Summary of a systematic review on enhanced nutritional support

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Global Guidelines for the Prevention of Surgical Site Infection. Geneva: World Health Organization; 2018.

Global Guidelines for the Prevention of Surgical Site Infection.

Show details

Contents

< Prev Next >

Web Appendix 11Summary of a systematic review on enhanced nutritional support

1. Introduction

Malnutrition, including protein-energy and micronutrient deficiencies, continues to be a major public health problem, particularly in developing countries. It affects also the rapidly growing elderly population in high-income countries (1, 2). Nutritional status can have a profound impact on the immune system (3) and some studies have documented the relationship between malnutrition and an impaired host immune response (2–4). These alterations in immunity may make patients more susceptible to postoperative infections and malnutrition was reported as a threat to surgical outcome (2–7). Similarly, several studies found an association between poor preoperative nutritional status and poor surgical outcomes, including delayed recovery, higher rates of morbidity and mortality, prolonged hospital stay, increased health care costs and a higher early readmission rate (2, 5, 7).

Some studies showed that early nutritional support can improve outcome and decrease the incidence of infectious complications following major surgery in selected malnourished or severely injured patients. The hypothesis is that the immune system may be modulated by the use of specific types of nutritional support (2, 3, 7, 8). Furthermore, surgery induces an altered protein metabolism, marked by a negative nitrogen balance and changes in amino acid patterns in blood. In addition, inflammation is integral to recovery after stress, such as a surgical procedure. Therefore, nutritional support is being used more and more as a means to increase protein and caloric intake during the perioperative period, particularly by using formulas high in specific amino acids, antioxidants and anti-inflammatory nutrients (9, 10).

Given the role of nutrition in the host response to surgery, many researchers believe that nutritional interventions would reduce surgical site infection (SSI) and related morbidity. However, an epidemiologic association between incisional SSI and malnutrition has been difficult to demonstrate consistently for all surgical subspecialties. Furthermore, there is very little consensus on the optimal timing and dosage of multiple nutrient-enhanced formulas, especially for the prevention of SSI.

There are currently no formal recommendations for nutrition supplementation for SSI prevention. Recent recommendations from the Society for Healthcare Epidemiology of America (SHEA)/Infectious Diseases Society of America (IDSA) state that the preoperative administration of parenteral nutrition should not delay surgery (11).

2. PICO question

In surgical patients, should enhanced nutritional support be used for the prevention of SSI?

Population: inpatients and outpatients of any age undergoing surgical operations (any type of procedure)
Intervention: enhanced nutritional support (oral, enteral, parenteral)
Comparator: standard nutrition formula or no nutritional support
Outcomes: SSI or SSI-attributable mortality

3. Methods

The following databases were searched: Medline (PubMed); Excerpta Medica Database (EMBASE); Cumulative Index to Nursing and Allied Health Literature (CINAHL); Cochrane Central Register of Controlled Trials (CENTRAL); and WHO regional medical databases. The time limit for the review was between 1 January 1990 and 24 July 2015. Language was restricted to English, French and Spanish. A comprehensive list of search terms was used, including Medical Subject Headings (MeSH) (Appendix 1).

Two independent reviewers screened the titles and abstracts of retrieved references for potentially relevant studies. The full text of all potentially eligible articles was obtained and then reviewed independently by two authors for eligibility based on inclusion criteria. Duplicate studies were excluded.

Two authors extracted data in a predefined evidence table (Appendix 2) and critically appraised the retrieved studies. Quality was assessed using the Cochrane Collaboration tool to assess the risk of bias of randomized controlled trials (RCTs) (12) (Appendix 3a) and the Newcastle-Ottawa Quality Assessment Scale for cohort studies (13) (Appendix 3b). Any disagreements were resolved through discussion or after consultation with the senior author, when necessary.

Meta-analyses of available comparisons were performed using Review Manager version 5.3 (14) as appropriate (Appendix 4). Odds ratios (OR) with 95% confidence intervals (CI) were extracted and pooled for each comparison with a random effects model. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (GRADE Pro software, http://gradepro.org/) (15) was used to assess the quality of the body of retrieved evidence (Appendix 5).

