<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/NCT03787849</url>
  </required_header>
  <id_info>
    <org_study_id>EPOPED-USP</org_study_id>
    <nct_id>NCT03787849</nct_id>
  </id_info>
  <brief_title>Epigenetics in PostOperative Pediatric Emergence Delirium</brief_title>
  <acronym>EPOPED</acronym>
  <official_title>Investigation of the DNA Methylation Profile in Children Who Presented Emergence Delirium</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo</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>
      Emergence delirium (ED) infers the occurrence of behavior and cognition changes during the&#xD;
      early postoperative period. Main signs and symptoms of ED are the disturbances of&#xD;
      consciousness and awareness of the environment, with disorientation and perceptual&#xD;
      alterations, including hypersensitivity to external stimuli and hyperactive motor behaviors.&#xD;
      The incidence may be higher than 80%. Risk factors include pre-school age, use of&#xD;
      sevoflurane, ophthalmologic and otorhinolaryngologic surgeries, child anxiety, parental or&#xD;
      caregiver anxiety. The recurrence of ED is controversial. The only validated scale for&#xD;
      diagnosis of ED is the PAED (Pediatric Anesthesia Emergence Delirium). Prevention is the best&#xD;
      approach, as well as the use of alpha-2 agonists, propofol and total intravenous anesthesia.&#xD;
      There are still no clear markers for postoperative delirium, especially ED. Cognitive&#xD;
      alterations may be related to epigenetic modifications. Anesthesia-induced epigenetic changes&#xD;
      may be the key to understanding perioperative complications and outcomes and is a field of&#xD;
      future research in anesthesia. The study aims to analyze the DNA methylation profile in&#xD;
      children with ED. A prospective, randomized study will be carried out in up to 322 children&#xD;
      undergoing general anesthesia (inhalation group or intravenous group) to perform endoscopic&#xD;
      procedures at the Instituto da Criança, Hospital das Clinicas, Faculdade de Medicina,&#xD;
      Universidade de Sao Paulo, Brazil. Patients will have blood samples drawn, and analysis of&#xD;
      the DNA methylation profile through the array technique will be performed in 40 children (20&#xD;
      of each group ) who presented ED as well as in 08 control cases. Also, the occurrence of ED&#xD;
      will be correlated with the degree of anxiety of the child, parents and during anesthetic&#xD;
      induction, in addition to comparing the two anesthetic techniques with the occurrence of ED&#xD;
      and late postoperative cognitive alterations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND: The risks of neurotoxicity and late cognitive impairment supported the recent US&#xD;
      Food and Drug Administration (FDA) recommendation on caution in the indication of anesthesia&#xD;
      in children up to 3 years of age. Among the cognitive alterations related to pediatric&#xD;
      anesthesia, emergence delirium (ED) is frequent in pre-school children. There is no consensus&#xD;
      on the risk factors and forms of ED prevention, which occurs more frequently after inhalation&#xD;
      anesthesia. On the other hand, anesthesia-induced epigenetic changes may be the key to&#xD;
      understanding various complications and perioperative outcomes. There are no specific&#xD;
      biomarkers for ED. Such biomarkers would be used to measure the risk of ED and would&#xD;
      contribute to prevention and treatment. It has been hypothesized that behavioral changes in&#xD;
      ED may be related to epigenetic modifications, analyzed through the DNA methylation profile.&#xD;
      OBJECTIVES: The primary aim of the study is to investigate the DNA methylation profile in&#xD;
      children with ED. The secondary objectives are to evaluate the correlation between the DNA&#xD;
      methylation profile with the anesthetic technique and the degree of preoperative anxiety.&#xD;
      METHODS: Children (N=322) from 1 to 12 years old, candidates to digestive endoscopy under&#xD;
      general anesthesia will be recruited in an outpatient clinic from a tertiary university&#xD;
      hospital. After informed consent, the child and parents' preoperative anxiety will be&#xD;
      assessed through the modified Yale Preoperative Anxiety Scale (mYPAS) and VAS-Anx (Anxiety&#xD;
      Visual Analogic Scale), respectively. The quality of anesthetic induction will be evaluated&#xD;
      through Pediatric Anesthesia Behavior (PAB) scale and Perioperative Adult Child Behavior&#xD;
      Interaction Scale (PACBIS). After inhaled induction with sevoflurane, blood sample collection&#xD;
      will be performed to evaluate DNA methylation, followed by randomization in two groups to&#xD;
      maintain anesthesia using the venous technique, with propofol or inhaled anesthesia with&#xD;
      sevoflurane. Upon awakening, the ED will be evaluated through PAED (Pediatric Anesthesia&#xD;
      Emergence Delirium) scale. Twenty children from each group presenting ED as well as 08&#xD;
      control cases will have their venous blood samples sent for DNA methylation analysis using&#xD;
      the array technique. After hospital discharge, the postoperative behavioral changes will be&#xD;
