Abstract
IntroductionGlutamine (GLN) has been suggested to have a beneficial influence on outcomes of critically ill patients. However, recent large-scale trials have suggested harm associated with GLN supplementation. Recently, systematic reviews on the use of parenteral GLN have been published; however, less information is available on the role of enteral GLN. Therefore, the aim of this systematic review was to study the effects of enteral GLN supplementation in patients with critical illness.MethodsWe identified randomized controlled trials conducted from 1980 to 2014 with enterally administered GLN in adult critically ill patients. Studies of parenteral GLN only or combined enteral-parenteral GLN were excluded. The methodological quality of studies was scored, and trial data were statistically combined. We examined a priori the treatment effects in subgroups of trials of burn and trauma patients.ResultsA total of 11 studies involving 1079 adult critically ill patients and enteral GLN supplementation were identified. Enteral GLN supplementation was not associated with a reduction of hospital mortality (risk ratio [RR] 0.94, 95 % confidence interval [CI] 0.65–1.36; p =0.74), infectious complications (RR 0.93, 95 % CI 0.79–1.10; p =0.39) or stay in the intensive care unit (weighted mean difference [WMD] −1.36 days, 95 % CI −5.51 to 2.78; p =0.52). However, there was a significant reduction in hospital stay (WMD 4.73 days, 95 % CI −8.53 to −0.90; p =0.02). In the subset of studies of patients with burns, enteral GLN supplementation was associated with significant reductions in hospital mortality (RR 0.19, 95 % 0.06–0.67; p =0.010) and hospital stay (WMD −9.16, 95 % CI −15.06 to −3.26; p =0.002). There was no effect in trauma patients.ConclusionsEnteral GLN supplementation does not confer significant clinical benefit in critically ill patients, with the exception of reduced hospital stay. There may be a significant benefit in patients with burns, but data are sparse and larger randomized trials are warranted to confirm this effect.
Highlights
Glutamine (GLN) has been suggested to have a beneficial influence on outcomes of critically ill patients
Enteral GLN supplementation was not associated with a reduction of hospital mortality, infectious complications (RR 0.93, 95 % confidence interval (CI) 0.79–1.10; p =0.39) or stay in the intensive care unit
Effect of enteral glutamine supplementation on hospital mortality When the data from 10 of the 11 total identified enteral nutrition (EN) GLN studies that reported on mortality (Fig. 1) were aggregated, enteral GLN supplementation was not associated with a reduction in hospital mortality (RR 0.94, 95 % CI 0.65–1.36; p =0.74; test for heterogeneity I2 = 21 %)
Summary
Glutamine (GLN) has been suggested to have a beneficial influence on outcomes of critically ill patients. Recent large-scale trials have suggested harm associated with GLN supplementation. The aim of this systematic review was to study the effects of enteral GLN supplementation in patients with critical illness. In catabolic and stress states that are commonly present in critically ill, trauma and burn patients, low plasma levels of GLN upon intensive care unit (ICU) admission have been encountered, leading to the assumption that these levels are too low for the actual medical condition and that GLN should be considered conditionally deficient [2]. The metabolic effects of GLN suggest a role in the inflammatory and oxidative stress responses [3]. On the basis of the association of low plasma GLN levels (
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