Fig 1.
*in one patient support was withdrawn due to poor neurological prognosis; one patient developed a diffuse rash after administration of study drugs and further administration was discontinued; in one patient the nasogastric tube was removed after extubation and discontinuation of mechanical ventilation, and was not replaced as per study protocol preventing further administration of study drugs.
Fig 2.
Serum brain injury biomarkers neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP) during study period.
Individual NSE corrected for the degree of hemolysis (A) and GFAP (B) values for patients in the placebo (red circles) and probenecid + NAC (Pro-NAC; open blue squares) groups during the study period. There were no differences between groups for NSE (P = 0.441) or GFAP (P = 0.596). Time 0 is in reference to drug administration. Both groups started with seven patients/group. Sample attrition due to patient death, discontinuation of continuous monitoring, or insufficient quantity of serum available to perform the assay.
Table 1.
Baseline characteristics in the intention to-treat-population.
Table 2.
Surgical interventions.
Table 3.
Medical interventions.
Table 4.
Adverse events and complications.
Table 5.
Information on protocol compliance.
Fig 3.
Serum and cerebrospinal fluid (CSF) N-acetylcysteine (NAC) and probenecid concentrations during study period.
NAC (A) and probenecid (B) concentrations measured using ultra-high performance liquid chromatography-mass spectrometry (MS)/MS are shown for the placebo (red circles) and probenecid + NAC (Pro-NAC; open blue squares) groups. Data are mean and SEM; sample sizes noted in parentheses (n); LOQ = lower limit of quantification for the assay. Hashed lines represent drug administration times. 1Sample attrition due to patient death, premature withdrawal from study due to adverse event (rash), inability to continue enteric administration of study drugs after removal of nasogastric tube, and/or removal of or inability to obtain CSF from externalized ventricular drain.
Table 6.
Patient outcomes.
Fig 4.
Mean arterial pressure (MAP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) during study period.
MAP (A), ICP (B), and CPP (C) in the placebo (red circles) and probenecid + NAC (Pro-NAC; open blue squares) groups during the study period. Time 0 refers to pediatric intensive care unit admission. Median time [range] to first drug dose for the placebo group was 20.5 [14.6–26.0] h and for the Pro-NAC group was 16.5 [8.8–22.0] h. Data are mean and SD; Both groups started with seven patients/group. Sample attrition due to patient death or discontinuation of continuous monitoring.