<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03791424</url>
  </required_header>
  <id_info>
    <org_study_id>Oxytocin01</org_study_id>
    <nct_id>NCT03791424</nct_id>
  </id_info>
  <brief_title>Changes of Skin Resistance After Midazolam and After the End of Anaesthesia</brief_title>
  <official_title>Changes of Skin Resistance After Midazolam and After the End of Anaesthesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Charles University, Czech Republic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Charles University, Czech Republic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      It has been described that sympathetic activity, measured as changes in electrical skin&#xD;
      resistance (SR), may be used to assess the adequacy of general anaesthesia. Our prospective&#xD;
      study investigated how far measurements of skin resistance can help determine level of&#xD;
      sedation. The secondary aim was to investigate if changes in skin resistance can be used for&#xD;
      assessing recovery from anaesthesia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction Before anaesthesia, benzodiazepines are routinely used to reduce anxiety before&#xD;
      anaesthesia and surgery. Usually anxiolysis is preferable to sedation, which may interfere&#xD;
      with recovery after short procedures. Unfortunately, although anxiolytic sedatives are widely&#xD;
      used in clinical practice, the methodology for assessing treatment effect of these compounds&#xD;
      has not been well developed. Psychologic tests like the Hamilton Anxiety Rating Scale (HARS),&#xD;
      the Wang Anxiety Rating Scale (WARS), or Zung Self-Rating Anxiety Scale (SAS) were used to&#xD;
      assess changes in anxiety were developed for measuring effect of long-term therapy and are&#xD;
      rather cumbersome and difficult to use in routine anaesthetic praxis.&#xD;
&#xD;
      More commonly used test in clinical perioperative use are the Ramsay sedation scale (RSS),&#xD;
      the Richmond Agitation-Sedation Scale (RASS) and the Observer's Assessment of Alertness and&#xD;
      Sedation scale (OAASS), but they focus mainly on level of sedation and not the level of&#xD;
      anxiolysis. There are several reports demonstrating that there is a correlation between level&#xD;
      of anxiety and changes in skin resistance.&#xD;
&#xD;
      Changes of skin resistance (SI) were first used in criminology in 1897 and in 1921 the method&#xD;
      was used in criminology by August Larson together with changes of heart rate, respiratory&#xD;
      rate and blood pressure for construction of polygraph. This method was many times validated&#xD;
      and polygraph is still used as a &quot;lie detector&quot;. More recently sever studies appeared&#xD;
      demonstrating correlation between changes of skin resistance and sedation grade, bispectral&#xD;
      index, reaction to stimulation, pain and motor activity.&#xD;
&#xD;
      The present double-blinded study was designed to refine methodology for objective evaluating&#xD;
      effect of sedative and anxiolytic agents. The primary aim of our study was to examine if of&#xD;
      changes in skin resistance after placebo pre-screening can be used for objective assessment&#xD;
      of an anxiolytic effect of drugs compared to commonly used subjective scales like Ramsay&#xD;
      sedation scale (RSS), or The Richmond Agitation-Sedation Scale (RASS) and Observer's&#xD;
      Assessment of Alertness and Sedation scale(OAASS). The secondary aim was to evaluate if&#xD;
      changes of skin resistance can be used for assessing recovery from anaesthesia.&#xD;
&#xD;
      Patients The study was performed in adult patients scheduled for knee arthroscopy or minor&#xD;
      plastic surgery under general anaesthesia. Consent was obtained the day before surgery during&#xD;
      pre-anaesthetic visit. Exclusion criteria were previous history of taking drugs affecting&#xD;
      mental functions, history of psychic illness, implanted electrical device, know allergy to&#xD;
      benzodiazepines, myasthenia gravis, ASA classification ASA 3 and more. All patients consented&#xD;
      not to use any medication for sedation or anxiety, opioid analgesics, ethanol and illicit&#xD;
      drugs 24 hours before surgery. Patients were instructed that they will be administered by a&#xD;
      random order first sedative agent or placebo and will be observed for their level of&#xD;
      sedation.&#xD;
&#xD;
      Measurements After arrival at the operating theatre, and venepuncture two standard AgCl ECG&#xD;
      electrodes (Medico Electrodes International ltd.) size 32 mm x 52 mm (27x35) were attached to&#xD;
      the palm side of the second and third finger of the non-dominating hand. Multimeter DM 3900&#xD;
      (Mastech) was used for measurements of SR. The device was controlled and approved for use in&#xD;
      humans by the Department of Medical Biophysics and Informatics of the 3rd Medical Faculty of&#xD;
      Charles University.&#xD;
&#xD;
      Observer's Assessment of Alertness and Sedation (OAAS) scale was used as a standard tool for&#xD;
      measurements of sedation level at the same intervals as measurements of SR. The person&#xD;
      providing OAAS assessment was blinded to the order of midazolam and placebo injection and&#xD;
      only the anaesthetist administering both injections knew the order of drugs.&#xD;
&#xD;
      Data recording Ten min. rest break was given to participants in order that they adapt to the&#xD;
      test situation. The rest value of SR was noticed and next all patients were administered&#xD;
      placebo first and after 5 min period midazolam 2 mg i.v. After next 5 minutes patients were&#xD;
      administered standard general anaesthesia with propofol, oxygen, nitrous oxide 60 % and&#xD;
      isoflurane 1 MAC via laryngeal mask and sufentanil as needed. Monitoring was standard for&#xD;
      this type of surgery (ECG, non-invasive blood pressure - NIBP, capnography and pulse&#xD;
      oximetry). SR and OASS were recorded again after stop of volatile anaesthetic agent till&#xD;
      opening eyes of the patient and obtaining verbal contact.&#xD;
&#xD;
      Statistical analysis SR values before placebo administration, 5 minutes after placebo, 5&#xD;
      minutes after midazolam, 5 min. after induction, at the end of surgery, 0 isoflurane level&#xD;
      after anaesthesia with closed eyes and after eyes opening were recorded. Changes in SR values&#xD;
      compared to baseline data were used for analyses by paired t-test. These relative changes&#xD;
      enabled to compare only the course of changes independently of different absolute values.&#xD;
      Pearson´s correlation coefficients were used to analyse relationship between OASS and SR&#xD;
