Session Name: Poster Session B: Liver: Hepatobiliary Surgery
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Ischemia and reperfusion injury (IRI) is one of the unavoidable complications in orthotopic liver transplantion. Hepatic ischemic injury begins during the preservation of the graft in ice cold organ preservation solution and the inflammatory response that occurs after reperfusion is a primary cause of liver injury . Treprostinil, (Remodulin), a prostanoid (prostacyclin, PGI2, analog) is a promising pharmacological agent to minimize IRI due to its ability to vasodilate, inhibit platelet aggregation and down-regulate pro-inflammatory cytokines. Our hypothesis for this pilot, single center,Phase I/II study is that Treprostinil can be safely administered perioperatively in subjects undergoing orthotopic liver transplantation.
*Methods: We performed a prospective, interventional, single center, dose escalation study (3+3 design) to investigate the safety and preliminary efficacy of continuous intravenous infusion of treprostinil in orthotopic liver transplant recipients. A total of 35 diseased donor liver transplant recipient were consented for the study and 13 subjects completed the entire study that was conducted in accordance to University of Pittsburgh IRB approved protocol (PRO10050268) and registered in ClinicalTrials.gov (NCT01481974). Treprostinil doses used ranged from 2.5 ng/kg/min to 7.5 ng/kg/min over a five day time period. Clinical and biochemical parameters, graft and subject survival was followed for 180 days.
*Results: Liver transplant recipients tolerated the continuous infusion of treprostinil at a dose of up to 5 ng/kg/min for 120 hours. Subjects in the treprostinil groups over all had better hepatic function on day 2 and 5 as reflected by the extraction of indocyanine green (ICG-(PDR) [>18 vs 12 (Control)]. The ICG PDR was similar to reported values (18-25) in healthy adults. Minimized need for ventilation support (1 .1 vs 2.5 days), reduced hospitalization time (8 vs 14.5 days) and absence of any primary graft non-function (PNF) was also observed. Parameters such as heart rate, cardiac output, AST, ALT, total Bilirubin, and SCr were not significantly different in those receiving treprostinil and the control group during the first week after transplantation. Subject and graph survival was 100% in Treprostinil group compared to 80% survival in control group on day 180 post surgery.
*Conclusions: Treprostinil administration to liver transplanted patients post-surgery appears to be safe. The maximum tolerated dose of Treprostinil is 5 ng/kg/min as a continuous IV infusion. Future studies are warranted to evaluate its efficacy in minimizing IRI of the liver in a larger phase 2 clinical study.
To cite this abstract in AMA style:Venkataramanan R, Shaik IH, Pillai VC, Almazroo OA, Miah MK, Xu R, Dharmayan S, Al-Khafaji A, Ganesh S, Molinari M, Tevar A, Hughes C, Humar A. Treprostinil is Safe and Potentially Useful in Preventing Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplant Recipients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/treprostinil-is-safe-and-potentially-useful-in-preventing-ischemia-and-reperfusion-injury-in-adult-orthotopic-liver-transplant-recipients/. Accessed December 6, 2023.
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