Study protocol
sepsis, critically ill, death
CRITICALLY ILL, RECRUITMENT, BLIND, BLOOD, SEPSIS
The study groups in this trial received either placebo (NaCl 0.9% and a clinically insignificant amount of riboflavin as colorant) or ascorbic acid. Participants were assigned to the placebo or ascorbic acid group in a 1:1 ratio using the online tool Research Randomizer [All patients had a central venous catheter and an arterial line and were resuscitated following international sepsis management guidelines to optimize their hemodynamics [The ascorbic acid manufacturer helped to ensure the blind format of the study. The 50 mL amber vials containing either ascorbic acid (concentration of 150 mg/mL) or placebo were supplied in separate kits for every patient. They were coded according to numbers, and unblinding occurred only after patient recruitment was complete. Placebo or ascorbic acid was diluted with 5% dextrose solution immediately before infusion into 50 mL amber-colored syringes, and light-protected infusion systems were used.Ascorbic acid and placebo vials were stored at 2–8 °C before use. The first dose was infused within 4 h after randomization. Study drug administration was stopped following the infusion of the last dose (96 h), ICU discharge, or death.Systemic hemodynamic variables, sublingual microcirculation, glycocalyx parameters, and arterial blood gas analysis results were evaluated at baseline and then within 30 min after the cessation of the first ascorbic acid or placebo infusion, and at 6, 12, 24, 48, 72, and 96 h from the beginning of the study. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score was calculated over the first 24 h following ICU admission. ΔSOFA score was evaluated within 96 h. Standard laboratory tests were performed daily, as usual, in critically ill patients.Blood samples to estimate interleukin-6 (IL6) and interleukin-10 (IL10) levels were drawn before the first study drug infusion and after 24 h. ICU mortality was registered.