Key Guidelines and Evidence

American Society of Health-System Pharmacists (ASHP) Guidelines on Stress Ulcer Prophylaxis (1999)

ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998 – PubMed (nih.gov)

• Recommends institutions decide on H2 receptor antagonists (H2RAs), antacids, or sucralfate for stress ulcer prophylaxis based on safety profile, cost, and ease of administration
• The choice of agent to use for stress ulcer prophylaxis should take into account concerns for  administration, adverse  drug event profile and  total costs

Danish Society of Intensive Care Medicine Guidelines on Stress Ulcer Prophylaxis (2014):

Guideline for stress ulcer prophylaxis in the intensive care unit – PubMed (nih.gov)

• Recommends proton pump inhibitors (PPIs) as the preferred agents for stress ulcer prophylaxis in critically ill patients
• They report there is insufficient evidence to make any recommendation on SUP and nutrition
• They report there is insufficient evidence to make any recommendation on SUP in ICU subpopulations: trauma, burn septic, and cardiothoracic patients.

Surviving Sepsis Campaign Guidelines on Stress Ulcer Prophylaxis (2016)

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 – PubMed (nih.gov):

• Recommends PPIs or H2RAs for stress ulcer prophylaxis in ICU patients at risk of gastrointestinal bleeding
• Does not recommend one class over the other
• The guideline suggest patients without risk factors should not receive SUP.

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Landmark Trials:

Cook et al. Risk Factors for Gastrointestinal Bleeding in Critically Ill Patients (1994)

Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group – PubMed (nih.gov):

• Multicenter prospective cohort study of 2252 ICU patients
• Identified mechanical ventilation ≥48 hours and coagulopathy as major independent risk factors for clinically important GI bleeding

Cook et al. A Comparison of Sucralfate and Ranitidine for the Prevention of Upper Gastrointestinal Bleeding in Patients Requiring Mechanical Ventilation (1998)

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group – PubMed (nih.gov):

• Randomized 1200 mechanically ventilated ICU patients to sucralfate vs ranitidine
• Patients receiving ranitidine had lower rates of clinically significant GI bleeding compared to sucralfate (1.7% vs 3.8%)
• No significant difference in rates of ventilator-associated pneumonia between ranitidine and sucralfate groups (19.1% vs 16.2%)
• No significant difference in ICU mortality between ranitidine and sucralfate groups (23.5% vs 22.9%)
• No significant difference in ICU length of stay between ranitidine and sucralfate groups (median 9 days for both)

Krag et al. Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU (2018)

Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP-ICU trial): study protocol for a randomised controlled trial – PubMed (nih.gov):

• Randomized 3298 ICU patients at risk of GI bleeding to pantoprazole vs placebo
• The primary outcome measure is 90-day mortality.
  • Secondary outcomes include the proportion of patients with clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection or myocardial ischemia, days alive without life support in the 90-day period, serious adverse reactions, 1-year mortality, and health economic analyses.
• Pantoprazole reduced clinically important GI bleeding compared to placebo (2.5% vs 4.2%; p=0.03)
• In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups.
• No difference in 90-day mortality

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In summary, current guidelines recommend stress ulcer prophylaxis with PPIs or H2RAs in ICU patients at high risk of bleeding. Key trials have identified major risk factors and demonstrated that acid-suppressive agents reduce clinically significant GI bleeding compared to placebo, with PPIs potentially more effective than H2RAs. However, no mortality benefit has been shown.