Immunonutrition in the critically ill: A systematic review of clinical outcome

Objective: To perform a meta-analysis addressing whether enteral nutrition with immune-enhancing feeds benefits critically ill patients after trauma, sepsis, or major surgery. Data Sources: Studies were identified by MEDLINE search (1967 to January 1998) for original articles in English using the search terms "human," "enteral nutrition," "arginine," "nucleotides," "omega-3 fatty acids," "immunonutrition," "IMPACT," and "Immun-Aid." Additionally, the authors of the studies and the manufacturers of the feeds were contacted for additional information. Access to original databases was obtained for the three largest studies. Study Selection: Fifteen randomized controlled trials comparing patients receiving standard enteral nutrition with patients receiving a commercially available immune-enhancing feed with arginine with or without glutamine, nucleotides, and omega-3 fatty acids were identified by two independent reviewers (Dr. Beale and Dr. Bryg). Data Extraction: Descriptive and outcome data were extracted independently from the papers by the same two reviewers, one of whom (Dr. Bryg) analyzed the original databases. Three studies were excluded from analysis, leaving 12 studies containing 1,557 subjects, 1,482 of whom were analyzed. Main outcome measures were mortality, infection, ventilator days, intensive care unit stay, hospital stay, diarrhea days, calorie intake, and nitrogen intake. The meta-analysis was performed on an intent-to-treat basis. Data Synthesis: There was no effect of immunonutrition on mortality (relative risk = 1.05, confidence interval [CI] = 0.78, 1.41; p = .76). There were significant reductions in infection rate (relative risk = 0.67, CI = 0.50, 0.89; p = .006), ventilator days (2.6 days, CI = 0.1, 5.1; p = .04), and hospital length of stay (2.9 days, CI = 1.4, 4.4; p = .0002) in the immunonutrition group. Conclusions: The benefits of enteral immunonutrition were most pronounced in surgical patients, although they were present in all groups. The reduction in hospital length of stay and infections has resource implications.