Clinical trial NCT03848780: Desflurane Preconditioning in Hepatectomies
Official title: Pharmacological Preconditioning With Desflurane in Liver Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemia Reperfusion Injury
Keywords: preconditioning
hepatectomy
ischemia reperfusion injury
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
First posted: 2019-02-21
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* hepatectomy of at least two segments

Exclusion Criteria:

* 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

Primary outcomes:
measure: Matrix Metalloproteinases (MMPs) 2 and 9 level
timeFrame: Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion
measure: Tissue Inhibitor Metalloproteinase (TIMPs) 1and 2
timeFrame: Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion
Secondary outcomes:
measure: Histological findings of hepatic parenchyma
timeFrame: Sample 1: Upon surgical dissection of the liver, before inflow occlusion, Sample: thirty minutes after reperfusion
Other outcomes:
Locations:
Study officials:
affiliation: Aristotle University Of Thessaloniki
name: Eleni Koraki, Dr
role: PRINCIPAL_INVESTIGATOR
References:
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