What are the indications and usage guidelines for Terlipressin in patients with bleeding esophageal varices and septic shock?

Indications and Usage Guidelines for Terlipressin in Bleeding Esophageal Varices and Septic Shock

Terlipressin is primarily indicated for the management of bleeding esophageal varices and as an adjunct vasopressor in septic shock, with strong evidence supporting its use in reducing mortality in variceal bleeding and improving hemodynamics in catecholamine-resistant septic shock. 1, 2, 3

Bleeding Esophageal Varices

Indications

• First-line treatment for acute esophageal variceal hemorrhage 4, 5
• Should be initiated as soon as variceal bleeding is suspected, even before diagnostic endoscopy 1

Dosing Protocol

• Initial dose: 2 mg IV every 4 hours for the first 48 hours until bleeding is controlled 1
• Maintenance dose: 1 mg IV every 4 hours for 2-5 days to prevent rebleeding 1
• Administration options:
  • Traditional: IV bolus injections
  • Alternative: Continuous infusion at 4 mg/24 hours (may be more effective at reducing portal pressure with fewer adverse events) 1

Duration of Treatment

• Standard duration: 2-5 days 1
• Shorter course (24-72 hours) may be considered in selected patients with:
  • Child-Pugh A or B cirrhosis
  • No active bleeding during endoscopy 1

Efficacy

• Decreases failure of initial hemostasis by 34% 4
• Reduces mortality by 34% compared to placebo 5
• Lowers portal pressure and decreases pressure in esophageal varices 3
• Particularly valuable when skilled endoscopists are not immediately available 3

Concomitant Therapy

• Should be administered alongside:
  • Prophylactic antibiotics (strong recommendation based on moderate quality evidence) 6
  • Albumin therapy (typically 20-40 g/day) 1

Septic Shock

Indications

• Adjunct vasopressor in catecholamine-resistant septic shock 7, 3
• Used to improve organ perfusion when standard vasopressors are insufficient 3

Mechanism in Septic Shock

• High and selective affinity to vascular V1 receptors 7
• Increases systemic vascular resistance, particularly in the splanchnic area 3
• Improves mean arterial pressure in vasodilatory hyperdynamic shock 7

Cautions in Septic Shock

• May contribute dose-dependently to excessive vasoconstriction 7
• Can cause a reflectory decrease in cardiac output 7
• Optimal timing of therapy initiation remains to be determined 7

Monitoring and Safety Considerations

Required Monitoring

• Oxygen saturation (continuous pulse oximetry recommended) 1
• Serum sodium levels 1
• Signs of cardiac ischemia 1
• Renal function 1

Contraindications

• Hypoxemia (SpO₂ <90%) 1
• Ongoing coronary, peripheral, or mesenteric ischemia 1
• Worsening respiratory symptoms 1
• Use with caution in acute-on-chronic liver failure (ACLF) grade 3 1

Adverse Effects

• Cardiovascular/ischemic complications (approximately 12% of patients) 1
• Hyponatremia 1
• Abdominal pain and diarrhea 1
• Hypoxemia 1

Practical Administration Notes

• Does not require intensive care unit monitoring 1
• Can be administered through a peripheral line 1
• Should be temporarily discontinued if:
  • SpO₂ falls below 90% 1
  • Signs of ischemia develop 1
  • Significant adverse effects occur 1

Special Considerations

• Non-selective beta-blockers should be temporarily suspended during acute bleeding episodes, especially in hypotensive patients (systolic BP <90 mmHg or MAP <65 mmHg) 6
• Anti-fibrinolytic therapy (ε-amino-caproic acid or tranexamic acid) may be considered as rescue therapy in patients with persistent bleeding 6