PharmacoEconomics

, Volume 32, Issue 1, pp 5–13

Use of Proton Pump Inhibitors for the Provision of Stress Ulcer Prophylaxis: Clinical and Economic Consequences

Review Article

Abstract

The provision of stress ulcer prophylaxis (SUP) for the prevention of clinically significant bleeding is widely recognized as a crucial component of care in critically ill patients. Nevertheless, SUP is often provided to non-critically ill patients despite a risk for clinically significant bleeding of roughly 0.1 %. The overuse of SUP therefore introduces added risks for adverse drug events and cost, with minimal expected benefit in clinical outcome. Historically, histamine-2-receptor antagonists (H2RAs) have been the preferred agent for SUP; however, recent data have revealed proton pump inhibitors (PPIs) as the most common modality (76 %). There are no high quality randomized controlled trials demonstrating superiority with PPIs compared with H2RAs for the prevention of clinically significant bleeding associated with stress ulcers. In contrast, PPIs have recently been linked to several adverse effects including Clostridium difficile diarrhea and pneumonia. These complications have substantial economic consequences and have a marked impact on the overall cost effectiveness of PPI therapy. Nevertheless, PPI use remains widespread in patients who are at both high and low risk for clinically significant bleeding. This article will describe the utilization of PPIs for SUP and present the clinical and economic consequences linked to their use/overuse.

