<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/NCT03775356</url>
  </required_header>
  <id_info>
    <org_study_id>BsR</org_study_id>
    <nct_id>NCT03775356</nct_id>
  </id_info>
  <brief_title>Reduction of Intraoperative EEG Burst Suppression</brief_title>
  <acronym>BsR</acronym>
  <official_title>Reduction of Intraoperative EEG Burst Suppression - Test of Efficacy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Technical University of Munich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Technical University of Munich</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Burst suppression (BS) is a not physiological pattern in the electroencephalogram (EEG). BS&#xD;
      during general anesthesia is mainly seen as a sign for too deep hypnosis and may increase the&#xD;
      risk of postoperative delirium (POD), a disturbance of consciousness arising within 24 hours&#xD;
      after surgery. This monocentric, simple masked randomized study aims primarily to&#xD;
      investigate, whether particular anesthesiological interventions reduce the occurrence of&#xD;
      intraoperative burst suppression. The investigator initiated trial includes 66 patients (male&#xD;
      and female) aged ≥ 60 years in two groups (intervention and control group). Secondary aims&#xD;
      will be the correlation of burst suppression and mean arterial pressure, concentration of&#xD;
      anesthetics and postoperative delirium.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intraoperative burst suppression represents a non physiological EEG pattern. According to the&#xD;
      literature and scientific knowledge, intraoperative burst suppression patterns might be&#xD;
      caused either by hypotension resulting in a reduced cerebral circulation or by an&#xD;
      oversedation of anesthetics correlating with a very deep level of hypnosis.&#xD;
&#xD;
      Some publications exist that discuss the occurrence of intraoperative burst suppression&#xD;
      especially in elderly people (aged ≥ 60 years) as a predictor of postoperative delirium and&#xD;
      postoperative cognitive dysfunction.&#xD;
&#xD;
      None of the studies however was able to prove a causal relationship between burst suppression&#xD;
      and postoperative delirium. Contrary it might simply be an epiphenomenon.&#xD;
&#xD;
      Conducting this interventional trail primarily aims to prove whether specific&#xD;
      anesthesiological interventions, such as the treatment of intraoperative hypotension in first&#xD;
      line and/or the reduction of the concentration of anesthetics in second line, reduce&#xD;
      intraoperative burst suppression. Hence it might be possible to investigate a possible&#xD;
      casualty between burst suppression and postoperative delirium in a second trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 8, 2019</start_date>
  <completion_date type="Actual">December 19, 2020</completion_date>
  <primary_completion_date type="Actual">December 19, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Care Provider, Investigator)</masking>
    <masking_description>Single masked. The entropy and EEG module will be masked for the responsible anesthetist as well as the study team during the entire investigation.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Chance of the total, cumulative burst suppression rate.</measure>
    <time_frame>During general anesthesia and within the intervention</time_frame>
    <description>The total, cumulative burst suppression rate (BSR) corresponds to area under the curve and is defined by the BSR (%) and the absolute duration of BSR (t).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Burst suppression rate during induction.</measure>
    <time_frame>During induction within the intervention</time_frame>
    <description>Rate of change of the burst suppression rate during induction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Burst suppression rate during maintenance.</measure>
    <time_frame>During maintenance within the intervention</time_frame>
    <description>Rate of change of the burst suppression ratio during maintenance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean arterial blood pressure.</measure>
    <time_frame>During burst suppression within general anesthesia</time_frame>
    <description>Evaluation of the mean arterial blood pressure with positive burst suppression rate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endtidal anesthetic concentration (ETAC) and infusion rate of propofol.</measure>
    <time_frame>During burst suppression within the intervention</time_frame>
    <description>Evaluation of the mean ETAC and infusion rate of propofol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Specific characteristics of the EEG frequency spectrum during burst suppression</measure>
    <time_frame>During burst suppression within general anesthesia</time_frame>
    <description>Evaluation of specific EEG frequencies differentiating BSR caused by hypotension or oversedation of anesthetics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative delirium.</measure>
    <time_frame>Within the first three postoperative days</time_frame>
    <description>Screening of the patients regarding a postoperative delirium by a brief confession assessment method (bCAM).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">106</enrollment>
  <condition>Burst Suppression</condition>
  <condition>EEG With Abnormally Slow Frequencies</condition>
  <condition>Postoperative Delirium</condition>
  <arm_group>
