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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.


  • 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
    Imperative

    CI: 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).

    • Conditions of Application

      • Availability and access to supplemental IV glutamine
      • Ability to tolerate increased volume of fluid with supplemental IV glutamine.

    • Potential Costs Associated with Application

      • Additional cost of supplemental enteral and IV glutamine. 

    • 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

        • 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.

      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. 

    • 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.

    • Minority Opinions

      None.