Norepinephrine is More Effective Than Midodrine/Octreotide in Patients With Hepatorenal Syndrome-Acute Kidney Injury: A Randomized Controlled Trial.

Eman Ibrahim El-Desoki Mahmoud,Noha O Mansour,Doaa H Abdelaziz,Sherief Abd-Elsalam

doi:10.3389/fphar.2021.675948

Abstract

Background: Terlipressin is the first-line pharmacological treatment for hepatorenal syndrome. When terlipressin is unavailable, midodrine/octreotide or norepinephrine, with albumin, represent the alternative treatments. The comparative efficacy of these alternative regimens remains unclear. Objective: To compare the efficacy of midodrine/octreotide to that of norepinephrine for the treatment of patients with hepatorenal syndrome. Methods: In the intensive care setting, sixty patients with hepatorenal syndrome were randomized to initially receive either 0.5 mg/h of norepinephrine (maximum 3 mg/h) or 5 mg of oral midodrine three times/day (maximum 12.5 mg three times/day) plus octreotide (100 μg/6 h) as subcutaneous injection (maximum 200 μg/6 h), together with albumin (20–40 g/day). Treatment was allowed for a maximum of 10 days. Survival was analyzed for up to 30 days. The primary efficacy outcome was the proportion of patients who achieved full response, defined as the return of serum creatinine to a value within 0.3 mg/dl of the baseline at the end of treatment. Results: There was a significantly higher rate of full response in the norepinephrine group (15/26, 57.60%) than the midodrine/octreotide group (5/25, 20%) (p = 0.006). Eleven (42.30%) patients in the norepinephrine group and 6 (24%) in the midodrine/octreotide group survived (p = 0.166). Conclusion: Norepinephrine plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with hepatorenal syndrome.(ClinicalTrials.gov, identifier: NCT03455322). https://clinicaltrials.gov/ct2/show/NCT03455322?cond = Hepatorenal+Syndrome&cntry = EG&draw = 2&rank = 1.

Highlights

Hepatorenal syndrome (HRS) is defined as renal failure occurring in patients with cirrhosis and ascites in the absence of other causes of renal dysfunction (Israelsen et al, 2017)
The baseline demographic profile and clinical and laboratory parameters were similar in patients receiving norepinephrine and midodrine plus octreotide (Table 1)
There was no significant difference between the mean dose of albumin (26.33 ± 5.6 g/day) in the norepinephrine group and that (29.33 ± 7.4 g/day) in the midodrine/octreotide one (p 0.11)

Summary

Introduction

Hepatorenal syndrome (HRS) is defined as renal failure occurring in patients with cirrhosis and ascites in the absence of other causes of renal dysfunction (Israelsen et al, 2017). The currently available pharmacological option for HRS-AKI management is the administration of systemic vasoconstrictors with albumin This approach has been found to be an effective option that ameliorates renal dysfunction and improves survival (Wang et al, 2018). According to the latest European Association for the Study of the Liver (EASL) practice guidelines, the first-line pharmacological treatment for HRS-AKI is terlipressin in combination with albumin (The European Association for the study of the Liver, 2018; Nanda et al, 2018); this vasopressin analog is not available in many countries, including the United States (Singh et al, 2012). Vasoconstrictors other than vasopressin analogs that have been used in the management of HRS-AKI include norepinephrine and midodrine plus octreotide, both in combination with albumin. The comparative efficacy of midodrine plus octreotide vs norepinephrine in the management of HRS-AKI remains unclear, and the data available are of low-quality evidence.

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