMO. VV ECMO is indicated in patients with significant isolated lung injury and provides respiratory support but not circulatory support. Thus, consideration for this modality should be made in patients suffering from respiratory failure, but in whom cardiac function is sufficient.11 In contrast, VA ECMO is used in patients with cardiac or cardiopulmonary failure and provides circulatory support as well as respiratory support.11 

ECMO devices use either a roller or centrifugal pump. Roller pumps function through continuous peristalsis of an inner tubing system which moves blood through the distal portion of the compressed region. Deoxygenated blood travels from this pump to the membrane oxygenator, where the blood is decarboxylated and oxygenated, and is then delivered back to the patient.13 Most well-funded centers, however, use a centrifugal pump, which is smaller and utilizes more advanced technology.13 Centrifugal pumps work by establishing a pressure differential that drives blood through a revolving impeller which further moves blood through the ECMO unit and return cannulae.13 Ironically, while centrifugal pumps require lower doses of heparin and are associated with decreased levels of hemolysis, they have been shown to result in higher rates of gastrointestinal, pulmonary, and intracranial hemorrhage.14 Another important component of the ECMO circuit is the membrane oxygenator which functions in lieu of a patient’s lungs to remove carbon dioxide and oxygenate blood. Currently, most ECMO oxygenators use a polymethylpentene membrane, which is a more durable material, allows for better gas exchange, and results in reduced rates of anemia and coagulopathy than other options.15 

Cannulation techniques and the associated resources required differ significantly depending on the type of ECMO employed. In VV ECMO, cannulation can be performed with either single lumen or double lumen catheters. When using single lumen catheters, carboxylated blood is typically drained from a cannulated femoral vein and decarboxylated blood is returned to the right internal jugular vein (IJV).15 In comparison, a single dual lumen catheter can be inserted into the right IJV with one lumen functioning to drain blood and the other to return it.16 Use of dual lumen catheters has been increasing in adult ECMO as this method results in decreased recirculation phenomenon.16 Recirculation results when, instead of providing support to systemic circulation, oxygenated blood is infused into the patient through a return cannula and exits immediately back to the ECMO circuit through the drainage cannula, creating a closed loop of circulation within the ECMO system.16 Other advantages of this approach include reduced sites for potential infection and increased mobility for the patient.16  Both single and dual lumen cannulation can be performed percutaneously by a trained provider at the bedside; however, transesophageal echocardiography or fluoroscopy is needed for accurate placement of the dual lumen cannula.15 

VA ECMO cannulation can be performed either centrally or peripherally, each with its own potential risks, benefits, indications, and resources required. In central cannulation, blood is typically drained from the right atrium and returned to the proximal ascending aorta. A surgeon, anesthesiologist, and staffing for the operating room are typically required to perform this type of cannulation as direct access to the right atrium and aorta involves a sternotomy.17 In contrast, peripheral cannulation can be performed using a percutaneous approach by a medical provider at bedside.18 This involves cannulation of the proximal femoral or jugular vein for drainage of deoxygenated blood and carotid, femoral or axillary artery cannulation for delivery of newly oxygenated blood back to the patient.19 One major complication in femoral arterial cannulation is distal limb ischemia.20 To mitigate this risk, providers may choose to place a distal perfusion catheter on the same side of femoral artery cannulation most often in the superficial femoral artery.20 Another important consideration in peripheral VA ECMO is coronary and cerebral hypoxia as a result of blood mixing. Blood mixing occurs when oxygenated blood from the ECMO device combines with blood ejected from the patient’s left ventricle.21 When myocardial function is significantly impaired, this mixing point typically occurs at the proximal ascending aorta and does not result in clinically significant cerebral hypoxia.21 However, as myocardial function improves, the mixing point moves to the aortic arch, resulting in deoxygenated blood being pumped to coronary and cerebral circulation.21 For this reason, it is important to frequently monitor arterial blood gases from the right upper extremity in order to identify and address cerebral or coronary hypoxemia.22 

When using VA ECMO, there is also risk of increased left atrial and left ventricular end-diastolic pressures resulting in left heart distention.23 A prophylactic approach to this involves placing an Impella to decompress the left ventricle or a transseptal drain to preserve normal left atrial pressure.23 For this reason, pressures in the left atrium and left ventricle and the chambers sizes should be closely and regularly followed using echocardiography. These are just a few examples of how physiology is manipulated with ECMO and some of the associated complications. Thus, it is imperative to carefully assess risks, cost, and resources required before implementing this intervention. 

