Sedation and Memory Consolidation
Condition: Memory Impairment; Amnesia; Recall; Recognition
MeSH terms: Amnesia
Study type: Interventional

Summary: 
      The study of plasticity processes, in particular, memory, is one of the fundamental
      directions in anesthesiology. To date, there are different views on the impact of sedation
      and anesthesia on memory. Memory consolidation is one of the most crucial processes that the
      anesthesiologist is interested in. Memory consolidation is the mechanism of transferring
      short-term memory to long-term memory. The investigators suppose that propofol or
      dexmedetomidine sedation disrupts memory consolidation. In addition, the investigators
      inquired about the impact of sedation on 'working memory'. Therefore, a better understanding
      of the influence of anesthesia and sedation on basic memory processes will allow the
      anesthesiologist to balance the choice of the drug and ensure the patient's safety in the
      intraoperative period.
    

Detailed description: 
      The study is a prospective, randomized, single blind design. Patients undergoing elective
      trauma surgery (arthroscopy, reconstructive foot surgery) under subarachnoidal anesthesia are
      enrolled in this study. All patients were randomly divided into three groups depending on the
      drug type: first - propofol, second - dexmedetomidine, third - control.

      The Montreal cognitive assessment test (MoCA - test) is a high validity test. MoCA - test is
      used to determine cognitive impairments in patients in the pre-operative period. The MoCA
      test time is approximately 10 minutes. The maximum possible score is 30; 26 points and more
      are considered normal, 25 or less is evidence of cognitive impairment.

      American Society of Anesthesiologists (ASA) physical status classification system is used to
      assess and communicate a patient's pre-anesthesia medical co-morbidities (ASA I - a normal
      healthy patient, ASA II - a patient with mild systemic disease, ASA III - a patient with
      severe systemic disease, ASA IV - a patient with severe systemic disease that is a constant
      threat to life, ASA V - a moribund patient who is not expected to survive without the
      operation, ASA VI - a declared brain-dead patient whose organs are being removed for donor
      purposes.

      To determine the level of anxiety and depression in the preoperative period, patients are
      tested using the Hospital Anxiety and Depression Scale (HADS). Values on the HADS scale<7
      points are interpreted as normal, with scores from 8 to 10 as subclinically expressed anxiety
      and/or depression, and above 10 points-clinically expressed anxiety and/or depression.

      In the operating room intravenous (i.v.) peripheral canulla Vasofix Certo (B. Braun, Germany)
      with a diameter of 18 or 20 Gauge is inserted before the start of regional anesthesia for
      infusion therapy. Before spinal anesthesia an anesthesiologist inject 0.9% saline infusion
      (Grotex, Russia) of 6-8 ml/kg.

      Following this procedure, the investigators perform a puncture of the subarachnoid space with
      a 27 Gauge Pencil Point needle (Bbraun, Germany) under aseptic conditions under local
      anesthesia with lidocaine (Pharmasyntez, Russia) at the L2-L4 level. The criterion for
      verifying the subarachnoid space is the appearance of liquor in the needle pavilion. After
      performing the aspiration test, 10-15 mg of an isobaric solution of moxicaine
      (Novosibhimfarm, Russia) is injected. To evaluate the sensory block, the investigators use
      the tactile sensitivity loss test ('pinprick' test), and the motor block-the Bromage test.

      0.9% saline (20 - 25 ml/kg) is administered to patients in the all groups. Propofol (1 group
      (Propofol Kabi, Registration number from the State Register of Medicines - 000875)) or
      dexmedetomidine (2 group (Dexmedetomidine, Registration number from the State Register of
      Medicines - 005916) are used for sedation. Intravenous infusion of propofol or
      dexmedetomidine is performed with a BBraun Space (B. Braun Melsungen AG, Registration
      certificate for a medical device RZN 2013/905). Target control infusion (TCI, Shnider model)
      is applied for the dosing of propofol concentration. At the beginning of sedation, the level
      of the target propofol concentration is 1.5 - 2 mcg ml-1, during operation - 2.5 mcg ml-1.
      Intravenous infusion of dexmedetomidine starts with a dose of 1 mcg/kg for 10 minutes, with
      maintaining dose from 0.6 to 0.7 mcg/kg/min follows by titration from 0.2 to 2 mcg/kg/h
      depending on the level of sedation. Propofol or dexmedetomidine infusion terminates 10
      minutes before the end of the operation. 0.9% saline (20 - 25 ml/kg) is administered to
      patients in the control group (3 group). Sedation is not performed in control group.