4. Study selection

Flow chart of the study selection process

5. Summary of the findings and quality of the evidence

A total of 23 studies (19 RCTs and 4 observational) investigating the use of enhanced nutritional support and reporting SSI as an outcome were identified (Appendix 2). Nutrition administration routes varied between oral, enteral and/or parenteral, but these data were not always presented in a stratified manner. Nutritional formulas varied across studies as nutrients were not identical and contained different doses of single and/or multiple nutrients. Several studies used nutritional or inflammatory biomarkers as primary outcomes and addressed SSI as a secondary outcome and thus the assessment period was short for some studies.

After careful appraisal of the included studies, the research team and the Guidelines Development Group (GDG) decided to perform meta-analysis comparisons including only studies in which the oral and enteral routes were used and excluding those using the parenteral route. The main reason was that the parenteral route is very different from the oral and enteral routes and the experts considered it inappropriate to administer enhanced nutritional formulas only for the purpose of preventing SSI given the infectious risk related to intravenous access. According to the type of formula used, the following comparisons were possible:

Single nutrient-enhanced nutrition
Six studies (5 RCTs (16–20) and one observational (21)) compared the use of nutritional formulas enhanced with a single nutrient (either arginine, glycine or branched chain amino acids) with the standard isocaloric, isonitrogenous enteral formula. These studies included adult patients with head and neck cancer, hepatocellular carcinoma and those with cardiac disease undergoing elective surgical procedures.
Among the 5 RCTs, 2 studies (16, 17) reported that supplementing the enteral nutrition with a single nutrient may have some benefit, but the effect was not statistically significant. Two other studies (18, 19) reported no SSI events in both intervention and control groups. One study (20) estimated that single nutrient-enhanced nutrition may increase SSI, but the effect was not statistically different from the control group.
Meta-analysis of these 5 studies showed that single nutrient-enhanced nutrition has neither benefit nor harm when compared to standard nutritional support in reducing the risk of SSI (OR: 0.61; 95% CI: 0.13–2.79) (Appendix 4). In addition, the observational study (21) showed a similar result with no difference between the two groups (OR: 0.29; 95% CI: 0.06–1.39).
The quality of the evidence for this comparison was very low for the RCTs due to the risk of bias and imprecision. Similarly, it was very low for the observational study due to imprecision (Appendix 5).
Multiple nutrient-enhanced nutrition
Ten studies comprising 8 RCTs (20, 22–28) and 2 observational (29, 30) compared the use of nutritional supplements enhanced with multiple nutrients with the standard formula. Eight studies included adult patients undergoing elective surgical procedures for head and neck, gastrointestinal, colorectal or gynaecological cancer. Two studies (20, 28) included cardiac surgical procedures. One study (23) included data from multiple centres. Patient conditions varied and included malnourished elderly persons as well as younger adult patients. The multiple nutrient-enhanced formulas used in the studies varied also and contained different combinations and doses of arginine, glutamine, omega-3 fatty acids and/or nucleotides. In most studies, it was observed that enteral tubal feeding was planned for most patients because of the nature of the surgery (for example, gastrointestinal resection) and not as part of the intervention.
The effect of the intervention varied among the 8 RCTs. Two studies (26, 27) showed that using multiple nutrient-enhanced nutrition has some benefit in reducing SSI compared to standard nutrition. Four studies (22, 23, 25, 28) showed similar results, but the effect was not statistically different from the standard nutrition group. One study (24) reported that multiple nutrient-enhanced formulas may increase SSI compared to standard nutrition.
Meta-analysis of these 8 studies showed a significant benefit of the use of multi-nutrient enhanced nutritional formulas in the risk of SSI compared to standard nutrition (OR: 0.53; 95% CI: 0.30–0.91) (Appendix 4). The test for funnel plot asymmetry among RCTs using multiple nutrient-enhanced formulas was not statistically significant (P=0.067), thus indicating the potential for publication bias. In addition, the meta-analysis of the 2 observational studies showed a similar result (OR: 0.07; 95% CI: 0.01–0.53).
The quality of the evidence for this comparison was very low due to risk of bias, inconsistency and publication bias for the RCTs. Similarly, it was very low for the observational studies due to imprecision (Appendix 5).

