Skip to main content
PMC home page
Archives of Disease in Childhood. Fetal and Neonatal Edition logoLink to Archives of Disease in Childhood. Fetal and Neonatal Edition
. 2001 May;84(3):F177–F182. doi: 10.1136/fn.84.3.F177

Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants

P Ng, K So, K Fung, C Lee, T Fok, E Wong, W Wong, K Cheung, A Cheng
PMCID: PMC1721258  PMID: 11320044

Abstract

AIM—To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants.
METHODS—A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to the neonatal unit. The infants were randomly allocated by minimisation to receive oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent volume of placebo solution (normal saline) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were compared between the two groups. Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes.
RESULTS—Twenty seven and 29 infants received oral erythromycin and placebo solution respectively. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo (p < 0.05, p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group (10v 5 infants). None of the infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric stenosis, or septicaemia caused by multiresistant organisms.
CONCLUSIONS—Oral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility. Treated infants can achieve full enteral feeding 10 days earlier, and this may result in a substantial saving on hyperalimentation. However, until the safety of erythromycin has been confirmed in preterm infants, this treatment modality should remain experimental. Prophylactic or routine use of this medication for treatment of mild cases of gastrointestinal dysmotility is probably not warranted at this stage.



Full Text

The Full Text of this article is available as a PDF (126.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Annese V., Janssens J., Vantrappen G., Tack J., Peeters T. L., Willemse P., Van Cutsem E. Erythromycin accelerates gastric emptying by inducing antral contractions and improved gastroduodenal coordination. Gastroenterology. 1992 Mar;102(3):823–828. doi: 10.1016/0016-5085(92)90164-t. [DOI] [PubMed] [Google Scholar]
  2. Berseth C. L. Gestational evolution of small intestine motility in preterm and term infants. J Pediatr. 1989 Oct;115(4):646–651. doi: 10.1016/s0022-3476(89)80302-6. [DOI] [PubMed] [Google Scholar]
  3. Berseth C. L., Nordyke C. Enteral nutrients promote postnatal maturation of intestinal motor activity in preterm infants. Am J Physiol. 1993 Jun;264(6 Pt 1):G1046–G1051. doi: 10.1152/ajpgi.1993.264.6.G1046. [DOI] [PubMed] [Google Scholar]
  4. Bisset W. M., Watt J. B., Rivers R. P., Milla P. J. Ontogeny of fasting small intestinal motor activity in the human infant. Gut. 1988 Apr;29(4):483–488. doi: 10.1136/gut.29.4.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bruley des Varannes S., Parys V., Ropert A., Chayvialle J. A., Rozé C., Galmiche J. P. Erythromycin enhances fasting and postprandial proximal gastric tone in humans. Gastroenterology. 1995 Jul;109(1):32–39. doi: 10.1016/0016-5085(95)90266-x. [DOI] [PubMed] [Google Scholar]
  6. Colombo M., Magni L. A. Biopsia digiunale con capsula di Watson ed eritromicina. Minerva Pediatr. 1995 Mar;47(3):97–98. [PubMed] [Google Scholar]
  7. Coulie B., Tack J., Peeters T., Janssens J. Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans. Gut. 1998 Sep;43(3):395–400. doi: 10.1136/gut.43.3.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cucchiara S., Minella R., Scoppa A., Emiliano M., Calabrese F., Az-Zeqeh N., Rea B., Salvia G. Antroduodenal motor effects of intravenous erythromycin in children with abnormalities of gastrointestinal motility. J Pediatr Gastroenterol Nutr. 1997 Apr;24(4):411–418. doi: 10.1097/00005176-199704000-00010. [DOI] [PubMed] [Google Scholar]
