<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/NCT03806270</url>
  </required_header>
  <id_info>
    <org_study_id>KAEK884</org_study_id>
    <nct_id>NCT03806270</nct_id>
  </id_info>
  <brief_title>Hydroxyzine Dihydrochloride Premedication is a Necessity for Strabismus Surgery</brief_title>
  <official_title>Hydroxyzine Dihydrochloride Premedication is a Necessity for Pediatric Patients Undergoing Strabismus Surgery; An Observational Clinical Trial Controlled With Midazolam</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yeditepe University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yeditepe University</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Oculocardiac reflex (OCR) is usually happening in pediatric strabismus surgery and observed&#xD;
      just when the surgent pulls the ocular muscles. The reflex is one of the trigemino-vagal&#xD;
      reflexes, and causes bradycardia, arrhythmia, and even cardiac arrest during eye surgery.&#xD;
&#xD;
      Premedication for relaxation with drugs like hydroxyzine dihydrochloride or midazolam before&#xD;
      surgery of the pediatric population is often used in Turkey, although it is not recommended&#xD;
      in foreign countries. Some recent studies showed that when midazolam and hydroxyzine&#xD;
      dihydrochloride used together not only, they lessen agitation before surgery but also they&#xD;
      prevent emergence agitation.&#xD;
&#xD;
      The primary aim of this prospective observational study is to show the effect of hydroxyzine&#xD;
      dihydrochloride on preventing the pediatric patient from Oculocardiac reflex related to&#xD;
      strabismus surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Strabismus surgery is a frequently performed surgery in the Turkish population from one year&#xD;
      of age to adults. Oculocardiac reflex(OCR) is the most recent complication happens during the&#xD;
      operation, and it occurs approximately 20% to 80% according to its definition, in strabismus&#xD;
      surgery.&#xD;
&#xD;
      OCR is defined as the presence of dysrhythmia or a sudden heart rate decreased by 20% after&#xD;
      traction on the extraocular muscles. OCR is one of the trigemino-vagal reflexes and causes&#xD;
      bradycardia, arrhythmia and even cardiac arrest during eye surgery. To prevent patients from&#xD;
      this complication the operator and anesthesiologist must cooperate during the operation&#xD;
      because the first treatment is to stop traction of the muscle, the second one is to use&#xD;
      atropine after diagnosing bradycardia.&#xD;
&#xD;
      Oculocardiac reflex related trials were done for decades; searching for how and when it&#xD;
      happens, which ocular muscles are related mostly, or which patients are at risk of OCR( age,&#xD;
      heart rate related) are the most researched ones. According to our knowledge, there is no&#xD;
      research about a premedication to prevent OCR during strabismus surgery.&#xD;
&#xD;
      Before this study has planned by the investigator, the investigator had seen many OCR&#xD;
      occurrence related to strabismus surgery, treated either with pausing the surgery or with&#xD;
      atropin intravenous utilization in other clinics. After started working in this university&#xD;
      hospital the investigator recognized those pediatric patients whom premedicated do not need&#xD;
      to treat in the strabismus surgery because the OCR incidence was decreased dramatically. The&#xD;
      investigator has planned this observational research at Yeditepe University Hospital because&#xD;
      in this hospital pediatric patients receive variable oral premedication for sedation before&#xD;
      surgery and for the prevention of emerging agitation. In Yeditepe University Hospital oral&#xD;
      premedication( with variable drugs and variable doses) is nearly always ordered by&#xD;
      anesthesiologists unless there is a comorbidity or allergy anamnesis related to the drugs&#xD;
      planning to use.&#xD;
&#xD;
      This current study is planned as observational. The investigator does not allow to give any&#xD;
      orders about premedications or treatments before or during strabismus surgery. The Induction&#xD;
      and the maintenance of anesthesia are also variable because there is no intervening to the&#xD;
      anesthetist who performs anesthesia. The anesthetist who orders the premedication and&#xD;
      performs anesthesia during strabismus surgery is not related to the trial and do not know the&#xD;
      aim of the trial.&#xD;
&#xD;
      The investigator is informed about the surgery on the day of the operation. The investigator&#xD;
      and the patient's encounter before the study are about having the written consent form after&#xD;
      explanation of the study. The only time to discriminate the patient from the study, by the&#xD;
      anamnesis of the patient that is taken (about any comorbidities) during the encounter,&#xD;
      according to the trials eligibility criteria if the patient and the patient has approved for&#xD;
      including the trial. The investigator has even no permission to access the demographic data&#xD;
      of the patient from the clinical papers which nurses have prepared because the investigator&#xD;
