<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/NCT03284307</url>
  </required_header>
  <id_info>
    <org_study_id>2015-1399</org_study_id>
    <secondary_id>A530900</secondary_id>
    <secondary_id>SMPH\ANESTHESIOLOGY\ANESTHESIO</secondary_id>
    <secondary_id>Protocol Version 10/18/2019</secondary_id>
    <nct_id>NCT03284307</nct_id>
  </id_info>
  <brief_title>UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study</brief_title>
  <acronym>UN-CONSCIOUS</acronym>
  <official_title>UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Wisconsin, Madison</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will be a single-site, controlled, unblinded study at the University of Wisconsin&#xD;
      to examine changes in the electroencephalogram during anesthesia and waking.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      * 20 subjects will be recruited per drug, and subjects can be recruited to undergo multiple&#xD;
      sedation protocols.&#xD;
&#xD;
      Screening:&#xD;
&#xD;
      Subjects will respond to the volunteer posts for the study by calling into a study specific&#xD;
      phone number. They will complete a phone screening to determine basic eligibility for the&#xD;
      study. At the beginning of the sedation session, participants will affirm that in the&#xD;
      interval since their baseline visit, they have not acquired any of the cited exclusion&#xD;
      criteria that would preclude participation. A review of these exclusion criteria will be&#xD;
      completed by the Anesthesiologist. A standard pre-anesthetic assessment will be performed,&#xD;
      including confirmation of NPO status, and documented using the standard Department of&#xD;
      Anesthesiology pre-operative evaluation form.&#xD;
&#xD;
      The first sedative will be dexmedetomidine followed by ketamine, propofol and then midazolam&#xD;
      (dependent on the availability of the drugs). Total enrollment in the study will be up to 80&#xD;
      subjects. Each sedation experiment will occur on separate days at least 28 days apart, if the&#xD;
      subject chooses to participate in more than one session.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 10, 2017</start_date>
  <completion_date type="Actual">March 12, 2020</completion_date>
  <primary_completion_date type="Actual">March 12, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occipital Delta Power Spectral Density by Conscious State and Study Group.</measure>
    <time_frame>Intraoperative (During sedation-- up to 8 hours)</time_frame>
    <description>The difference in spontaneous EEG slow wave activity over posterior cortex between states of consciousness measured with high-density EEG equipment and reported in spectral power in the delta band (1-4 Hz) at electrode Oz. Disconnected conscious experience (dreaming), connected conscious experience (awareness of the external world), and unconsciousness (no report) was assessed when participants were roused from sedation or sleep.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Instances of Disconnected Conscious Experience (Dreaming) vs Connected Conscious Experience (Awareness of External World).</measure>
    <time_frame>Intraoperative (During sedation-- up to 8 hours)</time_frame>
    <description>The number of instances of disconnected conscious experience (dreaming) versus connected conscious experience (awareness of the external world) during sedation is measured by subject self-report at the time of researcher initiated inquiry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of Study Drug on Ability to Correctly Identify Shapes/Images</measure>
    <time_frame>Intraoperative (During sedation-- up to 8 hours)</time_frame>
    <description>The ability to identify shapes/images in visual illusions measured by the NIH Toolbox. Will be reported by a computed score from NIH Toolbox for the Dimensional Change Card Sort Test (DCCS) and the Flanker Inhibitory Control &amp; Attention Test (Flanker). Both Flanker and DCCS use a 2-vector scoring method that takes accuracy and reaction time (if accuracy &gt;=80%) into account, resulting in a computed score that can range in value from 0-10. A higher score indicates better performance on the test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of Study Drug on Ability to Correctly Identify Images</measure>
    <time_frame>Intraoperative (During sedation-- up to 8 hours)</time_frame>
    <description>The ability to match sounds and images measured by the predictive coding task. Will be reported by a proportion correct as a decimal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of Study Drug on Ability to Form Implicit Memory</measure>
    <time_frame>Intraoperative (During sedation-- up to 8 hours)</time_frame>
    <description>Subjects will have a list of words read to them while under sedation and their ability to hear these words and form implicit memories of them will be assessed using a two-alternative forced choice task. Results will be reported as the average number of correct responses out of sixteen.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Unconsciousness</condition>
  <condition>Consciousness</condition>
  <arm_group>
    <arm_group_label>Drug Administrated</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sedatives will be administered to participants while their brain activity is measured.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmedetomidine</intervention_name>
    <description>20 participants will be administered Dexmedetomidine.</description>
    <arm_group_label>Drug Administrated</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>20 participants will be administered Ketamine.</description>
    <arm_group_label>Drug Administrated</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>20 participants will be administered Propofol.</description>
    <arm_group_label>Drug Administrated</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>20 participants will be administered Midazolam.</description>
    <arm_group_label>Drug Administrated</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-40&#xD;
&#xD;
          -  In good health, determined by the PI on the basis of medical history and a standard&#xD;
             assessment for anesthesia to be documented as part of the study record&#xD;
&#xD;
          -  Right handed, to standardize for asymmetry in brain functions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Adults &lt;18 years old or &gt;40 years old&#xD;
&#xD;
          -  Pregnancy confirmed on pregnancy test on day of sedation&#xD;
&#xD;
          -  Contraindication to anesthesia or allergy to study drug&#xD;
&#xD;
          -  Difficult anesthesia: American Society of Anesthesiologists Physical Status greater&#xD;
             than 1, per the discretion of the PI. Examples of ASA status include, but are not&#xD;
             limited to:&#xD;
&#xD;
               -  Any systemic disease present, such as diabetes, cardiac, pulmonary, or other&#xD;
                  acute or chronic disorder, or history of smoking&#xD;
&#xD;
               -  Narrow angle glaucoma&#xD;
&#xD;
               -  Abnormal airway examination&#xD;
&#xD;
               -  Any abnormality on medical history and physical examination&#xD;
&#xD;
               -  Snoring or sleep disorders including apnea&#xD;
&#xD;
               -  Antecedent pulmonary aspiration risk (e.g., history GI reflux, heartburn, hiatal&#xD;
