The Effect of Remote Ischemic Preconditioning in Living Donor Hepatectomy

Study Overview
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Brief Summary
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Liver transplantation is the gold standard treatment for patients with end-stage liver disease. Despite its outstanding success, liver transplantation still entails certain complications including ischemia-reperfusion injury. Remote ischemic preconditioning is a novel and simple therapeutic method to lessen the harmful effects of ischemia-reperfusion injury, however, the majority of remote ischemic preconditioning studies on hepatic ischemia-reperfusion injury have been animal studies. Therefore, our aim was to assess the effects of remote ischemic preconditioning on postoperative liver function in living donor hepatectomy.

Detailed Description
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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.

Official Title
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The Effect of Remote Ischemic Preconditioning on the Postoperative Liver Function in Living Donor Hepatectomy: a Randomized Clinical Trial

Conditions
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Tissue Donors, Liver Transplantation, Ischemia Reperfusion Injury

Intervention / Treatment
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* Procedure: remote ischemic preconditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Donors who plan to have living right hepatectomy for liver transplantation. age : between 18 to 60 years. Exclusion Criteria: donors who plan to donate left lobe donors who plan to have laparoscopic right hepatectomy donors who cannot proceed remote ischemic preconditioning

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: study group : remote ischemic preconditioning control group : none
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RIPC<br>intervention: RIPC groups receive remote ischaemic preconditioning after anaesthesia induction and before surgery started. | Procedure: remote ischemic preconditioning<br>* Remote ischemic preconditioning was performed following anesthesia induction in donors. 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<br>* Other names: RIPC;|
| No Intervention: Control<br>In the control group, the same maneuver was applied but without cuff inflation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postopera The Maximal Aspartate Aminotransferase Level Within 7 Postoperative Days | The serial assessments of routine laboratory values were used as early markers for postoperative liver function. The maximal aspartate aminotransferase level within 7 postoperative days were assessed following RIPC in living donor hepatectomy. | within 7 days after operation | 
| The Maximal Alanine Aminotransferase Level Within 7 Postoperative Days | The serial assessments of routine laboratory values were used as early markers for postoperative liver function. The maximal alanine aminotransferase level within 7 postoperative days were assessed following RIPC in living donor hepatectomy | within 7 days after operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Delayed Recovery of Liver Function | The incidence of delayed recovery of hepatic function (DRHF) were used as surrogate parameters indicating the possible benefits of RIPC. 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). | postoperative 7 days | 
| Postoperative Liver Regeneration | The postoperative liver regeneration index (LRI) at postoperative 1 month ) was 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. | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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remote ischemic preconditioning, liver donors