Extracorporeal Membrane Oxygenation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor-In-Chief: Parth Vikram Singh, MBBS[2]

Figure. ECMO pulls blood out of your body and puts it back after adding oxygen to it. (Adapted from https://my.clevelandclinic.org/health/treatments/21722-extracorporeal-membrane-oxygenation-ecmo)

Overview

Extracorporeal Membrane Oxygenation (ECMO), also referred to as Extracorporeal Life Support (ECLS), is an advanced life-support technique designed to provide prolonged cardiac and/or respiratory support in patients with severe and potentially reversible heart or lung failure unresponsive to conventional therapy. ECMO works by diverting blood from the patient’s circulation, oxygenating it via an artificial lung (membrane oxygenator), and returning it to the patient’s bloodstream. It serves as a temporary bridge to recovery, transplant, or long-term mechanical support.

Available Devices

Several prominent manufacturers produce ECMO (Extracorporeal Membrane Oxygenation) systems for clinical use.[1] These include:

  • Medtronic
  • Maquet (Getinge Group)
  • Xenios AG (Fresenius Medical Care)
  • Sorin Group
  • Terumo
  • Nipro
  • MicroPort

Components of the ECMO Circuit

  1. Cannulas: Large-bore catheters inserted in veins/arteries for blood drainage and return.
  2. Pump: Centrifugal or roller pumps to maintain blood flow.
  3. Oxygenator: Membrane oxygenator allows gas exchange (oxygen in, CO₂ out).
  4. Heat Exchanger: Maintains normothermia.
  5. Tubing: Biocompatible plastic that connects the circuit.
  6. Monitors: Assess pressure, flow, oxygenation, and temperature.
Fig. A MAQUET hollow fiber membrane oxygenator
Fig. Diagram of complete ECMO circuit labeled with components.

Types of ECMO

Veno-Venous (VV) ECMO

  • Provides only pulmonary support.
  • Venous blood is withdrawn (typically via femoral vein), oxygenated, and returned to a central vein (typically via right internal jugular vein).[2] Alternatively, a dual-lumen catheter can be placed in the right internal jugular vein, allowing blood to be withdrawn from both the superior and inferior vena cava and then returned directly into the right atrium.
  • Used in cases of isolated respiratory failure.
Fig. VV-ECMO setup for simultaneous drainage and reinfusion. (Adapted from https://www.albertasono.ca/echo-2/tee/veno-venous-ecmo-insertion/)

Veno-Arterial (VA) ECMO

  • Provides both cardiac and pulmonary support.
  • Blood is drained from a vein and returned to an artery, bypassing both the heart and lungs.
  • In VA ECMO, blood is typically drained via a cannula inserted into the femoral vein and returned through a cannula placed in the femoral artery. The venous cannula tip is positioned near the junction of the inferior vena cava and right atrium, while the arterial tip sits in the iliac artery. Femoral access is preferred in adults due to its relative ease of insertion.[3]
  • Used in cardiogenic shock, cardiac arrest, or combined heart-lung failure.
Fig. VA-ECMO configuration for cardiac or respiratory failure. (Adapted from Oliver M. et al. Int J Emerg Med 2024; 10;17(1):71)[4]

Hybrid ECMO (VAV, VVA)

  • Mixed configurations used in complex scenarios, e.g., differential hypoxia or partial cardiac support with respiratory failure.

Indications

The Extracorporeal Life Support Organization (ELSO) provides guidelines outlining when and how ECMO should be used. While specific initiation criteria may differ across institutions, ECMO is typically considered for patients with severe, potentially reversible cardiac or respiratory failure that does not respond to standard treatments. Common scenarios[5] warranting ECMO include critical heart or lung conditions requiring advanced support are:


1. Respiratory Failure (VV ECMO)

  • Acute Respiratory Distress Syndrome (ARDS): Severe hypoxemic respiratory failure with a PaO₂/FiO₂ ratio below 100 mmHg, even after optimizing ventilator settings such as FiO₂, PEEP, and the I:E ratio. In hypercapnic failure, ECMO may be considered when arterial pH drops below 7.20, indicating significant respiratory acidosis despite standard interventions.
  • Severe bacterial/viral pneumonia
  • Smoke inhalation
  • Pulmonary contusion
  • Status asthmaticus
  • Near-drowning
  • Bridge to lung transplant