      is not the anesthesiologist of the patient. Therefore the demographic data of the patient and&#xD;
      the premedication performed to the patient is recorded after the operation retrospectively as&#xD;
      the ethical committee approved. So, this current trial is not randomized, and there is no&#xD;
      placebo group also, as a control group which is needed for an interventional one. Patients&#xD;
      included to this trial were grouped after the end of the operation according to the&#xD;
      premedication utilized, while the patient is awake in the service room after the operation,&#xD;
      by having permission to access the demographic data and the premedication that had utilized&#xD;
      before operation retrospectively.&#xD;
&#xD;
      The prospective part of this study is planned to perform in the operation theatre&#xD;
      observationally without knowing which premedication is utilized to the patient. In the&#xD;
      operation theatre, the investigator observes the patient coming to the operation theatre and&#xD;
      records the patients Ramsey Sedation Score before the operation starts. The heart rate 1, the&#xD;
      heart rate 2 and the heart rate 3 data are planned to be recorded from the EKG monitorisation&#xD;
      of the patient; in cooperation with the operator( the operator warns the investigator before&#xD;
      the traction of the orbital muscle and informs about the name of the orbital muscle.). The&#xD;
      investigator calculates the difference between the heart rate3 and heart rate2 and records if&#xD;
      OCR occurred or not. If OCR occurred, the investigator observes and records how it is treated&#xD;
      by the anesthesiologist in the operation theatre and the orbital muscle name which OCR&#xD;
      occurred during its traction. The investigator is also not allowed to order any treatment&#xD;
      about OCR during the operation. Because it is hard to plan this kind of an observational&#xD;
      study the investigator had two years of paperwork to explain the planning of this&#xD;
      observational study to be approved from both &quot;Yeditepe University Clinical Trials Ethical&#xD;
      Committee,&quot; and from &quot;The Turkish Ministry of health, Turkish Medicines and Medical Devices&#xD;
      Agency.&quot; A medical doctor from another clinic is charged with the monitorisation of this&#xD;
      clinical trial by the ethical committee of the Yeditepe University whose identity is not&#xD;
      known by the investigator.&#xD;
&#xD;
      The primary aim of this prospective observational trial is to compare three different&#xD;
      premedication methods observationally, to see if there is any difference in the OCR&#xD;
      occurrence in strabismus surgery. The secondary aim is to compare the Ramsey Sedation Scores&#xD;
      of the patients before surgery, the heart rates during the operation and their effect on OCR.&#xD;
&#xD;
      The hypothesis is that; the pediatric patients premedicated with hydroxyzine dihydrochloride&#xD;
      would be prevented from OCR during strabismus surgery because of the drug's side-effect of&#xD;
      tachycardia while they are sedated before surgery as a positive effect.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2018</start_date>
  <completion_date type="Actual">February 15, 2019</completion_date>
  <primary_completion_date type="Actual">February 15, 2019</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <target_duration>1 Day</target_duration>
  <primary_outcome>
    <measure>Heart Rate-1</measure>
    <time_frame>1 minute, at the &quot;time out&quot;, through study completion an average of 6 months</time_frame>
    <description>The lowest heart rate observed from EKG monitorization at the &quot;time-out&quot; after the anesthesia induction, and just before the surgery starts. Heart rate-1 is a data, not an assessing change, which is recoded during the &quot;time-out&quot;. &quot;The time-out&quot; is when the patient's name, the procedure, the surgent name is repeated before the operation starts.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Heart Rate-2</measure>
    <time_frame>1 minute, at the strabismus surgery operation, through study completion an average of 6 months</time_frame>
    <description>The heart rate observed from EKG monitorization at the time operator warns the investigator just before the traction of the orbital muscle. Heart rate-2 is a data, not an assessing change, which is recorded during the operation at the time operator warns. The heart rate observed from EKG monitorization, before every orbital muscle traction at the time the operator's warning before traction.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Heart Rate-3</measure>
    <time_frame>within 120 seconds after the orbital muscle traction, at the strabismus surgery operation, through study completion an average of 6 months</time_frame>
    <description>The lowest heart rate observed from EKG monitorization, after every orbital muscle traction within 120 seconds. Heart rate-3 is a data, not an assessing change, which is recorded within 120 seconds after traction applied.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Observed Oculocardiac Reflex(OCR)</measure>