                  hernia)&#xD;
&#xD;
               -  Adverse reaction or allergy with anesthesia or other sedatives&#xD;
&#xD;
               -  Chronic medication use&#xD;
&#xD;
               -  History of difficult anesthesia, laryngoscopy or intubation&#xD;
&#xD;
               -  Family history of difficulty with anesthesia or sedation&#xD;
&#xD;
               -  History of vertigo, nausea or vomiting after anesthesia&#xD;
&#xD;
          -  BMI &gt; 35&#xD;
&#xD;
          -  Contraindication to HD-EEG, TMS or MRI for relative parts of the procedures. MRI&#xD;
             exclusion criteria: presence of metallic or electronic implants; history of&#xD;
             claustrophobia. TMS exclusion criteria: Presence or history of medical conditions that&#xD;
             could increase the chance of seizures (e.g. - stroke, aneurysm, brain surgery,&#xD;
             structural brain lesion) cranial metal implants; structural brain lesion; devices that&#xD;
             may be affected by TMS (pacemaker, medication pump, cochlear implant, implanted brain&#xD;
             stimulator); history of head trauma with loss of consciousness for greater than 5&#xD;
             minutes; family history of seizures; history of antecedent mood disorder.&#xD;
&#xD;
          -  Exclusion from Dexmedetomidine:&#xD;
&#xD;
             o Resting heart Rate&lt;60 bpm&#xD;
&#xD;
          -  Exclusion from Propofol:&#xD;
&#xD;
             o Reported egg allergy&#xD;
&#xD;
          -  Exclusion from Ketamine:&#xD;
&#xD;
               -  History of post-operative nausea and vomiting&#xD;
&#xD;
               -  History of motion sickness&#xD;
&#xD;
        Additional exclusion criteria on the day of sedation:&#xD;
&#xD;
          -  Anything to eat or drink for the preceding 8 hours&#xD;
&#xD;
          -  Any use of over-the-counter or recreational drugs (including alcohol or tobacco)&#xD;
             within the preceding 24 hours&#xD;
&#xD;
          -  Any use of sedative or sleep agents within the preceding 24 hours&#xD;
&#xD;
          -  Recent change in health, including cough, cold, or fever&#xD;
&#xD;
          -  Exposure to anesthesia or sedation in the last 6 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert A Pearce, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor and chair of Anesthesiology at UW- Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UW Hospital and Clinics</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <results_first_submitted>October 3, 2022</results_first_submitted>
  <results_first_submitted_qc>March 15, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">April 10, 2023</results_first_posted>
  <last_update_submitted>April 10, 2023</last_update_submitted>
  <last_update_submitted_qc>April 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sedation</keyword>
  <keyword>Propofol</keyword>
  <keyword>Dexmedetomidine</keyword>
  <keyword>Ketamine</keyword>
  <keyword>Sevoflurane</keyword>
  <keyword>Electroencephalogram</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Unconsciousness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Dexmedetomidine</mesh_term>
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Propofol</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 11, 2023</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03284307/Prot_SAP_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 15, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/07/NCT03284307/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited via an email that was sent to UW-Madison students and staff from August 2017 through March 2020. Interested participants would discuss study commitment and preliminary screening criteria with the study team over the phone. Eligible participants would meet with a faculty anesthesiologist at a screening visit to complete informed consent and for a history and physical examination and basic neuropsychological assessment to determine subsequent study visit eligibility.</recruitment_details>
      <pre_assignment_details>Participants were assigned to a drug if they were both eligible and reconsented the morning of the visit. Drug visits occurred in a sequence: Dexmedetomidine, Ketamine, Propofol, and then Midazolam. The same participant could participate in all drug visits if they were eligible, and a minimum of 28 days had past since their previous drug visit. All participants interested in a drug visit were asked to also complete a sleep visit which occurred before the first drug visit if possible.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Study Participants</title>
          <description>Participants completed sedation visits in the order of dexmedetomidine, ketamine, propofol, and midazolam. There was a washout period of at least 28 days between sedation visits. Subjects were also asked to complete a separate overnight sleep visit with an EEG. Participants reconsented at each sleep and sedation visit. If a patient was inappropriate for one sedative, due to a specific contraindication to that drug (and not the study in general) but were eligible for another drug, then they progressed through the order of sedatives while skipping that inappropriate drug.&#xD;
At each drug visit, participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Sedation and/or Sleep Visit</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Completed Sedation Visit</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Sleep</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Dexmedetomidine</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Ketamine</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Propofol</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Midazolam</title>
              <participants_list>
                <participants group_id="P1" count="0">No midazolam visit was ever conducted because no interested participants had reached that step of the drug sequence after it was added to the protocol in November of 2019.This was in large part due to the shutdown of in-person research activities in March of 2020 from the COVID-19 pandemic.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All participants who completed a sleep and/or sedation visit.</population>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>Participants completed sedation visits in the order of dexmedetomidine, ketamine, propofol, and midazolam. There was a washout period of at least 28 days between sedation visits. Subjects were also asked to complete a separate overnight sleep visit with an EEG. Participants reconsented at each sleep and sedation visit. If a patient was inappropriate for one sedative, due to a specific contraindication to that drug (and not the study in general) but were eligible for another drug, then they progressed through the order of sedatives while skipping that inappropriate drug.&#xD;
