Published online February 1, 2006
PEDIATRICS Vol. 117 No. 2 February 2006, pp. 531-532 (doi:10.1542/peds.2005-2230)
This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Patole, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Patole, S.
Related Collections
Right arrow Premature & Newborn
Right arrowRelated AAP Red Book topics:
Yersinia enterocolitica and...
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

COMMENTARY

Association of H2-Blocker Therapy and Higher Incidence of Necrotizing Enterocolitis: A Case of Excessive Collateral Damage?

Sanjay Patole, MD, DCH, FRACP

Department of Neonatal Paediatrics, King Edward Memorial Hospital for Women, University of Western Australia, Perth, Western Australia

Abbreviations: NEC, necrotizing enterocolitis

In this issue of Pediatrics Electronic Edition, Guillet et al1 report the association of H2-blocker therapy with higher incidence of stage II or greater necrotizing enterocolitis (NEC) in very low birth weight neonates using a case-control design. The finding is not necessarily surprising given the link between sepsis and NEC in preterm neonates24 and the association of antacid therapy with nosocomial infections that has been well known for at least 15 to 20 years in adult intensive care literature.512 Ironically, as the authors point out, as far back as in 1990 Carrion and Egan13 had reported that acidifying the feeds to a pH level low enough to inhibit bacterial proliferation in the stomach significantly lowered the risk (1 of 34 vs 8 of 34; P = .02) of NEC in preterm neonates. The median gastric pH level of the HCl-supplemented group was lower (3.0) than that of the control group (4.0) throughout the study (P < .001).13

The frequency of prophylactic H2-blocker therapy of up to 72.2% is disturbing given that there is not much high-quality evidence to support it.1418 Clinically significant bleeding as well as the mortality related to stress-related upper-gastrointestinal ulcerations are currently an uncommon phenomenon, possibly because of the improved management of hypoxia and shock, with its accompanying gastric hypoperfusion in critically ill neonates.5,1922 The fact that gastric acid alone is not the only culprit in the causation of stress ulcers was demonstrated clearly years ago by their occurrence in patients with congenital achlorhydria.23 Stress-ulcer prophylaxis has not been shown to significantly reduce the mortality rates in adult ICUs.24,25 It is also important to note that treatment with antacids or H2 blockers has been associated with significantly higher mortality rates in long-term ventilated patients compared with those treated with sucralfate.26

The study by Guillet et al has the strength of numbers, which are certainly needed for an uncommon and poorly understood illness such as NEC; however, a few drawbacks are worth mentioning.1 The single-most important risk factor for NEC is prematurity. It would have been helpful to analyze the data by controlling for at least gestational age rather than birth weight and for other confounding factors such as antenatal glucocorticoids, intrauterine growth retardation, enteral feeding, and Clinical Risk Index for Babies scores. Despite these issues, the findings by Guillet et al should serve as a reminder that everything, including gastric acid, is there for a purpose.10,27,28


    FOOTNOTES
 
Accepted Sep 8, 2005.

Address correspondence to Sanjay Patole, MD, DCH, FRACP, Department of Neonatal Paediatrics, King Edward Memorial Hospital for Women, University of Western Australia, Perth 6008, Western Australia. E-mail: sanjay.patole{at}health.wa.gov.au

The author has indicated he has no financial relationships relevant to this article to disclose.


