Abstract
BACKGROUND: Central nervous system (CNS) injury following initiation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) is common. An acute decrease in partial pressure of arterial carbon dioxide (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. Arterial blood gas measurements were obtained prior to initiation of VV-ECMO, and at every 2-4 h for the first 24 h. Neuroimaging was conducted within the first 7-14 days in patients who were suspected of having neurological injury or unable to be examined because of sedation. We collected blood biospecimens to measure brain biomarkers [neurofilament light (NF-L); glial fibrillary acidic protein (GFAP); and phosphorylated-tau 181] in the first 7 days following initiation of VV-ECMO. We assessed the relationship between both PaCO(2) over the first 24 h and brain biomarkers with CNS injury using mixed methods linear regression. Finally, we explored the effects of absolute change of PaCO(2) on serum levels of neurological biomarkers by separate mixed methods linear regression for each biomarker using three PaCO(2) exposures hypothesized to result in CNS injury. RESULTS: In our cohort, 12 of 59 (20%) patients had overt CNS injury identified on head computed tomography. The PaCO(2) decrease with VV-ECMO initiation was steeper in patients who developed a CNS injury (- 0.32%, 95% confidence interval - 0.25 to - 0.39) compared with those without (- 0.18%, 95% confidence interval - 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 with those without (127 [257]; P = 0.001). GFAP was higher in those with a CNS injury (4278 [11,653] pg/ml) compared with those without (116 [108] pg/ml; P < 0.001). The mean NF-L, GFAP, and tau over time in patients stratified by the three thresholds of absolute change of PaCO(2) showed no differences and had no significant interaction for time. CONCLUSIONS: Although rapid decreases in PaCO(2) following initiation of VV-ECMO were slightly greater in patients who had CNS injuries versus those without, data overlap and absence of relationships between PaCO(2) and brain biomarkers suggests other pathophysiologic variables are likely at play.