Brian Murray, BCCCP, PharmD
Clinical Pharmacy Specialist
University of North Carolina Hospitals
Chapel Hill, North Carolina
Disclosure information not submitted.
Andrea Bejjani, PharmD
Pharmacist
University of North Carolina Health, United States
Disclosure information not submitted.
Youqi Zhang, PharmD
Pharmacist
UC San Diego Health, California, United States
Disclosure information not submitted.
Allison Behrens, PharmD
Pharmacist
University of North Carolina Health, United States
Disclosure information not submitted.
Neil Shah, MD
Gastroenterologist
University of North Carolina Health, United States
Disclosure information not submitted.
Title: Droxidopa for the management of hepatorenal syndrome
Case Report Body
Introduction: Hepatorenal syndrome (HRS) is a type of renal dysfunction that occurs in patients with cirrhosis secondary to the hemodynamic effects of portal hypertension. HRS is associated with significant morbidity and mortality, and first-line therapy aimed at improving perfusion often fails. We report the use of the oral norepinephrine precursor droxidopa as an adjunct agent in the management of refractory HRS-AKI.
Description: A 51-year-old Caucasian male with alcoholic cirrhosis presented with a chief complaint of pre-syncope and falls. His presentation was complicated by acute kidney injury meeting diagnostic criteria of HRS-AKI owing to an absence of contributing factors. Volume expansion with albumin failed to improve laboratory markers or urine output. After lack of response to midodrine and octreotide, medical management was escalated to a norepinephrine infusion. On norepinephrine the patient’s urine output and renal function improved, but attempts to wean to an outpatient regimen subsequently failed. On day 13 of hospital admission, droxidopa was initiated at 100 mg three times daily and titrated each day to 400 mg three times daily over the next 3 days. Initiation of droxidopa allowed for weaning and eventual discontinuation of the norepinephrine infusion on day 16 of hospital admission while maintaining hemodynamic stability. The patient was eventually discharged on a thrice-daily regimen of droxidopa 400mg, midodrine 20mg, and octreotide 200mcg.
Discussion: In cirrhosis, increased production and activity of vasodilators causes splanchnic vasodilation and hemodynamic compromise. Compensatory systems (sympathetic nervous system, renin-angiotensin-aldosterone system) become activated, and sustained activation of these systems eventually leads to development of ascites and renal dysfunction (HRS). Medical management of HRS-AKI is problematic, owing to the frequent need for continuous infusion medications that require hospitalization (norepinephrine, terlipressin) and high failure rates even with maximal medical management. Irreversible HRS and persistent hemodynamic instability or reliance on continuous infusions are often roadblocks to transplant. Droxidopa, an oral norepinephrine precursor, provides a potentially effective adjunct treatment option for patients that fail maximal therapy for HRS.