A Pilot Double-Blind Placebo-Controlled Randomized Clinical Trial to Investigate the Effects of Early Enteral Nutrients in Sepsis

Preclinical studies from our laboratory demonstrated therapeutic effects of enteral dextrose administration in the acute phase of sepsis, mediated by the intestine-derived incretin hormone glucose-dependent insulinotropic peptide. The current study investigated the effects of an early enteral dextrose infusion on systemic inflammation and glucose metabolism in critically ill septic patients. DESIGN: Single-center, double-blind, placebo-controlled randomized pilot clinical trial (NCT03454087). SETTING: Tertiary-care medical center in Pittsburgh, PA. PATIENTS: Critically ill adult patients within 48 hours of sepsis diagnosis and with established enteral access. INTERVENTIONS: Participants were randomized 1:1 to receive a continuous water (placebo) or enteral dextrose infusion (50% dextrose; 0.5 g/mL) at 10 mL per hour for 24 hours. MEASUREMENTS AND MAIN RESULTS: We randomized 58 participants between June 2018 and January 2020 (placebo: n = 29, dextrose: n = 29). Protocol adherence was high with similar duration of study infusion in the placebo (median duration, 24 hr [interquartile range, 20.9–24 hr]) and dextrose (23.9 hr [23–24 hr]) groups (p = 0.59). The primary outcome of circulating interleukin-6 at end-infusion did not differ between the dextrose (median, 32 pg/mL [19–79 pg/mL]) and placebo groups (24 pg/mL [9–59 pg/mL]; p = 0.13) with similar results in other measures of the systemic host immune response. Enteral dextrose increased circulating glucose-dependent insulinotropic peptide (76% increase; 95% CI [35–119]; p < 0.01) and insulin (53% [17–88]; p < 0.01) compared with placebo consistent with preclinical studies, but also increased blood glucose during the 24-hour infusion period (153 mg/dL [119–223] vs 116 mg/dL [91–140]; p < 0.01). Occurrence of emesis, ICU and hospital length of stay, and 30-day mortality did not differ between the placebo and enteral dextrose groups. CONCLUSIONS: Early infusion of low-level enteral dextrose in critically ill septic patients increased circulating levels of insulin and the incretin hormone glucose-dependent insulinotropic peptide without decreasing systemic inflammation.