Question 3

College Answer

Critically evaluate implies evaluation (including risk/benefit assessment) is required rather than just providing a list of constituents. Immunonutrition usually refers to enteral feeding formulae that have been enriched with a variety of pharmaconutrients.  These include arginine, glutamine, omega-3 fatty acids, nucleotides, or a combination (eg. in commercial products such as Alitraq and Impact). Multiple randomised studies involving thousands of patients, and more recently meta-analyses have been performed.   Studies have been heterogeneous with regard to patient groups and nutritional limbs, and results have been variable with regard to specific outcomes (eg. infectious complications and mortality).   Some consistent benefits appear to be observed (eg. decreased infectious complications, or length of hospital stay) but are contradicted in other studies.  Given the increased cost, the lack of consistent benefit, and the potential for harm, the overall role in the critically ill is still to be established. Recent literature includes:
·           Montejo JC et al. Immunonutrition in the intensive care unit. A systematic review and consensus statement. Clin Nutr. 2003 Jun;22(3):221-33.
·           Bertolini G et al. Early enteral immunonutrition in patients with severe sepsis: results of an interim   analysis   of   a   randomized   multicentre   clinical   trial.   Intensive   Care   Med.   2003
May;29(5):834-40.
·           Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA. 2001 Aug 22-
29;286(8):944-53.

Discussion

The wacky topic of immunonutrition is discussed in greater detail elsewhere.

• Introduction: why this technique is important/controversial
  • Immunonutrition is the use of pharmacologically active nutritional supplements to modify the stress response to critical illness, the immune response, and the inflammatory response.
• Rationale: why this technique is proposed, the physiological basis for it
  • The theoretical benefits of immunonutrition include improved wound healing, improved resistance to infection, improved recovery from critical illness, diminished inflammatory and stress responses, decreased organ damage due to oxidative stress and decreased length of ICU stay.
  • Immunonutrition has been proposed both for the critical care population as a whole, and for select groups of ICU patients, such as burns patients, high risk surgical patients, patients recovering from gastrointestinal surgery and patients with acute lung injury.
• Evidence: what the recent trials say
  • In 2008, Marik et al conducted a meta-analysis of RCTs and found a slight benefit in infection risk among patients supplemented with fish oil.
  • In 2010, Marik et al also published a systematic review which supported the use of fish oil supplements in high-risk surgical patients.
  • A 2011 review of immunonutrition in gastrointestinal surgery patients found some improvement in hospital stay and infectious morbidity, but not in mortality.
  • A 2012 trial comparing immunonutrition to routine practice among preoperatively malnoursihed patients found no difference in major outcome measures.
  • The ASPEN guidelines make the following statements:
    • No evidence to recommend arginine
    • No evidence to recommend fish oil or antioxidants
    • No evidence to recommend ornithine ketoglutarate
    • No evidence to recommend zink supplements
    • Some evidence to support the use of glutamine (this recommendation has been downgraded since 2009)
    • Some evidence to support selenium
• Advantages and disadvantages
  • Advantages of immunonutrition are thus far unproven, but there is community consensus that some immunonutrients (eg. glutamine) may have a beneficial effect.
  • Disadvantages of immunonutrients include cost and potential for harm (eg. with dangerous oversupplementation). Some immunonutrients may have a detrimental effect in certain patient populations (eg. glutamine supplementation appears to increase mortality among patients with multi-organ system failure)
• In summary, the practice of immunonutrition remains controversial for lack of strng supportive evidence, and the routine use of immunonutrition cannot be supported. However, there may be a trend towards decreased mortality in carefully selected patients.

The three papers cited by the college answer are somewhat dated:

Montejo, Juan C., et al. "Immunonutrition in the intensive care unit. A systematic review and consensus statement." Clinical Nutrition 22.3 (2003): 221-233.

Bertolini, Guido, et al. "Early enteral immunonutrition in patients with severe sepsis." Intensive care medicine 29.5 (2003): 834-840.

Heyland, Daren K., et al. "Should immunonutrition become routine in critically ill patients?: A systematic review of the evidence." Jama 286.8 (2001): 944-953.

There is more recent data:

Marik, Paul E., and Gary P. Zaloga. "Immunonutrition in High-Risk surgical patients a systematic review and analysis of the literature." Journal of Parenteral and Enteral Nutrition 34.4 (2010): 378-386.

Hübner, Ma, et al. "Preoperative immunonutrition in patients at nutritional risk: results of a double-blinded randomized clinical trial." European journal of clinical nutrition 66.7 (2012): 850-855.

Cerantola, Y., et al. "Immunonutrition in gastrointestinal surgery." British Journal of Surgery 98.1 (2011): 37-48.

Marik, Paul E., and Gary P. Zaloga. "Immunonutrition in critically ill patients: a systematic review and analysis of the literature." Intensive care medicine 34.11 (2008): 1980-1990.

Heyland, Daren, et al. "A randomized trial of glutamine and antioxidants in critically ill patients." New England Journal of Medicine 368.16 (2013): 1489-1497.