Review question
Does ECMO improve longer-term survival in critically ill adults?
Key messages
– ECMO is effective at reducing death compared to conventional management, but it was associated with an increased risk of major bleeding.
– Other outcomes were poorly reported.
– There is uncertainty in the findings and further research is required.
What is extracorporeal membrane oxygenation?
Extracorporeal membrane oxygenation (ECMO) is a form of life support for the sickest patients in the intensive care unit. It is a machine that pumps and oxygenates a person's blood outside the body, allowing the heart and lungs to rest and recover. There are different types of ECMO that differ in how they return the blood to the body. Venoarterial ECMO (VA) is used for severe cardiac (heart) failure, venovenous (VV) ECMO for respiratory failure, and extracorporeal cardiopulmonary resuscitation (ECPR) is used during cardiac arrest (where the heart stops beating). Although potentially lifesaving, ECMO is associated with risks, including bleeding, neurologic injury (damage to the brain, spine, or nerves), and death. Therefore, we performed a systematic review to determine whether ECMO improves outcomes when compared to conventional cardiopulmonary support (for example, chest compressions and mouth-to-mouth breathing).
What did we want to find out?
We wanted to find out which of these treatments worked best and if they had any side effects.
What did we do?
We searched medical databases for well-designed clinical trials comparing ECMO with conventional cardiopulmonary support (control) in critically ill adults.
What did we find?
We found five trials comprising 757 participants randomly assigned to ECMO or control. Two trials were of VV ECMO (429 participants), one was of VA ECMO (41 participants), and two were of ECPR (285 participants). The main outcome was death (at day 90 up to one year).
Key results
Overall, ECMO was effective at reducing death compared to conventional management. However, ECMO was associated with an increased risk of major bleeding. There were no differences in outcomes across the different types of ECMO (VV, VA, or ECPR) and other effects of ECMO (such as neurologic injury or quality of life) were poorly reported.
What are the limitations of the evidence?
The overall quality of the evidence was low to moderate, mainly because of differences between the studies (including study design, definitions, and methods of measuring the outcomes) and differences in the study populations and the number of participants who received the intervention. This indicates there is uncertainty in the findings and further research is required to strengthen this evidence.
How up to date is this evidence?
The evidence is up to date to March 2022.
In this updated systematic review, which included four additional RCTs, we found that ECMO was associated with a reduction in day-90 to one-year all-cause mortality, as well as three times increased risk of bleeding. However, the certainty of this result was only low to moderate, limited by a low number of small trials, clinical heterogeneity, and indirectness across studies.
Extracorporeal membrane oxygenation (ECMO) may provide benefit in certain populations of adults, including those with severe cardiac failure, severe respiratory failure, and cardiac arrest. However, it is also associated with serious short- and long-term complications, and there remains a lack of high-quality evidence to guide practice. Recently several large randomized controlled trials (RCTs) have been published, therefore, we undertook an update of our previous systematic review published in 2014.
To evaluate whether venovenous (VV), venoarterial (VA), or ECMO cardiopulmonary resuscitation (ECPR) improve mortality compared to conventional cardiopulmonary support in critically ill adults.
We used standard, extensive Cochrane search methods. The latest search date was March 2022. The search was limited to English language only.
We included RCTs, quasi-RCTs, and cluster-RCTs that compared VV ECMO, VA ECMO or ECPR to conventional support in critically ill adults.
We used standard Cochrane methods. Our primary outcome was 1. all-cause mortality at day 90 to one year. Our secondary outcomes were 2. length of hospital stay, 3. survival to discharge, 4. disability, 5. adverse outcomes/safety events, 6. health-related quality of life, 7. longer-term health status, and 8. cost-effectiveness. We used GRADE to assess certainty of evidence.
Five RCTs met our inclusion criteria, with four new studies being added to the original review (total 757 participants). Two studies were of VV ECMO (429 participants), one VA ECMO (41 participants), and two ECPR (285 participants). Four RCTs had a low risk of bias and one was unclear, and the overall certainty of the results (GRADE score) was moderate, reduced primarily due to indirectness of the study populations and interventions.
ECMO was associated with a reduction in 90-day to one-year mortality compared to conventional treatment (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.70 to 0.92; P = 0.002, I2 = 11%). This finding remained stable after performing a sensitivity analysis by removing the single trial with an uncertain risk of bias. Subgroup analyses did not reveal a significant subgroup effect across VV, VA, or ECPR modes (P = 0.73).
Four studies reported an increased risk of major hemorrhage with ECMO (RR 3.32, 95% CI 1.90 to 5.82; P < 0.001), while two studies reported no difference in favorable neurologic outcome (RR 2.83, 95% CI 0.36 to 22.42; P = 0.32). Other secondary outcomes were not consistently reported across the studies.