<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/NCT04466579</url>
  </required_header>
  <id_info>
    <org_study_id>FNO-KARIM-14-PONV-ED</org_study_id>
    <nct_id>NCT04466579</nct_id>
  </id_info>
  <brief_title>Influence of Monitoring the Depth of General Anesthesia Upon the Incidence of PONV and Emergence Delirium in Children Undergoing Endoscopic Adenoidectomy in General Anesthesia</brief_title>
  <official_title>Influence of Monitoring the Depth of General Anesthesia Upon the Incidence of PONV and Emergence Delirium in Children Undergoing Endoscopic Adenoidectomy in General Anesthesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Ostrava</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Ostrava</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>
      The study has been designed as a prospective randomized clinical trial. Due to the use of a&#xD;
      bispectral (BIS) monitor in the interventional arm, the study will not be blinded for the&#xD;
      anesthetist. The total planned number of study subjects is 100. Patients will be randomly&#xD;
      randomized upon arrival to the operating theatre (using the envelope method) into the&#xD;
      interventional arm (BIS monitoring of the depth of general anesthesia), and into the control&#xD;
      group (standard management of general anesthesia to minimum alveolar concentration (MAC)&#xD;
      1,0). The target values of the depth of general anesthesia according to BIS are between 40&#xD;
      and 60.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The condition of postoperative nausea and vomiting (PONV) is defined as nausea and vomiting,&#xD;
      which appears within 24 hours after the performance of a surgical/diagnostic procedure in&#xD;
      general anesthesia. PONV is perceived as a complication of minor importance in perioperative&#xD;
      medicine, nevertheless, it is one of the most frequent causes of morbidity in pediatric&#xD;
      patients in the early postoperative period, associated with a number of adverse effects. The&#xD;
      incidence of PONV in pediatric age is reported in scientific literature to be between 8.9 and&#xD;
      42 percent. The pathogenesis of PONV is complex and has not been fully clarified yet. The&#xD;
      development of PONV depends on individual and anaesthesiology risk factors, and the type of&#xD;
      surgical procedure. The use of inhalation anesthetics demonstrably increases the incidence of&#xD;
      PONV, especially in the course of the first two hours after the procedure. The need for&#xD;
      inhalation anesthetic is individually variable, and it is not possible to empirically define,&#xD;
      which dose will lead to an adequate depth of anesthesia. Excessively deep, as well as too&#xD;
      shallow anesthesia may result in increasing the incidence of postoperative complications,&#xD;
      including PONV. The depth of anesthesia and unconsciousness may be monitored with BIS&#xD;
      (bispectral index). The investigators presume that optimization of the supply of inhalation&#xD;
      anesthetic according to BIS, so-called BIGA (Bispectral index guided anesthesia) will lead to&#xD;
      decreasing the incidence of PONV.&#xD;
&#xD;
      Several clinical studies performed on the adult population have demonstrated that using BIGA&#xD;
      leads to a decreased incidence of PONV in adult patients undergoing gynecological procedures.&#xD;
      As far as pediatric anesthesiology is concerned, similar studies are still lacking.&#xD;
&#xD;
      Inhalation anesthesia is also associated with another complication in the early postoperative&#xD;
      period - so-called emergence delirium (ED). It is a condition of psychomotor restlessness,&#xD;
      perception disorders, and excitation of the child observed after completion of anesthesia.&#xD;
      The incidence of ED in the pediatric population anesthesia is between 10 and 80 percent, most&#xD;
      frequently within the first 10-30 minutes after discontinuation of the administration of&#xD;
      anesthetics. The condition is characterized by confusion, loss of orientation, crying,&#xD;
      restlessness, and non-cooperation of the child. The causes of ED have not been fully&#xD;
      clarified.&#xD;
&#xD;
      One of the possible causes may be the rapid emergence of the child from anesthesia after&#xD;
      discontinuation of the inhalation anesthetic. The incidence of ED is highest with&#xD;
