International Journal of Clinical Pharmacy

, Volume 39, Issue 1, pp 181–186 | Cite as

Guidelines for proton pump inhibitor prescriptions in paediatric intensive care unit

  • P. Joret-Descout
  • S. Dauger
  • M. Bellaiche
  • O. Bourdon
  • S. Prot-LabartheEmail author
Research Article


Background Stress ulcer prophylaxis (SUP) is recommended in some situations to prevent upper gastrointestinal bleeding and is a component of standard care for patients admitted to the intensive care unit (ICU). Proton pump inhibitors (PPIs), already among the most widely prescribed drug classes, are being increasingly used. Objective To describe PPI prescribing patterns and their changes after the dissemination of guidelines. Setting Paediatric ICU (PICU), Robert-Debré Teaching Hospital, Paris, France, which admits about 800 patients annually, from full-term neonates to 18-year-olds. Method Prospective observational study with two 6-week observation periods (July–August and September–October, 2013), before and after dissemination in the PICU of PPI prescribing guidelines. Main outcome measure Changes in PPI prescribing patterns (prevalence, dosage, and indication) after the guidelines. Results The number of patients admitted to the PICU was 77 (mean age 4.6 years [range 1 day–18 years]) before and 70 (mean age 3.8 years [range 1 day–17 years]) after the guidelines. During both periods, SUP was the most common reason for PPI prescribing. The proportion of patients prescribed PPIs dropped significantly, from 51% before the guidelines to 30% after the guidelines (p < 0.001). Mean daily dosage also decreased significantly, from 1.5 mg/kg/(range 0.5–4.4) to 1.1 mg/kg (range 0.7–1.8) (p < 0.002). None of the patients experienced upper gastrointestinal bleeding during either period. Conclusion Off-label PPI prescribing for SUP was common in our PICU. The introduction of guidelines was associated with a significant decrease in PPI use and dosage. This study confirms that guidelines can change PPI prescribings patterns in paediatric practice.


Drug prescriptions France Guidelines Intensive care unit Off-label prescribing Pediatrics Proton pump inhibitors 