  9. Di Lorenzo C., Lachman R., Hyman P. E. Intravenous erythromycin for postpyloric intubation. J Pediatr Gastroenterol Nutr. 1990 Jul;11(1):45–47. doi: 10.1097/00005176-199007000-00009. [DOI] [PubMed] [Google Scholar]
  10. Farrar H. C., Walsh-Sukys M. C., Kyllonen K., Blumer J. L. Cardiac toxicity associated with intravenous erythromycin lactobionate: two case reports and a review of the literature. Pediatr Infect Dis J. 1993 Aug;12(8):688–691. doi: 10.1097/00006454-199308000-00011. [DOI] [PubMed] [Google Scholar]
  11. Fraser R., Shearer T., Fuller J., Horowitz M., Dent J. Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility. Gastroenterology. 1992 Jul;103(1):114–119. doi: 10.1016/0016-5085(92)91103-b. [DOI] [PubMed] [Google Scholar]
  12. Gouyon J. B., Benoit A., Bétremieux P., Sandre D., Sgro C., Bavoux F., Beneton C., Badoual J. Cardiac toxicity of intravenous erythromycin lactobionate in preterm infants. Pediatr Infect Dis J. 1994 Sep;13(9):840–841. doi: 10.1097/00006454-199409000-00028. [DOI] [PubMed] [Google Scholar]
  13. Gouyon J. B. The use of erythromycin lactobionate to facilitate the postpyloric passage of tubes in children. J Pediatr Gastroenterol Nutr. 1992 Jan;14(1):120–120. doi: 10.1097/00005176-199201000-00029. [DOI] [PubMed] [Google Scholar]
  14. Hill A. D., Walsh T. N., Hamilton D., Freyne P., O'Hare N., Byrne P. J., Hennessy T. P. Erythromycin improves emptying of the denervated stomach after oesophagectomy. Br J Surg. 1993 Jul;80(7):879–881. doi: 10.1002/bjs.1800800726. [DOI] [PubMed] [Google Scholar]
  15. Houin G., Tillement J. P., Lhoste F., Rapin M., Soussy C. J., Duval J. Erythromycin pharmacokinetics in man. J Int Med Res. 1980;8 (Suppl 2):9–14. [PubMed] [Google Scholar]
  16. Jadcherla S. R., Klee G., Berseth C. L. Regulation of migrating motor complexes by motilin and pancreatic polypeptide in human infants. Pediatr Res. 1997 Sep;42(3):365–369. doi: 10.1203/00006450-199709000-00018. [DOI] [PubMed] [Google Scholar]
  17. Janssens J., Hellemans J., Adrian T. E., Bloom S. R., Peeters T. L., Christofides N., Vantrappen G. R. Pancreatic polypeptide is not involved in the regulation of the migrating motor complex in man. Regul Pept. 1982 Jan;3(1):41–49. doi: 10.1016/0167-0115(82)90005-2. [DOI] [PubMed] [Google Scholar]
  18. Janssens J., Peeters T. L., Vantrappen G., Tack J., Urbain J. L., De Roo M., Muls E., Bouillon R. Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies. N Engl J Med. 1990 Apr 12;322(15):1028–1031. doi: 10.1056/NEJM199004123221502. [DOI] [PubMed] [Google Scholar]
  19. Kubota M., Nakamura T., Motokura T., Mori S., Nishida A. Erythromycin improves gastrointestinal motility in extremely low birthweight infants. Acta Paediatr Jpn. 1994 Apr;36(2):198–201. doi: 10.1111/j.1442-200x.1994.tb03161.x. [DOI] [PubMed] [Google Scholar]
  20. Lyon A. J., McColm J., Middlemist L., Fergusson S., McIntosh N., Ross P. W. Randomised trial of erythromycin on the development of chronic lung disease in preterm infants. Arch Dis Child Fetal Neonatal Ed. 1998 Jan;78(1):F10–F14. doi: 10.1136/fn.78.1.f10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mathis C., Malbert C. H. Changes in pyloric resistance induced by erythromycin. Neurogastroenterol Motil. 1998 Apr;10(2):131–138. doi: 10.1046/j.1365-2982.1998.00086.x. [DOI] [PubMed] [Google Scholar]
  22. Ng P. C., Fok T. F., Lee C. H., Wong W., Cheung K. L. Erythromycin treatment for gastrointestinal dysmotility in preterm infants. J Paediatr Child Health. 1997 Apr;33(2):148–150. doi: 10.1111/j.1440-1754.1997.tb01018.x. [DOI] [PubMed] [Google Scholar]
  23. Nieuwenhuijs V. B., van Duijvenbode-Beumer H., Verheem A., Visser M. R., Verhoef J., Gooszen H. G., Akkermans L. M. The effects of ABT-229 and octreotide on interdigestive small bowel motility, bacterial overgrowth and bacterial translocation in rats. Eur J Clin Invest. 1999 Jan;29(1):33–40. doi: 10.1046/j.1365-2362.1999.00364.x. [DOI] [PubMed] [Google Scholar]