      Sevoflurane, which is the most frequently used inhalation anesthetic in pediatric anesthesia.&#xD;
      Optimization of the depth of general anesthesia and decreasing the consumption of inhalation&#xD;
      anesthetic may lead to decreasing the incidence of emergence delirium objectified according&#xD;
      to the Paediatric Anaesthesia Emergence Delirium (PAED) score.&#xD;
&#xD;
      The study has been designed as a prospective randomized clinical trial. Due to the use of the&#xD;
      BIS monitor in the interventional arm, the study will not be blinded for the anesthetist. The&#xD;
      total planned number of study subjects is 100. Patients will be randomly randomized upon&#xD;
      arrival to the operating theatre (using the envelope method) into the interventional arm (BIS&#xD;
      monitoring of the depth of general anesthesia), and into the control group (standard&#xD;
      management of general anesthesia to minimum alveolar concentration (MAC) of 1.0). The target&#xD;
      values of the depth of general anesthesia according to BIS are between 40 and 60.&#xD;
&#xD;
      General anesthesia will be administered according to the following uniform anaesthesiology&#xD;
      protocol:&#xD;
&#xD;
      Inhalation introduction with Sevoflurane (8% on the vaporizer), in a carrier mixture of gases&#xD;
      oxygen : air, with the flow of 41/min and oxygen concentration of 50%. In the intervention&#xD;
      group, BIS will be introduced as soon as possible. After achieving a sufficient depth of&#xD;
      anesthesia, a peripheral venous catheter will be introduced, followed with intravenous&#xD;
      administration of opioid - Sufentanil in the dose of 0.2ucg/kg, and intravenous&#xD;
      administration of Paracetamol in the dose of 15mg/kg. The infusion will be administered in&#xD;
      the course of the surgical procedure - isotonic crystalloid solution Benelyte in the dose of&#xD;
      10ml/kg/hour. Breathing passageways will be secured with an armed laryngeal mask, according&#xD;
      to the standard procedure applied at the author's center. Considering the character of the&#xD;
      study, no antiemetic prophylaxis will be administered. After completion of the surgical&#xD;
      procedure and emergence from general anesthesia, the child will be transferred to&#xD;
      post-anesthesia care unit (PACU), where, apart from the monitoring of vital functions, also&#xD;
      the incidence of PONV and the PAED score (in the 10th minute, 30th minute, and 60th minute)&#xD;
      will be observed. At the Ear-Nose-Throat (ENT) department, the authors will record the Baxter&#xD;
      Retching Faces (BARF) scale in pre-determined time intervals, and the incidence of PONV in&#xD;
      the course of the whole hospitalization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">May 31, 2023</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>
    <intervention_model_description>The study subjects will be randomized into two study arms.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>No masking is being used in this study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of PONV</measure>
    <time_frame>During the hospitalisation of the patient, i.e. up to 5 days</time_frame>
    <description>The incidence of PONV will be observed and recorded using the Baxter Reetching Faces (BARF) scale and recording the number of PONV episodes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of ED</measure>
    <time_frame>During the hospitalisation of the patient, i.e. up to 5 days</time_frame>
    <description>The incidence of ED will be observed and recorded using the PAED score.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Postoperative Nausea</condition>
  <condition>Postoperative Vomiting</condition>
  <condition>Emergence Delirium</condition>
  <arm_group>
    <arm_group_label>BIS monitoring</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study subjects randomized in this study arm will have the depth of anesthesia controlled with the BIS monitor.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Study subjects randomized in this study arm will receive standard anesthesiology care according to the usual procedures used at the study centre.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>BIS monitor</intervention_name>
    <description>BIS monitor is used to control and monitor the depth of general anesthesia.</description>
    <arm_group_label>BIS monitoring</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard care</intervention_name>
