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Completed

NCT Number: NCT03848780

Desflurane Preconditioning in Hepatectomies

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Desflurane

Drug

Primary outcomes

  1. Matrix Metalloproteinases (MMPs) 2 and 9 level

    Time frame: 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.

  2. Tissue Inhibitor Metalloproteinase (TIMPs) 1and 2

    Time frame: 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.

Secondary outcomes

  1. Histological findings of hepatic parenchyma

    Time frame: Sample 1: Upon surgical dissection of the liver, before inflow occlusion, Sample: thirty minutes after reperfusion

    Hematoxylin Eosin, Gomori and Μasson staining were used. With Hematoxylin Eosin staining the degree of steatosis was assessed while Gomori and Masson staining was used to determine the level of fibrosis.

    Steatosis was characterized (x100 magnification) as mild (10%-30%), moderate (30%-60%), severe (>60%) according to the presence of fat droplets in hepatic cells.

    Fibrosis was also graded based on the METAVIR score as absent - F0, portal fibrosis without septa - F1, portal fibrosis with rare septa - F2, numerous septa - F3 and cirrhosis - F4.

Sponsors and collaborators

Lead sponsor

Aristotle University Of Thessaloniki

Other

Registry information

Official study title

Pharmacological Preconditioning With Desflurane in Liver Surgery

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Feb 21, 2019
Registry last updated
Feb 21, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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