Sedation and Memory Consolidation

The Influence of Propofol and Dexmedetomidine Sedation on Memory Consolidation

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.

Study Overview

• Status: Completed
• Conditions: Memory Impairment; Amnesia; Recall; Recognition
• Intervention / Treatment: Drug: Influence of propofol sedation on memory consolidation and 'working memory'; Drug: Influence of dexmedetomidine sedation on memory consolidation and 'working memory'; Drug: Influence of spinal anesthesia on memory consolidation and 'working memory'

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• 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 and ≤70 years
• Elective trauma surgery (arthroscopy, reconstructive foot surgery) under regional anesthesia (spinal anesthesia) with propofol, dexmedetomidine or without sedation
• Montreal cognitive assessment test ≥ 26
• Patients with American Society of Anesthesiologists (ASA) I-II

Non-inclusion criteria:

• Not written informed consent to participate in the research and/or perform regional blockade
• Age˂18 and ˃70 years
• Allergy to propofol, dexmedetomidine, lidocaine, bupivacaine
• Pregnancy
• Epilepsy anamnesis
• II-III degree atrioventricular block
• Montreal cognitive assessment test ˂ 26
• Patients with American Society of Anesthesiologists (ASA) ˃ II
• Emergency operation
• The presence of psychiatric disorders
• Сancer patients with a life expectancy of less than two years
• Taking anticoagulants, psychotropic drugs

Exclusion Criteria:

• Patient refuse from further participation
• Ineffective spinal anesthesia
• Allergy on anesthesia drugs during perioperative period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: propofol group; patients with American Society of Anesthesiologists (ASA) I-II, Montreal cognitive assessment test≥26, trauma surgery under spinal anesthesia with propofol sedation	Drug: Influence of propofol sedation on memory consolidation and 'working memory'; 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.
Experimental: dexmedetomidine group; patients with American Society of Anesthesiologists (ASA) I-II, Montreal cognitive assessment test≥26, trauma surgery under spinal anesthesia with dexmedetomidine sedation	Drug: Influence of dexmedetomidine sedation on memory consolidation and 'working memory'; 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.
Placebo Comparator: control group; patients with American Society of Anesthesiologists (ASA) I-II, Montreal cognitive assessment test≥26, trauma surgery under spinal anesthesia without sedation	Drug: Influence of spinal anesthesia on memory consolidation and 'working memory'; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
memory consolidation impairment with propofol sedation	Memorizing emotionally neutral words before, during and after propofol sedation. Evaluation of recall and recognition of words 24 hours after anesthesia.	24 hours after the end of anesthesia
memory consolidation impairment with dexmedetomidine sedation	: Memorizing emotionally neutral words before, during and after dexmedetomidine sedation. Evaluation of recall and recognition of words 24 hours after anesthesia.	24 hours after the end of anesthesia
memory consolidation impairment without sedation	Memorizing emotionally neutral words before, during and after operation. Evaluation of recall and recognition of words 24 hours after anesthesia.	24 hours after the end of anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
'working memory' impairment with propofol sedation	Memorizing emotionally neutral words during propofol sedation (stage 2). Evaluation of remembering and reproducing of words five minutes after learning.	5 minutes after memorizing emotionally neutral words during propofol sedation
'working memory' impairment with dexmedetomidine sedation	Memorizing emotionally neutral words during dexmedetomidine sedation (stage 2). Evaluation of remembering and reproducing of words five minutes after learning.	5 minutes after memorizing emotionally neutral words during dexmedetomidine sedation
'working memory' impairment without sedation	Memorizing emotionally neutral words during operation (stage 2). Evaluation of remembering and reproducing of words five minutes after learning.	5 minutes after memorizing emotionally neutral words during operation

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University
• Investigators: Principal Investigator: Vyacheslav Churakov, PgS, I.M. Sechenov First Moscow State Medical University (Sechenov University)

Publications and helpful links

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2021
• Primary Completion (Actual): January 13, 2022
• Study Completion (Actual): January 13, 2022

Study Registration Dates

• First Submitted: September 6, 2021
• First Submitted That Met QC Criteria: September 6, 2021
• First Posted (Actual): September 16, 2021

Study Record Updates

• Last Update Posted (Actual): February 9, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Propofol; Dexmedetomidine; sedation; Memory consolidation
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Memory Disorders; Amnesia; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Propofol; Dexmedetomidine
• Other Study ID Numbers: 2107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: The data will become available 31.10.2021
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; 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