Key result
Antithrombin supplementation during veno-venous ECMO did not significantly reduce overall plasma cytokine levels compared to control, although it was associated with a more rapid decrease in IL-6, IL-1β, TNF-α, and Pro-ADM over time.
Why the study?
Veno-venous ECMO exacerbates inflammatory status, and while antithrombin is supplemented for anticoagulation, its anti-inflammatory relationship during ECMO warranted evaluation.
Does antithrombin supplementation reduce inflammation in adult patients requiring veno-venous ECMO for severe respiratory failure?
RCT (n=46)
Single-blind
Randomized
Yes
Does antithrombin supplementation reduce inflammation in adult patients requiring veno-venous ECMO for severe respiratory failure?
Antithrombin supplementation during veno-venous ECMO may accelerate the reduction of pro-inflammatory cytokines, though its clinical relevance requires confirmation in appropriately powered studies.
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.
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Panigada et al. (2022) conducted an RCT in Severe respiratory failure requiring veno-venous ECMO (n=46). Antithrombin vs. No antithrombin supplementation was evaluated on Plasma levels of cytokines (IL-8, IL-6, IL-10, IL-1β, TNF-α, Pro-ADM) during the study. Antithrombin supplementation during veno-venous ECMO did not significantly reduce overall plasma cytokine levels compared to control, although it was associated with a more rapid decrease in IL-6, IL-1β, TNF-α, and Pro-ADM over time.
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