Sedation and Neuromediators Concentration

June 9, 2021 updated by: I.M. Sechenov First Moscow State Medical University

The Influence of Propofol Sedation on Neuromediators Concentration

Propofol (Propofol Kabi, Registration number from the State Register of Medicines - 000875) is a widely used intravenous anesthetic. It is well known about different effects of propofol infusion, including euphoria, psycholalia, disinhibition, talkativeness, satisfaction etc. However, the basic mechanisms of such effects remain unknown. We suppose that propofol sedation with various levels of sedation (from light to deep) leads to neuromediators changes. We examine dopamine, noradrenaline, acetylcholine, GABA and serotonin in peripheral venous blood before, during and after propofol sedation. Therefore, we suppose drugs for sedation, in particular, propofol will affect neuromediators concentration.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study is a prospective, nonrandomized, single center investigator design. Twenty-six healthy patients undergoing elective trauma surgery (arthroscopy, reconstructive foot surgery, osteosynthesis of intra-and periarticular fractures of the proxymal humerus) under regional anesthesia (spinal anesthesia or brachial plexus block) with medical propofol sedation are enrolled in this study. Montreal cognitive assessment test is a high validity test for detecting cognitive impairment before operation. American Society of Anesthesiologists (ASA) physical status classification system is used to assess the physical status of patients before operation. Hospital Anxiety and Depression Scale (HADS) is used to determine the levels of anxiety and depression before operation. Two 18 or 20 G venous cannulae are inserted in the left and/or right forearm for drug infusion and blood sampling. The Richmond Agitation and Sedation scale (RASS) and bispectral index monitor A-2000XP (BIS, Aspect Medical Systems, Inc. (USA), Registration certificate for a medical device RZN 2005/498) are used to determine the levels of sedation. Briefly (less than 10 seconds) awakens with eye contact to voice or any movement (but no eye contact) to voice, bispectral index values 70-90 correspond light-moderate sedation. No response to voice, but any movement to physical stimulation, bispectral index monitoring values 60-70 correspond deep sedation. BBraun Space with target control infusion sedation (TCIS, B. Braun Melsungen AG, Registration certificate for a medical device RZN 2013/905) is used for dosing of propofol with moderate (1-st group) or deep sedation (2-nd group). Philips Monitor IntelliVue MP40 (Medizin Systeme Boblingen GmbH, Germany, Registration certificate for a medical device RZN 2014/2009) is used for monitoring the electrocardiogram (ECG), noninvasive blood pressure (NIBP), pulse oximetry during the infusion of the propofol and 15-20 minutes thereafter. Peripheral venous blood samples are taken for analyzing neuromediators concentration 5 minutes before sedation (10 ml), after 35-40 min of propofol sedation (10 ml) and 10-15 minutes after the end of propofol infusion (emergence from sedation). The blood is centrifuged for at least 8 minutes at 4000 revolutions per minute (RPM) in the test tube 367525-BD VACUTAINER (Becton Dickinson), plasma is taken, which is further frozen at a temperature of -20 C in the test tube 363706-BD MICROTAINER (Becton Dickinson). After 26 patients are recruited, the blood plasma is analyzed by conducting the enzyme-linked immunosorbent assay (ELISA, IBL Hamburg) of neuromediators (dopamine (Catalog № Re59161), serotonin (Catalog № Re59121), gamma-aminobutyric acid (GABA), acetylcholine (Catalog № Re59161), noradrenaline (Catalog № Re59261)). Concentrations of neuromediators between moderate and deep sedation groups are compared using Student's t-test for independent samples. Concentrations of neuromediators before, during and after sedation are compared using Friedman-test for dependent samples. All data is presented as mean ± SD, a value of P less than 0.05 is taken as statistically significant.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Russian Federation
      • Moscow, Russian Federation
        • City Clinical Hospital № 31 of the Department of Health of Moscow

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Written informed consent
  • Age ≥ 18 years
  • Elective trauma surgery (arthroscopy, reconstructive foot surgery, osteosynthesis of intra-and periarticular fractures of the proxymal humerus) under regional anesthesia (spinal anesthesia or brachial plexus block) with propofol sedation
  • Montreal cognitive assessment test ≥ 26
  • Patients with American Society of Anesthesiologists (ASA) I-II

Non-inclusion criteria:

  • Not written informed consent
  • Age˂18 years
  • Allergy to sedation drugs
  • Pregnancy
  • Epilepsy anamnesis
  • II-III degree atrioventricular block
  • Montreal cognitive assessment test ˂ 26
  • Patients with American Society of Anesthesiologists (ASA) ˃ II
  • The presence of psychiatric disorders
  • Сancer patients with a life expectancy of less than two years

Exclusion Criteria:

  • Patient refuse from further participation
  • Transition from sedation to general anesthesia
  • Allergy on anesthesia drugs during perioperative period

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: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: moderate sedation
patients with American Society of Anesthesiologists (ASA) I-II, Montreal cognitive assessment test ≥ 26, trauma surgery under regional anesthesia with moderate propofol sedation
Drug: moderate propofol sedation (Bispectral index monitoring 70-90; The Richmond Agitation and Sedation scale (RASS) "-2" - "-3"
Two peripheral venous blood catheters are placed after admission in the operation room and venous blood sample is taken (10 ml). Complete monitoring of vital functions is provided (pulse oximetry, noninvasive blood pressure, electrocardiography, bispectral index monitoring). Doctor anesthesiologist performs regional anesthesia and propofol light-moderate sedation starts. The second blood sample (10 ml) is taken 35-40 minutes after the start of propofol sedation. The third blood sample (10 ml) is taken after emergence from propofol sedation (10-15 minutes after propofol discontinuation). Blood samples are centrifuged and received plasma is frozen at a temperature of -20 C*. After 26 patients are recruited, the blood plasma is analyzed by conducting the enzyme-linked immunosorbent assay (ELISA) of neuromediators (Dopamine, serotonin, Gamma-aminobutyric acid (GABA), acetylcholine, noradrenaline).
Experimental: deep sedation
Arm Description: patients with American Society of Anesthesiologists (ASA I-II), Montreal cognitive assessment test ≥ 26, trauma surgery under regional anesthesia with deep propofol sedation
Drug: deep propofol sedation (BIS 60-70, The Richmond Agitation and Sedation scale (RASS) "-4")
Two peripheral venous blood catheter is placed after admission in the operation room and venous blood sample is taken (10 ml). Complete monitoring of vital functions is provided (pulse oximetry, blood pressure, electrocardiography, bispectral index monitoring). Doctor anesthesiologist performs regional anesthesia and propofol deep sedation starts. The second blood sample (10 ml) is taken 35-40 minutes after the start of propofol sedation. The third blood sample (10 ml) is taken after emergence from propofol sedation (10-15 minutes after propofol discontinuation). Blood samples are centrifuged and received plasma is frozen at a temperature of -20 C*. After 26 patients are recruited, the blood plasma is analyzed by conducting enzyme-linked immunosorbent assay (ELISA) of neuromediators (Dopamine, serotonin, Gamma-aminobutyric acid (GABA), acetylcholine, noradrenaline).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dopamine concentration changes during moderate and deep sedation
Time Frame: 2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) dopamine conducting
Venous blood sampling and enzyme-linked immunosorbent assay (ELISA) are used to evaluate the influence of medical sedation on dopamine concentration
2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) dopamine conducting
Serotonin concentration changes during moderate and deep sedation
Time Frame: 2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) serotonin conducting
Venous blood sampling and enzyme-linked immunosorbent assay (ELISA) are used to evaluate the influence of medical sedation on serotonin concentration
2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) serotonin conducting
GABA concentration changes during moderate and deep sedation
Time Frame: 2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) GABA conducting
Venous blood sampling and enzyme-linked immunosorbent assay (ELISA) are used to evaluate the influence of medical sedation on GABA concentration
2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) GABA conducting
Acetylcholine concentration changes during moderate and deep sedation
Time Frame: 2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) acetylcholine conducting
Venous blood sampling and enzyme-linked immunosorbent assay (ELISA) are used to evaluate the influence of medical sedation on acetylcholine concentration
2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) acetylcholine conducting
Noradrenaline concentration changes during moderate and deep sedation
Time Frame: 2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) noradrenaline conducting
Venous blood sampling and enzyme-linked immunosorbent assay (ELISA) are used to evaluate the influence of medical sedation on noradrenaline concentration
2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) noradrenaline conducting

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Target control infusion (TCI) values of propofol sedation
Time Frame: intraoperative period
Bbraun Perfusor Space is used for target control propofol infusion. TCI values for moderate sedation are 1,0-2 mcg/ml, deep sedation 2,5-3,5 mcg/ml.
intraoperative period
Richmond agitation and sedation scale (RASS) scores
Time Frame: intraoperative period
RASS is measured during propofol infusion and the target scores for moderate sedation are "-1" - "-3", deep sedation "-4"
intraoperative period
Bispectral index monitoring (BIS) values during moderate and deep sedation
Time Frame: intraoperative period
BIS-monitor А-2000XP (Aspect Medical Systems, USA) is used for evaluating the level of sedation. BIS values for moderate sedation are 70-90, deep sedation 60-70
intraoperative period

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
I.M. Sechenov First Moscow State Medical University

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.

Helpful Links

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 5, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 15, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 15, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 18, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 5, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 10, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 502

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Sharing Time Frame

The data will become available 11/01/2021

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)

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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