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University of Virginia Health System

Nutrition Support E-Journal Club

September 2007



We just completed our September session with trainees from Texas, Maryland, Mississippi, and Missouri.  We had a great week, with some interesting cases and wonderful discussions.  The trainees were treated to balmy summer weather now that the humidity has eased, and we were able to dine outside for our night out.  


The journal club article this month discusses physiologic changes that result after starting enteral feeding in patients that had received long-term TPN.

September Citation: 

  • Ren JA, Mao Y, Wang GF, Wang XB, Fan CG, Wang ZM, Li JS.  Enteral refeeding syndrome after long-term total parenteral nutrition.  Chin Med J 2006;119(22):1856-1860.


This was a prospective, observational study of 100 patients with GI fistulas that received "long-term" parenteral nutrition (PN), and then began enteral nutrition (EN).  The patients were subcategorized into three groups; those that received PN less than 15 days (n=2), 15-30 days (n=23) or greater than 30 days (n=52).

The investigators collected data prior to starting EN, and on days 1, 3, 5, 10 and 15 after initiating EN.  The parameters monitored were stool frequency, body temperature, heart rate, respiratory rate, total and direct bilirubin, alkaline phosphatase (Alk Phos), serum transaminases (AST, ALT), gamma-glutamyltransferase (GGT), white blood cell count (WBC), and systemic inflammatory response syndrome (SIRS) score.  SIRS score was based on 2 or more of the following criteria: body temperature > 38C or < 36C, heart rate > 90/min, respiratory rate > 20/min, PaCO2 < 32mmHg, WBC > 12 X 109/L or < 4 X 109/L.

The authors reported that after GI fistula losses "were controlled" EN was initiated at 500 calories/day, then advanced by ¼ of the final goal each day to reach goal calories (~ 35 calories/kg) on day 4.

Inclusion and Exclusion Criteria were:

The study enrolled patients with a GI fistula between April 2001 and July 2002 that had an intact gut without massive loss of GI fluid (never defined).  The exclusion factors were diabetes mellitus, tumor, s/p chemo or radiation therapy, and hospitalization < 7 days.

Major Results reported by authors:

The authors reported that the alkaline phosphatase, GGT, and total bilirubin levels significantly increased in the first several days after starting enteral feeding, then levels decreased either to normal (total bilirubin) or to pre-enteral feeding values (alk phos and GGT).  There were no significant changes in transaminase levels or direct bilirubin. 

The SIRS score was significantly increased after initiation of enteral feeding in those patients that had received PN greater than 15 days. The group receiving PN 15-30 days had increased SIRS score on day 1 after starting EN, but SIRS score returned to previous levels on day 3 of EN.  The group without enteral nutrition greater than 30 days had increased SIRS score on days 1 and day 3 after starting EN with return to previous levels on day 5 of EN.  Increased WBC and fever were reported in 26 patients in the first 3 days of EN, but only 7 patients (26% of those with fever) had positive catheter tip cultures.  Stool frequency and the incidence of diarrhea (defined as > 3 stools/day) were significantly increased after the start of EN.

Three patients developed cholecystitis and cholestasis within the first 3 days after starting EN.  Five patients were reported to have gallbladder sludge by ultrasound.

Author's Conclusions:

The investigators use the term "enteral refeeding syndrome" to describe the lab changes and increased SIRS scores noted in their patients following the start of EN after a period of gut rest/ PN.  They postulate that this syndrome is caused by cholestasis and atrophy or edema of the intestinal mucosa resulting from long-term fasting, and that the only solution for this "syndrome" is continued enteral feeding.


This was not a randomized or blinded study, and there was no comparison group that did not begin EN.  The investigators simply described physiologic events that occurred after starting EN.  In such a design, without a control group it is not appropriate to assume that starting EN was the cause of these changes.  The authors report that catheter-related sepsis was suspected in 26 patients due to fever and elevated WBC after starting EN, but that a positive catheter tip was found in only 7 patients.  However, a catheter related sepsis is not the only cause for fever, increased WBC or elevated hepatic enzymes.  Pneumonia, urinary tract infection, and medication related reactions are among the myriad of other factors that can also contribute to these changes, and frequently occur in hospitalized patients.  No mention was made of antibiotic or other medication changes that occurred after a patient developed fever or SIRS. 

The authors reported increased stool output after initiation of enteral feeding, and an increased number of patients with more than 3 stools per day on days 1, 3, 5, and 15th day after starting EN.  However, there is no record of medications given through the feeding tube such as sorbitol-containing liquids and elixirs, laxatives and stool softeners, or enteral electrolyte replacement.  Finally, the author provides no information about the underlying etiology of 100 patients presenting with fistula in a 15 month period-one wonders if there are factors relating to the underlying disease that contributed to lab changes associated with starting enteral feeding.  The article does not provide information if this is a specialty facility that so many patients would have fistulas, or why there would be such a high incidence of fistula formation.

Importantly, although mean body temperature was reported to be statistically increased after starting enteral feeding, a glance at the tables tells us that body temperature increased from 37.1 +/- 0.8 to only 37.3 +/- 0.7.  A temperature of increase of 0.2 degrees Celsius is not a clinically significant increase in temperature.  Likewise, there is no evidence that these changes in lab values or physiologic variables resulted in significant clinical sequelae. 

Although it is not possible to ascribe cause and effect to enteral feeding with the current study methods, it IS possible that restarting EN after a period of "GI tract starvation" may have physiologic consequences.  The observational nature of this study is appropriate to form theories and collect data necessary for a randomized study. 

Our Take home message:

Although the theory of "enteral refeeding syndrome" should be investigated further, there is no evidence that there is a clinically significant sequelae caused by the initiation of enteral feeding after a period of gut rest, nor that it is in any way related to what is currently thought of as "refeeding syndrome." 

Other News:

•1)     Check out the latest Practical Gastroenterology articles/info at:

Scroll down to GI Nutrition to the pull down menu with links within the GI nutrition site and look for "Nutrition Articles in Practical Gastroenterology."  The August and September articles are:

  • ¨ Krenitsky, J., Makola D., Parrish, C. Parenteral Nutrition in Pancreatitis is Passé: But Are We Ready for Gastric Feeding? A Critical Evaluation of the Literature - Part I. Practical Gastroenterology 2007;XXXI(9):92.
  • ¨ Barrett J,Gibson P. Clinical ramifications offructosemalabsorption offructose and other short-chain carbohydrates. Practical Gastroenterology 2007;XXXI(7):51.

Joe Krenitsky MS, RD

Carol Parrish RD, MS

PS - Please feel free to forward this on to friends and colleagues.