Publication: A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation
Issued Date
2014-02-12
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ISSN
19326203
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2-s2.0-84895748372
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Mahidol University
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SCOPUS
Bibliographic Citation
PLoS ONE. Vol.9, No.2 (2014)
Suggested Citation
John D. Lang, Alvin B. Smith, Angela Brandon, Kelley M. Bradley, Yuliang Liu, Wei Li, D. Ralph Crowe, Nirag C. Jhala, Richard C. Cross, Luc Frenette, Kenneth Martay, Youri L. Vater, Alexander A. Vitin, Gregory A. Dembo, Derek A. DuBay, J. Steven Bynon, Jeff M. Szychowski, Jorge D. Reyes, Jeffrey B. Halldorson, Stephen C. Rayhill, Andre A. Dick, Ramasamy Bakthavatsalam, Jared Brandenberger, Jo Ann Broeckel-Elrod, Laura Sissons-Ross, Terry Jordan, Lucinda Y. Chen, Arunotai Siriussawakul, Devin E. Eckhoff, Rakesh P. Patel A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation. PLoS ONE. Vol.9, No.2 (2014). doi:10.1371/journal.pone.0086053 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/33056
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Title
A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation
Author(s)
John D. Lang
Alvin B. Smith
Angela Brandon
Kelley M. Bradley
Yuliang Liu
Wei Li
D. Ralph Crowe
Nirag C. Jhala
Richard C. Cross
Luc Frenette
Kenneth Martay
Youri L. Vater
Alexander A. Vitin
Gregory A. Dembo
Derek A. DuBay
J. Steven Bynon
Jeff M. Szychowski
Jorge D. Reyes
Jeffrey B. Halldorson
Stephen C. Rayhill
Andre A. Dick
Ramasamy Bakthavatsalam
Jared Brandenberger
Jo Ann Broeckel-Elrod
Laura Sissons-Ross
Terry Jordan
Lucinda Y. Chen
Arunotai Siriussawakul
Devin E. Eckhoff
Rakesh P. Patel
Alvin B. Smith
Angela Brandon
Kelley M. Bradley
Yuliang Liu
Wei Li
D. Ralph Crowe
Nirag C. Jhala
Richard C. Cross
Luc Frenette
Kenneth Martay
Youri L. Vater
Alexander A. Vitin
Gregory A. Dembo
Derek A. DuBay
J. Steven Bynon
Jeff M. Szychowski
Jorge D. Reyes
Jeffrey B. Halldorson
Stephen C. Rayhill
Andre A. Dick
Ramasamy Bakthavatsalam
Jared Brandenberger
Jo Ann Broeckel-Elrod
Laura Sissons-Ross
Terry Jordan
Lucinda Y. Chen
Arunotai Siriussawakul
Devin E. Eckhoff
Rakesh P. Patel
Abstract
Decreases in endothelial nitric oxide synthase derived nitric oxide (NO) production during liver transplantation promotes injury. We hypothesized that preemptive inhaled NO (iNO) would improve allograft function (primary) and reduce complications post-transplantation (secondary). Patients at two university centers (Center A and B) were randomized to receive placebo (n = 20/center) or iNO (80 ppm, n = 20/center) during the operative phase of liver transplantation. Data were analyzed at set intervals for up to 9-months post-transplantation and compared between groups. Patient characteristics and outcomes were examined with the Mann-Whitney U test, Student t-test, logistic regression, repeated measures ANOVA, and Cox proportional hazards models. Combined and site stratified analyses were performed. MELD scores were significantly higher at Center B (22.5 vs. 19.5, p<0.0001), surgical times were greater at Center B (7.7 vs. 4.5 hrs, p <0.001) and warm ischemia times were greater at Center B (95.4 vs. 69.7 min, p<0.0001). No adverse metabolic or hematologic effects from iNO occurred. iNO enhanced allograft function indexed by liver function tests (Center B, p<0.05; and p<0.03 for ALT with center data combined) and reduced complications at 9-months (Center A and B, p = 0.0062, OR = 0.15, 95% CI (0.04, 0.59)). ICU (p = 0.47) and hospital length of stay (p = 0.49) were not decreased. iNO increased concentrations of nitrate (p<0.001), nitrite (p<0.001) and nitrosylhemoglobin (p<0.001), with nitrite being postulated as a protective mechanism. Mean costs of iNO were $1,020 per transplant. iNO was safe and improved allograft function at one center and trended toward improving allograft function at the other. ClinicalTrials.gov with registry number 00582010 and the following URL:http://clinicaltrials.gov/show/NCT00582010. © 2014 Lang et al.