Q6. Does nutrition intervention improve outcomes? - Surgery
The European Society of Parenteral and Enteral Nutrition (ESPEN) Guidelines on Enteral Nutrition: Surgery Including Organ Transplantation  report that pre operative enteral nutrition should be given to patients with severe nutritional risk (weight loss of >10-15% in last 6 months, body mass index (BMI) <18.5, Subjective Global Assessment (SGA) C (i.e. severely malnourished), albumin <30 with no evidence of renal/liver dysfunction) for 10-14 days pre operatively (Grade A Recommendation, ESPEN, 2006).
Immunonutrition has been a focus of nutrition intervention in surgery and the critical care setting for several years. It is a term encompassing a form of nutritional supplement or enteral feeding formula, which has added nutrients for a proposed immune modulating effect. It is hypothesized that the nutrition factors may play a role in modulating the immune system, which can then impact upon patients’ clinical outcomes such as reduced infections. The most common types of formula have conditionally essential amino acids arginine and/or glutamine, n-3 fatty acids and/or ribonucleic acids added. The majority of studies have involved arginine enhanced feeds; however two studies have looked at the role of n-3 fatty acids as an immune modulating factor .
There are two level I studies, one positive quality paper  and one negative quality which report on results of a systematic review on the role of immunonutrition in patients undergoing surgery for head and neck cancer. The first paper included 10 randomised controlled trials (RCT’s)(total n=605), six were in patients with carcinoma of the oral cavity or larynx, three studies also included pharyngeal tumours, and one study did not fully specify the tumour groups for inclusion. Three studies only recruited patients with recent weight loss. The pooled data showed a significant reduction in length of stay by 3.5 days, but no effect on complication rates. The trials were deemed to be small with incomplete reporting of outcomes, and the results should be interpreted with some degree of caution given that six of the ten studies were also undertaken by the same author group. The conclusions state that adequately powered trials are required to substantiate the benefit and determine the mechanism. The second systematic review included 14 RCT’s (total n=836). Although the aim was to examine the effect of perioperative immunonutrition, only five of the 14 studies utilised preoperative supplementation. The remaining nine studies examined the effect of postoperative supplementation alone. The paper was more narrative than analytic in review style with no meta analysis, making it difficult to draw conclusions. However the authors concluded there was little evidence to guide the use or value of preoperative supplementation, while a suitably powered clinical trial is required before firm recommendations can be made regarding the use of post operative immunonutrition in this patient group. Another systematic review  reported on perioperative use of arginine supplemented diets in a range of elective surgical patients. Although this review was graded as a level I positive quality paper, there were concerns about the grouping of patients with head and neck cancer (3 RCT perioperative n=241, 6 RCT postoperative n=369), with upper gastrointestinal patients (5 RCT perioperative n=869, 12 RCT postoperative n=1353). There were no additional studies in head and neck cancer patients that had been identified since the publication of the systematic review in 2009, and so this was still deemed the most appropriate to use to guide practice.
For preoperative immunonutrition, all studies compare perioperative immunonutrition (i.e. given before and after surgery), which makes it difficult to determine at which point the intervention may be having an effect. In addition to the studies in the systematic review by Stableforth et al., one level II neutral study  demonstrated less major complications (infections and wound complications) in the group that received immunonutrition pre and postoperatively, compared to the group which received no preoperative nutrition support and standard postoperative enteral feeding. One level II neutral quality pilot study  was underpowered to show any statistical differences, other than reduced C-reactive protein levels in the perioperative immunonutrition group on day one postop only, compared to the standard feeds. Another level II neutral quality pilot study was unable to demonstrate any significant differences in inflammatory markers, postop complications or LOS between groups due to being underpowered. Two level II neutral quality studies , which were included in the systematic review, also included a third control group of no preoperative nutrition support. They found that malnourished patients with preoperative standard nutrition support compared to no preoperative nutrition support had improved quality of life . The addition of preoperative immunonutrition with arginine had no additional benefit compared to standard preoperative nutrition support . In a longitudinal study by the same group of authors, level II neutral quality,  the group that received immunonutrition pre and postoperatively had improved long term survival at 10 years compared to those that received standard formula.
There is one level III-1 neutral quality study  which studied the effect of preoperative nutrition support (either counselling or supplements) to reduce length of stay and complications, however the results need to be interpreted with caution as there was no statistical analysis. One level III-3 neutral quality study  describes patient outcomes pre and post implementation of Diagnosis Related Groups (DRGs). The impact of this change in the US health system had was a reduction in preoperative admission time, which resulted in less nutrition intervention preoperatively and therefore higher rates of malnutrition at the time of surgery which resulted in increased complications, infections and length of stay. This provides support for nutrition intervention preoperatively even if it can only be given as an outpatient. There was one level IV negative quality study  which examined the effect of preoperative nutrition intervention of counselling, supplements or tube feeding, but outcome data was limited.
For postoperative immunonutrition interventions, there is the level I positive quality paper , and in addition to the papers included within this review, there is one level II positive quality study , six level II neutral quality studies  and one level III-3 positive quality study. The level II positive quality study demonstrates a significant reduction in both length of stay of 12 days and fistula rates (17.6% compared to 5.2%), and no difference in infection rates. For the neutral studies, other statistical differences were seen with reduction in fistula rates in one study, reduced infections and wound complications in one study and improved survival in one study. The level III-3 study did not find any significant differences between groups apart from a reduced fistula rate in the immunonutrition group.
Despite the volume of literature in this area, well designed clinical studies are still required to confirm how the mechanism of immunonutrition is beneficial in this group of patients, with several studies unable to distinguish between effects seen preoperatively or postoperatively.
With regards to n-3 fatty acids, the level II neutral quality paper  compared arginine enriched oral nutrition support with n-3 fatty acid enriched oral nutrition support for 12 weeks post discharge. They found the n-3 fatty acid supplement resulted in significantly greater weight gain and fat mass gain. The level IV neutral quality study  demonstrated that patients who were given n-3 fatty acid enriched nutrition support (orally or tube fed) perioperatively had improved outcomes in terms of weight maintenance and increased lean body mass at the time of discharge.
In terms of general postoperative nutrition care, there are five level IV neutral quality studies  and one level IV negative quality study , examining outcomes with either postoperative nasogastric or gastrostomy feeding. All of the neutral studies, irrespective of method of feeding, demonstrate a significant weight loss or drop in Body Mass Index (BMI) in the immediate postoperative period (one week to one month). The negative quality study, demonstrated that following postoperative gastrostomy feeding, weight gain of 3kg was achieved by one month postoperatively.
|Peri operative n-3 fatty acid enriched nutrition support may improve nutritional outcomes such as weight, lean body mass and fat mass.||C|
|Tube feeding using standard formula can be used to minimise weight loss in the acute post operative period.||C|
|Pre operative nutrition intervention in malnourished patients may lead to improved outcomes such as quality of life and reduce adverse related consequences of malnutrition.||B|
|Pre operative immunonutrition has no additional benefits compared to standard nutrition support for patients undergoing surgery for head and neck cancer.||C|
|Post operative immunonutrition may be considered to reduce length of stay, although the mechanism is unclear, as other clinical benefits such as reduced complications and infections were not demonstrated.||B|
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