    <time_frame>2 minutes, at the strabismus surgery operation after recording Heart Rate-3, through study completion an average of 6 months</time_frame>
    <description>The OCR is a heartbeat anomaly(bradycardia, any arrhythmia, or cardiac arrest) associated with traction applied to the extraocular muscles during strabismus surgery. The specific criteria were as follows: the lowest heart rate observed within 120 seconds from EKG monitorization, after every orbital muscle traction, was less than 20% of the heart rate observed directly preceding traction of the orbital muscle. Additionally, any kind of arrhythmia or cardiac arrest occurrence within 120 seconds after orbital muscle traction was also defined as an OCR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ramsay Sedation Score</measure>
    <time_frame>After patient transferred into the operation theatre and before anesthesia induction, through study completion an average of 6 months</time_frame>
    <description>If Awake; Ramsay 1: Anxious, agitated, restless; Ramsay 2: Cooperative, oriented, tranquil; Ramsay 3: Responsive to commands only If Asleep; Ramsay 4: Brisk response to a light glabellar tap or loud auditory stimulus;&#xD;
Ramsay 5: Sluggish response to a light glabellar tap or loud auditory stimulus; Ramsay 6:&#xD;
No response to a light glabellar tap or loud auditory stimulus</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Orbital Muscles of the Participants With Different Considerations Taken With Respect to the Treatment of OCR</measure>
    <time_frame>within 5 minutes after defining the OCR occurrence, at the strabismus surgery operation, through study completion an average of 6 months</time_frame>
    <description>The investigator records every OCR treatment like; pausing surgery, atropin 20mcg/kg intravenous treatment or cardiac resuscitation.</description>
  </other_outcome>
  <other_outcome>
    <measure>The Orbital Muscle Name Which OCR Occurred During it's Traction</measure>
    <time_frame>within 5 minutes after defining the OCR occurrence, at the strabismus surgery operation, through study completion an average of 6 months</time_frame>
    <description>The investigator records the orbital muscle name which OCR occurred during its traction; like Right eye medial rectus muscle, Right eye inferior oblique muscle, Right eye lateral rectus muscle, Left eye medial rectus muscle, Left eye inferior oblique muscle, Left eye lateral rectus muscle.</description>
  </other_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">45</enrollment>
  <condition>Strabismus</condition>
  <condition>Reflex, Oculocardiac</condition>
  <condition>Hydroxyzine</condition>
  <condition>Bradycardia Sinus</condition>
  <arm_group>
    <arm_group_label>Midazolam</arm_group_label>
    <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Midazolam&amp;Hydroxyzine dihydrochloride1/2</arm_group_label>
    <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Midazolam&amp;Hydroxyzine dihydrochloride</arm_group_label>
    <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <description>Demizolam 15mg/ml ampules, given orally with cherry juice</description>
    <arm_group_label>Midazolam</arm_group_label>
    <arm_group_label>Midazolam&amp;Hydroxyzine dihydrochloride</arm_group_label>
    <arm_group_label>Midazolam&amp;Hydroxyzine dihydrochloride1/2</arm_group_label>
    <other_name>Dormicum,8699505751689,N05CD08</other_name>
    <other_name>Demizolam,8699769750077,N05CD08</other_name>
    <other_name>Zolamide,8680184750025,N05CD08</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxyzine Dihydrochloride</intervention_name>
    <description>Atarax 2mg/ml syrup, given orally</description>
    <arm_group_label>Midazolam&amp;Hydroxyzine dihydrochloride</arm_group_label>
    <arm_group_label>Midazolam&amp;Hydroxyzine dihydrochloride1/2</arm_group_label>
    <other_name>ATARAX 200 ml syrup,8699624570062,N05BB01</other_name>
    <other_name>VALIDOL,8699705590019,N05BB01</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Pediatric patients aged between 1 to 10 years who are diagnosed as strabismus or esotropia,&#xD;
        and scheduled for strabismus surgery.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Strabismus, surgery needed&#xD;
&#xD;
          -  Esotropia, surgery needed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic disease&#xD;
&#xD;
          -  Arrhythmia&#xD;
&#xD;
          -  Glaucoma(narrow-angle)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>10 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ferda F Kartufan, Assist.Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yeditepe University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yeditepe University Ophtalmology Research Center</name>
      <address>
        <city>İstanbul</city>
        <state>Beşiktaş</state>
        <zip>34349</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yeditepe University Hospital</name>
      <address>
        <city>Istanbul</city>
        <state>İçerenköy</state>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <reference>
    <citation>Oh JN, Lee SY, Lee JH, Choi SR, Chin YJ. Effect of ketamine and midazolam on oculocardiac reflex in pediatric strabismus surgery. Korean J Anesthesiol. 2013 Jun;64(6):500-4. doi: 10.4097/kjae.2013.64.6.500. Epub 2013 Jun 24.</citation>