    <description>Standard anesthesiology care according to the protocol of the study</description>
    <arm_group_label>Standard care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  3-8 years of age&#xD;
&#xD;
          -  Indication for the performance of endoscopic adenoidectomy in general anesthesia&#xD;
&#xD;
          -  ASA I a II&#xD;
&#xD;
          -  Consent of a parent/a guardian&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ASA III and more&#xD;
&#xD;
          -  Disapproval of a parent/a guardian&#xD;
&#xD;
          -  Disapproval of the patient&#xD;
&#xD;
          -  Allergies to medication used in the course of the study&#xD;
&#xD;
          -  Contraindication of inhalation introduction to anesthesia and the way of securing&#xD;
             breathing passageways in the study, according to the attending anesthetist&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>8 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michal Frelich, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Ostrava</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Ostrava</name>
      <address>
        <city>Ostrava</city>
        <state>Moravian-Silesian Region</state>
        <zip>70852</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
  </location_countries>
  <reference>
    <citation>Kovac AL. Management of postoperative nausea and vomiting in children. Paediatr Drugs. 2007;9(1):47-69. doi: 10.2165/00148581-200709010-00005.</citation>
    <PMID>17291136</PMID>
  </reference>
  <reference>
    <citation>Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, Watcha M, Chung F, Angus S, Apfel CC, Bergese SD, Candiotti KA, Chan MT, Davis PJ, Hooper VD, Lagoo-Deenadayalan S, Myles P, Nezat G, Philip BK, Tramer MR; Society for Ambulatory Anesthesia. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014 Jan;118(1):85-113. doi: 10.1213/ANE.0000000000000002. Erratum In: Anesth Analg. 2014 Mar;118(3):689. Anesth Analg. 2015 Feb;120(2):494.</citation>
    <PMID>24356162</PMID>
  </reference>
  <reference>
    <citation>Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999 Sep;91(3):693-700. doi: 10.1097/00000542-199909000-00022.</citation>
    <PMID>10485781</PMID>
  </reference>
  <reference>
    <citation>Dahmani S, Delivet H, Hilly J. Emergence delirium in children: an update. Curr Opin Anaesthesiol. 2014 Jun;27(3):309-15. doi: 10.1097/ACO.0000000000000076.</citation>
    <PMID>24784918</PMID>
  </reference>
  <reference>
    <citation>Locatelli BG, Ingelmo PM, Emre S, Meroni V, Minardi C, Frawley G, Benigni A, Di Marco S, Spotti A, Busi I, Sonzogni V. Emergence delirium in children: a comparison of sevoflurane and desflurane anesthesia using the Paediatric Anesthesia Emergence Delirium scale. Paediatr Anaesth. 2013 Apr;23(4):301-8. doi: 10.1111/pan.12038. Epub 2012 Oct 9.</citation>
    <PMID>23043512</PMID>
  </reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>postoperative nausea</keyword>
  <keyword>postoperative vomiting</keyword>
  <keyword>emergence delirium</keyword>
  <keyword>bispectral monitor</keyword>
  <keyword>pediatric anesthesia</keyword>
  <keyword>adenoidectomy</keyword>
  <keyword>general anesthesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delirium</mesh_term>
    <mesh_term>Emergence Delirium</mesh_term>
    <mesh_term>Nausea</mesh_term>
    <mesh_term>Vomiting</mesh_term>
    <mesh_term>Postoperative Nausea and Vomiting</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The authors have no plan to make individual participant data available to other researchers. The data may be provided upon request.</ipd_description>
  </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/NCT04466579
org study id: FNO-KARIM-14-PONV-ED
nct id: NCT04466579
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study has been designed as a prospective randomized clinical trial. Due to the use of a
      bispectral (BIS) monitor in the interventional arm, the study will not be blinded for the
      anesthetist. The total planned number of study subjects is 100. Patients will be randomly
      randomized upon arrival to the operating theatre (using the envelope method) into the
      interventional arm (BIS monitoring of the depth of general anesthesia), and into the control
      group (standard management of general anesthesia to minimum alveolar concentration (MAC)
      1,0). The target values of the depth of general anesthesia according to BIS are between 40
      and 60.
