S roberts ebr

Scott Roberts BS, LPN, DTR
Prof. Anne Davis, PhD, RD
06/26/2012
GI Nutritional Therapy Evidence-Based Review

NUTR590: Gastrointestinal Nutrition
1

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).

NUTR590: Gastrointestinal
Nutrition 2

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 studies
Study 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 immuonutrition
may 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 enteral
and 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 enteral
immunonutrition 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 enteral
immunonutrition 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 Parenter
Enteral 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.

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 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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