Discussion
The primary finding of this study is that among the 20 COVID-positive patients that we treated with ECMO, the survival rate to hospital discharge was 55%. Also, our results suggest that proper patient selection and control of bacterial infections prior to and/or during ECMO placement may be key to improving survival, as culture-positive septic shock and culture-negative SIRS were the main causes of death and were only observed in patients who failed to survive to hospital discharge.
The treatment of ARDS with ECMO remains disputed, even though its use in treating ARDS has increased in the past decade.(11,12) While the exact mortality rate of treating ARDS with ECMO varies by research study, it is generally accepted to range between 34-39%.(11,13,14) Thus, it is generally recognized that ECMO should be primarily used for refractory cases of ARDS, in which a patient remains severely hypoxic despite aggressive treatment.(12)
Interestingly, our study and others on COVID-19 have found that the mortality rates of treating ARDS due to COVID-19 with ECMO are similar to the previously reported mortality rates of treating non-COVID ARDS. Recently, there have been a few articles published that specifically investigated the use of ECMO in treating ARDS due to COVID-19. The largest of these studies was conducted by Barbaro et al., who drew from an Extracorporeal Life Support Organization (ELSO) registry to analyze the outcomes of 1035 COVID-positive patients who were treated with ECMO.(15) The researchers found that among these patients, the 90-day post-ECMO mortality rate was 37.4%. The study included data from 213 different hospitals and included patients treated from January 16th to May 1st of 2020. Another study that more closely resembles our own is from Schmidt et al, who documented the outcomes of 83 COVID-positive patients who were treated at their hospital.(16) They discovered that the 60-day mortality of these patients was 31%. Compared to these studies, our patients had a slightly higher mortality rate of 45%; however, it should be noted that our sample size was significantly smaller than either of these two articles.
Based on this current research on the use of ECMO in ARDS due to COVID-19, the mortality rate appears to be anywhere between 31-45%. This mortality rate is similar to the 34-39% mortality rate in treating non-COVID ARDS with ECMO in select patients. Therefore, it is possible that ECMO is just as effective at treating ARDS due to COVID-19 as it is at treating ARDS due to non-COVID-19 etiologies if appropriate patient selection was applied. For example, none of the patients in our study had cardiac dysfunction. This is because our selection committee considered COVID-19 patients with cardiac dysfunction and ARDS to have multiorgan failure, which was a contraindication for ECMO placement. While there needs to be far more research done on this topic to definitively state that ECMO is effective in treating COVID-19, it is possible that it is an effective treatment option for refractory cases of ARDS due to COVID-19.
Sepsis and SIRS were the causes of death in all but one patient in our study, suggesting that bacterial infections during ECMO placement may be a significant factor in mortality rates. While immunomodulation therapy has been shown to decrease the mortality rate of COVID-19,(20,21) it has also been associated with an increased infection rate. For example, one study demonstrated that 13% of patients treated with tocilizumab were diagnosed with new infections, compared to only 4% of patients treated solely with the standard of care.(21) There should be particular attention to preventing, monitoring for, and responding early to bacterial infections in COVID-19 patients placed on ECMO.
During the first wave of COVID-19 in Pennsylvania, the highest number of daily COVID-19 cases occurred on April 8th with 2,059 cases. By the end of our study period on June 11th, the daily number of cases fell to 680, which was one of the lowest number of daily cases in Pennsylvania since the beginning of the pandemic. Our study beings on April 1st and ends on June 11th, which fairly accurately represents the beginning and end of the first wave of COVID-19 in Pennsylvania. Beginning in late October, Pennsylvania entered a second wave, with daily cases greatly exceeding those of the first wave. Future studies of the second wave of COVID-19 will differ from this study, for multiple reasons, including changes in pre-ECMO immunomodulation treatment. During the second wave, interleukin inhibitors are no longer recommended and steroids are more widely used.
Our study is limited by its small sample size and being based in one hospital center. It is also possible that there was selection bias in this study, even though ECMO placement was determined by a multidisciplinary team of physicians.
Despite its limitations, this study provides extensive data on 20 patients with ARDS due to COVID-19 who were treated with ECMO. While we cannot extrapolate from a sample size of 20 patients, we hope our evidence can complement other studies and contribute to meaningful meta-analyses and statistical analyses. Cases of ARDS due to COVID-19 will continue in the coming months and years, and we hope that our analysis contributes to the growing research on how to treat this deadly disease.