Recommendations Summary
CI: Supplemental Glutamine 2012
Click here to see the explanation of recommendation ratings (Strong, Fair, Weak, Consensus, Insufficient Evidence) and labels (Imperative or Conditional). To see more detail on the evidence from which the following recommendations were drawn, use the hyperlinks in the Supporting Evidence Section below.
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Recommendation(s)
CI: Supplemental Enteral Glutamine
In the critically ill adult patient, the Registered Dietitian (RD) should not routinely recommend supplemental enteral glutamine. When studies of burn patients are excluded, research has not shown glutamine-supplemented enteral nutrition (EN) to be associated with reduced hospital length of stay (LOS), cost of medical care, days on mechanical ventilation or mortality. There is limited evidence that supplemental enteral glutamine is associated with reduced infectious complications in the trauma patient.
Rating: Fair
ImperativeCI: Supplemental Intravenous Glutamine
If a critically ill adult patient is receiving parenteral nutrition (PN), the Registered Dietitian (RD) should consider use of supplemental intravenous (IV) glutamine to reduce infectious complications. Research indicates that glutamine-supplemented PN reduced infectious complications in adult critically ill patients in four of five positive quality randomized controlled trials (RCTs). However, research shows that glutamine-supplemented PN does not reduce hospital length of stay (LOS) and there is no association between glutamine-supplementated PN and reduced cost of medical care, days on mechanical ventilation or mortality.
Rating: Strong
Conditional-
Risks/Harms of Implementing This Recommendation
- Use caution in fluid-restricted patients receiving supplemental IV glutamine outside the primary PN solution. A commercially available IV glutamine solution with a concentration of 2.5% is currently available; therefore an increased volume of fluid is required to provide effective dosing (McClave et al, 2009; Vanek et al, 2011).
- Use caution in patients who are at risk for hyperammonemia (hepatic dysfunction) or azotemia (renal dysfunction) (Sacks, 2003; and Vanek et al, 2011).
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Conditions of Application
- Availability and access to supplemental IV glutamine
- Ability to tolerate increased volume of fluid with supplemental IV glutamine.
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Potential Costs Associated with Application
- Additional cost of supplemental enteral and IV glutamine.
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Recommendation Narrative
In the evaluation of supplemental glutamine, all patients received PN. An analysis of patients receiving IV glutamine, without PN was not conducted. Studies of burn patients were not included in the evidence analysis.
A total of 17 studies were included in the evidence analysis for this recommendation:
- Twelve positive quality randomized controlled trials (RCTs) (Cai et al, 2008; Déchelotte et al, 2006; Estívariz et al, 2008; Fuentes-Orozco et al, 2004; Fuentes-Orozco et al 2008; Goeters et al, 2002; Griffiths et al, 2002; Griffiths and Jones, 1997; Hall et al, 2003; Houdijk et al, 1998; Kumar et al, 2007; and Ziegler et al, 2005)
- One positive quality non-randomized controlled trial (Schulman et al, 2006)
- Four neutral quality RCTs (Conejero et al, 2002; Powell-Tuck et al, 1999; Spindler-Vesel et al, 2007; and Yang and Xu, 2007).
Impact on Mortality in Critically Ill Adult Patients
- EN: Five studies show that the evidence does not support use of supplemental enteral glutamine (GLN) to reduce mortality in adult critically ill patients
- Evidence is based on the following studies: Conejero et al, 2002; Hall et al, 2003; Kumar et al, 2007; Schulman et al, 2006; and Spindler-Vesel et al, 2007
- IV: Based only on eight adequately powered studies, GLN-supplemented PN is unlikely to reduce intensive care unit (ICU) mortality in adult critically ill patients
- Evidence is based on the following studies: Cai et al, 2008; Déchelotte et al, 2006; Estívariz et al, 2008; Fuentes-Orozco et al, 2004; Fuentes-Orozco et al, 2008; Goeters et al, 2002; Griffiths et al, 2002; and Powell-Tuck et al, 1999.
