What is the initial treatment for hepatorenal syndrome?

Initial Treatment for Hepatorenal Syndrome

The initial treatment for hepatorenal syndrome is terlipressin plus albumin, which should be started immediately at 1 mg IV every 4-6 hours along with albumin 1 g/kg body weight on day 1 (maximum 100g) followed by 20-40 g/day. 1, 2

First-Line Treatment: Terlipressin Plus Albumin

Terlipressin combined with albumin is the most effective first-line pharmacological treatment for hepatorenal syndrome type 1 (HRS-AKI). 1, 2 This combination has demonstrated superior efficacy compared to alternative regimens:

• Start terlipressin at 1 mg IV every 4-6 hours 1, 2
• If serum creatinine does not decrease by at least 25% after 3 days, increase the dose stepwise to a maximum of 2 mg every 4 hours 1, 2
• Continue treatment until complete response or for a maximum of 14 days 1
• Administer albumin 1 g/kg body weight on day 1 (maximum 100g), followed by 20-40 g/day 1, 2

The evidence strongly favors terlipressin: a randomized trial showed 70.4% recovery of renal function with terlipressin plus albumin versus only 28.6% with the alternative midodrine/octreotide regimen (P = 0.01). 3

Alternative Treatment When Terlipressin Is Unavailable

In regions where terlipressin is not available (such as the United States), use the combination of midodrine plus octreotide plus albumin. 4, 1, 2

Dosing Algorithm for Midodrine/Octreotide/Albumin:

• Midodrine: Start at 7.5 mg orally three times daily, titrate up to maximum 12.5 mg three times daily to achieve a mean blood pressure increase of 15 mm Hg 4, 1, 2
• Octreotide: 100-200 μg subcutaneously three times daily (target dose 200 μg) 4, 1, 2
• Albumin: 10-20 g IV daily for up to 20 days 4, 1, 2

This regimen can be administered outside the ICU and even at home, which is a practical advantage. 4, 2 A retrospective study showed reduced mortality with this combination (43% versus 71% in controls, P < 0.05). 4

Third-Line Option: Norepinephrine Plus Albumin

Norepinephrine plus albumin is an effective alternative but requires ICU admission. 4, 1, 2

• Norepinephrine: 0.5-3.0 mg/hour IV to increase mean arterial pressure by 15 mm Hg 5, 1
• Albumin: Same dosing as above 1
• Success rate: 83% in reversing type 1 HRS in pilot studies 4, 2

Critical Pitfalls and Considerations

Octreotide Alone Is Ineffective

Never use octreotide as monotherapy—it requires midodrine to be effective. 4, 6 Two studies, including one randomized crossover design, definitively showed octreotide alone provides no benefit. 4

Volume Overload Management

If anasarca develops during treatment, discontinue albumin but continue vasoconstrictors. 5 The development of severe peripheral edema indicates significant fluid overload that will not benefit from continued albumin administration. 5 However, vasoconstrictor therapy (terlipressin, norepinephrine, or midodrine/octreotide) should be maintained. 5

Prevention Is Key

Always administer albumin with antibiotics when treating spontaneous bacterial peritonitis to prevent HRS development. 1 The dose is 1.5 g/kg body weight at diagnosis, followed by 1 g/kg on day 3, which reduces HRS type 1 incidence from 30% to 10% and mortality from 29% to 10%. 1

Transplant Considerations

Liver transplantation remains the definitive treatment and should be expedited for all HRS patients. 1, 2 Treatment with vasoconstrictors before transplantation may improve post-transplant outcomes. 2 Post-transplant survival is approximately 65% in type 1 HRS. 1, 2

Monitoring Response

Monitor serum creatinine every 2-3 days to assess treatment response. 1, 2 Complete response is defined as serum creatinine ≤1.5 mg/dL on two occasions. 4 Even if creatinine improves and MELD score decreases, this should not change the decision to proceed with liver transplantation, as prognosis remains poor. 2