Promoting tolerance of enteral feeds in children and young people: domperidone

Evidence review: efficacy

During the development of this evidence summary, a search was carried out for published studies using domperidone to promote tolerance of enteral feeds in children and young people (under the age of 18). No publication date or study design search limitations were used in the initial search. For important evidence selection information, see the Evidence selection section.

The search highlighted a very limited amount of directly applicable research relevant to this specific off-label use of domperidone. The most relevant published information came from a single study (Gounaris et al. 2010), which was a small randomised, crossover study in very low birth weight preterm neonates receiving enteral feeding. The authors describe the study as partially blinded, but it is not clear who was blind to treatments other than the radiologists involved in measuring gastric emptying times in the neonates.

Because of the small sample size (n=22) and short-term nature (48-hour treatment) of the study, its results have limited reliability for determining the effectiveness of domperidone in these neonates. Its results also have limited applicability to the use of domperidone for promoting the tolerance of enteral feeds in older children and young people.

The study, based in Greece, included 22 preterm (gestational age less than 34 weeks, mean age 30.2 weeks) very low birth weight neonates (birth weight less than 2000 grams, mean weight 1377 grams) with a clinical history of 1 or more problems in gut motility, such as regurgitation, vomiting, abdominal distension and delay in stool passage.

All neonates were fully enterally fed, receiving 200 ml/kg/day of milk (either standard premature infant formula [n=12] or their mother's own supplemented milk [n=10]) by nasogastric tube given by gravity. In addition, neonates were randomised to first receive either domperidone (Cilroton, Janssen) at a dose of 0.3 mg/kg/8 hours or an equal quantity of sterile water (the control group), given for a 48-hour period. This was followed by a 1 to 3-day treatment-free washout period. Then a second 48-hour treatment period was started in which the neonates were switched to the other treatment option (a crossover design).

Gastric emptying was the primary outcome and the authors report that this was measured on 2 occasions in each infant; first on administration of domperidone and second after discontinuation of domperidone while receiving an equal quantity of sterile water for an additional 48-hour period. The authors state that 11 infants received domperidone before the first measurement of gastric emptying and the other 11 infants received domperidone after sterile water treatment just before the second measurement. Gastric emptying was assessed by ultrasound using serial measurements of the antral cross-sectional area (ACSA) of the stomach taken before enteral feeding, immediately after feeding, then every 10 minutes for the first half hour, and then every 30 minutes up to 2 hours. Two radiologists carried out the ultrasound assessments; both were blinded to the treatment allocation of the neonates. The primary outcome and main statistical comparison was the average time (mean time, in minutes) it took the ACSA to reach half of its initial value after feeding in both groups, called the ACSA half-time.

Secondary outcomes included number of stools passed in the 48-hour treatment period and the differences in gastric emptying in neonates fed their mother's own supplemented milk compared with neonates fed formula milk. Throughout the study neonates were observed for gastric residual volume (considered significant if it exceeded 25% of the previous 2 hours' feeding volume), vomiting and abdominal distension. These were assessed and recorded by a nurse. All neonates completed the study and were included in the analysis.

The study found that neonates had shorter mean gastric emptying times (ACSA half-time) when receiving domperidone (47.6 minutes, standard deviation [SD] 23.9 minutes) compared with sterile water (68.2 minutes, SD 25.5 minutes). This was a statistically significant difference (p=0.008). In total, 18 of 22 neonates showed shorter gastric emptying times while on domperidone compared with water. In the other 4 neonates, 2 had a shorter gastric emptying time while receiving water and 2 showed equal times on both treatments.

For the secondary outcomes, the mean number of stools passed while receiving domperidone (2.4, SD 1.9) was statistically significantly greater than while receiving water (1.8, SD 0.7, p=0.038). There was no significant difference in gastric emptying between neonates receiving milk formula and those receiving their mother's supplemented milk (p=0.418 domperidone group, p=0.610 water group).

There were no differences between the 2 groups in the number of times vomiting occurred, but no figures were reported for this outcome. Similarly, no results were presented for gastric residual volume or frequency of abdominal distension.