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Predictors of gastrointestinal bleeding in adult ICU patients: a systematic review and meta-analysis

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Abstract

Purpose

To systematically identify predictors of gastrointestinal (GI) bleeding in adult intensive care unit (ICU) patients.

Methods

We conducted a systematic review and meta-analysis of cohort studies including trial cohorts. We searched MEDLINE, EMBASE, and trial registries up to March 2019. Eligible studies assessed potential predictors of clinically important GI bleeding (CIB; primary outcome) or overt GI bleeding (secondary outcome), had > 20 events, and presented adjusted effect estimates. Two reviewers assessed study eligibility, extracted data, and assessed risk of bias and certainty of evidence using GRADE. We meta-analysed adjusted effect estimates if data from ≥ 2 studies were available.

Results

We included 8 studies (116,497 patients). 4 studies (including 74,456 patients) assessed potential predictors of CIB, and we meta-analysed 12 potential predictors from these. Acute kidney injury (relative effect [RE] 2.38, 95% confidence interval [CI] 1.07–5.28, moderate certainty) and male gender (RE 1.24, 95% CI 1.03–1.50, low certainty) were associated with increased incidence of CIB. After excluding high risk of bias studies, coagulopathy (RE 4.76, 95% CI 2.62–8.63, moderate certainty), shock (RE 2.60, 95% CI 1.25–5.42, low certainty), and chronic liver disease (RE 7.64, 95% CI 3.32–17.58, moderate certainty) were associated with increased incidence of CIB. The effect of mechanical ventilation on CIB was unclear (RE 1.93, 0.57–6.50, very low certainty).

Conclusions

We identified predictors of CIB and overt GI bleeding in adult ICU patients. These findings may be used to identify ICU patients at higher risk of GI bleeding who are most likely to benefit from stress ulcer prophylaxis.

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References

  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 5:368–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Cook DJ, Fuller HD, Guyatt GH et al (1994) Risk factors for gastrointestinal bleeding in critically Ill patients. N Engl J Med 330:377–381

    Article  CAS  PubMed  Google Scholar 

  3. Cook D, Guyatt G (2018) Prophylaxis against upper gastrointestinal bleeding in hospitalized patients. N Engl J Med 378:2506–2516

    Article  CAS  PubMed  Google Scholar 

  4. Krag M, Perner A, Wetterslev J et al (2015) Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med 41:833–845

    Article  CAS  PubMed  Google Scholar 

  5. 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 174:564–574

    Article  CAS  PubMed  Google Scholar 

  6. 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 153:378–386

    Article  PubMed  Google Scholar 

  7. Krag M, Marker S, Perner A et al (2018) Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU. N Engl J Med 379:2199–2208

    Article  CAS  PubMed  Google Scholar 

  8. Barbateskovic M, Marker S, Granholm A et al (2019) Stress ulcer prophylaxis with proton pump inhibitors or histamin-2 receptor antagonists in adult intensive care patients: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med 45:143–158

    Article  PubMed  Google Scholar 

  9. Riley RD, Moons KGM, Snell KIE et al (2019) A guide to systematic review and meta-analysis of prognostic factor studies. BMJ 364:k4597

    Article  PubMed  Google Scholar 

  10. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535

    Article  PubMed  PubMed Central  Google Scholar 

  11. Walpole SC (2019) Including papers in languages other than English in systematic reviews: important, feasible, yet often omitted. J Clin Epidemiol. https://doi.org/10.1016/j.jclinepi.2019.03.004

    Article  PubMed  Google Scholar 

  12. Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C (2013) Assessing bias in studies of prognostic factors. Ann Intern Med 158:280–286

    Article  PubMed  Google Scholar 

  13. Foroutan F, Guyatt GH, O’Brien K et al (2016) Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe symptomatic aortic stenosis: systematic review of observational studies. BMJ 354:i5065

    Article  PubMed  PubMed Central  Google Scholar 

  14. Iorio A, Spencer FA, Falavigna M et al (2015) Use of GRADE for assessment of evidence about prognosis: rating confidence in estimates of event rates in broad categories of patients. BMJ 350:h870

    Article  PubMed  Google Scholar 

  15. Lau J, Ioannidis JP, Terrin N, Schmid CH, Olkin I (2006) The case of the misleading funnel plot. BMJ 333:597–600

    Article  PubMed  PubMed Central  Google Scholar 

  16. Alhazzani W, Alshamsi F, Belley-Cote E et al (2018) Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials. Intensive Care Med 44:1–11

    Article  CAS  PubMed  Google Scholar 

  17. Higgins JPT, Green S (eds) (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration. http://handbook.cochrane.org

  18. Altman DG, Bland JM (2011) How to obtain the confidence interval from a P value. BMJ 343:d2090

    Article  PubMed  Google Scholar 

  19. Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J (1999) Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med 27:2812–2817

    Article  CAS  PubMed  Google Scholar 

  20. Ellison RT, Perez-Perez G, Welsh CH et al (1996) Risk factors for upper gastrointestinal bleeding in intensive care unit patients: role of helicobacter pylori. Federal hyperimmune immunoglobulin therapy study group. Crit Care Med 24:1974–1981

