Accepting that the world is full of uncertainty and ambiguity does not and should not stop people from being pretty sure about a lot of things. Julian Baggini
Pantoprazole or Placebo for Stress Ulcer Prophylaxis (POP-UP Study)
In this randomized Double-Blind Exploratory Study by Selvanderan et el 214 patients were randomized to pantoprazole 40mg vs placebo. They found that prophylactic administration of pantoprazole was neither beneficial or harmful to mechanically ventilated critically ill patients who were expected to receive enteral nutrition. There were no episodes of clinically significant gastrointestinal bleeding in either group
Skillman et el in 1969 found that 5% of consecutive ICU patients had stress ulceration. He also proved that Histamine receptor blocker reduced stress ulcers from 25% to 4% in 100 patients. These findings were later confirmed by Cook et el in 1991 and 1996. Another cohort study by Cook et el in 1994 found risk factors of respiratory failure and coagulopathy but by this time, stress ulcer prophylaxis became standard of care. None of the studies found any mortality benefit. Alhazzani et al.in a metaanalysis of 14 trials found that PPIs were more effective than histamine receptor blockers in reducing both clinical and overt gastrointestinal bleeding. There were only two trials comparing use of proton pump inhibitors with placebo to prevent gastrointestinal bleeding in critically ill patients (Reference 7, 8)
Krag el el in a systematic review in 2014 showed no difference in the risk of bleeding in groups treated with stress ulcer prophylaxis vs no prophylaxis. Sasabuchi et al compared two groups and demonstrated no difference in the rate of significant gastrointestinal bleeding, 30-day mortality, or C. difficile infection. Hospital acquired pneumonia was higher in the group treated with stress ulcer prophylaxis. Selvanderan et al did a prospective randomized double-blind study of 214 mechanically ventilated patients. None of the randomized patients had an episode of clinically significant gastrointestinal bleeding.
Likely increases the risk of hospital-acquired pneumonia by colonization of harmful bacteria.( Herzig et al showed 30% increased odds ratio of hospital-acquired pneumonia). Furthermore, the use of gastric acid suppressive therapy together with the use of broad spectrum antibiotics has been associated with an increased risk of Clostridia difficile infection. An increased risk of cardiovascular events in patients receiving PPI has been suggested by various authors. (Reference 12-16)
Incidence of significant GI bleeding is low in today’s critical care patients. Stress ulcer prophylaxis does not make any difference and may actually harm based on several studies. Moreover, once started on these medications, physicians forget to stop them. It is time to say good bye to routine stress ulcer prophylaxis in critically ill patients.
- Pantoprazole or Placebo for Stress Ulcer Prophylaxis (POP-UP): Randomized Double-Blind Exploratory Study : Selvanderan, Shane P. BMEdSci (Hon), MBBS; Summers, Matthew J. BSc, MDiet; Critical Care Medicine: October 2016 – Volume 44 – Issue 10 – p 1842–1850
- Krag M, Perner A, Wetterslev J, et al. 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 2014; 40:11–22
- Sasabuchi Y, Matsui H, Lefor AK, et al.Risks and benefits of stress ulcer prophylaxis for patietns with severe sepsis.Crit Care Med201644e464–e469
- Selvanderan SP, Summers MJ, Finnis ME, et al.Pantoprazole or Placebo for Stress Ulcer Prophylaxis (POP-UP): Randomized Double-Blind Exploratory Study.Crit Care Med2016441842–1850
- Herzig SJ, Howell MD, Ngo LH, et al.Acid-suppressive medication use and the risk for hospital-acquired pneumonia.JAMA20093012120–2128
- Kantorova I, Svoboda P, Scheer P, et al.Stress ulcer prophylaxis in critically ill patients: A randomized controlled trial.Hepatogastroenterology200451757–761
- Powell H, Morgan M, Li SK, et al.Inhibition of gastric acid secretion in the intensive care unit after coronary artery bypass graft. A pilot control study of intravenous omeprazole by bolus and infusion, ranitidine and placebo.Theor Surg19938125–130
- Alhazzani W, Alenezi F, Jaeschke RZ, et al. 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
- Cook D, Heyland D, Griffith L, et al. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med 1999; 27:2812–2817
- Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 1994; 330:377–381
- Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010; 363:1909–1917.
- Charlot M, Ahlehoff O, Norgaard ML, et al. Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study. Ann Intern Med 2010; 153:378–386
- Juurlink DN, Dormuth CR, Huang A, et al. Proton pump inhibitors and the risk of adverse cardiac events. PLoS One 2013; 8:e8489
- Simon T, Steg PG, Gilard M, et al. Clinical events as a function of proton pump inhibitor use, clopidogrel use, and cytochrome P450 2C19 genotype in a large nationwide cohort of acute myocardial infarction: results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocard. Circulation 2011; 123:474–482
- Van Boxel OS, van Oijen MG, Hagenaars MP, et al. Cardiovascular and gastrointestinal outcomes in clopidogrel users on proton pump inhibitors: results of a large Dutch cohort study. Am J Gastroenterol 2010; 105:2430–2436