      observed through the PHBQ (Post Hospitalization Behavior Questionnaire) questionnaire.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 24, 2018</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 7, 2021</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>Screening</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Participants are not aware of anesthesia technique. Outcome assessor of DNA methylation are not aware of anesthesia technique since they will analyze blood samples.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>DNA methylation profile of children who presented emergence delirium</measure>
    <time_frame>An average of one month after discharge from outpatient clinic.</time_frame>
    <description>DNA methylation profile will be measured through an array experiment in the Illumina iScanSQ (Illumina®) platform using the BeadChip Infinium MethylationEPIC and BeadChip HumanCytoSNP850K kits, following the protocol and manufacturer's instructions. The extracted samples will be initially treated with bisulfite using the EZ DNA Methylation Kit (Zymo Research®). The methylation profile is measured by the Beta value. This value ranges from 0 to 1. Closer to zero, more hypomethylated is the DNA and closer to 1, more hypermethylated is the DNA. To compare the profile, the average Beta value of each patient with emergence delirium and their controls will be used. All raw data obtained will be analyzed by bioinformatics methods to compose the DNA methylation profile of each patient.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Emergence delirium</measure>
    <time_frame>First, 5th, 10th and 15th minutes after anesthesia awakening</time_frame>
    <description>Emergence delirium will be measured through Pediatric Anesthesia Emergence Delirium (PAED) scale. This scale measures 5 items regarding child's awakening: eye contact with the caregiver, purposefulness of child's action, awareness of child's surroundings, child's restlessness and if the child is inconsolable. The first three items are scored from 4 to 1 as follow: 4 not at all, 3 just a little, 2 quite a bit, 1 very much, 0 extremely. Items 4 and 5 are scored as follow: 0 not at all, 1 just a little, 2 quite a bit, 3 very much, 4 extremely. The scores of each item were summed to obtain a total Pediatric Anesthesia Emergence Delirium (PAED) scale score. The degree of emergence delirium increased directly with the total score. We considered a score of ≥ 10 as a cutoff of emergence delirium.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Children's preoperative anxiety</measure>
    <time_frame>10 minutes before induction of anesthesia</time_frame>
    <description>This outcome will be measured through modified Yale Preoperative Anxiety Scale (mYPAS). This scale analysis 5 items regarding child's behavior right before induction of anesthesia. A. Activity 1 Looking around. 2 Not exploring. 3 Moving from toy to parent in unfocused manner. 4 Actively trying to get away. B. Vocalizations 1 Reading or asking questions. 2 Responding to adults but whispers. 3 Quiet or no sounds. 4 Whimpering or silently crying. 5 Crying. 6 Crying or screaming loudly. C. Emotional expressivity 1 Manifestly happy. 2 Neutral. 3 Worried to frightened. 4 Distressed. D. State of apparent arousal 1 Alert. 2 Child sitting still and quiet. 3 Vigilant. 4 Panicked. E. Use of parents 1 Busy playing. 2 Reaches out to parent. 3 Looks to parents quietly. 4 Keeps parent. To calculate the final score, we divide each item rating by the highest possible, add all of the produced values, divide by 5, and multiply by 100. Score of ≥ 30 indicates high anxiety before anesthesia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Caregiver's anxiety before anesthesia</measure>
    <time_frame>10 minutes before induction of anesthesia</time_frame>
    <description>This outcome will be measured through a Visual Analogic Scale (VAS) validated for anxiety. This is a 100-mm scale, which will be applied to caregivers right before induction of anesthesia. Score higher than or equal to 70 mm will be considered as high caregiver's anxiety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Children's behavior and adult interaction during anesthesia induction</measure>
    <time_frame>First minute during monitoring and anesthesia induction</time_frame>
    <description>This outcome will be measured through Perioperative Adult Child Behavior Interaction Scale (PACBIS). The PACBIS consists of four domains (Child Coping, Child Distress, Parent Positive, and Parent Negative), each of which is assigned one of three possible scores (0, 1 or 2). Scores for each domain are assigned based upon the observer's impression of the most typical expression of the subject's behavior within that domain during the observation period. By identifying the specific area leading to maladaptive behavioral responses, we will be able to correlate with occurrence of emergence delirium.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Children's behavior during anesthesia induction</measure>
    <time_frame>First minute during anesthesia induction</time_frame>
