Liver Protection of RIPC in Pediatric Living Donor Liver Transplantation (RIPC-PLDT)

Remote Ischemic Preconditioning Protects Against Hepatic Ischemic and Reperfusion Injury in Pediatric Living Donor Liver Transplantation

Remote ischemic preconditioning(RIPC) is emerging as an promising therapeutic paradigm to combat the detrimental impact of ischemic and reperfusion injury. In liver transplantation, ischemic and reperfusion injury severely impacts the post-surgery liver function and patient outcome. This prospective, double blind, randomized clinical trial is aimed to test the protective effect of RIPC against hepatic ischemic and reperfusion injury in pediatric liver transplantation.

Pediatric liver transplantation remains the major therapeutic strategy for pediatric biliary atresia patients. With almost 60 years of improvements and refinements in surgical techniques and perioperative management standards, liver transplantation is gaining popularity and gradually turns out to be the only curative treatment option for patients with irrevocable liver failure, such as childhood acute or chronic liver failure, inherited liver diseases and also biliary atresia. In liver transplantation, hepatic ischemic and reperfusion injury (HIRI) remains to be a critical clinical issue. Importantly, it is well known that the severity of HIRI may have fundamental impact on the transplanted organ function and long term graft survival. Furthermore, pediatric patients are more venerable and less tolerated to receive an ischemic donor liver due to their small body weight.Although detrimental impact of HIPI on graft function has long been recognized, little progress has been made to attenuate the severity of the HIPI compared to cardiac ischemic and reperfusion (IR) injury. In experimental animal models, remote ischemic preconditioning has been consistently shown to have beneficial effects. However, this protective paradigm has yet not been tested in liver transplantation patients in clinical scenario. Considering the growing number of pediatric patients undergoing liver transplantation and their possibly underdeveloped organ function, the investigators sought to determine whether remote ischemic preconditioning could ameliorate HIPI and improve long term graft/patient survival in pediatric liver transplantation patients using this double-blind randomized clinical trial.

Both donors and recipients receive remote ischemic preconditioning, with three 5-min cycles of remote limb ischemia, which was induced by an automated cuff-inflator placed on the right upper arm(donor) or right lower limb(recipient) and inflated to 15 mmHg above systolic pressure, with an intervening 5 min of reperfusion during which the cuff was deflated.

Recipients receive remote ischemic preconditioning, with three 5-min cycles of remote limb ischemia, which was induced by an automated cuff-inflator placed on the right lower limb and inflated to 15 mmHg above systolic pressure, with an intervening 5 min of reperfusion during which the cuff was deflated.

Donors receive remote ischemic preconditioning, with three 5-min cycles of remote limb ischemia, which was induced by an automated cuff-inflator placed on the right upper arm and inflated to 15 mmHg above systolic pressure, with an intervening 5 min of reperfusion during which the cuff was deflated.

After anesthesia induction, donors or recipients will be treated with automated blood pressure cuffs on their upper arms to receive RIPC by cuff inflation (to 15mmHg above systolic pressure) for 5 minutes and left inflated for 5 minutes. The cuff will then be deflated to 0 mm Hg and left uninflated for 5 minutes. This cycle will be performed 3 times in total.

Only blood pressure cuff will be placed to the patient, but no inflation or deflation will be performed.

The inclusion criteria were as follows: American society of anesthesiologists score of I-III; age of 3-72 months elective living LT surgery. The exclusion criteria were as follows: peripheral vascular disease; history of thromboembolism; systemic or local infection before surgery; autoimmune diseases; severe congenital heart disease history of LT.

Zarbock A, Schmidt C, Van Aken H, Wempe C, Martens S, Zahn PK, Wolf B, Goebel U, Schwer CI, Rosenberger P, Haeberle H, Gorlich D, Kellum JA, Meersch M; RenalRIPC Investigators. Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial. JAMA. 2015 Jun 2;313(21):2133-41. doi: 10.1001/jama.2015.4189.

Bulluck H, Candilio L, Hausenloy DJ. Remote Ischemic Preconditioning: Would You Give Your Right Arm to Protect Your Kidneys? Am J Kidney Dis. 2016 Jan;67(1):16-9. doi: 10.1053/j.ajkd.2015.08.018. Epub 2015 Sep 16. No abstract available.