Lower versus higher dose of enteral caloric intake in adult critically ill patients: A systematic review and meta-analysis

Background: There is conflicting evidence about the relationship between the dose of enteral caloric intake and survival in critically ill patients. The objective of this systematic review and meta-analysis is to compare the effect of lower versus higher dose of enteral caloric intake in adult critically ill patients on outcome. Methods: We reviewed MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from inception through November 2015. We included randomized and quasi-randomized studies in which there was a significant difference in the caloric intake in adult critically ill patients, including trials in which caloric restriction was the primary intervention (caloric restriction trials) and those with other interventions (non-caloric restriction trials). Two reviewers independently extracted data on study characteristics, caloric intake, and outcomes with hospital mortality being the primary outcome. Results: Twenty-one trials mostly with moderate bias risk were included (2365 patients in the lower caloric intake group and 2352 patients in the higher caloric group). Lower compared with higher caloric intake was not associated with difference in hospital mortality (risk ratio (RR) 0.953; 95 % confidence interval (CI) 0.838-1.083), ICU mortality (RR 0.885; 95 % CI 0.751-1.042), total nosocomial infections (RR 0.982; 95 % CI 0.878-1.077), mechanical ventilation duration, or length of ICU or hospital stay. Blood stream infections (11 trials; RR 0.718; 95 % CI 0.519-0.994) and incident renal replacement therapy (five trials; RR 0.711; 95 % CI 0.545-0.928) were lower with lower caloric intake. The associations between lower compared with higher caloric intake and primary and secondary outcomes, including pneumonia, were not different between caloric restriction and non-caloric restriction trials, except for the hospital stay which was longer with lower caloric intake in the caloric restriction trials. Conclusions: We found no association between the dose of caloric intake in adult critically ill patients and hospital mortality. Lower caloric intake was associated with lower risk of blood stream infections and incident renal replacement therapy (five trials only). The heterogeneity in the design, feeding route and timing and caloric dose among the included trials could limit our interpretation. Further studies are needed to clarify our findings.