Pre-Emptive Initiation of Continuous Renal Replacement Therapy in Patients With Acute Liver Failure With Cerebral...

An early initiation of continuous renal replacement therapy (CRRT) for ammonia reduction has shown a reduction in deaths due to cerebral edema (CE) in acute liver failure (ALF); however, there are no controlled trials assessing the same.

We performed an open-label pilot randomized controlled trial (RCT) on ALF patients with CE. Patients underwent therapeutic plasma-exchange (PLEX) by centrifugal apheresis after initial resuscitation. Group 1 received CRRT initiation within the first 12 h, while Group 2, CRRT was initiated for PLEX non-responders. The primary endpoint was 28-day survival.

Patients aged 28.11 ± 10.10 years, 56.67% viral, 69% hyperacute were randomized. At day 28, 46% died and 11% underwent liver transplant. There were a total of 31 protocol violations, significantly more in group 2 (55.6% vs. 13.3%; p < 0.001). On ITT and piece-wise exponential regression analysis, pre-emptive CRRT was associated with a significantly lower hazard of death during the first 7 days (2.2% vs. 17.8% Hazard ratio [HR] 0.12, 95% confidence interval [CI] 0.02-0.96) with comparable survival at 28-days. Notably, higher 28-day mortality was observed on PP analysis in group 2 (80% vs. 46%, HR 3.10, 95% CI 1.57-6.12) with a significantly higher reduction in ammonia and improvement in mean arterial pressure and lower number of sessions of TPE. Each hour delay in CRRT was associated with increased mortality (HR 1.01, 1.00-1.02).

A pre-emptive initiation of CRRT in ALF patients is synergistic to TPE, reduces early deaths by rapid improvement in hemodynamics, ammonia and cerebral edema (NCT04991259).