The Effect of Remote Ischemic Preconditioning on the Postoperative Liver Function in Living Donor Hepatectomy: a Randomized Clinical Trial
Phase: NA
Conditions: Tissue Donors, Liver Transplantation, Ischemia Reperfusion Injury
Sponsor: Asan Medical Center

 
Official Title of the study: The Effect of Remote Ischemic Preconditioning in Living Donor 
Hepatectomy: a randomized clinical trial 
 
 
 
NCT number : NCT03386435 
IRB approval date: 1th August 2015 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Introduction 
Liver transplantation(LT) is the gold standard treatment for patients with end-stage liver 
disease. In light of advancements in surgical techniques, immunosuppressive agents, and 
perioperative critical care, the overall 3-year survival of patients undergoing LT has exceeded 
80%. Despite its outstanding success, LT still entails certain complications including ischemia-
reperfusion injury (IRI). 
IRI occurs when the blood supply to an organ or tissue is temporarily cut-off and then restored, 
and it is well-known as an underlying cause of primary non-function, biliary complications, 
and eventual graft loss after LT. Despite many attempts to ameliorate hepatic IRI, no definitive 
therapies have been established. In addition, the mechanisms of IRI remain largely unclear. 
Remote ischemic preconditioning (RIPC) is a novel and simple therapeutic method to lessen 
the harmful effects of IRI. RIPC indicate that brief episodes of ischemia with intermittent 
reperfusion are introduced at a remote site, leading to systemic protection against subsequent 
insults as evinced on kidney, heart, liver, and other tissues. While RIPC has been shown to 
reduce hepatic IRI in several small animal studies, the beneficial effects of RIPC in hepatic IRI 
have been inconsistent. By far, the majority of RIPC studies on hepatic IRI have been animal 
studies; hence, there are limitations relating to the lack of human clinical trials. 
Therefore, our aim was to assess the effects of RIPC on postoperative liver function in living 
donor hepatectomy. 
 
 
 
 
 
 

Study Protocol 
Study design and ethical approval 
For the donors, the single‐center, double-blinded, randomized controlled study was 
approved by the institutional review board of the Asan Medical Center (2015-0851) and 
registered with ClinicalTrials.gov (NCT03386435). We collected and analyzed the data in 
accordance with the ethical standards set in the 1964 Declaration of Helsinki and its 
amendments. 
 
Participants 
For the donor group, adult (aged 18-60 years) liver donors scheduled for elective donor 
right hepatectomy from August 2016 to July 2017 at Asan Medical Center in Seoul, Korea, 
were screened for eligibility. Total 160 participants were assessed for eligibility and randomly 
assigned to either the RIPC group (n=80) or the control group (n=80). 12 donors whose surgical 
plan changed unexpectedly from open right hepatectomy to other than open right hepatectomy 
(e.g., laparoscopic right lobectomy [n=9], left lobectomy [n=2], and right posterior 
segmentectomy [n=1]) were dropped out of the study. The remaining 148 donors (RIPC group 
[n=75] and control group [n=73]) were analyzed. For randomization, random computer-
generated numbers were stored in sealed envelopes that were opened following the induction 
of anesthesia by an anesthesia nurse who was unaware of the study. 
 
Intervention 
After induction of anesthesia and before skin incision, we performed RIPC. The protocol 
involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to one upper 
arm, followed by 5-minute reperfusion with the cuff deflated. In the control group, the same 
maneuver was applied but without cuff inflation. All interventions were performed by the 

anesthetic nurses who were not involved in the study. 
 
Outcomes 
In donors, plasma concentrations of AST and alanine aminotransferase (ALT) were 
measured daily during the first postoperative week to assess the extent of hepatocellular 
damage. The postoperative liver regeneration index (LRI) at postoperative 1 month and the 
incidence of delayed recovery of hepatic function (DRHF) were used as surrogate parameters 
indicating the possible benefits of RIPC. The LRI was defined as [(VLR − VFLR)/VFLR)] × 100, 
where VLR is the volume of the liver remnant and VFLR is the volume of the future liver remnant. 
Liver volume was calculated by CT volumetry using 3-mm-thick dynamic CT images. The 
graft weight was subtracted from the total liver volume to define the future liver remnant. 
DRHF was defined based on a proposal by the International Study Group of Liver Surgery, as 
follows: an impaired ability of the liver to maintain its synthetic, excretory, and detoxifying 
functions, which are characterized by an increased PT INR and concomitant 
hyperbilirubinemia (considering the normal limits of the local laboratory) on or after 
postoperative day 5. The normal upper limits of PT and bilirubin in our institutional laboratory 
were 1.30 INR and 1.2 mg/dL, respectively. If either the PT INR or serum bilirubin 
concentration was preoperatively elevated, DRHF was defined by an increasing PT INR and 
increasing serum bilirubin concentration on or after postoperative day 5 (compared with the 
values of the previous day). 
 
Statistical analysis plan 
Between-group differences in preoperative and intraoperative characteristics and 
postoperative outcomes were compared using the Chi-square test or Fisher exact test for 
categorical variables and the Student t test or Mann-Whitney U test for continuous variables, 

as appropriate. P < 0.05 was considered statistically significant. SPSS 23 (IBM Corp., Armonk, 
NY, USA) software was used for all statistical analyses.