References

  1. 1.
    Barletta JF, Lat I, Micek S, Cohen H, Olsen K, Haas C. Off label use of gastrointestinal medications in the intensive care unit. J Intensive Care Med. 2011 (in press).Google Scholar
  2. 2.
    Daley RJ, Rebuck JA, Welage LS, Rogers FB. Prevention of stress ulceration: current trends in critical care. Crit Care Med. 2004;32(10):2008–13.PubMedCrossRefGoogle Scholar
  3. 3.
    Erstad BL, Barletta JF, Jacobi J, Killian AD, Kramer KM, Martin SJ. Survey of stress ulcer prophylaxis. Critical care (London, England). 1999;3(6):145–9.CrossRefGoogle Scholar
  4. 4.
    Cook DJ, Fuller HD, Guyatt GH, Marshall JC, Leasa D, Hall R, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med. 1994;330(6):377–81.PubMedCrossRefGoogle Scholar
  5. 5.
    Herzig SJ, Vaughn BP, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for nosocomial gastrointestinal tract bleeding. Arch Intern Med. 2011;171(11):991–7.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Cook DJ, Griffith LE, Walter SD, Guyatt GH, Meade MO, Heyland DK, et al. Critical care (London, England). 75. 2001;5(6):368–75.Google Scholar
  7. 7.
    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(3):693–705.PubMedCrossRefGoogle Scholar
  8. 8.
    Lin PC, Chang CH, Hsu PI, Tseng PL, Huang YB. The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis. Crit Care Med. 2010;38(4):1197–205.PubMedCrossRefGoogle Scholar
  9. 9.
    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;56(4):347–79.Google Scholar
  10. 10.
    Krag M, Perner A, Wetterslev J, Moller MH. Stress ulcer prophylaxis in the intensive care unit: is it indicated? A topical systematic review. Acta Anaesthesiologica Scandinavica. 2013;57(7):835–47.PubMedCrossRefGoogle Scholar
  11. 11.
    Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med. 1999;27(12):2812–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Hurt RT, Frazier TH, McClave SA, Crittenden NE, Kulisek C, Saad M, et al. Stress prophylaxis in intensive care unit patients and the role of enteral nutrition. JPEN J Parent Enter Nutr. 2012;36(6):721–31.CrossRefGoogle Scholar
  13. 13.
    Marik PE. Stress ulcer prophylaxis in the new millennium! ICU Dir. 2010;1(1):12–6.CrossRefGoogle Scholar
  14. 14.
    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(11):2222–8.PubMedCrossRefGoogle Scholar
  15. 15.
    van der Voort PH, Zandstra DF. Pathogenesis, risk factors, and incidence of upper gastrointestinal bleeding after cardiac surgery: is specific prophylaxis in routine bypass procedures needed? J Cardiothorac Vasc Anesth. 2000;14(3):293–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Rosen HR, Vlahakes GJ, Rattner DW. Fulminant peptic ulcer disease in cardiac surgical patients: pathogenesis, prevention, and management. Crit Care Med. 1992;20(3):354–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Herzig SJ, Rothberg MB, Feinbloom DB, Howell MD, Ho KK, Ngo LH, et al. Risk factors for nosocomial gastrointestinal bleeding and use of acid-suppressive medication in non-critically ill patients. J Gen Intern Med. 2013;28(5):683–90.PubMedCrossRefGoogle Scholar
  18. 18.
    Ali T, Harty RF. Stress-induced ulcer bleeding in critically ill patients. Gastroenterol Clin N Am. 2009;38(2):245–65.CrossRefGoogle Scholar
  19. 19.
    Conrad SA, Gabrielli A, Margolis B, Quartin A, Hata JS, Frank WO, et al. Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med. 2005;33(4):760–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Solouki M, Marashian S, Kouchak M. Comparison between the preventive effects of ranitidine and omeprazole on upper gastrointestinal bleeding among ICU patients. Tanaffos. 2009;8:37–42.Google Scholar
  21. 21.
    Levy MJ, Seelig CB, Robinson NJ, Ranney JE. Comparison of omeprazole and ranitidine for stress ulcer prophylaxis. Dig Dis Sci. 1997;42(6):1255–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Kantorova I, Svoboda P, Scheer P, Doubek J, Rehorkova D, Bosakova H, et al. Stress ulcer prophylaxis in critically ill patients: a randomized controlled trial. Hepato Gastroenterol. 2004;51(57):757–61.Google Scholar
  23. 23.
