Endotoxin Activity in Patients With Extracorporeal Membrane Oxygenation Life Support: An Observational Pilot Study

Abstract

Background: Extracorporeal membrane oxygenation (ECMO) life support has become an integral part of intensive care. The endotoxin activity assay (EAA) is a useful test to measure endotoxemia severity in whole blood. To date, no information is available regarding the EAA levels and their effect on clinical outcomes in critically ill patients with ECMO support.Methods: This prospective observational pilot study enrolled adult critically ill patients with ECMO support from August 2019 to December 2020. The EAA levels were measured within 24 h (T1), and at 25–48 (T2), 49–72 (T3), and 73–96 h (T4) after ECMO initiation. This study primarily aimed to investigate the incidence of high EAA levels (≥0.6) at each time point. Subsequent exploratory analyses were conducted to compare the EAA levels of venoarterial ECMO (VA-ECMO) patients between 30-day survivors and non-survivors. Post-hoc analysis was performed to compare the clinical outcomes of VA-ECMO patients with elevated EAA levels at T3 (vs. T1) and those without elevated EAA levels.Results: A total of 39 VA-ECMO patients and 15 venovenous ECMO (VV-ECMO) patients were enrolled. At T1, the incidence of high EAA level (≥0.6) was 42% in VV-ECMO patients and 9% in VA-ECMO patients (P = 0.02). At T2, the incidence of high EAA level was 40% in VV-ECMO patients and 5% in VA-ECMO patients (P = 0.005). In VA-ECMO patients, EAA levels at T3 were significantly higher in 30-day non-survivors than in survivors (median [interquartile range]: 0.49 [0.37–0.93] vs. 0.31 [0.19–0.51], median difference 0.16 [95% confidence interval [CI], 0.02–0.31]; P = 0.024). Moreover, VA-ECMO patients with elevated EAA levels at T3 (vs. T1) had lower 30-day survival than patients without elevated EAA levels (39 vs. 83%, P = 0.026) and fewer ECMO free days by day 30 (median: 3 vs. 23 days, median difference 12 days [95% CI, 0–22]; P = 0.028).Conclusions: A certain proportion of patients experienced high EAA levels (≥0.6) after VV-ECMO or VA-ECMO initiation. VA-ECMO patients with an elevated EAA level at 49–72 h were associated with poor clinical outcomes.

Endotoxemia in Acute Heart Failure and Cardiogenic Shock: Evidence, Mechanisms and Therapeutic Options

“…The fourth study reported endotoxin activity in 39 patients under venoarterial extracorporeal membrane oxygenation (VA-ECMO). In these patients (16 cardiac arrest, 17 heart failure, 4 post cardiotomy and 2 septic shock), the incidence of endotoxemia was only 9% within the first 24 h and 5% between 24 and 48 h. There was no difference in endotoxin activity between survivors and non-survivors [ 54 ].…”

Extending the ‘host response’ paradigm from sepsis to cardiogenic shock: evidence, limitations and opportunities

“…Endotoxemia reduces cardiac performance [57] and can propagate a low cardiac output state [58]. Despite sound rationale, three small studies [59][60][61] have failed to identify direct proof of endotoxemia in patients with CS with the caveat that no study has hitherto reported quantitative measurement (i.e. mass) of circulating endotoxins and many endotoxin assays have inherent detection limitations.…”