Protocol for a prospective randomized controlled trial of recipient remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial)

Abstract

Ischaemic reperfusion (IR) injury is a major cause of graft loss, morbidity and mortality following orthotopic liver transplantation (OLT). Demand for liver transplantation has resulted in increasing use of marginal grafts that are more prone to IR injury. Remote ischaemic preconditioning (RIPC) reduces IR injury in experimental models, but recipient RIPC has not been evaluated clinically.MethodsA single-centre double-blind randomized controlled trial (RCT) is planned to test the hypothesis that recipient RIPC will reduce IR injury. RIPC will be performed following recipient anaesthetic induction but prior to skin incision. The protocol involves 3 cycles of 5 min of lower limb occlusion with a pneumatic tourniquet inflated to 200 mmHg alternating with 5 min of reperfusion. In the control group, the sham will involve the cuff being placed on the thigh but without being inflated.The primary endpoint is ability to recruit patients to the trial and safety of RIPC. The key secondary endpoint is a reduction in serum aspartate transferase levels on the third post-operative day.DiscussionRIPC is a promising strategy to reduce IR injury in liver transplant recipients as there is a clear experimental basis, and the intervention is both inexpensive and easy to perform. This is the first trial to investigate RIPC in liver transplant recipients.Trial registrationClinicaltrials.gov NCT00796588Electronic supplementary materialThe online version of this article (doi:10.1186/s13737-016-0033-4) contains supplementary material, which is available to authorized users.

Remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial): a pilot randomized controlled feasibility study

“…No patient suffered a complication secondary to RIPC and in no patient was surgery delayed as result of undergoing RIPC. This study satisfied the primary objectives of the feasibility study 21 .Ninety day mortality and graft loss was low in this cohort of patients with one perioperative death and only one other graft loss within the study period. It is therefore unsurprising that RIPC was unable to demonstrate any benefit by a reduction in 90 day morbidity and mortality in this small population of patients.…”

“…No patient suffered a complication secondary to RIPC and in no patient was surgery delayed as result of undergoing RIPC. This study satisfied the primary objectives of the feasibility study 21 .…”

Remote ischemic conditioning: a promising therapeutic intervention for multi-organ protection

“…(1) Liver injury after cardiac valve replacement surgery [ 221 ], the levels of total bilirubin, instead of serum transaminases and albumin, were lower in the RIC group; (2) major liver resection for colorectal liver metastasis [ 226 ], RIC significantly ameliorated liver injury after hepatectomy as presented by decreased serum transaminases and higher indocyanine green clearance; and (3) liver transplantation [ 227 , 228 ], a single center, randomized clinical trial aiming to elucidate RIC-mediated protection in liver transplant recipients is underway.…”

The Macrophage Activation Marker Soluble CD163 is Associated With Early Allograft Dysfunction After Liver Transplantation

“…Please refer to the original trial protocol for the exhaustive list. 21 All patients were characterised by the clinical disease severity score Model for End-Stage Liver Disease (MELD) 22 and standard biochemical analysis at baseline and on day 1, day 3 and day 7. Information regarding the donor, graft and course of the liver transplantation was recorded.…”