2. Cardiac Failure (VA ECMO)

  • Refractory Cardiogenic shock
  • Fulminant myocarditis
  • Cardiac arrest (eCPR)
  • Post-cardiotomy shock
  • Massive pulmonary embolism
  • Failure to wean from cardiopulmonary bypass after cardiac surgery
  • Bridge to ventricular assist device (VAD) or heart transplant

3. Other Indications

  • Septic shock
  • Hypothermia, with a core temperature between 28 and 24 °C and cardiac instability, or with a core temperature below 24 °C.[6]
  • Drug overdose with cardiovascular collapse
  • Bridge to decision or recovery
  • Thyroid Storm[7]
  • COVID-19 patients: Beginning in February 2020, ECMO was increasingly adopted in China to support patients with severe COVID-19-related pneumonia when mechanical ventilation alone was insufficient to maintain adequate oxygenation.[8] Early data suggested that ECMO improved blood oxygen levels and reduced mortality in about 3% of the most critically ill patients.[9] Compared to conventional therapy, which had mortality rates of 59–71%, ECMO use brought this down to approximately 46%.[10] High-profile cases, such as a severely ill patient covered in the Los Angeles Times in March 2021 and three critically ill pregnant women in Israel in February 2021, further highlighted ECMO’s role as a potentially life-saving intervention during the pandemic.[11][12]

Contraindications

Absolute

  • Irreversible heart or lung disease without transplant option
  • Severe neurologic injury (e.g., massive stroke)
  • Prolonged cardiac arrest without effective CPR
  • Advanced malignancy

Relative

  • Age > 75 years
  • Multiorgan failure
  • Severe coagulopathy or active bleeding
  • Inability to anticoagulate

Procedure

Initiation

ECMO should be initiated and managed only by healthcare professionals trained in its initiation, maintenance, and discontinuation. Cannulation is typically performed in an operating room by a cardiothoracic surgeon, while ongoing management is handled by specialized staff such as nurses, respiratory therapists, or perfusionists. Before starting ECMO, patients receive an intravenous bolus of heparin to prevent clot formation, with the goal of reaching an activated clotting time (ACT) of 300–350 seconds. Once this range is achieved, ECMO is initiated, and a continuous heparin infusion is started for maintenance.[13]

1.     Cannulation for ECMO: can be performed using either the percutaneous Seldinger technique or surgical cutdown, with the goal of inserting the largest feasible cannula to optimize blood flow and reduce shear stress. While limb ischemia is a known risk, it can often be prevented by ensuring adequate distal limb perfusion.[14] In post-cardiac surgery complications, cannulas may be placed directly into the heart or major vessels. Peripheral cannulation (e.g., via femoral or jugular sites) is particularly beneficial in lung transplant candidates, as it enables patients to remain conscious and mobile, which correlates with improved post-transplant recovery.[15][16] ECMO is also effectively utilized during lung transplantation surgeries to stabilize patients, leading to favorable outcomes.[17][18]

2.     Titration: After establishing ECMO support, blood flow is adjusted based on hemodynamic data and physical examination to ensure adequate organ perfusion while maintaining enough natural heart flow to prevent blood stasis and clot formation.

Maintenance

After meeting the initial respiratory and circulatory targets, ECMO blood flow is kept stable at that level. Ongoing evaluations and necessary adjustments are guided by continuous venous oximetry, which monitors oxygen saturation in the venous side of the circuit. Few important monitoring parameters:

  • Hemodynamics: Flow rate, MAP, cardiac output
  • Respiratory: Blood gases, oxygen saturation, sweep gas adjustments
  • Neurologic: Glasgow Coma Scale, pupillary response, neuroimaging
  • Renal: Urine output, creatinine, need for CRRT
  • Anticoagulation: Heparin, ACT target 180–220 sec; alternatives include bivalirudin
  • Special Considerations:
    • VV ECMO is primarily indicated for respiratory failure, whereas VA ECMO is used for cases involving cardiac dysfunction. Each modality presents distinct management challenges that must be carefully addressed.
    • Blood Flow: In VV ECMO, higher flow rates are typically needed to ensure sufficient oxygen delivery. For VA ECMO, the flow must be carefully balanced—high enough to maintain adequate tissue perfusion and venous oxygen saturation, yet low enough to preserve left ventricular preload and prevent impaired cardiac output.
    • Diuresis: Patients are often fluid overloaded at ECMO initiation, so once stable, aggressive fluid removal is recommended. Ultrafiltration can be incorporated into the ECMO circuit for patients with low urine output. However, signs such as waveform instability (“ECMO chatter”) may suggest hypovolemia, indicating a need to pause diuresis or ultrafiltration. Notably, ECMO increases the risk of acute kidney injury, partly due to systemic inflammation.[19]
    • Left Ventricular Monitoring: In VA ECMO, careful monitoring of left ventricular function is essential. Elevated afterload from ECMO support can impair cardiac output and increase the risk of intracardiac thrombus formation, necessitating vigilant assessment and management.[20][21]
Fig. A respiratory therapist takes a blood sample from a newborn in preparation for ECMO therapy.

