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Intensive Care Medicine

, Volume 41, Issue 5, pp 833–845 | Cite as

Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients

  • Mette Krag
  • Anders Perner
  • Jørn Wetterslev
  • Matt P. Wise
  • Mark Borthwick
  • Stepani Bendel
  • Colin McArthur
  • Deborah Cook
  • Niklas Nielsen
  • Paolo Pelosi
  • Frederik Keus
  • Anne Berit Guttormsen
  • Alma D. Moller
  • Morten Hylander Møller
  • the SUP-ICU co-authors
Original

Abstract

Purpose

To describe the prevalence of, risk factors for, and prognostic importance of gastrointestinal (GI) bleeding and use of acid suppressants in acutely ill adult intensive care patients.

Methods

We included adults without GI bleeding who were acutely admitted to the intensive care unit (ICU) during a 7-day period. The primary outcome was clinically important GI bleeding in ICU, and the analyses included estimations of baseline risk factors and potential associations with 90-day mortality.

Results

A total of 1,034 patients in 97 ICUs in 11 countries were included. Clinically important GI bleeding occurred in 2.6 % (95 % confidence interval 1.6–3.6 %) of patients. The following variables at ICU admission were independently associated with clinically important GI bleeding: three or more co-existing diseases (odds ratio 8.9, 2.7–28.8), co-existing liver disease (7.6, 3.3–17.6), use of renal replacement therapy (6.9, 2.7–17.5), co-existing coagulopathy (5.2, 2.3–11.8), acute coagulopathy (4.2, 1.7–10.2), use of acid suppressants (3.6, 1.3–10.2) and higher organ failure score (1.4, 1.2–1.5). In ICU, 73 % (71–76 %) of patients received acid suppressants; most received proton pump inhibitors. In patients with clinically important GI bleeding, crude and adjusted odds for mortality were 3.7 (1.7–8.0) and 1.7 (0.7–4.3), respectively.

Conclusions

In ICU patients clinically important GI bleeding is rare, and acid suppressants are frequently used. Co-existing diseases, liver failure, coagulopathy and organ failures are the main risk factors for GI bleeding. Clinically important GI bleeding was not associated with increased adjusted 90-day mortality, which largely can be explained by severity of comorbidity, other organ failures and age.

Keywords

Stress ulcer prophylaxis Gastrointestinal bleeding Proton pump inhibitors Histamine-2 receptor antagonists Critically ill patients Intensive care 

Notes

Financial support

We received support from Aase and Ejnar Danielsens Foundation, Ehrenreichs Foundation, Scandinavian Society of Anaesthesia and Intensive Care Medicine (SSAI), the Danish Society of Anaesthesiology and Intensive care Medicine (DASAIM) and the Danish Medical Association. The funding sources had no influence on design or execution of the study, data analyses or writing of the manuscript.

Conflicts of interest

All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare the following interests: DC received donated study drugs in 1992 from a company that does not exist anymore while leading an RCT funded by the Canadian government. The ICU at Rigshospitalet receives support for other research projects from Fresenius Kabi and CSL Behring. MW reports personal fees from KaloBios Pharmaceuticals, personal fees from Wiley Publishing, personal fees from Fisher & Paykel, personal fees from Merck (MSD) and non-financial support from Qualitech Healthcare, outside the submitted work. On behalf of all other authors the corresponding author states that there are no conflicts of interest.

Supplementary material

134_2015_3725_MOESM1_ESM.doc (338 kb)
Supplementary material 1 (DOC 337 kb)
134_2015_3725_MOESM2_ESM.pdf (744 kb)
Supplementary material 2 (PDF 743 kb)
134_2015_3725_MOESM3_ESM.pdf (190 kb)
Supplementary material 3 (PDF 190 kb)