      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 assess the depth of sedation. RASS values '-2' - '-3' (short-term eyes
      opening for less than 10 seconds or voluntary movements without eye contact in response to a
      call) correspond to light-moderate sedation, '-4' (eyes opening or voluntary movements in
      response to physical stimulation) - deep sedation. BIS values 70 - 90 correspond to light -
      moderate sedation, 60 - 70 - deep sedation.

      To ensure patient safety, the investigators use the basic monitoring standard: noninvasive
      arterial pressure (NAP), heart rate (HR), electrocardiogram (ECG), SpO2, capnography (Philips
      Monitor IntelliVue MP40 (Medizin Systeme Boblingen GmbH, Germany, Registration certificate
      for a medical device RZN 2014/2009)).

      Memory testing is conducted in three stages. Stage 1 - immediately prior to sedation, stage 2
      - 5-10 minutes after the start of sedation (RASS '-1' - '-2', BIS 70 - 90), stage 3 - 10
      minutes after sedation is finished and consciousness is restored (RASS '0', BIS 95 - 100).
      Five emotionally neutral words are heard by the patients twice at each stage to assess the
      impact of sedation on memory consolidation. The experimental words are different at each
      stage. The patients repeat the memorized words after each audition. To assess the effect of
      sedation on the 'working memory', anesthesiologist asked the patient to remember and
      reproduce the memorized words five minutes after learning in the second stage. Approximately,
      24 hours after the end of anesthesia, recall and recognition of the experimental words are
      tested. To assess recall, the patients remember all the words listened before, during and
      after anesthesia. To test recognition, patients use to mark the words learned during surgery
      in the list of words, which consists of 15 experimental and 10 control. The number of words
      in recall and recognition testing is recorded by researcher.

      Statistical analysis is perfomed in MS Excel and Jamovi 2.0.0 programs. The Shapiro-Wilk and
      Kolmogorov-Smirnov tests are used to determine the normality of the distribution. The
      analysis of the categorical variables is evaluated using the criterion χ2. For inter-group
      comparison of quantitative variables, one-way analysis of variance (one-way ANOVA) followed
      by post-hoc Bonferroni test are used. Repeated measures analysis of variance (RM-ANOVA)
      followed by post hoc tests for multiple comparisons, which are Bonferroni-adjusted, are
      performed to compare data within groups. Statistical significance level is set at P < 0.05.
    

Intervention name(s): Influence of propofol sedation on memory consolidation and 'working memory'; Influence of dexmedetomidine sedation on memory consolidation and 'working memory'; Influence of spinal anesthesia on memory consolidation and 'working memory'
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Spinal anesthesia is performed by anesthesiologist. Memory testing is conducted immediately prior to propofol sedation (stage 1), 5-10 minutes after the start of propofol sedation (stage 2), 10 minutes after propofol sedation is finished and consciousness is restored (stage 3). Five emotionally neutral words are heard by the patients twice at each stage to assess the impact of sedation on memory consolidation. The patients repeat the memorized words after each audition. To assess the effect of sedation on the 'working memory', anesthesiologist asked the patient to remember and reproduce the memorized words five minutes after learning in the second stage. Approximately, 24 hours after the end of anesthesia, recall and recognition of the experimental words are tested. The number of words in recall and recognition testing is recorded by researcher.; Spinal anesthesia is performed by anesthesiologist. Memory testing is conducted immediately prior to dexmedetomidine sedation (stage 1), 5-10 minutes after the start of dexmedetomidine sedation (stage 2), 10 minutes after dexmedetomidine sedation is finished and consciousness is restored (stage 3). Five emotionally neutral words are heard by the patients twice at each stage to assess the impact of sedation on memory consolidation. The patients repeat the memorized words after each audition. To assess the effect of sedation on the 'working memory', anesthesiologist asked the patient to remember and reproduce the memorized words five minutes after learning in the second stage. Approximately, 24 hours after the end of anesthesia, recall and recognition of the experimental words are tested. The number of words in recall and recognition testing is recorded by researcher.; Spinal anesthesia is performed by anesthesiologist. Memory testing is conducted immediately prior to operation (stage 1), 5-10 minutes after the start of operation (stage 2), 10 minutes before the end of operation (stage 3). Five emotionally neutral words are heard by the patients twice at each stage to assess the impact of sedation on memory consolidation. The patients repeat the memorized words after each audition. To assess the effect of sedation on the 'working memory', anesthesiologist asked the patient to remember and reproduce the memorized words five minutes after learning in the second stage. Approximately, 24 hours after the end of anesthesia, recall and recognition of the experimental words are tested. The number of words in recall and recognition testing is recorded by researcher.
Intervention MeSH terms: Dexmedetomidine; Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: sedation; Memory consolidation; Propofol; Dexmedetomidine