Clinical trial NCT03772054: Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery.
Official title: Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery. A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemia Reperfusion Injury
Keywords: Syndecan-1
Heparan sulfate
Thrombomodulin
Ischemia Reperfusion
Anesthesia
Lead sponsor: University of Chile
Sponsor class: OTHER
First posted: 2018-12-11
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: Inclusion Criteria:

* American Society of Anesthesiologists Classification (ASA Class) I and II
* Elective knee ligament surgery
* Use of a femoral tourniquet

Exclusion Criteria:

* Allergies to egg or soya
* Previous history of critical events during surgery and perioperative period
* Patients at risk of hyperthermia malignant
* Patients with 3 or more predictor of difficult airway management

Primary outcomes:
measure: Syndecan-1 levels
timeFrame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
Secondary outcomes:
measure: Heparan sulfate levels
timeFrame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
measure: Thrombomodulin
timeFrame: At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
Other outcomes:
Locations:
city: Independencia
country: Chile
facility: Hospital Clínico de la Universidad de Chile
state: Santiago
Study officials:
affiliation: Hospital Clìnico de la Universidad de Chile.
name: Felipe Maldonado, M.D., M.Sc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maldonado F, Morales D, Gutierrez R, Barahona M, Cerda O, Caceres M. Effect of sevoflurane and propofol on tourniquet-induced endothelial damage: a pilot randomized controlled trial for knee-ligament surgery. BMC Anesthesiol. 2020 May 20;20(1):121. doi: 10.1186/s12871-020-01030-w.