University of Virginia Health System
Nutrition Support E-Journal Club
We hosted a great Weekend Warrior group the first weekend in March. Fortunately, our program was scheduled on a weekend with mild weather, so our participants and guest speakers had no problems with travel (we had snow the week before!). Our journal club this month is from The Annals of Surgery. Although the title suggests an Immunonutrition study, their results may be used by some to generate conclusions (and controversy) regarding the use of parenteral nutrition.
Klek S, Kulig J, Sierzega M, et al. The impact of immunostimulating nutrition on infectious complications after upper gastrointestinal surgery: a prospective, randomized, clinical trial. Ann Surg 2008 Aug;248(2):212-20.
This was a randomized, unblinded study of parenteral and enteral immunonutrition in 214 patients who received subtotal gastrectomy or pancreaticoduodenectomy. Patients were randomized (2 X 2 factorial design) into 4 groups - standard parenteral nutrition (PN), PN with glutamine and fish oil (IMPN), standard enteral (EN) or immunonutrition enteral formula (IMEN). Patients received the study nutrition within 24 hours after surgery and continued for 7 days. The standard enteral formula was a 1 calorie/mL semi-elemental (Peptisorb), and the Immune enteral formula was 1.25 calorie/mL (Stresson). The Immuno-parenteral nutrition group was supplemented with 2mg/kg/d glutamine and 1 mg/kg/day omega-3 fatty acids as Omegaven.
PN was provided at 0.15gmN/kg (approx 0.9 gm protein/kg) and 150 calories/gm nitrogen (as non-nitrogen calories). Enteral nutrition was provided based on flow rate:
- 25mL/hr day 1 (600/750 kcal/day Peptisorb/Stresson respectively)
- 50mL/hr day 2 (1200/1500 kcal/day Peptisorb/Stresson respectively)
- 75mL/hr day 3 (1800/2250 kcal/day Peptisorb/Stresson respectively)
- 100mL/hr days 4-7 (2400/3000kcal/day Peptisorb/Stresson respectively)
(if patients received 100% of expected EN).
The primary outcome was the rate of infectious complications, and secondary outcomes included overall morbidity, mortality and postoperative hospital stay.
Inclusion and Exclusion Criteria were:
Inclusion criteria were patients between 18 and 80 who received subtotal gastrectomy or pancreaticoduodenectomy, who had a Karnofsky score of 80 or more, and "adequate organ function." Exclusion criteria were those who required preoperative nutrition support, those with disseminated tumors, serious co-morbidities, renal or hepatic failure.
Major Results reported by authors:
The authors reported that there was no difference in either the primary or secondary outcomes between the immunonutrition and standard groups for either the PN or EN group. In addition, there was no difference in infection rates between those patients that received PN compared to the patients that received EN. The authors also reported that there was "a similar amount" of nutrition provided between the four groups. The percentage of patients with mild malnutrition was between 16.7 and 21.2% (based on preoperative wt. loss > 10%) and was not significantly different between the groups.
The authors concluded that there was no measurable advantage to postoperative immunonutrition in patient's undergoing elective upper GI surgery. They also concluded that EN and PN showed similar efficacy and complications.
Some positive aspects of this study are that it was randomized and had objective end-points. It also studied a relatively homogenous group of patients which helps to offset the relatively modest size of the groups.
Some of the concerns that were expressed during our journal club included the fact that this was a well nourished group of patients, with only 20% (or less) having only mild malnutrition. This population is generally not considered a group that would benefit from post-op nutrition support, except in those patients with a more complicated course that were unable to return to oral intake in 7-10 days. Failure to discern a difference between the groups may be interpreted as confirmation that well-nourished patients do not benefit from any type of routine nutrition support post-operatively.
Another aspect of this study was the choice of immunonutrition product for the enteral formula. The product used provides only 7.12 gm of arginine/L; meta-analysis of immunonutrition has illustrated that only those formulas providing > 12 gm of arginine/L were associated with a reduction in infectious complications. Failure to demonstrate a benefit from relatively modest doses of arginine, fish oil and antioxidants should not necessarily be taken as proof of non-efficacy of peri-operative immunonutrition for all patients for all products.
