Pharmacotherapy

Non-pharmacologic Management

• Enteral nutrition:
  • Should be initiated early in critically ill patients when feasible. Enteral feeding helps maintain mucosal integrity and blood flow.
  • Observational studies suggest enteral nutrition may decrease risk of overt bleeding compared to no feeding.
  • One meta-analysis found prophylactic agents were not effective in reducing bleeding in enterally fed patients, but study quality was limited.
  • Current evidence does not support withholding pharmacologic prophylaxis in patients receiving enteral nutrition.

• Elevation of the head of the bed to at least 30 degrees in patients receiving mechanical ventilation reduces risk of aspiration and nosocomial pneumonia.

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Pharmacologic Management

• Prophylactic agents reduce pH and/or increase mucosal protection. They do not treat underlying risk factors for stress ulceration.

Antacids

• Mechanism of action: Neutralize gastric acid and raise intragastric pH. Do not affect gastric acid secretion.
• Dosing: 30-60 mL PO/NG every 1-2 hours.
• Adverse effects:
  • Systemic alkalosis, diarrhea, constipation, nausea
  • Hypermagnesemia, hypercalcemia, hypophosphatemia with long-term use
  • Increased aspiration risk
  • Tube occlusion with NG administration

• Monitoring: Electrolytes, residual volumes
• Interactions: May interfere with absorption of other medications
• Limitations: Requires very frequent dosing, adverse effect risks

Sucralfate

• Mechanism of action: Forms protective coating over ulcers via binding to proteins. Does not alter gastric pH.
• Dosing: 1 g PO/NG every 6 hours. Does not come in IV formulation.
• Adverse effects:
  • Constipation
  • Hypophosphatemia
  • Bezoar formation
  • Aluminum toxicity (with impaired renal function)
  • Decreased absorption of other drugs (chelating effect)

• Monitoring: Renal function, phosphate level, abdominal X-ray (bezoar)
• Interactions: Quinolones, tetracyclines, fluoroquinolones, thyroid hormones
• Limitations:
  • Less effective than H2RAs
  • Need for frequent dosing
  • Lack of an IV formulation
  • Chelation of other drugs
  • Risk of tube occlusion with NG use

• Clinical Pearls: Not preferred to H2RA or PPIs

Histamine-2 Receptor Antagonists (H2RAs)

• Mechanism of action: Block histamine H2 receptors on gastric parietal cells, decreasing acid secretion
• Agents:
  • Cimetidine
  • Ranitidine
  • Famotidine
  • Nizatidine

• Dosing:
  • Cimetidine: 300 mg IV/NG bolus, then 50-100 mg/hr continuous infusion
  • Ranitidine: 50 mg IV/NG every 8 hours
  • Famotidine: 20 mg IV/NG every 12 hours

• Adverse effects:
  • Headache, dizziness, confusion (cimetidine)
  • Bradycardia
  • Thrombocytopenia
  • Increased liver enzymes
  • Hypersensitivity reactions
  • Theoretical increased risk of nosocomial pneumonia

• Monitoring:
  • Mental status
  • CBC, LFTs
  • Heart rate
  • Serum creatinine (with cimetidine)

• Interactions:
  • Cimetidine inhibits CYP enzymes, increasing levels of medications like warfarin, phenytoin, theophylline
  • Clinically relevant drug interactions unlikely with other H2RAs

• Limitations:
  • Tachyphylaxis can occur requiring increased doses
  • Not as effective as PPIs based on meta-analyses
  • Only cimetidine FDA approved for SUP

Proton Pump Inhibitors (PPIs)

• Mechanism of action: Irreversibly bind and inhibit H+/K+ ATPase proton pumps on gastric parietal cells. Potent acid suppression.
• Agents:
  • Omeprazole
  • Esomeprazole
  • Pantoprazole
  • Lansoprazole
  • Dexlansoprazole 

• Dosing:
  • Omeprazole suspension 40 mg NG/PO daily (only PPI with FDA approval for SUP)
  • Pantoprazole given as 40 mg IV/PO daily
  • Esomeprazole given as 40 mg IV/PO daily
  • Lansoprazole 30 mg NG/PO daily
  • Dexlansoprazole 30 mg NG/PO daily

• Adverse effects:
  • Headache, dizziness, confusion
  • Increased risk of pneumonia is controversial
  • Increased risk of C. difficile infection is controversial
  • Hypomagnesemia
  • Fracture risk with long-term use

• Monitoring:
  • CBC, magnesium level
  • Signs of pneumonia
  • Stool testing for C. difficile if diarrhea develops

• Interactions:
  • Metabolized by CYP2C19 and CYP3A4; omeprazole inhibits CYP2C19
  • May interact with warfarin, phenytoin, clopidogrel

• Limitations:
  • Cost is higher than H2RAs
  • Safety concerns with long-term use

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Key Summary Points

• Identify risk factors for stress ulcer bleeding and avoid overuse of prophylactic agents
• Preferred agents are PPIs or H2RAs. Sucralfate has more limited efficacy.
• Oral agents preferred if NG/PO route available.
• Controversy exists over pneumonia and C. difficile infection risks.
• Frequent reassessment needed for appropriate duration of prophylaxis.
• Tailor therapy based on comorbidities and potential for adverse effects.

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