    Article  CAS  PubMed  Google Scholar 

  21. Kumar S, Ramos C, Garcia-Carrasquillo RJ, Green PH, Lebwohl B (2017) Incidence and risk factors for gastrointestinal bleeding among patients admitted to medical intensive care units. Frontline Gastroenterol 8(1):67–173

    Google Scholar 

  22. Lilly CM, Aljawadi M, Badawi O et al (2018) Comparative effectiveness of proton pump inhibitors vs histamine type 2 receptor blockers for preventing clinically important gastrointestinal bleeding during intensive care: a population-based study. Chest 154:557–566

    Article  PubMed  PubMed Central  Google Scholar 

  23. Wei J, Jiang R, Li L et al (2019) Stress-related upper gastrointestinal bleeding in adult neurocritical care patients: a Chinese multicenter, retrospective study. Curr Med Res Opin 35:181–187

    Article  PubMed  Google Scholar 

  24. Cook D, Guyatt G, Marshall J et al (1998) 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 338:791–797

    Article  CAS  PubMed  Google Scholar 

  25. Donta ST, Peduzzi P, Cross AS et al (1996) Immunoprophylaxis against klebsiella and pseudomonas aeruginosa infections. The Federal Hyperimmune Immunoglobulin Trial Study Group. J Infect Dis 174:537–543

    Article  CAS  PubMed  Google Scholar 

  26. Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA et al (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342:1301–1308

    Article  Google Scholar 

  27. Petrucci N, De Feo C (2013) Lung protective ventilation strategy for the acute respiratory distress syndrome. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD003844.pub4

    Article  PubMed  PubMed Central  Google Scholar 

  28. Marker S, Perner A, Wetterslev J et al (2019) Pantoprazole prophylaxis in ICU patients with high severity of disease: a post hoc analysis of the placebo-controlled SUP-ICU trial. Intensive Care Med 45:609–618

    Article  PubMed  Google Scholar 

  29. Iwashyna TJ, Burke JF, Sussman JB, Prescott HC, Hayward RA, Angus DC (2015) Implications of heterogeneity of treatment effect for reporting and analysis of randomized trials in critical care. Am J Respir Crit Care Med 192:1045–1051

    Article  PubMed  PubMed Central  Google Scholar 

  30. Labarère J, Bertrand R, Fine MJ (2014) How to derive and validate clinical prediction models for use in intensive care medicine. Intensive Care Med 40:513–527

    Article  PubMed  Google Scholar 

  31. Vetter TR, Mascha EJ (2017) Bias, confounding, and interaction: lions and tigers, and bears, oh my! Anesth Analg 125:1042–1048

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Ms. Sarah Culgin, research coordinator at the GUIDE Group and the Research Institute of St. Joseph’s Healthcare Hamilton, who coordinated practical aspects of this review; Ms. Karin Dearness, director of the Library Services at St. Joseph’s Healthcare Hamilton, who developed the electronic search strategy and conducted the searches; and Mr. Farid Foroutan, Department of Health Research Methods, Evidence, and Impact at McMaster University, who provided templates and materials used for the review.

Funding

The Guidelines in Intensive Care, Development and Evaluation (GUIDE) Group.

Author information

Authors and Affiliations

  1. Department of Intensive Care 4131, Copenhagen University Hospital-Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Anders Granholm, Anders Perner, Søren Marker, Mette Krag & Morten Hylander Møller

  2. Pharmacy Department-Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China

    Linan Zeng

  3. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada

    Linan Zeng, Joanna Colleen Dionne, Zhikang Ye & Waleed Alhazzani

  4. Department of Medicine, Division of Critical Care, McMaster University, Hamilton, Canada

    Joanna Colleen Dionne & Waleed Alhazzani

  5. Centre for Research in Intensive Care, Copenhagen, Denmark

    Anders Perner, Søren Marker, Mette Krag & Morten Hylander Møller

  6. Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA

    Robert MacLaren

Authors
  1. Anders Granholm
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  2. Linan Zeng
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  3. Joanna Colleen Dionne
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  4. Anders Perner
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  6. Mette Krag
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  7. Robert MacLaren
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  8. Zhikang Ye
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  9. Morten Hylander Møller
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  10. Waleed Alhazzani
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Consortia

the GUIDE Group

Corresponding author

Correspondence to Morten Hylander Møller.

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Conflicts of interest

The Department of Intensive Care at Rigshospitalet—Copenhagen University Hospital receives support for other research projects from Ferring Pharmaceuticals, Denmark, and the Novo Nordisk Foundation, Denmark. RM received support for other research projects from CSL Behring, USA. AG, AP, SM, MK, and MHM are involved in the SUP-ICU research programme, and AP, MK, and MHM were directly involved in one of the studies included [4]. RM was the lead author of one of the included studies [5]. Two of the included studies [2, 19] were led from McMaster University, Hamilton, Canada, where LZ, JCD, ZY, and WA are employed.

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Granholm, A., Zeng, L., Dionne, J.C. et al. Predictors of gastrointestinal bleeding in adult ICU patients: a systematic review and meta-analysis. Intensive Care Med 45, 1347–1359 (2019). https://doi.org/10.1007/s00134-019-05751-6

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  • DOI: https://doi.org/10.1007/s00134-019-05751-6

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