What is the treatment approach for critically ill patients requiring vasopressor support and volume expansion using terlipressin and albumin?

Treatment Approach for Critically Ill Patients Using Terlipressin and Albumin

For critically ill patients requiring vasopressor support, terlipressin combined with albumin is the first-line treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin administered at 1 mg every 6 hours intravenously and albumin at 20-40 g/day, carefully monitoring for respiratory complications. 1

Diagnostic Criteria for HRS-AKI

Before initiating terlipressin-albumin therapy, confirm HRS-AKI diagnosis using these criteria:

• Cirrhosis with ascites
• Stage 2 AKI or higher (increase in serum creatinine >2-3 times from baseline)
• No response after 2 days of diuretic withdrawal and albumin (1 g/kg up to 100 g/day)
• Absence of shock, nephrotoxic drugs, and parenchymal kidney disease 1

Terlipressin Administration Protocol

Dosing:

• Initial dose: 1 mg IV every 6 hours (administered as bolus over 2 minutes)
• If serum creatinine decreases <30% by day 4, increase to 2 mg every 6 hours
• Maximum treatment duration: 14 days
• Discontinue 24 hours after creatinine decreases to <1.5 mg/dL 1, 2

Administration:

• Can be administered through peripheral or central line
• No ICU monitoring required unless patient has ACLF grade 3 or respiratory concerns
• Continuous infusion (starting at 2 mg/day) may be equally effective with fewer side effects 1

Albumin Administration

• Initial volume expansion: 1 g/kg (maximum 100 g) on day 1
• Maintenance: 20-40 g/day during terlipressin treatment 1, 3
• Reassess need for continued albumin after 1-2 days based on volume status
• Consider using point-of-care ultrasonography to guide albumin administration 1, 4

Monitoring and Safety Considerations

Respiratory Monitoring:

• Obtain baseline oxygen saturation before starting treatment
• Use continuous pulse oximetry during treatment
• Do not initiate terlipressin in hypoxic patients (SpO₂ <90%)
• Monitor for pulmonary edema, especially in patients with:
  • ACLF grade 3 (avoid use if possible)
  • Cirrhotic cardiomyopathy
  • Diastolic dysfunction 2, 1

Contraindications:

• Hypoxemia or worsening respiratory symptoms
• Ongoing coronary, peripheral, or mesenteric ischemia
• Serum creatinine >5 mg/dL (unlikely to benefit)
• MELD score ≥35 (risks may outweigh benefits) 2, 1

Predictors of Response to Terlipressin-Albumin Therapy

Better response rates are associated with:

• Serum bilirubin ≤10 mg/dL
• Serum creatinine ≤5 mg/dL
• Increase in mean arterial pressure ≥5 mmHg with treatment
• Lower ACLF grades
• Normal cardiac function on echocardiography 1, 5, 4

Alternative Vasopressors

• In patients with AKI and shock: norepinephrine is first-line
• For patients without access to terlipressin: norepinephrine (requires ICU admission)
• Midodrine and octreotide combination is less effective and not recommended 1

Common Pitfalls and Caveats

1. Respiratory failure risk: Serious or fatal respiratory failure occurs in 14% of terlipressin-treated patients vs. 5% with placebo. This risk increases with:

   • Higher volumes of albumin administration
   • Pre-existing cardiac dysfunction
   • ACLF grade 3 2, 1

2. Ischemic complications: Monitor for cardiac, intestinal, or peripheral ischemia, especially in patients with pre-existing cardiovascular disease 2

3. Treatment timing: Early initiation of therapy is critical, as higher creatinine levels (>5 mg/dL) are associated with poor response 1

4. Volume management: Carefully balance albumin administration with risk of volume overload, particularly in patients with cardiac dysfunction 4, 1

5. Cirrhotic cardiomyopathy: Presence of cirrhotic cardiomyopathy predicts terlipressin non-response and poor survival in HRS-AKI patients 4

By following this structured approach to terlipressin-albumin therapy in critically ill patients, clinicians can optimize treatment outcomes while minimizing potential complications.