In conclusion, the retrieved evidence can be summarized as follows:

Overall, a very low quality of evidence (RCTs and one observational study) shows that single nutrient-enhanced nutrition is neither beneficial nor harmful in reducing SSI rates when compared to standard nutritional support.
Overall, a very low quality of evidence indicates that multiple nutrient-enhanced nutritional formulas are beneficial compared with standard nutrition in reducing the risk of SSI.

Some serious limitations can be observed within the available studies. Many studies were conducted by the same authors with or without commercial funding, which could potentially be a source of intellectual risk of bias. Studies reported that it was difficult to blind participants, clinical teams and/or outcome assessors, thus increasing the possible risk of bias.

6. Other factors considered in the review

The systematic review team identified the following other factors to be considered.

Potential harms

Oral administration of nutritional supplementation should not cause undesirable effects. Enteral feeding with either standard or enhanced formulas is generally well tolerated. There is an increased possibility of discomfort from the location and insertion of gastric feeding tubes, as well as nausea and perforation from the tube itself.

The use of nutritional formulas may introduce some concern for accidental contamination during reconstitution, particularly in areas with limited access to potable water. Therefore, it is very important that infection prevention and control guidelines be followed while preparing these formulas. The use of enteral feeding tubes should be reserved for patients who will require their use, regardless of the administration of nutritional formulas. Some of the formulas studied were dairy-based, which may be problematic for individuals who avoid dairy products for dietary, ethical or cultural reasons.

Resource use

The use of enhanced nutrition support is expensive and requires additional work for health care providers. The availability of enhanced nutrition supplements may be limited, particularly in low- and middle-income countries. With nutritional interventions, there is an additional need for dietitians to be available in the clinic, including an increased need to train staff in the appropriate use and preparation of nutritional formulas. In addition to the added cost of multiple nutrient formulas, there is uncertainty that the benefits outweigh the costs due to the infrastructure and training needed to support such interventions.

7. Key uncertainties and future research priorities

Trials studying the efficacy and safety of enhanced nutritional support for the prevention of SSI were small and generally of low quality. They were also often conducted in populations at high risk for malnutrition (for example, gastrointestinal cancer), which may have more profound effects on healing and the immune response. Many studies are funded by manufacturers of proprietary formulas, thus increasing the potential for bias. Future studies should be conducted in larger populations of individuals undergoing a variety of general surgical procedures who may benefit from short-term nutritional support. The impact of nutritional support should be investigated further in populations with a high risk of malnutrition, such as in low- and middle-income countries. The optimal timing and duration of administration of nutritional support in relation to the time of surgery should be further assessed by well-designed RCTs. The effect of other nutrients (for example, iron and zinc) on reducing the risk of SSI should be investigated, either individually or combined.

Appendices

Appendix 1. Search terms

Medline (via PubMed)

1): (“nutrition therapy”[Mesh] OR “diet therapy”[Mesh] OR “caloric restriction”[Mesh] OR “diabetic diet”[Mesh] OR “diet, carbohydrate-restricted” [Mesh] OR “diet, fat-restricted”[Mesh] OR “diet, gluten-free”[Mesh] OR “diet, Mediterranean”[Mesh] OR “diet, Paleolithic”[Mesh] OR “diet, protein-restricted”[Mesh] OR “diet, reducing”[Mesh] OR “diet, sodium-restricted”[Mesh] OR “diet, vegetarian”[Mesh] OR “diet, macrobiotic”[Mesh] OR “ketogenic diet”[Mesh] OR “nutritional support”[Mesh] OR “enteral nutrition”[Mesh] OR “parenteral nutrition”[Mesh] OR “parenteral nutrition, total”[Mesh] OR “parenteral nutrition solutions”[Mesh] OR “amino acid”[TIAB] OR “arginine”[TIAB] OR “fish oil”[TIAB] OR “omega-3”[TIAB] OR “nucleotides”[TIAB] OR “ribonucleic acid”[TIAB] OR “nutritional support”[TIAB] OR “immune nutrition” OR “immune-nutrition” OR “immunonutrition” OR “immune-nutrition”[TIAB] OR “enhanced nutrition”[TIAB] OR “specialized nutrition”[TIAB] OR “fortified nutrition”[TIAB] OR “dietary supplements” [Mesh] OR “prebiotics”[Mesh] OR “probiotics”[Mesh] OR “synbiotics”[Mesh] OR “yeast, dried”[Mesh] OR “food, specialized”[Mesh] OR “food, formulated”[Mesh] OR “food, fortified”[Mesh] OR “functional food”[Mesh] OR “micronutrients”[Mesh] OR “trace elements”[Mesh] OR “vitamins”[Mesh] OR “nutritional requirements”[Mesh] OR “recommended dietary allowances”[Mesh] OR “nutritive value”[Mesh] OR “nutrition policy”[Mesh] OR “appetite regulation”[Mesh])
2): (“surgical wound infection“[MeSH] OR “surgical site infection” OR “surgical site infections” [TIAB] OR “wound infection” [TIAB] OR “wound infections” [TIAB] OR” surgical wound infection” [TIAB] OR “prosthesis-related infection” [TIAB] OR “prosthesis-related infections”[TIAB] OR “surgical site infection” [tiab] OR “surgical site infections” [tiab] OR SSI [tiab] OR SSIs [tiab])
3): #1 AND #2
4): LIMIT to 1990-Present

