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

Abstract

IntroductionGuidelines 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.MethodWe 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.ResultsIn 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.ConclusionThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0902-0) contains supplementary material, which is available to authorized users.

Pathophysiology of Critical Illness and Role of Nutrition

“…Meta‐analysis and other reviews suggest that high‐calorie, low‐protein feeding increases complications in patients who are not malnourished. This points to the importance of protein supplementation in this group of patients.…”

High‐Protein Hypocaloric Nutrition for Non‐Obese Critically Ill Patients

“…The combined effects of these factors can largely explain why greater rates of nutrient provision, ie, protein provision, are frequently associated with better clinical outcomes. With regard to the potential benefits of permissive underfeeding, it seems likely that energy substrate resistance can make even minor energy overfeeding toxic in critical illness . Given the unreliability of existing methods for estimating energy expenditure in critical illness, coupled with uncertainty about exactly how much exogenous energy is toxic for a particular patient, the risk of inadvertent energy overfeeding is very real.…”

“…Differing magnitudes of these 3 effects, ie, sicker patients are more difficult to feed enterally, protein dose, and energy substrate resistance, coupled with the failure or inability of authors to identify or adjust for them in their analyses, may well explain why permissive underfeeding is associated with better outcomes in some observational studies but worse outcomes in others. The clinching evidence for this conclusion is provided by the many RCTs that compared high‐energy, protein‐deficient SNS with low‐energy, protein‐deficient SNS (permissive underfeeding) and found it of little or no benefit . In conclusion, the benefits of permissive underfeeding, when they occur, are not due to protein deprivation, but rather because it avoids energy overfeeding.…”

“…Thus, despite differences in protein doses and the timing of PN, both organizations suggest full energy provision. This is a problem, because full energy provision is physiologically irrational, risks energy toxicity and volume overload, and has repeatedly failed in large RCTs to benefit critically ill patients …”

“…7,23 It eventually became clear that the energy expenditure of most critically ill patients is not much increased, and that energy overfeeding, either with dextrose or fat, is potentially toxic for them. 1,6,7,12,[16][17][18][23][24][25][26][27][28][29][30][31][32][33][34] As the drawbacks of parenteral nutrition (PN) were becoming evident, enteral nutrition (EN) products and administration methods improved. Head-to-head comparisons between EN and PN suggested that EN was in general somewhat safer than PN, partly because of the ease of energy-overfeeding with PN 6,18 and partly because, until recently, energy overfeeding was unavoidable because of the low amino acids-to-dextrose ratio of available PN solutions.…”