Rationale for and Design of the Study of Early Enteral Dextrose in Sepsis: A Pilot Placebo‐Controlled Randomized Clinical Trial

Abstract

Background Sepsis is characterized by life‐threatening organ dysfunction caused by a dysregulated host response to infection and affects over 1 million Americans annually. Loss of glycemic control in sepsis is associated with increased morbidity and mortality, and novel approaches are needed to promote euglycemia and improve outcomes in sepsis. Recent studies from our laboratory demonstrate that early low‐level enteral dextrose infusion in septic mice attenuates the systemic inflammatory response and improves glycemic control by inducing intestine‐derived incretin hormone secretion. Aim The aim of the Study of Early Enteral Dextrose in Sepsis (SEEDS) is to test the effect of a 24‐hour enteral dextrose infusion in critically ill septic patients as a therapeutic agent to decrease systemic inflammation and promote euglycemia. Methods SEEDS is a single‐center, double‐blind, randomized, controlled trial that will enroll 60 septic patients admitted to the intensive care units at the University of Pittsburgh Medical Center Health System in Pittsburgh. Participants will be randomized 1:1 to receive enteral dextrose (n = 30) or water (placebo, n = 30) infusion for 24 hours. The primary outcome is the circulating interleukin‐6 level measured after the 24‐hour infusion compared between dextrose and placebo groups. Secondary outcomes include postinfusion circulating insulin, incretin, and other proinflammatory cytokine levels, as well as incidence of hyperglycemia and hypoglycemia during the infusion period. Discussion This trial will characterize the effects of early enteral dextrose on endogenous endocrine pathways and the systemic inflammatory response in sepsis. The results of this trial will inform future larger interventional studies of early enteral nutrients in critically ill patients with sepsis.

A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice

“…Several related questions are currently subject to ongoing research including comparing early trophic EN with no EN in the first 24 h [25][26][27][28][29].…”

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

“…SEEDS was a pilot single-center randomized placebo-controlled clinical trial testing an early enteral dextrose infusion in critically ill patients with sepsis (ClinicalTrials.gov registration number NCT03454087). Details of the design and rationale have been previously published ( 16 ). The trial protocol was approved by the University of Pittsburgh Institutional Review Board (PRO17010532, STUDY19080314) and funding was provided by the National Institutes of Health (K23GM122069).…”