Pharmacological Preconditioning With Desflurane in Liver Surgery
Phase: NA
Conditions: Ischemia Reperfusion Injury
Sponsor: Aristotle University Of Thessaloniki

Pharmacological Preconditioning With Desflurane in Liver Surgery   
 
Last update: 30 April 2018, Thessaloniki, Greece 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study protocol 
Objective 
Ischemia-reperfusion injury is a major concern for hepatectomies. During 
hepatic resection the surgeon implements ischemia through inflow occlusion 
(Pringle maneuver) to prevent excessive and life threatening hemorrhage. 
Though, the pathophysiologic events occurring during ischemia are further 
promoted upon reperfusion. This entity may lead to liver failure and even 
Multiple Organ Disease Syndrome. Preconditioning has been identifying as a 
measure tackle ischemia – reperfusion injury in many organs. It refers to the 
exposure of a tissue at ischemic conditions to mitigate the subsequent 
reaction at re-exposure. Pharmacological preconditioning with the volatile 
anesthetic sevoflurane has been studied and proved beneficial for liver 
surgery. Our objective is to investigate the potential hepatoprotective role of 
another volatile anesthetic, desflurane. As sevoflurane has some properties 
that have been characterized as hepatotoxic, we have posed the hypotheses 
that desflurane may provide a beneficial advantage over ischemia – 
reperfusion injury. 
Design 
This is a randomized, double blind, clinical trial. Participants were allocated 
1:1 using electronic software to receive either pharmacological 
preconditioning with desflurane (Group Desflurane, D) or no intervention 
(Group Control, C). 46 adult patients presented for elective hepatic excision of 
two or more liver segments, were recruited in the study. Informed consent 
was obtained by all patients. Exclusion criteria were presence of Hepatitis B, 
Hepatitis C or Human immunodeficiency virus infection, pregnancy, 
autoimmune disease, inflammatory bowel disease, liver cirrhosis, liver 
ablation therapy. 
Methods 
All patients were managed by the same surgical team and the same 
anesthesiologist. Only the anesthesiologist was aware of the group assigned 
to each patient. The surgeon was blinded as to the intervention and was 
asked to inform the anesthesiologist 30 minutes before the initiation of 
ischemia. At that point, the propofol infusion used to maintain anesthesia was 
substituted by desflurane to achieve pharmacological preconditioning for 30 
minutes. After that interval, propofol infusion was reinitiated and desflurane 
ceased. Upon preoperative visit and at 30 minutes post reperfusion blood 
samples were taken for MMP 2, 9 and TIMP 1, 2 measurement. Specimens 
for histological test were taken before inflow occlusion and 30 minutes post 
reperfusion. 
 
 
 

Statistical Αnalysis Plan 
The SPSS v.22.0 software (SPSS, Inc., Chicago, Ill, USA) was utilized for all 
statistical analyses. . The significance level was set at p≤0.05 for the tested 
hypotheses. All data distributed normally according to Kolmogorov - Smirnov 
test. Independent samples T-test and independent samples Mann-Whitney test 
were performed for group (investigation and control) comparisons. The Fisher’s 
Exact test and X2 test were used for comparisons of groups relative to 
qualitative variables. Data for biological markers were explores within the frame 
of General Linear Models with the ANOVA method according to the model 
which involves one factor between patients (factor “Group” with two levels) and 
one factor within patients (factor “Time” with five levels, with repeated 
measures). Means’ comparisons were done with the Least Significant 
Difference (LSD) criterion.