Effects Of Remote Ischemic Preconditioning On Perioperative Liver Function And Prognosis In Pediatric Living Donor Liver Transplantation

Part 1 Effect of Remote Ischemic Preconditioning on Postoperative Liver Function and Prognosis in Biliary Atresia Children with Living Donor Liver Transplantation:A Randomized Controlled Clinical TrialOBJECTIVE:Studies have shown that remote ischemic preconditioning(RIPC)can effectively reduce the risk of ischemia reperfusion injury(IRI)during organ transplantation.However,it is still unclear whether RIPC can alleviate the transplanted IRI in children with living donor liver transplantation and promote the recovery of liver function in children with biliary atresia after living donor liver transplantation.In order to explore the potential application value of RIPC in pediatric liver transplantation,we conducted a prospective randomized double-blind clinical trial,hoping to explore the role of RIPC in pediatric liver transplantation and provide a new strategy for perioperative liver function protection in pediatric living donor liver transplantation patients.METHODS:This study screened patients from January 2016 to July 2017 in Renji Hospital.289 cases of children met the inclusion and exclusion criteria and received living donor liver transplantation.Next,a total of 220 cases were randomly assigned to four groups:S-RIPC group(no intervention;n=55),D-RIPC group(donors received RIPC;n=55),R-RIPC group(recipients received RIPC,n=55)and DR-RIPC group(both donors and recipients received RIPC;n=55).Finally,a total of 208 children finished the study,including 51 in the DR-RIPC group,51 in the D-RIPC group,51 in the R-RIPC group,and 55 in the S-RIPC group.Among them,D-RIPC group only performed RIPC treatment on the donor;The R-RIPC group only received RIPC treatment for the recipient children,the DR-RIPC group received RIPC treatment for both the donor and recipient patients,and the S-RIPC group did not receive any RIPC intervention for the donor and recipient patients.RIPC was performed in the interval after general anesthesia and before the operation.The steps were as follows:the donor applied 200 mmHg of cuff pressure to the upper limb with pneumatic hemostasis device for 5 minutes of ischemia,and then relaxed for 5 minutes of reperfusion,a total of 3 cycles;The recipient was also subjected to ischemia for 5 min with a cuff pressure of 150 mmHg using a pneumatic hemostasis device,followed by relaxation for reperfusion for 5 min,a total of 3 cycles.Then,the preoperative general condition indexes,intraoperative and postoperative related indexes were recorded,and the dynamic changes of liver and kidney function indexes such as alanine aminotransferase(ALT),aspartic aminotransferase(AST),total bilirubin(TB)and creatinine(Cr)in the donor and recipient groups were compared.The incidence of postoperative complications and mortality were recorded,as well as the incidence of early allograft dysfunction(EAD)and primary nonfunction(PNF),the length of stay in ICU,the duration of mechanical ventilation,the incidence of postoperative complications and 3-year all-cause mortality of the recipient children.RESULTS:An analysis of perioperative general data found that no significant differences were observed in demographic or preoperative/intraoperative characteristics of the receptors,and that subjects in all four groups showed good comparability and consistency.Compared with S-RIPC group,RIPC treatment did not significantly improve the levels of ALT,AST and TB in donors or recipients after surgery.Compared with the S-RIPC group,RIPC also had no significant effect on postoperative plasma albumin,Cr,white blood cells,neutrophils,hemoglobin and platelets.Only the Cr level immediately after surgery was significantly different among the four groups,indicating that the Cr level immediately after surgery was significantly decreased in the D-RIPC group compared with that in the S-RIPC group(p=0.029).The postoperative ICU hospitalization time and mechanical ventilation time index analysis showed that there was no significant difference in the postoperative mechanical ventilation time among the groups,but there was a statistical difference in the postoperative ICU hospitalization time of the children,which indicated that compared with the DR-RIPC group,the ICU hospitalization time of the children in the D-RIPC group was shorter(p=0.041).In addition,the results suggested that RIPC treatment did not significantly improve the incidence of postoperative EAD,PNF and acute kidney injury.For postoperative complications,RIPC did not significantly reduce the incidence of postoperative complications in the recipients.Survival analysis showed that the 3-year overall survival rates in the S-RIPC,D-RIPC,R-RIPC and DR-RIPC groups were 90.9%,96.1%,90.2%and 92.2%,respectively,and there was no statistical difference in overall survival rates among the four groups.Finally,subgroup analysis also indicated that the recipients groups had similar clinical outcomes,with no variables that significantly affected primary end points or overall survival.CONCLUSIONS:According to the current clinical randomized controlled study,we found that D-RIPC,R-RIPC and DR-RIPC did not significantly improve postoperative liver function or reduce the incidence of EAD,PNF and postoperative complications in patients with biliary atresia after living donor liver transplantation,and the beneficial effect on the long-term survival rate of patients is also very limited.In conclusion,more clinical studies are needed to further explore the potential protective effect of RIPC in pediatric liver transplantation.Part 2 Effects of Remote Ischemic Preconditioning on Postoperative Liver Function Recovery in Donors of Pediatric Living Donor Liver Transplantation:A Retrospective studyOBJECTIVE:This study aimed to assess the effects of remote ischemic preconditioning(RIPC)on of postoperative liver function recovery in donors of pediatric living donor liver transplantation,so as to provide a new strategy for perioperative liver function protection of donors of pediatric living donor liver transplantation.METHODS:Electronic record of donors of pediatric living donor liver transplantation were retrieved for this retrospective analysis.A total of 102 donors receiving RIPC intervention on the upper limb after anesthesia induction and before operation were allocated into the RIPC group(n=102);While,a total of 106 donors not receiving RIPC intervention were allocated into the Control group(n=106).The changes of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TB)and albumin(ALB)of the two arms within 3 days after surgery were analyzed.By assessing the difference of postoperative liver function recovery between the two groups,the effects of RIPC on postoperative liver function in donors was evaluated.RESULTS:There was no significant difference in serum ALT,AST,TB and ALB levels between the RIPC group and the control group(p>0.05).CONCLUSIONS:The results of this study suggest that the preoperative RIPC intervention of upper limbs of donorsin pediatric living donor liver transplantation did not have definite protective effect on the donors’ liver function.