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University of Virginia Health System

Nutrition Support E-Journal Club

November 2007


We had a wonderful November traineeship session.  This month 3 of our trainees traveled from Texas, and one from British Columbia.  Our weather here was mild, with temperatures in the 50's-60's, and we still had our Fall foliage to show off during our traineeship week.   

November Citation: 

  • Nguyen NQ, Chapman M, Fraser RJ, et al. Prokinetic therapy for feed intolerance in critical illness: One drug or two? Crit Care Med 2007;35(11):2561-2567.


This was a prospective, randomized, double-blind study that investigated the effectiveness of combination therapy of intravenous erythromycin plus intravenous metoclopramide compared to intravenous erythromycin alone as a prokinetic for treatment of enteral feeding intolerance in critically ill patients.  Patients that met the study definition for gastric enteral feeding intolerance (see inclusion criteria below) were randomized to receive either combination therapy (erythromycin 200 mg iv twice daily with intravenous metoclopramide 10 mg iv four times daily; n= 37) or intravenous erythromycin alone (200 mg iv erythromycin twice daily and four placebo injections of 0.9% normal saline for blinding purposes; n=38).

The primary outcomes of the study were gastric residual volumes (GRV) q 6 hours, volume of daily prescribed and administered feeds, occurrence of vomiting, and requirement for postpyloric feeding tube insertion. Secondary outcomes were length of hospital stay and mortality, as well as what the authors called "potential side effects of therapy" such as development of diarrhea.  The feeding tube position was confirmed daily by radiograph over the 7-day study period to ensure that the tube had not migrated into the duodenum.

Inclusion and Exclusion Criteria were:

The study enrolled 75 consecutive mechanically ventilated patients who "failed NG feeding."  Failure of feeding was defined as a GRV > 250 mL (6 hrs or greater after commencement of feeding) at a rate of at least 40 mL/hr.  Patients had a 12-Fr (or larger) NG tubes placed into the stomach before the study, with the distal tip 10 cm below the gastroesophageal junction and clearly visible in the stomach on a routine abdominal radiograph.

Exclusion criteria were:

1) Use of prokinetic drugs (metoclopramide, cisapride, or erythromycin) within the previous 24 hrs;

2) Known allergy to a macrolide antibiotic or metoclopramide;

3) Receiving drugs known to interact with erythromycin;

4) Major gastrointestinal surgery (laparotomy with part of the gastrointestinal tract removed or repaired) within the previous 6 wks, or had a past history of esophagectomy or partial or total gastrectomy;

5) Suspected bowel obstruction or perforation;

6) Evidence of liver dysfunction

7) Myasthenia gravis

Major Results reported by authors:

The investigators reported that GRV was significantly lower after 24 hrs of treatment with combination therapy, compared with erythromycin alone (136 ± 23 mL vs. 293 ± 45 mL, p = .04). In addition, patients treated with combination therapy had greater feeding success, received significantly more daily calories, and had a significantly lower requirement for postpyloric feeding, compared with erythromycin alone. There was no difference in the incidence of vomiting, length of hospital stay or mortality rate between the groups. Watery diarrhea was more common with combination therapy (20 of 37 vs. 10 of 38, p = .01) but was not associated with enteric infections, including Clostridium difficile.

The authors reported that the effectiveness of both prokinetic therapies diminished over the 7 day study.  The diminished prokinetic effectiveness (tachyphylaxis) occurred in both groups, but less so with combination therapy.

Author's Conclusions:

The investigators concluded that in critically ill patients with feeding intolerance, combination therapy with erythromycin and metoclopramide is more effective than erythromycin alone in improving the delivery of nasogastric nutrition and should be considered as the first-line treatment.


This is a well designed study with a number of strengths, including randomized allocation, double-blinding and analysis done both intention to treat (on all patients that were randomized) and per-protocol (only those patients that completed the full study protocol).  Another virtue of this study is that, unlike some past studies of prokinetic treatment, only patients with elevated GRV were enrolled.  One limitation of this study is that sorbitol-containing liquid/ syrup/ elixir medications that may have affected diarrhea incidence were not accounted for.  The randomized design of this study should limit differences between the groups, but with relatively small studies it is possible for differences to occur.

The group discussed why the study definition of feeding intolerance makes practical sense, given that many hospitals will stop enteral feeding for GRV > 250 mL.  However, we must point out that the study definition of feeding intolerance, i.e. GRV > 250 mL, is not a sensitive, proven, or even clinically significant indicator of feeding intolerance/failure.  A single gastric residual volume of 250 mL is not necessarily an indication of the need to reduce tube feeding volume, or to add additional medications.  Considering that one purpose of the stomach is to act as a "reservoir" it is physiologic to see pooling of secretions/feeding in the gastric fundus in patients with intact gastric emptying.  We commonly see patients with a single GRV greater than 250 mL that "returns to normal" at the next check with continued feeding.  Positioning the patient on the right side (with elevated head of bed) for a short period prior to the next GRV check also frequently results in GRV returning to "normal." 

This study was much too small to examine outcomes such as length of stay or mortality, but ultimately the effect of prokinetics on these outcomes IS an important question.  Considering the unexpected findings from large studies in recent years, it will be important to find out if prokinetic medications offer a net benefit, or if there are unexpected disadvantages there were not clinically apparent.

Our Take home message:

Combination therapy with metoclopramide plus erythromycin appears to offer advantages over erythromycin alone in treating GRV.  Larger studies are necessary to learn what is the best way to treat the patient.

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 November article is:

  • ¨ McCray S. Balaban D. The Gourmet Colon Prep. Practical Gastroenterology 2007;XXXI(11):41.
  • ¨ December's will be:
  • o Anderson T. Beyond the Scope: The Hidden Images of Eating Disorders. Practical Gastroenterology 2007;XXXI(12):In press.

Joe Krenitsky MS, RD

Carol Parrish RD, MS


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