Impact on Infectious Complications in Critically Ill Adult Patients
- EN: Six studies show that the balance of the evidence does not support use of supplemental enteral GLN to reduce infectious complications in adult critically ill patients
- Evidence is based on the following studies: Conejero et al, 2002; Hall et al, 2003; Houdjik et al, 1998; Kumar et al, 2007; Schulman et al, 2006; and Spindler-Vesel et al, 2007
- IV: Six studies provide evidence that GLN-supplemented PN reduced infectious complications in adult critically ill patients in four of five positive quality RCTs
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Evidence is based on the following studies: Déchelotte et al, 2006; Estívariz et al, 2008; Fuentes-Orozco et al, 2004; Fuentes-Orozco et al, 2008; Griffiths et al, 2002; and Yang and Xu, 2007.
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Impact on ICU LOS and Hospital LOS in Critically Ill Adult Patients
- EN: Three studies show that the evidence does not support the use of supplemental enteral GLN to reduce LOS in adult critically ill patients
- Evidence is based on the following studies: Conejero et al, 2002; Hall et al, 2003; and Houdjik et al, 1998
- IV: Nine studies provide evidence that GLN-supplemented PN does not reduce either ICU or hospital LOS in adult critically ill patients. Nine of 10 RCTs reported no difference in either hospital or ICU LOS with GLN added to PN.
- Evidence is based on the following studies: Cai et al, 2008; Déchelotte et al, 2006; Estívariz et al, 2008; Fuentes-Orozco et al, 2004; Fuentes-Orozco et al, 2008; Goeters et al, 2002; Powell-Tuck et al, 1999; Yang DL and Xu JF, 2007; and Ziegler et al, 2005.
Impact on Mechanical Ventilation Days in Critically Ill Adult Patients
- EN: Three studies show that the evidence does not support the use of supplemental enteral glutamine to reduce days on mechanical ventilation in adult critically ill patients
- Evidence is based on the following studies: Conejero et al, 2002; Houdjik et al, 1998; and Spindler-Vesel et al, 2007
- IV: Five studies provide evidence that IV GLN is unlikely to reduce days on mechanical ventilation in adult critically ill patients. Four of five RCTs reported no difference in mechanical ventilation days with GLN added to PN.
- Evidence is based on the following studies: Cai et al, 2008; Estívariz et al, 2008; Fuentes-Orozco et al, 2004; Fuentes-Orozco et al, 2008; and Ziegler et al, 2005.
Impact on Cost of Care in Critically Ill Adult Patients
- EN: There were no studies identified to evaluate supplemental enteral GLN and cost of care in adult critically ill patients
- IV: One study provides evidence that it is unclear whether IV GLN impacts cost of care in the ICU. An older study from the United Kingdom concluded that GLN-supplemented PN reduced costs in six-month survivors. However, methodologic concerns may limit generalizability.
- Evidence is based on the following study: Griffiths et al, 1997.
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Recommendation Strength Rationale
- Subjects were critically ill, trauma patients. Studies for IV glutamine were of primarily middle-aged and predominantly male subjects.
- Grade I evidence is available for the conclusion statements regarding the impact of supplemental IV glutamine in adult critically ill patients on infectious complications and ICU LOS and hospital LOS
- Grade II evidence is available for the conclusion statement regarding the impact of supplemental IV glutamine in critically ill adult patients on mechanical ventilation days
- Grade II evidence is available for conclusion statements regarding the impact of supplemental enteral glutamine in adult critically ill patients on:
- Mortality
- Infectious complications
- ICU LOS and hospital LOS
- Mechanical ventilation days
- Grade V evidence is available for the conclusion statement regarding the impact of supplemental IV glutamine on mortality and cost of care in adult critically ill patients.
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Minority Opinions
None.
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Risks/Harms of Implementing This Recommendation
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Supporting Evidence
The recommendations were created from the evidence analysis on the following questions. To see detail of the evidence analysis, click the blue hyperlinks below (recommendations rated consensus will not have supporting evidence linked).
In adult patients who are critically ill, does supplemental enteral glutamine impact mortality?
In adult patients who are critically ill, does supplemental enteral glutamine impact infectious complications?
In adult patients who are critically ill, does supplemental enteral glutamine impact ICU length of stay (LOS) and hospital LOS?
In adult patients who are critically ill, does supplemental enteral glutamine impact ventilator days?
In adult patients who are critically ill, does supplemental enteral glutamine impact cost of care?
In adult patients who are critically ill, does intravenous (IV) glutamine impact mortality?
In adult patients who are critically ill, does intravenous (IV) glutamine impact infectious complications?
