Feasibility and Effectiveness of Norepinephrine Outside the Intensive Care Setting for Treatment of Hepatorenal Syndrome

Abstract

Vasoconstrictors are the treatment of choice for hepatorenal syndrome (HRS). We evaluate the real-life effectiveness of a sequential vasoconstrictor regimen of midodrine-octreotide followed by norepinephrine in a nonintensive care unit (non-ICU) setting in the United States, where terlipressin is not available. The diagnosis of HRS and definitions of response to therapy were based on 2015 guidelines from the International Club of Ascites. In adult patients with HRS without partial or full response to oral midodrine and subcutaneous octreotide, norepinephrine was administered at a starting dose of 5 mcg/minute, with a goal to achieve a mean arterial pressure (MAP) of 10 mm Hg above baseline. We assessed predictors of response and treatment outcomes. A total of 61 patients were administered midodrine and octreotide for the treatment of HRS, with a 28% response rate. The median MELD-Na (Model for End-Stage Liver Disease-sodium) score was 30 (interquartile range [IQR] 24-35). Responders were more likely to have alcohol-related liver disease and lower Acute-on-Chronic Liver Failure (ACLF) grade. Of the nonresponders, 20 were then administered norepinephrine, of whom 45% achieved full or partial response. Achieving an MAP increase of ≥10 mm Hg was associated with a greater probability of response. Patients who responded to norepinephrine experienced improved transplant-free survival at 90 days (88% versus 27%; P = 0.02); 5 of 20 patients experienced norepinephrine treatment-related adverse events, namely arrhythmias. Norepinephrine can be effectively used in a non-ICU setting as rescue therapy in patients who have not responded to midodrine and octreotide. Based on these data, we propose a practical stepwise algorithm for vasoconstrictor therapy to manage HRS in situations where terlipressin is not an option.

Management of hepatorenal syndrome in liver cirrhosis: a recent update

“… 79 Further assessment of the use of norepinephrine was reported in a small feasibility study from North America where norepinephrine was used in the non-ICU setting in the treatment of HRS in patients who were non-responders to midodrine and octreotide. 80 Forty-five percent of patients showed a complete or partial response with the median duration of treatment of 2 days. Improved transplant-free survival at 90 days was also noted in responders.…”

“…Improved transplant-free survival at 90 days was also noted in responders. 80 Midodrine and octreotide. Midodrine is an alphaadrenergic agonist, commonly used in North America to treat HRS1 due to non-availability of terlipressin.…”

Advances in management of hepatorenal syndrome

“…In countries where terlipressin is not available, such as the United States, the use of norepinephrine has been limited because of the requirement for ICU. In a recent study by Kwong et al [29], the feasibility of norepinephrine use as a continuous infusion in a nonintensive care setting in high MELD patients with HRS-AKI was demonstrated. Norepinephrine use was associated with full or partial response in 45% of those who failed improvement following the use of midodrine and octreoide.…”

Hepatorenal Syndrome Type 1: From Diagnosis Ascertainment to Goal-Oriented Pharmacologic Therapy

“…A recent report shared a successful single-center experience of a norepinephrine-based HRS-1 protocol executed outside of the ICU. However, the protocol required 3:1 nursing and was associated with 25% incidence of cardiac arrhythmias (69). Therefore, widespread implementation of such approach may require additional studies.…”

“…The question remains as to what the ideal target of MAP is. Some studies suggest that a rise >10 mm Hg may suffice, whereas other studies suggest >15 mm Hg may be necessary for optimal response (54,69,72). In clinical grounds, ICU nursing personnel and practitioners are familiar with a MAP target of 65 mm Hg for shock.…”