EMBASE

1): ‘diet therapy’/exp OR ‘amino acid’/exp OR ‘fish oil’/exp OR ‘RNA’/exp OR ‘nucleotide’/exp OR ‘trace element’/exp OR ‘nutritional requirement’/exp OR ‘nutritional value’/exp OR (‘health care policy’/exp OR nutrition*:ti,ab) OR ‘food intake’/exp OR ‘nutritional science’/exp OR ‘nutrition’/exp OR ‘nutrition therapy’:ti,ab,de OR ‘diet therapy’:ti,ab,de OR ‘caloric restriction’:ti,ab,de OR ‘diabetic diet’:ti,ab,de OR ‘carbohydrate-restricted‘:ti,ab,de OR ‘fat-restricted’:ti,ab,de OR ‘gluten-free’:ti,ab,de OR ‘Mediterranean diet’:ti,ab,de OR ‘Paleolithic diet’:ti,ab,de OR ‘protein-restricted’:ti,ab,de OR ‘reducing diet’:ti,ab,de OR ‘sodium-restricted’:ti,ab,de OR ‘vegetarian diet’:ti,ab,de OR ‘macrobiotic diet’:ti,ab,de OR ‘ketogenic diet’:ti,ab,de OR ‘nutritional support’:ti,ab,de OR ‘enteral nutrition’:ti,ab,de OR ‘parenteral nutrition’:ti,ab,de OR ‘amino acid’:ti,ab,de OR ‘amino acids’:ti,ab,de OR ‘arginine’:ti,ab,de OR ‘fish oil’:ti,ab,de OR ‘fish oils’:ti,ab,de OR ‘fish oils’:ti,ab,de OR ‘omega-3’:ti,ab,de OR ‘nucleotides’:ti,ab,de OR ‘RNA’:ti,ab,de OR ‘nucleotides’:ti,ab,de OR ‘ribonucleic acid’:ti,ab,de OR ‘nutritional support’:ti,ab,de OR ‘immune nutrition’:ti,ab,de OR ‘immune-nutrition‘:ti,ab,de OR ‘immunonutrition’:ti,ab,de OR ‘enhanced nutrition’:ti,ab,de OR ‘specialized nutrition’:ti,ab,de OR ‘fortified nutrition’:ti,ab,de OR ‘dietary supplements’:ti,ab,de ‘dietary supplements’:ti,ab,de OR ‘dietary supplement’:ti,ab,de OR ‘prebiotics’:ti,ab,de OR ‘probiotics’:ti,ab,de OR ‘synbiotics’:ti,ab,de OR ‘dried yeast’:ti,ab,de OR ‘formulated food‘:ti,ab,de OR ‘fortified food’:ti,ab,de OR ‘functional food’:ti,ab,de OR ‘formulated foods’:ti,ab,de OR ‘fortified foods’:ti,ab,de OR ‘functional foods’:ti,ab,de OR ‘micronutrients’:ti,ab,de OR ‘trace elements’:ti,ab,de OR ‘vitamins’:ti,ab,de OR ‘nutritional requirements’:ti,ab,de OR ‘recommended dietary’:ti,ab,de OR ‘dietary allowances’:ti,ab,de OR ‘dietary allowance’:ti,ab,de OR ‘nutritive value’:ti,ab,de OR ‘nutrition policy’:ti,ab,de OR ‘appetite regulation’:ti,ab,de OR ‘appetite regulation’:ti,ab,de OR ‘micronutrients’:ti,ab,de OR ‘nutritional sciences’:ti,ab,de OR ‘nutritional physiological phenomena’:ti,ab,de OR ‘nutrition assessment’:ti,ab,de OR ‘nutrition therapy’:ti,ab,de OR diet:ti,ab,de OR diets:ti,ab,de OR nutrition:ti,ab,de OR nutritional:ti,ab,de OR nutritive:ti,ab,de
2): ‘surgical infection‘/exp OR ‘surgical infection’ OR ‘surgical site infection’:de,ab,ti OR ‘surgical site infections’:de,ab,ti OR ssis:de,ab,ti OR ssi:de,ab,ti OR ‘surgical infection wound’:de,ab,ti OR ‘surgical infection wounds’:de,ab,ti OR ‘surgical infection’:de,ab,ti OR ‘postoperative wound infection’:de,ab,ti OR ‘postoperative wound infections’:de,ab,ti OR ‘post-operative wound infection’:de,ab,ti OR ‘post-operative wound infections‘:de,ab,ti OR (‘wound infection‘:de,ab,ti OR ‘wound infections‘:de,ab,ti AND (operation*:de,ab,ti OR surgical:de,ab,ti OR surger*:de,ab,ti OR postoperat*:de,ab,ti OR ‘post-operative’:de,ab,ti OR ‘post-operation’:de,ab,ti)) OR ‘prosthesis related infections’:de,ab,ti OR ‘prosthesis related infection’:de,ab,ti
3): #1 AND #2

