What medications control bleeding in a patient with esophageal variceal bleeding due to liver cirrhosis and portal hypertension?

Medications for Controlling Esophageal Variceal Bleeding

Initiate vasoactive drugs immediately upon clinical suspicion of variceal bleeding—even before endoscopy—with terlipressin as the preferred agent (if available) or octreotide as the alternative, combined with ceftriaxone 1g IV daily for antibiotic prophylaxis. 1, 2

First-Line Vasoactive Agents

Terlipressin (Preferred Agent)

• Terlipressin is the only vasoactive drug proven to reduce mortality by 34% (RR 0.66) compared to placebo, making it the superior choice when available 2, 3
• Dosing: Start with 2 mg IV bolus every 4 hours until bleeding is controlled, then reduce to 1 mg IV every 4 hours for 2-5 days total 2, 3
• Alternative continuous infusion: 4 mg/24 hours provides superior hepatic venous pressure gradient reduction 2
• Mechanism: Causes splanchnic vasoconstriction, reducing portal venous inflow and lowering portal pressure 3, 4

Critical contraindications to terlipressin: 2, 3

• Active coronary, peripheral, or mesenteric ischemia
• Hypoxia or worsening respiratory symptoms
• Pregnancy

Octreotide (Alternative When Terlipressin Unavailable)

• Octreotide is the preferred agent available in the United States (terlipressin remains investigational in the U.S.) 1
• Dosing: 50 mcg IV bolus, followed by continuous infusion of 50 mcg/hour for 2-5 days 1, 2
• Octreotide has a favorable safety profile with fewer cardiovascular complications than vasopressin 1
• Monitor for adverse effects including abdominal pain, nausea, and hyperglycemia 1

Somatostatin (Alternative)

• Dosing: 250 mcg IV bolus followed by continuous infusion of 250 mcg/hour 2
• Similar efficacy to octreotide but less commonly used in the U.S. 5

Mandatory Adjunctive Antibiotic Therapy

Ceftriaxone 1g IV daily for maximum 7 days is mandatory in all patients with variceal bleeding 5, 1

• Reduces mortality (RR 0.73), bacterial infections (RR 0.40), and rebleeding rates 1
• Discontinue when hemorrhage resolves and vasoactive drugs are stopped 5

Critical Timing and Combination Strategy

Start vasoactive drugs immediately upon clinical suspicion—do NOT wait for endoscopy 5, 1, 2

• Early administration facilitates endoscopy, improves hemostasis rates, and reduces 5-day mortality 5, 1
• Combination therapy (vasoactive drugs + endoscopic variceal ligation) achieves 77% 5-day hemostasis versus only 58% with endoscopy alone 5, 1
• Endoscopy should be performed within 12 hours after initial resuscitation and hemodynamic stabilization 5, 2

Supportive Pharmacological Measures

Restrictive Transfusion Strategy

• Target hemoglobin of 7-9 g/dL to avoid increasing portal pressure from excessive volume expansion 5, 2
• Overtransfusion (maintaining hemoglobin >8 g/dL) increases portal pressure and rebleeding risk 2

Proton Pump Inhibitors

• PPIs are NOT required when using somatostatin analogs (octreotide) because these agents already inhibit gastric acid secretion 1

Rescue Therapy for Treatment Failure

10-20% of patients will have persistent bleeding or early rebleeding despite optimal therapy 5, 2

Early TIPS (Transjugular Intrahepatic Portosystemic Shunt)

• Indicated for high-risk patients within 24-72 hours (ideally <24 hours): 5, 2
  • Child-Pugh class B with active bleeding at endoscopy
  • Child-Pugh class C with MELD score <14
  • Hepatic venous pressure gradient (HVPG) ≥20 mmHg measured within 24 hours
• Also indicated as rescue therapy when bleeding cannot be controlled despite combined pharmacological and endoscopic therapy 5, 2

Temporary Bridge Measures

• Balloon tamponade can be used as a bridge therapy for maximum 24 hours in uncontrolled bleeding 5
• Removable covered self-expanding esophageal stents are an alternative to balloon tamponade and can stay in place up to 7 days 5

Critical Pitfalls to Avoid

Do NOT use non-selective beta-blockers during acute bleeding 5, 2

• Beta-blockers and vasodilators should be avoided during the acute bleeding episode 5
• These are reserved for secondary prophylaxis after bleeding is controlled 5, 2

Do NOT delay vasoactive drugs waiting for endoscopy—start immediately upon clinical suspicion 5, 1, 2

Do NOT use vasopressin alone due to severe cardiovascular side effects 2

Duration of Therapy

• Continue vasoactive drugs for 2-5 days after initial hemostasis is achieved 5, 1, 2
• Antibiotic prophylaxis for maximum 7 days 5, 1
• Once bleeding is controlled and vasoactive drugs discontinued, initiate non-selective beta-blockers for secondary prophylaxis 5