Effect of initial calorie intake via enteral nutrition in critical illness: a meta-analysis of randomised controlled trials

Feng Tian, Xinying Wang, Xuejin Gao, Xiao Wan, Chao Wu, Li Zhang, Ning Li, Jieshou Li

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 analyse randomised controlled trials (RCTs) with regard to clinical outcomes related with varying calorie and protein administration in critically ill adult patients. We searched the Medline, EMBASE, and Cochrane databases to identify RCTs 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. With the 8 RCTs that enrolled 1895 patients, there was no statistical difference between the low-energy (LE) and high-energy (HE) 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 LE subgroup, fed 33.3-66.6% of goal energy, showed a lower mortality than the HE 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 LE group. HE 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, an HE intake did not decrease the infections. No statistical differences were observed in other secondary outcomes. This meta-analysis indicates that HE intake does not improve outcomes and may increase complications in critically ill patients who are not malnourished. Initial moderate nutrient intake (33.3-66.6% of goal energy), compared to HE, may reduce mortality, and a higher protein intake combined with HE (≥0.85 g/kg/day) may decrease the infection rate. However, the contribution of energy versus protein intake to outcomes remains unknown.