What is the recommended administration method for terlipressin (vasopressin analogue) in patients with hepatorenal syndrome, bolus or continuous infusion?

Terlipressin Administration for Hepatorenal Syndrome: Continuous Infusion vs. Bolus Dosing

Continuous infusion of terlipressin is recommended over bolus dosing for hepatorenal syndrome as it remains equally effective while enabling lower daily doses and reducing the risk of adverse events such as cardiac or intestinal ischemia, pulmonary edema, and distal necrosis. 1

Efficacy Comparison

• Both administration methods (continuous infusion and bolus dosing) demonstrate similar efficacy in improving renal function in hepatorenal syndrome patients 1
• Response rates in terms of improvement in renal function (complete or partial response) range from 64% to 76% with terlipressin treatment 1
• The continuous administration of terlipressin at the same daily doses (2-12 mg/24h) appears to be an interesting alternative to bolus dosing 1

Advantages of Continuous Infusion

• Continuous infusion provides a more stable lowering effect on portal pressure compared to bolus dosing 1
• Continuous infusion allows for lower daily doses while maintaining efficacy, thereby reducing the risk of adverse events 1
• Adverse events such as cardiac or intestinal ischemia, pulmonary edema, and distal necrosis occur less frequently with continuous infusion 1
• A recent retrospective observational study showed that terlipressin infusion at 4 mg/day was well-tolerated with favorable outcomes in HRS-AKI patients 2

Standard Dosing Protocols

Bolus Dosing Protocol

• Initial dose: 0.5-1 mg every 4-6 hours by intravenous bolus 1
• Dose escalation: Up to 2 mg every 4-6 hours if serum creatinine does not decrease by more than 25% 1
• Maximum daily dose: 8-12 mg/day 3
• Duration: Until complete response or maximum of 14 days in case of partial response 1

Continuous Infusion Protocol

• Initial dose: 2 mg/day as continuous intravenous infusion 1, 3
• Dose adjustment: Based on clinical response and serum creatinine levels 3
• Duration: Same as bolus protocol - until complete response or maximum of 14 days 1

Concomitant Albumin Administration

• Terlipressin should always be administered with albumin for optimal results in hepatorenal syndrome 1
• Recommended albumin dosing: 1 g/kg on first day, followed by 20-40 g/day 1, 3
• The combination of terlipressin plus albumin has been shown to improve short-term survival in patients with HRS 1

Monitoring and Response Assessment

• Response should be assessed by monitoring serum creatinine levels 1
• Complete response: Serum creatinine below 1.5 mg/dl 1
• Partial response: Decrease of serum creatinine ≥50% with final value still higher than 1.5 mg/dl 1
• If serum creatinine decreases by less than 25% after 2-3 days, dose escalation is recommended 3

Adverse Events and Precautions

• Common adverse effects include diarrhea, abdominal pain, circulatory overload, and cardiovascular ischemic complications 1
• Adverse events occur in up to 45-46% of patients when terlipressin is delivered by IV boluses 1
• Rate of discontinuation due to side effects, mainly cardiovascular, is around 20% 1
• Careful clinical screening including electrocardiogram is recommended before starting treatment 1
• Terlipressin is contraindicated in patients with hypoxemia (SpO2 <90%) 3

Clinical Pearls

• Early response to treatment is associated with better survival 3
• For each 1 mg/dL reduction in creatinine with terlipressin therapy, there is a 27% reduction in relative risk of mortality 3
• Patients with advanced liver disease have lower probability of response and may require higher doses 3
• Terlipressin can be administered via a peripheral vein, unlike norepinephrine which requires a central venous catheter 1

In conclusion, while both administration methods are effective for treating hepatorenal syndrome, continuous infusion offers significant advantages in terms of safety profile while maintaining similar efficacy compared to bolus dosing.