Standard-Volume Plasma Exchange Improves Outcomes in Patients With Acute Liver Failure: A Randomized Controlled Trial.
BACKGROUND
High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain.


METHODS
In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5.


RESULTS
ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) μg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE.


CONCLUSION
In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. ClinicalTrial.gov (identifier: NCT02718079).
['Maiwall|Rakhi|R|', 'Bajpai|Meenu|M|', 'Singh|Akanksha|A|', 'Agarwal|Tanvi|T|', 'Kumar|Guresh|G|', 'Bharadwaj|Ankit|A|', 'Nautiyal|Nidhi|N|', 'Tevethia|Harsh|H|', 'Jagdish|Rakesh Kumar|RK|', 'Vijayaraghavan|Rajan|R|', 'Choudhury|Ashok|A|', 'Mathur|Rajendra Prasad|RP|', 'Hidam|Ashini|A|', 'Pati|Nirupama Trehan|NT|', 'Sharma|Manoj Kumar|MK|', 'Kumar|Anupam|A|', 'Sarin|Shiv Kumar|SK|']
DAMPs Endotoxin SIRS Lactate Artificial Liver Support Systems CRRT Liver Transplant