Since the first SARS-CoV-2 (COVID-19) outbreak in Wuhan, China, in December 2019, more than 6.6 million deaths have occurred. . One of the strategies for those cases refractory to traditional ARDS treatments has been the use of extracorporeal membrane oxygenation (ECMO).
Before the COVID-19 pandemic, a substantial amount of data regarding the use of ECMO in ARDS was gathered during the H1N1 influenza outbreak in 2009. Mortality ranged from 8% to 65% (Zangrillo, et al. Crit Care. 2013;17[1]:R30). From these data, we learned the importance of patient selection. Young patients with few co-morbidities and less than 7 days supported by mechanical ventilation did remarkably better than elderly patients or those who had prolonged positive-pressure ventilation prior to ECMO.
To date, the mortality rate for COVID-19 patients with ARDS requiring ECMO is 48% based on data from ELSO. Interestingly though, using May 1, 2020, as a cutoff date, mortality rates for patients with COVID-19 receiving ECMO significantly increased from 37% to 52% (Barbaro, et al. Lancet. 2021;398[10307]:1230). This escalation in mortality engendered concern that ECMO may not be useful in treating patients with COVID-19 and ARDS.
Several factors can be cited for this increase in mortality. First, many new ECMO programs launched after May 1. These new programs had a higher mortality rate (59%) compared with established programs, suggesting that program and provider experience play a significant role in patient outcomes (Barbaro, et al. Lancet. 2021;398[10307]:1230). Second, patients in the latter part of 2020 experienced much longer intervals between the onset of symptoms and time of intubation. Clinicians had a tendency to delay intubation as long as possible. Subsequently, the number of days receiving high flow nasal oxygen or noninvasive ventilation (NIV) was significantly longer (Schmidt, et al. Crit Care. 2021;25[1]:355). These data suggest that prolonged NIV on high Fio2 may be a negative prognostic indicator and should be considered when assessing a patient’s candidacy for ECMO.
Early in the pandemic, clinicians realized that average ECMO run times for patients with COVID-19 and ARDS were significantly longer, 15 vs 9 days, respectively (Jacobs, et al. Ann Thorac Surg. 2022;113[5]:1452). With such long run times, beds were slow to turn over, and a shortage of ECMO beds resulted during the height of the pandemic. In a retrospective study, Gannon looked at 90 patients, all of whom were deemed medically appropriate for ECMO. Two groups were created: (1) no capacity for ECMO vs (2) ECMO provided. Mortality rates were staggering at 89% and 43%, respectively (P =.001) (Gannon, et al. Am J Respir Crit Care Med. 2022;205[11]:1354). This study demonstrated a profound point: during a pandemic, when demand overcomes supply, there is a unique opportunity to see the effect of lifesaving therapies, such as ECMO, on outcomes. This study was particularly poignant, as the average age of the patients was 40 years old.
It is now widely accepted that prone positioning has survival benefit in ARDS. Prone positioning while receiving ECMO has generally been avoided due to concern for potential complications associated with the cannula(s). However, it has been shown that prone positioning while receiving veno-venous (VV) -ECMO reduces mortality rates, 37% proned vs 50% supine positioning (P =.02) (Giani, et al. Ann Am Thorac Soc. 2021;18[3]:495). In this study, no major complications occurred, and minor complications occurred in 6% of the proning events. Prone positioning improves ventilation-perfusion mismatch and reduces hypoxic vasoconstriction, which is thought to be right-sided heart-protective.
Right-sided heart dysfunction (RHD) is common in ARDS, whether COVID-19-related or not. The pathogenesis includes hypoxic vasoconstriction, pulmonary fibrosis, and ventilator-induced lung injury. Pulmonary microthrombi and patient-specific characteristics, such as obesity, are additional factors leading to RHD in patients with COVID-19. During the pandemic, several articles described using right-sided heart protective cannulation strategies for patients with COVID-19 requiring ECMO with favorable results (Mustafa, et al. JAMA Surg. 2020;155[10]:990; Cain, et al. J Surg Res. 2021;264:81-89). This right-sided heart protective strategy involves inserting a single access dual lumen cannula into the right internal jugular vein, which is advanced into the pulmonary artery, effectively bypassing the right ventricle. This setup is more typical of right ventricle assist device (RVAD), rather than typical VV-ECMO, which returns blood to the right atrium. Unfortunately, these studies did not include echocardiographic information to evaluate the effects of this intervention on RVD, and this is an area for future research. However, this vein to pulmonary artery strategy was found to facilitate decreased sedation, earlier liberation from mechanical ventilation, reduced need for tracheostomy, improved mobilization out of bed, and ease in prone positioning (Mustafa, et al. JAMA Surg. 2020;155[10]:990).
In conclusion, there is evidence to support the use of ECMO in patients with COVID-19 patients and ARDS failing conventional mechanical ventilation. The success of ECMO therapy is highly dependent on patient selection. Prolonged use of NIV on high Fio2 may be a negative predictor of ECMO survival and should be considered when assessing a patient for ECMO candidacy. Prone positioning with ECMO has been shown to have survival benefit and should be considered in all patients receiving ECMO.
Dr. Gaillard, Dr. Staples, and Dr. Kapoor are with the Department of Anesthesiology, Section on Critical Care, at Wake Forest School of Medicine in Winston-Salem, N.C. Dr. Gaillard is also with the Department of Emergency Medicine and Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy, and Immunology at Wake Forest School of Medicine.