What are the indications for Proton Pump Inhibitors (PPIs) in patients admitted to the Intensive Care Unit (ICU)?

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Indications for PPI Inhibitors in ICU Patients

Proton pump inhibitors (PPIs) should be administered to critically ill ICU patients with risk factors for stress-related upper gastrointestinal bleeding (UGIB), specifically those with coagulopathy, shock, or chronic liver disease. 1

Risk Factors for Stress-Related UGIB in ICU Patients

  • Coagulopathy is associated with an increased absolute risk of stress-related UGIB of 4.8% (95% CI, 2.6–8.6) 1
  • Shock is associated with an increased absolute risk of stress-related UGIB of 2.6% (95% CI, 1.2–5.4) 1
  • Chronic liver disease is associated with an increased absolute risk of stress-related UGIB of 7.6% (95% CI, 3.3–17.6) 1
  • Mechanical ventilation alone is not considered an independent risk factor for UGIB and does not necessitate stress ulcer prophylaxis (SUP) 1

Role of Enteral Nutrition in Stress Ulcer Prophylaxis

  • Enteral nutrition (EN) reduces the risk of clinically important stress-related UGIB in critically ill adults 1
  • Enteral nutrition is associated with a decreased absolute risk of stress-related UGIB of 0.3% (95% CI, 0.1–0.7) 1
  • However, even patients receiving enteral nutrition should receive SUP if they have one or more risk factors for clinically important stress-related UGIB 1
  • For patients who are enterally fed but at low risk for UGIB, SUP is not recommended 1

Medication Selection for Stress Ulcer Prophylaxis

  • Either PPIs or histamine-2 receptor antagonists (H2RAs) are recommended as first-line agents for SUP in critically ill adults with risk factors 1
  • PPIs have been shown to reduce clinically important UGIB (relative risk 0.52; 95% CI, 0.30–0.81) 1
  • While PPIs may be more effective than H2RAs at preventing UGIB, there is uncertainty regarding their influence on mortality in patients with high severity of illness 1
  • For patients with acute liver failure, H2 blocking agents or PPIs are recommended for prophylaxis of acid-related GI bleeding 1

Administration Considerations

  • Either enteral or intravenous routes can be used when administering SUP 1
  • Low-dose SUP should be administered rather than high-dose SUP 1
  • "Low-dose" PPI therapy is defined as a daily dose of ≤40mg esomeprazole, omeprazole, or pantoprazole and ≤30mg lansoprazole 1
  • "Low-dose" H2RA therapy is defined as a daily dose of ≤40mg famotidine, ≤150mg IV ranitidine, ≤300mg enteral ranitidine, and ≤1200mg cimetidine 1

Duration of Therapy

  • SUP should be discontinued when critical illness is no longer evident or when risk factors are no longer present despite ongoing critical illness 1
  • Discontinuation of SUP before transfer out of the ICU is necessary to prevent inappropriate prescribing 1
  • For patients already on SUP before ICU admission, the indications should be reviewed and consideration made for discontinuing or changing to the preferred agent 1

Potential Risks and Considerations

  • Concurrent administration of SUP with enteral nutrition may increase pneumonia risk 1
  • Some studies suggest PPIs may be associated with increased risk of Clostridioides difficile-associated diarrhea (CDAD) 2, 3
  • However, the benefits of preventing clinically important UGIB in high-risk patients outweigh these potential risks 1, 4
  • SUP is not recommended for general medicine patients outside the ICU without specific risk factors 5

Special Populations

  • In neurocritical care patients, SUP is recommended to reduce clinically important stress-related UGIB 1
  • These patients may be at additional risk due to physiologic changes resulting in hypersecretion of gastric acid 1

By following these evidence-based recommendations, clinicians can appropriately identify ICU patients who would benefit from PPI therapy while minimizing unnecessary medication use and potential adverse effects.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Stress-related mucosal disease in the critically ill patient.

Nature reviews. Gastroenterology & hepatology, 2015

Research

Stress ulcer prophylaxis in hospitalized patients not in intensive care units.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2007

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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