At each drug visit, participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>Number analyzed for each row is the number of participants who completed that visit.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Total</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.44" spread="4.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25.13" spread="5.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dexmedetomidine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.95" spread="3.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ketamine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21.47" spread="3.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Propofol</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.83" spread="4.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Midazolam</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <population>Number analyzed for each row is the number of participants who completed that visit.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Total</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dexmedetomidine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ketamine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Propofol</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Midazolam</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                </category>
                <category>
                  <title>Male</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <population>Number analyzed for each row is the number of participants who completed that visit.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Total</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dexmedetomidine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ketamine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Propofol</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Midazolam</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>Number analyzed for each row is the number of participants who completed that visit.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Total</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Dexmedetomidine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ketamine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Propofol</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Midazolam</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                </category>
                <category>
                  <title>Asian</title>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                </category>
                <category>
                  <title>Black or African American</title>
                </category>
                <category>
                  <title>White</title>
                </category>
                <category>
                  <title>More than one race</title>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Occipital Delta Power Spectral Density by Conscious State and Study Group.</title>
        <description>The difference in spontaneous EEG slow wave activity over posterior cortex between states of consciousness measured with high-density EEG equipment and reported in spectral power in the delta band (1-4 Hz) at electrode Oz. Disconnected conscious experience (dreaming), connected conscious experience (awareness of the external world), and unconsciousness (no report) was assessed when participants were roused from sedation or sleep.</description>
        <time_frame>Intraoperative (During sedation-- up to 8 hours)</time_frame>
        <population>No midazolam visit was ever conducted because no interested participants had reached that step of the drug sequence after it was added to the protocol in November of 2019.This was in large part due to the shutdown of in-person research activities in March of 2020 from the COVID-19 pandemic.</population>
        <group_list>
          <group group_id="O1">
            <title>Dexmedetomidine</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Dexmedetomidine-specific activities: Rapid infusion of 3.0 mg kg-1 h-1 was administered over a 10 min period followed by a 0.5 mg kg-1 h-1 maintenance infusion to achieve the first drug step. The second drug step was similarly achieved by a 10 min infusion of 3.0 mg kg-1 h-1 followed by a 1.5 mg kg-1 h-1 maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O2">
            <title>Ketamine</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Ketamine-specific activities: Ketamine was titrated using up to a 4.5mg/kg bolus over 10 minutes followed by 0.1-0.5mg/min intravenous infusion with 5 minutes between increments and titrated to desired observed alertness/sedation level. This infusion rate may be slowed further or stopped for patient safety concerns. Infusion rates will be adjusted using information from the target-controlled infusion model clinical judgment. Short-lived emergence delirium (confusion on awakening) may occur on emergence from ketamine anesthesia and this will be managed through standard clinical practice including administration of midazolam (up to 4mg IV) if required. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O3">
            <title>Propofol</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Propofol-specific activities: A target-controlled infusion model used to predict plasma concentrations of propofol at 0.5 mcg/mL increments allowing 5-minutes to equilibrate between any step change. Dosing will be confined to FDA approved limits with up to a 2.5mg/kg bolus over 1 to 3 minute followed by an infusion of 50-200mcg/kg/min titrated to the desired observed alertness/sedation levels. Drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O4">
            <title>Midazolam</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Midazolam-specific activities: Initial boluses of up to 0.35mg/kg followed by doses up to 0.1mg/kg/h as a maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O5">
            <title>Sleep</title>
            <description>Participants were fitted with a saline gel EEG cap and a pre-sleep recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. After the pre-sleep recording, participants laid down within 30 minutes of their usual bedtime and were left to sleep for 2-3 hours. After this period, the participant was woken up every 15-30 minutes to answer standardized wake report form questions. After awaking a final time, the participant repeated 10 minutes of awake eyes open and eyes closed recordings as well as the predictive coding cognitive task on a computer.</description>
          </group>
        </group_list>
        <measure>
          <title>Occipital Delta Power Spectral Density by Conscious State and Study Group.</title>
          <description>The difference in spontaneous EEG slow wave activity over posterior cortex between states of consciousness measured with high-density EEG equipment and reported in spectral power in the delta band (1-4 Hz) at electrode Oz. Disconnected conscious experience (dreaming), connected conscious experience (awareness of the external world), and unconsciousness (no report) was assessed when participants were roused from sedation or sleep.</description>
          <population>No midazolam visit was ever conducted because no interested participants had reached that step of the drug sequence after it was added to the protocol in November of 2019.This was in large part due to the shutdown of in-person research activities in March of 2020 from the COVID-19 pandemic.</population>
          <units>log10(μV^2)</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Connected Consciousness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.37" lower_limit="2.31" upper_limit="2.46"/>
                    <measurement group_id="O2" value="1.62" lower_limit="1.57" upper_limit="1.68"/>
                    <measurement group_id="O3" value="2.05" lower_limit="1.94" upper_limit="2.15"/>
