Sedation and Neuromediators Concentration
Condition: Moderate Sedation; Deep Sedation
Study type: Interventional

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.
    

Intervention name(s): moderate propofol sedation (Bispectral index monitoring 70-90; The Richmond Agitation and Sedation scale (RASS) "-2" - "-3"; deep propofol sedation (BIS 60-70, The Richmond Agitation and Sedation scale (RASS) "-4")
Intervention type(s): Drug; Drug
Intervention description(s): 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).; 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).
Intervention MeSH terms: Propofol
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Sedation; Neuromediators