Context: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-sustaining therapy for severe refractory cardiogenic shock. Although VA-ECMO provides various degrees of cardiopulmonary support, mortality rates remain high. Serum biomarkers have potential to identify the rising risk of mortality in patients receiving ECMO, but evidence supporting their prognostic value is inconsistent.

Objectives: This study aims to systematically investigate existing evidence on the relationship between biomarkers and mortality in adult patients with refractory cardiogenic shock undergoing VA-ECMO support.

Methods: A systematic review was conducted conforming to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Analogous search strings were developed to complete a comprehensive literature search across multiple databases that included Embase, Scopus, PubMed, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Search limits include studies published in the last 5 years (>2018) and in the English language. The inclusion criteria were: all genders aged 18 and older being treated for cardiogenic shock with VA-ECMO and intra-ECMO biomarker data with corresponding mortality data. Biomarkers included in the criteria were: lactate, creatinine, bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), troponin, C-reactive protein (CRP), and white blood cell (WBC) count. Identified articles were included within the main findings after unanimous approval by all authors. The quality of the evidence was assessed systematically utilizing a standardized and validated checklist.

Results: Our search yielded 1,033 studies, with 650 studies remaining after the removal of duplicates, leaving 538 studies to be screened for title and abstract study relevance. Subsequently, 112 studies remained for full-text review. Reasons for exclusion during full-text review include conference abstract, no mention of specific biomarkers, and wrong comparison of treatment modalities. Five studies remained for data extraction. Data gathered from five retrospective cohort studies reported a total of 589 patients supported by VA-ECMO following a diagnosis of cardiogenic shock, with the most common inciting factor being postcardiac surgery. Most patients were male. The age range for all participants was between 45 and 77 years. Common comorbidities include diabetes mellitus, hypertension, and vascular disease. Overall mortality was 59.9 % (353/589) based on survival to 30-day post-ECMO initiation or hospital discharge. In three of the studies, the patients in the survivor cohort had statistically significant lower intra-ECMO lactate levels compared to the non-survivors (p<0.01). One of the studies found statistically significant differences between survivors and non-survivors in the intra-ECMO values for serum lactate (p<0.001), creatinine (p<0.023), bilirubin (p<0.001), AST (p<0.05), and ALT (p<0.05). Another study reported statistically significant differences in nadir lactate levels through 24 and 48 h of ECMO initiation in survivors vs. non-survivors (p=0.001 and p=0.001 respectively).

Conclusions: Serum lactate was the biomarker most utilized to assess the risk of mortality. Serum creatinine (Scr), bilirubin, AST, and ALT also demonstrated significance in predicting mortality, although not as widely studied as serum lactate. Future research is needed to further investigate the usage of Scr, bilirubin, AST, and ALT to better assess their significance, regarding VA-ECMO mortality in patients diagnosed with cardiogenic shock. Further research is also warranted to investigate the minimal concentration of these biomarkers and their association with mortality to allow clinicians a better predictor of a patient’s mortality risk while receiving VA-ECMO.