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

December 11, 2019 updated by: Felipe Andrés Maldonado Caniulao, University of Chile

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

16

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Chile
    • Santiago
      • Independencia, Santiago, Chile, 8380456
        • Hospital Clinico de la Universidad de Chile

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Syndecan-1 levels
Time Frame: 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
At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Heparan sulfate levels
Time Frame: 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
At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR
Thrombomodulin
Time Frame: 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
At the moment of IV placement (baseline values), during surgery before of tourniquet release (TR), 10, 60 and 90 min minutes after TR

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Chile

Investigators

  • Principal Investigator: Felipe Maldonado, M.D., M.Sc., Hospital Clìnico de la Universidad de Chile.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 20, 2018

Primary Completion (ACTUAL)

December 11, 2019

Study Completion (ACTUAL)

December 11, 2019

Study Registration Dates

First Submitted

December 9, 2018

First Submitted That Met QC Criteria

December 9, 2018

First Posted (ACTUAL)

December 11, 2018

Study Record Updates

Last Update Posted (ACTUAL)

December 12, 2019

Last Update Submitted That Met QC Criteria

December 11, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 903/17

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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