Common Indications for ECMO
Consideration to initiate ECMO depends largely on patient risk factors, response to resuscitative efforts, and pathology being addressed. In the setting of cardiogenic shock or cardiac failure refractory to optimal medical management, VA ECMO may be appropriate.24,25 Certain pathologies that seem to benefit from VA ECMO include “acute coronary syndrome (ACS), cardiac arrhythmias, sepsis with cardiac depression, drug toxicity with profound cardiac depression, myocarditis, pulmonary embolism, cardiac trauma, acute anaphylaxis, post-surgical cardiac complications, primary cardiac allograft failure, and cardiac cardiomyopathy.”26 

In contrast, patients with acute respiratory failure not responsive to initial aggressive interventions may benefit from VV ECMO. Common pathologies that have shown benefit with the use of VV ECMO include “ARDS (bacterial or viral pneumonia, aspiration events, alveolar proteinosis), lung rest from pulmonary contusion, smoke inhalation and airway obstruction, post-lung transplant with primary graft failure, bridge to lung transplant, lung hyperinflation in setting of status asthmaticus, pulmonary hemorrhage or massive hemoptysis, congenital diaphragmatic hernia, and meconium aspiration.”26 

Role in the ED
In ED setting, physicians are tasked with initiating the appropriate treatment plan for their patients in a timely manner. Patients who present with severe illness often require immediate intervention with frequent reassessments for improvement or worsening of their initial presentation. In some scenarios where patients continue to clinically deteriorate despite vigorous resuscitative efforts, further cardiorespiratory support in the form of ECMO may be useful. 

While the underlying mechanics remain the same, ECMO performed in the ED is termed either extracorporeal life support (ECLS) or extracorporeal cardiopulmonary resuscitation (ECPR). ECLS describes the use of ECMO as a temporizing measure in the critically ill patient.27 ECPR is the term applied when VA ECMO is initiated in the setting of cardiac arrest.27 Even when optimal cardiopulmonary resuscitation (CPR) is performed, only a fraction of normal cardiac output is achieved, rendering the patient susceptible to significant anoxic brain injury and multi-system organ failure.27 The fraction of normal cardiac output (CO) attained in the setting of CPR is approximately 30%. This is associated with a cardiac index of 0.6L/min/m2 compared to 2.0L/min/m2 when using ECPR (normal cardiac index is 2.5-4L/min/m2).28 In the setting of out-of-hospital cardiac arrest, global survival rates are 2-11%.29 In contrast, between the years 1990 and 2012, the Extracorporeal Life Support Organization (ELSO) reported survival rates of 27% when ECPR was initiated.30 In 2017, Wang et al. published a meta-analysis of six studies comparing ECPR to conventional CPR and found significant improvement with regards to survival rate to discharge and neurologic outcome when ECPR was employed.31 This study highlighted a number of additional factors contributing to the better outcomes including early recognition of pulselessness, time to CPR, immediate defibrillation, initial rhythm, etiology of cardiac arrest, and time to ECPR.31 Kuroki et al. further posits that a unique advantage of ECPR is the ability to use this technology to simultaneously performing coronary angiography and fibrinolysis which may also contribute to treating the underlying pathology leading to the cardiac arrest.32 While more studies are needed to further identify the suitable candidates for whom positive outcomes can be achieved and the appropriate timelines for such interventions, present data suggests that ECPR may play an essential role in effective management of cardiac arrest in the ED. 

