Nonintensive Care Unit Norepinephrine as an Alternative to Terlipressin in Hepatorenal Syndrome-Acute Kidney Injury

Terlipressin is approved in the United States for the treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI). At our institution, low-dose norepinephrine (NE) can be administered outside the intensive care unit (ICU) on a step-down unit for treatment of HRS-AKI.

We conducted a retrospective, single-center study of adults outside the ICU with HRS-AKI treated with terlipressin or NE from 2021 to 2025 at our institution. The primary outcome was verified reversal of HRS, defined as 2 consecutive serum creatinine measurements ≤1.5 mg/dL by day 14 and survival free of renal replacement therapy at least 10 days after treatment. Secondary outcomes included adverse events (AEs), AKI response, overall survival, and liver transplant-free survival.

Among 50 patients treated within each cohort, baseline characteristics were generally balanced, except a higher proportion of males in the terlipressin group (76% vs 48%, P = .007). Verified HRS reversal (16% vs 14% P = 1.00), 90-day overall survival (64% vs 60%, log-rank P = .83), and 90-day liver transplant-free survival (30% vs 18%, log-rank P = .47) were comparable. Terlipressin was associated with higher discontinuation rates (38% vs 10%, P = .002) primarily from respiratory failure, peripheral ischemia, and gastrointestinal AEs. Median daily albumin was higher in the terlipressin group (25.0 vs 13.2 g/day, P = .002) but did not differ within the terlipressin cohort between patients who developed respiratory failure and those who did not.

In this real-world cohort, terlipressin and non-ICU NE demonstrated comparable efficacy in HRS-AKI, but terlipressin was associated with higher rates of AEs and discontinuation. In centers where NE can be administered outside the ICU, NE remains a safe and cost-effective alternative to terlipressin.