The Effects of Conservative Fluid Management and Active Deresuscitation on Markers of Tissue Perfusion, Kidney Injury, and Vascular Injury in Critically Ill Adults: A Secondary Analysis of the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) Trial

OBJECTIVES: Test the hypothesis that conservative fluid management with active deresuscitation would not adversely affect tissue perfusion or kidney injury and would be associated with reduced vascular injury compared with usual care. DESIGN: Secondary analysis of the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) trial. SETTING: ICUs. PATIENTS OR SUBJECTS: Critically ill patients enrolled in the RADAR-2 trial. INTERVENTIONS: Conservative fluid management with active deresuscitation vs. usual care. MEASUREMENTS AND MAIN RESULTS: Measures of tissue hypoperfusion (whole blood lactate), acute kidney injury (AKIRisk score and urinary cystatin-C), and vascular injury (plasma hyaluronan, syndecan-1, and angiopoietin-2) were compared between groups. For each analyte, change from baseline was compared between groups and the median inter-group difference at each timepoint was estimated with bootstrapped CIs. Exploratory logistic regression examined associations between plasma biomarker levels (including N-terminal pro-B-type natriuretic peptide [NT-proBNP]), 28-day mortality, and treatment allocation. Whole blood lactate levels were similar between groups at all timepoints. Using change from baseline comparisons, no statistically detectable between-group differences were observed in AKIRisk scores or urinary cystatin-C levels. Plasma vascular injury biomarkers showed no statistically detectable between-group differences at any timepoint. High baseline hyaluronan (adjusted odds ratio [aOR], 5.75; 95% CI, 1.94-17.02; p = 0.002), syndecan-1 (aOR, 8.82; 95% CI, 2.67-29.15; p < 0.001), and NT-proBNP greater than 2500 pg/mL (aOR, 21.48; 95% CI, 3.57-129.41; p < 0.001) were independently associated with increased 28-day mortality. There was no evidence of differential treatment response based on these biomarker levels. CONCLUSIONS: Conservative fluid management and active deresuscitation were not associated with worsening tissue perfusion or acute kidney injury. A reduction in vascular injury markers was not observed. Given the modest sample size and resultant imprecision, clinically important effects cannot be excluded.