What is the recommended dosage of terlipressin for hepatorenal syndrome?

Terlipressin Dosage in Hepatorenal Syndrome

The recommended dosage of terlipressin for hepatorenal syndrome is 1 mg intravenously every 4-6 hours initially, with an increase to 2 mg every 4-6 hours if serum creatinine does not decrease by at least 25% after 3 days of treatment. 1

Administration Protocol

Initial Dosing

• Start with 1 mg IV every 4-6 hours 2, 1
• Administer as an IV bolus injection over 2 minutes 3
• Can be administered via peripheral vein (central venous access not required) 1

Dose Adjustment

• If serum creatinine does not decrease by at least 25% by day 3 of treatment, increase dose to 2 mg every 4-6 hours 2, 1
• If serum creatinine is at or above baseline value on day 4, consider discontinuing treatment 3

Alternative Administration Method

• Continuous infusion at the same daily doses (2-12 mg/24h) is an effective alternative 2
• Continuous infusion may reduce risk of adverse events such as cardiac or intestinal ischemia, pulmonary edema, or distal necrosis 2
• Recent evidence suggests continuous infusion at 4 mg/day may be well-tolerated with similar efficacy to bolus dosing 4

Concurrent Albumin Administration

• Albumin should be administered concurrently with terlipressin 2, 1
• Initial albumin dose: 1 g/kg on day 1 (maximum 100 g) 2, 1, 3
• Maintenance albumin dose: 20-40 g/day thereafter 2, 1, 3

Treatment Duration

• Continue treatment until serum creatinine decreases below 1.5 mg/dl 2
• Maximum treatment duration is 14 days 2, 1, 3
• Median time to response is approximately 14 days, usually shorter in patients with lower baseline serum creatinine 2

Monitoring During Treatment

• Monitor vital signs regularly, especially blood pressure and heart rate 1
• Continuous pulse oximetry for respiratory status 1
• Regular renal function tests 1
• ECG screening before starting treatment 1

Efficacy and Response

• Treatment is effective in 40-50% of patients with HRS 2, 1
• Response is characterized by progressive reduction in serum creatinine, increase in arterial pressure, urine volume, and serum sodium concentration 2
• Predictors of positive response include:
  • Serum bilirubin <10 mg/dl before treatment 2, 1
  • Increase in mean arterial pressure >5 mmHg at day 3 of treatment 2, 1
  • Lower baseline serum creatinine 2
  • Lower grades of acute-on-chronic liver failure 1

Adverse Effects and Contraindications

• Cardiovascular or ischemic complications occur in approximately 12% of patients 2, 1
• Respiratory complications occur in 8-30% of patients 1
• Other side effects include hyponatremia, abdominal pain, and diarrhea 1
• Contraindications include:
  • Hypoxemia (oxygen saturation <90%) 1
  • Ischemic heart disease 1
  • Acute-on-chronic liver failure grade 3 1
  • High MELD scores (≥35) 1

When to Discontinue Treatment

• When serum creatinine returns to ≤0.3 mg/dL of baseline value for 2 consecutive days 1
• If SpO₂ <90% 1
• If cardiac or ischemic symptoms occur 1
• If there is no response after 3-4 days with maximum tolerated doses 1

Alternative Vasoconstrictors

• Norepinephrine (0.5-3 mg/h as continuous infusion) is a viable alternative if central venous access is available 2, 1
• Midodrine plus octreotide is less effective but can be used when terlipressin is unavailable 2, 1, 5

Terlipressin plus albumin has been shown to be significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS (70.4% vs 28.6% recovery rate) 5.