                    <measurement group_id="O5" value="2.1" lower_limit="2.03" upper_limit="2.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Disconnected Consciousness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.57" lower_limit="2.53" upper_limit="2.61"/>
                    <measurement group_id="O2" value="1.7" lower_limit="1.57" upper_limit="1.84"/>
                    <measurement group_id="O3" value="2.34" lower_limit="2.22" upper_limit="2.5"/>
                    <measurement group_id="O5" value="2.58" lower_limit="2.52" upper_limit="2.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unconsciousness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.68" lower_limit="2.61" upper_limit="2.75"/>
                    <measurement group_id="O2" value="1.46" lower_limit="1.16" upper_limit="1.83"/>
                    <measurement group_id="O3" value="2.51" lower_limit="2.31" upper_limit="2.68"/>
                    <measurement group_id="O5" value="2.63" lower_limit="2.47" upper_limit="2.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Dexmedetomidine, Unconsciousness vs Disconnected Consciousness</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.012</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>0.110</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.043</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Estimate is a slope from a linear mixed effects model representing the difference in occipital delta power between unconsciousness and disconnected consciousness after adjusting for within-subject effects.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Ketamine, Unconsciousness vs Disconnected Consciousness</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.236</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>-0.238</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.199</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Estimate is a slope from a linear mixed effects model representing the difference in occipital delta power between unconsciousness and disconnected consciousness after adjusting for within-subject effects.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Propofol, Unconsciousness vs Disconnected Consciousness</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.174</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>0.166</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.120</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Estimate is a slope from a linear mixed effects model representing the difference in occipital delta power between unconsciousness and disconnected consciousness after adjusting for within-subject effects.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O5</group_id>
            </group_id_list>
            <groups_desc>Sleep, Unconsciousness vs Disconnected Consciousness</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.640</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>Mixed Models Analysis</method>
            <param_type>Slope</param_type>
            <param_value>0.052</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.111</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <estimate_desc>Estimate is a slope from a linear mixed effects model representing the difference in occipital delta power between unconsciousness and disconnected consciousness after adjusting for within-subject effects.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Instances of Disconnected Conscious Experience (Dreaming) vs Connected Conscious Experience (Awareness of External World).</title>
        <description>The number of instances of disconnected conscious experience (dreaming) versus connected conscious experience (awareness of the external world) during sedation is measured by subject self-report at the time of researcher initiated inquiry.</description>
        <time_frame>Intraoperative (During sedation-- up to 8 hours)</time_frame>
        <population>There was no data collected for Midazolam or Sleep for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Dexmedetomidine</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Dexmedetomidine-specific activities: Rapid infusion of 3.0 mg kg-1 h-1 was administered over a 10 min period followed by a 0.5 mg kg-1 h-1 maintenance infusion to achieve the first drug step. The second drug step was similarly achieved by a 10 min infusion of 3.0 mg kg-1 h-1 followed by a 1.5 mg kg-1 h-1 maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O2">
            <title>Ketamine</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Ketamine-specific activities: Ketamine was titrated using up to a 4.5mg/kg bolus over 10 minutes followed by 0.1-0.5mg/min intravenous infusion with 5 minutes between increments and titrated to desired observed alertness/sedation level. This infusion rate may be slowed further or stopped for patient safety concerns. Infusion rates will be adjusted using information from the target-controlled infusion model clinical judgment. Short-lived emergence delirium (confusion on awakening) may occur on emergence from ketamine anesthesia and this will be managed through standard clinical practice including administration of midazolam (up to 4mg IV) if required. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O3">
            <title>Propofol</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Propofol-specific activities: A target-controlled infusion model used to predict plasma concentrations of propofol at 0.5 mcg/mL increments allowing 5-minutes to equilibrate between any step change. Dosing will be confined to FDA approved limits with up to a 2.5mg/kg bolus over 1 to 3 minute followed by an infusion of 50-200mcg/kg/min titrated to the desired observed alertness/sedation levels. Drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O4">
            <title>Midazolam</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Midazolam-specific activities: Initial boluses of up to 0.35mg/kg followed by doses up to 0.1mg/kg/h as a maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O5">
            <title>Sleep</title>
            <description>Participants were fitted with a saline gel EEG cap and a pre-sleep recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. After the pre-sleep recording, participants laid down within 30 minutes of their usual bedtime and were left to sleep for 2-3 hours. After this period, the participant was woken up every 15-30 minutes to answer standardized wake report form questions. After awaking a final time, the participant repeated 10 minutes of awake eyes open and eyes closed recordings as well as the predictive coding cognitive task on a computer.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Instances of Disconnected Conscious Experience (Dreaming) vs Connected Conscious Experience (Awareness of External World).</title>
          <description>The number of instances of disconnected conscious experience (dreaming) versus connected conscious experience (awareness of the external world) during sedation is measured by subject self-report at the time of researcher initiated inquiry.</description>
          <population>There was no data collected for Midazolam or Sleep for this outcome measure.</population>
          <units>number of instances</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Instances of Connected Consciousness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70"/>
