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Objectives To identify, appraise, and synthesize the most current evidence to determine whether early enteral nutrition alters patient outcomes from critical illness. Data sources Medline and Embase were searched. The close out date was November 20, 2017. Study selection Early enteral nutrition was defined as a standard formula commenced within 24 hours of ICU admission. Comparators included any form of nutrition support "except" early enteral nutrition. Only randomized controlled trials conducted in adult patients requiring treatment in an ICU were eligible for inclusion. Data extraction The primary outcome was mortality. Secondary outcomes included pneumonia, duration of mechanical ventilation, and ICU and hospital stay. Data synthesis Six-hundred ninety-nine full-text articles were retrieved and screened. Sixteen randomized controlled trials enrolling 3,225 critically ill participants were included. Compared with all other types of nutrition support, commencing enteral nutrition within 24 hours of ICU admission did not result in a reduction in mortality (odds ratio, 1.01; 95% CI, 0.86-1.18; p = 0.91; I = 32%). However, there was a differential treatment effect between a priori identified subgroups (p = 0.032): early enteral nutrition reduced mortality compared with delayed enteral intake (odds ratio, 0.45; 95% CI, 0.21-0.95; p = 0.038; I = 0%), whereas a mortality difference was not detected between early enteral nutrition and parenteral nutrition (odds ratio, 1.04; 95% CI, 0.89-1.22; p = 0.58; I = 30%). Overall, patients who were randomized to receive early enteral nutrition were less likely to develop pneumonia (odds ratio, 0.75; 95% CI, 0.60-0.94; p = 0.012; I = 48%). Conclusions Overall, there was no difference between early enteral nutrition and all other forms of nutrition support. A priori planned subgroup analysis revealed early enteral nutrition reduced mortality and pneumonia compared with delayed enteral intake; however, there were no clear clinical advantages of early enteral nutrition over parenteral nutrition.

Introduction Guidelines support the use of enteral nutrition to improve clinical outcomes in critical illness; however, the optimal calorie and protein intake remains unclear. The purpose of this meta-analysis was to quantitatively analyze randomised controlled trials with regard to clinical outcomes related to varying calorie and protein administration in critically ill adult patients. Method We searched Medline, EMBASE, and Cochrane databases to identify randomised controlled trials that compared the effects of initially different calorie and protein intake in critical illness. The risk ratio (RR) and weighted mean difference with 95% confidence intervals (CI) were calculated using random-effects models. The primary endpoint was mortality; secondary endpoints included infection, pneumonia, gastrointestinal intolerance, hospital and intensive care unit lengths of stay, and mechanical ventilation days. Results In the eight randomised controlled trials that enrolled 1,895 patients there was no statistical difference between the low-energy and high-energy groups in mortality (RR, 0.90; 95% CI, 0.71 to 1.15; P = 0.40), infection (RR, 1.09; 95% CI, 0.92 to 1.29; P = 0.32), or the risk of gastrointestinal intolerance (RR, 0.84; 95% CI, 0.59 to 1.19; P = 0.33). In subgroup analysis, the low-energy subgroup, fed 33.3 to 66.6% of goal energy, showed a lower mortality than the high-energy group (RR, 0.68; 95% CI, 0.51 to 0.92; P = 0.01). The improvements in mortality and gastrointestinal intolerance were absent when calorie intake was >66.6% of goal energy in the low-energy group. High-energy intake combined with high-protein intake reduced the infections (RR, 1.25; 95% CI, 1.04 to 1.52; P = 0.02); however, when the daily protein intake was similar in both groups, a high-energy intake did not decrease the infections. No statistical differences were observed in other secondary outcomes. Conclusion This meta-analysis indicates that high-energy intake does not improve outcomes and may increase complications in critically ill patients who are not malnourished. Initial moderate nutrient intake (33.3 to 66.6% of goal energy), compared to high energy, may reduce mortality, and a higher protein intake combined with high energy (≥0.85 g/kg per day) may decrease the infection rate. However, the contribution of energy versus protein intake to outcomes remains unknown.