Dismal Survival in COVID-19 Patients Requiring ECMO as Rescue Therapy after Corticosteroid Failure

Abstract

(1) Background: COVID-19 may lead to refractory hypoxemia requiring venovenous extracorporeal membrane oxygenation (ECMO). Survival rate if ECMO is implemented as rescue therapy after corticosteroid failure is unknown. We aimed to investigate if ECMO implemented after failure of the full-recommended 10-day corticosteroid course can improve outcome. (2) Methods: We conducted a three-center cohort study including consecutive dexamethasone-treated COVID-19 patients requiring ECMO between 03/2020 and 05/2021. We compared survival at hospital discharge between patients implemented after (ECMO-after group) and before the end of the 10-day dexamethasone course (ECMO-before group). (3) Results: Forty patients (28M/12F; age, 57 years (51–62) (median (25th–75th percentiles)) were included, 28 (70%) in the ECMO-before and 12 (30%) in the ECMO-after group. In the ECMO-before group, 9/28 patients (32%) received the 6 mg/day dexamethasone regimen versus 12/12 (100%) in the ECMO-after group (p < 0.0001). The rest of the patients received an alternative dexamethasone regimen consisting of 20 mg/day during 5 days followed by 10 mg/day during 5 days. Patients in the ECMO-before group tended to be younger (57 years (51–59) versus 62 years (57–67), p = 0.053). In the ECMO-after group, no patient (0%) survived while 12 patients (43%) survived in the ECMO-before group (p = 0.007). (4) Conclusions: Survival is poor in COVID-19 patients requiring ECMO implemented after the full-recommended 10-day dexamethasone course. Since these patients may have developed a particularly severe presentation, new therapeutic strategies are urgently required.

Prognostic factors associated with mortality among patients receiving venovenous extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis

“…Of 2888 studies identified ( figure ), we selected 123 for full-text review. We included 42 observational cohort studies 13 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 involving 17 449 patients ( table 1 ), predominantly from North America or Europe. We did not identify any randomised controlled trials that met our eligibility criteria.…”

“… 35 , 36 , 37 , 38 , 39 Studies were judged to be at some risk of bias for confounding adjustment and for statistical analysis and reporting if they did not account for clinically important confounders using either logistic regression or Cox proportional hazards models. 15 , 39 , 44 , 46 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 Studies reporting adjusted analyses were judged to be at some risk of bias for statistical analysis 35 , 36 , 37 , 40 , 41 , 42 , 43 , 44 , 45 , 46 if they did not adhere to methodological standards set by the PROGRESS guidelines, 19 , 20 , 21 , 22 in particular with regards to a priori selection of clinically important confounders and consideration of an appropriate sample size to minimise potential overfitting. 28 , 76 The composition and methodological quality of individual prediction models for each study and funnel plots used to evaluate for publication bias among variables that were assessed in at least ten studies are included in the appendix (p 36–41 ).…”

“… 45 Similarly, when the effect of age was measured in 10-year increments in eight studies, 35 , 40 , 41 , 42 , 44 , 60 , 69 , 73 older age remained associated with mortality (aOR 1·19 [95% CI 1·11–1·27]). Of the 26 studies 36 , 37 , 39 , 40 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 58 , 60 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 71 , 74 that included sex as a prognostic factor, male sex was found to be probably associated with increased mortality (uOR 1·34 [95% CI 1·20–1·49]; moderate certainty) and of the three studies 13 , 35 , 71 that included lung disease as a prognostic factor, chronic lung disease was found to be probably associated with increased mortality (aHR 1·55 [95% CI 1·20–2·00]; moderate certainty). In the 14 studies 35 , 41 , 49 , 51 , 54 , 55 , 61 , 62 , 66 , 67 , 68 , 72 , 73 , 74 that included obesity as a prognostic factor, obesity may have been associated with decreased mortality (uOR 0·84 [0·72–0·97]), although this finding was based on low-certainty evidence with a serious risk of bias and imprecision.…”

“…Higher driving pressure was defined as greater than 16 cm H 2 O in both studies that examined this variable. 38 , 74 Eight studies 37 , 42 , 56 , 58 , 63 , 65 , 69 , 71 included symptom duration before cannulation as a prognostic factor, and showed that longer symptom duration was probably associated with increased mortality (mean difference 1·51 days [95% CI 0·36 to 2·65]; moderate certainty). 16 studies 35 , 37 , 40 , 41 , 43 , 46 , 49 , 51 , 53 , 54 , 58 , 60 , 64 , 71 , 72 , 74 included partial pressure of arterial carbon dioxide (PaCO 2 ) as a prognostic factor, and showed that higher PaCO 2 was probably associated with increased mortality (mean difference 4·04 mm Hg [95% CI 1·64 to 6·44]; moderate certainty).…”

Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis

“…As such, the increase in mortality might stem from selection bias for patients with more severe ARDS refractory to adjunctive therapies than earlier on in the pandemic. Even amongst those who eventually require ECMO, a study of 40 patients found that mortality rates of patients receiving ECMO after a full 10-day course of dexamethasone was 100% compared to 57% where ECMO was instituted before completing the course of dexamethasone [ 69 ]. In addition to this, immunomodulatory treatment might be associated with increased rates of secondary infections, which itself is associated with increased mortality rates [ 70 ], though this is not confirmed by all the available evidence [ 71 ].…”