Weaning and Discontinuation

In patients with respiratory failure, readiness for ECMO removal is indicated by improvements in chest imaging, lung compliance, and arterial oxygenation levels. For those with cardiac failure, increased aortic pulsatility suggests better left ventricular performance, signaling potential readiness for weaning. If clinical and physiological indicators are favorable, ECMO flow is gradually reduced while closely monitoring the patient’s response to ensure stability. Once the flow is decreased to below 2 L/min, decannulation is considered, with continuous monitoring throughout the process.[22]

Veno-Venous (VV) ECMO Weaning Trial: Reduce sweep gas to 0 and monitor ABGs. In VV ECMO, weaning is assessed by stopping the sweep gas to the oxygenator while maintaining blood flow. This halts gas exchange, allowing clinicians to evaluate if the patient's lungs can independently manage oxygenation and ventilation over several hours, guided by blood gas analyses.

Veno-Arterial (VA) ECMO Weaning Trial: Reduce sweep gas to 0 and monitor ABGs. For VA ECMO, both the drainage and return lines are briefly clamped, allowing circuit blood to circulate via a bridging loop between the arterial and venous sides. This prevents blood stasis and clotting within the circuit. During the trial, continuous flushing with heparinized saline or blood is essential. VA ECMO trials are typically shorter than VV trials due to a higher risk of thrombosis.

Complications

  • Blood Related
    • Bleeding: Anticoagulation is essential during ECMO to prevent circuit thrombosis but increases the risk of bleeding. Managing this balance is challenging and requires close monitoring for bleeding, particularly at cannulation sites and within organs.  Cannulation can lead to several complications, such as vascular perforation with hemorrhage, arterial dissection, distal limb ischemia, or malpositioning of the cannula. Anticoagulation protocols often need to be tailored based on the patient's clinical response.[23] Heparin-induced thrombocytopenia (HIT) is also a known complication in ECMO patients and typically necessitates switching to a non-heparin anticoagulant.[24]
    • Thrombosis: Clots in the circuit, oxygenator failure, systemic embolism. Thrombotic events may still arise within the ECMO circuit despite anticoagulation, potentially causing device failure or embolism. Routine assessment of circuit function and imaging help detect clots early. Preventive measures include maintaining adequate flow rates, careful anticoagulation monitoring, and replacing circuit components when needed.[25] In VA ECMO via femoral access, retrograde aortic flow can also lead to blood stasis and thrombosis if left ventricular output is insufficient.
    • Hemolysis: Mechanical stress within the ECMO circuit can cause hemolysis, or red blood cell destruction, potentially leading to anemia, jaundice, and kidney injury. Indicators such as elevated LDH and hemoglobin in urine help detect hemolysis early, prompting interventions like modifying pump speed or replacing circui components to reduce further damage.[26]
  • Limb ischemia: Especially in femoral VA ECMO
  • Neurologic: Neurologic complications[27] are common in adults on ECMO and may include hemorrhage, ischemic stroke, encephalopathy, coma, or brain death. Major bleeding occurs in 30–40% of patients, often due to continuous heparin use and platelet dysfunction. Careful surgical technique, adequate platelet counts (>100,000/mm³), and maintaining appropriate clotting times can help mitigate this risk.
  • Infections: Line sepsis, ventilator-associated pneumonia. Hospital-acquired infections occur in 10–12% of ECMO patients, a rate higher than in other critically ill populations. Common pathogens include coagulase-negative staphylococci, Candida spp., Enterobacteriaceae, and Pseudomonas aeruginosa. Ventilator-associated pneumonia is notably frequent, especially involving Enterobacteriaceae. Infection risk increases with ECMO duration and is further influenced by patient illness severity, gut bacterial translocation, immune suppression, and colonization of catheters, cannulae, and the oxygenator.[28]

History

The development of ECMO began in the 1950s, initially pioneered by John Gibbon and later advanced by C. Walton Lillehei. Its first successful application in neonates occurred in 1965.[29]

Banning Gray Lary[30] was among the earliest to demonstrate that life could be sustained through intravenous oxygen delivery. In a 1951 Surgical Forum publication,[31] Lary described an experimental setup where animals survived while inhaling pure nitrogen, thanks to microbubbles of oxygen injected directly into the bloodstream. These bubbles were created by passing oxygen mixed with a wetting agent through a porcelain filter. Walton Lillehei later reviewed Lary’s work and, along with Richard DeWall, developed the first practical heart-lung machine using a bubble oxygenator—a design that remained in use, with modifications, for the next two decades.

