Ischemia Reperfusion Injury, Liver Transplant; Complications
Conditions
Keywords
ischemia reperfusion injury, remote ischemic preconditioning, liver transplantation
Brief summary
Ischemia and reperfusion injury is unavoidable during a liver transplantation. Remote ischemic preconditioning, a safe and feasible method, has previously been shown to reduce ischemia and reperfusion injury. In the transplantation setting, focus of remote ischemic preconditioning has been on the donor. However, preconditioning of the recipient may be a better approach due to the mechanisms by which ischemic preconditioning protects against ischemia and reperfusion injury. The aim of this randomised, double-blinded clinical trial is to biochemically assess the liver function after application of remote ischemic preconditioning on the recipient.
Detailed description
Background The use of solid organ transplantation, including liver transplantation, is the golden standard for many end-stage solid organ diseases. Ischemia and reperfusion injury is unavoidable during a liver transplantation. Remote ischemic preconditioning, a safe and feasible method, has previously been shown to reduce ischemia and reperfusion injury. This may have a similar effect in a liver transplantation setting. In the transplantation setting, focus of remote ischemic preconditioning has been on the donor. However, preconditioning of the recipient may be a better approach due to the mechanisms by which ischemic preconditioning protects against ischemia and reperfusion injury. The aim of this randomised, double-blinded clinical trial is to biochemically assess the liver function after application of remote ischemic preconditioning on the recipient. Methods 52 patients undergoing a liver transplantation, included in accordance to the inclusion criteria, will be allocated to an intervention group (rIC-group) and compared to a retrospective non-intervention control group (non-rIC group) consisting of 52 patients. Patients in the non-intervention group will also be included in accordance to the inclusion criteria. Within two hours before surgery, patients in the intervention group will be subjected to four rounds of five-minute inflations and five-minute deflations of a pneumatic tourniquet applied on the right leg. Follow-up time will be 30 days. Measurements The aim of this trial is to assess the effect of remote ischemic preconditioning on the extent of liver injury and inflammation as a result of ischemia and reperfusion injury. Assessment will be done by measurement of biomarkers relevant to liver function and liver injury.
Interventions
PROCEDUREremote ischemic preconditioning (rIC)
Short intermittent peripheral occlusions and reperfusions of the blood flow in the right lower extremity with the help of a tourniquet.
OTHERnon remote ischemic preconditioning (non-rIC)
Retrospective group who have not undergone intervention.
Sponsors
Rigshospitalet, Denmark
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
The patient enrolment will be done by the on-call doctor and intervention will be performed by unblinded research personnel who won't be involved in sample collection or data analysis.
Intervention model description
Patients will be allocated to an intervention group (rIC) and compared to a retrospective control group. Data assessment will be blinded to the assessor.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients undergoing liver transplantation * Patients aged 18 or above * Patients who have given an informed consent
Exclusion criteria
* Patients undergoing re-transplantation. * Patients who do not or cannot give an informed consent. * Patients who have undergone surgery six weeks prior to liver transplantation. * Patients with known peripheral vascular disease. * Patients with an infection localized to the area of rIC-intervention * Patients with at a high risk or with previous history of multiple thrombo-embolic diseases. * Patients undergoing active immunosuppressive therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-operative change in ALT | Day 0-4 | Extent of liver injury measured as change in ALT postoperative from day zero to day four . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-operative change in Bilirubin | Day 0-4 | Serological markers of liver function |
| Post-operative change in Aspartate Amonitransferase | Day 0-4 | Serological markers of liver function |
| Post-operative change in Alkaline Phosphatase | Day 0-4 | Serological markers of liver function |
| Post-operative change in International Normalised Ratio | Day 0-4 | Serological markers of liver function |
Other
| Measure | Time frame | Description |
|---|---|---|
| Total length of hospital-stay | Follow-up on day 30 | — |
| Days in ICU (Intensive Care Unit) | Follow-up on day 30 | Length of post-operative stay in ICU |
| Complication rate | Follow-up on day 30 | Rate of post-operative complications |
Outcome results
None listed