Ulcer Prophylaxis

Physiological stress-related gastric and intestinal mucosal bleeding occurs in 8-45% of patients. Ulcer prophylaxis:

Historical risks which do not appear borne out in randomised trials include ↑ risk of:

  • HAP/VAP
    Via gastric bacterial overgrowth and microaspiration.
  • C. difficile infection

Management

Approach:

This only applies to prophylaxis, UGIB should be treated differently and is covered Gastrointestinal Bleeding.

  • Non-pharmacological prophylaxis for all patients
    • Cease primary prevention aspirin
    • Avoid NSAID
    • Enteral nutrition
  • Pharmacological prophylaxis
    • For all patients with ⩾1 risk factor:
      • Intubated
      • Multiple risk factors for ulceration
        • Shock
        • Previous GI bleed
        • High-dose steroid
      • Occult bleeding
      • COVID
    • PPI
      PO or NG preferred if available.
      • Omeprazole 40mg PO/IV/NG daily
      • Pantoprazole 40mg PO/IV/NG daily

Compared with PPI, H2RB:

  • Possible ↓ mortality
    Unclear reason - possibly less effective acid suppression ↓ VAP rates.
  • Relative ↑ UGIB
  • ↑ Delirium
  • Cheaper
    Are no longer available. RIP, ranitidine 150mg PO/NG BD.

Key Studies

  • SUP-ICU (2018)
    • ~3300 adult non-pregnant Europeans admitted to ICU with some risk of GIB, no active GIB or transplant, and for active treatment
    • Block randomised trial of 40mg pantoprazole OD vs. placebo
    • No change in 90 day mortality (31.1% vs 30.4%)
    • Secondary outcomes:
      • Significant ↓ in clinically important GIB (2.5% vs 4.2%)
      • No change in VAP, C. difficile infection, or other SAE
  • PEPTIC (2020)
    • 26,777 adults requiring ICU admission and invasive ventilation
    • Unblinded multi-centre cluster randomised crossover trial
      Units used one class of drug for 6 months, then swapped to the other.
    • Powered to detect 2% ARR
    • PPI vs. histamine-2 receptor blocker
      • PPI group
        5% received H2RB.
      • H2RB group
        20% received PPI.
      • Indication for stress ulcer prophylaxis at clinician discretion
      • Average duration 2.7 days
    • No difference in 90 day mortality (18.3% vs 17.5%, 95% CI 1.00 – 1.10))
      Results have been controversial, interpretations include:
      • Use H2RBs as signal towards death is stronger than risk of non-fatal UGIB
      • Significant cross-over and cluster design limit interpretability of weak results
      • 2.7 days of PPI seems en face unlikely to be fatal
    • Secondary outcomes:
      • ↓ UGIB in PPI group (1.3% vs 1.8%, RR 0.73 (0.57-0.92))
      • ↑ Mortality in cardiac subgroup
      • No change in C. difficile infections
  • REVISE (2024)
    • 4821 invasively-ventilated (<72 hours) adults, without definitive contra/indication to acid suppression
    • Multicentre (68), double-blinded RCT of 40mg pantoprazole vs. placebo
    • 4800 patients would give 85% power to detect 1.5% absolute risk difference in clinically important UGIB at 90 days, assuming 3% baseline event rate
      Defined as UGIB with:
      • Haemodynamic compromise
      • Requiring therapeutic intervention
    • Significant difference in primary outcome (1% vs. 3.5%)
    • No change in:
      • 90-day mortality
      • Pneumonia
      • C. difficile infections

References

  1. The PEPTIC Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Alberta Health Services Critical Care Strategic Clinical Network, and the Irish Critical Care Trials Group, Young PJ, Bagshaw SM, et al. Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial. JAMA. 2020;323(7):616. doi:10.1001/jama.2019.22190
  2. Krag M, Marker S, Perner A, et al. Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU. New England Journal of Medicine. 2018;379(23):2199-2208. doi:10.1056/NEJMoa1714919