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Recommendations Summary

CI: Immune-Enhancing Enteral Nutrition and Critical Illness 2006

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: Immune-enhancing enteral nutrition

    Immune-enhancing EN is not recommended for routine use in critically ill patients in the ICU. Immune-enhancing EN is not associated with reduced infectious complications, LOS, reduced cost of medical care, days on mechanical ventilation or mortality in moderately to less severely ill ICU patients. Their use may be associated with increased mortality in severely ill ICU patients, although adequately-powered trials evaluating this have not been conducted. For the trauma patient, it is not recommended to routinely use immune-enhancing EN, as its use is not associated with reduced mortality, reduced LOS, reduced infectious complications or fewer days on mechanical ventilation.

    Rating: Fair
    Imperative

    • Risks/Harms of Implementing This Recommendation

      • Use of immune-enhancing EN in severely ill ICU patients may be associated with increased harm
      • There are mixed results and varying interpretations of the efficacy of immune-enhancing EN.

    • Conditions of Application

      • This recommendation applies to critically ill patients in an ICU setting
      • Pharmacological doses of single nutrients were not evaluated, therefore this recommendation only applies to immune-enhancing EN with more than one nutrient.

    • Potential Costs Associated with Application

      A greater cost is associated with using immune-enhancing EN, compared to standard EN.

    • Recommendation Narrative

      Mortality

      • Seven primary research articles showed no significant effect on mortality with the use of immune-enhancing EN
        • Three positive quality RCTs (Atkinson et al, 1998; Caparros et al, 2001; Kieft et al, 2005) and four neutral quality RCTs (Cerra et al, 1990; Moore et al, 1994; Bower et al, 1995; Weimann et al, 1998) agreed that mortality was not statistically impacted by immune-enhancing EN
          • The largest positive quality study, a prospective randomized, double-blind controlled intervention study of positive quality (Kieft et al, 2005), with a sample size of 597 ICU patients, showed no effect on mortality.
      • In contrast, two studies showed increased mortality with the use of immune-enhancing EN
        • A positive quality RCT (Bertolini et al, 2003) with 237 patients showed increased mortality with the use of immune-enhancing EN 
        • A positive quality prospective double-blind clinical trial (Atkinson et al, 1998), with 390 critically ill patients,  showed increased mortality with immune-enhancing EN, although not statistically significant.
      • One RCT of positive quality (Galban et al, 2000) demonstrated reduced mortality in critically ill patients who received immune-enhancing EN
      • Four positive-quality meta-analyses (Beale et al, 1999; Heyland et al, 2001; Heyland et al, 2003; Montejo et al, 2003) and one neutral quality meta-analysis (Heys et al, 1999) reported no statistically significant effect on mortality for those who received immune-enhancing EN
        • Although Heyland et al, 2001, reported no significant effect on mortality, in a subgroup analysis of higher quality studies of critically ill patients, Heyland found an increase in mortality in patients receiving immune-enhancing EN with higher arginine content (RR=2.13; 95% CI=1.08-4.21)
      • A meta-analysis of positive quality (Heyland et al, 2001), evaluating critically ill and elective surgical patients reported no significant effect on mortality.

      Infectious Complications

      • Three primary research articles, one positive quality (Keift, et al, 2005) and two neutral quality (Brown et al,  1994; Weimann et al, 1998) showed no reductions in infectious complications with immune-enhancing EN
        • The largest positive quality study, a prospective randomized, double-blind controlled intervention (Kieft et al, 2005) with 597 patients reported no benefit with immune-enhancing EN in reduction of infectious complications.
      • Five primary studies, two of positive quality (Galban et al,  2000; Caparros et al,  2001) and three of neutral quality (Moore et al, 1994; Bower et al, 1995; Kudsk et al, 1996) showed fewer infectious complications with the use of immune-enhancing EN 
        • In the Bower study, infections were decreased only in septic patients who received immune-enhancing EN.
      • Five meta-analyses reported mixed results in reducing infectious complications with immune-enhancing EN
        • Two positive quality meta-analyses (Heyland et al, 2003; Montejo et al, 2003) reported no significant effect on infectious complications
        • Two positive quality meta-analyses (Beale et al, 1999; Heyland et al, 2001) and one neutral quality meta-analysis (Heys et al,  1999) reported significant reductions in infectious complications.

      Length of Hospital Stay

      • Eight primary research articles showed no reductions in LOS with immune-enhancing EN
        • Two positive quality RCTs (Galban et al, 2000; Caparros et al, 2001) reported a higher LOS for the immune-enhancing EN groups, but this was not statistically significant
        • Another positive quality RCT (Bertolini et al, 2003) reported no statistically significant difference in LOS among 39 septic patients, although randomization of patients with severe sepsis was stopped early due to increased mortality
        • The largest positive quality study, a prospective randomized, double-blind controlled intervention (Kieft et al, 2005) with 597 patients, specifically designed to evaluate ICU LOS, reported no benefit with immune-enhancing EN
        • Four neutral quality studies (Cerra et al, 1990; Brown et al, 1994; Moore et al, 1994; Weimann et al, 1998) agreed that LOS was not impacted by immune-enhancing EN.
      • Three studies reported reductions in LOS with immune-enhancing EN
        • A positive quality RCT (Atkinson et al, 1998) in 390 critically ill patients reported no significant reduction in ICU or LOS for patients receiving immune-enhancing EN
          • A subgroup analysis of 101 patients receiving EEN reported significant reductions ICU and LOS.
      • Two neutral quality studies of adult trauma patients (Bower et al, 1995; Kudsk et al, 1996) demonstrated a decreased LOS with immune-enhancing EN 
      • Four positive quality meta-analyses (Beale et al, 1999; Heyland et al, 2001; Heyland et al, 2003; Montejo et al, 2003) and one neutral quality meta-analysis (Heys et al, 1999) reported significant reductions in LOS for those who received immune-enhancing EN
        • It should be noted that all the meta-analyses were conducted prior to publication of the largest positive quality study (Kieft et al, 2005).

      Days on Mechanical Ventilation

      • A positive quality prospective, double-blind clinical trial (Atkinson et al, 1998) showed that in patients who received adequate nutrition early, a decrease in mechanical ventilation days was shown with immune-enhancing EN
      • One positive quality meta-analysis (Heyland et al, 2003) found no difference in mechanical ventilation days
      • Two other positive quality meta-analyses (Beale et al, 1999; Montejo et al, 2003) found a significant reduction in mechanical ventilation days
      • Four primary research articles, two of positive quality (Galban et al, 2000; Keift et al, 2005) and two of neutral quality (Moore et al, 1994; Weimann et al, 1998) showed no reduction in days on mechanical ventilation with immune-enhancing EN
      • One neutral quality PRCT (Kudsk et al, 1996) reported no statistically significant reduction of days on mechanical ventilation
        • Although not statistically significant, patients fed immune-enhancing EN had reduced days on mechanical ventilation (2.4 vs. 6.4 days, p = .09).

      Cost of Medical Care

      • One positive quality meta-analysis (Montejo et al,  2003) found no statistically difference in cost of medical care
      • One neutral quality PRCT (Kudsk et al, 1996) of trauma patients showed no differences in medical costs between immune-enhancing EN and standard formulas.

    • Recommendation Strength Rationale

      • Trials of immune-enhancing 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
      • Conclusion statements are Grade II and III.