What is the use of terlipressin in clinical practice?

Clinical Uses of Terlipressin

Terlipressin is primarily indicated for the treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI) and acute variceal hemorrhage (AVH) in patients with cirrhosis, with proven efficacy in improving outcomes in these life-threatening complications of chronic liver disease. 1

Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI)

First-line Treatment

• Terlipressin is the vasoactive drug of choice for HRS-AKI 2, 1
• Must be administered with albumin for optimal efficacy 1
• Reverses HRS-AKI in 36-50% of patients 1

Administration Protocol

• Initial dose: 2 mg/day IV as continuous infusion
• May increase every 24-48 hours up to 12 mg/day if no response
• Albumin administration: 1 g/kg IV (maximum 100 g) on day 1, followed by 20-40 g/day 1
• Continue until serum creatinine returns to within ≤0.3 mg/dL of baseline for 2 consecutive days, or maximum of 14 days 1

Efficacy Predictors

• Better liver function (bilirubin ≤10 mg/dL)
• Better kidney function (serum creatinine ≤5 mg/dL)
• Increase in mean arterial pressure ≥5 mmHg with treatment 1
• Lower grades of acute-on-chronic liver failure (ACLF) 1

Acute Variceal Hemorrhage (AVH)

Treatment Protocol

• Initiate as soon as variceal bleeding is suspected, preferably before endoscopy 2, 1
• Initial dose: 2 mg IV bolus, followed by 1-2 mg IV every 4-6 hours 2
• Continue for 2-5 days after initial endoscopic hemostasis to prevent early rebleeding 2, 1

Efficacy

• Reduces 7-day mortality (relative risk 0.74) 2, 1
• Improves hemostasis rate (relative risk 1.21) 2, 1
• Lowers transfusion requirements 1
• Shortens hospitalization 1

Mechanism of Action

Terlipressin is a synthetic vasopressin analogue with twice the selectivity for vasopressin V1 receptors versus V2 receptors 3. It acts through:

1. Vasoconstriction of splanchnic vessels via V1 receptor stimulation
2. Reduction of portal hypertension and blood circulation in portal vessels
3. Increase in effective arterial volume and mean arterial pressure 3
4. Improvement of glomerular filtration and sodium excretion in patients with ascites 4

Safety Considerations and Contraindications

Contraindications

• Hypoxemia (oxygen saturation <90%) 2, 1
• Ongoing coronary, peripheral, or mesenteric ischemia 2, 1
• Serum creatinine ≥5 mg/dL 1

Use with Caution

• Acute-on-chronic liver failure grade 3 2, 1
• High MELD scores (≥35) 2

Common Adverse Effects

1. Cardiovascular complications (12% of patients) 1

   • Angina
   • Arrhythmias
   • Digital ischemia

2. Respiratory complications (8-30% of patients) 1

   • Pulmonary edema
   • Respiratory failure

3. Other side effects 2

   • Hyponatremia
   • Abdominal pain
   • Diarrhea

Monitoring During Treatment

• Regular vital sign monitoring, especially blood pressure and heart rate
• Continuous pulse oximetry for respiratory status
• Renal function tests
• ECG before starting treatment 1
• Discontinue if SpO₂ <90% 1

Comparison with Other Vasoactive Agents

• In the US, octreotide is often preferred for variceal hemorrhage due to a better safety profile 1
• Terlipressin and vasopressin have 2.39-fold higher adverse event rates compared to octreotide/somatostatin 1
• However, terlipressin may have greater portal pressure reduction effects than somatostatin 1
• For HRS-AKI, alternatives include:
  • Norepinephrine (requires central venous line and ICU admission)
  • Midodrine plus octreotide (less effective) 1

Practical Considerations

• Terlipressin treatment does not require intensive care unit monitoring 2
• Can be administered intravenously through a peripheral line 2
• In variceal bleeding, discontinue if endoscopy reveals non-variceal bleeding 1
• For HRS-AKI, treatment should be repeated if recurrence occurs after treatment cessation 1

Terlipressin remains a cornerstone in the management of these severe complications of cirrhosis, with documented mortality benefits when used appropriately and with proper monitoring for adverse effects.