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Critical Care
Published in: Critical Care 1/2014

Open Access 01-02-2014 | Research

The effect of glutamine therapy on outcomes in critically ill patients: a meta-analysis of randomized controlled trials

Authors: Qi-Hong Chen, Yi Yang, Hong-Li He, Jian-Feng Xie, Shi-Xia Cai, Ai-Ran Liu, Hua-Ling Wang, Hai-Bo Qiu

Published in: Critical Care | Issue 1/2014

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Abstract

Introduction

Glutamine supplementation is supposed to reduce mortality and nosocomial infections in critically ill patients. However, the recently published reducing deaths due to oxidative stress (REDOX) trials did not provide evidence supporting this. This study investigated the impact of glutamine-supplemented nutrition on the outcomes of critically ill patients using a meta-analysis.

Methods

We searched for and gathered data from the Cochrane Central Register of Controlled Trials, MEDLINE, Elsevier, Web of Science and ClinicalTrials.gov databases reporting the effects of glutamine supplementation on outcomes in critically ill patients. We produced subgroup analyses of the trials according to specific patient populations, modes of nutrition and glutamine dosages.

Results

Among 823 related articles, eighteen Randomized Controlled Trials (RCTs) met all inclusion criteria. Mortality events among 3,383 patients were reported in 17 RCTs. Mortality showed no significant difference between glutamine group and control group. In the high dosage subgroup (above 0.5 g/kg/d), the mortality rate in the glutamine group was significantly higher than that of the control group (relative risk (RR) 1.18; 95% confidence interval (CI), 1.02 to 1.38; P = 0.03). In 15 trials, which included a total of 2,862 patients, glutamine supplementation reportedly affected the incidence of nosocomial infections in the critically ill patients observed. The incidence of nosocomial infections in the glutamine group was significantly lower than that of the control group (RR 0.85; 95% CI, 0.74 to 0.97; P = 0.02). In the surgical ICU subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.70; 95% CI, 0.52 to 0.94; P = 0.04). In the parental nutrition subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.83; 95% CI, 0.70 to 0.98; P = 0.03). The length of hospital stay was reported in 14 trials, in which a total of 2,777 patients were enrolled; however, the patient length of stay was not affected by glutamine supplementation.

