When should proton pump inhibitor (PPI) prophylaxis be started in critically ill patients?

When to Start PPI Prophylaxis in Critically Ill Patients

Proton pump inhibitor (PPI) or H2-receptor antagonist (H2RA) prophylaxis should be initiated immediately upon ICU admission in critically ill patients who have risk factors for clinically important gastrointestinal bleeding. 1, 2

Risk Assessment for Initiating Prophylaxis

The decision to start stress ulcer prophylaxis hinges on identifying high-risk patients. Start prophylaxis immediately if any of the following risk factors are present: 1, 2

High-Risk Criteria (>4% bleeding risk):

• Mechanical ventilation expected to last >48 hours 1, 2, 3
• Coagulopathy (the strongest predictor with OR = 4.3 for gastrointestinal bleeding) 2, 3
• Combination of mechanical ventilation with enteral nutrition PLUS two or more of: acute kidney injury, sepsis, or shock 1, 4
• Severe liver disease (MELD score ≥35) 2, 3
• History of gastrointestinal bleeding or peptic ulcer disease 3
• Burns >40% total body surface area (Curling's ulcers develop within 24-48 hours) 5

Moderate-Risk Criteria:

• Major vascular or abdominal surgery 2, 3
• Hypovolemic shock causing gastric hypoperfusion 2
• Acute kidney injury 2

Timing of Initiation

Do not delay prophylaxis. The evidence is clear that stress-related gastric ulcers can develop within 24-48 hours of critical illness onset, particularly in patients with the risk factors listed above. 2, 5 Prophylaxis must be started immediately upon ICU admission, not after bleeding develops, as mortality from stress ulcer bleeding in critically ill patients reaches 48.5% compared to 9.1% in those without bleeding. 2, 5

The 2024 Society of Critical Care Medicine guidelines explicitly recommend starting prophylaxis as soon as risk factors are identified, with the understanding that waiting for bleeding to occur is associated with significantly worse outcomes. 1

Agent Selection

Either PPIs or H2RAs are acceptable first-line agents (conditional recommendation, moderate certainty of evidence). 1 However, PPIs are probably more effective than H2RAs at preventing clinically important bleeding (OR 0.38,95% CI 0.20-0.73). 6, 4

Practical considerations:

• For patients with severe liver disease or highest bleeding risk, prefer intravenous pantoprazole 40 mg daily 2, 3
• Either enteral or IV routes are acceptable when administering prophylaxis 1
• Use low-dose prophylaxis (standard once-daily dosing), not high-dose regimens 1

Patients Who Should NOT Receive Prophylaxis

Do not initiate prophylaxis in critically ill patients without risk factors for gastrointestinal bleeding (conditional recommendation, moderate certainty). 1 The balance of benefits and harms does not favor routine prophylaxis in low-risk patients, particularly given the potential for increased pneumonia risk (OR 1.27-1.65 for PPIs vs. alternatives) and C. difficile infection (OR 3.11). 7, 6

Duration and Discontinuation

Discontinue prophylaxis when: 1

• Risk factors are no longer present
• The patient is transferred out of the ICU
• The patient achieves independent mobility and tolerates enteral nutrition 2, 3

For patients on prophylaxis before ICU admission: Review the indication and consider discontinuation if no ICU-specific risk factors are present. 1 If risk factors exist, continue the prophylaxis but consider switching to the most appropriate agent for the ICU setting. 1

Critical Pitfalls to Avoid

• Delaying initiation until bleeding occurs - this is associated with dramatically increased mortality 2, 5
• Using prophylaxis in all ICU patients indiscriminately - this exposes low-risk patients to unnecessary harm from pneumonia and C. difficile infection 7, 6
• Continuing prophylaxis after transfer from ICU - this leads to inappropriate long-term prescribing 1
• Inadequate attention to enteral nutrition - early enteral feeding provides independent protection beyond acid suppression when feasible 5

Monitoring Requirements

Monitor daily for: 3

• Signs of gastrointestinal bleeding (melena, hematemesis, hemoglobin drop)
• Resolution of risk factors to guide discontinuation decisions
• Development of complications (pneumonia, C. difficile infection)