ECLS is another therapeutic option available for use in the ED. In 2016, Allen et al., in collaboration with The American College of Emergency Physicians commented on the use of ECMO and ECLS in the ED and specified patients who may be appropriate and ethical candidates.33 In this paper, Allen proposed that the decision to initiate ECMO should be made quickly and with the primary goal of being used as a bridge to definitive therapy for patients in whom the provider anticipates a meaningful outcome.33 This article also reported that the current data would support clinical consideration for ECLS or ECPR in patients who “are 18 to 70 years old, have a witnessed arrest, have ventricular fibrillation or ventricular tachycardia as their initial rhythm, have a presumed cardiac cause, and have received high-quality CPR delivered with minimal interruptions.”33 While this publication recommends that eligibility for ECMO should be restricted to a rather small cohort of patients, it also suggests that candidacy is ultimately best determined by a clinician’s overall gestalt and comfort with initiating this intervention. 

Conclusion
The use of ECMO has been expanding in the advent of more advanced technology and increased training opportunities for intensivists, surgeons, and emergency medicine physicians, leading to its implementation at more health care centers. Access to ECMO centers is growing, and its early initiation has demonstrated significant positive impact on patient outcomes in a number of clinical trials and case reports. Emergency physicians are considered experts at resuscitating patients with the most severe presentations of both acute and chronic pathologies, and are tasked with maintaining a broad knowledge of available interventions that may be life-saving or life-altering. For this reason, ED physicians should consider ECMO for patients in cardiac arrest or those suffering from acute cardiopulmonary failure refractory to conventional methods of resuscitation and in whom a meaningful recovery is anticipated if they can be bridged to definitive therapy. Future studies are needed to further identify the appropriate candidates for ECMO in the ED, its efficacy in certain pathologies, and its usefulness as a therapeutic modality in the initial intervention of a patient in cardiac arrest.


