Older Age, Male Sex Linked to Higher Mortality in Venovenous ECMO for COVID-19

Among patients who received venovenous extracorporeal membrane oxygenation (ECMO) for COVID-19, older age, male sex, and chronic lung disease have a moderate or high certainty of association with increased mortality, according to findings published in The Lancet Respiratory Medicine.

The systematic review and meta-analysis sought to summarize the association between precannulation prognostic factors (including patient factors, disease factors, and center factors) and the risk of in-hospital mortality in adult patients who received venovenous ECMO for acute respiratory failure secondary to COVID-19.

Investigators searched the MEDLINE and Embase databases from December 1, 2019, to April 14, 2022, for randomized controlled trials and observational studies published in English that included adult patients (aged ≥16 years) with COVID-19 confirmed by polymerase chain reaction, patients who required any configuration of ECMO for COVID-19-associated acute respiratory distress syndrome (ARDS), and the assessment of precannulation prognostic factors associated with in-hospital mortality.

The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess overall certainty in pooled estimates. The primary outcome was in-hospital mortality. A total of 42 observational cohort studies with 17,449 patients were included. The studies were mostly from North America and Europe.

Of the patient factors, older age (5 studies; adjusted hazard ratio [aHR] 2.27 [95% CI, 1.63-3.16]; high certainty), was associated with increased mortality. Among 26 studies that included sex as a prognostic factor, male sex was probably associated with increased mortality (unadjusted odds ratio [uOR] 1.34 [95% CI, 1.20-1.49]; moderate certainty). Of 3 studies with lung disease as a prognostic factor, chronic lung disease was probably associated with increased mortality (aHR 1.55 [95% CI, 1.20-2.00]; moderate certainty).

Precannulation disease factors were included in 2 studies, which showed that increased driving pressure was associated with higher mortality (aHR 2.36 [95% CI, 1.40-3.97]; high certainty). Also, 8 studies that assessed symptom duration before cannulation as a prognostic factor showed that a greater symptom duration was probably associated with increased mortality (mean difference 1.51 days [95% CI, 0.36-2.65]; moderate certainty).

A total of 16 studies evaluated partial pressure of arterial carbon dioxide (PaCO₂) as a prognostic factor and demonstrated that increased PaCO₂ was probably associated with increased mortality (mean difference 4.04 mm Hg [95% CI, 1.64-6.44]; moderate certainty).

The duration of invasive mechanical ventilation before cannulation was assessed in 6 studies, which showed that longer ventilation duration was probably associated with increased mortality (uOR 1.94 [95% CI, 1.40-2.67]; moderate certainty). In addition, according to 2 studies that evaluated center volume, lower patient volume (or less experienced center) was probably associated with increased mortality (adjusted odds ratio 2.27 [95% CI, 1.28-4.05]; moderate certainty).

Study limitations included the use of prognostic factors of importance for patients who ultimately received ECMO, rather than for all patients potentially eligible for ECMO; the lack of appropriate adjustment for extrapulmonary organ failure in many included studies, which might have affected patient selection and outcomes; and variability in the quality of the prognostic modeling methodology used by the included studies.

“We advocate for the careful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient’s potential indication for venovenous ECMO for the treatment of COVID-19,” said the investigators.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.