S roberts ebr

Scott Roberts BS, LPN, DTRProf. Anne Davis, PhD, RD06/26/2012GI Nutritional Therapy Evidence-Based Review

1NUTR590: Gastrointestinal Nutrition

The patient with gastrointestinal cancer always has an increased risk of developing malnutrition for several reasons, including;

Mechanical obstruction

Limitation of food intake,

Tumor-induced cachexia

Obstruction of pancreaticobiliary

Malabsorption

Ongoing blood loss

Malnutrition depresses both cellular immunity and humoral

immunity. In addition, complex surgical procedures and injury can potentially lead to immunity dysfunction (1).

2NUTR590: Gastrointestinal

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Multiple factors have an effect on the outcome of treatment, such as;

Antibacterial drugs

Immunoenhancers such as naltrexone or Imunovir

Aseptic techniques

Surgical skills

Immunonutrition may be useful in decreasing infection rates in patients undergoing gastrointestinal surgery, especially those with malnutrition-related immune depression.

The addition of immune-modulating nutrients such as n-3 fatty acids, arginine, and nucleotides to enteral formulas has been examined in numerous clinical trials.


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The aim of this review is to evaluate the current scientific evidence of available research on the infectious outcomes from immunonutrition applied in major UGI surgical patients.


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PubMed and Medline were the search engines used in June of 2012

The key search terms:

Enteral nutrition Parenteral nutrition Major upper gastrointestinal surgery Cancer Immunonurtrition, Arginine N-3 fatty acids Nucleotides


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Inclusion Criteria:

Major UGI cancer surgeries Resections of esophagus stomach, and pancreas liver transplantation. Both parenteral and nutrition routs where evaluated. Postoperative infections to be evaluated were: Infection at surgical site Systemic infections Pneumonia. The search was restricted to human studiesStudy designs included were limited to: clinical trials meta-analysis systematic analysis Cochrane reviews Randomized clinical trials (RCTs)Only publications in English, were included Only core clinical journals were evaluated.


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Exclusion Criteria

Other types GI surgeries were not considered and studies involving them were excluded.

Articles using formulas without all three substrates of arginine, n-3 fatty acids, and nucleotied were excluded from the review

Case reports as well as reviews were also excluded from comparison as where non-English publications.


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Articles collected◦ 11◦ All were randomized control trial (RCT)

Articles included◦ 7◦ RCT

Articles excluded◦ 4◦ RCT◦ The remaining 4 RCTs evaluated were not specific

enough to the study question. For example, they looked at other GI and head and neck cancer surgeries but not major UGI surgeries. For this reason these studies were excluded


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The outcomes of the included trials of immunonutrition in UGI cancer (Table 1) were substantially flawed in their study designs.

Few patients, especially in the earliest studies, received goal feedings.

Researchers had published 2 main protocols: either preoperative + postoperative nutrition with a control group or a postoperative-feeding only strategy without a control group.

Table 1 displays a benefit of immunonutrition for infectious complications in UGI cancer patients undergoing surgery.


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Among the exclude articles were several studies with results worth noting (Table 2).

The study by Braga et al (11) focused on a study population with weight losses of > 10% of body weight over the preceding 6 months, were randomly assigned to 3 different treatments:

1) preoperative and postoperative immunonutrition 2) preoperative immunonutrition plus postoperative control solution 3) postoperative control solution only

The group receiving immunonutrition both before and after surgery had fewer complications than did those fed the control solution postoperatively.

Although statistically significant, the clinical significance of immunonutrition both before and after surgery in malnourished patients showed a trend toward the best outcomes.

Riso et al were the only other authors to consider the most malnourished patients independently (12).

Their study of head and neck cancer patients showed no overall benefit of immunonutrition; however the malnourished subgroups provided immunonutrition versus control benefited in terms of infectious and wound complications (12).


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A significant benefit of immunonutrition for postoperative infections and length of stay was found in the majority of studies evaluated.

The most common flaw was a failure to deliver an adequate nutrition volume.

When feeding volumes are low, immunonutrition is usually not better than an isonitrogenous control.

In more recent studies, practitioners have been increasingly aggressive with enteral feeding, and this has been reflected in improved outcomes from immunonutrition.

Early delivery of immunonutrition (preoperatively in surgical patients with cancer) might be particularly beneficial.


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The most popular formulas studied in this context are Impact (Novartis Nutrition, Minneapolis) and Immun-Aid (B Braun, Irvine, CA). Of the articles considered in this review, 10 out of the 11 used Impact as their formula of choice (Table 3).

Table 3: Impact Formula: Novartis Nutrition, Minneapolis


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After compiling the data of the various study designs, there were several strategies mentioned to maximize the success of immunonutrition formulas; they are as follows:

1) Arginine should be > 12 g/L

2) Duration should be > 3 d, preferably 5–10 d

3) Nasogastric feeding should be used aggressively, with nursing protocols to advance feeding every 4–6 h, and gastric residuals of >200 mL should be accepted

4) Feeding goals should approach 25 kcal/kg, and ≥ 800 mL/d should be given for optimum outcome.