      values. P-value &lt; 0.05 was considered statistically significant.&#xD;
&#xD;
      The primary aim of our study was to assess if SR can be used as an objective measurement of&#xD;
      level of sedation compared to much or less subjective OAAS. OASS was chosen because scoring&#xD;
      was originally introduced to assess sedation with benzodiazepines, which was used in our&#xD;
      study, too. The categories were responsiveness, speech, facial expression and eye appearance&#xD;
      and each category was originally scored in 5 dimensions. The OAAS scale was found to have a&#xD;
      high discriminatory power for the different levels of sedation (3), but may vary between&#xD;
      observers. There is a limited number of methods for assessment onset and intensity of&#xD;
      sedation. Commonly used Bispectral Index Score (BIS) monitoring is not dependent on a person&#xD;
      and is used mainly during general anaesthesia. On the other hand the authors of a large&#xD;
      meta-analysis concluded that its use for sedation in largely unreliable.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2014</start_date>
  <completion_date type="Actual">June 26, 2015</completion_date>
  <primary_completion_date type="Actual">June 26, 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Multimeter DM 3900 was used for measurements of SR. The device was approved for use in humans by the Department of Medical Biophysics and Informatics of the 3rd Medical Faculty of Charles University. Observer's Assessment of Alertness and Sedation scale was used as a standard tool for measurements of sedation level at the same intervals as measurements of SR. 10 min. rest break was given to participants in order that they adapt to the test situation. The rest value of SR was noticed and next all patients were administered placebo first and after 5 min period midazolam 2 mg i.v. After next 5 minutes patients were administered standard general anaesthesia with propofol, oxygen, nitrous oxide 60 % and isoflurane 1 MAC via laryngeal mask and sufentanil as needed. Changes in skin resistance were measured again immediately after stop of volatile anaesthetics till eye opening and verbal contact.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Placebo of the same volume and colour as active substance</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Changes of skin resistence (percent from base-line values measured in ohms) during sedation</measure>
    <time_frame>10 min. before administration and 5 min. after administration of midazolam (total 15 min.)</time_frame>
    <description>Investigation how far measurements of skin resistance can help determine level of sedation induced by intravenous midazolam</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes of skin resistence (percent from base-line values and values before termination of inhalational agent administration measured in ohms) during recovery from anaesthesia</measure>
    <time_frame>From termination of inhalational agent administration till recovery to verbal comunication (expected time max. 15 min)</time_frame>
    <description>Investigation how far measurements of skin resistance can help determine level of recovery from general anaesthesia</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Anesthesia</condition>
  <arm_group>
    <arm_group_label>Midazolam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Midazolam 2 mg was administered 5 min. after placebo and 5 min. before inducton to general anaesthesia IV.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline 5 ml was administered 10 min. after insertion of intravenous cannula IV..</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>Administering premedication with sedative drug to relieve anxiety</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Midazolam</arm_group_label>
    <other_name>Sedation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adult patients scheduled for knee arthroscopy or minor plastic surgery under general&#xD;
             anaesthesia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous history of taking drugs affecting mental functions, history of psychic&#xD;
             illness, implanted electrical device, know allergy to benzodiazepines, myasthenia&#xD;
             gravis, ASA classification ASA 3 and more. All patients consented not to use any&#xD;
             medication for sedation or anxiety, opioid analgesics, ethanol and illicit drugs 24&#xD;
             hours before surgery.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jiri Malek, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Kralovske Vinohrady</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alice Kurzova, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>University Hospital Kralovske Vinohrady</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Kralovske Vinohrady</name>
      <address>
        <city>Praha</city>
        <zip>100 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>September 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>December 31, 2018</last_update_submitted>
  <last_update_submitted_qc>December 31, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Charles University, Czech Republic</investigator_affiliation>
    <investigator_full_name>Jiri Malek</investigator_full_name>
    <investigator_title>Assoc. Prfo. Jiri Malek, CSc.</investigator_title>
  </responsible_party>
  <keyword>sedation</keyword>
  <keyword>midazolam</keyword>
  <keyword>skin resistance</keyword>
  <keyword>measurements</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03791424
org study id: Oxytocin01
nct id: NCT03791424
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
It has been described that sympathetic activity, measured as changes in electrical skin
      resistance (SR), may be used to assess the adequacy of general anaesthesia. Our prospective
      study investigated how far measurements of skin resistance can help determine level of
      sedation. The secondary aim was to investigate if changes in skin resistance can be used for
      assessing recovery from anaesthesia.
Introduction Before anaesthesia, benzodiazepines are routinely used to reduce anxiety before
      anaesthesia and surgery. Usually anxiolysis is preferable to sedation, which may interfere
      with recovery after short procedures. Unfortunately, although anxiolytic sedatives are widely
      used in clinical practice, the methodology for assessing treatment effect of these compounds
      has not been well developed. Psychologic tests like the Hamilton Anxiety Rating Scale (HARS),
      the Wang Anxiety Rating Scale (WARS), or Zung Self-Rating Anxiety Scale (SAS) were used to
      assess changes in anxiety were developed for measuring effect of long-term therapy and are
      rather cumbersome and difficult to use in routine anaesthetic praxis.