The condition of postoperative nausea and vomiting (PONV) is defined as nausea and vomiting,
      which appears within 24 hours after the performance of a surgical/diagnostic procedure in
      general anesthesia. PONV is perceived as a complication of minor importance in perioperative
      medicine, nevertheless, it is one of the most frequent causes of morbidity in pediatric
      patients in the early postoperative period, associated with a number of adverse effects. The
      incidence of PONV in pediatric age is reported in scientific literature to be between 8.9 and
      42 percent. The pathogenesis of PONV is complex and has not been fully clarified yet. The
      development of PONV depends on individual and anaesthesiology risk factors, and the type of
      surgical procedure. The use of inhalation anesthetics demonstrably increases the incidence of
      PONV, especially in the course of the first two hours after the procedure. The need for
      inhalation anesthetic is individually variable, and it is not possible to empirically define,
      which dose will lead to an adequate depth of anesthesia. Excessively deep, as well as too
      shallow anesthesia may result in increasing the incidence of postoperative complications,
      including PONV. The depth of anesthesia and unconsciousness may be monitored with BIS
      (bispectral index). The investigators presume that optimization of the supply of inhalation
      anesthetic according to BIS, so-called BIGA (Bispectral index guided anesthesia) will lead to
      decreasing the incidence of PONV.

      Several clinical studies performed on the adult population have demonstrated that using BIGA
      leads to a decreased incidence of PONV in adult patients undergoing gynecological procedures.
      As far as pediatric anesthesiology is concerned, similar studies are still lacking.

      Inhalation anesthesia is also associated with another complication in the early postoperative
      period - so-called emergence delirium (ED). It is a condition of psychomotor restlessness,
      perception disorders, and excitation of the child observed after completion of anesthesia.
      The incidence of ED in the pediatric population anesthesia is between 10 and 80 percent, most
      frequently within the first 10-30 minutes after discontinuation of the administration of
      anesthetics. The condition is characterized by confusion, loss of orientation, crying,
      restlessness, and non-cooperation of the child. The causes of ED have not been fully
      clarified.

      One of the possible causes may be the rapid emergence of the child from anesthesia after
      discontinuation of the inhalation anesthetic. The incidence of ED is highest with
      Sevoflurane, which is the most frequently used inhalation anesthetic in pediatric anesthesia.
      Optimization of the depth of general anesthesia and decreasing the consumption of inhalation
      anesthetic may lead to decreasing the incidence of emergence delirium objectified according
      to the Paediatric Anaesthesia Emergence Delirium (PAED) score.

      The study has been designed as a prospective randomized clinical trial. Due to the use of the
      BIS monitor in the interventional arm, the study will not be blinded for the anesthetist. The
      total planned number of study subjects is 100. Patients will be randomly randomized upon
      arrival to the operating theatre (using the envelope method) into the interventional arm (BIS
      monitoring of the depth of general anesthesia), and into the control group (standard
      management of general anesthesia to minimum alveolar concentration (MAC) of 1.0). The target
      values of the depth of general anesthesia according to BIS are between 40 and 60.

      General anesthesia will be administered according to the following uniform anaesthesiology
      protocol:

      Inhalation introduction with Sevoflurane (8% on the vaporizer), in a carrier mixture of gases
      oxygen : air, with the flow of 41/min and oxygen concentration of 50%. In the intervention
      group, BIS will be introduced as soon as possible. After achieving a sufficient depth of
      anesthesia, a peripheral venous catheter will be introduced, followed with intravenous
      administration of opioid - Sufentanil in the dose of 0.2ucg/kg, and intravenous
      administration of Paracetamol in the dose of 15mg/kg. The infusion will be administered in
      the course of the surgical procedure - isotonic crystalloid solution Benelyte in the dose of
      10ml/kg/hour. Breathing passageways will be secured with an armed laryngeal mask, according
      to the standard procedure applied at the author's center. Considering the character of the
      study, no antiemetic prophylaxis will be administered. After completion of the surgical
      procedure and emergence from general anesthesia, the child will be transferred to
      post-anesthesia care unit (PACU), where, apart from the monitoring of vital functions, also
      the incidence of PONV and the PAED score (in the 10th minute, 30th minute, and 60th minute)
      will be observed. At the Ear-Nose-Throat (ENT) department, the authors will record the Baxter
      Retching Faces (BARF) scale in pre-determined time intervals, and the incidence of PONV in
      the course of the whole hospitalization.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study subjects will be randomized into two study arms.