                    <measurement group_id="O2" value="180"/>
                    <measurement group_id="O3" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Instances of Disconnected Consciousness</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="226"/>
                    <measurement group_id="O2" value="30"/>
                    <measurement group_id="O3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Effect of Study Drug on Ability to Correctly Identify Shapes/Images</title>
        <description>The ability to identify shapes/images in visual illusions measured by the NIH Toolbox. Will be reported by a computed score from NIH Toolbox for the Dimensional Change Card Sort Test (DCCS) and the Flanker Inhibitory Control &amp; Attention Test (Flanker). Both Flanker and DCCS use a 2-vector scoring method that takes accuracy and reaction time (if accuracy &gt;=80%) into account, resulting in a computed score that can range in value from 0-10. A higher score indicates better performance on the test.</description>
        <time_frame>Intraoperative (During sedation-- up to 8 hours)</time_frame>
        <population>No data was collected for this outcome measure for Midazolam or Sleep</population>
        <group_list>
          <group group_id="O1">
            <title>Dexmedetomidine</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Dexmedetomidine-specific activities: Rapid infusion of 3.0 mg kg-1 h-1 was administered over a 10 min period followed by a 0.5 mg kg-1 h-1 maintenance infusion to achieve the first drug step. The second drug step was similarly achieved by a 10 min infusion of 3.0 mg kg-1 h-1 followed by a 1.5 mg kg-1 h-1 maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O2">
            <title>Ketamine</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Ketamine-specific activities: Ketamine was titrated using up to a 4.5mg/kg bolus over 10 minutes followed by 0.1-0.5mg/min intravenous infusion with 5 minutes between increments and titrated to desired observed alertness/sedation level. This infusion rate may be slowed further or stopped for patient safety concerns. Infusion rates will be adjusted using information from the target-controlled infusion model clinical judgment. Short-lived emergence delirium (confusion on awakening) may occur on emergence from ketamine anesthesia and this will be managed through standard clinical practice including administration of midazolam (up to 4mg IV) if required. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O3">
            <title>Propofol</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Propofol-specific activities: A target-controlled infusion model used to predict plasma concentrations of propofol at 0.5 mcg/mL increments allowing 5-minutes to equilibrate between any step change. Dosing will be confined to FDA approved limits with up to a 2.5mg/kg bolus over 1 to 3 minute followed by an infusion of 50-200mcg/kg/min titrated to the desired observed alertness/sedation levels. Drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O4">
            <title>Midazolam</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Midazolam-specific activities: Initial boluses of up to 0.35mg/kg followed by doses up to 0.1mg/kg/h as a maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O5">
            <title>Sleep</title>
            <description>Participants were fitted with a saline gel EEG cap and a pre-sleep recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. After the pre-sleep recording, participants laid down within 30 minutes of their usual bedtime and were left to sleep for 2-3 hours. After this period, the participant was woken up every 15-30 minutes to answer standardized wake report form questions. After awaking a final time, the participant repeated 10 minutes of awake eyes open and eyes closed recordings as well as the predictive coding cognitive task on a computer.</description>
          </group>
        </group_list>
        <measure>
          <title>Effect of Study Drug on Ability to Correctly Identify Shapes/Images</title>
          <description>The ability to identify shapes/images in visual illusions measured by the NIH Toolbox. Will be reported by a computed score from NIH Toolbox for the Dimensional Change Card Sort Test (DCCS) and the Flanker Inhibitory Control &amp; Attention Test (Flanker). Both Flanker and DCCS use a 2-vector scoring method that takes accuracy and reaction time (if accuracy &gt;=80%) into account, resulting in a computed score that can range in value from 0-10. A higher score indicates better performance on the test.</description>
          <population>No data was collected for this outcome measure for Midazolam or Sleep</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="2"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline NIH Toolbox Card Sorting Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.83" spread="1.21"/>
                    <measurement group_id="O2" value="9.29" spread="0.59"/>
                    <measurement group_id="O3" value="9.45" spread="0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sedation NIH Toolbox Card Sorting Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.85" spread="1.49"/>
                    <measurement group_id="O2" value="8.2" spread="0.99"/>
                    <measurement group_id="O3" value="6.94" spread="4.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline NIH Toolbox Flanker Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.14" spread="0.67"/>
                    <measurement group_id="O2" value="8.99" spread="0.83"/>
                    <measurement group_id="O3" value="9.48" spread="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sedation NIH Toolbox Flanker Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.62" spread="0.88"/>
                    <measurement group_id="O2" value="8.47" spread="0.93"/>
                    <measurement group_id="O3" value="8.36" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>NIH Toolbox Card Sorting Score</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.134</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>3 degrees of freedom</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>NIH Toolbox Card Sorting Score</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.012</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>6 degrees of freedom</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>NIH Toolbox Card Sorting Score</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.487</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>1 degree of freedom</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>NIH Toolbox Flanker Score</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.046</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>3 degrees of freedom</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>NIH Toolbox Flanker Score</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.010</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>6 degrees of freedom</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>NIH Toolbox Flanker Score</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.356</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Effect of Study Drug on Ability to Correctly Identify Images</title>
        <description>The ability to match sounds and images measured by the predictive coding task. Will be reported by a proportion correct as a decimal.</description>
