What is the appropriate use of Proton Pump Inhibitors (PPIs) in Intensive Care Unit (ICU) patients?

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Last updated: November 30, 2025View editorial policy

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Appropriate Use of Proton Pump Inhibitors in ICU Patients

PPIs should be used for stress ulcer prophylaxis only in ICU patients with specific risk factors (coagulopathy, shock, or chronic liver disease), administered at low doses, and discontinued promptly when risk factors resolve or before ICU transfer. 1

Risk-Based Approach to PPI Initiation

Patients Who SHOULD Receive PPIs

Use PPIs or H2RAs for stress ulcer prophylaxis in ICU patients with these specific risk factors: 1

  • Coagulopathy (absolute risk increase of 4.8% for GI bleeding) 2
  • Shock (absolute risk increase of 2.6% for GI bleeding) 2
  • Chronic liver disease (absolute risk increase of 7.6% for GI bleeding) 2

Patients Who Should NOT Receive PPIs

Do not use PPIs for stress ulcer prophylaxis in: 1

  • Patients on mechanical ventilation alone (not an independent risk factor) 2
  • Low-risk ICU patients without the three risk factors above 1
  • Patients receiving enteral nutrition without other risk factors 1

Important caveat: Even enterally fed patients should receive SUP if they have one or more of the three risk factors listed above 2

Medication Selection and Dosing

Agent Choice

Either PPIs or H2RAs are acceptable first-line agents with no clear superiority of one over the other 1. The 2024 Society of Critical Care Medicine guideline provides conditional recommendation for either agent with moderate certainty of evidence 1. This represents a shift from the 2017 Surviving Sepsis Campaign guideline that weakly favored PPIs over H2RAs 1.

Route of Administration

Either enteral or IV routes are acceptable for SUP administration 1. The choice should be based on patient-specific factors such as enteral access and absorption capability 1.

Dosing Strategy

Always use low-dose PPI therapy, never high-dose 1, 2. Low-dose is defined as: 2

  • ≤40 mg daily of esomeprazole, omeprazole, or pantoprazole
  • ≤30 mg daily of lansoprazole

For H2RAs, low-dose is defined as: 2

  • ≤40 mg daily famotidine
  • ≤150 mg IV or ≤300 mg enteral ranitidine daily
  • ≤1200 mg cimetidine daily

Discontinuation Strategy

Discontinue PPIs when risk factors resolve or before ICU transfer to prevent inappropriate continuation 1, 2. This is a good practice statement with strong emphasis on preventing post-ICU overuse 1.

For Patients on PPIs Before ICU Admission

Review indications and consider discontinuation if no appropriate ongoing indication exists 1. If the patient has ICU-specific risk factors and was already on a PPI for another indication, weigh changing to the preferred SUP agent against maintaining the pre-existing indication 1.

Appropriate Long-Term Indications (if applicable)

According to the 2022 AGA guideline, PPIs are conditionally indicated for acute/short-term use for stress ulcer prophylaxis in ICU patients with risk factors 1. This is NOT a long-term indication 1.

Risks and Benefits Balance

Benefits

PPIs reduce clinically important upper GI bleeding with a relative risk of 0.52 (95% CI, 0.30-0.81) in high-risk ICU patients 2.

Risks to Monitor

Concurrent SUP with enteral nutrition may increase pneumonia risk 1, 2. However, one large study found no association between PPI use and bloodstream infections in ICU patients 3.

Other documented risks include: 4, 5

  • Clostridium difficile-associated diarrhea (odds ratio 3.11 in medical ICU patients) 5
  • Acute tubulointerstitial nephritis 4
  • Hypomagnesemia with prolonged use 4
  • Thrombophlebitis at injection sites 4

Common Pitfalls to Avoid

  1. Do not continue PPIs after ICU discharge without documented indication - this is the most common source of inappropriate long-term PPI use 1, 6

  2. Do not use mechanical ventilation alone as justification for SUP - it is not an independent risk factor 2

  3. Do not use high-dose or twice-daily PPI regimens for stress ulcer prophylaxis 1, 2

  4. Do not assume enteral nutrition eliminates the need for SUP in patients with coagulopathy, shock, or chronic liver disease 2

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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