    <description>This outcome will be measured through Pediatric Anesthesia Behavior (PAB) score. The Pediatric Anesthesia Behavior (PAB) score is scored from one to three based upon the criteria: Group 1 happy calm and controlled, compliant with induction, Group 2 (sad) tearful and/or withdrawn but compliant with induction or Group 3 (mad) loud vocal resistance (screaming or shouting) and/or physical resistance to induction requiring physical restraint by staff and/or parents. Higher scores (2 or 3) could be associated with emergence delirium, and the development of posthospitalization behavior changes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post hospitalization behavior changes</measure>
    <time_frame>First, 7th and 14th day after discharge from outpatient clinic</time_frame>
    <description>This outcome will be measured through Post Hospital Behavior Questionnaire. This questionnaire is composed by the following questions: Does your child make a fuss about eating? Does your child spend time just sitting or lying? Is your child uninterested in what goes on around him/her? Does your child get upset when you leave him/her alone for a few minutes? Does your child need a lot of help doing things? Is it difficult to get your child interested in doing things? Does your child have temper tantrums? Is it difficult to get your child to talk to you? Does your child have bad dreams or wake up and cry? Does your child have trouble getting to sleep? Does your child have a poor appetite? For each item, parents are asked to compare their child's behavior before hospitalization to their current behavior as follows: much less than before (1), less than before (2), same as before (3), more than before (4), and much more than before (5). Score ≥ 3 will be considered positive.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">175</enrollment>
  <condition>Emergence Delirium</condition>
  <condition>Postoperative Complications</condition>
  <condition>DNA Methylation</condition>
  <arm_group>
    <arm_group_label>Sevoflurane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% for anesthesia induction . After induction and peripheral vein puncture, the anesthesia will be maintained only with sevoflurane 3% until completion of the procedure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Propofol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% until lost of conscience and peripheral vein puncture. After that, sevoflurane will be turned off and its clearance will be analyzed through gas analyzer monitor. From here, anesthesia will be maintained as total venous with continuous propofol infusion 100 mcg.kg.min-1 until completion of the procedure.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sevoflurane</intervention_name>
    <description>All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% for anesthesia induction. After induction and peripheral vein puncture, the anesthesia will be maintained only with sevoflurane 3% until completion of the procedure.</description>
    <arm_group_label>Sevoflurane</arm_group_label>
    <other_name>Inhalation Anesthesia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% until lost of conscience and peripheral vein puncture. After that, sevoflurane will be turned off and its clearance will be analyzed through gas analyzer monitor. From here, anesthesia will be maintained as total venous with continuous propofol infusion 100 mcg.kg.min-1 until completion of the procedure.</description>
    <arm_group_label>Propofol</arm_group_label>
    <other_name>Intravenous Anesthesia</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  children with ASA physical status 1, 2 or 3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  children under psychiatric medication&#xD;
&#xD;
          -  developmental delays&#xD;
&#xD;
          -  genetics syndromes that course with developmental delays&#xD;
&#xD;
          -  contraindication to randomization&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maria JC Carmona, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto da Criança do Hospital das Clinicas da FMUSP</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
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  <verification_date>January 2022</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 26, 2018</study_first_posted>
  <last_update_submitted>January 19, 2022</last_update_submitted>
  <last_update_submitted_qc>January 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo</investigator_affiliation>
    <investigator_full_name>Maria José Carvalho Carmona</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Emergence delirium</keyword>
  <keyword>Child</keyword>
  <keyword>Postoperative complications</keyword>
  <keyword>DNA methylation</keyword>
  <keyword>Epigenetic</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>Postoperative Complications</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
    <mesh_term>Propofol</mesh_term>
    <mesh_term>Sevoflurane</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/NCT03787849
org study id: EPOPED-USP
nct id: NCT03787849
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Emergence delirium (ED) infers the occurrence of behavior and cognition changes during the
      early postoperative period. Main signs and symptoms of ED are the disturbances of
      consciousness and awareness of the environment, with disorientation and perceptual
      alterations, including hypersensitivity to external stimuli and hyperactive motor behaviors.
