Pharmacological Preconditioning With Desflurane in Liver Surgery
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 46
- 主要终点
- Matrix Metalloproteinases (MMPs) 2 and 9 level
研究概览
简要总结
Hepatectomies are considered as operations of high bleeding risk. The history of massive hemorrhage in liver surgery led to the emergence of techniques to control excessive blood loss. These techniques temporarily occlude the blood vessels that supply liver (the Pringle Maneuver) limiting subsequent losses. However, this leads to the ischemia - reperfusion injury impairing liver function. Research points to methods targeting on tempering reperfusion pathophysiology. Volatile anesthetics have been used for pharmacological preconditioning and proved to protect against organ damage. The aim of this study was to investigate the potential beneficial effect of desflurane on ischemia-reperfusion injury of the liver. Patients presenting for elective hepatectomy were randomized equally into two groups. The Control Group received no pharmacological preconditioning and the Desflurane Group received pharmacological preconditioning with Desflurane before induction of ischemia.
详细描述
Hepatectomies are characterized by an elevated risk of severe hemorrhage. The high vascular supply of the liver has historically troubled surgeons who resolved to techniques to control excessive blood loss. The Pringle Maneuver commonly employed in liver surgery is a temporary method to occlude the vascular supply of the liver. As a result, ischemia is developed and a pathophysiologic cascade is initiated. Upon the resolution of ischemia, reperfusion occurs which is linked to further damage and the ischemia-reperfusion injury is developed. Ischemia and reperfusion lead to activation of the innate immune response, which interacts with the adaptive immune response. Result of this interaction is the production of inflammatory cytokines, chemokines, complement products, and the recruitment of neutrophils to the site of injury. Previous studies have shown that animal's livers suffered from ischemia-reperfusion injury had increased neutrophil infiltration and pharmacological agents attenuating neutrophil's activity improved hepatic Ischemia-Reperfusion Injury (IRI). Preconditioning refers to the exposure of an organ to short intervals of ischemia which has been shown to mitigate the aforementioned ischemia-reperfusion injury. Preconditioning can be pharmacological and volatile anesthetics have been successfully used in preconditioning models. Sevoflurane have been proved beneficial for a series of hepatectomies in limiting transaminase levels postoperatively. However, sevoflurane by virtue can be hepatotoxic through Compound A production, elevated free calcium and reactive oxide species activation. On the other hand, desflurane undergoes minimum liver metabolism. In liver ischemia-reperfusion models, desflurane preconditioning led to decreased cell death and inflammatory cytokines inhibition.
The goal of the investigator's study was to investigate the effect of desflurane preconditioning in patients undergoing elective hepatectomy of at least two segments. Patients were randomized 1:1 to receive pharmacological preconditioning (Desflurane Group, Group D) or not (Control Group, Group C). The surgeon and the Intensive Care Unit were blinded as to the intervention. Anesthetic management was the same for all patients. For GroupD thirty minutes before the initiation of ischemia desflurane was delivered and propofol was stopped for the same interval.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •hepatectomy of at least two segments
排除标准
- •Hepatitis B, C or HIV infection
- •liver cirrhosis
- •autoimmune disease, inflammatory bowel disease
- •pregnancy
- •prior additional ablation therapies (cryosurgery or radiofrequency)
- •liver resections without inflow occlusion
研究组 & 干预措施
Desflurane Group
Thirty minutes before initiation of ischemia the surgeon was instructed to notify the anesthesiologist. At this single time point, propofol infusion was stopped and substituted with the volatile anesthetic desflurane to achieve a Minimum Alveolar Concentration of 1. The procedure included a 5-minute induction of desflurane, a 20-minute preconditioning and a 5-minute washout period when propofol was reintroduced and desflurane stopped.
干预措施: Desflurane (Drug)
结局指标
主要结局
Matrix Metalloproteinases (MMPs) 2 and 9 level
时间窗: Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion
The levels of Matrix Metalloproteinase 2 and Matrix Metalloproteinase 9 as evaluated by the relative gene expression using RT-PCR. The comparative CT method also referred to as the 2-ΔΔCT method was used to calculate the fold change and then convert it to percentage. Their presence has been linked to hepatic cellular injury so increased levels represent worse injury.
Tissue Inhibitor Metalloproteinase (TIMPs) 1and 2
时间窗: Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion
The levels of Tissue Inhibitor Metalloproteinase 1 and Tissue Inhibitor Metalloproteinase 2 as evaluated by the relative gene expression using RT-PCR. The comparative CT method also referred to as the 2-ΔΔCT method was used to calculate the fold change and then convert it to percentage. Their inhibitory effect on Matrix Metalloproteinases has been associated with a limitation of cellular injury. Thus, the higher the levels of Tissue Inhibitor Metalloproteinases the greater their protective activity.
次要结局
- Histological findings of hepatic parenchyma(Sample 1: Upon surgical dissection of the liver, before inflow occlusion, Sample: thirty minutes after reperfusion)
研究者
Eleni Koraki
Principal investigator, Anesthesiologist
Aristotle University Of Thessaloniki
