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Cat review - erythromycin corrected
Erythromycin is more effective than
metoclopramide in the treatment of feed
intolerance in critical illness
In intensive care patients with feed intolerance, erythromycin reduces gastric residual volume more effectively than
metoclopramide (NNT 4). Both drugs rapidly become ineffective. In patients who fail monotherapy, an open-label,
non-controlled extension of this study suggests combination therapy may be effective.
Level of evidence: 1+ (RCT with a low risk of bias)
Citation: Nguyen NQ, Chapman MJ, Fraser RJ, et al
medical and surgical intensive care unit, who failed nasogastric
Erythromycin is more effective than metoclopramide in the
feeding (six hourly gastric residual volume >250 mL, >6 h after
treatment of feed intolerance in critical illness. Crit Care Med
starting enteral feeding at >40 mL/h).
contraindication to prokinetics, major abdominal surgery orsuspected obstruction or perforation. Seventeen of the 107
patients enrolled were excluded from the analysis because their
Mechanically ventilated intensive care patients with
participation in the trial was <7 days (as per trial protocol),
nine due to early recovery and tolerance of oral diet and eight
Erythromycin or metoclopramide.
due to death from withdrawal of medical therapy.
Demographics similar in the two groups in most respects:
Search terms: Ovid Medline MeSH terms: enteral nutrition;
Admission APACHE II 25, 73% male, BMI 27, six days in ICU
gastrointestinal agents; critical illness.
before randomisation, pre-treatment gastric residual volume(GRV), feeding rate achieved before development of feed
The study: Double-blinded concealed randomised controlled
intolerance, blood glucose, medication and ventilation rates.
trial but without intention-to-treat. Patients randomised to
However, there were significantly more septic patients in the
either metoclopramide or erythromycin. Feeding recommenced
erythromycin group and trauma patients in the
at 40 mL/h after the first dose of trial drug. Stomach aspirated
two hours after first dose then six hourly. If GRV <250 mL the
Erythromycin group (N=53; 45 analysed): 200 mg IV twice
feeding rate was increased by 20 mL/h every six hours up to
predicted requirement. Therapy continued for seven days oruntil discharge in feed-tolerant patients. Patients who failed
Metoclopramide group (N=54; 45 analysed): 10 mg IV four
with either erythromycin or metoclopramide were treated with
1. Do the methods allow the accurate testing of the hypothesis?
Mechanically ventilated patients in a mixed
Yes. However the effects of combined therapy must be
Rescue therapy (51 patients)
interpreted with care as this phase of the study was non-
7. Is this study relevant to my clinical practice?
Yes – feed
blinded, uncontrolled and under-powered.
intolerance is a common problem. This trial uses the
2. Do the statistical tests correctly test the results to allow
surrogate marker of residual gastric volume to measure the
differentiation of statistically significant result?
success of enteral feeding. There are no measures of clinical
to detect a 20% difference in the rate of successful feeding.
outcomes such as mortality, length of stay, nutritional state
Tests seem appropriate. They describe the two groups as
or ventilator associated pneumonia (related to gastric
“similar” in demographics including diagnosis, but there
paresis and aspiration). Other studies of prokinetics and
are statistically significant differences (using chi squared)
post-pyloric feeding have failed to show outcome benefit
with more sepsis and less trauma in the erythromycin
group. These were not among the factors associated with
8. What level of evidence does this study represent?
9. What grade of recommendation can I make on this result
3. Are conclusions valid in light of the results?
erythromycin is more effective than metoclopramide in
10. What grade of recommendation can I make when this study is
treating feed intolerance as they have defined it. However
considered along with other available evidence?
the effectiveness of both diminishes over time. Although
improving gastric motility – no studies on prokinetics have
combination therapy may provide a more sustained
improvement it will need further investigation with an
11. Should I change my practice because of these results?
adequately powered, randomised controlled trial.
Possibly. Erythromycin seems a better single agent prior to
4. Did results get omitted, and why?
Yes. (see study patients)
combination therapy for non-responders. Future, larger
5. Did they suggest areas of further research?
studies ruling out antibiotic resistance as a concern would
investigation of combination therapy and potential role as
be reassuring. Prolonged single agent use seems ineffective.
first line, role of prokinetics such as tegaserod (5HT4 partial
12. Should I audit my current practice because of these results?
agonist) and loxiglumide (CCK- A antagonist).
6. Did they make recommendations based on the results and were
“the short term use of low-dose
erythromycin is a reasonable approach for the treatment of
SpR Anaesthetics Glasgow Royal Infirmary, UK.
feed intolerance in critical illness”. Probably appropriate –
difficult to say without more evidence on antibioticresistance and adverse effects.
Reviewed and edited by Chris Cairns and Bruce Taylor
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