      The incidence may be higher than 80%. Risk factors include pre-school age, use of
      sevoflurane, ophthalmologic and otorhinolaryngologic surgeries, child anxiety, parental or
      caregiver anxiety. The recurrence of ED is controversial. The only validated scale for
      diagnosis of ED is the PAED (Pediatric Anesthesia Emergence Delirium). Prevention is the best
      approach, as well as the use of alpha-2 agonists, propofol and total intravenous anesthesia.
      There are still no clear markers for postoperative delirium, especially ED. Cognitive
      alterations may be related to epigenetic modifications. Anesthesia-induced epigenetic changes
      may be the key to understanding perioperative complications and outcomes and is a field of
      future research in anesthesia. The study aims to analyze the DNA methylation profile in
      children with ED. A prospective, randomized study will be carried out in up to 322 children
      undergoing general anesthesia (inhalation group or intravenous group) to perform endoscopic
      procedures at the Instituto da Criança, Hospital das Clinicas, Faculdade de Medicina,
      Universidade de Sao Paulo, Brazil. Patients will have blood samples drawn, and analysis of
      the DNA methylation profile through the array technique will be performed in 40 children (20
      of each group ) who presented ED as well as in 08 control cases. Also, the occurrence of ED
      will be correlated with the degree of anxiety of the child, parents and during anesthetic
      induction, in addition to comparing the two anesthetic techniques with the occurrence of ED
      and late postoperative cognitive alterations.
BACKGROUND: The risks of neurotoxicity and late cognitive impairment supported the recent US
      Food and Drug Administration (FDA) recommendation on caution in the indication of anesthesia
      in children up to 3 years of age. Among the cognitive alterations related to pediatric
      anesthesia, emergence delirium (ED) is frequent in pre-school children. There is no consensus
      on the risk factors and forms of ED prevention, which occurs more frequently after inhalation
      anesthesia. On the other hand, anesthesia-induced epigenetic changes may be the key to
      understanding various complications and perioperative outcomes. There are no specific
      biomarkers for ED. Such biomarkers would be used to measure the risk of ED and would
      contribute to prevention and treatment. It has been hypothesized that behavioral changes in
      ED may be related to epigenetic modifications, analyzed through the DNA methylation profile.
      OBJECTIVES: The primary aim of the study is to investigate the DNA methylation profile in
      children with ED. The secondary objectives are to evaluate the correlation between the DNA
      methylation profile with the anesthetic technique and the degree of preoperative anxiety.