References
1. Mosier JM, Kelsey M, Raz Y, et al. Extracorporeal membrane oxygenation (ECMO) for critically ill adults in the emergency department: history, current applications, and future directions. Crit Care. 2015;19:431.
2. Wolfson P. (2003). The development and use of extracorporeal membrane oxygenation in neonates. Ann Thoracic Surg. 2003;76(6):S2224-S2229.
3. Bartlett RH. Esperanza. ASAIO Journal. 2017;63(6):832-843.
4. Zapol W. Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Failure. JAMA. 1979;242(20):2193.
5. Morris A, Wallace C, Menlove R, et al. Randomized Clinical Trial of Pressure-Controlled Inverse Ratio Ventilation and Extracorporeal CO2 Removal for Adult Respiratory Distress Syndrome. Survey Anesthesiol. 1995;39(2):94.
6. Peek G, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. The Lancet. 2009;374(9698):1351-1363.
7. Davies A, Jones D, Bailey M, et al. Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome. JAMA. 2009;302(17):1888.
8. Alain C, David H, Capellier G, et al. (2019). Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2019; online ahead of print.
9. Gattinoni L, Vasques F, Quintel M. Use of ECMO in ARDS: does the EOLIA trial really help? Crit Care. 2018;22(1).
10. Desai M, Dalton HJ. Half-empty or half-full?-interpretation of the EOLIA trial and thoughts for the future. J Thorac Dis. 2018;10(Suppl 26):S3248–S3251.
11. Squiers JJ, Lima B, Dimaio JM. Contemporary extracorporeal membrane oxygenation therapy in adults: Fundamental principles and systematic review of the evidence. J Thorac Cardiovasc Surg. 2016;152(1):20-32.
12. Lequier L, Horton SB, McMullan DM, Bartlett RH. Extracorporeal membrane oxygenation circuitry. Pediatr Crit Care Med. 2013;14(5 Suppl 1):S7–S12.
13. Toomasian JM, Bartlett RH. Hemolysis and ECMO pumps in the 21st Century. Perfusion. 2010;26(1):5-6.
14. Halaweish I, Cole A, Cooley E, Lynch WR, Haft JW. Roller and Centrifugal Pumps. ASAIO Journal. 2015;61(5):496-501.
15. Bermudez CA, Rocha RV, Sappington PL, Toyoda Y, Murray HN, Boujoukos AJ. Initial Experience With Single Cannulation for Venovenous Extracorporeal Oxygenation in Adults. Ann Thorac Surg. 2010;90(3):991-995.
16. Jayaraman AL, Cormican D, Shah P, Ramakrishna H. Cannulation strategies in adult veno-arterial and veno-venous extracorporeal membrane oxygenation: Techniques, limitations, and special considerations. Ann Card Anaesth. 2017;20(Supplement):S11–S18. 17. Pavlushkov E, Berman M, Valchanov K. Cannulation techniques for extracorporeal life support. Ann Transl Med. 2017;5(4):70.
18. Schaheen BW, Thiele RH, Isbell JM. Extracorporeal life support for adult cardiopulmonary failure. Best practice & research. Best Pract Res Clin Anaesthesiol. 2015;29(2):229-239.
19. Jayaraman AL, Cormican D, Shah P, Ramakrishna H. Cannulation strategies in adult veno-arterial and veno-venous extracorporeal membrane oxygenation: Techniques, limitations, and special considerations. Ann Card Anaesth. 2017;20(Supplement):S11–S18.
20. Vallabhajosyula P, Kramer M, Lazar S, et al. Lower-extremity complications with femoral extracorporeal life support. J Thorac Cardiovasc Surg. 2016;151(6):1738-1744.
21. Alwardt CM, Patel BM, Lowell A, Dobberpuhl J, Riley JB, DeValeria PA. Regional perfusion during venoarterial extracorporeal membrane oxygenation: a case report and educational modules on the concept of dual circulations. J Extra Corpor Technol. 2013;45(3):187–194.
22. Chung M, Shiloh AL, Carlese A. Monitoring of the Adult Patient on Venoarterial Extracorporeal Membrane Oxygenation. Scientific World Journal. 2014;2014:1-10.
23. Aiyagari RM, Rocchini AP, Remenapp RT, Graziano JN. Decompression of the left atrium during extracorporeal membrane oxygenation using a transseptal cannula incorporated into the circuit. Crit Care Med. 2006;34(10):2603-2606.
24. Martinez G, Vuylsteke A. Extracorporeal membrane oxygenation in adults. Continuing Education in Anaesthesia Critical Care & Pain. 2012;12(2):57-61.
25. Marasco SF, Esmore DS, Negri J, et al. Early Institution of Mechanical Support Improves Outcomes in Primary Cardiac Allograft Failure. J Heart Lung Transplant. 2005;24(12):2037-2042.
26. Makdisi G, Wang IW. Extra Corporeal Membrane Oxygenation (ECMO) review of a lifesaving technology. J Thorac Dis. 2015;7(7):E166–E176.
27. Singer B, Reynolds JC, Lockey DJ, O'Brien B. Pre-hospital extra-corporeal cardiopulmonary resuscitation. Scand J Trauma Resusc Emerg Med. 2018;26(1):21. 
28. Guercio LRMD, Feins NR, Cohn JD, Coomaraswamy RP, Wollman SB, State D. Comparison of Blood Flow During External and Internal Cardiac Massage in Man. Circulation. 1965;31(4s1).

29. Berdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of out-of-hospital cardiac arrest and survival rates: Systematic review of 67 prospective studies. Resuscitation. 2010;81(11):1479-1487.

Related Articles

Reflections of a Rising MSIV

Zach Jarou, MD 08/06/2013
Reflections of a Rising MSIV The Darkest Year? A recent article in Slate magazine describes the transition from preclinical to clinical medical education as the “darkest” year of medical school. It

A Seat at the Table: Physicians as Policymakers

Zach Jarou, MD 10/06/2013
A Seat at the Table: Physicians as Policymakers Imagine a world where patients in need of emergent treatment were turned away because of their race, religious beliefs, or ability to pay. Believe it o