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

Liver Transpl. 2021 Aug;27(8):1095-1105. doi: 10.1002/lt.26065. Epub 2021 Jul 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Critical Care
  • End Stage Liver Disease* / drug therapy
  • Feasibility Studies
  • Hepatorenal Syndrome* / diagnosis
  • Hepatorenal Syndrome* / drug therapy
  • Humans
  • Liver Transplantation*
  • Lypressin / therapeutic use
  • Norepinephrine / therapeutic use
  • Severity of Illness Index
  • Treatment Outcome
  • Vasoconstrictor Agents / therapeutic use


  • Vasoconstrictor Agents
  • Lypressin
  • Norepinephrine