Sweep Flow Nitric Oxide Effects on Coagulation, Inflammation, and Endothelial System Activation During Extracorporeal Membrane Oxygenation

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Abstract
Extracorporeal membrane oxygenation (ECMO) can trigger a systemic inflammatory response syndrome (SIRS) with activation of inflammatory, endothelial, and coagulation system pathways. We assessed in a randomized trial whether a) sweep flow nitric oxide (sNO) reduces these responses, b) what the temporal trajectory of these markers post-ECMO commencement is, and c) how serum marker concentrations are associated with survival. Fifty-three patients were randomized (25 sNO, 28 control). Serum levels of inflammatory cytokines (IL-1, IL-6, IL-8, IL-10, TNF-α), complement (C1q, C3, C4, C5a, C9, factor H, factor B), immune regulators (CD40L, P-Selectin), and coagulation factors (PF4, MBL, ADAMTS13) were measured at (t0) and 1, 12, 24 hours post ( t 1– t 3) ECMO initiation. Sweep flow nitric oxide did not alter serum biomarker trajectories. Across sNO and control groups, serum marker concentrations declined from t 0 to t 1 with variable patterns thereafter, but no consistent ECMO-associated elevation. Elevated IL-6 and IL-8 before and after ECMO commencement were associated with mortality, whereas higher P-Selectin, CD40 Ligand, and PF4 correlated with survival. Sweep flow nitric oxide did not modify markers of inflammation, endothelial, or coagulation activation during ECMO. Evidence of an ECMO-induced cytokine storm was absent, but serum biomarkers predicted mortality in ECMO-supported neonates and children.

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