      More commonly used test in clinical perioperative use are the Ramsay sedation scale (RSS),
      the Richmond Agitation-Sedation Scale (RASS) and the Observer's Assessment of Alertness and
      Sedation scale (OAASS), but they focus mainly on level of sedation and not the level of
      anxiolysis. There are several reports demonstrating that there is a correlation between level
      of anxiety and changes in skin resistance.

      Changes of skin resistance (SI) were first used in criminology in 1897 and in 1921 the method
      was used in criminology by August Larson together with changes of heart rate, respiratory
      rate and blood pressure for construction of polygraph. This method was many times validated
      and polygraph is still used as a "lie detector". More recently sever studies appeared
      demonstrating correlation between changes of skin resistance and sedation grade, bispectral
      index, reaction to stimulation, pain and motor activity.

      The present double-blinded study was designed to refine methodology for objective evaluating
      effect of sedative and anxiolytic agents. The primary aim of our study was to examine if of
      changes in skin resistance after placebo pre-screening can be used for objective assessment
      of an anxiolytic effect of drugs compared to commonly used subjective scales like Ramsay
      sedation scale (RSS), or The Richmond Agitation-Sedation Scale (RASS) and Observer's
      Assessment of Alertness and Sedation scale(OAASS). The secondary aim was to evaluate if
      changes of skin resistance can be used for assessing recovery from anaesthesia.

      Patients The study was performed in adult patients scheduled for knee arthroscopy or minor
      plastic surgery under general anaesthesia. Consent was obtained the day before surgery during
      pre-anaesthetic visit. Exclusion criteria were previous history of taking drugs affecting
      mental functions, history of psychic illness, implanted electrical device, know allergy to
      benzodiazepines, myasthenia gravis, ASA classification ASA 3 and more. All patients consented
      not to use any medication for sedation or anxiety, opioid analgesics, ethanol and illicit
      drugs 24 hours before surgery. Patients were instructed that they will be administered by a
      random order first sedative agent or placebo and will be observed for their level of
      sedation.

      Measurements After arrival at the operating theatre, and venepuncture two standard AgCl ECG
      electrodes (Medico Electrodes International ltd.) size 32 mm x 52 mm (27x35) were attached to
      the palm side of the second and third finger of the non-dominating hand. Multimeter DM 3900
      (Mastech) was used for measurements of SR. The device was controlled and approved for use in
      humans by the Department of Medical Biophysics and Informatics of the 3rd Medical Faculty of
      Charles University.