Technological Advancements

  • Compact ECMO systems: Miniaturization has led to the development of compact ECMO systems, enhancing portability and usability. These smaller devices are particularly valuable in resource-limited settings and during intra-hospital transport, offering continuous life support where traditional, larger systems may be impractical.[32]
  • Ambulatory ECMO: portable ECMO systems that allow patients to remain mobile and participate in rehabilitation while on support. This approach improves quality of life, supports physical recovery, and reflects a shift toward more patient-centered, activity-integrated ECMO care.[33]
  • Extracorporeal CO2 removal: Extracorporeal CO₂ Removal (ECCO₂R) systems are devices developed through miniaturization advances to manage hypercapnic respiratory failure. By efficiently removing carbon dioxide, they allow the lungs to rest and recover. Their smaller size enhances flexibility across clinical settings, expanding the range of respiratory support options within the ECMO spectrum.[34]
  • Closed-loop systems: Closed-loop systems are a major innovation in ECMO, enabling real-time monitoring and automatic adjustment of pump speed and oxygenation based on blood gas levels. By minimizing the need for manual changes, these systems improve efficiency, enhance precision, and offer more responsive and individualized patient care.[35]
  • Biocompatible materials: Advancements in biomaterials have led to ECMO circuits with improved biocompatibility, reducing clotting and inflammation triggered by traditional systems. These materials minimize adverse physiological responses, enhancing the safety and effectiveness of prolonged ECMO support.[36]
  • Data analytics and artificial intelligence: The integration of data analytics and artificial intelligence (AI) marks a significant advancement in ECMO technology. AI can process large volumes of patient data to detect trends, forecast complications, and fine-tune ECMO parameters for individual patients. This enables more personalized and adaptive management, with interventions tailored to each patient’s specific needs. Predictive modeling further enhances proactive care by helping clinicians anticipate issues and optimize treatment strategies accordingly.[37]

Research

Initial studies demonstrated that ECMO improves survival in patients with acute respiratory failure, particularly those with ARDS.[38][39] Data from the ELSO registry, which includes nearly 51,000 ECMO cases, show survival rates of 75% in neonates, 56% in pediatric patients, and 55% in adults with respiratory failure.[40] Other studies have reported survival ranging from 50% to 70%,[41][42] surpassing historical outcomes.[43][44][45] Early identification and timely initiation of ECMO are critical to improving prognosis and preventing clinical decline.[46]

Many randomized controlled trials (RCTs) have assessed the efficacy of ECMO in patients with respiratory failure. The initial studies by Zapol et al. and Morris et al. were limited by the technological constraints of ECMO systems available during the 1970s and 1990s. In contrast, the CESAR and EOLIA trials employed contemporary ECMO technology and are regarded as the most pivotal RCTs in evaluating ECMO's clinical utility.

CESAR Trial (2009)

  • The Conventional Ventilatory Support vs. Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) Trial[47] was a UK-based multicenter RCT comparing ECMO to conventional mechanical ventilation in adults with severe, potentially reversible respiratory failure. The primary outcome was death or severe disability at six months or hospital discharge. Among 180 enrolled patients, 75% of those referred for ECMO actually received it. The ECMO group showed significantly higher survival (63% vs. 47%, p=0.03) and a small gain in quality-adjusted life years, though with longer hospital stays and higher costs. A key limitation was the lack of a standardized protocol in the control group,[48] leading to inconsistent use of lung-protective strategies. The study concluded that referral to an ECMO center improves survival free of severe disability at six months.


