What is the role of noradrenaline (norepinephrine) plus albumin in the management of Hepato-Renal Syndrome (HRS)?

Noradrenaline Plus Albumin Regimen in Hepatorenal Syndrome

Noradrenaline plus albumin is an effective alternative to terlipressin plus albumin for the treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), particularly when terlipressin is unavailable, though it requires a central venous line and intensive care unit admission. 1

Efficacy of Noradrenaline in HRS

• Noradrenaline, administered by continuous IV infusion at doses of 0.5-3 mg/h with albumin, has demonstrated efficacy comparable to terlipressin in increasing mean arterial pressure, reversing renal impairment, and improving one-month survival in HRS 1
• Noradrenaline has been proven effective in achieving complete response rates of 50-70% in patients with HRS-AKI when combined with albumin 2, 3
• However, the total number of patients treated with noradrenaline in clinical trials remains relatively small compared to terlipressin, limiting the strength of evidence supporting its definitive efficacy 1

Administration Protocol

• Noradrenaline should be administered as a continuous IV infusion at an initial dose of 0.5 mg/h, with titration up to a maximum of 3 mg/h to achieve a target increase in mean arterial pressure of 10 mmHg 1
• Albumin should be administered concurrently at an initial dose of 1 g/kg (up to a maximum of 100 g/day) for the first 2 days, followed by 20-40 g/day thereafter 1
• Treatment should continue until reversal of HRS or for a maximum of 14 days in cases of partial response 1

Practical Considerations and Limitations

• Unlike terlipressin, noradrenaline administration always requires a central venous line and, in most countries, transfer of the patient to an intensive care unit (ICU) 1
• Careful cardiac screening including electrocardiogram is recommended before starting treatment due to potential ischemic and cardiovascular adverse events 1
• Close monitoring of patients during treatment is essential, with modification or discontinuation of therapy based on the type and severity of side effects 1

Comparative Efficacy

• Terlipressin plus albumin is considered the first-line therapeutic option for HRS-AKI based on more robust evidence 1
• Recent evidence suggests terlipressin may be superior to noradrenaline in ACLF patients with HRS-AKI, with better response rates (40% vs. 16.7%), reduced need for renal replacement therapy, and improved 28-day survival (48.3% vs. 20%) 4
• Noradrenaline is significantly more effective than the midodrine/octreotide combination for HRS-AKI treatment (57.6% vs. 20% full response rate) 5

Response Assessment and Follow-up

• Complete response to treatment should be defined as a final serum creatinine within 0.3 mg/dl (26.5 μmol/L) from the baseline value 1
• Partial response is defined as regression of AKI stage with a final serum creatinine ≥0.3 mg/dl from baseline 1
• In cases of recurrence of HRS-AKI after treatment cessation, a repeat course of therapy should be given 1

Predictors of Response

• Lower baseline serum creatinine, higher creatinine clearance, higher mean arterial pressure, and lower plasma renin activity are independent predictors of favorable response to vasoconstrictor therapy 2
• A decrease in serum creatinine of ≥0.15 mg/dL/day by day 4 of therapy accurately predicts response to treatment 2

Cost Considerations

• Noradrenaline therapy has been shown to be significantly less expensive than terlipressin, making it a more cost-effective option in resource-limited settings 2

Caveats and Pitfalls

• Vasoconstrictors alone are ineffective; they must always be combined with albumin for optimal management of HRS-AKI 6
• Careful monitoring for fluid overload is essential when administering albumin, as excessive use can lead to pulmonary edema 6
• Noradrenaline plus albumin is not recommended for HRS outside the criteria of AKI (formerly known as HRS type II) due to high recurrence rates after treatment withdrawal 1