  24. Otterson M. F., Sarna S. K. Gastrointestinal motor effects of erythromycin. Am J Physiol. 1990 Sep;259(3 Pt 1):G355–G363. doi: 10.1152/ajpgi.1990.259.3.G355. [DOI] [PubMed] [Google Scholar]
  25. Parkman H. P., Pagano A. P., Vozzelli M. A., Ryan J. P. Gastrokinetic effects of erythromycin: myogenic and neurogenic mechanisms of action in rabbit stomach. Am J Physiol. 1995 Sep;269(3 Pt 1):G418–G426. doi: 10.1152/ajpgi.1995.269.3.G418. [DOI] [PubMed] [Google Scholar]
  26. Parsons R. L., David J. A., Raymond K., Stamp S. M. Pharmacokinetics of intravenous erythromycin lactobionate. J Int Med Res. 1980;8 (Suppl 2):15–23. [PubMed] [Google Scholar]
  27. Pennathur A., Tran A., Cioppi M., Fayad J., Sieren G. L., Little A. G. Erythromycin strengthens the defective lower esophageal sphincter in patients with gastroesophageal reflux disease. Am J Surg. 1994 Jan;167(1):169–173. doi: 10.1016/0002-9610(94)90069-8. [DOI] [PubMed] [Google Scholar]
  28. Pilot M. A. Macrolides in roles beyond antibiotic therapy. Br J Surg. 1994 Oct;81(10):1423–1429. doi: 10.1002/bjs.1800811006. [DOI] [PubMed] [Google Scholar]
  29. Simkiss D. E., Adams I. P., Myrdal U., Booth I. W. Erythromycin in neonatal postoperative intestinal dysmotility. Arch Dis Child. 1994 Sep;71(2):F128–F129. doi: 10.1136/fn.71.2.f128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Siu Y. K., Ng P. C., Fung S. C., Lee C. H., Wong M. Y., Fok T. F., So K. W., Cheung K. L., Wong W., Cheng A. F. Double blind, randomised, placebo controlled study of oral vancomycin in prevention of necrotising enterocolitis in preterm, very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 1998 Sep;79(2):F105–F109. doi: 10.1136/fn.79.2.f105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stenson B. J., Middlemist L., Lyon A. J. Influence of erythromycin on establishment of feeding in preterm infants: observations from a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 1998 Nov;79(3):F212–F214. doi: 10.1136/fn.79.3.f212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stern M. A., Wolf D. C. Erythromycin as a prokinetic agent: a prospective, randomized, controlled study of efficacy in nasoenteric tube placement. Am J Gastroenterol. 1994 Nov;89(11):2011–2013. [PubMed] [Google Scholar]
  33. Su B. H., Lin H. C., Peng C. T., Tsai C. H. Effect of erythromycin on feeding intolerance in very low birth weight infants: a preliminary observation. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1998 Sep-Oct;39(5):324–326. [PubMed] [Google Scholar]
  34. Tack J., Janssens J., Vantrappen G., Peeters T., Annese V., Depoortere I., Muls E., Bouillon R. Effect of erythromycin on gastric motility in controls and in diabetic gastroparesis. Gastroenterology. 1992 Jul;103(1):72–79. doi: 10.1016/0016-5085(92)91097-n. [DOI] [PubMed] [Google Scholar]
  35. Tomomasa T., Miyazaki M., Koizumi T., Kuroume T. Erythromycin increases gastric antral motility in human premature infants. Biol Neonate. 1993;63(6):349–352. doi: 10.1159/000243954. [DOI] [PubMed] [Google Scholar]
  36. Vantrappen G., Janssens J., Peeters T. L., Bloom S. R., Christofides N. D., Hellemans J. Motilin and the interdigestive migrating motor complex in man. Dig Dis Sci. 1979 Jul;24(7):497–500. doi: 10.1007/BF01489315. [DOI] [PubMed] [Google Scholar]
  37. Verhagen M. A., Samsom M., Maes B., Geypens B. J., Ghoos Y. F., Smout A. J. Effects of a new motilide, ABT-229, on gastric emptying and postprandial antroduodenal motility in healthy volunteers. Aliment Pharmacol Ther. 1997 Dec;11(6):1077–1086. doi: 10.1046/j.1365-2036.1997.00260.x. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood. Fetal and Neonatal Edition are provided here courtesy of BMJ Publishing Group

RESOURCES