EOLIA Trial (2018)

  • The ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) Trial[49] assessed early ECMO initiation versus conventional mechanical ventilation in severe ARDS patients, with 60-day mortality as the primary endpoint. The study enrolled 249 of a planned 331 patients before being terminated for futility. No significant mortality difference was found between groups (35% ECMO vs. 46% control), though interpretation was complicated by 28% of control patients crossing over to ECMO.[50] Treatment failure was lower in the ECMO group (RR 0.62, p<0.001), in favor of the ECMO group. Safety concerns included more bleeding and thrombocytopenia with ECMO, but fewer strokes. While early ECMO did not show a clear mortality benefit, it may offer value as a rescue therapy in refractory cases.[51]

Conclusion

ECMO has revolutionized the management of refractory cardiopulmonary failure. While resource-intensive and not without risk, its judicious use in appropriate clinical contexts can lead to meaningful survival and recovery. Ongoing research, improved technology, and multidisciplinary expertise are key to optimizing its outcomes.

References

  1. ↑ "ExtraCorporeal Membrane Oxygenation Market 2020 Recent Trends, Analysis, Business Growth, Share Estimation and Regional Overview Forecast by 2026 - MarketWatch".
  2. ↑ Wang D, Zhou X, Liu X, Sidor B, Lynch J, Zwischenberger JB (2008). "Wang-Zwische double lumen cannula-toward a percutaneous and ambulatory paracorporeal artificial lung". ASAIO J. 54 (6): 606–11. doi:10.1097/MAT.0b013e31818c69ab. PMID 19033774.
  3. ↑ Madershahian N, Nagib R, Wippermann J, Strauch J, Wahlers T (2006). "A simple technique of distal limb perfusion during prolonged femoro-femoral cannulation". J Card Surg. 21 (2): 168–9. doi:10.1111/j.1540-8191.2006.00201.x. PMID 16492278.
  4. ↑ Oliver M, Coggins A, Kruit N, Burns B, Plunkett B, Morgan S, Southwood TJ, Totaro R, Forrest P, Russell SB, Carey R, Dennis M (June 2024). "Implementing enhanced extracorporeal membrane oxygenation for CPR (ECPR) in the emergency department". Int J Emerg Med. 17 (1): 71. doi:10.1186/s12245-024-00652-y. PMC 11163769 Check |pmc= value (help). PMID 38858639 Check |pmid= value (help).
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  44. ↑ Rich PB, Awad SS, Kolla S, Annich G, Schreiner RJ, Hirschl RB, Bartlett RH (March 1998). "An approach to the treatment of severe adult respiratory failure". J Crit Care. 13 (1): 26–36. doi:10.1016/s0883-9441(98)90026-0. PMID 9556124.
  45. ↑ Ullrich R, Lorber C, Röder G, Urak G, Faryniak B, Sladen RN, Germann P (December 1999). "Controlled airway pressure therapy, nitric oxide inhalation, prone position, and extracorporeal membrane oxygenation (ECMO) as components of an integrated approach to ARDS". Anesthesiology. 91 (6): 1577–86. doi:10.1097/00000542-199912000-00007. PMID 10598597.
  46. ↑ "Lich B (2004). The Manual of Clinical Perfusion (2nd ed.). Fort Myers, Florida: Perfusion.com. ISBN 978-0-9753396-0-2".
  47. ↑ Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D (October 2009). "Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial". Lancet. 374 (9698): 1351–63. doi:10.1016/S0140-6736(09)61069-2. PMID 19762075.
  48. ↑ Gattinoni L, Vasques F, Quintel M (July 2018). "Use of ECMO in ARDS: does the EOLIA trial really help?". Crit Care. 22 (1): 171. doi:10.1186/s13054-018-2098-6. PMC 6034241. PMID 29976250.
  49. ↑ Combes A, Hajage D, Capellier G, Demoule A, Lavoué S, Guervilly C, Da Silva D, Zafrani L, Tirot P, Veber B, Maury E, Levy B, Cohen Y, Richard C, Kalfon P, Bouadma L, Mehdaoui H, Beduneau G, Lebreton G, Brochard L, Ferguson ND, Fan E, Slutsky AS, Brodie D, Mercat A (May 2018). "Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome". N Engl J Med. 378 (21): 1965–1975. doi:10.1056/NEJMoa1800385. PMID 29791822.
  50. ↑ Hardin CC, Hibbert K (May 2018). "ECMO for Severe ARDS". N Engl J Med. 378 (21): 2032–2034. doi:10.1056/NEJMe1802676. PMID 29791819.
  51. ↑ Sameed M, Meng Z, Marciniak ET (September 2019). "EOLIA trial: the future of extracorporeal membrane oxygenation in acute respiratory distress syndrome therapy?". Breathe (Sheff). 15 (3): 244–246. doi:10.1183/20734735.0363-2018. PMC 6717615 Check |pmc= value (help). PMID 31508163.
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