[The impact of glutamine-enhanced enteral nutrition on clinical outcome of patients with critical illness: a systematic review of randomized controlled trials].

Objective: To systematically evaluate the influence of glutamine-enhanced enteral nutrition on clinical prognosis and treatment cost of patients with critical illness.

Methods: Randomized controlled trials (RCTs) since 1976 were searched in 8 biomedical databases, such as MEDLINE, EMBASE, SCI, Cochran Library, and Chinese Biomedicine Database. Bibliography of retrieved papers and personal files were searched as well. RCTs were evaluated with inclusion criteria: (1) RCTs were enrolled, parallel control was set up; (2) Patients with critical illness, with their acute physiology and chronic health evaluation score over 10, or with total burn surface area over 30%TBSA; (3) The only difference between experimental and control groups was the addition of glutamine in enteral nutrition; (4) Clinical outcome index included mortality, nosocomial infection rate, length of hospital stay, organ dysfunction rate, and treatment cost. Methodological quality of the study was assessed based on Cochrane Reviewers' Handbook and Jadad's Score Scale. Statistical software RevMan 5.0 was used for Meta-analysis.

Results: Among 224 related articles, 7 RCTs met all inclusion criteria. Mortality: death events among 545 patients were reported in 5 RCTs. There was no heterogeneity among the 5 RCTs (P = 0.46), relative risk (RR) = 0.94, 95% confidence interval (CI) 0.68 - 1.30, P = 0.70. No statistical difference was found between glutamine group and control group in respect of death risk (P > 0.05). Nosocomial infection rate:nosocomial infection events among 489 patients were reported in 3 RCTs. No heterogeneity was found among the 3 RCTs (P = 0.08). Fixed-effect model was applied. RR = 0.72, 95%CI 0.52 - 0.99, P = 0.04. Nosocomial infection rate of glutamine group was 28% lower than that of control group. Organ dysfunction rate: organ dysfunction events among 460 patients were reported in 3 RCTs. No heterogeneity was found among the 3 RCTs (P = 0.65). Fixed-effect model was applied. RR = 1.27, 95%CI 0.70 - 2.30, P = 0.43. No statistical difference was found between glutamine group and control group in respect of organ dysfunction rate (P > 0.05). Length of hospital stay:length of intensive care unit (ICU) stay of patients were reported in 4 RCTs, but 3 of them reported by median (interquartile ranges) and thus made Meta-analysis unavailable. No statistical difference was found between glutamine group and control group in respect of length of ICU stay. The other RCT reported length of ICU stay by mean standard deviation and showed no statistical difference between glutamine group and control group. Length of hospital stay was reported in 3 RCTs with severely burned patients. No heterogeneity was found among the 3 RCTs (P = 0.08). Fixed-effect model (Inverse Variance method) was applied, and it was shown that length of hospital stay of patients in glutamine group was 7.24 days fewer than that of control group by a mean difference of -7.24, 95%CI -13.28 to -1.19, P = 0.02.

Conclusions: Administration of Glutamine-enhanced enteral nutrition in patients with critical illness may reduce nosocomial infection rate, and shorten length of hospital stay. Studies with a large sample are needed to verify the efficiency of glutamine-enhanced enteral nutrition on lowering mortality of patients with critical illness and its cost-effectiveness.