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Recommendations Summary

CI: Immune-Modulating Enteral Nutrition 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: Enteral Formulas Containing Immune-Modulating Nutrients in Patients Without ARDS or Acute Lung Injury

    For intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS),  acute lung injury or severe sepsis, the Registered Dietitian (RD) should carefully evaluate using immune-modulating enteral formulas containing some combination of arginine, glutamine, nucleotides, antioxidants and fish oil. Some primary studies and meta-analyses with mixed populations have shown benefits in reducing infectious complications and hospital length of stay (LOS). Research is inconclusive regarding reducing cost of medical care, days on mechanical ventilation, or mortality for mixed ICU patients, including surgical and trauma patients. Research on patients with ARDS or acute lung injury was not included in this analysis.

    Rating: Fair
    Conditional

    CI: Enteral Formulas Containing Immune-Modulating Nutrients in Patients with ARDS or Acute Lung Injury

    For intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS) or acute lung injury, the Registered Dietitian (RD) may consider using immune-modulating enteral formulas with fish oil,  borage oil and antioxidants.

    Rating: Strong
    Conditional

    • Risks/Harms of Implementing This Recommendation

      Use of immune-modulating EN containing arginine in severely ill, septic ICU patients may be associated with increased mortality.

    • Conditions of Application

      • CI: Enteral Formulas Containing Immune-Modulating Nutrients in Patients without ARDS or Acute Lung Injury: This recommendation applies to critically ill patients without ARDS, acute lung injury or severe sepsis in an ICU setting
      • CI: Enteral Formulas Containing Immune-Modulating Nutrients in Patients with ARDS or Acute Lung Injury: This recommendation applies to critically ill patients with ARDS or Acute Lung Injury in an ICU setting
      • Pharmacological doses of single nutrients were not evaluated, therefore this recommendation only applies to immune-modulating EN with more than one nutrient.

    • Potential Costs Associated with Application

      Immune-modulating formulas are more costly than standard enteral formulas.

    • Recommendation Narrative

      After review of the recommendation, the expert work group determined that recent evidence  would not affect this statement. Thus, the CI: Enteral Formulas Containing Immune-Modulating Nutrients in Patients without ARDS or Acute Lung Injury recommendation is based on the original evidence analysis and the 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.). The CI: Enteral Formulas Containing Immune-Modulating Nutrients in Patients with ARDS or Acute Lung Injury recommendation is based on the A.S.P.E.N./SCCM Guidelines only (McClave et al, 2009). Please see the methodology for guideline revisions for more information.

      CIU: Enteral Formulas Containing Immune-Modulating Nutrients in ICU Patients without ARDS or Acute Lung Injury 

      A total of 16 studies were included in the evidence analysis for this recommendation:

      • Six positive quality randomized controlled trials (RCTs) (Atkinson et al, 1998; Bertolini et al, 2003; Caparros et al, 2001; Galban et al, 2000; Kieft et al, 2005; and Montejo et al, 2003) 
      • Three positive quality meta-analyses/systematic reviews (Beale et al, 1999; Heyland et al, 2003; and Heyland et al, 2001) 
      • Six neutral quality RCTs (Bower et al, 1995; Brown et al, 1994; Cerra et al, 1990; Kudsk et al,  1996; Moore et al, 1994; and Weimann et al, 1998) 
      • One neutral quality meta-analysis (Heys et al, 1999). 

      Mortality

      • Twelve studies provide evidence that:
        • The addition of immune-modulating EN to enteral feeding of severely ill ICU patients may be associated with increased mortality,  though adequately powered trials have not been conducted
        • The addition of immune-modulating EN to enteral feeding of moderate or less severely ill ICU patients demonstrates no effect on mortality
      • Evidence is based on the following studies: Atkinson et al, 1998; Beale et al, 1999; Bertolini et al, 2003; Bower et al, 1995; Caparros et al, 2001; Cerra et al, 1990; Galban et al, 2000; Heys et al, 1999; Heyland et al, 2003; Heyland et al, 2001; Kieft et al, 2005; Montejo et al, 2003; Moore et al, 1994; and Weimann et al, 1998. 

      Infectious Complications

      • Thirteen studies provide evidence that the use of immune-modulating EN in some critically ill ICU patients has shown benefit in reducing infectious complications in some patients
      • Evidence is based on the following studies: Beale et al, 1999; Bower et al, 1995; Brown et al, 1994; Caparros et al, 2001; Galban et al, 2000; Heyland et al, 2003; Heyland et al, 2001; Heys et al, 1999; Kieft et al, 2005; Kudsk et al,  1996; Montejo et al, 2003;  Moore et al, 1994; and Weimann et al, 1998.