      Observer's Assessment of Alertness and Sedation (OAAS) scale was used as a standard tool for
      measurements of sedation level at the same intervals as measurements of SR. The person
      providing OAAS assessment was blinded to the order of midazolam and placebo injection and
      only the anaesthetist administering both injections knew the order of drugs.

      Data recording Ten min. rest break was given to participants in order that they adapt to the
      test situation. The rest value of SR was noticed and next all patients were administered
      placebo first and after 5 min period midazolam 2 mg i.v. After next 5 minutes patients were
      administered standard general anaesthesia with propofol, oxygen, nitrous oxide 60 % and
      isoflurane 1 MAC via laryngeal mask and sufentanil as needed. Monitoring was standard for
      this type of surgery (ECG, non-invasive blood pressure - NIBP, capnography and pulse
      oximetry). SR and OASS were recorded again after stop of volatile anaesthetic agent till
      opening eyes of the patient and obtaining verbal contact.

      Statistical analysis SR values before placebo administration, 5 minutes after placebo, 5
      minutes after midazolam, 5 min. after induction, at the end of surgery, 0 isoflurane level
      after anaesthesia with closed eyes and after eyes opening were recorded. Changes in SR values
      compared to baseline data were used for analyses by paired t-test. These relative changes
      enabled to compare only the course of changes independently of different absolute values.
      Pearson´s correlation coefficients were used to analyse relationship between OASS and SR
      values. P-value < 0.05 was considered statistically significant.

      The primary aim of our study was to assess if SR can be used as an objective measurement of
      level of sedation compared to much or less subjective OAAS. OASS was chosen because scoring
      was originally introduced to assess sedation with benzodiazepines, which was used in our
      study, too. The categories were responsiveness, speech, facial expression and eye appearance
      and each category was originally scored in 5 dimensions. The OAAS scale was found to have a
      high discriminatory power for the different levels of sedation (3), but may vary between
      observers. There is a limited number of methods for assessment onset and intensity of
      sedation. Commonly used Bispectral Index Score (BIS) monitoring is not dependent on a person
      and is used mainly during general anaesthesia. On the other hand the authors of a large
      meta-analysis concluded that its use for sedation in largely unreliable.
allocation: Non-Randomized
intervention model: Crossover Assignment
intervention model description: Multimeter DM 3900 was used for measurements of SR. The device was approved for use in humans by the Department of Medical Biophysics and Informatics of the 3rd Medical Faculty of Charles University. Observer's Assessment of Alertness and Sedation scale was used as a standard tool for measurements of sedation level at the same intervals as measurements of SR. 10 min. rest break was given to participants in order that they adapt to the test situation. The rest value of SR was noticed and next all patients were administered placebo first and after 5 min period midazolam 2 mg i.v. After next 5 minutes patients were administered standard general anaesthesia with propofol, oxygen, nitrous oxide 60 % and isoflurane 1 MAC via laryngeal mask and sufentanil as needed. Changes in skin resistance were measured again immediately after stop of volatile anaesthetics till eye opening and verbal contact.
primary purpose: Diagnostic
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Placebo of the same volume and colour as active substance
measure: Changes of skin resistence (percent from base-line values measured in ohms) during sedation
time frame: 10 min. before administration and 5 min. after administration of midazolam (total 15 min.)
description: Investigation how far measurements of skin resistance can help determine level of sedation induced by intravenous midazolam
measure: Changes of skin resistence (percent from base-line values and values before termination of inhalational agent administration measured in ohms) during recovery from anaesthesia
time frame: From termination of inhalational agent administration till recovery to verbal comunication (expected time max. 15 min)
description: Investigation how far measurements of skin resistance can help determine level of recovery from general anaesthesia
arm group label: Midazolam
arm group type: Experimental
description: Midazolam 2 mg was administered 5 min. after placebo and 5 min. before inducton to general anaesthesia IV.
arm group label: Control
arm group type: Placebo Comparator
description: Normal saline 5 ml was administered 10 min. after insertion of intravenous cannula IV..
intervention type: Drug
intervention name: Midazolam
description: Administering premedication with sedative drug to relieve anxiety
arm group label: Control
arm group label: Midazolam
other name: Sedation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jiri Malek, M.D.
role: Principal Investigator
affiliation: University Hospital Kralovske Vinohrady
last name: Alice Kurzova, M.D.
role: Study Chair
affiliation: University Hospital Kralovske Vinohrady
facility: 
country: Czechia
responsible party type: Principal Investigator
investigator affiliation: Charles University, Czech Republic
investigator full name: Jiri Malek
investigator title: Assoc. Prfo. Jiri Malek, CSc.
mesh term: Midazolam
sharing ipd: No