    <PMID>23814649</PMID>
  </reference>
  <reference>
    <citation>Koner O, Ture H, Mercan A, Menda F, Sozubir S. Effects of hydroxyzine-midazolam premedication on sevoflurane-induced paediatric emergence agitation: a prospective randomised clinical trial. Eur J Anaesthesiol. 2011 Sep;28(9):640-5. doi: 10.1097/EJA.0b013e328344db1a.</citation>
    <PMID>21822077</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>December 24, 2018</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <results_first_submitted>February 25, 2019</results_first_submitted>
  <results_first_submitted_qc>October 3, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 4, 2019</results_first_posted>
  <last_update_submitted>October 9, 2019</last_update_submitted>
  <last_update_submitted_qc>October 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Yeditepe University</investigator_affiliation>
    <investigator_full_name>Fatma Ferda Kartufan</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Strabismus surgery</keyword>
  <keyword>Oculocardiac reflex</keyword>
  <keyword>Hydroxyzine dihydrochloride</keyword>
  <keyword>Midazolam</keyword>
  <keyword>Premedication</keyword>
  <keyword>The Ramsay Scale</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Strabismus</mesh_term>
    <mesh_term>Bradycardia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Hydroxyzine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No individual data will be shared.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT03806270/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT03806270/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Midazolam</title>
          <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice</description>
        </group>
        <group group_id="P2">
          <title>Midazolam&amp;Hydroxyzine dihydrochloride1/2</title>
          <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
        </group>
        <group group_id="P3">
          <title>Midazolam&amp;Hydroxyzine Dihydrochloride</title>
          <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Midazolam</title>
          <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice</description>
        </group>
        <group group_id="B2">
          <title>Midazolam&amp;Hydroxyzine dihydrochloride1/2</title>
          <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
        </group>
        <group group_id="B3">
          <title>Midazolam&amp;Hydroxyzine Dihydrochloride</title>
          <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="15"/>
            <count group_id="B4" value="45"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.3" spread="2.5"/>
                    <measurement group_id="B2" value="3.5" spread="2.2"/>
                    <measurement group_id="B3" value="2.9" spread="1.8"/>
                    <measurement group_id="B4" value="4.2" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Turkey</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Heart Rate 1</title>
          <units>beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="114.4" spread="22.1"/>
                    <measurement group_id="B2" value="125.8" spread="13.5"/>
                    <measurement group_id="B3" value="122.33" spread="13.7"/>
                    <measurement group_id="B4" value="120.8" spread="17.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Heart Rate-1</title>
        <description>The lowest heart rate observed from EKG monitorization at the &quot;time-out&quot; after the anesthesia induction, and just before the surgery starts. Heart rate-1 is a data, not an assessing change, which is recoded during the &quot;time-out&quot;. &quot;The time-out&quot; is when the patient's name, the procedure, the surgent name is repeated before the operation starts.</description>
        <time_frame>1 minute, at the &quot;time out&quot;, through study completion an average of 6 months</time_frame>
        <population>Heart Rate1 was measured from each of the 45 participants, during &quot;time-out&quot; right after anesthesia induction and before surgery begins. This measurement is not related to orbital muscle traction.</population>
        <group_list>
          <group group_id="O1">
            <title>Midazolam</title>
            <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice</description>
          </group>
          <group group_id="O2">
            <title>Midazolam&amp;Hydroxyzine dihydrochloride1/2</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
          <group group_id="O3">
            <title>Midazolam&amp;Hydroxyzine Dihydrochloride</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Heart Rate-1</title>
          <description>The lowest heart rate observed from EKG monitorization at the &quot;time-out&quot; after the anesthesia induction, and just before the surgery starts. Heart rate-1 is a data, not an assessing change, which is recoded during the &quot;time-out&quot;. &quot;The time-out&quot; is when the patient's name, the procedure, the surgent name is repeated before the operation starts.</description>
