Association between arterial carbon dioxide, brain biomarkers and central nervous system injury during veno-venous extracorporeal membrane oxygenation: A Prospective Cohort Study.

Background: Central nervous system (CNS) injury following initiation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) is common. An acute decrease in PaCO 2 following VV-ECMO initiation has been suggested as an etiological factor, but the challenges of diagnosing CNS injuries has made discerning a relationship between PaCO 2 and CNS injury difficult. Methods: We conducted a prospective cohort study of adult patients undergoing VV-ECMO for acute respiratory failure. We collected blood biospecimens to measure brain biomarkers (neurofilament light [NF-L]; glial fibrillary acidic protein [GFAP]; and phosphorylated-tau 181 [p-tau 181]) in the first seven days following initiation of VV-ECMO. We assessed the relationship between both PaCO 2 over the first 24-hours and brain biomarkers with CNS injury using mixed methods linear regression. Results: In our cohort twelve of 59 (20%) patients had overt CNS injury identified on head CT. The PaCO 2 decrease with VV-ECMO initiation was steeper in patients who developed a CNS injury (-0.32%, 95%CI: -0.25 to -0.39) compared to those without (-0.18%, 95%CI: -0.14 to -0.21, P-interaction < 0.001). The mean concentration of NF-L increased over time and was higher in those with a CNS injury (464 [739]) compared to those without (127 [257])(P = 0.001). GFAP was higher in those with a CNS injury (4278 [11653] pg/ml) compared to those without (116 [108] pg/ml) (P < 0.001). Conclusions: Although rapid decreases in PaCO 2 following initiation of VV-ECMO were slightly greater in patients that had CNS injuries vs. those without, data overlap and absence of relationships between PaCO 2 and brain biomarkers suggests other pathophysiologic variables are likely at play.