Sevoflurane vs Propofol Effect on Endothelial Damage Markers After Knee Ligament Surgery.
Condition: Ischemia Reperfusion Injury
MeSH terms: Reperfusion Injury; Ischemia
Study type: Interventional

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.
    

Intervention name(s): Sevoflurane; Propofol
Intervention type(s): Drug; Drug
Intervention description(s): Inhalation anesthetic agent; Intravenous anesthetic agent
Intervention MeSH terms: Propofol; Sevoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention
Keywords: Syndecan-1; Heparan sulfate; Thrombomodulin; Ischemia Reperfusion; Anesthesia