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Limitations

Articles selected were all earlier studies which is due to the lack of current research focused specifically on the immunonutrition effect on major UGI surgeries.

Review was conduction over the course of only 6 weeks which is a limited amount of time to compile research data.


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Strengths

The primary strength of this review was that 7 articles were directly related to and evaluated the implications of immunonutrition in major UGI cancer surgeries.

All studies were RCTs


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I found this evidence to be fair.

The research evaluated shows the potential benefit of immunonutrition in preventing the occurrence of postoperative infections in major UGI surgeries involving cancer.

After reviewing the research, it is my belief that the benefits of the use of immuonutrition in this specific population exceed the harms, although quality evidence is still elusive.

In clearly identified circumstances the use of immuonutritionmay be made based on lesser evidence when high-quality evidence is still absent.

Practitioners should consider immuonutrition in major UGI surgeries involving cancer but remain alert to new information and be sensitive to individual patient needs.


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Future research should evaluate whether these patients benefit from preoperative supplementation with an immune-enhancing formula or whether they require postoperative continuation (perioperative approach) to combat their risk of complications after surgery and if these formulae can be used safely in those patients who develop sepsis.


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1. Harry C. Sax, MD. Immunonutrition and Upper Gastrointestinal Surgery: What Really Matters. Nutrition in Clinical Practice 2005; 20: 540–543.

2. Daly JM, Lieberman MD, Goldfine J, et al. Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome. Surgery 1992;112:56–67.

3. Daly JM, Weintraub FN, Shou J, Rosato EF, Lucia M. Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients. Ann Surg 1995;221:327–38.

4. Gianotti L, Braga M, Nespoli L, Radaelli G, Beneduce A, Di Carlo V. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterology 2002;122:1763–70.

5. Heslin MJ, Latkany L, Leung D, et al. A prospective, randomized trial of early enteral feeding after resection of upper gastrointestinal malignancy. Ann Surg 1997;226:567–77.

6. Schilling J, Vranjes N, Fierz W, et al. Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotideenriched enteral feeding: a randomized prospective comparison with standard enteraland low calorie/low fat i.v. solutions. Nutrition 1996;

12:423–9.

7. Senkal M, Mumme A, Eickhoff U, et al. Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients. Crit Care Med 1997;25:1489–96.

8. Senkal M, Zumtobel V, Bauer KH, et al. Outcome and cost-effectiveness of perioperative enteralimmunonutrition in patients undergoing elective upper gastrointestinal tract surgery: a prospective randomized study. Arch Surg 1999;134:1309–16.

9. Snyderman CH, Kachman K, Molseed L, et al. Reduced postoperative

infections with an immune-enhancing nutritional supplement. Laryngoscope 1999;109:915–21.

10. Braga M, Gianotti L, Nespoli L, Radaelli G, Di Carlo V. Nutritional approach in malnourished surgical patients: a prospective randomized study. Arch Surg 2002;137:174–80.

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11.Braga M, Gianotti L, Radaelli G, et al. Perioperative immunonutrition in patients undergoing cancer surgery: results of a randomized double-blind phase 3 trial. Arch Surg 1999;134:428–33.

12. Riso S, Aluffi P, Brugnani M, Farinetti F, Pia F, D’Andrea F. Postoperative enteralimmunonutrition in head and neck cancer patients. Clin Nutr 2000;19:407–12.

13. Merimee TJ, Rabinowitz S, Fineberg SE. Arginine-initiated release of human growth hormone. Factors modifying the response in normal man. N Engl J Med 1969;280:1434–8.

14. Barbul A. Arginine: biochemistry, physiology, and therapeutic implications. JPEN J ParenterEnteral Nutr 1986;10:227–38

15. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993;329:2002–12

16. Daly JM, Reynolds J, Thom A, et al. Immune and metabolic effects of arginine in the surgical patient. Ann Surg 1988;208:512–23. .

17. Billiar TR, Bankey PE, Svingen BA, et al. Fatty acid intake and Kupffer cell function: fish oil alters eicosanoid and monokine production to endotoxin stimulation. Surgery 1988;104:343–9.

18. Calder PC. Sir David Cuthbertson Medal Lecture. Immunomodulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids. Proc Nutr Soc 1996;55:737–45.

19. Sheldon TA. Systematic reviews and meta-analyses: the value for surgery. Br J Surg 1999; 86: 977-978.

20. Grimble GK: Dietary nucleotides and gut mucosal defence. Gut 1994; 35:S46-5.


21. McClave SA, Martindale RG, Vanek VW et al. 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. 33, 277–316 (2009).

22. Kreymann KG, Berger MM, Deutz NEP et al. ESPEN guidelines on enteral nutrition: intensive care. Clin. Nutr. 25, 210–223 (2003).

23. Weimann A, Braga A, Harsanyi L et al. ESPEN guidelines on enteral nutrition: surgery including organ transplantation. Clin. Nutr. 25, 224–244 (2006).

24. Galban C, Montejo JC, Mesejo A, et al. An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients. Crit Care Med 2000;28:643–8.

25. McClave SA. Et al JPEN. 2009; 33(3):277-316.


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