CINAHL

1): (“nutrition therapy” OR “diet therapy” OR “nutritional support” OR “enteral nutrition” OR “parenteral nutrition” OR “parenteral nutrition, total” OR “parenteral nutrition solutions” OR “amino acid” OR “arginine” OR “fish oil” OR “omega-3” OR “nucleotides” OR “ribonucleic acid” OR “nutritional support” OR “immune nutrition” OR “immune-nutrition” OR “immunonutrition” OR “immune-nutrition” OR “enhanced nutrition” OR “specialized nutrition” OR “fortified nutrition” OR “dietary supplements” OR “prebiotics” OR “probiotics” OR “synbiotics” OR “food, specialized” OR “food, formulated” OR “food, fortified” OR “functional food”OR “micronutrients” OR “trace elements” OR “vitamins”)
2): (“surgical wound infection” OR “surgical site infection” OR “wound infection” OR “prosthesis-related infection” OR “SSI” OR “SSIs”))
3): #1 AND #2

Cochrane CENTRAL

“nutrition” AND (“surgical site infection” OR “wound infection” OR “surgical wound infection”)

WHO Global Health Library

“nutrition” AND (“Surgical site infection” OR “surgical wound infection”)

ti:: title;
ab:: abstract

Appendix 2. Evidence table

Download PDF (359K)