          <population>Heart Rate1 was measured from each of the 45 participants, during &quot;time-out&quot; right after anesthesia induction and before surgery begins. This measurement is not related to orbital muscle traction.</population>
          <units>beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="114.4" spread="22.1"/>
                    <measurement group_id="O2" value="125.8" spread="13.5"/>
                    <measurement group_id="O3" value="122.3" spread="13.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Heart Rate-2</title>
        <description>The heart rate observed from EKG monitorization at the time operator warns the investigator just before the traction of the orbital muscle. Heart rate-2 is a data, not an assessing change, which is recorded during the operation at the time operator warns. The heart rate observed from EKG monitorization, before every orbital muscle traction at the time the operator's warning before traction.</description>
        <time_frame>1 minute, at the strabismus surgery operation, through study completion an average of 6 months</time_frame>
        <population>&quot;Orbital muscles&quot; which surgery performed. It is not equal to the participant number. Related to strabismus surgery, the number of muscles surgery performed on a participant might change; like as one eye 2 muscles, two eyes but 1 muscle for each eye or two eyes 2 muscle for each.</population>
        <group_list>
          <group group_id="O1">
            <title>Midazolam</title>
            <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice</description>
          </group>
          <group group_id="O2">
            <title>Midazolam&amp;Hydroxyzine dihydrochloride1/2</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
          <group group_id="O3">
            <title>Midazolam&amp;Hydroxyzine Dihydrochloride</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Heart Rate-2</title>
          <description>The heart rate observed from EKG monitorization at the time operator warns the investigator just before the traction of the orbital muscle. Heart rate-2 is a data, not an assessing change, which is recorded during the operation at the time operator warns. The heart rate observed from EKG monitorization, before every orbital muscle traction at the time the operator's warning before traction.</description>
          <population>&quot;Orbital muscles&quot; which surgery performed. It is not equal to the participant number. Related to strabismus surgery, the number of muscles surgery performed on a participant might change; like as one eye 2 muscles, two eyes but 1 muscle for each eye or two eyes 2 muscle for each.</population>
          <units>beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Orbital Muscles</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Orbital Muscles</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
                <count group_id="O3" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="110.4" spread="14.1"/>
                    <measurement group_id="O2" value="125.3" spread="13.1"/>
                    <measurement group_id="O3" value="124.8" spread="11.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Heart Rate-3</title>
        <description>The lowest heart rate observed from EKG monitorization, after every orbital muscle traction within 120 seconds. Heart rate-3 is a data, not an assessing change, which is recorded within 120 seconds after traction applied.</description>
        <time_frame>within 120 seconds after the orbital muscle traction, at the strabismus surgery operation, through study completion an average of 6 months</time_frame>
        <population>&quot;Orbital muscles&quot; which surgery performed. It is not equal to the participant number. Related to strabismus surgery, the number of muscles surgery performed on a participant might change; like as one eye 2 muscles, two eyes but 1 muscle for each eye or two eyes 2 muscle for each.</population>
        <group_list>
          <group group_id="O1">
            <title>Midazolam</title>
            <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice</description>
          </group>
          <group group_id="O2">
            <title>Midazolam&amp;Hydroxyzine dihydrochloride1/2</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
          <group group_id="O3">
            <title>Midazolam&amp;Hydroxyzine Dihydrochloride</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Heart Rate-3</title>
          <description>The lowest heart rate observed from EKG monitorization, after every orbital muscle traction within 120 seconds. Heart rate-3 is a data, not an assessing change, which is recorded within 120 seconds after traction applied.</description>
          <population>&quot;Orbital muscles&quot; which surgery performed. It is not equal to the participant number. Related to strabismus surgery, the number of muscles surgery performed on a participant might change; like as one eye 2 muscles, two eyes but 1 muscle for each eye or two eyes 2 muscle for each.</population>
          <units>beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>Orbital Muscles</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Orbital Muscles</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