        <time_frame>Intraoperative (During sedation-- up to 8 hours)</time_frame>
        <population>No data was collected for this outcome measure for Midazolam or Sleep</population>
        <group_list>
          <group group_id="O1">
            <title>Dexmedetomidine</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Dexmedetomidine-specific activities: Rapid infusion of 3.0 mg kg-1 h-1 was administered over a 10 min period followed by a 0.5 mg kg-1 h-1 maintenance infusion to achieve the first drug step. The second drug step was similarly achieved by a 10 min infusion of 3.0 mg kg-1 h-1 followed by a 1.5 mg kg-1 h-1 maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O2">
            <title>Ketamine</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Ketamine-specific activities: Ketamine was titrated using up to a 4.5mg/kg bolus over 10 minutes followed by 0.1-0.5mg/min intravenous infusion with 5 minutes between increments and titrated to desired observed alertness/sedation level. This infusion rate may be slowed further or stopped for patient safety concerns. Infusion rates will be adjusted using information from the target-controlled infusion model clinical judgment. Short-lived emergence delirium (confusion on awakening) may occur on emergence from ketamine anesthesia and this will be managed through standard clinical practice including administration of midazolam (up to 4mg IV) if required. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O3">
            <title>Propofol</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Propofol-specific activities: A target-controlled infusion model used to predict plasma concentrations of propofol at 0.5 mcg/mL increments allowing 5-minutes to equilibrate between any step change. Dosing will be confined to FDA approved limits with up to a 2.5mg/kg bolus over 1 to 3 minute followed by an infusion of 50-200mcg/kg/min titrated to the desired observed alertness/sedation levels. Drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O4">
            <title>Midazolam</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Midazolam-specific activities: Initial boluses of up to 0.35mg/kg followed by doses up to 0.1mg/kg/h as a maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O5">
            <title>Sleep</title>
            <description>Participants were fitted with a saline gel EEG cap and a pre-sleep recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. After the pre-sleep recording, participants laid down within 30 minutes of their usual bedtime and were left to sleep for 2-3 hours. After this period, the participant was woken up every 15-30 minutes to answer standardized wake report form questions. After awaking a final time, the participant repeated 10 minutes of awake eyes open and eyes closed recordings as well as the predictive coding cognitive task on a computer.</description>
          </group>
        </group_list>
        <measure>
          <title>Effect of Study Drug on Ability to Correctly Identify Images</title>
          <description>The ability to match sounds and images measured by the predictive coding task. Will be reported by a proportion correct as a decimal.</description>
          <population>No data was collected for this outcome measure for Midazolam or Sleep</population>
          <units>proportion correct</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Predictive Coding Task Accuracy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.916" spread="0.07"/>
                    <measurement group_id="O2" value="0.899" spread="0.07"/>
                    <measurement group_id="O3" value="0.91" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sedation Predictive Coding Task Accuracy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.793" spread="0.09"/>
                    <measurement group_id="O2" value="0.763" spread="0.1"/>
                    <measurement group_id="O3" value="0.734" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Predictive Coding Task Accuracy</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>17 degrees of freedom</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Predictive Coding Task Accuracy</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>14 degrees of freedom</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Predictive Coding Task Accuracy</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.067</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>4 degrees of freedom</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Effect of Study Drug on Ability to Form Implicit Memory</title>
        <description>Subjects will have a list of words read to them while under sedation and their ability to hear these words and form implicit memories of them will be assessed using a two-alternative forced choice task. Results will be reported as the average number of correct responses out of sixteen.</description>
        <time_frame>Intraoperative (During sedation-- up to 8 hours)</time_frame>
        <population>There was no data collected for this outcome measure for Midazolam or Sleep.</population>
        <group_list>
          <group group_id="O1">
            <title>Dexmedetomidine</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Dexmedetomidine-specific activities: Rapid infusion of 3.0 mg kg-1 h-1 was administered over a 10 min period followed by a 0.5 mg kg-1 h-1 maintenance infusion to achieve the first drug step. The second drug step was similarly achieved by a 10 min infusion of 3.0 mg kg-1 h-1 followed by a 1.5 mg kg-1 h-1 maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O2">
            <title>Ketamine</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Ketamine-specific activities: Ketamine was titrated using up to a 4.5mg/kg bolus over 10 minutes followed by 0.1-0.5mg/min intravenous infusion with 5 minutes between increments and titrated to desired observed alertness/sedation level. This infusion rate may be slowed further or stopped for patient safety concerns. Infusion rates will be adjusted using information from the target-controlled infusion model clinical judgment. Short-lived emergence delirium (confusion on awakening) may occur on emergence from ketamine anesthesia and this will be managed through standard clinical practice including administration of midazolam (up to 4mg IV) if required. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O3">
            <title>Propofol</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Propofol-specific activities: A target-controlled infusion model used to predict plasma concentrations of propofol at 0.5 mcg/mL increments allowing 5-minutes to equilibrate between any step change. Dosing will be confined to FDA approved limits with up to a 2.5mg/kg bolus over 1 to 3 minute followed by an infusion of 50-200mcg/kg/min titrated to the desired observed alertness/sedation levels. Drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O4">
            <title>Midazolam</title>
            <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Midazolam-specific activities: Initial boluses of up to 0.35mg/kg followed by doses up to 0.1mg/kg/h as a maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
          </group>
          <group group_id="O5">
            <title>Sleep</title>
