What is the recommended management for a patient with type 1 Hepatorenal Syndrome (HRS) characterized by rapid deterioration of renal function?

Management of Type 1 Hepatorenal Syndrome (HRS-AKI)

For type 1 HRS characterized by rapid deterioration of renal function, immediately initiate terlipressin plus albumin as first-line therapy while urgently evaluating for liver transplantation, which remains the definitive treatment. 1

Pre-Treatment Assessment and Safety Screening

Before initiating vasoconstrictor therapy, you must complete critical safety assessments:

• Obtain baseline oxygen saturation (SpO2) - Do not start terlipressin if SpO2 <90% until hypoxia resolves 2
• Perform electrocardiogram to exclude active coronary ischemia, as terlipressin is contraindicated in ongoing coronary, peripheral, or mesenteric ischemia 1, 2
• Assess volume status and ACLF grade - Patients with volume overload or ACLF Grade 3 are at increased risk of respiratory failure 2
• Confirm diagnosis by ensuring serum creatinine >2.25 mg/dL with doubling trajectory over 2 weeks, no improvement after 48 hours of diuretic withdrawal and albumin expansion, and exclusion of shock, nephrotoxic drugs, and structural kidney disease 1

First-Line Treatment: Terlipressin Plus Albumin

Terlipressin is the preferred vasoconstrictor based on the highest quality evidence showing 29.1% verified HRS reversal versus 15.8% with placebo (p=0.012) 1, 2:

Terlipressin Dosing Protocol

• Start with 0.85 mg (1 mg terlipressin acetate) IV bolus every 6 hours administered slowly over 2 minutes on Days 1-3 1, 2
• Alternatively, use continuous IV infusion starting at 2 mg/24 hours, which reduces side effects while maintaining efficacy 1, 3
• On Day 4, assess response:
  • If serum creatinine decreased ≥30% from baseline: continue same dose 1, 2
  • If serum creatinine decreased <30%: increase to 1.7 mg (2 mg terlipressin acetate) every 6 hours 1, 2
  • If serum creatinine at or above baseline: discontinue therapy 1
• Maximum dose: 12 mg/day for continuous infusion or 2 mg every 4 hours for bolus dosing 1
• Maximum duration: 14 days 1

Mandatory Albumin Co-Administration

Terlipressin must always be combined with albumin 1, 3:

• Day 1: 1 g/kg IV (maximum 100 g) 1, 3
• Subsequent days: 40-50 g/day IV 1, 3
• Adjust albumin dose if volume overload develops - reduce or discontinue albumin while continuing vasoconstrictors 2

Monitoring Requirements During Terlipressin Therapy

Continuous pulse oximetry is mandatory - discontinue terlipressin immediately if SpO2 drops below 90% 2:

• Check serum creatinine daily to assess for ≥25-30% reduction by days 3-4 3
• Monitor for ischemic complications: abdominal pain, chest pain, digital ischemia, skin necrosis (occur in ~12% of patients) 1, 3
• Watch for respiratory complications: pulmonary edema, respiratory failure (14% with terlipressin vs 5% with placebo) 2
• Assess heart rate (expect decrease of ~10 beats/minute) and ideally monitor central venous pressure 4

Treatment Response Definitions

• Complete response: Serum creatinine ≤1.5 mg/dL or return to within 0.3 mg/dL of baseline on two occasions at least 2 hours apart 1, 3
• Partial response: Serum creatinine reduction ≥25% but still >1.5 mg/dL 1, 3
• Non-response: Serum creatinine remains at or above baseline after 4 days at maximum tolerated dose - discontinue therapy 1

Alternative Vasoconstrictors When Terlipressin Unavailable

Norepinephrine Plus Albumin (Second-Line)

Norepinephrine is equally effective to terlipressin but requires ICU-level monitoring 1:

• Start at 0.5 mg/hour continuous IV infusion via central line (attempting peripheral administration risks tissue necrosis) 1, 4
• Titrate up to 3 mg/hour to increase mean arterial pressure by 10-15 mmHg 1
• Combine with albumin to maintain central venous pressure 4-10 mmHg 1
• Requires continuous hemodynamic monitoring in ICU setting 4

Midodrine Plus Octreotide Plus Albumin (Third-Line)

This combination has much lower efficacy than terlipressin or norepinephrine and should only be used when neither is available 1:

• Midodrine: Start 5-7.5 mg orally three times daily, titrate up to 12.5-15 mg three times daily 1, 4
• Octreotide: 100-200 μg subcutaneously three times daily or 50 μg/hour IV 1, 4
• Albumin: 10-20 g/day IV for up to 20 days 1, 4

Renal Replacement Therapy

Initiate RRT based on clinical grounds, not as first-line therapy 1:

Indications for RRT

• Worsening kidney function despite maximum vasoconstrictor therapy 1
• Severe electrolyte disturbances (hyperkalemia, severe acidosis) unresponsive to medical management 1
• Diuretic intolerance or increasing volume overload 1
• Symptomatic uremia 1

RRT Modality Selection

• Continuous RRT is preferred over intermittent hemodialysis in hemodynamically unstable patients 1
• RRT should primarily serve as bridge to liver transplantation - mortality exceeds 80% in non-transplant candidates regardless of HRS etiology 1
• Consider limited trial of RRT in selected non-transplant candidates only with clear endpoint and reversible organ failures 1

Urgent Liver Transplantation Evaluation

All patients with type 1 HRS require urgent transplant evaluation given high short-term mortality even in responders to vasoconstrictors 1:

• Liver transplantation is the definitive treatment with ~65% survival rates 1, 5, 4
• Treatment with vasoconstrictors before transplantation may improve post-transplant outcomes 5, 4
• HRS reversal improves survival: Patients achieving verified HRS reversal with terlipressin had significantly better 90-day survival (p<0.001) 2
• MELD score considerations: Successful HRS treatment reduces MELD score, potentially disadvantaging patients - some countries maintain pre-treatment MELD or assign extra points 1

Management of HRS Recurrence

Recurrence after treatment discontinuation should be retreated with the same vasoconstrictor regimen 1:

• Recurrence is common, particularly in type 2 HRS 1
• Repeat courses of terlipressin plus albumin are effective 1
• Long-term therapy can serve as bridge to transplantation 6

Critical Pitfalls to Avoid

Do not delay treatment initiation - type 1 HRS has median survival of only 2 weeks without treatment, and patients with baseline creatinine <3-5 mg/dL have better response rates 5, 3, 6:

• Patients with serum creatinine >5 mg/dL are unlikely to benefit from terlipressin 2
• Do not use TIPS in acute HRS-AKI - insufficient evidence and most patients have contraindications due to severe liver failure 1
• Do not use vasoconstrictors for type 2 HRS (HRS-NAKI) - recurrence after withdrawal is the norm and no proven survival benefit 1
• Multidisciplinary decision-making is essential - involve hepatology, nephrology, critical care, and transplant surgery specialists 1