                <count group_id="O3" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.8" spread="16.6"/>
                    <measurement group_id="O2" value="113.4" spread="15.6"/>
                    <measurement group_id="O3" value="117.9" spread="12.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Observed Oculocardiac Reflex(OCR)</title>
        <description>The OCR is a heartbeat anomaly(bradycardia, any arrhythmia, or cardiac arrest) associated with traction applied to the extraocular muscles during strabismus surgery. The specific criteria were as follows: the lowest heart rate observed within 120 seconds from EKG monitorization, after every orbital muscle traction, was less than 20% of the heart rate observed directly preceding traction of the orbital muscle. Additionally, any kind of arrhythmia or cardiac arrest occurrence within 120 seconds after orbital muscle traction was also defined as an OCR.</description>
        <time_frame>2 minutes, at the strabismus surgery operation after recording Heart Rate-3, through study completion an average of 6 months</time_frame>
        <population>OCR occurrence (0: no and 1: yes) was recorded for every orbital muscle. So it is not equal to the participant number.</population>
        <group_list>
          <group group_id="O1">
            <title>Midazolam</title>
            <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice</description>
          </group>
          <group group_id="O2">
            <title>Midazolam&amp;Hydroxyzine dihydrochloride1/2</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
          <group group_id="O3">
            <title>Midazolam&amp;Hydroxyzine Dihydrochloride</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Observed Oculocardiac Reflex(OCR)</title>
          <description>The OCR is a heartbeat anomaly(bradycardia, any arrhythmia, or cardiac arrest) associated with traction applied to the extraocular muscles during strabismus surgery. The specific criteria were as follows: the lowest heart rate observed within 120 seconds from EKG monitorization, after every orbital muscle traction, was less than 20% of the heart rate observed directly preceding traction of the orbital muscle. Additionally, any kind of arrhythmia or cardiac arrest occurrence within 120 seconds after orbital muscle traction was also defined as an OCR.</description>
          <population>OCR occurrence (0: no and 1: yes) was recorded for every orbital muscle. So it is not equal to the participant number.</population>
          <units>orbital muscles</units>
          <param>Count of Units</param>
          <units_analyzed>orbital muscles</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>orbital muscles</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
                <count group_id="O3" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ramsay Sedation Score</title>
        <description>If Awake; Ramsay 1: Anxious, agitated, restless; Ramsay 2: Cooperative, oriented, tranquil; Ramsay 3: Responsive to commands only If Asleep; Ramsay 4: Brisk response to a light glabellar tap or loud auditory stimulus;&#xD;
Ramsay 5: Sluggish response to a light glabellar tap or loud auditory stimulus; Ramsay 6:&#xD;
No response to a light glabellar tap or loud auditory stimulus</description>
        <time_frame>After patient transferred into the operation theatre and before anesthesia induction, through study completion an average of 6 months</time_frame>
        <population>every participant that had only midazolam or one of the midazolam and hydroxizine premedications before surgery. Ramsay sedation score is evaluated by the investigator before surgery, in the operating theatre without knowing which premedication was utilized to the participant.</population>
        <group_list>
          <group group_id="O1">
            <title>Midazolam</title>
            <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice</description>
          </group>
          <group group_id="O2">
            <title>Midazolam&amp;Hydroxyzine dihydrochloride1/2</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
          <group group_id="O3">
            <title>Midazolam&amp;Hydroxyzine Dihydrochloride</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Ramsay Sedation Score</title>
          <description>If Awake; Ramsay 1: Anxious, agitated, restless; Ramsay 2: Cooperative, oriented, tranquil; Ramsay 3: Responsive to commands only If Asleep; Ramsay 4: Brisk response to a light glabellar tap or loud auditory stimulus;&#xD;
Ramsay 5: Sluggish response to a light glabellar tap or loud auditory stimulus; Ramsay 6:&#xD;
No response to a light glabellar tap or loud auditory stimulus</description>
          <population>every participant that had only midazolam or one of the midazolam and hydroxizine premedications before surgery. Ramsay sedation score is evaluated by the investigator before surgery, in the operating theatre without knowing which premedication was utilized to the participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Ramsay 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Ramsay 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="15"/>