In adult patients who are critically ill, does intravenous (IV) glutamine impact intensive care unitl (ICU) and hospital length of stay (LOS)?
In adult patients who are critically ill, does intravenous (IV) glutamine impact ventilator days?
In adult patients who are critically ill, does intravenous (IV) glutamine impact cost of care?-
References
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, multi-center study. Nutrition. 2002 Sep; 18 (9): 716-721.
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 Oct; 29(10): 1,710-1,716.
Houdijk AP, Rijnsburger ER, Jansen J, Wesdorp RI, Weiss JK, McCamish MA, Teerlink T, Meuwissen SG, Haarman HJ, Thijs LG, van Leeuwen PA. Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma. Lancet. 1998 Sep 5; 352(9,130): 772-776.
Kumar S, Kumar R, Sharma SB, Jain BK. Effect of oral glutamine administration on oxidative stress, morbidity and mortality in critically ill surgical patients. Indian J Gastroenterol. 2007 Mar-Apr; 26(2): 70-73.
Schulman AS, Willcutts KF, Claridge JA, O'Donnell KB, Radigan AE, Evans HL, McElearney ST, Hedrick TL, Lowson SM, Schirmer BD, Young JS, Sawyer RG. Does enteral glutamine supplementation decrease infectious morbidity? Surg Infect. 2006 Feb; 7(1): 29-35.
Spindler-Vesel A, Bengmark S, Vovk I, Cerovic O, Kompan L. Synbiotics, prebiotics, glutamine or peptide in early enteral nutrition: A randomized study in trauma patients. J Parenter Enteral Nutr. 2007 Mar-Apr; 31 (2): 119-126.
Cai G, Yan J, Zhang Z, Yu Y. Immunomodulatory effects of glutamine enriched nutritional support in elderly patients with severe sepsis: A prospective, randomized, controlled study. J Organ Dysfunction. 2008, 4: 31-37.
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 Mar; 34(3): 598-604.
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, CotsonisGA, 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 Jul-Aug; 32 (4): 389-402.
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 Feb; 23(1): 13-21.
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. J Parenter Enteral Nutr. 2008 Jul-Aug; 32 (4): 403-411.
Goeters C, Wenn A, Mertes N, Wempe C, Van Aken H, Stehle P, Bone HG. Parenteral L-alanyl-L-glutamine improves SIX-month outcome in critically ill patients. Crit Care Med. 2002 Sep; 30 (9): 2,032-2,037.
Griffiths RD, Allen KD, Andrews FJ, Jones C. Infection, multiple organ failure, and survival in the intensive care unit: Influence of glutamine-supplemented parenteral nutrition on acquired infection. Nutrition. 2002 Jul-Aug; 18(7-8): 546-552.
Powell-Tuck J, Jamieson CP, Bettany GE, Obeid O, Fawcett HV, Archer C, Murphy DL. A double-blind, randomized, controlled trial of glutamine supplementation in parenteral nutrition. Gut. 1999 Jul; 45 (1): 82-88.
Yang DL, Xu JF. Effect of dipeptide of glutamine and alanine on severe traumatic brain injury. Chin J Traumatol. 2007; 10(3): 145-149.
Ziegler TR, Ogden LG, Singleton KD, Luo M, Fernandez-Estivariz C, Griffith DP,Galloway JR, Wischmeyer PE. Parenteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Med. 2005 Aug; 31 (8): 1,079-1,086. Epub 2005 Jun 23.
Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition. 1997 Apr; 13 (4): 295-302. -
References not graded in Academy of Nutrition and Dietetics Evidence Analysis Process
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 May-Jun; 33(3): 277-316. No abstract available. PMID: 19398613.
Sacks GS. The data in support of glutamine supplementation. Nutr Clin Pract. 2003 Oct; 18 (5): 386-390. No abstract available. PMID: 16215070.
Vanek VW, Matarese LE, Robinson M, Sacks GS, Young LS, Kochevar M; Novel Nutrient Task Force, Parenteral Glutamine Workgroup; American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. A.S.P.E.N. position paper: parenteral nutrition glutamine supplementation. Nutr Clin Pract. 2011 Aug; 26 (4): 479-494. Epub 2011 Jun 22. No abstract available. PMID: 216975.
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References