    <arm_group_label>1 - Blinded</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>EEG and Entropy will be blinded. The anesthesiological management will be performed by the anesthetist according to clinical standard operations.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2 - Unblinded</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>EEG and Entropy will be unblinded. The intervention starts with the start of a positive burst suppression rate. In the case of a concurrent hypotension the anesthetist treats the hypotension according to clinical standard operations in the first step. Hypotension means blood pressure values blow the baseline value which is defined by the lowest, preoperatively measured value. If after this treatment and a reevaluation of the BSR, BSR remains positive, the anesthetist is going to reduce the concentration of anesthetics in a second step. In case of positive BSR and a blood pressure value ≥ the baseline value, the concentration of anesthetics will be reduced as a first measure. The aim is to figure out whether one or both of these interventions can reduce to total, cumulative BSR.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Treatment of hypotension and/or reduction of anesthetics</intervention_name>
    <description>The treatment of hypotension can be done by the responsible anesthetist according to the clinical standard operations including any accepted drug typically used in this hospital. The reduction of anesthetics can be done either by reducing the volatile end tidal anesthetics concentration (ETAC) or the infusion rate of propofol.</description>
    <arm_group_label>2 - Unblinded</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 60 years&#xD;
&#xD;
          -  Surgical interventions in general anesthesia (volatile or total intravenous&#xD;
             anesthesia)&#xD;
&#xD;
          -  expected surgery duration ≥ 1h&#xD;
&#xD;
          -  American Society of Anesthesiologists (ASA) 1-4&#xD;
&#xD;
          -  written informed consent prior to study participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Neurological or psychiatric disorders&#xD;
&#xD;
          -  hearing difficulty&#xD;
&#xD;
          -  deafness&#xD;
&#xD;
          -  neurosurgical (intra)cranial surgery&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  expected continuous mandatory ventilation after surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gerhard Schneider, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Clinic director - Department of anesthesiology and intensive care</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinikum rechts der Isar - Klinik fuer Anaesthesiologie und Intensivmedizin</name>
      <address>
        <city>München</city>
        <state>Bayern</state>
        <zip>81675</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Soehle M, Dittmann A, Ellerkmann RK, Baumgarten G, Putensen C, Guenther U. Intraoperative burst suppression is associated with postoperative delirium following cardiac surgery: a prospective, observational study. BMC Anesthesiol. 2015 Apr 28;15:61. doi: 10.1186/s12871-015-0051-7.</citation>
    <PMID>25928189</PMID>
  </reference>
  <reference>
    <citation>Fritz BA, Kalarickal PL, Maybrier HR, Muench MR, Dearth D, Chen Y, Escallier KE, Ben Abdallah A, Lin N, Avidan MS. Intraoperative Electroencephalogram Suppression Predicts Postoperative Delirium. Anesth Analg. 2016 Jan;122(1):234-42. doi: 10.1213/ANE.0000000000000989.</citation>
    <PMID>26418126</PMID>
  </reference>
  <reference>
    <citation>Radtke FM, Franck M, Lendner J, Kruger S, Wernecke KD, Spies CD. Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction. Br J Anaesth. 2013 Jun;110 Suppl 1:i98-105. doi: 10.1093/bja/aet055. Epub 2013 Mar 28.</citation>
    <PMID>23539235</PMID>
  </reference>
  <reference>
    <citation>Sessler DI, Sigl JC, Kelley SD, Chamoun NG, Manberg PJ, Saager L, Kurz A, Greenwald S. Hospital stay and mortality are increased in patients having a &quot;triple low&quot; of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia. Anesthesiology. 2012 Jun;116(6):1195-203. doi: 10.1097/ALN.0b013e31825683dc.</citation>
    <PMID>22546967</PMID>
  </reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>May 10, 2021</last_update_submitted>
  <last_update_submitted_qc>May 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intraoperative EEG based monitoring</keyword>
  <keyword>Level of hypnosis</keyword>
  <keyword>Burst suppression</keyword>
  <keyword>Postoperative delirium</keyword>
  <keyword>EEG-signal characteristics</keyword>
  <keyword>Entropy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Vision Disorders</mesh_term>
    <mesh_term>Emergence Delirium</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03775356
org study id: BsR
nct id: NCT03775356
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Burst suppression (BS) is a not physiological pattern in the electroencephalogram (EEG). BS
      during general anesthesia is mainly seen as a sign for too deep hypnosis and may increase the
      risk of postoperative delirium (POD), a disturbance of consciousness arising within 24 hours
      after surgery. This monocentric, simple masked randomized study aims primarily to
      investigate, whether particular anesthesiological interventions reduce the occurrence of
      intraoperative burst suppression. The investigator initiated trial includes 66 patients (male
      and female) aged ≥ 60 years in two groups (intervention and control group). Secondary aims
      will be the correlation of burst suppression and mean arterial pressure, concentration of
      anesthetics and postoperative delirium.
Intraoperative burst suppression represents a non physiological EEG pattern. According to the
      literature and scientific knowledge, intraoperative burst suppression patterns might be
      caused either by hypotension resulting in a reduced cerebral circulation or by an
      oversedation of anesthetics correlating with a very deep level of hypnosis.

      Some publications exist that discuss the occurrence of intraoperative burst suppression
      especially in elderly people (aged ≥ 60 years) as a predictor of postoperative delirium and
      postoperative cognitive dysfunction.

      None of the studies however was able to prove a causal relationship between burst suppression
      and postoperative delirium. Contrary it might simply be an epiphenomenon.

