Guidelines that describe the indications and practice of ECMO are published by the Extracorporeal Life Support Organization (ELSO). Criteria for the initiation of ECMO vary by institution, but generally include acute severe cardiac or pulmonary failure that is potentially reversible and unresponsive to conventional management. Examples of clinical situations that may prompt the initiation of ECMO include the following:
In those with cardiac arrest or cardiogenic shock, it is believed to improve survival and good outcomes. However, a recent clinical trial has shown that in patients with cardiogenic shock following acute myocardial infarction, ECLS did not improve survival (as measured via 30-day mortality); on the contrary, it resulted in increased complications (e.g., major bleeding, lower limb ischemia). This finding is corroborated by a recent meta-analysis that used data from four previous clinical trials, indicating a need to reassess current guidelines for initiation of ECLS treatment.
Early studies had shown survival benefit with use of ECMO for people in acute respiratory failure especially in the setting of acute respiratory distress syndrome. A registry maintained by ELSO of nearly 51,000 people that have received ECMO has reported outcomes with 75% survival for neonatal respiratory failure, 56% survival for pediatric respiratory failure, and 55% survival for adult respiratory failure. Other observational and uncontrolled clinical trials have reported survival rates from 50 to 70%. These reported survival rates are better than historical survival rates. Even though ECMO is used for a range of conditions with varying mortality rates, early detection is key to prevent the progression of deterioration and increase survival outcomes.
Most contraindications are relative, balancing the risks of the procedure versus the potential benefits. The relative contraindications are:
A common consequence in ECMO-treated adults is neurological injury, which may include intracerebral hemorrhage, subarachnoid hemorrhage, ischemic infarctions in susceptible areas of the brain, hypoxic-ischemic encephalopathy, unexplained coma, and brain death. Bleeding occurs in 30 to 40% of those receiving ECMO and can be life-threatening. It is due to both the necessary continuous heparin infusion and platelet dysfunction. Meticulous surgical technique, maintaining platelet counts greater than 100,000/mm3, and maintaining the target activated clotting time reduce the likelihood of bleeding.
There is retrograde blood flow in the descending aorta whenever the femoral artery and vein are used for VA (Veno-Arterial) ECMO. Stasis of the blood can occur if left ventricular output is not maintained, which may result in thrombosis.
In VA ECMO, those whose cardiac function does not recover sufficiently to be weaned from ECMO may be bridged to a ventricular assist device (VAD) or transplant. A variety of complications can occur during cannulation, including vessel perforation with bleeding, arterial dissection, distal ischemia, and incorrect location.
Preterm infants, having inefficiency of the heart and lungs, are at unacceptably high risk for intraventricular hemorrhage (IVH) if ECMO is performed at a gestational age less than 32 weeks.
The prevalence of hospital-acquired infections during ECMO is 10-12% (higher compared to other critically ill patients). Coagulase-negative staphylococci, Candida spp., Enterobacteriaceae and Pseudomonas aeruginosa are the most frequently involved pathogens. ECMO patients display a high incidence of ventilator-associated pneumonia (24.4 cases/1000 ECMO days), with a major role played by Enterobacteriaceae. The infectious risk was shown to increase along the duration of the ECMO run, which is the most important risk factor for the development of infections. Other ECMO-specific factors predisposing to infections include the severity of illness in ECMO patients, the high risk of bacterial translocation from the gut and ECMO-related impairment of the immune system. Another important issue is the microbial colonisation of catheters, ECMO cannulae and the oxygenator.
There are several forms of ECMO; the two most common are veno-arterial (VA) ECMO and veno-venous (VV) ECMO. In both modalities, blood drained from the venous system is oxygenated outside of the body. In VA ECMO, this blood is returned to the arterial system and in VV ECMO the blood is returned to the venous system. In VV ECMO, no cardiac support is provided.
VA ECMO is typically reserved when native cardiac function is minimal to mitigate increased cardiac stroke work associated with pumping against retrograde flow delivered by the aortic cannula.
In veno-venous (VV) ECMO, cannulae are usually placed in the right common femoral vein for drainage and right internal jugular vein for infusion. Alternatively, a dual-lumen catheter is inserted into the right internal jugular vein, draining blood from the superior and inferior vena cavae and returning it to the right atrium.
ECMO should be performed only by clinicians with training and experience in its initiation, maintenance, and discontinuation. ECMO insertion is typically performed in the operating room setting by a cardiothoracic surgeon. ECMO management is commonly performed by a registered nurse, respiratory therapist, or a perfusionist. Once it has been decided to inititiate ECMO, the patient is anticoagulated with intravenous heparin to prevent thrombus formation from clotting off the oxygenator. Prior to initiation, an IV bolus of heparin is given and measured to ensure that the activated clotting time (ACT) is between 300 and 350 seconds. Once the ACT is between this range, ECMO can be initiated and a heparin drip will be started after as a maintenance dose.: 143
ECMO required for complications post-cardiac surgery can be placed directly into the appropriate chambers of the heart or great vessels. Peripheral (femoral or jugular) cannulation can allow patients awaiting lung transplantation to remain awake and ambulatory with improved post-transplant outcomes.
Following cannulation and connection to the ECMO circuit, the appropriate amount of blood flow through the ECMO circuit is determined using hemodynamic parameters and physical exam. Goals of maintaining end-organ perfusion via ECMO circuit are balanced with sufficient physiologic blood flow through the heart to prevent stasis and subsequent formation of blood clot.
Once the initial respiratory and hemodynamic goals have been achieved, the blood flow is maintained at that rate. Frequent assessment and adjustments are facilitated by continuous venous oximetry, which directly measures the oxyhemoglobin saturation of the blood in the venous limb of the ECMO circuit.
VV ECMO is typically used for respiratory failure, while VA ECMO is used for cardiac failure. There are unique considerations for each type of ECMO, which influence management.
High flow rates are usually desired during VV ECMO to optimize oxygen delivery. In contrast, the flow rate used during VA ECMO must be high enough to provide adequate perfusion pressure and venous oxyhemoglobin saturation (measured on drainage blood) but low enough to provide sufficient preload to maintain left ventricular output.
Left ventricular output is rigorously monitored during VA ECMO because left ventricular function can be impaired from increased afterload, which can in turn lead to formation of thrombus within the heart.
For those with respiratory failure, improvements in radiographic appearance, pulmonary compliance, and arterial oxyhemoglobin saturation indicate that the person may be ready to be taken off ECMO support. For those with cardiac failure, enhanced aortic pulsatility correlates with improved left ventricular output and indicates that they may be ready to be taken off ECMO support. If all markers are in good status, the blood flows on the ECMO will be slowly decreased and the patients parameters will be observed during this time to ensure that the patient can tolerate the changes. When the flows are below 2 liters per minute, permanent removal is attempted and the patient is continuously monitored during this time until the cannulae can be removed.: 149
VV ECMO trials are performed by eliminating all countercurrent sweep gas through the oxygenator. Extracorporeal blood flow remains constant, but gas transfer does not occur. They are then observed for several hours, during which the ventilator settings that are necessary to maintain adequate oxygenation and ventilation off ECMO are determined as indicated by arterial and venous blood gas results.
VA ECMO trials require temporary clamping of both the drainage and infusion lines, while allowing the ECMO circuit to circulate through a bridge between the arterial and venous limbs. This prevents thrombosis of stagnant blood within the ECMO circuit. In addition, the arterial and venous lines should be flushed continuously with heparinized saline or intermittently with heparinized blood from the circuit. In general, VA ECMO trials are shorter in duration than VV ECMO trials because of the higher risk of thrombus formation.
Banning Gray Lary first demonstrated that intravenous oxygen could maintain life. His results were published in Surgical Forum in November 1951. Lary commented on his initial work in a 2007 presentation wherein he writes, "Our research began by assembling an apparatus that, for the first time, kept animals alive while breathing pure nitrogen. This was accomplished with very small bubbles of oxygen injected into the blood stream. These bubbles were made by adding a 'wetting agent' to oxygen being forced through a porcelain filter into the venous blood stream. Shortly after its initial presentation to the American College of Surgeons, this apparatus was reviewed by Walton Lillehei who with DeWall made the first practical heart[–]lung machine that employed a bubble oxygenator. With variations such machines were used for the next twenty years."
Four randomized controlled trials (RCTs) have been conducted to evaluate the effectiveness of ECMO in respiratory failure patients. Early trials conducted by Zapol et al. and Morris et al. were plagued by technical challenges related to the ECMO technology available in the 1970s and 1990s. The CESAR and EOLIA trials utilized modern ECMO systems and are considered the central ECMO RCTs.
The Conventional Ventilatory Support vs. Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) Trial was a UK-based multicenter RCT aiming to evaluate the safety, efficacy and cost effectiveness of ECMO compared to conventional mechanical ventilation in adults with severe but reversible respiratory failure. Death or severe disability at 6 months or prior to hospital discharge was the primary outcome. The primary outcome was analyzed by intention to treat only. Economic analysis included quality-adjusted life-years (QALYs), analysis of cost generating events, cost-utility 6-months post-randomization and modelling of life-time cost utility. The trial planned to enroll 180 patients; 90 to each arm.
The Trial met its enrollment goal of 180 patients. 68 of the 90 (75%) of the patients intended to be treated with ECMO were actually treated with ECMO. Survival of patients allocated to the ECMO group (i.e. referred for consideration for treatment with ECMO) was significantly higher than patients allocated to the conventional ventilation group (63% vs 47%, p=0.03). The referral to ECMO group gained 0.03 QALY compared to the conventional ventilation group at the 6-month follow-up. The referral to ECMO group had longer lengths of stay and higher costs.
No standardized treatment protocol for the conventional ventilation group is the main limitation of the CESAR study. The trial authors note that this occurred due to the inability of enrolling sites to agree on a protocol. This resulted in control patients not receiving lung protective ventilation which is known to improve mortality in ARDS patients.
