What is the recommended treatment and dosage of terlipressin for a patient with hepatorenal syndrome (HRS)?

Terlipressin Dosing for Hepatorenal Syndrome

Start terlipressin at 1 mg IV bolus every 4-6 hours combined with albumin (1 g/kg day 1, then 20-40 g/day), escalating to 2 mg every 4-6 hours if serum creatinine fails to decrease by ≥25-30% by day 3-4, with a maximum dose of 12 mg/day for up to 14 days. 1

Initial Dosing Strategy

Bolus dosing remains the standard approach despite continuous infusion being an alternative:

• Begin with 1 mg IV bolus every 4-6 hours (total 4 mg/day) for the first 3 days 1
• Some guidelines suggest starting at 0.5-1 mg every 4-6 hours, though 1 mg is more commonly used 2, 1
• Continuous infusion at 2 mg/day is an alternative that provides equal efficacy with lower total daily doses and fewer ischemic side effects 1, 3

The American Association for the Study of Liver Diseases and FDA both support the 1 mg every 6 hours starting dose, which represents the most recent consensus 1.

Mandatory Albumin Co-Administration

Terlipressin must always be combined with albumin - terlipressin alone has only a 25% response rate versus 77% with combination therapy 1:

• Day 1: 1 g/kg IV (maximum 100 g) 2, 1
• Subsequent days: 20-40 g/day IV until treatment completion 2, 1

Dose Escalation Protocol

Escalate to 2 mg IV every 4-6 hours on day 4 if serum creatinine has not decreased by at least 25-30% from baseline 2, 1:

• Maximum dose is 12 mg/day regardless of administration method 1
• A sustained increase in mean arterial pressure of ≥5-10 mmHg at day 3 predicts treatment response 1
• Continue treatment for up to 14 days or until HRS reversal occurs 1, 4

Pre-Treatment Assessment and Contraindications

Absolute contraindications that must be screened before initiating therapy 1:

• SpO₂ <90% on room air or supplemental oxygen
• Active coronary, peripheral, or mesenteric ischemia
• Serum creatinine >5 mg/dL
• Obtain baseline electrocardiogram to screen for ischemic heart disease 1

Administration Setting and Monitoring

Terlipressin can be safely administered on the ward via peripheral IV line in most patients 1:

• ICU admission is not required for patients with ACLF grade <3 1
• Monitor vital signs including pulse oximetry every 2-4 hours 1
• ICU monitoring is mandatory for patients with ACLF grade 3 (≥3 organ failures) due to increased risk of respiratory failure 1
• Check serum creatinine daily looking for ≥25-30% reduction by days 3-4 1

Safety Monitoring During Treatment

Monitor for ischemic complications, which occur in approximately 12% of patients 1:

• Abdominal pain, chest pain, digital ischemia, arrhythmias 1
• Respiratory failure occurs in 14-30% of patients 1
• Diarrhea and circulatory overload are common adverse effects 3

Response Definitions

Complete response: Serum creatinine returning to within 0.3 mg/dL of baseline 1

Partial response: Regression of AKI stage with serum creatinine ≥0.3 mg/dL from baseline or ≥25% reduction in creatinine 1

Each 1 mg/dL reduction in creatinine (even partial response) reduces mortality risk by 27% 5.

Management of Non-Response

If no response by day 4 after dose escalation, switch to norepinephrine 5:

• Start at 0.5 mg/hour (or 5 μg/min) continuous IV infusion 1, 5
• Titrate up to 3 mg/hour (or 10 μg/min) to achieve MAP increase >10 mmHg above baseline 1, 5
• Norepinephrine demonstrates non-inferiority to terlipressin with response rates of 39-70% 1, 5
• Continue albumin during norepinephrine therapy 2

Predictors of Treatment Success

Favorable prognostic factors that predict HRS reversal 1, 6:

• Baseline bilirubin <10 mg/dL
• Baseline serum creatinine <5 mg/dL
• MAP increase ≥5-10 mmHg by day 3
• Absence of known precipitating factors for HRS

Continuous Infusion as Alternative

Continuous infusion provides equal efficacy with potentially fewer adverse events 3:

• Start at 2 mg/day as continuous IV infusion 1, 3
• Escalate every 24-48 hours up to maximum 12 mg/day if serum creatinine does not decrease by ≥25% 1
• Provides more stable lowering effect on portal pressure compared to bolus dosing 3
• Adverse events such as cardiac or intestinal ischemia, pulmonary edema, and distal necrosis occur less frequently 3