What medications are used to manage hepatorenal syndrome?

Medications for Hepatorenal Syndrome

First-Line Treatment

Terlipressin plus albumin is the first-line pharmacological treatment for hepatorenal syndrome, with terlipressin 0.5-1 mg IV every 4-6 hours (increased stepwise to maximum 2 mg every 4 hours if creatinine doesn't decrease by ≥25% after 3 days) combined with albumin 1 g/kg on day 1 (maximum 100 g) followed by 20-40 g/day for up to 14 days. 1, 2, 3

• This combination achieves reversal of HRS in 64-76% of patients and is significantly superior to albumin alone 3
• The American Association for the Study of Liver Diseases and European Association for the Study of the Liver both recommend this as first-line therapy 2, 3
• Treatment should continue until complete response (creatinine ≤1.5 mg/dL on two occasions) or maximum 14 days 2, 3

Alternative Regimens When Terlipressin Unavailable

Midodrine + Octreotide + Albumin

In regions where terlipressin is unavailable (such as the United States), use midodrine 7.5 mg orally three times daily (titrated to maximum 12.5 mg three times daily) plus octreotide 100-200 μg subcutaneously three times daily plus albumin 10-20 g IV daily for up to 20 days. 1, 2, 3

• This combination can be administered outside the ICU and even at home 2, 3
• However, this regimen is significantly less effective than terlipressin plus albumin, with only 28.6% response rate compared to 70.4% with terlipressin in a randomized trial 4
• Critical pitfall: Never use octreotide as monotherapy—it requires midodrine to be effective and provides no benefit alone 2

Norepinephrine + Albumin

Norepinephrine 0.5-3.0 mg/hour IV (titrated to increase mean arterial pressure by 15 mmHg) plus albumin 20-40 g/day is an effective alternative but requires ICU admission with central venous access. 1, 2, 3

• This achieves 83% success rate in reversing HRS, comparable to terlipressin 2, 3
• Norepinephrine is equivalent in efficacy to midodrine-octreotide combination but requires intensive monitoring 5
• Critical pitfall: Attempting peripheral administration of norepinephrine risks tissue necrosis—central access is mandatory 3

Prevention Strategies

Spontaneous Bacterial Peritonitis

Administer albumin 1.5 g/kg at diagnosis of spontaneous bacterial peritonitis, followed by 1 g/kg on day 3, to prevent HRS development. 2, 3

• This reduces HRS incidence from 30% to 10% and mortality from 29% to 10% compared to antibiotics alone 2, 3
• Patients with bilirubin ≥4 mg/dL or creatinine ≥1 mg/dL are at highest risk and benefit most 2

Prophylactic Antibiotics

• Norfloxacin 400 mg/day reduces HRS incidence in advanced cirrhosis 2, 3
• Pentoxifylline 400 mg three times daily prevents HRS in severe alcoholic hepatitis 2, 3

Important Management Considerations

Albumin Management in Volume Overload

Discontinue albumin when anasarca develops, but continue vasoconstrictors (terlipressin, norepinephrine, or midodrine/octreotide). 1, 2

• Albumin has limited utility once severe peripheral edema indicates significant fluid overload 1
• Vasoconstrictor therapy should be maintained even after albumin discontinuation 1
• Implement sodium restriction (<2 g/day) and consider diuretics for volume management 1

Monitoring Protocol

• Check serum creatinine every 2-3 days to assess treatment response 2, 3
• Complete response: creatinine ≤1.5 mg/dL on two occasions 2, 3
• Partial response: creatinine decrease ≥25% but still >1.5 mg/dL 3
• Monitor for complications: cardiac/intestinal ischemia, pulmonary edema, distal necrosis with terlipressin 3

Definitive Treatment

Liver transplantation is the only curative treatment for hepatorenal syndrome and should be expedited for all patients with type 1 HRS. 2, 3

• Post-transplant survival is approximately 65% in type 1 HRS 2, 3
• Treatment of HRS before transplantation with vasoconstrictors may improve post-transplant outcomes 3
• Critical consideration: Even if creatinine improves with treatment and MELD score decreases, this should not delay transplantation as prognosis remains poor 3

Adjunctive Therapies

TIPS (Transjugular Intrahepatic Portosystemic Shunt)

• May be considered in selected patients with lower MELD scores 1
• Improves renal function and ascites control in type 2 HRS 3
• Limited evidence base with small uncontrolled studies 3

Renal Replacement Therapy

• Consider only as a bridge to liver transplantation in patients unresponsive to vasoconstrictors 1, 3
• Indicated for worsening kidney function, fluid overload despite diuretics, or problematic acid-base status 1