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

Abstract

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.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and accompanying study flow diagram. RCT, randomised controlled trial.

Figure 2

Risk of bias summary: authors’ judgments regarding the risk of bias factor for each included study.

Figure 3

Funnel plots showing the impact of initial low energy intake on mortality. LE, low-energy; RR, risk ratio; SE, standard error.

Figure 4

Funnel plots showing the impact of initial low energy intake on infections. RR, risk ratio; SE, standard error.

Figure 5

Funnel plots showing the impact of initial low energy intake on pneumonia. LE, low-energy; RR, risk ratio; SE, standard error.

Figure 6

Impact of initial low energy intake on mortality. CI, confidence interval; LE, low energy; MH, Mantel-Haenszel.

Figure 7

Impact of initial low energy intake on infections. CI, confidence interval; MH, Mantel-Haenszel.

Figure 8

Impact of initial low energy intake on pneumonia. CI, confidence interval; LE, low energy; MH, Mantel-Haenszel.

Figure 9

Impact of initial low energy intake on gastrointestinal intolerance. CI, confidence interval; LE, low energy; MH, Mantel-Haenszel.

Figure 10

Impact of initial low energy intake on mechanical ventilation days. CI, confidence interval; IV, inverse variance; LE, low energy.