Ischemic Preconditioning at a Distance in Liver Surgery

Study Overview
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Brief Summary
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During hepatic transection, it exists a high risk of perioperative blood loss. The haemorrhage and its consequences (hypovolemia and blood transfusion) might impact the short and long term morbidity The vascular control by hepatic pedicle clamping (Pringle's maneuver) or total hepatic vascular exclusion, helps minimizing blood loss and leads to a more extensive hepatic resection. Side effects of vascular control result of ischemia-reperfusion injury (IRI) : these reperfusion lesions results of different mechanisms than those responsible for the ischemic one. IRI cause lesions and postoperative dysfunction of the remaining liver. Among strategies to reduce the adverse effects of IRI : ischaemic preconditioning (IPC) has been described. It can be either mechanical (intermittent hepatic pedicle clamping) or pharmacological (sevoflurane inhalation). Short intermittent vascular occlusions in a organ might produce a resistance to a longer ischaemic period. It is certainly a physiological organ adaptation to tissue hypoxemia, which has a therapeutic potential when targeted. During liver resection, ischaemic preconditioning is realised with periods of hepatic pedicle clamping and unclamping. It decrease morbidity and mortality and prevent postoperative hepatocellular insufficiency due to clamping and IRI at day 5. Ischaemic preconditioning may also be applied remotely. Indeed, it is shown that short ischaemic periods in a target organ can also have a protective effect on distant others. This mechanism involve three signalling pathways : neuronal , humoral and systemic pathways. In a previous randomized study, Kanoria and al, demonstrated that the remote ischaemic preconditioning group has shown significant lower rates of serum transaminases and higher liver clearance (spectrophotometry method) than the control group. A latest study, measuring postoperative prothrombin rates has shown improved liver recovery due to halogen agents such as sevoflurane.

Official Title
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Randomized, Single-blind Study of Remote Ischemic Preconditioning in Hepatectomies

Conditions
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Liver Diseases

Intervention / Treatment
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* Procedure: pneumatic tourniquet
* Other: No inflation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled carcinogenic laparoscopy or laparotomy liver resection Insured under the social security system Inclined to comply to the study protocol and its duration. Exclusion Criteria: Patient under guardianship Pregnancy or breastfeeding Severe lower limb vascular disease Emergency surgery Contraindication of a treatment from the protocol Psychological disorder with difficulty to accede the protocol Absence of written informed consent Refusal to sign the protocol Non-registration to the social security system

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inflation of a pneumatic tourniquet<br> | Procedure: pneumatic tourniquet<br>* a pneumatic tourniquet around 200 mmHg after venous chase of the lower limb, during 5 minutes then deflated. Repeated twice after general anaesthesia and prior to incision.<br>|
| Sham Comparator: No inflation<br>No inflation of the pneumatic tourniquet placed on the lower limb | Other: No inflation<br>* No inflation of the pneumatic tourniquet placed on the lower limb<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Indocyanine green clearance | Indocyanine green clearance (%/min) by indocyanine green retention, measured with Limon pulse spectrophotometry method. | at 5 days after liver resection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum transaminases rates |  | at day 1,day 3 and day 5 post-hepatectomy. | 
| Prothrombin rate |  | at day 5 post-hepatectomy. | 
| the Kidney Disease: Improving Global Outcomes (KDIGO) score | The score varies from 1 to 4. | at day 1,day 3 and day 5 post-hepatectomy. | 
| the Clavien & Dindo score | this classification in order to rank a post operative complications. It consists of 7 grades (I, II, IIIa, IIIb, IVa, IVb and V) | at day 30 post-hepatectomy | 
| duration of stay in the hospital. |  | at day 30 post-hepatectomy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remote ischemic preconditioning, liver resection, liver clearance.