Appendix 3. Risk of bias assessment of the included studies

Appendix 3a. Risk of bias assessment of included randomized controlled trials

RCTs author, year, reference	Sequence generation	Allocation concealment	Participants and personnel blinded	Outcome assessors blinded	Incomplete outcome data	Selective outcome reporting	Other sources of bias
Beattie, 2000 (31)	LOW	UNCLEAR	HIGH	HIGH	LOW	LOW	UNCLEAR
Burden, 2011 (32)	LOW	LOW	HIGH	LOW	LOW	LOW	LOW
Casas-Rodera, 2008 (16)	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR
Celik, 2009 (22)	LOW	LOW	LOW	LOW	LOW	LOW	UNCLEAR
De Luis, 2002 (17)	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW	UNCLEAR
De Luis, 2004 (18)	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	UNCLEAR	UNCLEAR
De Luis, 2007 (19)	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	UNCLEAR	UNCLEAR
Falewee, 2014 (23)	LOW	LOW	LOW	LOW	LOW	LOW	UNCLEAR
Fujitani, 2012 (24)	LOW	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	LOW
Gianotti, 2002 (25)	LOW	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Klek, 2008 (33)	LOW	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Klek, 2010 (26)	LOW	UNCLEAR	LOW	LOW	LOW	LOW	LOW
Oguz, 2006 (34)	UNCLEAR	UNCLEAR	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Roth, 2012 (35)	LOW	UNCLEAR	HIGH	LOW	LOW	LOW	LOW
Snyderman, 1999 (27)	UNCLEAR	UNCLEAR	LOW	LOW	LOW	LOW	UNCLEAR
Suzuki, 2010 (36)	LOW	LOW	UNCLEAR	UNCLEAR	LOW	LOW	UNCLEAR
Tepaske, 2007 (20)	LOW	LOW	LOW	LOW	LOW	LOW	LOW
Tepaske, 2001 (28)	LOW	LOW	LOW	LOW	LOW	LOW	UNCLEAR
Wei, 2014 (37)	UNCLEAR	UNCLEAR	LOW	UNCLEAR	LOW	LOW	LOW

: RCT: randomized controlled trials.

Appendix 3b. Risk of bias assessment of the included non-randomized studies

Cohort studies Author, year, reference	Representativeness of cohort	Selection of non-exposed cohort	Ascertainment of exposure	Demonstration that outcome of interest was not present at start	Comparability of cohorts	Assessment of outcome	Follow-up long enough	Adequacy of follow-up of cohorts
Horie, 2006 (29)	B(*)	A(*)	A(*)	B	B(*)	B(*)	A(*)	B(*)
Okabayashi, 2008 (21)	B(*)	A(*)	A(*)	B	AB(**)	D	A(*)	B(*)
Takeuchi, 2007 (30)	B(*)	A(*)	A(*)	B	AB(**)	A(*)	A(*)	A(*)
Yeh, 2008 (38)	B(*)	A(*)	A(*)	B	AB(**)	B(*)	B	A(*)

Appendix 4. Comparisons

Comparison 1aSingle nutrient-enhanced nutrition (RCTs)

Funnel plot 1aSingle nutrient-enhanced nutrition (RCTs)

Comparison 1bSingle nutrient-enhanced nutrition (non-RCT)

Comparison 2aMultiple nutrient-enhanced nutrition (RCTs)

Funnel plot 2aMultiple nutrient-enhanced nutrition (RCTs)

Comparison 2bMultiple nutrient-enhanced nutrition (non-RCTs)

RCT: randomized controlled trial; M-H: Mantel-Haenszel (test); CI: confidence interval

Appendix 6. GRADE Tables

Comparisons 1a and 1b. Single nutrient-enhanced nutrition compared to standard nutrition support for the prevention of SSI (PDF, 311K)

Comparisons 2a and 2b. Multiple nutrient-enhanced formula compared to control for the prevention of SSI (PDF, 299K)

