Ischemia Reperfusion Injury Clinical Trial
Official title:
Pharmacological Preconditioning With Desflurane in Liver Surgery
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.
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.
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