References

  1. 1.
    Cook DJ, Griffith LE, Walter SD et al (2001) The attributable mortality and length of intensive care unit stay of clinically important gastrointestinal bleeding in critically ill patients. Crit Care 5:368–375CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Sesler JM (2007) Stress-related mucosal disease in the intensive care unit: an update on prophylaxis. AACN Adv Crit Care 18:119–126 (quiz 127–8)CrossRefPubMedGoogle Scholar
  3. 3.
    Eddleston JM, Pearson RC, Holland J et al (1994) Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. Crit Care Med 22:1949–1954CrossRefPubMedGoogle Scholar
  4. 4.
    Van der Voort PH, van der Hulst RW, Zandstra DF et al (2001) Prevalence of Helicobacter pylori infection in stress-induced gastric mucosal injury. Intensive Care Med 27:68–73CrossRefPubMedGoogle Scholar
  5. 5.
    Plummer MP, Blaser Reintam A, Deane AM (2014) Stress ulceration: prevalence, pathology and association with adverse outcomes. Crit Care 18:213CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Cook DJ, Fuller HD, Guyatt GH et al (1994) Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 330:377–381CrossRefPubMedGoogle Scholar
  7. 7.
    Ben-Menachem T, Fogel R, Patel RV et al (1994) Prophylaxis for stress-related gastric hemorrhage in the medical intensive care unit. A randomized, controlled, single-blind study. Ann Intern Med 121:568–575CrossRefPubMedGoogle Scholar
  8. 8.
    Zandstra DF, Stoutenbeek CP (1994) The virtual absence of stress-ulceration related bleeding in ICU patients receiving prolonged mechanical ventilation without any prophylaxis. A prospective cohort study. Intensive Care Med 20:335–340CrossRefPubMedGoogle Scholar
  9. 9.
    Holst LB, Haase N, Wetterslev J et al (2014) Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 371:1381–1391CrossRefPubMedGoogle Scholar
  10. 10.
    Haase N, Wetterslev J, Winkel P, Perner A (2013) Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc analyses of a randomized clinical trial. Intensive Care Med 39:2126–2134CrossRefPubMedGoogle Scholar
  11. 11.
    Kaukonen K-M, Bailey M, Suzuki S et al (2014) Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA 311:1308–1316CrossRefPubMedGoogle Scholar
  12. 12.
    Citerio G, Bakker J, Bassetti M et al (2014) Year in review in Intensive Care Medicine 2013: I. Acute kidney injury, ultrasound, hemodynamics, cardiac arrest, transfusion, neurocritical care, and nutrition. Intensive Care Med 40:147–159CrossRefPubMedGoogle Scholar
  13. 13.
    Dellinger RP, Levy MM, Rhodes A et al (2013) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 39:165–228CrossRefPubMedGoogle Scholar
  14. 14.
    Institute for Healthcare Improvement (2011) IHI ventilator bundle: peptic ulcer disease prophylaxis. http://www.ihi.org/resources/Pages/Changes/PepticUlcerDiseaseProphylaxis.aspx. Accessed 6 Jun 2014
  15. 15.
    American Society of Health-System Pharmacists (1999) 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 56:347–79Google Scholar
  16. 16.
    Krag M, Perner A, Wetterslev J et al (2015) Stress ulcer prophylaxis in the intensive care unit. An international survey of 97 units in 11 countries. Acta Anaesthesiol Scand (in press)Google Scholar
  17. 17.
    Daley RJ, Rebuck JA, Welage LS, Rogers FB (2004) Prevention of stress ulceration: current trends in critical care. Crit Care Med 32:2008–2013CrossRefPubMedGoogle Scholar
  18. 18.
    Barletta JF, Kanji S, MacLaren R et al (2014) Pharmacoepidemiology of stress ulcer prophylaxis in the United States and Canada. J Crit Care 29:955–960CrossRefPubMedGoogle Scholar
  19. 19.
    Faisy C, Guerot E, Diehl JL et al (2003) Clinically significant gastrointestinal bleeding in critically ill patients with and without stress-ulcer prophylaxis. Intensive Care Med 29:1306–1313CrossRefPubMedGoogle Scholar
  20. 20.
    Krag M, Perner A, Wetterslev J et al (2014) Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Intensive Care Med 40:11–22CrossRefPubMedGoogle Scholar
  21. 21.
    Von Elm E, Altman DG, Egger M et al (2008) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61:344–349CrossRefGoogle Scholar
  22. 22.
    Maclaren R, Reynolds PM, Allen RR (2014) Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med 174:564–574CrossRefPubMedGoogle Scholar
  23. 23.
    Faul F, Erdfelder E, Lang A-G, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191CrossRefPubMedGoogle Scholar
  24. 24.
    Alberti C, Boulkedid R (2014) Describing ICU data with tables. Intensive Care Med 40:667–673CrossRefPubMedGoogle Scholar
  25. 25.
    Vesin A, Azoulay E, Ruckly S et al (2013) Reporting and handling missing values in clinical studies in intensive care units. Intensive Care Med 39:1396–1404CrossRefPubMedGoogle Scholar
