Terlipressin Dosing for Hepatorenal Syndrome
Start terlipressin at 1 mg IV bolus every 4-6 hours combined with albumin (1 g/kg on day 1, then 40-50 g/day), escalating to 2 mg every 4-6 hours if serum creatinine fails to decrease by ≥25% after 2-4 days, with a maximum dose of 12 mg/day for up to 14 days. 1, 2
Initial Dosing Regimen
Bolus Administration (Standard Approach)
- Begin with 1 mg IV bolus every 4-6 hours as the initial dose, which is the FDA-approved and most widely studied regimen 1, 3
- The European guidelines suggest starting at 0.5-1 mg every 4-6 hours for the first 3 days, though 1 mg is more commonly used 1, 2
- Continue treatment for up to 14 days or until creatinine returns to within 0.3 mg/dL of baseline 1
Continuous Infusion (Alternative)
- Start at 2 mg/day as continuous IV infusion, which achieves equal efficacy with lower total daily doses and fewer ischemic side effects compared to bolus dosing 1, 2
- This approach is not FDA-approved in the United States but is widely used internationally 1
- Increase every 24-48 hours up to 12 mg/day based on response 1
Mandatory Albumin Co-Administration
Always combine terlipressin with albumin to optimize circulatory function and treatment efficacy 1, 2:
- 1 g/kg on day 1 (up to 100 g maximum) 1, 2
- 40-50 g/day thereafter until treatment completion 1
- Some protocols use 20-40 g/day after day 1 1, 2
Dose Escalation Protocol
When to Escalate
- Increase to 2 mg every 4-6 hours if serum creatinine has not decreased by at least 25% from baseline after 2-4 days 1, 2
- For continuous infusion, increase in stepwise fashion every 24-48 hours 1
- Maximum dose is 12 mg/day regardless of administration method 1
Predictors of Response
- Mean arterial pressure (MAP) increase of ≥5-10 mmHg by day 3 predicts treatment response 1, 2
- Baseline bilirubin <10 mg/dL and serum creatinine <5 mg/dL are favorable prognostic factors 1, 2
- Lower ACLF grade (particularly ACLF-0 or ACLF-1) predicts better response 1
Treatment Duration and Discontinuation
When to Continue
- Maintain treatment until creatinine returns to within 0.3 mg/dL of baseline for 2 consecutive days, up to 14 days maximum 1
- Some patients with very high pretreatment creatinine may need longer than 14 days 1
- Consider prolonged infusions to prevent early recurrence after discontinuation 1
When to Stop
- Discontinue if creatinine remains at or above pretreatment level after 4 days with maximum tolerated doses 1
- Stop immediately if severe ischemic complications develop (angina, arrhythmia, digital ischemia, intestinal ischemia) 1
- Discontinue if respiratory failure develops, particularly in patients with ACLF-3 or baseline hypoxemia 1
Critical Safety Monitoring
Pre-Treatment Assessment
- Obtain baseline electrocardiogram to screen for ischemic heart disease 1
- Check baseline oxygen saturation—do not use if SpO₂ <90% per FDA warning 1, 2
- Assess ACLF grade—exercise extreme caution in ACLF-3 due to increased respiratory failure risk 1, 2
- Verify baseline creatinine is <5 mg/dL (FDA restriction) 1, 2
During Treatment
- Monitor for ischemic complications (occur in ~12% of patients): abdominal pain, chest pain, digital ischemia, arrhythmias 1
- Watch for respiratory failure (occurs in ~30% of patients, particularly with ACLF-3) 1, 2
- Assess for volume overload from albumin infusions, which can precipitate pulmonary edema 1
- Monitor MAP and urine output as markers of response 1, 2
Common Pitfalls
- Overly aggressive albumin administration can cause pulmonary edema, especially in patients with underlying cardiac dysfunction or diastolic dysfunction from cirrhotic cardiomyopathy 1
- Failure to recognize respiratory compromise early in ACLF-3 patients, where terlipressin may worsen outcomes 1
- Not escalating dose appropriately when initial response is inadequate 1
Alternative Vasoconstrictor if Terlipressin Fails or is Contraindicated
Switch to norepinephrine 0.5 mg/hour continuous infusion (or 5 μg/min), titrated up to 3 mg/hour (or 10 μg/min) to achieve MAP increase >10 mmHg above baseline, which demonstrates similar efficacy with response rates of 39-70% 1, 2, 4:
- Requires intensive care unit monitoring 1
- Continue albumin at same doses 1
- Norepinephrine is preferred in patients with shock or contraindications to terlipressin 1
Response Definitions
Complete Response
- Serum creatinine returns to within 0.3 mg/dL of baseline (new AKI-HRS criteria) 1
- Older studies used creatinine ≤1.5 mg/dL as the threshold 1, 5, 6
Partial Response
- Regression of AKI stage with serum creatinine ≥0.3 mg/dL from baseline 1
- ≥25% reduction in creatinine is often used as an early marker of response 1, 2