According to an international study of 1,035 patients who faced a staggeringly high risk of death, as ventilators and other care failed to support their lungs, substantially improved their survival potential after being placed on extracorporeal membrane oxygenation (ECMO), with their actual death rate being less than 40%. That’s similar to the rate for patients treated with ECMO in past outbreaks of lung-damaging viruses, and other severe forms of viral pneumonia.
The study provides strong support for the use of ECMO in appropriate patients as the pandemic rages on worldwide. It may help more hospitals that have ECMO capability understand which of their COVID-19 patients might benefit from the technique, which channels blood out of the body and into a circuit of equipment that adds oxygen directly to the blood before pumping it back into regular circulation. Small studies published early in the pandemic had cast doubt on the technique’s usefulness.
Still, the international team of authors cautions that patients who show signs of needing advanced life support should receive it at hospitals with experienced ECMO teams, and that hospitals shouldn’t try to add ECMO capability mid-pandemic.
The study was made possible by a rapidly created international registry that has given critical care experts near real-time data on the use of ECMO in COVID-19 patients since early in the year.
Hosted by the organisation called Extracorporeal Life Support Organisation (ELSO) the registry includes data submitted by the 213 hospitals on four continents whose patients were included in the new analysis. The paper includes data on patients age 16 or older who were started on ECMO between 16 January and 1 May, and follows them until death, discharge from the hospital, or 5 August, whichever occurred first.
“These results from hospitals experienced in providing ECMO are similar to past reports of ECMO-supported patients, with other forms of acute respiratory distress syndrome or viral pneumonia,” says co-lead author Dr Ryan Barbaro, of Michigan Medicine, the University of Michigan’s academic medical centre. “These results support recommendations to consider ECMO in COVID-19 if the ventilator is failing. We hope these findings help hospitals make decisions about this resource-intensive option.”
Co-lead author Dr Graeme MacLaren, of the National University Health System-Singapore, notes, “Most centres in this study did not need to use ECMO for COVID-19 very often. By bringing data from over 200 international centres together into the same study, ELSO has deepened our knowledge about the use of ECMO for COVID-19 in a way that would be impossible for individual centres to learn on their own.”
Study said 70% of the patients were transferred to the hospital where they received ECMO. Half of these were actually started on ECMO – likely by the receiving hospital’s team – before they were transferred. This reinforces the importance of communication between ECMO-capable hospitals and non-ECMO hospitals that might have COVID-19 patients who could benefit from ECMO.
The new study could also help identify which patients will benefit most if they are placed on ECMO.
“Our findings also show that mortality risk rises significantly with patient age, and that those who are immunocompromised, have acute kidney injuries, worse ventilator outcomes or COVID-19-related cardiac arrests are less likely to survive,” continues Barbaro, who chairs ELSO’s COVID-19 registry committee and provides ECMO care as a paediatric intensive care physician at Michigan Medicine CS Mott Children’s Hospital. “Those who need ECMO to replace cardiac function as well as lung function also did worse. All of this knowledge can help centres and families understand what patients might face if they are placed on ECMO.”
“The lack of reliable information early in the pandemic hampered our ability to understand the role of ECMO for COVID-19,” says co-senior author Dr Daniel Brodie, of New York Presbyterian Hospital. “The results of this large-scale international registry study, while hardly definitive evidence, provides a real-world understanding of the potential for ECMO to save lives in a highly selected population of COVID-19 patients.” Brodie shares senior authorship with Dr Roberto Lorusso, of the Maastricht University Medical Centre in the Netherlands and Dr Alain Combes, of Sorbonne University in Paris.
Because the ELSO database does not track what happens to patients once they are discharged to home, other hospitals and long-term acute care or rehabilitation facilities, the study used a statistical approach based on in-hospital mortality up to 90 days after the patient was put on ECMO. This also allows the team to account for the 67 patients who were still in the hospital as of 5 August, whether they were still on ECMO, in the intensive care unit or in step-down units.
Dr Philip Boonstra, of the U-M School of Public Health, helped design the study using a “competing risk” approach, based on his experience handling the statistical design and analysis of long-term data from clinical trials for cancer.
“We used 90-day in-hospital mortality because this is the highest-risk period, and because it allows us to use the information we have to the fullest, even if we don’t know the final outcome for every patient,” he says.
Having data through August, when only a small number of the patients in the study remained in the hospital, was important – though data are missing on a small number of patients. And even though patients who were discharged to their homes or a rehabilitation facility will likely have a long recovery ahead after the intensive level of care involved in ECMO, they are likely to survive based on past data. However, the fate of those who went to LTAC facilities, which provide long-term care at a near-ICU level, is less certain.
More than half of the patients in the study were treated in hospitals in the US and Canada, including Michigan Medicine’s own hospitals. U-M’s Dr Robert Bartlett, emeritus professor of surgery and a co-author of the new paper, is considered a key figure in the development of ECMO, including the first use in adults in the 1980s. Bartlett led the development of the initial guidance for the use of ECMO in COVID-19. “ECMO is the final step in the algorithm for managing life-threatening lung failure in advanced ICUs,” says Bartlett. “Now we know it is effective in COVID-19.”
Background: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date.
Methods: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality.
Findings: Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4–40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20–2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6–41·5).
Interpretation: In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19.
Ryan P Barbaro, Graeme MacLaren, Philip S Boonstra, Theodore J Iwashyna, Arthur S Slutsky, Eddy Fan, Robert H Bartlett, Joseph E Tonna, Robert Hyslop, Jeffrey J Fanning, Peter T Rycus, Steve J Hyer, Marc M Anders, Cara L Agerstrand, Katarzyna Hryniewicz, Rodrigo Diaz, Roberto Lorusso, Alain Combes, Daniel Brodie
Michigan Medicine material
The Lancet abstract