The authors conclude that referral of patients with severe, potentially reversible respiratory failure to an ECMO center can significantly improve 6-month, severe disability free survival. The CESAR trial results do provide a direct survival comparison for treatment with ECMO versus conventional mechanical ventilation alone since only 75% of the ECMO group were actually treated with ECMO.
The ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) Trial was designed to evaluate the effects of early ECMO initiation compared to continued standard of care (conventional mechanical ventilation) in severe ARDS patients. Mortality at 60 days was the primary endpoint. The calculated sample size was 331 patients with an intent to show a 20% reduction in absolute mortality in the ECMO group. The main secondary endpoint was treatment failure – cross-over to ECMO due to refractory hypoxemia or death in the control group and death in the ECMO group.
Following the fourth planned interim analysis the trial was ended due to futility. A total of 249 patients were enrolled at study termination. Thirty-five control group patients (28%) required emergency cross-over to ECMO. Results of EOLIA demonstrated no significant difference in 60-day mortality between the ECMO group and the control group (35% vs 46%, respectively). The interpretation of this result however is complicated by the cross-over patients. The secondary endpoint, treatment failure, demonstrated a relative risk of 0.62 (p<0.001) in favor of the ECMO group. Results of the secondary endpoint should be interpreted cautiously due to the primary end point results. With respect to safety, the ECMO group had significantly higher rates of severe thrombocytopenia and bleeding requiring transfusion, but lower rates of ischemic stroke.
The primary limitation to the EOLIA Trial was that it was underpowered. For EOLIA to have been properly powered to detect significance of an 11% reduction in mortality a total of 624 patients would need to have been enrolled. Such a trial would take 9 years based on the EOLIA recruitment rates and is likely not feasible.
The main conclusion the study authors drew from these results is that early ECMO initiation in severe ARDS patients does not provide a mortality benefit compared to continued standard of care treatment. Subsequent editorials by key opinion leaders suggest that the practical implication is that ECMO may improve mortality if used as a rescue therapy for patients failing conventional ARDS therapies.
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"ExtraCorporeal Membrane Oxygenation Market 2020 Recent Trends, Analysis, Business Growth, Share Estimation and Regional Overview Forecast by 2026". MarketWatch. April 16, 2020. Archived from the original on June 25, 2020. https://web.archive.org/web/20200625234308/https://www.marketwatch.com/press-release/extracorporeal-membrane-oxygenation-market-2020-recent-trends-analysis-business-growth-share-estimation-and-regional-overview-forecast-by-2026-2020-04-16?mod=mw_quote_news&tesla=y
"ExtraCorporeal Membrane Oxygenation Market 2020 Recent Trends, Analysis, Business Growth, Share Estimation and Regional Overview Forecast by 2026". MarketWatch. April 16, 2020. Archived from the original on June 25, 2020. https://web.archive.org/web/20200625234308/https://www.marketwatch.com/press-release/extracorporeal-membrane-oxygenation-market-2020-recent-trends-analysis-business-growth-share-estimation-and-regional-overview-forecast-by-2026-2020-04-16?mod=mw_quote_news&tesla=y
"ExtraCorporeal Membrane Oxygenation Market 2020 Recent Trends, Analysis, Business Growth, Share Estimation and Regional Overview Forecast by 2026". MarketWatch. April 16, 2020. Archived from the original on June 25, 2020. https://web.archive.org/web/20200625234308/https://www.marketwatch.com/press-release/extracorporeal-membrane-oxygenation-market-2020-recent-trends-analysis-business-growth-share-estimation-and-regional-overview-forecast-by-2026-2020-04-16?mod=mw_quote_news&tesla=y
"ExtraCorporeal Membrane Oxygenation Market 2020 Recent Trends, Analysis, Business Growth, Share Estimation and Regional Overview Forecast by 2026". MarketWatch. April 16, 2020. Archived from the original on June 25, 2020. https://web.archive.org/web/20200625234308/https://www.marketwatch.com/press-release/extracorporeal-membrane-oxygenation-market-2020-recent-trends-analysis-business-growth-share-estimation-and-regional-overview-forecast-by-2026-2020-04-16?mod=mw_quote_news&tesla=y
"ExtraCorporeal Membrane Oxygenation Market 2020 Recent Trends, Analysis, Business Growth, Share Estimation and Regional Overview Forecast by 2026". MarketWatch. April 16, 2020. Archived from the original on June 25, 2020. https://web.archive.org/web/20200625234308/https://www.marketwatch.com/press-release/extracorporeal-membrane-oxygenation-market-2020-recent-trends-analysis-business-growth-share-estimation-and-regional-overview-forecast-by-2026-2020-04-16?mod=mw_quote_news&tesla=y
"ExtraCorporeal Membrane Oxygenation Market 2020 Recent Trends, Analysis, Business Growth, Share Estimation and Regional Overview Forecast by 2026". MarketWatch. April 16, 2020. Archived from the original on June 25, 2020. https://web.archive.org/web/20200625234308/https://www.marketwatch.com/press-release/extracorporeal-membrane-oxygenation-market-2020-recent-trends-analysis-business-growth-share-estimation-and-regional-overview-forecast-by-2026-2020-04-16?mod=mw_quote_news&tesla=y
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