Glutamine enteral therapy for critically ill adult patients: An updated meta-analysis of randomized controlled trials and trial sequential analysis

Background: The efficacy of supplemental enteral glutamine (GLN) in critical illness patients remains uncertainty. Objective: Based on a recently published large-scale randomized controlled trials (RCTs) as regards the use of enteral GLN, we updated a meta-analysis of RCTs for further investigating the effects of enteral GLN administration in critically ill patients. Methods: We searched RCTs reporting the impact of supplemental enteral GLN about clinical outcomes in adult critical illness patients from EMBASE, PubMed, Clinical Trials.gov, Scopus and Web of Science and subsequently registered the protocol in the PROSPERO (CRD42023399770). RCTs of combined enteralparenteral GLN or parenteral GLN only were excluded. Hospital mortality was designated as the primary outcome. We conducted subgroup analyses of primary outcome based on specific patient populations, dosages and therapy regimens, and further performed trial sequential analysis (TSA) for clinical outcomes. Results: Eighteen RCTs involving 2552 adult critically ill patients were identified. There were no remarkable influences on hospital mortality regardless of different subgroups (OR, 1.05; 95% CI, 0.85 -1.30; p = 0.67), intensive care unit (ICU) length of stay (LOS) (MD, -0.07; 95% CI, -1.12 - 0.98; p = 0.89) and infectious complications (OR, 0.90; 95% CI, 0.75-1.10; p = 0.31) with enteral GLN supplementation. Additionally, the results of hospital mortality were confirmed by TSA. However, enteral GLN therapy was related to a reduction of hospital LOS (MD, -2.85; 95% CI, -5.27 to -0.43; p = 0.02). Conclusions: In this meta-analysis, it seems that enteral GLN supplementation is unlikely ameliorate clinical outcomes in critical illness patients except for the reduction of hospital LOS. Our data do not support enteral GLN supplementation used routinely in critical illness patients. (c) 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.