Association of specialized enteral nutrition with glycemic control and clinical outcomes in critically ill patients: A meta-analysis of randomized controlled trials

Abstract

Objective: To evaluate the association of glycemic-control formulae (GCF) with measurements of glycemic control and clinical outcomes compared to standard enteral formulae (SF) in critically ill patients.

Data sources: MEDLINE, EMBASE, Scopus and the Cochrane Central Register of Controlled Trials were searched from inception up to January, 2021.

Study selection: RCTs that assessed the effects of GCF relative to SF in adult critically ill patients.

Data extraction: Measurements of glycemic control were the primary outcomes. Secondary outcomes included insulin requirements, mechanical ventilation (MV), length of intensive care unit (ICU) stay and mortality. Two authors independently extracted data and assessed risk of bias using the Cochrane's RoB 2 tool and the GRADE approach was used to assess the quality of evidence.

Data synthesis: Ten studies (12 reports, 685 patients) were included. The use of GCFs was associated with lower blood glucose (WMD, -16.06 mg/dL; 95% CI -23.48 to -8.63; I² = 47%) and lower daily administered insulin (WMD, -7.20 IU; 95% CI -13.92 to -0.48; I² = 53%). Glycemic variability, measured by the coefficient of variation, was also associated with the use of GCFs (WMD, -6.84%; 95% CI, -13.57 to -0.11; I² = 95%). In contrast, analyses for length of ICU stay (WMD, -0.12, 95% CI -1.77 to 1.52; I² = 0%), duration of MV (WMD, -0.34 days; 95% CI, -1.72 to 1.04; I² = 0%) and mortality (RR, 1.13; 95% CI 0.82 to 1.56; I² = 0%) were not statistically significant. Quality of evidence ranged from low to very low, and only one study was judged as at low risk of bias.

Conclusions: In this meta-analysis, GCFs were significantly associated with lower insulin requirements and improved glycemic control. Although results for clinical outcomes were not statistically significant, there is insufficient evidence to confirm or exclude important differences due to serious imprecision in the effect estimates and overall low quality of evidence. The effects of GCFs on clinical outcomes require confirmation in larger randomized trials.

Keywords: Critical illness; Enteral feeding; Glycemic variability; Hyperglycemia; Meta-analysis; Nutrition therapy.