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Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness.
Three-part Clinical Question: Patients: Mechanically ventilated intensive care patients with feed intolerance. Intervention: Erythromycin or metoclopramide. Outcome: Feed tolerance.
The Study: Double-blinded concealed randomised controlled trial but without intention-to-treat. Patients randomised to either metoclopramide or erythromycin. Feeding recommenced at 40ml/h after the first dose of trial drug. Stomach aspirated 2h after first dose then 6 hourly. If GRV <250ml the feeding rate was increased by 20ml/h every 6 hours up to predicted requirement. Therapy continued for 7 days or until discharge in feed tolerant patients. Patients who failed with either erythromycin or metoclopramide were treated with open-label combination therapy.
Inclusion criteria: Mechanically ventilated patients in a mixed medical & surgical intensive care unit, who failed nasogastric feeding (6-hourly gastric residual volume >250ml, >6h after starting enteral feeding at >40ml/h). Main exclusion criteria: recent administration of or contraindication to prokinetics, major abdominal surgery or suspected obstruction or perforation. 17 of the 107 patients enrolled were excluded from the analysis because their participation in the trial was <7 days (as per trial protocol). Nine due to early recovery and tolerance of oral diet and eight due to death from withdrawal of medical therapy. Demographics similar in the 2 groups in most respects: Admission APACHE II 25, 73% male, BMI 27, 6 days in ICU before randomisation, pre-treatment gastric residual volume (GRV), feeding rate achieved before development of feed intolerance, blood glucose, medication and ventilation rates. However, there were significantly more septic patients in the erythromycin group and trauma patients in the metoclopramide group.
Erythromycin group (N = 53; 45 analysed): 200mg i.v. twice daily. Placebo i.v., twice daily.
Metoclopramide group (N = 54; 45 analysed): 10mg i.v. four times a day.
The Evidence (EN=enteral nutrition):
EBM Questions:
1. Do the methods allow the adequate testing of the hypothesis? Yes. However the effects of combined therapy must be interpreted with care as this phase of the study was non-blinded, uncontrolled and under powered. 2. Do the statistical tests correctly test the results to allow differentiation of statistically significant result? Yes. Powered to detect a 20% difference in the rate of successful feeding. Tests seem appropriate. They describe the two groups as "similar" in demographics including diagnosis, but there are statistically significant differences (using chi squared) with more sepsis and less trauma in the erythromycin group. These were not among the factors associated with poor response to prokinetics. 3. Are conclusions valid in light of results? Partly - erythromycin is more effective than metoclopramide in treating feed intolerance as they have defined it. However the effectiveness of both diminishes over time. Although combination therapy may provide a more sustained improvement it will need further investigation with an adequately powered, randomised controlled trial. 4. Did results get omitted, and why? Yes. (see study patients) 5. Did they suggest areas of further research? Yes: Further investigation of combination therapy and potential role as first line, role of prokinetics such as tegaserod (5HT4 partial agonist) and loxiglumide (CCK1 antagonist).
6.
Did they make recommendations based on results and were they
appropriate? 7. Is this study relevant to my clinical practice? Yes - feed intolerance is a common problem. This trial uses the surrogate marker of residual gastric volume to measure the success of enteral feeding. There is no measure of clinical outcomes such as mortality, length of stay, nutritional state, ventilator associated pneumonia (related to gastric paresis & aspiration). Other studies of prokinetics and post-pyloric feeding have failed to show outcome benefit despite reduced gastric volumes.
8. What level of evidence does this study represent? 1+
9. What grade of recommendation can I make on this result alone? B
10.
What grade of
recommendation can I make when this study is considered along with other
available evidence? 11. Should I change my practice because of these results? Possibly, erythromycin seems a better single agent prior to combination therapy for non-responders. Future, larger studies ruling out antibiotic resistance as a concern would be reassuring. Prolonged single agent use seems ineffective.
12. Should I audit my current practice because of these results? Yes.
Appraised by: Kate Janossy, SpR Anaesthetics Glasgow Royal Infirmary, UK. 30
June 2007
Reviewed & Edited by Chris Cairns & Bruce Taylor
©SICS EBMG 2009
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