Conclusions

Glutamine supplementation conferred no overall mortality and length of hospital stay benefit in critically ill patients. However, this therapy reduced nosocomial infections among critically ill patients, which differed according to patient populations, modes of nutrition and glutamine dosages.
Appendix
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Literature
1.
Lacey JM, Wilmore DW: Is glutamine a conditionally essential amino acid? Nutr Rev 1990, 48: 297-309.CrossRefPubMed
2.
Long CL, Borghesi L, Stahl R, Clark JA, Geiger JW, DiRienzo DB, Weis JK, Laws HL, Blakemore WS: Impact of enteral feeding of a glutamine-supplemented formula on the hypoaminoacidemic response in trauma patients. J Trauma 1996, 40: 97-102. 10.1097/00005373-199601000-00018CrossRefPubMed
3.
Parry-Billings M, Evans J, Calder PC, Newsholme EA: Does glutamine contribute to immunosuppression after major burns? Lancet 1990, 336: 523-525. 10.1016/0140-6736(90)92083-TCrossRefPubMed
4.
Oudemans-van Straaten HM, Bosman RJ, Treskes M, van der Spoel HJ, Zandstra DF: Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med 2001, 27: 84-90. 10.1007/s001340000703CrossRefPubMed
5.
Khan J, Iiboshi Y, Cui L, Wasa M, Sando K, Takagi Y, Okada A: Alanyl-glutamine-supplemented parenteral nutrition increases luminal mucus gel and decreases permeability in the rat small intestine. JPEN J Parenter Enteral Nutr 1999, 23: 24-31. 10.1177/014860719902300124CrossRefPubMed
6.
Gianotti L, Alexander JW, Gennari R, Pyles T, Babcock GF: Oral glutamine decreases bacterial translocation and improves survival in experimental gut-origin sepsis. JPEN J Parenter Enteral Nutr 1995, 19: 69-74. 10.1177/014860719501900169CrossRefPubMed
7.
Inoue Y, Grant JP, Snyder PJ: Effect of glutamine-supplemented intravenous nutrition on survival after Escherichia coli-induced peritonitis. JPEN J Parenter Enteral Nutr 1993, 17: 41-46. 10.1177/014860719301700141CrossRefPubMed
8.
Ardawi MS: Effect of glutamine-enriched total parenteral nutrition on septic rats. Clin Sci (Lond) 1991, 81: 215-222.CrossRef
9.
Saito H, Furukawa S, Matsuda T: Glutamine as an immunoenhancing nutrient. JPEN J Parenter Enteral Nutr 1999, 23: S59-S61. 10.1177/014860719902300515CrossRefPubMed
10.
Buchman AL: Glutamine: is it a conditionally required nutrient for the human gastrointestinal system? J Am Coll Nutr 1996, 15: 199-205. 10.1080/07315724.1996.10718590CrossRefPubMed
11.
Estívariz CF, Griffith DP, Luo M, Szeszycki EE, Bazargan N, Dave N, Daignault NM, Bergman GF, McNally T, Battey CH, Furr CE, Hao L, Ramsay JG, Accardi CR, Cotsonis GA, Jones DP, Galloway JR, Ziegler TR: Efficacy of parenteral nutrition supplemented with glutamine dipeptide to decrease hospital infections in critically ill surgical patients. JPEN J Parenter Enteral Nutr 2008, 32: 389-402. 10.1177/0148607108317880PubMedCentralCrossRefPubMed
12.
Pérez-Bárcena J, Regueiro V, Marsé P: Glutamine as a modulator of the immune system of critical care patients: effect on Toll-like receptor expression. A preliminary study. Nutrition 2008, 24: 522-527. 10.1016/j.nut.2008.01.056CrossRefPubMed
13.
Fuentes-Orozco C, Cervantes-Guevara G, Muciño-Hernández I, López-Ortega A, Ambriz-González G, Gutiérrez-de-la-Rosa JL, Gómez-Herrera E, Hermosillo-Sandoval JM, González-Ojeda A: L-alanyl-L-glutamine-supplemented parenteral nutrition decreases infectious morbidity rate in patients with severe acute pancreatitis. JPEN J Parenter Enteral Nutr 2008, 32: 403-411. 10.1177/0148607108319797CrossRefPubMed
14.
Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG, Canadian Critical Care Trials Group: A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 2013, 368: 1489-1497. 10.1056/NEJMoa1212722CrossRefPubMed
15.
Andrews PJ, Avenell A, Noble DW, Campbell MK, Croal BL, Simpson WG, Vale LD, Battison CG, Jenkinson DJ, Cook JA, Scottish Intensive care Glutamine or seleNium Evaluative Trial Trials Group: Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ 2011, 342: d1542. 10.1136/bmj.d1542CrossRefPubMed
16.
Hozo SP, Djulbegovic B, Hozo I: Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005, 5: 13. 10.1186/1471-2288-5-13PubMedCentralCrossRefPubMed
17.
Bollhalder L, Pfeil AM, Tomonaga Y, Schwenkglenks M: A systematic literature review and meta-analysis of randomized clinical trials of parenteral glutamine supplementation. Clin Nutr 2013, 32: 213-223. 10.1016/j.clnu.2012.11.003CrossRefPubMed
18.
Griffiths RD, Jones C, Palmer TE: Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 1997, 13: 295-302.PubMed
19.
Jones C, Palmer TE, Griffiths RD: Randomized clinical outcome study of critically ill patients given glutamine-supplemented enteral nutrition. Nutrition 1999, 15: 108-115. 10.1016/S0899-9007(98)00172-5CrossRefPubMed