    Barkun AN, Bardou M, Pham CQ, Martel M. Proton pump inhibitors vs. histamine 2 receptor antagonists for stress-related mucosal bleeding prophylaxis in critically ill patients: a meta-analysis. Am J Gastroenterol. 2012;107(4):507–20 (quiz 21).PubMedCrossRefGoogle Scholar
  24. 24.
    Cook D, Guyatt G, Marshall J, Leasa D, Fuller H, Hall R, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med. 1998;338(12):791–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Cook DJ, Reeve BK, Guyatt GH, Heyland DK, Griffith LE, Buckingham L, et al. Stress ulcer prophylaxis in critically ill patients. Resolving discordant meta-analyses. JAMA. 1996;275(4):308–14.PubMedCrossRefGoogle Scholar
  26. 26.
    Guillamondegui OD, Gunter Jr OL, Bonadies JA, Coates JE, Kurek SJ, DeMoya MA, et al. Practice management guidelines for stress ulcer prophylaxis. EAST Practice Management Guidelines Committee. http://wwweastorg/resources/treatment-guidelines/stress-ulcer-prophylaxis (2008). Accessed 3 July 2013.
  27. 27.
    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637.PubMedCrossRefGoogle Scholar
  28. 28.
    Barletta JF, Erstad BL, Fortune JB. Stress ulcer prophylaxis in trauma patients. Critical care (London, England). 2002;6(6):526–30.CrossRefGoogle Scholar
  29. 29.
    Gupta R, Garg P, Kottoor R, Munoz JC, Jamal MM, Lambiase LR, et al. Overuse of acid suppression therapy in hospitalized patients. South Med J. 2010;103(3):207–11.PubMedCrossRefGoogle Scholar
  30. 30.
    Issa IA, Soubra O, Nakkash H, Soubra L. Variables associated with stress ulcer prophylaxis misuse: a retrospective analysis. Dig Dis Sci. 2012;57(10):2633–41.PubMedCrossRefGoogle Scholar
  31. 31.
    Judd WR, Davis GA, Winstead PS, Steinke DT, Clifford TM, Macaulay TE. Evaluation of continuation of stress ulcer prophylaxis at hospital discharge. Hosp Pharm. 2009;44:888–93.CrossRefGoogle Scholar
  32. 32.
    Nardino RJ, Vender RJ, Herbert PN. Overuse of acid-suppressive therapy in hospitalized patients. Am J Gastroenterol. 2000;95(11):3118–22.PubMedGoogle Scholar
  33. 33.
    Parente F, Cucino C, Gallus S, Bargiggia S, Greco S, Pastore L, et al. Hospital use of acid-suppressive medications and its fall-out on prescribing in general practice: a 1-month survey. Aliment Pharmacol Therap. 2003;17(12):1503–6.CrossRefGoogle Scholar
  34. 34.
    Zink DA, Pohlman M, Barnes M, Cannon ME. Long-term use of acid suppression started inappropriately during hospitalization. Aliment Pharmacol Therap. 2005;21(10):1203–9.CrossRefGoogle Scholar
  35. 35.
    Farrell CP, Mercogliano G, Kuntz CL. Overuse of stress ulcer prophylaxis in the critical care setting and beyond. J Crit Care. 2010;25(2):214–20.PubMedCrossRefGoogle Scholar
  36. 36.
    Murphy CE, Stevens AM, Ferrentino N, Crookes BA, Hebert JC, Freiburg CB, et al. Frequency of inappropriate continuation of acid suppressive therapy after discharge in patients who began therapy in the surgical intensive care unit. Pharmacotherapy. 2008;28(8):968–76.PubMedCrossRefGoogle Scholar
  37. 37.
    Wohlt PD, Hansen LA, Fish JT. Inappropriate continuation of stress ulcer prophylactic therapy after discharge. Ann Pharmacother. 2007;41(10):1611–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Zeigler AJ, McAllen KJ, Slot MG, Barletta JF. Medication reconciliation effect on prolonged inpatient stress ulcer prophylaxis. Ann Pharmacother. 2008;42(7):940–6.PubMedCrossRefGoogle Scholar
  39. 39.
    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(4):270–3.PubMedCrossRefGoogle Scholar
  40. 40.
    Hussain S, Stefan M, Visintainer P, Rothberg M. Why do physicians prescribe stress ulcer prophylaxis to general medicine patients? South Med J. 2010;103(11):1103–10.PubMedCrossRefGoogle Scholar
  41. 41.
    Koczka CP, Geraldino-Pardilla LB, Goodman AJ. Physicians’ opinions of stress ulcer prophylaxis: survey results from a large urban medical center. Dig Dis Sci. 2013;58(3):777-81.PubMedCrossRefGoogle Scholar
  42. 42.
    Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009;301(20):2120–8.PubMedCrossRefGoogle Scholar
  43. 43.
    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(9):784–90.PubMedCrossRefGoogle Scholar
  44. 44.
