What is the recommended dose of norepinephrine (noradrenaline) in hepatorenal syndrome?

From the Guidelines

Norepinephrine should be used as a continuous intravenous infusion at a starting dose of 0.5 mg/h and the dose increased every 4 hours by 0.5 mg/h to a maximum of 3 mg/h in patients with hepatorenal syndrome (HRS). This recommendation is based on the most recent and highest quality study available, which provides guidance on the management of acute kidney injury in patients with cirrhosis 1. The goal of norepinephrine therapy in HRS is to increase the mean arterial pressure by ≥10 mm Hg and/or the urine output to >50 mL/h for at least 4 hours.

Key Considerations

• Norepinephrine is used to improve renal perfusion by causing peripheral vasoconstriction, which counteracts the splanchnic vasodilation characteristic of HRS.
• The medication should be administered through a central venous catheter with continuous hemodynamic monitoring in an ICU setting.
• Patients should be monitored for potential side effects including arrhythmias, tissue ischemia, and hypertension.
• Norepinephrine is often used when terlipressin is unavailable, as both medications have similar efficacy in improving renal function in HRS patients, though terlipressin is considered first-line therapy in many guidelines when available 1.

Comparison with Other Studies

While other studies have investigated the use of norepinephrine in HRS, the most recent and highest quality study provides the best guidance on dosing and administration 1. Earlier studies, such as those published in 2010 and 2009, provide some insight into the use of norepinephrine and other vasoconstrictors in HRS, but their findings are not as relevant to current practice 1.

From the Research

Norepinephrine Dose in Hepatorenal Syndrome

• The dose of norepinephrine used in the treatment of hepatorenal syndrome varies across studies.
• In one study 2, norepinephrine was administered at a dose of 0.5 mg/h, with a maximum dose of 3 mg/h.
• Another study 3 used a starting dose of 5 mcg/minute, with a goal to achieve a mean arterial pressure (MAP) of 10 mm Hg above baseline.
• The efficacy of norepinephrine in the treatment of hepatorenal syndrome has been compared to other vasoconstrictors, such as terlipressin and midodrine/octreotide 2, 4, 5.
• Norepinephrine has been shown to be effective in improving renal function and reducing mortality in patients with hepatorenal syndrome 2, 3, 4, 5.
• The use of norepinephrine in the treatment of hepatorenal syndrome is considered a viable alternative to terlipressin, especially in situations where terlipressin is not available 4, 5.

Comparison with Other Vasoconstrictors

• Norepinephrine has been compared to terlipressin in several studies, with mixed results 4, 5.
• One study found that norepinephrine was as effective as terlipressin in reversing hepatorenal syndrome, but with fewer adverse events 4.
• Another study found that norepinephrine was less expensive than terlipressin, but with similar efficacy and safety profiles 5.
• Norepinephrine has also been compared to midodrine/octreotide, with one study finding that norepinephrine was more effective in improving renal function 2.

Clinical Implications

• The use of norepinephrine in the treatment of hepatorenal syndrome requires careful consideration of the patient's hemodynamic status and renal function.
• The dose of norepinephrine should be titrated to achieve a mean arterial pressure (MAP) of 10 mm Hg above baseline, while minimizing the risk of adverse events 3.
• Further studies are needed to fully elucidate the efficacy and safety of norepinephrine in the treatment of hepatorenal syndrome, particularly in comparison to other vasoconstrictors 2, 4, 5.