Desflurane Preconditioning in Hepatectomies
Keywords
Abstract
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.
Dates
| Last Verified: | 01/31/2019 |
| First Submitted: | 01/28/2019 |
| Estimated Enrollment Submitted: | 02/18/2019 |
| First Posted: | 02/20/2019 |
| Last Update Submitted: | 02/18/2019 |
| Last Update Posted: | 02/20/2019 |
| Actual Study Start Date: | 03/31/2016 |
| Estimated Primary Completion Date: | 06/29/2018 |
| Estimated Study Completion Date: | 06/29/2018 |
Condition or disease
Intervention/treatment
Drug: Desflurane Group
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: 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. | Drug: Desflurane Group |
| No Intervention: Control Group No pharmacological preconditioning was implemented |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| 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 |
Outcome
Primary Outcome Measures
1. Matrix Metalloproteinases (MMPs) 2 and 9 level [Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion]
2. Tissue Inhibitor Metalloproteinase (TIMPs) 1and 2 [Sample 1: At surgery, before initiation of the procedure , Sample 2: Thirty minutes after reperfusion]
Secondary Outcome Measures
1. Histological findings of hepatic parenchyma [Sample 1: Upon surgical dissection of the liver, before inflow occlusion, Sample: thirty minutes after reperfusion]