            <description>Participants were fitted with a saline gel EEG cap and a pre-sleep recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. After the pre-sleep recording, participants laid down within 30 minutes of their usual bedtime and were left to sleep for 2-3 hours. After this period, the participant was woken up every 15-30 minutes to answer standardized wake report form questions. After awaking a final time, the participant repeated 10 minutes of awake eyes open and eyes closed recordings as well as the predictive coding cognitive task on a computer.</description>
          </group>
        </group_list>
        <measure>
          <title>Effect of Study Drug on Ability to Form Implicit Memory</title>
          <description>Subjects will have a list of words read to them while under sedation and their ability to hear these words and form implicit memories of them will be assessed using a two-alternative forced choice task. Results will be reported as the average number of correct responses out of sixteen.</description>
          <population>There was no data collected for this outcome measure for Midazolam or Sleep.</population>
          <units>correct responses</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="12"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" spread="2.47"/>
                    <measurement group_id="O2" value="8.17" spread="1.70"/>
                    <measurement group_id="O3" value="9" spread="1.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis is a 50% recall rate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>17 degrees of freedom</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis is a 50% recall rate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.37</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>11 degrees of freedom</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Null hypothesis is a 50% recall rate.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.12</p_value>
            <p_value_desc>Statistical significance defined by p &lt; 0.05.</p_value_desc>
            <method>t-test, 2 sided</method>
            <method_desc>4 degrees of freedom</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>24 hours after drug or sleep visit.</time_frame>
      <desc>Every participant was called by the study team the day after a drug or sleep visit and asked to report any adverse events experienced since the visit. If any reported, study team reported them to study physician, and completed a serious adverse event tracking log if needed. If the adverse event fulfilled criteria outlined in protocol, it would be reported to the internal review board at UW- Madison.</desc>
      <group_list>
        <group group_id="E1">
          <title>Dexmedetomidine</title>
          <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Dexmedetomidine-specific activities: Rapid infusion of 3.0 mg kg-1 h-1 was administered over a 10 min period followed by a 0.5 mg kg-1 h-1 maintenance infusion to achieve the first drug step. The second drug step was similarly achieved by a 10 min infusion of 3.0 mg kg-1 h-1 followed by a 1.5 mg kg-1 h-1 maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
        </group>
        <group group_id="E2">
          <title>Ketamine</title>
          <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Ketamine-specific activities: Ketamine was titrated using up to a 4.5mg/kg bolus over 10 minutes followed by 0.1-0.5mg/min intravenous infusion with 5 minutes between increments and titrated to desired observed alertness/sedation level. This infusion rate may be slowed further or stopped for patient safety concerns. Infusion rates will be adjusted using information from the target-controlled infusion model clinical judgment. Short-lived emergence delirium (confusion on awakening) may occur on emergence from ketamine anesthesia and this will be managed through standard clinical practice including administration of midazolam (up to 4mg IV) if required. Duration of drug exposure was limited to 4 hours.</description>
        </group>
        <group group_id="E3">
          <title>Propofol</title>
          <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Propofol-specific activities: A target-controlled infusion model used to predict plasma concentrations of propofol at 0.5 mcg/mL increments allowing 5-minutes to equilibrate between any step change. Dosing will be confined to FDA approved limits with up to a 2.5mg/kg bolus over 1 to 3 minute followed by an infusion of 50-200mcg/kg/min titrated to the desired observed alertness/sedation levels. Drug exposure was limited to 4 hours.</description>
        </group>
        <group group_id="E4">
          <title>Midazolam</title>
          <description>Standard drug visit activities: Participants were fitted with a saline gel EEG cap and a pre-sedation recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. Once the pre-sedation recording was collected, the faculty anesthesiologist began administering the study drug. A new EEG recording was started to monitor brain waves while all of the pre-sedation activities were repeated after the administration of the study drug.&#xD;
Midazolam-specific activities: Initial boluses of up to 0.35mg/kg followed by doses up to 0.1mg/kg/h as a maintenance infusion. Duration of drug exposure was limited to 4 hours.</description>
        </group>
        <group group_id="E5">
          <title>Sleep</title>
          <description>Participants were fitted with a saline gel EEG cap and a pre-sleep recording was collected. Participants' brain waves were recorded during rest, while responding to a standardized wake report form, and while performing a predictive coding cognitive task on a computer. After the pre-sleep recording, participants laid down within 30 minutes of their usual bedtime and were left to sleep for 2-3 hours. After this period, the participant was woken up every 15-30 minutes to answer standardized wake report form questions. After awaking a final time, the participant repeated 10 minutes of awake eyes open and eyes closed recordings as well as the predictive coding cognitive task on a computer.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Mild Chest Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Pain at injection site</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The fourth study drug was changed from sevoflurane to midazolam in November of 2019 due to concerns about conducting experiments in patients inhaling a volatile anesthetic through a face mask and the difficulty we would have with communicating with patients. The cessation of human subjects research due to the COVID-19 pandemic and amended institutional guidelines for conducting in-person research caused far fewer participants to be recruited than was planned.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Robert Sanders, MBBS, PhD, FRCA</name_or_title>
      <organization>University of Sydney</organization>
      <phone>02 9036 3136</phone>
      <email>robert.sanders@sydney.edu.au</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03284307
org study id: 2015-1399
secondary id: A530900
secondary id: SMPH\ANESTHESIOLOGY\ANESTHESIO
secondary id: Protocol Version 10/18/2019
nct id: NCT03284307
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This study will be a single-site, controlled, unblinded study at the University of Wisconsin
      to examine changes in the electroencephalogram during anesthesia and waking.