      Hospital Length of Stay

      • Sixteen studies provide evidence that the addition of immune-modulating EN to enteral feeding of critically ill ICU patients has limited impact on LOS
      • Evidence is based on the following studies: Atkinson et al, 1998; Beale et al, 1999; Bertolini et al, 2003; Bower et al, 1995; Brown et al, 1994; Caparros et al, 2001; Cerra et al, 1990; Galban et al, 2000; Heyland et al, 2003; Heyland et al, 2001; Heys et al, 1999; Kieft et al, 2005; Kudsk et al,  1996; Montejo et al, 2003; Moore et al, 1994; and Weimann et al, 1998.

      Days on Mechanical Ventilation

      • Nine studies provide evidence that the addition of immune-modulating EN to enteral feeding of critically ill ICU patients is not associated with reduced number of days on mechanical ventilation
      • Evidence is based on the following studies: Atkinson et al, 1998; Beale et al, 1999; Galban et al, 2000; Heyland et al, 2003; Kieft et al, 2005; Kudsk et al,  1996; Montejo et al, 2003; Moore et al, 1994; and Weimann et al, 1998. 

      Cost of Medical Care

      • Two studies provide evidence that the addition of immune-modulating EN to enteral feeding of critically ill ICU patients is not associated with reduced cost of medical care 
      • Evidence is based on the following studies: Kudsk et al,  1996; and Montejo et al, 2003.

      The following statement is included in Selection of Appropriate Enteral Formulation (McClave et al, 2009) and supports the recommendation CIU: Enteral Formulas Containing Immune-Modulating Nutrients in Patients without ARDS or Acute Lung Injury:

      • E1. Immune-modulating enteral formulations (supplemented with agents such as arginine, glutamine, nucleic acid, omega-3 fatty acids, and antioxidants) should be used for the appropriate patient population (major elective surgery, trauma, burns, head and neck cancer, and critically ill patients on mechanical ventilation), with caution in patients with severe sepsis.
        • (For surgical ICU patients, Grade: A)
        • (For medical ICU patients, Grade: B)
        • ICU patients not meeting criteria for immune-modulating formulations should receive standard enteral formulations (Grade: B).

      CIU: Enteral Formulas Containing Immune Modulating Nutrients in Patients with ARDS or Acute Lung Injury

      The following statement is included in Selection of Appropriate Enteral Formulation (McClave et al, 2009) and supports the recommendation CIU: Enteral Formulas Containing Immune Modulating Nutrients in Patients with ARDS or Acute Lung Injury:

      • E2. Patients with ARDS and severe acute lung injury (ALI) should be placed on an enteral formulation characterized by an anti-inflammatory lipid profile (i.e., n-3 fish oils, borage oil) and antioxidants (Grade: A).

    • Recommendation Strength Rationale

      • The Academy of Nutrition and Dietetics (A.N.D.) Critical Illness Expert Work Group concurs with the 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.). The Critical Illness Expert Work Group approved the following equivalency scale:

        • Grading System Used by SCCM/A.S.P.E.N. Guidelines, 2009 compared to The Academy's Evidence Analysis Library (EAL):

          • A: Supported by at least two level I investigations (EAL Rating Equivalent: Strong)
          • B: Supported by one level I investigation (EAL Rating Equivalent: Fair)
          • C: Supported by level II investigations only (EAL Rating Equivalent: Fair)
          • D: Supported by at least two level III investigations (EAL Rating Equivalent: Weak)
          • E: Supported by level IV or level V evidence (EAL Rating Equivalent: Consensus).
      • Trials of immune-modulating EN have not been designed with a large enough sample size to adequately evaluate mortality
      • The population of critically ill adult trauma patients was consistent across the studies included in the evidence analysis
      • The CI: Enteral Formulas Containing Immune Modulating Nutrients in Patients without ARDS or Acute Lung Injury recommendation is based on the following:  
        • Grades II evidence for the conclusion statements regarding:
          • Impact of the addition of immune-modulating EN to enteral feeding on mortality in moderately to severely ill ICU patients
          • Impact of the addition of immune-modulating EN to enteral feeding on days on mechanical ventilation and LOS in critically ill ICU patients
        • Grade III evidence for the conclusion statements regarding:
          • Impact of the addition of immune-modulating EN to enteral feeding on mortality in severely ill ICU patients 
          • Impact of the addition of immune-modulating EN to enteral feeding on infectious complications and cost of medical care in critically ill ICU patients
        • Grade A evidence (McClave et al, 2009) for surgical ICU patients (EAL Rating Equivalent: Strong) and Grade B evidence for medical ICU patients and ICU patients not meeting criteria for immune-modulating formulations (EAL Rating Equivalent: Fair).
      • The CI: Enteral Formulas Containing Immune Modulating Nutrients in Patients with ARDS or Acute Lung Injury recommendation is based on Grade A evidence (EAL Rating Equivalent: Strong).

    • Minority Opinions

      None.