Dexmedetomidine Infusion to Prevent Hepatic Ischemia-reperfusion Injury-induced Glycocalyx Degradation and Early Allograft Dysfunction in the Sitting of Adult Living Donor Liver Transplantation
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- syndecan-1 level
研究概览
简要总结
the aim of the study is to approve the hypothesis that dexmedetomidine can protect against glycocalyx degradation induced by hepatic ischemia-reperfusion injury and hence can reduce the subsequent complications as early allograft dysfunction, other organ dysfunction and hemodynamic instability
详细描述
The endothelial glycocalyx (EGCX) is a carbohydrate conjugate. It forms the vascular endothelial surface layer and is an important mediator of vascular permeability, coagulation, and inflammation. Inflammation, ischemia reperfusion, diabetes, and hypervolemia can cause EGCX damage.
When the EGCX is damaged by different mechanisms, glycocalyx-shedding products can be measured in the plasma. Syndecan-1 and heparan sulfate are two of components of the endothelial glycocalyx that have increased plasma concentrations after glycocalyx injury. The amount of glycocalyx-shedding correlates with the severity of the underlying pathological condition as different studies have shown.
The EGCX is an important target in the pathophysiological process of ischemia-reperfusin injury (IRI). Its destruction appears to play a central pathophysiological role in the development of IRI in conditions like shock, myocardial infarction, stroke, traumatic blood loss and during solid organ transplantation.
That damage to the endothelial glycocalyx significantly contributes to the development of IRI as recent studies have suggested. Schiefer et al. reported significantly higher plasma levels of syndecan-1 in liver graft recipients after transplantation than before transplantation, indicating destruction of the endothelial glycocalyx.
In animal studies, various drugs that may protect and/or restore the endothelial glycocalyx have been tested, while human trials are still lacking. Glycocalyx-protective strategies have been investigated during major surgery and the results indicated that preventive measures may be effective against glycocalyx destruction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18-60 years.
- •Model for end-stage liver disease (MELD) score 12-
- •No severe hemodynamic instability.
- •The liver donors aged 18-50 years and the sum of macro- and microvesicular hepatic steatosis has to be less than 30%.
排除标准
- •History of psychiatric/neurological illness.
- •Cardiovascular disease.
- •Hypertensive patients.
- •Morbid obese patients (body mass index (BMI) > 35).
- •Chronic obstructive pulmonary disease; pulmonary dysfunction (PaO2 less than 60 mmHg).
- •Known allergic reaction to any of the study medications.
研究组 & 干预措施
donor group
where donors only will receive dexmedetomidine
干预措施: Dexmedetomidine (Drug)
recpient group
where recepients only will receive dexmedetomidine
干预措施: Dexmedetomidine (Drug)
control group
both donors and recipients will receive a placebo
干预措施: Normal Saline (Drug)
结局指标
主要结局
syndecan-1 level
时间窗: 48 hours
Change in syndecan-1 level 5 minutes after hepatic artery declamping
次要结局
- Incidence of Primary nonunction (PNF) which is defined as graft loss, retransplantation, or participant death due to graft non-function in first 30 days without detectable technical or immunological problems.(30 days)
- Incidence of acute kidney injury ( AKI ) during postoperative days 1-7.(7 days)
- duration of post-operative mechanical ventilation(30 days)
- ICU and hospital stay after surgery.(60 days)
- Incidence of acute respiratory distress syndrome ( ARDS ) during postoperative days 1-7. Defined according to Berlin modification of the American European Consensus Committee (AECC) definitions published in 2012(7 days)
- All-cause 30-day mortality(30 days)
- Incidence of early hepatic allograft dysfunction ( EAD ) Defined according to Olthoff's criteria published in 2010: (1) bilirubin ≥10 mg/dL on day 7, or (2) INR > 1.6 on day 7, or (3) AST/ ALT > 2000 IU/L within first 7 days(7 days)
研究者
Aboubakr Youssef Ahmed
Assistant lecturer
Assiut University