Conflicts of Interest



  1. 1.
    Ward RM, Kearns GL. Proton pump inhibitors in pediatrics. Paediatr Drugs. 2013;15:119–31.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Smith CH, Israel DM, Schreiber R, Goldman RD. Proton pump inhibitors for irritable infants. Can Fam Physician. 2013;59:153–6.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Tjon JA, Pe M, Soscia J, Mahant S. Efficacy and safety of proton pump inhibitors in the management of pediatric gastroesophageal reflux disease. Pharmacotherapy. 2013;33:956–71.CrossRefPubMedGoogle Scholar
  4. 4.
    Tafuri G, Trotta F, Leufkens HGM, Martini N, Sagliocca L, Traversa G. Off-label use of medicines in children: can available evidence avoid useless paediatric trials? The case of proton pump inhibitors for the treatment of gastroesophageal reflux disease. Eur J Clin Pharmacol. 2009;65:209–16.CrossRefPubMedGoogle Scholar
  5. 5.
    ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm. 1999;15(56):347–79.Google Scholar
  6. 6.
    Krag M, Perner A, Wetterslev J, Møller MH. Stress ulcer prophylaxis in the intensive care unit: is it indicated? A topical systematic review. Acta Anaesthesiol Scand. 2013;57:835–47.CrossRefPubMedGoogle Scholar
  7. 7.
    Pimentel M, Roberts DE, Bernstein CN, Hoppensack M, Duerksen DR. Clinically significant gastrointestinal bleeding in critically ill patients in an era of prophylaxis. Am J Gastroenterol. 2000;95:2801–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Cook DJ, Griffith LE, Walter SD, Guyatt GH, Meade MO, Heyland DK, et al. The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care. 2001;5:368–75.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Alhazzani W, Alenezi F, Jaeschke RZ, Moayyedi P, Cook DJ. Proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis. Crit Care Med. 2013;41:693–705.CrossRefPubMedGoogle Scholar
  10. 10.
    Eom CS, Jeon CY, Lim JW, Cho EG, Park SM, Lee KS. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011;183:310–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Howell MD, Novack V, Grgurich P, Soulliard D, Novack L, Pencina M, et al. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med. 2010;170:784–90.CrossRefPubMedGoogle Scholar
  12. 12.
    MacLaren R, Reynolds PM, Allen RR. Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med. 2014;174:564–74.CrossRefPubMedGoogle Scholar
  13. 13.
    Marik PE, Vasu T, Hirani A, Pachinburavan M. Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis. Crit Care Med. 2010;38:2222–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Ther Adv Gastroenterol. 2012;5:219–32.CrossRefGoogle Scholar
  15. 15.
    Thomas L, Culley EJ, Gladowski P, Goff V, Fong J, Marche SM. Longitudinal analysis of the costs associated with inpatient initiation and subsequent outpatient continuation of proton pump inhibitor therapy for stress ulcer prophylaxis in a large managed care organization. J Manag Care Pharm. 2010;16:122–9.PubMedGoogle Scholar
  16. 16.
    Lightdale JR, Gremse DA. Section on gastroenterology, hepatology and nutrition. Gastroesophageal reflux: management guidance for the pediatrician. Pediatrics. 2013;131:1684–95.CrossRefGoogle Scholar
  17. 17.
    French National Agency for the Safety of Medicines and Health Products. Good practice guidelines for the use of gastric anti-secretory agents in children issued in June 2008. Accessed 08 Dec 2016.
  18. 18.
    Winter H, Gunasekaran T, Tolia V, Gottrand F, Barker PN, Illueca M. Esomeprazole for the treatment of GERD in infants ages 1–11 months. J Pediatr Gastroenterol Nutr. 2012;55:14–20.CrossRefPubMedGoogle Scholar
  19. 19.
    Vandenplas Y, Rudolph CD, Di Lorenzo C, Hassall E, Liptak G, Mazur L, et al. Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2009;49:498–547.CrossRefPubMedGoogle Scholar
  20. 20.
    Farrell CP, Mercogliano G, Kuntz CL. Overuse of stress ulcer prophylaxis in the critical care setting and beyond. J Crit Care. 2010;25:214–20.CrossRefPubMedGoogle Scholar
  21. 21.
    Pollack MM, Ruttimann UE, Getson PR. Pediatric risk of mortality (PRISM) score. Crit Care Med. 1988;16:1110–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Slater A, Shann F, Pearson G. Paediatric Index of Mortality (PIM) Study Group. PIM2: a revised version of the Paediatric Index of Mortality. Intensive Care Med. 2003;29:278–85.CrossRefPubMedGoogle Scholar
  23. 23.
    Leteurtre S, Duhamel A, Grandbastien B, Lacroix J, Leclerc F. Paediatric logistic organ dysfunction (PELOD) score. Lancet. 2006;367:897 (author reply 900–2).CrossRefPubMedGoogle Scholar
  24. 24.
    Carnovale C, Conti V, Perrone V, Antoniazzi S, Pozzi M, Merlino L, et al. Paediatric drug use with focus on off-label prescriptions in Lombardy and implications for therapeutic approaches. Eur J Pediatr. 2013;172:1679–85.CrossRefPubMedGoogle Scholar
  25. 25.
    Lenz K, Buder R, Firlinger F, Lohr G, Voglmayr M. Effect of proton pump inhibitors on gastric pH in patients exposed to severe stress. Wien Klin Wochenschr. 2015;127:51–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Haroon M, Yasin F, Gardezi S, Adeeb F. Inappropriate use of proton pump inhibitors among medical inpatients: a questionnaire-based observational study. JRSM Short Rep. 2013;4:1–6.CrossRefGoogle Scholar
  27. 27.
    Barletta JF, Kanji S, MacLaren R, Lat I, Erstad BL. American-Canadian consortium for Intensive care Drug utilization (ACID) Investigators. Pharmacoepidemiology of stress ulcer prophylaxis in the United States and Canada. J Crit Care. 2014;29:955–60.CrossRefPubMedGoogle Scholar
  28. 28.
    Gautam A, Ganu SS, Tegg OJ, Andresen DN, Wilkins BH, Schell DN. Ventilator-associated pneumonia in a tertiary paediatric intensive care unit: a 1-year prospective observational study. Crit Care Resusc. 2012;14:283–9.PubMedGoogle Scholar
  29. 29.
    Atkins R, Smith L. Impact of pharmacy intervention on the use of proton-pump inhibitors in the hospital setting. Consult Pharm. 2013;28:786–92.CrossRefPubMedGoogle Scholar
  30. 30.
    Leri F, Ayzenberg M, Voyce SJ, Klein A, Hartz L, Smego RA Jr. Four-year trends of inappropriate proton pump inhibitor use after hospital discharge. South Med J. 2013;106:270–3.CrossRefPubMedGoogle Scholar
  31. 31.
    Machado-Alba JE, Castrillón-Spitia JD, Londoño-Builes MJ, Fernández-Cardona A, Campo-Betancourth CF, Ochoa-Orozco SA, et al. An economic analysis of inadequate prescription of antiulcer medications for in-hospital patients at a third level institution in Colombia. Rev Esp Enferm Dig. 2014;106:77–85.CrossRefPubMedGoogle Scholar
  32. 32.
    MacLaren R, Campbell J. Cost-effectiveness of histamine receptor-2 antagonist versus proton pump inhibitor for stress ulcer prophylaxis in critically ill patients. Crit Care Med. 2014;42:809–15.CrossRefPubMedGoogle Scholar
  33. 33.
    Barletta JF, Sclar DA. Use of proton pump inhibitors for the provision of stress ulcer prophylaxis: clinical and economic consequences. Pharmacoeconomics. 2014;32:5–13.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  • P. Joret-Descout
    • 1
  • S. Dauger
    • 2
    • 3
    • 4
  • M. Bellaiche
    • 5
  • O. Bourdon
    • 1
    • 6
    • 7
  • S. Prot-Labarthe
    • 1
    • 7
    • 8
    Email author
  1. 1.Département de PharmacieHôpital Robert-Debré, AP-HPParis Cedex 19France
  2. 2.Réanimation et surveillance continue pédiatriqueHôpital Robert-Debré, AP-HPParisFrance
  3. 3.Université Paris 7- Paris DiderotParisFrance
  4. 4.INSERM U1141Hôpital Robert-Debré, AP-HPParisFrance
  5. 5.Gastroentérologie pédiatriqueHôpital Robert-Debré, AP-HPParisFrance
  6. 6.Pharmacie CliniqueUniversité Paris Descartes, Sorbonne Paris CitéParisFrance
  7. 7.Laboratoire Education et Pratiques de Santé, EA 3412Université Paris 13, Sorbonne Paris CitéBobignyFrance
  8. 8.INSERM, U1123ECEVEParisFrance

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