primary purpose: Diagnostic
masking: None (Open Label)
masking description: No masking is being used in this study.
measure: Incidence of PONV
time frame: During the hospitalisation of the patient, i.e. up to 5 days
description: The incidence of PONV will be observed and recorded using the Baxter Reetching Faces (BARF) scale and recording the number of PONV episodes.
measure: Incidence of ED
time frame: During the hospitalisation of the patient, i.e. up to 5 days
description: The incidence of ED will be observed and recorded using the PAED score.
arm group label: BIS monitoring
arm group type: Experimental
description: Study subjects randomized in this study arm will have the depth of anesthesia controlled with the BIS monitor.
arm group label: Standard care
arm group type: Active Comparator
description: Study subjects randomized in this study arm will receive standard anesthesiology care according to the usual procedures used at the study centre.
intervention type: Other
intervention name: BIS monitor
description: BIS monitor is used to control and monitor the depth of general anesthesia.
arm group label: BIS monitoring
intervention type: Other
intervention name: Standard care
description: Standard anesthesiology care according to the protocol of the study
arm group label: Standard care
criteria: 
gender: All
minimum age: 3 Years
maximum age: 8 Years
healthy volunteers: No
last name: Michal Frelich, MD,PhD
role: Principal Investigator
affiliation: University Hospital Ostrava
facility: 
country: Czechia
citation: Kovac AL. Management of postoperative nausea and vomiting in children. Paediatr Drugs. 2007;9(1):47-69. doi: 10.2165/00148581-200709010-00005.
PMID: 17291136
citation: Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, Watcha M, Chung F, Angus S, Apfel CC, Bergese SD, Candiotti KA, Chan MT, Davis PJ, Hooper VD, Lagoo-Deenadayalan S, Myles P, Nezat G, Philip BK, Tramer MR; Society for Ambulatory Anesthesia. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014 Jan;118(1):85-113. doi: 10.1213/ANE.0000000000000002. Erratum In: Anesth Analg. 2014 Mar;118(3):689. Anesth Analg. 2015 Feb;120(2):494.
PMID: 24356162
citation: Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999 Sep;91(3):693-700. doi: 10.1097/00000542-199909000-00022.
PMID: 10485781
citation: Dahmani S, Delivet H, Hilly J. Emergence delirium in children: an update. Curr Opin Anaesthesiol. 2014 Jun;27(3):309-15. doi: 10.1097/ACO.0000000000000076.
PMID: 24784918
citation: Locatelli BG, Ingelmo PM, Emre S, Meroni V, Minardi C, Frawley G, Benigni A, Di Marco S, Spotti A, Busi I, Sonzogni V. Emergence delirium in children: a comparison of sevoflurane and desflurane anesthesia using the Paediatric Anesthesia Emergence Delirium scale. Paediatr Anaesth. 2013 Apr;23(4):301-8. doi: 10.1111/pan.12038. Epub 2012 Oct 9.
PMID: 23043512
responsible party type: Sponsor
mesh term: Delirium
mesh term: Emergence Delirium
mesh term: Nausea
mesh term: Vomiting
mesh term: Postoperative Nausea and Vomiting
sharing ipd: No
ipd description: The authors have no plan to make individual participant data available to other researchers. The data may be provided upon request.