Influence Of Parecoxib On Inflammatory Mediators Level In Serum After Hepatic Ischemia-reperfusion In The Patients Underwent Right Hepatectomy

Objective:Hepatic ischemia reperfusion injury(IRI)is not only a pathophysiological process involving the liver,but also leading to remote organ damage such as acute lung injury and kidney failure.It is of great significance to take effective measures to minimize the IRI casued by the blocking and opening of the hepatic portal system in the patients undergoing liver cancer surgery.The aim of the study was to provied certain evidence for the clinical use of parecoxib by investigating its influence on inflammatory mediators after hepatic ischemiareperfusion in the patients underwent right hepatectomyand toexplore the underlying mechanisms.Methods:Forty patients underwent right hemihepatectomy were selected in the First Clinical Hospital of Jilin University during November 2014-November2015.ASAⅡorⅢ,BIM18-25,age 35-65 years old.The patients were divided into two groups randomly: control group(C group)and parecoxib group(P group),(n=20).Every case wasroutinely restricted with a fasting period of 6 hours.Patients in theparecoxib group was injected intravenously with 40 mg parecoxib(dissolved in 10 ml saline solution)12hoursbefore and at the beginning anesthesia induction,the control group received 10 ml saline solution in the same way.Intraoperative monitoring included a three-leadelectrocardiogram,non-invasive and invasive bloodpressure monitoring,pulse oximetry,and measurements of PETCO2,and BIS.Every patient in two groups underwent left radial artery puncture and catheterization to monitor invasive arterial blood pressure under the local anesthesia,each cases underwent right lateral jugular vein catheterization under the local anesthesia to monitor central venous pressure.Midazolam0.03 mg/kg,cisatracurium0.15mg/kg,fentanyl 2-4 μg/kg and propofol 1.5-2.0 mg/kgweregivenfortheinduction.Ventilation was mechanically controlled.Anesthesia was maintained withpropofol 4-6 mg/kg/h.The package red blood cell was infused if Hb<90g/L or Hct<30%.The incidence ofpostoperative dizziness,nausea,vomiting and other complicationswas recorded.Blood samples 3-5ml for cytokine analysis were collected from the internaljugular vein at the following timepoints: before the induction(T0),whichwasconsidered as the baseline value before surgery;hepaticportalopening up immediately(T1);1h after reperfusion(T2);6h after reperfusion(T3);24h after reperfusion(T4)and 48 h after reperfusion(T5).Levels of the pro-inflammatorycytokines tumor necrosis factor(TNF)-α,and IL-6were measured usingquantitative sandwich enzyme immunoassay kits,and the ALT,AST were measured as well.All statistical analyseswere performed using SPSS version 22.0(SPSSInc.,Chicago,IL,USA)for Windows.All datawere presented as the means± standard(x ±s).Inter-group comparison were conducted with the independent sample t-test,intra-group data compared with paired t-test,and χ2test was adopted to compare the continuous data.Values of P<0.05 were considered to indicate statisticalsignificance.Results:There were no significant differences in baseline(T0)before anesthesiabetween the two groups(P>0.05).The patients in two groups had significantly higher TNF-α,IL-6concentrations and ALT,AST concentrations during and after surgery thanthose before induction(P<0.05).The parecoxib group had lower serum concentrations of TNF-α,IL-6 and ALT,AST concentration at each time points than that in the control groupin thehepatic portal open instantly(T1)and after reperfusion(T2-T5).The parecoxib group had higher serum concentrations of IL-10 concentration at each time points than that in the control group after reperfusion(T2-T5).Conclusions:Parecoxib had a positive effect on liver cancer patients underwent hemihepatectomy,which might be related to the inhibition of inflammatory mediatorsreleaseinduced by hepatic ischemia-reperfusion.