    REFERENCES
 TOP
 REFERENCES
 

  1. Guillet R, Stoll BJ, Cotton CM, et al. Association of H2-blocker therapy and higher incidence of necrotizing enterocolitis in very low birth weight infants. Pediatrics. 2006;117 (2). Available at: www.pediatrics.org/cgi/content/full/117/2/e137
  2. Walther FJ, Verloove-Vanhorick SP, Brand R, Ruys JH. A prospective survey of necrotising enterocolitis in very low birthweight infants. Paediatr Perinat Epidemiol. 1989;3 :53 –61[CrossRef][Medline]
  3. Chan KL, Saing H, Yung RW, Yeung YP, Tsoi NS. A study of pre-antibiotic bacteriology in 125 patients with necrotizing enterocolitis. Acta Paediatr Suppl. 1994;396 :45 –48[Medline]
  4. Stoll BJ. Epidemiology of necrotizing enterocolitis. Clin Perinatol. 1994;21 :205 –218[Web of Science][Medline]
  5. Tryba M. Role of acid suppressants in intensive care medicine. Best Pract Res Clin Gastroenterol. 2001;15 :447 –461[CrossRef][Medline]
  6. Ortiz JE, Sottile FD, Siegel P, Nasraway SA. Gastric colonization as a consequence of stress ulcer prophylaxis: a prospective, randomized trial. Pharmacotherapy. 1998;18 :486 –491[Web of Science][Medline]
  7. Tryba M, Cook DJ. Gastric alkalinization, pneumonia, and systemic infections: the controversy. Scand J Gastroenterol Suppl. 1995;210 :53 –59[Medline]
  8. Sing RF, Marino PL. A new perspective on stress ulcer prophylaxis. J Am Osteopath Assoc. 1992;92 :1026 –1027[Abstract]
  9. Tryba M. The gastropulmonary route of infection: fact or fiction? Am J Med. 1991;91 :135S –146S[CrossRef][Medline]
  10. Mazzacca G, Sabbatini F. Inhibition of gastric acid secretion: advantages and risks in short and long-term treatment. Ital J Gastroenterol. 1990;22 (suppl 1):11–12
  11. Triba M. Prevention of stress bleeding with ranitidine or pirenzepine and the risk of pneumonia. J Clin Anesth. 1988;1 :12 –20[CrossRef][Medline]
  12. Stockbruegger RW. Bacterial overgrowth as a consequence of reduced gastric acidity. Scand J Gastroenterol Suppl. 1985;111 :7 –16[Medline]
  13. Carrion V, Egan EA. Prevention of neonatal necrotizing enterocolitis. J Pediatr Gastroenterol Nutr. 1990;11 :317 –323[Web of Science][Medline]
  14. Kuusela AL, Ruuska T, Karikoski R, et al. A randomized, controlled study of prophylactic ranitidine in preventing stress-induced gastric mucosal lesions in neonatal intensive care unit patients. Crit Care Med. 1997;25 :346 –351[CrossRef][Web of Science][Medline]
  15. Lazzaroni M, Petrillo M, Tornaghi R, et al. Upper GI bleeding in healthy full-term infants: a case-control study. Am J Gastroenterol. 2002;97 :89 –94[CrossRef][Web of Science][Medline]
  16. Sarna MS, Saili A, Dutta AK, Sharma D. Stress associated gastric bleeding in newborn: role of ranitidine. Indian Pediatr. 1991;28 :1305 –1308[Medline]
  17. Agarwal AK, Saili A, Pandey KK, Saxena AK, Sarna MS, Dutta AK. Role of cimetidine in prevention and treatment of stress induced gastric bleeding in neonates. Indian Pediatr. 1990;27 :465 –469[Medline]
  18. Vandenplas Y, Scare L. The use of cimetidine in newborns. Am J Perinatol. 1987;4 :131 –133[CrossRef][Web of Science][Medline]
  19. Kuusela AL, Maki M, Ruuska T, Laippala P. Stress-induced gastric findings in critically ill newborn infants: frequency and risk factors. Intensive Care Med. 2000;26 :1501 –1506[CrossRef][Web of Science][Medline]
  20. Maki M, Ruuska T, Kuusela AL, Karikoski-Leo R, Ikonen RS. High prevalence of asymptomatic esophageal and gastric lesions in preterm infants in intensive care. Crit Care Med. 1993;21 :1863 –1867[Web of Science][Medline]
  21. Metz DC. Preventing the gastrointestinal consequences of stress-related mucosal disease. Curr Med Res Opin. 2005;21 :11 –18[CrossRef][Web of Science][Medline]
  22. Miller TA. Mechanisms of stress-related mucosal damage. Am J Med. 1987;83 :8 –14[CrossRef][Medline]
  23. Lulu DJ, Dragstedt LR 2nd. Massive bleeding due to acute hemorrhagic gastritis. Arch Surg. 1970;101 :550 –554[Abstract/Free Full Text]
  24. Kantorova I, Svoboda P, Scheer P, et al. Stress ulcer prophylaxis in critically ill patients: a randomized controlled trial. Hepatogastroenterology. 2004;51 :757 –761[Medline]
  25. Cook DJ, Witt LG, Cook RJ, Guyatt GH. Stress ulcer prophylaxis in the critically ill: a meta-analysis. Am J Med. 1991;91 :519 –527[CrossRef][Web of Science][Medline]
  26. Tryba M. Prophylaxis of stress ulcer bleeding: a meta-analysis. J Clin Gastroenterol. 1991;13 (suppl 2):S44–S55
  27. Cothran DS, Borowitz SM, Sutphen JL, Dudley SM, Donowitz LG. Alteration of normal gastric flora in neonates receiving ranitidine. J Perinatol. 1997;17 :383 –388[Medline]
  28. MacLean LD. Prophylactic treatment of stress ulcers: first do no harm. Can J Surg. 1988;31 :76 –77[Web of Science][Medline]

PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Patole, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Patole, S.
Related Collections
Right arrow Premature & Newborn
Right arrowRelated AAP Red Book topics:
Yersinia enterocolitica and...
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?