The relationship between antithrombin administration and inflammation during veno-venous ECMO

Abstract

Veno-venous Extracorporeal Membrane Oxygenation (ECMO) is used in the most severe cases of respiratory failure and further exacerbates the patients' inflammatory status. Antithrombin is supplemented during ECMO for its anticoagulant effects, but it also deploys anti-inflammatory properties. In this pre-specified ancillary study of the GATRA trial [NCT03208270] we aimed to evaluate the relationship between antithrombin and inflammation during ECMO. Forty-six patients were included in the study, 23 were randomized to receive antithrombin to maintain a level of 80-120% (study group) and 23 were randomized not to be supplemented (control group). Anticoagulation was provided in both groups with heparin infusion. Six cytokines were measured at 5 timepoints from prior to ECMO start to 7 days after ECMO removal. Cytokines decreased during the study but overall were not very different in the two groups. Testing the interaction between the study group and timepoints suggests that the administration of antithrombin led to a more rapid decrease over time of IL-6, IL-1β, TNF-⍺ and Pro-ADM. Plasma levels of antithrombin (either endogenous or exogenous) were negatively associated with all cytokines. Inflammation decreases during ECMO but a causal effect of antithrombin administration on the reduction of inflammation (and its clinical relevance) must be confirmed by appropriately powered studies.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Figure 1

Cytokine sampling time during the study. Timepoints: Day 0 (prior to ECMO start), Day 1 (24 h after ECMO start), Day 3 (72 h after ECMO start), Day R (before ECMO removal), Day R + 7 (7 days after ECMO removal or before discharge from the ICU whichever happened first). n number of patients sampled.

Figure 2

Cytokine trend in the study groups. Geometric means and standard error of the means of cytokines during the study. Day 0 (prior to ECMO start), Day 1 (24 h after ECMO start), Day 3 (72 h after ECMO start), Day R (before ECMO removal), Day R + 7 (7 days after ECMO removal or before discharge from the ICU whichever happened first). Dashed lines: control group, solid line: treatment group. P values for interaction are from models who treated time (timepoints) as a quantitative variable (i.e., we assigned values from 0 to 4 to the five timepoints).

Figure 3

Correlation between cytokines and antithrombin. Pearson’s correlation coefficients, regression slopes and percent change in cytokine for 10% increase in antithrombin plasma level (%) with 95% CI from random-intercept linear regression models.