      METHODS: Children (N=322) from 1 to 12 years old, candidates to digestive endoscopy under
      general anesthesia will be recruited in an outpatient clinic from a tertiary university
      hospital. After informed consent, the child and parents' preoperative anxiety will be
      assessed through the modified Yale Preoperative Anxiety Scale (mYPAS) and VAS-Anx (Anxiety
      Visual Analogic Scale), respectively. The quality of anesthetic induction will be evaluated
      through Pediatric Anesthesia Behavior (PAB) scale and Perioperative Adult Child Behavior
      Interaction Scale (PACBIS). After inhaled induction with sevoflurane, blood sample collection
      will be performed to evaluate DNA methylation, followed by randomization in two groups to
      maintain anesthesia using the venous technique, with propofol or inhaled anesthesia with
      sevoflurane. Upon awakening, the ED will be evaluated through PAED (Pediatric Anesthesia
      Emergence Delirium) scale. Twenty children from each group presenting ED as well as 08
      control cases will have their venous blood samples sent for DNA methylation analysis using
      the array technique. After hospital discharge, the postoperative behavioral changes will be
      observed through the PHBQ (Post Hospitalization Behavior Questionnaire) questionnaire.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Screening
masking: Double (Participant, Outcomes Assessor)
masking description: Participants are not aware of anesthesia technique. Outcome assessor of DNA methylation are not aware of anesthesia technique since they will analyze blood samples.
measure: DNA methylation profile of children who presented emergence delirium
time frame: An average of one month after discharge from outpatient clinic.
description: DNA methylation profile will be measured through an array experiment in the Illumina iScanSQ (Illumina®) platform using the BeadChip Infinium MethylationEPIC and BeadChip HumanCytoSNP850K kits, following the protocol and manufacturer's instructions. The extracted samples will be initially treated with bisulfite using the EZ DNA Methylation Kit (Zymo Research®). The methylation profile is measured by the Beta value. This value ranges from 0 to 1. Closer to zero, more hypomethylated is the DNA and closer to 1, more hypermethylated is the DNA. To compare the profile, the average Beta value of each patient with emergence delirium and their controls will be used. All raw data obtained will be analyzed by bioinformatics methods to compose the DNA methylation profile of each patient.
measure: Emergence delirium
time frame: First, 5th, 10th and 15th minutes after anesthesia awakening
description: Emergence delirium will be measured through Pediatric Anesthesia Emergence Delirium (PAED) scale. This scale measures 5 items regarding child's awakening: eye contact with the caregiver, purposefulness of child's action, awareness of child's surroundings, child's restlessness and if the child is inconsolable. The first three items are scored from 4 to 1 as follow: 4 not at all, 3 just a little, 2 quite a bit, 1 very much, 0 extremely. Items 4 and 5 are scored as follow: 0 not at all, 1 just a little, 2 quite a bit, 3 very much, 4 extremely. The scores of each item were summed to obtain a total Pediatric Anesthesia Emergence Delirium (PAED) scale score. The degree of emergence delirium increased directly with the total score. We considered a score of ≥ 10 as a cutoff of emergence delirium.
measure: Children's preoperative anxiety
time frame: 10 minutes before induction of anesthesia
description: This outcome will be measured through modified Yale Preoperative Anxiety Scale (mYPAS). This scale analysis 5 items regarding child's behavior right before induction of anesthesia. A. Activity 1 Looking around. 2 Not exploring. 3 Moving from toy to parent in unfocused manner. 4 Actively trying to get away. B. Vocalizations 1 Reading or asking questions. 2 Responding to adults but whispers. 3 Quiet or no sounds. 4 Whimpering or silently crying. 5 Crying. 6 Crying or screaming loudly. C. Emotional expressivity 1 Manifestly happy. 2 Neutral. 3 Worried to frightened. 4 Distressed. D. State of apparent arousal 1 Alert. 2 Child sitting still and quiet. 3 Vigilant. 4 Panicked. E. Use of parents 1 Busy playing. 2 Reaches out to parent. 3 Looks to parents quietly. 4 Keeps parent. To calculate the final score, we divide each item rating by the highest possible, add all of the produced values, divide by 5, and multiply by 100. Score of ≥ 30 indicates high anxiety before anesthesia.
measure: Caregiver's anxiety before anesthesia
time frame: 10 minutes before induction of anesthesia
description: This outcome will be measured through a Visual Analogic Scale (VAS) validated for anxiety. This is a 100-mm scale, which will be applied to caregivers right before induction of anesthesia. Score higher than or equal to 70 mm will be considered as high caregiver's anxiety.
