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Multicenter Study
. 2021 Feb;47(2):208-221.
doi: 10.1007/s00134-020-06331-9. Epub 2021 Feb 2.

Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19

Shahzad Shaefi #  1 , Samantha K Brenner #  2   3 , Shruti Gupta #  4 , Brian P O'Gara  5 , Megan L Krajewski  5 , David M Charytan  6 , Sobaata Chaudhry  6 , Sara H Mirza  7 , Vasil Peev  8 , Mark Anderson  9   10 , Anip Bansal  11 , Salim S Hayek  12 , Anand Srivastava  13 , Kusum S Mathews  14 , Tanya S Johns  15 , Amanda Leonberg-Yoo  16 , Adam Green  17 , Justin Arunthamakun  18 , Keith M Wille  19 , Tanveer Shaukat  4 , Harkarandeep Singh  4 , Andrew J Admon  20 , Matthew W Semler  21 , Miguel A Hernán  22   23 , Ariel L Mueller #  24 , Wei Wang #  25 , David E Leaf #  4 ; STOP-COVID Investigators
Collaborators, Affiliations
Multicenter Study

Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19

Shahzad Shaefi et al. Intensive Care Med. 2021 Feb.

Abstract

Purpose: Limited data are available on venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure from coronavirus disease 2019 (COVID-19).

Methods: We examined the clinical features and outcomes of 190 patients treated with ECMO within 14 days of ICU admission, using data from a multicenter cohort study of 5122 critically ill adults with COVID-19 admitted to 68 hospitals across the United States. To estimate the effect of ECMO on mortality, we emulated a target trial of ECMO receipt versus no ECMO receipt within 7 days of ICU admission among mechanically ventilated patients with severe hypoxemia (PaO2/FiO2 < 100). Patients were followed until hospital discharge, death, or a minimum of 60 days. We adjusted for confounding using a multivariable Cox model.

Results: Among the 190 patients treated with ECMO, the median age was 49 years (IQR 41-58), 137 (72.1%) were men, and the median PaO2/FiO2 prior to ECMO initiation was 72 (IQR 61-90). At 60 days, 63 patients (33.2%) had died, 94 (49.5%) were discharged, and 33 (17.4%) remained hospitalized. Among the 1297 patients eligible for the target trial emulation, 45 of the 130 (34.6%) who received ECMO died, and 553 of the 1167 (47.4%) who did not receive ECMO died. In the primary analysis, patients who received ECMO had lower mortality than those who did not (HR 0.55; 95% CI 0.41-0.74). Results were similar in a secondary analysis limited to patients with PaO2/FiO2 < 80 (HR 0.55; 95% CI 0.40-0.77).

Conclusion: In select patients with severe respiratory failure from COVID-19, ECMO may reduce mortality.

Keywords: ARDS; COVID-19; Extracorporeal membrane oxygenation; Mortality; Severe respiratory failure; VV-ECMO.

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Conflict of interest statement

DEL received research support from BioPorto outside the submitted work. DMC reports grants and personal fees from NovoNordisk, personal fees from PLC medical, grants from Bioporto, personal fees from Fresenius, personal fees from AstraZeneca, grants and personal fees from Jannssen, grants and personal fees from Gilead, and personal fees from Merck, all outside the submitted work. AS reports personal fees from Horizon Therapeutics PLC, AstraZeneca, and CVS Caremark. SG is a scientific coordinator for the ASCEND trial (GlaskoSmithKline), outside the submitted work. KSM reports serving on the BREATHE Trial Steering Committee, funded by Roivant/Kinevant Sciences, outside the submitted work. BOG receives consulting fees from Sedana Medical outside the submitted work. The authors of the writing committee are supported by the following grants from the National Institutes of Health: K08GM134220 and R03AG060179 (SS); R01HL144566 and R01DK125786 (DEL); K23HL130648 (KSM); R37 AI102634 (MAH); F32DC017342 (SG); K23DK120811 (AS); K23HL143053 (MWS).

Figures

Fig. 1
Fig. 1
Study cohort. Two populations of patients are shown: the descriptive analysis, which includes all patients who initiated ECMO in the first 14 days following ICU admission, and the target trial emulation, which includes patients who did or did not initiate ECMO in the first 7 days following ICU admission. For the target trial emulation, patients who initiated ECMO appeared in the pooled dataset up to and including the day that ECMO was initiated. For example, a patient who initiated ECMO on ICU day one did not have a corresponding observation on ICU days two through seven. A patient who initiated ECMO on ICU day three, meanwhile, appeared as both an ECMO non-initiator on days one and two and as an ECMO initiator on day three. ECMO extracorporeal membrane oxygenation, ICU intensive care unit, PaO2/FiO2 partial pressure of arterial oxygen over the fraction of inspired oxygen
Fig. 2
Fig. 2
The estimated effect of ECMO on mortality. a Shows the unadjusted survival curves for ECMO-treated versus ECMO non-treated patients. b Shows the hazard ratios for survival for ECMO-treated versus ECMO non-treated patients. The following covariates were included in the multivariable models: age; sex; race; body mass index; hypertension; diabetes mellitus; coronary artery disease; congestive heart failure; chronic obstructive pulmonary disease; shock; suspected or confirmed secondary infection; the renal, liver, and coagulation components of the Sequential Organ Failure Assessment score [25, 26]; and receipt of rescue therapies for hypoxemia (prone position ventilation, neuromuscular blockade, and inhaled vasodilators, each assessed separately). Sensitivity analysis #1 treated hospital discharge as a competing risk rather than as a censoring event. Sensitivity analysis #2 matched each ECMO-treated patient on day 1 with two randomly selected eligible control patients (PaO2/FiO2 ratio < 100 mmHg while receiving invasive mechanical ventilation) who did not initiate ECMO, and the process was then repeated on days 2 through 7, with ECMO non-treated patients only being used once. Sensitivity analysis #3 was limited to patients with the following characteristics: < 65 years old; absence of coronary artery disease, congestive heart failure, and COPD; mechanically ventilated and with a PaO2/FiO2 ratio < 80 mmHg; and receipt of at least one rescue therapy for hypoxemia (prone position ventilation, neuromuscular blockade, or inhaled vasodilators) prior to ECMO initiation or non-initiation. ECMO extracorporeal membrane oxygenation, PaO2/FiO2 partial pressure of arterial oxygen over the fraction of inspired oxygen
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