Extracorporeal Membrane Oxygenation for COVID-19

A Systematic Review and Meta-Analysis

Kollengode Ramanathan; Kiran Shekar; Ryan Ruiyang Ling; Ryan P. Barbaro; Suei Nee Wong; Chuen Seng Tan; Bram Rochwerg; Shannon M. Fernando; Shinhiro Takeda; Graeme MacLaren; Eddy Fan; Daniel Brodie

Disclosures

Crit Care. 2021;25(211) 

In This Article

Results

Study Details and Demographics

Of 2259 references screened, we identified 37 potentially relevant studies and one national database that reported on the outcomes of ECMO in COVID-19 patients (Figure 1).[5,6,12–15,27–43] After excluding 11 studies with overlapping information, we included twenty-two retrospective observational studies with 1896 patients in the meta-analysis. There were 20 single-centre studies and two registry reports (Table 1 and Table 2). There were 4 studies (422 patients) from Asia, 13 studies (320 patients) from Europe, 4 studies (102 patients) from North America and one multinational study (1035 patients). Modality of ECMO support was reported in 19 studies (1845 patients), and VV ECMO was the predominant technique used (98.6%). In total, 89 patients required venoarterial or venoarterial venous configurations. The pooled patient demographics are summarised in Additional file 1: Table S3.

Figure 1.

Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow chart

Assessment of Study Quality

Appraisal using the JBI checklist for cohort studies and case series suggested a high level of quality across the included studies for this review. All studies, except two,[13,32] had scores above 8/10 (Additional file 1: Table S2). A summary of the GRADE assessment for certainty of evidence is provided in Additional file 1: Table S4.

Pre-ECMO Variables

Fifteen studies (1344 patients) reported on PaO2/FiO2 prior to ECMO initiation. The pooled mean PaO2/FiO2 was 67.76 (95% CI 64.72–70.80). Pre-ECMO SOFA score was reported in 11 studies (275 patients) with a pooled mean SOFA score prior to ECMO initiation of 9.62 (95% CI 8.40–10.84). The pre-ECMO ventilatory parameters are summarised in Additional file 1: Table S5.

Pre-ECMO Adjunctive Therapies

Patients with COVID-19 who received ECMO also received various adjunctive therapies prior to ECMO. Pooled incidence of prone positioning prior to ECMO was 85.3% (95% CI 74.6–93.7%) while 96.3% (95% CI 87.6–100.0%) of the patients received neuromuscular blockers. Additional details on the use of inotropic agents, corticosteroids, immuno-modulators and antiviral drugs are highlighted in Additional file 1: Table S6.

In-hospital Mortality

The pooled in-hospital mortality of COVID-19 patients receiving ECMO (22 studies, 1896 patients) was 37.1% (95% CI 32.3–42.0%, high certainty) (Figure 2). Two studies had a JBI score lower than 8; pooled in-hospital mortality after excluding these studies was 37.9% (95% CI 32.9–42.9%). There was no evidence of publication bias (Figure 3) (pegger = 0.21). We also analysed the proportion of non-survivors supported on VV ECMO for COVID-19 (17 studies, 1737 patients); pooled in-hospital mortality was 35.7% (95% CI 30.7–40.7%, high certainty) (Additional file 2: Figure S1). Mortality, after removal of studies that did not report on pre-ECMO PaO2/FiO2 ratio, was 36.4% (95% CI 30.2–42.9%). Two studies compared mortality rates of patients on mechanical ventilation to those on ECMO; patients needing mechanical ventilation had mortality rates of 47.8% and 63.2% as compared to 46.15% and 57.1%, respectively, in those needing ECMO in these two studies.

Figure 2.

Proportion of non-survivors among coronavirus disease 2019 patients requiring extracorporeal membrane oxygenation support

Figure 3.

Funnel plot for primary meta-analysis

Subgroup Analysis

There were no overall differences in regional outcomes for COVID-19 patients treated with ECMO (Additional file 3: Figure S2).

Meta-regression Analysis

Univariable meta-regression analysis identified increasing age and reduced ECMO duration as variables associated with mortality, while increasing BMI was protective (Additional file 4: Figure S3, Additional file 5: Figure S4 and Additional file 6: Figure S5). Increasing SOFA score was not associated with higher mortality. Other pre-ECMO factors (PaO2/FiO2 ratio, duration of mechanical ventilation prior to ECMO) or coexisting comorbidities (diabetes mellitus, hypertension, smoking) were not associated with increased mortality (Table 3).

Secondary Outcomes

In total, 141 of 1733 patients (21 studies) remained in hospital, while 68 of 1720 patients (20 studies) were still being supported with ECMO at the time of publication. Pooled ICU LOS (8 studies, 216 patients) and hospital LOS (6 studies, 1177 patients) were 32 days (95% CI 26–38, moderate certainty) and 40 days (95% CI 30–49, low certainty), respectively. There were 17 studies (1412 patients) that reported on weaning from ECMO with 67.6% (95% CI 50.5–82.7%, low certainty) of patients successfully weaned off ECMO. The pooled mean duration of mechanical ventilation prior to ECMO (16 studies, 1427 patients) was 4.40 days (95% CI 4.03–4.79, moderate certainty), while the pooled ECMO duration (18 studies, 1711 patients) was 15.81 days (95% CI 13.26–18.35, moderate certainty). Complications during ECMO were reported in 18 studies (1721 patients). There were a total of 1583 reported complications; renal complications (559/1583) were the most common, followed by mechanical (429/1583) and infectious complications (171/1583). A summary of all the outcomes including complications is provided in Table 2.

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