* 20 subjects will be recruited per drug, and subjects can be recruited to undergo multiple
      sedation protocols.

      Screening:

      Subjects will respond to the volunteer posts for the study by calling into a study specific
      phone number. They will complete a phone screening to determine basic eligibility for the
      study. At the beginning of the sedation session, participants will affirm that in the
      interval since their baseline visit, they have not acquired any of the cited exclusion
      criteria that would preclude participation. A review of these exclusion criteria will be
      completed by the Anesthesiologist. A standard pre-anesthetic assessment will be performed,
      including confirmation of NPO status, and documented using the standard Department of
      Anesthesiology pre-operative evaluation form.

      The first sedative will be dexmedetomidine followed by ketamine, propofol and then midazolam
      (dependent on the availability of the drugs). Total enrollment in the study will be up to 80
      subjects. Each sedation experiment will occur on separate days at least 28 days apart, if the
      subject chooses to participate in more than one session.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Occipital Delta Power Spectral Density by Conscious State and Study Group.
time frame: Intraoperative (During sedation-- up to 8 hours)
description: The difference in spontaneous EEG slow wave activity over posterior cortex between states of consciousness measured with high-density EEG equipment and reported in spectral power in the delta band (1-4 Hz) at electrode Oz. Disconnected conscious experience (dreaming), connected conscious experience (awareness of the external world), and unconsciousness (no report) was assessed when participants were roused from sedation or sleep.
measure: Number of Instances of Disconnected Conscious Experience (Dreaming) vs Connected Conscious Experience (Awareness of External World).
time frame: Intraoperative (During sedation-- up to 8 hours)
description: The number of instances of disconnected conscious experience (dreaming) versus connected conscious experience (awareness of the external world) during sedation is measured by subject self-report at the time of researcher initiated inquiry.
measure: Effect of Study Drug on Ability to Correctly Identify Shapes/Images
time frame: Intraoperative (During sedation-- up to 8 hours)
description: The ability to identify shapes/images in visual illusions measured by the NIH Toolbox. Will be reported by a computed score from NIH Toolbox for the Dimensional Change Card Sort Test (DCCS) and the Flanker Inhibitory Control & Attention Test (Flanker). Both Flanker and DCCS use a 2-vector scoring method that takes accuracy and reaction time (if accuracy >=80%) into account, resulting in a computed score that can range in value from 0-10. A higher score indicates better performance on the test.
measure: Effect of Study Drug on Ability to Correctly Identify Images
time frame: Intraoperative (During sedation-- up to 8 hours)
description: The ability to match sounds and images measured by the predictive coding task. Will be reported by a proportion correct as a decimal.
measure: Effect of Study Drug on Ability to Form Implicit Memory
time frame: Intraoperative (During sedation-- up to 8 hours)
description: Subjects will have a list of words read to them while under sedation and their ability to hear these words and form implicit memories of them will be assessed using a two-alternative forced choice task. Results will be reported as the average number of correct responses out of sixteen.
arm group label: Drug Administrated
arm group type: Experimental
description: Sedatives will be administered to participants while their brain activity is measured.
intervention type: Drug
intervention name: Dexmedetomidine
description: 20 participants will be administered Dexmedetomidine.
arm group label: Drug Administrated
intervention type: Drug
intervention name: Ketamine
description: 20 participants will be administered Ketamine.
arm group label: Drug Administrated
intervention type: Drug
intervention name: Propofol
description: 20 participants will be administered Propofol.
arm group label: Drug Administrated
intervention type: Drug
intervention name: Midazolam
description: 20 participants will be administered Midazolam.
arm group label: Drug Administrated
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Robert A Pearce, MD, PhD
role: Principal Investigator
affiliation: Professor and chair of Anesthesiology at UW- Madison
facility: 
country: United States
responsible party type: Sponsor
mesh term: Unconsciousness
mesh term: Midazolam
mesh term: Dexmedetomidine
mesh term: Ketamine
mesh term: Propofol
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The fourth study drug was changed from sevoflurane to midazolam in November of 2019 due to concerns about conducting experiments in patients inhaling a volatile anesthetic through a face mask and the difficulty we would have with communicating with patients. The cessation of human subjects research due to the COVID-19 pandemic and amended institutional guidelines for conducting in-person research caused far fewer participants to be recruited than was planned.
point of contact: 