Visual Abstract

Visual Abstract
Visual Abstract.
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Keywords:
Acute kidney injury, Continuous renal replacement therapy, Sepsis, Critical illness, Stress ulcer prophylaxis, Gastrointestinal bleeding

Background: Intensive care unit (ICU) patients with acute kidney injury requiring renal replacement therapy (RRT) are considered at high risk of gastrointestinal (GI) bleeding and stress ulcer prophylaxis (SUP) is often prescribed. We aimed to assess the incidence of GI bleeding and effects of SUP in these patients. Methods: We assessed GI bleeding in ICU patients receiving RRT at baseline (and at any time in the ICU) and effects of prophylactic pantoprazole versus placebo in the international SUP in the ICU (SUP-ICU) trial. All analyses were conducted according to a published protocol and statistical analysis plan. Results: Data of 3,291 acutely admitted adult ICU patients with one or more risk factors for GI bleeding randomized to pantoprazole or placebo intravenously once daily during ICU stay (until ICU discharge, death, or a maximum of 90 days) were analyzed. Some 20 out of 258 (7.8%, 95% CI 4.5–11.1%) and 52 out of 568 (9.2%, 95% CI 6.8–11.6%) of the patients receiving RRT at baseline and at any time in ICU, respectively, developed clinically important GI bleeding in the ICU. We did not observe statistically significant differences in the intervention effect (pantoprazole vs. placebo) in the proportion of patients with clinically important GI bleeding, clinically important events, infectious adverse events, use of interventions to stop GI bleeding, or 90-day mortality in patients with versus without RRT at baseline. Conclusions: In adult ICU patients receiving RRT at baseline, we observed high incidences of clinically important GI bleeding, but did not observe effects of pantoprazole versus placebo in this subgroup.

Keywords:
Acute kidney injury, Continuous renal replacement therapy, Sepsis, Critical illness, Stress ulcer prophylaxis, Gastrointestinal bleeding
1.
Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, et al.; SUP-ICU co-authors. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients.
Intensive Care Med
. 2015 May;41(5):833–45.
2.
Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.
Crit Care Med
. 2017 Mar;45(3):486–552.
3.
Krag M, Marker S, Perner A, Wetterslev J, Wise MP, Schefold JC, et al.; SUP-ICU trial group. Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU.
N Engl J Med
. 2018 Dec;379(23):2199–208.
4.
Bellomo R, Kellum JA, Ronco C. Acute kidney injury.
Lancet
. 2012 Aug;380(9843):756–66.
5.
Lutz J, Menke J, Sollinger D, Schinzel H, Thürmel K. Haemostasis in chronic kidney disease.
Nephrol Dial Transplant
. 2014 Jan;29(1):29–40.
6.
Oudemans-van Straaten HM. Hemostasis and thrombosis in continuous renal replacement treatment.
Semin Thromb Hemost
. 2015 Feb;41(1):91–8.
7.
Pschowski R, Briegel S, Von Haehling S, Doehner W, Bender TO, Pape UF, et al. Effects of dialysis modality on blood loss, bleeding complications and transfusion requirements in critically ill patients with dialysis-dependent acute renal failure.
Anaesth Intensive Care
. 2015 Nov;43(6):764–70.
8.
Remuzzi G. Bleeding disorders in uremia: pathophysiology and treatment.
Adv Nephrol Necker Hosp
. 1989;18:171–86.
9.
Schoorl M, Grooteman MP, Bartels PC, Nubé MJ. Aspects of platelet disturbances in haemodialysis patients.
Clin Kidney J
. 2013 Jun;6(3):266–71.
10.
Castaldi PA, Rozenberg MC, Stewart JH. The bleeding disorder of uraemia. A qualitative platelet defect.
Lancet
. 1966 Jul;2(7454):66–9.
11.
Lutz J, Jurk K. Antiplatelet agents and anticoagulants in patients with chronic kidney disease - from pathophysiology to clinical practice.
Curr Pharm Des
. 2017;23(9):1366–76.
12.
Rocşoreanu A, Cernea D, Simionescu CE, MoŢa E. The complexity of hemorrhage-generating factors in various organs in acute kidney injury.
Rom J Morphol Embryol
. 2016;57(2):491–4.
13.
Sagripanti A, Barsotti G. Bleeding and thrombosis in chronic uremia.
Nephron
. 1997;75(2):125–39.
14.
Schefold JC, Filippatos G, Hasenfuss G, Anker SD, von Haehling S. Heart failure and kidney dysfunction: epidemiology, mechanisms and management.
Nat Rev Nephrol
. 2016 Oct;12(10):610–23.
15.
Bouchard J, Mehta RL. Acute Kidney Injury in Western Countries.
Kidney Dis (Basel)
. 2016 Oct;2(3):103–10.
16.
Gómez H, Kellum JA. Sepsis-induced acute kidney injury.
Curr Opin Crit Care
. 2016 Dec;22(6):546–53.
17.
Schefold JC, von Haehling S, Pschowski R, Bender T, Berkmann C, Briegel S, et al. The effect of continuous versus intermittent renal replacement therapy on the outcome of critically ill patients with acute renal failure (CONVINT): a prospective randomized controlled trial.
Crit Care
. 2014 Jan;18(1):R11.
18.
Schefold JC, Perner A, Lange T, Wetterslev J, Wise MP, Borthwick M, et al.; SUP-ICU investigators. Effects of stress ulcer prophylaxis in adult ICU patients receiving renal replacement therapy (Sup-Icu RENal, SIREN): study protocol for a pre-planned observational study.
Trials
. 2018 Jan;19(1):26.
19.
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.
BMJ
. 2007 Oct;335(7624):806–8.
20.
Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, et al.; SUP-ICU investigators. Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial.
Trials
. 2016 Apr;17(1):205.
21.
Krag M, Perner A, Wetterslev J, Lange T, Wise MP, Borthwick M, et al. Stress ulcer prophylaxis in the intensive care unit trial: detailed statistical analysis plan.
Acta Anaesthesiol Scand
. 2017 Aug;61(7):859–68.
22.
Jakobsen J, Tamborrino M, Winkel P. Count data analysis in randomised clinical trials.
J Biom Biostat
. 2015;6:227.
23.
Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study.
JAMA
. 1993 Dec;270(24):2957–63.
24.
Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al.; STROBE initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration.
Ann Intern Med
. 2007 Oct;147(8):W163-94.
25.
Lins RL, Elseviers MM, Van der Niepen P, Hoste E, Malbrain ML, Damas P, et al.; SHARF investigators. Intermittent versus continuous renal replacement therapy for acute kidney injury patients admitted to the intensive care unit: results of a randomized clinical trial.
Nephrol Dial Transplant
. 2009 Feb;24(2):512–8.
26.
Vinsonneau C, Camus C, Combes A, Costa de Beauregard MA, Klouche K, Boulain T, et al.; Hemodiafe Study Group. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial.
Lancet
. 2006 Jul;368(9533):379–85.
27.
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.
Intensive Care Med
. 1996 Jul;22(7):707–10.
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2019
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