John D. LangAlvin B. SmithAngela BrandonKelley M. BradleyYuliang LiuWei LiD. Ralph CroweNirag C. JhalaRichard C. CrossLuc FrenetteKenneth MartayYouri L. VaterAlexander A. VitinGregory A. DemboDerek A. DuBayJ. Steven BynonJeff M. SzychowskiJorge D. ReyesJeffrey B. HalldorsonStephen C. RayhillAndre A. DickRamasamy BakthavatsalamJared BrandenbergerJo Ann Broeckel-ElrodLaura Sissons-RossTerry JordanLucinda Y. ChenArunotai SiriussawakulDevin E. EckhoffRakesh P. PatelUniversity of Washington School of MedicineJilin UniversityUniversity of Alabama at BirminghamPerelman School of MedicineUniversity of Texas Medical School at HoustonUC San Diego HealthMahidol University2018-11-092018-11-092014-02-12PLoS ONE. Vol.9, No.2 (2014)193262032-s2.0-84895748372https://repository.li.mahidol.ac.th/handle/20.500.14594/33056Decreases 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.Mahidol UniversityAgricultural and Biological SciencesBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1371/journal.pone.0086053