measure: Children's behavior and adult interaction during anesthesia induction
time frame: First minute during monitoring and anesthesia induction
description: This outcome will be measured through Perioperative Adult Child Behavior Interaction Scale (PACBIS). The PACBIS consists of four domains (Child Coping, Child Distress, Parent Positive, and Parent Negative), each of which is assigned one of three possible scores (0, 1 or 2). Scores for each domain are assigned based upon the observer's impression of the most typical expression of the subject's behavior within that domain during the observation period. By identifying the specific area leading to maladaptive behavioral responses, we will be able to correlate with occurrence of emergence delirium.
measure: Children's behavior during anesthesia induction
time frame: First minute during anesthesia induction
description: This outcome will be measured through Pediatric Anesthesia Behavior (PAB) score. The Pediatric Anesthesia Behavior (PAB) score is scored from one to three based upon the criteria: Group 1 happy calm and controlled, compliant with induction, Group 2 (sad) tearful and/or withdrawn but compliant with induction or Group 3 (mad) loud vocal resistance (screaming or shouting) and/or physical resistance to induction requiring physical restraint by staff and/or parents. Higher scores (2 or 3) could be associated with emergence delirium, and the development of posthospitalization behavior changes.
measure: Post hospitalization behavior changes
time frame: First, 7th and 14th day after discharge from outpatient clinic
description: This outcome will be measured through Post Hospital Behavior Questionnaire. This questionnaire is composed by the following questions: Does your child make a fuss about eating? Does your child spend time just sitting or lying? Is your child uninterested in what goes on around him/her? Does your child get upset when you leave him/her alone for a few minutes? Does your child need a lot of help doing things? Is it difficult to get your child interested in doing things? Does your child have temper tantrums? Is it difficult to get your child to talk to you? Does your child have bad dreams or wake up and cry? Does your child have trouble getting to sleep? Does your child have a poor appetite? For each item, parents are asked to compare their child's behavior before hospitalization to their current behavior as follows: much less than before (1), less than before (2), same as before (3), more than before (4), and much more than before (5). Score ≥ 3 will be considered positive.
arm group label: Sevoflurane
arm group type: Active Comparator
description: All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% for anesthesia induction . After induction and peripheral vein puncture, the anesthesia will be maintained only with sevoflurane 3% until completion of the procedure.
arm group label: Propofol
arm group type: Active Comparator
description: All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% until lost of conscience and peripheral vein puncture. After that, sevoflurane will be turned off and its clearance will be analyzed through gas analyzer monitor. From here, anesthesia will be maintained as total venous with continuous propofol infusion 100 mcg.kg.min-1 until completion of the procedure.
intervention type: Drug
intervention name: Sevoflurane
description: All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% for anesthesia induction. After induction and peripheral vein puncture, the anesthesia will be maintained only with sevoflurane 3% until completion of the procedure.
arm group label: Sevoflurane
other name: Inhalation Anesthesia
intervention type: Drug
intervention name: Propofol
description: All children will receive inhalation anesthesia with sevoflurane through facial mask in concentrations between 3-8% until lost of conscience and peripheral vein puncture. After that, sevoflurane will be turned off and its clearance will be analyzed through gas analyzer monitor. From here, anesthesia will be maintained as total venous with continuous propofol infusion 100 mcg.kg.min-1 until completion of the procedure.
arm group label: Propofol
other name: Intravenous Anesthesia
criteria: 
gender: All
minimum age: 1 Year
maximum age: 12 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Maria JC Carmona, PhD
role: Principal Investigator
affiliation: Associate Professor
facility: 
country: Brazil
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responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo
investigator full name: Maria José Carvalho Carmona
investigator title: Associate Professor
mesh term: Delirium
mesh term: Emergence Delirium
mesh term: Postoperative Complications
mesh term: Anesthetics
mesh term: Propofol
mesh term: Sevoflurane
sharing ipd: No