20.
Conejero R, Bonet A, Grau T, Esteban A, Mesejo A, Montejo JC, López J, Acosta JA: Effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity at 28 days in critically ill patients with systemic inflammatory response syndrome: a randomized, single-blind, prospective, multicenter study. Nutrition 2002, 18: 716-721. 10.1016/S0899-9007(02)00847-XCrossRefPubMed
21.
Wischmeyer PE, Lynch J, Liedel J, Wolfson R, Riehm J, Gottlieb L, Kahana M: Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med 2001, 29: 2075-2080. 10.1097/00003246-200111000-00006CrossRefPubMed
22.
McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, Taylor B, Ochoa JB, Napolitano L, Cresci G, A.S.P.E.N. Board of Directors, American College of Critical Care Medicine, Society of Critical Care Medicine: Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2009, 33: 277-316. 10.1177/0148607109335234CrossRefPubMed
23.
Schulman AS, Willcutts KF, Claridge JA, Evans HL, Radigan AE, O'Donnell KB, Camden JR, Chong TW, McElearney ST, Smith RL, Gazoni LM, Farinholt HM, Heuser CC, Lowson SM, Schirmer BD, Young JS, Sawyer RG: Does the addition of glutamine to enteral feeds affect patient mortality? Crit Care Med 2005, 33: 2501-2506. 10.1097/01.CCM.0000185643.02676.D3CrossRefPubMed
24.
Fuentes-Orozco C, Anaya-Prado R, González-Ojeda A, Arenas-Márquez H, Cabrera-Pivaral C, Cervantes-Guevara G, Barrera-Zepeda LM: L-alanyl-L-glutamine-supplemented parenteral nutrition improves infectious morbidity in secondary peritonitis. Clin Nutr 2004, 23: 13-21. 10.1016/S0261-5614(03)00055-4CrossRefPubMed
25.
Marik PE, Zaloga GP: Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med 2008, 34: 1980-1990. 10.1007/s00134-008-1213-6CrossRefPubMed
26.
Goeters C, Wenn A, Mertes N, Wempe C, Van Aken H, Stehle P, Bone HG: Parenteral L-alanyl-L-glutamine improves 6-month outcome in critically ill patients. Crit Care Med 2002, 30: 2032-2037. 10.1097/00003246-200209000-00013CrossRefPubMed
27.
Hall JC, Dobb G, Hall J, de Sousa R, Brennan L, McCauley R: A prospective randomized trial of enteral glutamine in critical illness. Intensive Care Med 2003, 29: 1710-1716. 10.1007/s00134-003-1937-2CrossRefPubMed
28.
Falcão de Arruda IS, de Aguilar-Nascimento JE: Benefits of early enteral nutrition with glutamine and probiotics in brain injury patients. Clin Sci (Lond) 2004, 106: 287-292. 10.1042/CS20030251CrossRef
29.
Déchelotte P, Hasselmann M, Cynober L, Allaouchiche B, Coëffier M, Hecketsweiler B, Merle V, Mazerolles M, Samba D, Guillou YM, Petit J, Mansoor O, Colas G, Cohendy R, Barnoud D, Czernichow P, Bleichner G: L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study. Crit Care Med 2006, 34: 598-604. 10.1097/01.CCM.0000201004.30750.D1CrossRefPubMed
30.
Pérez-Bárcena J, Crespí C, Regueiro V, Marsé P, Raurich JM, Ibáñez J, García de Lorenzo-Mateos A, Bengoechea JA: Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit. Crit Care 2010, 14: R233. 10.1186/cc9388PubMedCentralCrossRefPubMed
31.
Wernerman J, Kirketeig T, Andersson B, Berthelson H, Ersson A, Friberg H, Guttormsen AB, Hendrikx S, Pettilä V, Rossi P, Sjöberg F, Winsö O, Scandinavian Critical Care Trials Group: Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients. Acta Anaesthesiol Scand 2011, 55: 812-818. 10.1111/j.1399-6576.2011.02453.xCrossRefPubMed
32.
Grau T, Bonet A, Miñambres E, Piñeiro L, Irles JA, Robles A, Acosta J, Herrero I, Palacios V, Lopez J, Blesa A, Martínez P, Metabolism, Nutrition Working Group, SEMICYUC, Spain: The effect of L-alanyl-L-glutamine dipeptide supplemented total parenteral nutrition on infectious morbidity and insulin sensitivity in critically ill patients. Crit Care Med 2011, 39: 1263-1268. 10.1097/CCM.0b013e31820eb774CrossRefPubMed
33.
Heyland DK, Dhaliwal R: Role of glutamine supplementation in critical illness given the results of the REDOXS study. JPEN J Parenter Enteral Nutr 2013, 37: 442-443. 10.1177/0148607113488421CrossRefPubMed
34.
Rodas PC, Rooyackers O, Hebert C, Norberg Å, Wernerman J: Glutamine and glutathione at ICU admission in relation to outcome. Clin Sci (Lond) 2012, 122: 591-597. 10.1042/CS20110520CrossRef
Metadata
Title
The effect of glutamine therapy on outcomes in critically ill patients: a meta-analysis of randomized controlled trials
Authors
Qi-Hong Chen
Yi Yang
Hong-Li He
Jian-Feng Xie
Shi-Xia Cai
Ai-Ran Liu
Hua-Ling Wang
Hai-Bo Qiu
Publication date
01-02-2014
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2014
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc13185

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