    Meijvis SC, Cornips MC, Voorn GP, Souverein PC, Endeman H, Biesma DH, et al. Microbial evaluation of proton-pump inhibitors and the risk of pneumonia. Eur Resp J. 2011;38(5):1165–72.CrossRefGoogle Scholar
  45. 45.
    Barletta JF, El-Ibiary SY, Davis LE, Nguyen B, Raney CR. Proton pump inhibitors and the risk for hospital-acquired Clostridium difficile infection. Mayo Clin Proc. 2013;88(10):1085-90.PubMedCrossRefGoogle Scholar
  46. 46.
    Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005;294(23):2989–95.PubMedCrossRefGoogle Scholar
  47. 47.
    Gulmez SE, Holm A, Frederiksen H, Jensen TG, Pedersen C, Hallas J. Use of proton pump inhibitors and the risk of community-acquired pneumonia: a population-based case-control study. Arch Intern Med. 2007;167(9):950–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Laheij RJ, Sturkenboom MC, Hassing RJ, Dieleman J, Stricker BH, Jansen JB. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004;292(16):1955–60.PubMedCrossRefGoogle Scholar
  49. 49.
    Loo VG, Bourgault AM, Poirier L, Lamothe F, Michaud S, Turgeon N, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med. 2011;365(18):1693–703.PubMedCrossRefGoogle Scholar
  50. 50.
    Sarkar M, Hennessy S, Yang YX. Proton-pump inhibitor use and the risk for community-acquired pneumonia. Ann Intern Med. 2008;149(6):391–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Bateman BT, Bykov K, Choudhry NK, Schneeweiss S, Gagne JJ, Polinski JM, et al. Type of stress ulcer prophylaxis and risk of nosocomial pneumonia in cardiac surgical patients: cohort study. BMJ (Clinical research ed). 2013;347:f5416.Google Scholar
  52. 52.
    Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947–53.PubMedCrossRefGoogle Scholar
  53. 53.
    Maggio M, Corsonello A, Ceda GP, Cattabiani C, Lauretani F, Butto V, et al. Proton pump inhibitors and risk of 1-year mortality and rehospitalization in older patients discharged from acute care hospitals. JAMA Intern Med. 2013;173(7):518–23.PubMedCrossRefGoogle Scholar
  54. 54.
    Parker DR, Luo X, Jalbert JJ, Assaf AR. Impact of upper and lower gastrointestinal blood loss on healthcare utilization and costs: a systematic review. J Med Econ. 2011;14(3):279–87.PubMedCrossRefGoogle Scholar
  55. 55.
    Heyland D, Gafni A, Griffith L, Cook D, Marshall J, Fuller H, et al. The clinical and economic consequences of clinically important gastro-intestinal bleeding in critically ill patients. Clin Intensive Care. 1996;7:121–5.Google Scholar
  56. 56.
    Barkun AN, Adam V, Martel M, Bardou M. Cost-effectiveness analysis: stress ulcer bleeding prophylaxis with proton pump inhibitors, H2 receptor antagonists. Value Health. 2013;16(1):14–22.PubMedCrossRefGoogle Scholar
  57. 57.
    Thomas CP, Ryan M, Chapman JD, Stason WB, Tompkins CP, Suaya JA, et al. Incidence and cost of pneumonia in Medicare beneficiaries. Chest. 2012;142(4):973–81.PubMedCrossRefGoogle Scholar
  58. 58.
    Eber MR, Laxminarayan R, Perencevich EN, Malani A. Clinical and economic outcomes attributable to health care-associated sepsis and pneumonia. Arch Intern Med. 2010;170(4):347–53.PubMedCrossRefGoogle Scholar
  59. 59.
    Neidell MJ, Cohen B, Furuya Y, Hill J, Jeon CY, Glied S, et al. Costs of healthcare- and community-associated infections with antimicrobial-resistant versus antimicrobial-susceptible organisms. Clin Infect Dis. 2012;55(6):807–15.PubMedCrossRefGoogle Scholar
  60. 60.
    O’Brien JA, Lahue BJ, Caro JJ, Davidson DM. The emerging infectious challenge of Clostridium difficile-associated disease in Massachusetts hospitals: clinical and economic consequences. Infect Control Hosp Epidemiol. 2007;28(11):1219–27.PubMedCrossRefGoogle Scholar
  61. 61.
    Heidelbaugh JJ, Inadomi JM. Magnitude and economic impact of inappropriate use of stress ulcer prophylaxis in non-ICU hospitalized patients. Am J Gastroenterol. 2006;101(10):2200–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Udeh BL, Udeh C, Hata JS. Cost-effectiveness of stress ulcer prophylaxis: role of proton pump inhibitors. Am J Pharm Benefits. 2010;2(5):304–12.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Department of Pharmacy Practice, College of Pharmacy-GlendaleMidwestern UniversityGlendaleUSA

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