References

1.: Muller O, Krawinkel M. Malnutrition and health in developing countries. CMAJ. 2005;173(3):279–86. [PMC free article: PMC1180662] [PubMed: 16076825]
2.: Culebras JM. Malnutrition in the twenty-first century: an epidemic affecting surgical outcome. Surg Infect (Larchmt). 2013;14(3):237–43. [PMC free article: PMC3696934] [PubMed: 23676121]
3.: Mainous MR, Deitch EA. Nutrition and infection. Surg Clin North Am. 1994;74(3):659–76. [PubMed: 8197536]
4.: Waitzberg DL, Ravacci GR, Raslan M. [Hospital hyponutrition]. Nutr Hosp. 2011;26(2):254–64. [PubMed: 21666960]
5.: Studley HO. Percentage of weight loss: a basic indicator of surgical risk in patients with chronic peptic ulcer. 1936 Nutr Hosp. 2001;16(4):141–3; discussion 0–1. [PubMed: 11680474]
6.: Fry DE. Fifty ways to cause surgical site infections. Surg Infect (Larchmt). 2011;12(6):497–500. [PubMed: 22142318]
7.: Culebras-Fernandez JM, de Paz-Arias R, Jorquera-Plaza F, Garcia de Lorenzo A. [Nutrition in the surgical patient: immunonutrition.] Nutr Hosp. 2001;16(3):67–77. [PubMed: 11475680]
8.: Di Carlo V, Gianotti L, Balzano G, Zerbi A, Braga M. Complications of pancreatic surgery and the role of perioperative nutrition. Dig Surg. 1999;16(4):320–6. [PubMed: 10449977]
9.: Mazaki T, Ishii Y, Murai I. Immunoenhancing enteral and parenteral nutrition for gastrointestinal surgery: a multiple-treatments meta-analysis. Ann Surg. 2015;261(4):662–9. [PubMed: 25405556]
10.: Yue C, Tian W, Wang W, Huang Q, Zhao R, Zhao Y, et al. The impact of perioperative glutamine-supplemented parenteral nutrition on outcomes of patients undergoing abdominal surgery: a meta-analysis of randomized clinical trials. Am Surg. 2013;79(5):506–13. [PubMed: 23635587]
11.: Anderson DJ, Podgorny K, Berrios-Torres SI, Bratzler DW, Dellinger EP, Greene L, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35(Suppl. 2):S66–88. [PubMed: 25376070]
12.: Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration‘s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. [PMC free article: PMC3196245] [PubMed: 22008217]
13.: Wells GA SB, O‘Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute, 2011 (http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp., accessed 19 January 2016).
14.: The Nordic Cochrane Centre TCC. Review Manager (RevMan). Version 5.3 ed. Copenhagen: The Cochrane Collaboration; 2014.
15.: GRADEpro Guideline Development Tool. Ontario: McMaster University and Evidence Prime Inc.; 2014 (http://www.gradepro.org, accessed 5 May 2016).
16.: Casas-Rodera P, Gomez-Candela C, Benitez S, Mateo R, Armero M, Castillo R, et al. Immunoenhanced enteral nutrition formulas in head and neck cancer surgery: a prospective, randomized clinical trial. Nutr Hosp. 2008;23(2):105–10. [PubMed: 18449445]
17.: de Luis DA, Aller R, Izaola O, Cuellar L, Terroba MC. Postsurgery enteral nutrition in head and neck cancer patients. Europ J Clin Nutr. 2002;56(11):1126–9. [PubMed: 12428179]
18.: de Luis DA, Izaola O, Cuellar L, Terroba MC, Aller R. Randomized clinical trial with an enteral arginine-enhanced formula in early postsurgical head and neck cancer patients. Europ J Clin Nutr. 2004;58(11):1505–8. [PubMed: 15138461]
19.: De Luis DA, Izaola O, Cuellar L, Terroba MC, Martin T, Aller R. High dose of arginine enhanced enteral nutrition in postsurgical head and neck cancer patients. A randomized clinical trial. Europ Rev Med Pharmacol Sci. 2009;13(4):279–83. [PubMed: 19694342]
20.: Tepaske R, te Velthuis H, Oudemans-van Straaten HM, Bossuyt PM, Schultz MJ, Eijsman L, et al. Glycine does not add to the beneficial effects of perioperative oral immune-enhancing nutrition supplements in high-risk cardiac surgery patients. J Parenter Enter Nutr. 2007;31(3):173–80. [PubMed: 17463141]
21.: Okabayashi T, Nishimori I, Sugimoto T, Maeda H, Dabanaka K, Onishi S, et al. Effects of branched-chain amino acids-enriched nutrient support for patients undergoing liver resection for hepatocellular carcinoma. J Gastroenterol Hepatol. 2008;23(12):1869–73. [PubMed: 18717761]
22.: Çelik JB, Gezginç K, Özçelik K, Çelik Ç. The role of immunonutrition in gynecologic oncologic surgery. Europ J Gynaecol Oncol. 2009;30(4):418–21. [PubMed: 19761135]
