Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery.

Sponsor

University of Chile (Other)

Overall Status

Completed

CT.gov ID

NCT03772054

Collaborator

(none)

Enrollment

Location

Arms

11.7

Actual Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Endothelial damage has been reported after ischemia-reperfusion events. This can be characterized by measurements of glycocalyx and endothelial components that are released to blood after the insult. Sevoflurane and inhaled anesthetic commonly used for surgery have shown protective endothelial effects in animal and in-vitro models. Knee-ligament surgery with the use of a femoral tourniquet generates a transient ischemia-reperfusion (IR) state after the tourniquet is released. This research aims to compare the effect of sevoflurane and propofol in the release of glycocalyx and endothelial biomarkers after IR in this surgical scenario.

Condition or Disease	Intervention/Treatment	Phase
Ischemia Reperfusion Injury	Drug: Sevoflurane Drug: Propofol	N/A

Detailed Description

To study the anesthetics effect on the endothelial damage induced by Ischemia-reperfusion (IR) in knee-ligament surgery, we will perform a randomized controlled clinical trial comparing the concentrations of syndecan-1 and heparan sulfate, both markers of superficial glycocalyx shedding and the concentration of thrombomodulin, a marker of endothelial cell damage, in serum of patients under hypnosis with sevoflurane or propofol after a spinal anesthesia.

After ethical review board approval and patients consent, 16 subjects (8 per group) scheduled for Knee-ligament replacement will be randomly allocated in one of the two parallel arms of the study. All patients will enter the operating room and after standard ASA monitorization and placement of an intravenous line (IV), a spinal anesthesia will be performed under midazolam sedation. After analgesia and motor block establishment, an intravenous or inhalation hypnosis induction will be performed (according to the study arm allocation). The airway will be secured by a laryngeal mask placement and the surgery will be started. A femoral tourniquet will be installed and inflated by surgeon indication at 100-120 mmHg over patient systolic blood pressure. Blood samples to measure endothelial damage biomarkers will be taken in five different moments to follow concentration changes before and after the IR insult. Fluid and drugs administration will be standardized.

Venous blood samples will be collected at the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR. After obtaining all samples, serum syndecan-1, heparan sulfate, and thrombomodulin will be measured by a researcher blinded to patient allocation using commercial available Elisa kits. The concentration of each biomarker at each sample time will be compared.

A sample size calculation was performed based on a few clinical reports to detect a 25% reduction in the mean concentration of syndecan-1 in the sevoflurane group with an alpha of 0,05 and a power of 80%. Then 16 patients (8 patients per arm) will be enrolled for a two-sides test analysis.

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

Blood samples will be codified by the principal investigator. Laboratory team will receive all samples for biomarkers measures. Results will be analyzed by the principal investigator.

Primary Purpose:

Prevention

Official Title:

Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery. A Randomized Controlled Trial

Actual Study Start Date :

Dec 20, 2018

Actual Primary Completion Date :

Dec 11, 2019

Actual Study Completion Date :

Dec 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Propofol After spinal anesthesia, patients in this arm will receive an intravenous target controlled infusion to site effect (TCI/Ce) infusion of propofol to achieve hypnosis guided to a bispectral index (BIS) level of 40-60 during surgery.	Drug: Propofol Intravenous anesthetic agent
Experimental: Sevoflurane After spinal anesthesia, patients in this arm will receive an inhalation induction with sevoflurane to achieve hypnosis guided to 0.7-0.9 minimum alveolar concentration (MAC) during surgery.	Drug: Sevoflurane Inhalation anesthetic agent

Arm

Intervention/Treatment

Active Comparator: Propofol

After spinal anesthesia, patients in this arm will receive an intravenous target controlled infusion to site effect (TCI/Ce) infusion of propofol to achieve hypnosis guided to a bispectral index (BIS) level of 40-60 during surgery.

Drug: Propofol

Intravenous anesthetic agent

Experimental: Sevoflurane

After spinal anesthesia, patients in this arm will receive an inhalation induction with sevoflurane to achieve hypnosis guided to 0.7-0.9 minimum alveolar concentration (MAC) during surgery.

Drug: Sevoflurane

Inhalation anesthetic agent

Outcome Measures

Primary Outcome Measures

Syndecan-1 levels [At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR]
Differences in the concentration of syndecan-1 in blood serum during and after surgery

Secondary Outcome Measures

Heparan sulfate levels [At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR]
Differences in the concentration of heparan sulfate in blood serum during and after surgery
Thrombomodulin [At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR]
Differences in the concentration of thrombomodulin in blood serum during and after surgery