Is terlipressin (vasopressin analogue) safe to use in patients with Acute Kidney Injury (AKI)?

Terlipressin in Acute Kidney Injury

Terlipressin is indicated for the treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI) but should not be used in patients with serum creatinine ≥5 mg/dL or oxygen saturation <90% due to safety concerns. 1

Indications for Terlipressin in AKI

Terlipressin is specifically indicated for HRS-AKI, not for other forms of AKI in cirrhosis. The appropriate use follows this algorithm:

1. Diagnosis of HRS-AKI: Confirm HRS-AKI diagnosis by excluding other causes of AKI through:

   • Clinical history and examination
   • Blood biochemistry
   • Urine microscopy and chemistry
   • Renal ultrasound 1

2. Initial Management:

   • Hold diuretics and nonselective beta-blockers
   • Discontinue NSAIDs
   • Treat precipitating causes
   • Replace fluid losses with albumin 1 g/kg/day for 2 days 1

3. Initiation of Terlipressin: When serum creatinine remains >2× baseline despite initial measures 1

Dosing and Administration Protocol

Terlipressin can be administered in two ways:

1. Bolus Administration:

   • Initial dose: 1 mg IV every 4-6 hours (total 4-6 mg/day)
   • Increase to maximum 2 mg every 4-6 hours (8-12 mg/day) if no reduction in serum creatinine by at least 25% by day 3 1, 2

2. Continuous Infusion (preferred due to fewer side effects):

   • Starting dose: 2 mg/day
   • Gradually increase every 24-48 hours up to maximum 12 mg/day 1, 3
   • Some centers use 4 mg/day continuous infusion with similar efficacy and safety 3

3. Concurrent Albumin:

   • 1 g/kg IV on day 1
   • Followed by 20-40 g daily 1, 2
   • Consider patient's volume status when deciding on continued albumin administration 1

Contraindications and Precautions

Terlipressin is contraindicated in:

• Patients with serum creatinine ≥5 mg/dL 1
• Oxygen saturation <90% 1
• Ongoing coronary, peripheral, or mesenteric ischemia 1

Use with caution in:

• Patients with acute-on-chronic liver failure grade 3 1
• Patients with cardiovascular conditions 2
• Patients with high MELD scores (≥35) 1

Monitoring and Duration

• Continue treatment until serum creatinine returns to within ≤0.3 mg/dL of baseline for 2 consecutive days or for a maximum of 14 days 1
• Monitor:
  • Serum creatinine regularly
  • Vital signs, particularly arterial pressure
  • Urine output
  • Continuous pulse oximetry 2
  • Signs of ischemic complications (angina, digital ischemia) 1
  • Respiratory status for pulmonary edema 1, 2

Efficacy and Outcomes

Terlipressin is superior to other vasoconstrictors for HRS-AKI:

• Response rates of 40-50% 2
• Superior to noradrenaline in ACLF patients with HRS-AKI (41.7% vs. 20% response at day 7) 4
• Reduces need for renal replacement therapy (56.6% vs. 80% with noradrenaline) 4
• Improves 28-day survival compared to noradrenaline (48.3% vs. 20%) 4

Adverse Events

Common adverse events include:

• Respiratory complications (8-30%): pulmonary edema, respiratory failure 2
• Cardiovascular complications (12%): angina, arrhythmias, digital ischemia 2
• Abdominal pain, diarrhea, hyponatremia 2

These adverse events can be minimized by:

• Starting at the lowest effective dose
• Gradually titrating upward
• Using continuous infusion rather than bolus dosing 1, 3
• Careful patient selection and monitoring 2

Special Considerations

• Terlipressin does not require ICU monitoring and can be administered through a peripheral line 1
• Liver transplantation remains the definitive treatment for HRS-AKI 1
• Terlipressin responders have improved transplant-free and post-transplant survival 5
• Non-response to terlipressin is a predictor of mortality in ACLF patients with HRS-AKI 6

By following these guidelines, terlipressin can be effectively and safely used in the management of HRS-AKI to improve outcomes in this high-mortality condition.