23.: Falewee MN, Schilf A, Boufflers E, Cartier C, Bachmann P, Pressoir M, et al. Reduced infections with perioperative immunonutrition in head and neck cancer: exploratory results of a multicenter, prospective, randomized, double-blind study. Clin Nutr. 2014;33(5):776–84. [PubMed: 24182765]
24.: Fujitani K, Tsujinaka T, Fujita J, Miyashiro I, Imamura H, Kimura Y, et al. Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer. Br J Surg. 2012;99(5):621–9. [PubMed: 22367794]
25.: 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(7):1763–70. [PubMed: 12055582]
26.: Klek S, Sierzega M, Szybinski P, Szczepanek K, Scislo L, Walewska E, et al. The immunomodulating enteral nutrition in malnourished surgical patients - a prospective, randomized, double-blind clinical trial. Clin Nutr. 2011;30(3):282–8. [PubMed: 21074910]
27.: Snyderman CH, Kachman K, Molseed L, Wagner R, D‘Amico F, Bumpous J, et al. Reduced postoperative infections with an immune-enhancing nutritional supplement. Laryngoscope. 1999;109(6):915–21. [PubMed: 10369282]
28.: Tepaske R, Velthuis H, Oudemans-van Straaten HM, Heisterkamp SH, van Deventer SJ, Ince C, et al. Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial. Lancet. 2001;358(9283):696–701. [PubMed: 11551575]
29.: Horie H, Okada M, Kojima M, Nagai H. Favorable effects of preoperative enteral immunonutrition on a surgical site infection in patients with colorectal cancer without malnutrition. Surg Today. 2006;36(12):1063–8. [PubMed: 17123134]
30.: Takeuchi H, Ikeuchi S, Kawaguchi Y, Kitagawa Y, Isobe Y, Kubochi K, et al. Clinical significance of perioperative immunonutrition for patients with esophageal cancer. World J Surg. 2007;31(11):2160–7. [PubMed: 17876664]
31.: Beattie AH, Prach AT, Baxter JP, Pennington CR. A randomised controlled trial evaluating the use of enteral nutritional supplements postoperatively in malnourished surgical patients. Gut. 2000;46(6):813–8. [PMC free article: PMC1756438] [PubMed: 10807893]
32.: Burden ST, Hill J, Shaffer JL, Campbell M, Todd C. An unblinded randomised controlled trial of preoperative oral supplements in colorectal cancer patients. J Hum Nutr Diet. 2011;24(5):441–8. [PubMed: 21699587]
33.: Klek S, Kulig J, Sierzega M, Szybinski P, Szczepanek K, Kubisz A, et al. The impact of immunostimulating nutrition on infectious complications after upper gastrointestinal surgery: a prospective, randomized, clinical trial. Ann Surg. 2008;248(2):212–20. [PubMed: 18650630]
34.: Oguz M, Kerem M, Bedirli A, Mentes BB, Sakrak O, Salman B, et al. L-alanin-L-glutamine supplementation improves the outcome after colorectal surgery for cancer. Colorectal Dis. 2007;9(6):515–20. [PubMed: 17573745]
35.: Roth B, Birkhauser FD, Zehnder P, Thalmann GN, Huwyler M, Burkhard FC, et al. Parenteral nutrition does not improve postoperative recovery from radical cystectomy: results of a prospective randomised trial. Eur Urol. 2013;63(3):475–82. [PubMed: 22695241]
36.: Suzuki D, Furukawa K, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, et al. Effects of perioperative immunonutrition on cell-mediated immunity, T helper type 1 (Th1)/Th2 differentiation, and Th17 response after pancreaticoduodenectomy. Surgery. 2010;148(3):573–81. [PubMed: 20227099]
37.: Wei Z, Wang W, Chen J, Yang D, Yan R, Cai Q. A prospective, randomized, controlled study of ω-3 fish oil fat emulsion-based parenteral nutrition for patients following surgical resection of gastric tumors. Nutr J. 2014;13(1). [PMC free article: PMC3974447] [PubMed: 24655407]
38.: Yeh CN, Lee HL, Liu YY, Chiang KC, Hwang TL, Jan YY, et al. The role of parenteral glutamine supplement for surgical patient perioperatively: Result of a single center, prospective and controlled study. Langenbecks Arch Surg. 2008;393(6):849–55. [PubMed: 18712409]

Sales, rights and licensing. To purchase WHO publications, see http://apps.who.int/bookorders. To submit requests for commercial use and queries on rights and licensing, see http://www.who.int/about/licensing.

Third-party materials. If you wish to reuse material from this work that is attributed to a third party, such as tables, figures or images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the copyright holder. The risk of claims resulting from infringement of any third-party-owned component in the work rests solely with the user.

Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).

Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization.

Bookshelf ID: NBK536413

Contents