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

BACKGROUND & AIMS Vasoconstrictors are the treatment of choice for hepatorenal syndrome (HRS), a potentially lethal complication of end-stage liver disease. We evaluate the real-life effectiveness of a sequential vasoconstrictor regimen of midodrine-octreotide followed by norepinephrine in a non-ICU setting in the United States, where terlipressin is not available. APPROACH & RESULTS Adult patients diagnosed with HRS were treated with oral midodrine and subcutaneous octreotide in conjunction with albumin. The diagnosis of HRS and definitions of acute kidney injury were based on 2015 guidelines from the International Club of Ascites. A partial response was defined as regression of acute kidney injury (AKI) stage with reduction in serum creatinine to ≥0.3 mg/dL above baseline, whereas a full response was regression of AKI stage with return to a value within 0.3 mg/dL of baseline. In patients without partial or full response, norepinephrine was administered at a starting dose of 5 mcg/min, with a goal to achieve a mean arterial pressure (MAP) of 10 mmHg above baseline. We assessed predictors of response and treatment outcomes. 61 patients received midodrine and octreotide for the treatment of HRS, with a 28% response rate. The median MELD-Na was 30 (IQR 24-35), with median MAP of 73 mmHg (IQR 67-79) at the start of treatment. Responders were more likely to have alcohol-related liver disease and lower ACLF grade. Of the non-responders, 20 then received norepinephrine, of whom 45% achieved full or partial response. Achieving MAP increase of ≥10 mmHg was associated with a greater probability of response. Patients who responded to norepinephrine experienced improved transplant-free survival at 90 days (88% v. 27%, p=0.02). Five of 20 patients experienced norepinephrine treatment-related adverse events, namely arrhythmias. CONCLUSION 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.