  26. 26.
    Marshall A, Altman DG, Holder RL, Royston P (2009) Combining estimates of interest in prognostic modelling studies after multiple imputation: current practice and guidelines. BMC Med Res Methodol 9:57CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Kirkwood B, Sterne J (2003) Essential Medical Statistics, 2nd edn. Blackwell Science, MassachusettsGoogle Scholar
  28. 28.
    Thomas L, Peterson ED (2012) The value of statistical analysis plans in observational research: defining high-quality research from the start. JAMA 308:773–774CrossRefPubMedGoogle Scholar
  29. 29.
    Barletta JF, Sclar DA (2014) Proton pump inhibitors increase the risk for hospital-acquired Clostridium difficile infection in critically ill patients. Crit Care 18:714CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Charlot M, Ahlehoff O, Norgaard ML et al (2010) Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study. Ann Intern Med 153:378–386CrossRefPubMedGoogle Scholar
  31. 31.
    Cook DJ, Witt LG, Cook RJ, Guyatt GH (1991) Stress ulcer prophylaxis in the critically ill: a meta-analysis. Am J Med 91:519–527CrossRefPubMedGoogle Scholar
  32. 32.
    Apte NM, Karnad DR, Medhekar TP et al (1992) Gastric colonization and pneumonia in intubated critically ill patients receiving stress ulcer prophylaxis: a randomized, controlled trial. Crit Care Med 20:590–593CrossRefPubMedGoogle Scholar
  33. 33.
    Cook D, Heyland D, Griffith L et al (1999) Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med 27:2812–2817CrossRefPubMedGoogle Scholar
  34. 34.
    Barletta JF (2014) Histamine-2-receptor antagonist administration and gastrointestinal bleeding when used for stress ulcer prophylaxis in patients with severe sepsis or septic shock. Ann Pharmacother 48:1276–1281CrossRefPubMedGoogle Scholar
  35. 35.
    Linde-Zwirble WT, Angus DC (2004) Severe sepsis epidemiology: sampling, selection, and society. Crit Care 8:222–226CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Guyatt GH, Oxman AD, Kunz R et al (2011) GRADE guidelines 6. Rating the quality of evidence—imprecision. J Clin Epidemiol 64:1283–1293CrossRefPubMedGoogle Scholar
  37. 37.
    Erstad BL, Barletta JF, Jacobi J et al (1999) Survey of stress ulcer prophylaxis. Crit Care 3:145–149CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Farrell CP, Mercogliano G, Kuntz CL (2010) Overuse of stress ulcer prophylaxis in the critical care setting and beyond. J Crit Care 25:214–220CrossRefPubMedGoogle Scholar
  39. 39.
    Frandah W, Colmer-Hamood J, Nugent K, Raj R (2013) Patterns of use of prophylaxis for stress-related mucosal disease in patients admitted to the intensive care unit. J Intensive Care Med 29:96–103CrossRefGoogle Scholar
  40. 40.
    Khalili H, Huang E (2012) Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study. BMJ 344:1–13CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • Mette Krag
    • 1
  • Anders Perner
    • 1
  • Jørn Wetterslev
    • 2
  • Matt P. Wise
    • 3
  • Mark Borthwick
    • 4
  • Stepani Bendel
    • 5
  • Colin McArthur
    • 6
  • Deborah Cook
    • 7
  • Niklas Nielsen
    • 8
  • Paolo Pelosi
    • 9
  • Frederik Keus
    • 10
  • Anne Berit Guttormsen
    • 11
  • Alma D. Moller
    • 12
  • Morten Hylander Møller
    • 1
  • the SUP-ICU co-authors
  1. 1.Department of Intensive Care 4131Copenhagen University Hospital, RigshospitaletCopenhagenDenmark
  2. 2.Copenhagen Trial Unit, Centre for Clinical Intervention ResearchCopenhagen University Hospital RigshospitaletCopenhagenDenmark
  3. 3.Department of Adult Critical CareUniversity Hospital of WalesCardiffUK
  4. 4.Pharmacy DepartmentOxford University Hospitals NHS TrustOxfordUK
  5. 5.Department of Intensive Care MedicineKuopio University HospitalKuopioFinland
  6. 6.Department of Critical Care MedicineAuckland City HospitalAucklandNew Zealand
  7. 7.Department of MedicineMcMaster UniversityHamiltonCanada
  8. 8.Department of Anaesthesiology and Intensive Care, Helsingborg Hospital, Sweden and Department of Clinical SciencesLund UniversityLundSweden
  9. 9.Department of Surgical Sciences and Integrated Diagnostics, IRCCS San Martino ISTUniversity of GenoaGenoaItaly
  10. 10.University of Groningen, Department of Critical CareUniversity Medical Center GroningenGroningenThe Netherlands
  11. 11.Department of Anaesthesia and Intensive CareHaukeland University Hospital and Clinical Institute 1 UiBBergenNorway
  12. 12.Department of Anaesthesia and Intensive CareLandspitali University Hospital ReykjavikReykjavikIceland

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