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Figure 9-1.

Pathophysiology of cirrhosis, portal hypertension, & complications.

Primary Prevention of Variceal Bleeding

  • Esophagogastroduodenoscopy (EGD) to identify presence of varices & measure diameter; no varices → repeat in 2–3y; small varices (<5mm): repeat in 1–2y; large varices (>5mm): repeat yearly
  • Nonselective β-blockers (e.g., propranolol, nadolol) 1st line in patients with varices
    • Goal: ↓ HR by 25% or to ≈55–60bpm → reduce bleeding risk from 25% to 15% over 2y, slight reduction in mortality; NNT = 10 (Semin Liver Dis 1999;19:475)
    • Life-long treatment; risk of bleeding returns when drug discontinued
    • Combined with β-blocker to ↓ rate of first hemorrhage; questionable advantage
  • Endoscopic variceal ligation (EVL) for pts with contraindications or intolerance to β-blockers; repeat every 1–2wk until obliteration; surveillance EGD at 1–3mo & every 6–12mo after to check for recurrence; complications: 14% (transient dysphagia, chest discomfort)
  • Isosorbide mononitrate NOT recommended → ↓ portal pressure; however, ↑ mortality in age >50y & ↑ development of ascites (Gastroenterology 1997;113:1632)

Secondary Prevention of Variceal Bleeding

  • Nonselective β-blockers 1st line, with or without nitrates (e.g., isosorbide mononitrate)
    • Goal: ↓ HR by 25% or to ≈55–60bpm; non-invasive surrogate marker for ↓ portal pressure
    • If contraindications or intolerance: EVL then pantoprazole 40mg IV, then 40mg PO daily × 9d (same number of varices day 10 post-EVL but smaller size) (Hepatology 2005;41:588)
  • Drugs = banding for rebleeding & mortality
  • Therapeutic failure: TIPS vs endoscopic therapy
    • TIPS: decompresses portal venous system; less rebleeding, more hepatic encephalopathy; drugs to control bleeding not required after TIPS/shunt placement
  • Monitor: HR, BP, surveillance EGD

Figure 9-2.

Mechanisms of action for agents for prevention of variceal bleeding. (Reproduced with permission from DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A pathophysiologic Approach, 8th ed. New York: McGraw-Hill, 2011.)

Acute variceal bleeding → treatment goals: control bleeding, prevent rebleeding & avoid acute complications such as SBP

  • Fluid resuscitation → hemodynamic stability & Hb ≈ 8g/dL
    • Do not replace all lost volume with blood (↑portal pressure; ↑ bleeding & ↑ mortality) or saline (↑ hemorrhage, ascites, peripheral edema)
    • FFP/platelets: only for significant coagulopathy &/or thrombocytopenia; do not use recombinant factor VIIa (no benefit over standard therapy) (Gastroenterology 2004;127:1123)
  • Control bleeding/prevent rebleed
  • Pharmacological
    • Octreotide 50–100mcg bolus then 25–50mcg/h continuous infusion for up to 5d (highest risk of rebleeding); continue at least 24–72h after bleeding has stopped
    • Terlipressin 2mg Q4h × 24h & 1mg Q4h for next 24h; up to 5d—improves control of bleeding & reduces mortality (Lancet 1995;346:865); not available in the United States
    • Do not use vasopressin → nonselective vasoconstriction; ↑ risk of systemic effects (hypertension, severe headaches, coronary ischemia, MI)
    • Antibiotics for acute SBP prophylaxis → hemorrhage w/o ascites—↓ infectious complications & mortality (Scand J Gastroenterol 2003;36:193)
      • IV ...

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