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

Methods

Search Strategy and Selection Criteria

This study was registered with PROSPERO (CRD42020192627) and was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Statement.[17] We searched MEDLINE, Embase, Cochrane and Scopus databases from 1 December 2019, to 10 January 2021, using the following keywords and their variations: "extracorporeal membrane oxygenation", "extracorporeal life support", "adult", "SARS-CoV-2" and "COVID-19" (Additional file 1: Table S1). We assessed all relevant studies and their citation lists to identify articles for inclusion.

We included data from all studies as well as available online national registries reporting on 10 or more adult patients with COVID-19 supported on ECMO. We excluded any animal or paediatric studies (< 18 years). In the case of overlapping patient data, we included the largest study and excluded any other overlapping studies. Studies from centres that contributed to the ELSO registry report[5] were also excluded to avoid duplication. Two reviewers (RRL and KR) independently screened the articles for eligibility by going through the titles and abstract. Full text of the shortlisted articles was searched thereafter; any conflicts were resolved by consensus or by a third reviewer (KS).

Data Collection

Data were collected independently by two reviewers (RRL and KR) using a prespecified data extraction form; any conflicts were resolved by consensus or by a third reviewer (KS). Data collection covered study characteristics (study design, study duration, year of publication, name and country of origin of ECMO centre, indications for ECMO); patient demographics (number of patients, proportion of male/female patients, age, body mass index [BMI], comorbidities); pre-ECMO characteristics (ventilation parameters: partial pressure of arterial oxygen to fraction of inspired oxygen ratio [PaO2/FiO2], serum pH, lactate, duration of mechanical ventilation before ECMO initiation, adjunctive therapies, Sequential Organ Failure Assessment [SOFA] score); ECMO characteristics (type of ECMO at initiation, cannulation site, adjunctive therapies [prone positioning, neuromuscular blockade, inotropes/vasopressors, inhaled nitric oxide, corticosteroids and immunomodulatory agents]); mortality (in-hospital as well as substitution of the closest common mortality time point); and other relevant clinical outcomes (intensive care unit [ICU] and hospital length of stay [LOS], ECMO duration and complications during ECMO). Complications were represented broadly as per the ELSO reporting guidelines. Authors were contacted for additional data where necessary.

Assessment of Risk of Bias and Certainty of Evidence

Using the Joanna Briggs Institute (JBI) checklists for case series and cohort studies (Additional file 1: Table S2), we assessed studies for quality. We assessed the possibility of publication bias using Egger's test. We assessed statistical heterogeneity using the I2 statistics, the Chi-squared test and visual inspection of the forest plots. We used the Grading of Recommendations, Assessments, Developments and Evaluations (GRADE) approach to assess the certainty of evidence[18,19] (GRADEpro app available online: https://www.gradepro.org [accessed on 10 January 2021].

Outcomes of Interest

The primary outcome was in-hospital mortality. Secondary outcomes were analysed in the overall cohort and included those remaining in hospital and on ECMO, ICU and hospital length of stay, duration of mechanical ventilation before ECMO, duration of ECMO and complications during ECMO.

Statistical Analysis

We performed statistical analyses in R 3.6.1, using the meta (v4.12–0) and dmetar (v0.0.9000) packages.[20–22] For continuous variables, we pooled the means from the aggregate data presented in each study as per Wan et al..[23] We anticipated significant interstudy heterogeneity given the varied presentation of COVID-19 and general lack of guidelines for patient management with ECMO during the early pandemic. As such, we conducted inverse-variance weighted random-effects meta-analyses (DerSimonian and Laird), and 95% confidence intervals (CIs) were computed using the Clopper–Pearson method.[24–26] Survival outcomes are presented as pooled proportions, while continuous outcomes are presented as pooled means, both with corresponding 95% CIs.

Subgroup/Sensitivity Analysis

We conducted planned subgroup analyses with continuity correction to include studies with zero events and include geographical region (Asia, Europe, North America and International). Summary-level meta-regression was conducted when at least 6 data points were collected to explore potential sources of heterogeneity or prognostically relevant prespecified study-level covariates.[26] Two sensitivity analyses were conducted for our meta-analysis: analysing the mortality among studies where all patients were supported with VV ECMO and another by excluding studies with a JBI score of less than 7.

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