Clinical trial NCT04695509: Sedation and Neuromediators Concentration
Official title: The Influence of Propofol Sedation on Neuromediators Concentration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Moderate Sedation
Deep Sedation
Keywords: Sedation
Neuromediators
Lead sponsor: I.M. Sechenov First Moscow State Medical University
Sponsor class: OTHER
First posted: 2021-01-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Dopamine concentration changes during moderate and deep sedation
timeFrame: 2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) dopamine conducting
measure: Serotonin concentration changes during moderate and deep sedation
timeFrame: 2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) serotonin conducting
measure: GABA concentration changes during moderate and deep sedation
timeFrame: 2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) GABA conducting
measure: Acetylcholine concentration changes during moderate and deep sedation
timeFrame: 2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) acetylcholine conducting
measure: Noradrenaline concentration changes during moderate and deep sedation
timeFrame: 2 months for each patient from venous blood sampling to enzyme-linked immunosorbent assay (ELISA) noradrenaline conducting
Secondary outcomes:
measure: Target control infusion (TCI) values of propofol sedation
timeFrame: intraoperative period
measure: Richmond agitation and sedation scale (RASS) scores
timeFrame: intraoperative period
measure: Bispectral index monitoring (BIS) values during moderate and deep sedation
timeFrame: intraoperative period
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: City Clinical Hospital № 31 of the Department of Health of Moscow
Study officials:
References: