Responsiveness to Vasoconstrictor Therapy in Hepatorenal Syndrome Type 1.

Abstract

Raising mean arterial pressure (MAP) during treatment of hepatorenal syndrome type 1 (HRS-1) with vasoconstrictors is associated with renal recovery. However, the optimal MAP target and factors associated with response to vasoconstrictors remain unclear. Records from hospitalized patients with HRS-1 treated with vasoconstrictors without shock were reviewed searching for those who achieved ≥5 mmHg rise in MAP within 48 hours. We examined the relationship between the mean MAP achieved during the first 48-72 hours of vasoconstrictor therapy and the change in serum creatinine (sCr) up to day 14. Endpoints were >30% reduction in sCr without need for dialysis or death by day 14 (primary) or by day 30 (secondary). Seventy-seven patients with HRS-1 treated for 2-10 days with either norepinephrine (n=49) or midodrine/octreotide (n=28) were included. Median age was 52 (IQR 46-60), 40% were female and 48% had alcoholic cirrhosis. At vasoconstrictor initiation, median MAP was 70 mmHg (IQR 66-73) and median sCr was 3.8 mg/dL (IQR 2.6-4.9). When analyzed by tertiles of mean MAP increment (5-9, 10-14, ≥15 mmHg), there was greater reduction in sCr with greater rise in MAP (ANOVA for trend, p<0.0001). By multivariate logistic regression analysis, mean MAP rise during the first 48-72 hrs [OR 1.15 (1.02 - 1.299), p=0.025], norepinephrine as vasoconstrictor [OR 5.46 (1.36-21.86), p=0.017] and baseline sCr [OR 0.63 (0.41-0.97), p=0.034] were associated with the primary endpoint; whereas mean MAP rise during the first 48-72 hrs [OR 1.17 (1.04-1.33), p=0.012] and baseline sCr [OR 0.63 (0.39-0.98), p=0.043] were associated with the secondary endpoint. Greater magnitude of rise in MAP with vasoconstrictor therapy in HRS-1, lower baseline sCr, and use of norepinephrine over midodrine/octreotide are associated with kidney recovery. Targeting an increment of MAP ≥15 mmHg may lead to favorable renal outcomes.