      Conducting this interventional trail primarily aims to prove whether specific
      anesthesiological interventions, such as the treatment of intraoperative hypotension in first
      line and/or the reduction of the concentration of anesthetics in second line, reduce
      intraoperative burst suppression. Hence it might be possible to investigate a possible
      casualty between burst suppression and postoperative delirium in a second trial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Care Provider, Investigator)
masking description: Single masked. The entropy and EEG module will be masked for the responsible anesthetist as well as the study team during the entire investigation.
measure: Chance of the total, cumulative burst suppression rate.
time frame: During general anesthesia and within the intervention
description: The total, cumulative burst suppression rate (BSR) corresponds to area under the curve and is defined by the BSR (%) and the absolute duration of BSR (t).
measure: Burst suppression rate during induction.
time frame: During induction within the intervention
description: Rate of change of the burst suppression rate during induction.
measure: Burst suppression rate during maintenance.
time frame: During maintenance within the intervention
description: Rate of change of the burst suppression ratio during maintenance.
measure: Mean arterial blood pressure.
time frame: During burst suppression within general anesthesia
description: Evaluation of the mean arterial blood pressure with positive burst suppression rate.
measure: Endtidal anesthetic concentration (ETAC) and infusion rate of propofol.
time frame: During burst suppression within the intervention
description: Evaluation of the mean ETAC and infusion rate of propofol.
measure: Specific characteristics of the EEG frequency spectrum during burst suppression
time frame: During burst suppression within general anesthesia
description: Evaluation of specific EEG frequencies differentiating BSR caused by hypotension or oversedation of anesthetics.
measure: Postoperative delirium.
time frame: Within the first three postoperative days
description: Screening of the patients regarding a postoperative delirium by a brief confession assessment method (bCAM).
arm group label: 1 - Blinded
arm group type: No Intervention
description: EEG and Entropy will be blinded. The anesthesiological management will be performed by the anesthetist according to clinical standard operations.
arm group label: 2 - Unblinded
arm group type: Active Comparator
description: EEG and Entropy will be unblinded. The intervention starts with the start of a positive burst suppression rate. In the case of a concurrent hypotension the anesthetist treats the hypotension according to clinical standard operations in the first step. Hypotension means blood pressure values blow the baseline value which is defined by the lowest, preoperatively measured value. If after this treatment and a reevaluation of the BSR, BSR remains positive, the anesthetist is going to reduce the concentration of anesthetics in a second step. In case of positive BSR and a blood pressure value ≥ the baseline value, the concentration of anesthetics will be reduced as a first measure. The aim is to figure out whether one or both of these interventions can reduce to total, cumulative BSR.
intervention type: Other
intervention name: Treatment of hypotension and/or reduction of anesthetics
description: The treatment of hypotension can be done by the responsible anesthetist according to the clinical standard operations including any accepted drug typically used in this hospital. The reduction of anesthetics can be done either by reducing the volatile end tidal anesthetics concentration (ETAC) or the infusion rate of propofol.
arm group label: 2 - Unblinded
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Gerhard Schneider, Prof. Dr.
role: Principal Investigator
affiliation: Clinic director - Department of anesthesiology and intensive care
facility: 
country: Germany
citation: Soehle M, Dittmann A, Ellerkmann RK, Baumgarten G, Putensen C, Guenther U. Intraoperative burst suppression is associated with postoperative delirium following cardiac surgery: a prospective, observational study. BMC Anesthesiol. 2015 Apr 28;15:61. doi: 10.1186/s12871-015-0051-7.
PMID: 25928189
citation: Fritz BA, Kalarickal PL, Maybrier HR, Muench MR, Dearth D, Chen Y, Escallier KE, Ben Abdallah A, Lin N, Avidan MS. Intraoperative Electroencephalogram Suppression Predicts Postoperative Delirium. Anesth Analg. 2016 Jan;122(1):234-42. doi: 10.1213/ANE.0000000000000989.
PMID: 26418126
citation: Radtke FM, Franck M, Lendner J, Kruger S, Wernecke KD, Spies CD. Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium but not postoperative cognitive dysfunction. Br J Anaesth. 2013 Jun;110 Suppl 1:i98-105. doi: 10.1093/bja/aet055. Epub 2013 Mar 28.
PMID: 23539235
citation: Sessler DI, Sigl JC, Kelley SD, Chamoun NG, Manberg PJ, Saager L, Kurz A, Greenwald S. Hospital stay and mortality are increased in patients having a "triple low" of low blood pressure, low bispectral index, and low minimum alveolar concentration of volatile anesthesia. Anesthesiology. 2012 Jun;116(6):1195-203. doi: 10.1097/ALN.0b013e31825683dc.
PMID: 22546967
responsible party type: Sponsor
mesh term: Delirium
mesh term: Vision Disorders
mesh term: Emergence Delirium
mesh term: Anesthetics
sharing ipd: No