Although the authors state that there was no difference in the amount of nutrition provided, it should be noted that there was no mention of the actual amount of enteral formula actually infused into the patients. Considering that a number of studies have demonstrated that most enterally-fed patients do not typically receive the full amount of prescribed nutrition (Mackenzie, McClave, Rice, van den Broek), and EN-fed patients generally receive less calories actually infused compared to PN (Abou-Assi), we would have liked to see documentation of actual EN received by the patients (especially in patients post-op subtotal gastrectomies/pancreaticoduodenectomies). Additionally, the immunonutrition EN provided 25% more calories per volume than the standard EN formula, and enteral feeding goals were based on flow rate, not on calories or patient size. Our group felt that one significant flaw in the methods of this study was that the PN groups nutrition goals were based on the individual weight of the patient, while the enterally-fed group ultimately received 100mL/hour for 4 days. This would mean that a 110 lb patient could potentially receive 3000 calories/day in the immunonutrition EN group (60kcals/kg), but the same patient would have received 1125 calories/day (22.5kcals/kg) in the PN group!
Regarding the lack of difference in infectious complications in the EN and PN groups, one must remember that this was an incidental finding, and was not one of the pre-set objectives of the study. Certainly the potential for overfeeding smaller patients in the EN group and not in the PN group is a real factor to be considered. Another aspect is that the control and immunonutrition PN groups received a lipid emulsion that was a mix of MCT and long-chain triglycerides, which may reduce the risk of PN complications and infections. These results may not be applicable to patients in the U.S. who would have received all long-chain omega-6 fatty acids in the lipid emulsion, or to all critically ill or septic patients that may have a higher risk of infectious complications.
The authors do point out that even if glucose control and formula modifications to PN result in similar infection rates between EN and PN one day, that the cost difference between the two modalities is still sufficient to justify EN over PN.
Our Take Home message:
Well-nourished patients without high operative risk factors or organ failure do not seem to benefit from low-arginine EN immunonutrition in the post-operative period, nor do the same patients benefit from glutamine and fish oils added to PN when compared to PN providing lipid emulsion as LCT/MCT mix. This study does not provide strong enough evidence regarding infection rates between EN and PN due to the methodological problems noted above to support PN as equal to EN.
- 1) Mackenzie SL, Zygun DA, Whitmore BL, et al. Implementation of a nutrition support protocol increases the proportion of mechanically ventilated patients reaching enteral nutrition targets in the adult intensive care unit. J Parenter Enteral Nutr 2005;29:74-80.
- 2) McClave SA, Sexton LK, Spain DA, et al. Enteral tube feeding in the intensive care unit: factors impeding adequate delivery. Crit Care Med 1999;27:1252-1256.
- 3) Rice TW, Swope T, Bozeman S, et al. Variation in enteral nutrition delivery in mechanically ventilated patients. Nutrition 2005;21(7-8):786-792.
- 4) van den Broek PWJH, Rasmussen-Conrad EL, Naber AHJ, et al. What you think is not what they get: significant discrepancies between prescribed and administered doses of tube feeding. Brit J Nutr 2009;101(1):68-71.
- 5) Abou-Assi S, Craig K, O'Keefe SJ. Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study. Am J Gastroenterol. 2002 Sep;97(9):2255-62.
Our next Weekend Warrior 2 day mini-traineeship program is scheduled for Saturday and Sunday, July 11 - July 12, 2009. If you know anyone who might not be able to get away for our full week traineeship, please let them know about our weekend program, and to check out our website for full information-we have a few slots left!
Our next webinar, Nutrition Support in the Gastric Bypass Patient, is scheduled for April 14th and will be presented by Kelly O'Donnell, MS, RD, CNSD. Check out the full schedule of webinar programs at: http://www.healthsystem.virginia.edudh/webinars.html
See the latest Practical Gastroenterology articles/info at: http://www.healthsystem.virginia.edu/pub/digestive-health/nutrition/resources.html
- Dasher K, Worthington M. Iron: Not Too Much and Not Too Little. Practical Gastroenterology 2008;XXXIII(2):16.
- DeLegge MH, Amy Berry A. Enteral Feeding: Should it be Continued in the Patient with Clostridium Difficile Enterocolitis? Practical Gastroenterology 2008;XXXIII(3):40.
Joe Krenitsky MS, RD
Carol Parrish RD, MS
PS - Please feel free to forward this on to friends and colleagues.