Should perioperative immune-modulating nutrition therapy be the standard of care? A systematic review

Abstract

Introduction: Major surgery carries a significant risk of postoperative infections, such as surgical site infections. An estimated 500,000 surgical site infections occur annually at a cost of more the $1 billion/year in the US alone. Surgical trauma leads to an initial excessive inflammatory response, together with an almost immediate and dramatic depression of cell‐mediated immunity. This immnosuppression may be due to a significant decrease in plasma arginine levels observed following surgery. This arginine deficiency can severely impair T‐cell proliferation and key T‐cell receptor function. Perioperative arginine administration can prevent arginine deficiency and restore cellular immunity. The purpose of this metaanalysis was to examine the relationship between immunemodulating enteral nutrition therapy (IMENT) containing arginine and infectious complications, length of stay, and mortality rates in surgical patients. Methods: All prospective randomized controlled trials of argininecontaining IMENT versus standard enteral nutrition in surgical patients conducted from 1990 to 2008 were identified from multiple databases. Studies included in the analysis evaluated infectious complication, length of stay, and/or mortality rates. Methodological quality of individual studies was scored and necessary data were abstracted in duplicate and independently. Results: Thirty randomized trials with a total of 2,789 patients compared the use of arginine‐containing IMENT with standard enteral nutrition in surgical patients. Arginine‐containing IMENT significantly decreased infectious complications (relative risk = 0.58, 95% CI = 0.48 to 0.69, P <0.00001) and overall length of stay (weighted mean difference = ‐2.09, 95% CI = ‐3.20 to ‐0.97, P = 0.0002) versus standard enteral nutrition. As expected in a low‐mortality surgical population, however, no effect was observed on mortality (relative risk = 1.06, 95% CI = 0.60 to 1.80, P = 0.84). Conclusions: The cumulative results show that arginine‐containing IMENT significantly reduces overall infections and length of stay in surgical patients. Based on this evidence, arginine‐containing IMENT could soon become the standard of care in the surgical patient. This large treatment effect demands definitive evaluation in a large multicenter trial.