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.
Background and objectivesTransversus abdominis plane (TAP) blocks are associated with an improvement in postoperative analgesia following kidney transplant surgery. However, these blocks carry inherent risk and require a degree of expertise to perform successfully. Continuous intravenous lidocaine may be an effective alternative. In this randomized, non-inferiority study, we hypothesized that a continuous lidocaine infusion provides similar postoperative analgesia to a TAP block.MethodsSubjects presenting for kidney transplant surgery were randomized in a 1:1 ratio to either an ultrasound-guided unilateral, single-injection TAP block (TAP group) or a continuous infusion of lidocaine (Lido group). The primary outcome of this non-inferiority study was opioid consumption within the first 24 hours following surgery. Secondary outcomes included pain scores, patient satisfaction, opioid-related adverse events, time to regular diet, and persistent opioid use.ResultsOne hundred and twenty subjects, 59 from the TAP group and 61 from the Lido group, completed the study per protocol. Analysis of the primary outcome showed a cumulative geometric mean intravenous morphine equivalent difference between the TAP (14.6±3.2 mg) and Lido (15.9±2.4 mg) groups of 1.27 mg (95% CI −4.25 to 6.79; p<0.001), demonstrating non-inferiority of the continuous lidocaine infusion. No secondary outcomes showed clinically meaningful differences between groups.ConclusionsThis study demonstrates that a continuous infusion of lidocaine offers non-inferior postoperative analgesia compared with an ultrasound-guided unilateral, single-injection TAP block in the first 24 hours following kidney transplant surgery.Trial registration numberNCT03843879.
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