Targeting an Early and Substantial Increase in Mean Arterial Pressure Is Critical in the Management of Type 1 Hepatorenal Syndrome: A Combined Retrospective and Pilot Study

Abstract

Appreciation of the central role for arterial vasodilatation in the pathogenesis of hepatorenal syndrome (HRS) has led to routine use of vasoconstrictors in combination with albumin as a medical therapy for HRS. Various vasoconstrictors have been explored but the optimal approach for such therapies has not yet been established. The purpose of this study was to examine the role of targeting an early and substantial increase in mean arterial pressure (MAP) in the management of type 1 HRS, a condition associated with very poor prognosis. A total of 59 patients with type 1 HRS who received a combination therapy of vasoconstrictors and albumin were enrolled into a retrospective cohort study. Subjects having a substantial increase of more than 10mmHg in MAP by day 3 after initiation of therapy were categorized as MAP responders and the rest as MAP non-responders. In addition, five patients were enrolled into a prospective pilot study in which a titration protocol of vasoconstrictors was followed to achieve early goal-directed therapy (EGDT). MAP responders achieved significantly higher incidence of treatment success or total response, less requirement of dialysis and more incidence of liver transplantation. More importantly, this response is associated with better short-term and long-term overall survival as well as transplant-free survival. The effectiveness of such an approach was further confirmed in the pilot study which followed an EGDT protocol. Using an early and substantial increase in MAP as a therapeutic target is associated with favorable clinical outcomes in the management of type 1 HRS.