Elimination of glutamate using CRRT for 72 h in patients with post-cardiac arrest syndrome: A randomized clinical pilot trial

Abstract

AimGlutamine and glutamate are major mediators of secondary brain cell death during post-cardiac arrest syndrome. As there is an equilibrium between brain tissue and plasma concentrations of glutamine and glutamate, their elimination from systemic circulation by extracorporeal blood purification may ultimately lead to reduced secondary cell death in the brain. We hypothesized that systemic glutamine and glutamate can be significantly reduced by continuous venovenous hemodiafiltration (CVVHDF). MethodsThis was a prospective, randomized clinical trial in post cardiac-arrest survivors evaluating standard of care or additional CVVHDF over 72 h immediately after admission. Glutamine and glutamate plasma concentrations were analyzed at eight time points in both groups. Primary endpoint was reduction of glutamine and glutamate plasma concentrations. The trial has been registered at clinical trial.gov (NCT02963298). ResultsIn total, 41 patients were randomized over a period of 12 months (control n = 21, CVVHDF n = 20). The primary aim reduction of glutamine and glutamate plasma concentrations by CVVHDF, was not achieved; both groups-maintained concentrations within a normal range over the study period (glutamate: 4.7–11.1 mg/dL; glutamine: 0.2–3.7 mg/dL). However, post-filter concentrations of glutamine and glutamate in CRRT patients were significantly decreased as compared to pre-filter concentrations (glutamate: pre-filter median 8.85 mg/dL IQR 7.1–9.6; post-filter 0.95 mg/dL IQR 0.5–2; p < 0.001; glutamine: pre-filter 0.7 mg/dL IQR 0.6–1; post-filter 0.2 mg/dL IQR 0–0.2; p < 0.001). ConclusionIn this trial, CVVHDF was not able to statistically significantly lower systemic plasma glutamine and glutamate levels. Post-cardiac arrest patients had plasma glutamine and glutamate levels within the normal range.