Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
terlipressin or norepinephrine + albumin
Combined therapy with a vasoconstrictor plus albumin is the recommended treatment for HRS-AKI. The updated diagnostic criteria, with the removal of minimum serum creatinine concentration, allows for immediate drug therapy after an unsuccessful fluid challenge (compared to the previous criteria). Earlier treatment likely results in higher reversal rates and better outcomes given that response to vasoconstrictors is dependent on the serum creatinine concentration at the start of treatment.[2][8][29][31][32]
The preferred vasoconstrictor is terlipressin, a vasopressin analog with increased selectivity for the V1 receptor, administered either as a continuous intravenous infusion or as an intravenous bolus. Although intravenous bolus administration is the method approved in the US, continuous infusion may be considered to reduce the risk of adverse events.[2] If terlipressin is not available, norepinephrine (noradrenaline) should be administered.[2] In general, terlipressin may be given on medical wards, whereas norepinephrine is preferably administered in the intensive care unit.
One meta-analysis of 16 studies reported no significant differences in HRS reversal, serious adverse events, and liver transplantation-free patient survival with terlipressin compared with norepinephrine.[33] Both terlipressin and norepinephrine were found to be superior to the combination of midodrine plus octreotide in HRS reversal.[33]
Evidence suggests that terlipressin may reduce the incidence of persistent HRS, compared with alternative vasoactive pharmacotherapy, and may improve renal function in patients with HRS-AKI.[34][35][36][37][38]
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However, terlipressin is more commonly associated with adverse effects, such as diarrhea/abdominal pain, peripheral cyanosis, minor cardiovascular events, and respiratory failure.
The Food and Drug Administration (FDA) has approved terlipressin to improve kidney function in adults with HRS and rapid reduction in kidney function.[39] The approval includes safety recommendations regarding the potential for serious or fatal respiratory failure, particularly for patients with volume overload or acute-on-chronic liver failure grade 3. Oxygen saturation should be assessed via pulse oximetry before starting terlipressin. Treatment is contraindicated in patients with hypoxia (SpO₂ <90%) until their oxygenation levels improve, or if they have respiratory symptoms that are worsening. Continuous pulse oximetry should be used to monitor patients during treatment, and treatment stopped if hypoxia or increased respiratory symptoms develop. Intravascular volume overload should be managed by discontinuing albumin and/or other fluids with the use of intravenous furosemide; terlipressin should be paused, reduced, or stopped until volume status has improved. Treatment is also contraindicated in patients with ongoing coronary, peripheral, or mesenteric ischemia and should be discontinued in any patients showing signs or symptoms of an ischemic adverse reaction. Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit with terlipressin.[39]
The European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK also recommend several safety measures when using terlipressin.[37][40][41] Safety recommendations follow a safety review based on the findings of one large randomized controlled trial in patients with HRS-AKI.[37][40] The trial results suggest that patients treated with terlipressin are more likely to experience, and die from, respiratory disorders (e.g., respiratory failure) within 90 days of the first dose, compared with placebo, and identified a previously unreported risk of sepsis.[37] Respiratory disorders are a known risk of terlipressin; however, the frequency of respiratory failure seen in this study (11%) was higher than that previously reported.
Norepinephrine plus albumin is an alternative to terlipressin. It was associated with HRS reversal in one network meta-analysis, and may be associated with fewer adverse effects than terlipressin plus albumin.[34][35]
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The norepinephrine dose should be titrated to achieve a 10 mmHg increase in mean arterial pressure from baseline.
Response to terlipressin or norepinephrine is defined by creatinine decrease to <1.5mg/dL, or a return to within 0.3 mg/dL of baseline over a maximum of 14 days. In patients who maintain a creatinine level at, or above, the pretreatment level over 4 days, with the maximum tolerated doses of the vasoconstrictor, therapy may be discontinued.[2]
Prior to initiating vasopressor therapy, the patient's risk of ischemic or cardiovascular events should be evaluated. This should include an electrocardiogram.[8] During vasopressor treatment, patients should be closely monitored for the possible development of adverse effects of vasoconstrictors and albumin, including ischemic complications and pulmonary edema.[2]
Primary options
terlipressin: consult specialist for guidance on dose
or
norepinephrine: consult specialist for guidance on dose
-- AND --
albumin (human): see local protocol for administration guidelines
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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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