                    <measurement group_id="O3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Ramsay 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Ramsay 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Ramsay 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Ramsay 6</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Orbital Muscles of the Participants With Different Considerations Taken With Respect to the Treatment of OCR</title>
        <description>The investigator records every OCR treatment like; pausing surgery, atropin 20mcg/kg intravenous treatment or cardiac resuscitation.</description>
        <time_frame>within 5 minutes after defining the OCR occurrence, at the strabismus surgery operation, through study completion an average of 6 months</time_frame>
        <population>midazolam group includes 15 participants; total 29 orbital muscles operated, in 15 of them OCR occurred.&#xD;
Midazolam&amp;Hydroxyzine1/2 group includes 15 participants; total 28 orbital muscles operated, in 6 of them OCR occurred.&#xD;
Midazolam&amp;Hydroxyzine group includes 15 participants; total 30 orbital muscles operated, in 1 of them OCR occurred.</population>
        <group_list>
          <group group_id="O1">
            <title>Midazolam</title>
            <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice</description>
          </group>
          <group group_id="O2">
            <title>Midazolam&amp;Hydroxyzine dihydrochloride1/2</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
          <group group_id="O3">
            <title>Midazolam&amp;Hydroxyzine Dihydrochloride</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Orbital Muscles of the Participants With Different Considerations Taken With Respect to the Treatment of OCR</title>
          <description>The investigator records every OCR treatment like; pausing surgery, atropin 20mcg/kg intravenous treatment or cardiac resuscitation.</description>
          <population>midazolam group includes 15 participants; total 29 orbital muscles operated, in 15 of them OCR occurred.&#xD;
Midazolam&amp;Hydroxyzine1/2 group includes 15 participants; total 28 orbital muscles operated, in 6 of them OCR occurred.&#xD;
Midazolam&amp;Hydroxyzine group includes 15 participants; total 30 orbital muscles operated, in 1 of them OCR occurred.</population>
          <units>number of orbital muscle/s, OCR occured</units>
          <param>Number</param>
          <units_analyzed>number of orbital muscle/s, OCR occured</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>number of orbital muscle/s, OCR occured</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>pausing surgery</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>atropin administration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>cardiac resuscitation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>The Orbital Muscle Name Which OCR Occurred During it's Traction</title>
        <description>The investigator records the orbital muscle name which OCR occurred during its traction; like Right eye medial rectus muscle, Right eye inferior oblique muscle, Right eye lateral rectus muscle, Left eye medial rectus muscle, Left eye inferior oblique muscle, Left eye lateral rectus muscle.</description>
        <time_frame>within 5 minutes after defining the OCR occurrence, at the strabismus surgery operation, through study completion an average of 6 months</time_frame>
        <population>The names of the orbital muscles which OCR occurred after traction was performed</population>
        <group_list>
          <group group_id="O1">
            <title>Midazolam</title>
            <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice</description>
          </group>
          <group group_id="O2">
            <title>Midazolam&amp;Hydroxyzine dihydrochloride1/2</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
          <group group_id="O3">
            <title>Midazolam&amp;Hydroxyzine Dihydrochloride</title>
            <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
          </group>
        </group_list>
        <measure>
          <title>The Orbital Muscle Name Which OCR Occurred During it's Traction</title>
          <description>The investigator records the orbital muscle name which OCR occurred during its traction; like Right eye medial rectus muscle, Right eye inferior oblique muscle, Right eye lateral rectus muscle, Left eye medial rectus muscle, Left eye inferior oblique muscle, Left eye lateral rectus muscle.</description>
          <population>The names of the orbital muscles which OCR occurred after traction was performed</population>
          <units>Orbital muscles which OCR occurred</units>
          <param>Count of Units</param>
          <units_analyzed>Orbital muscles which OCR occurred</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Orbital muscles which OCR occurred</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Right eye medial rectus</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Right eye lateral rectus</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Left eye medial rectus</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Left eye lateral rectus</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 day, during strabismus surgery(including anesthesia induction to emerge from anesthesia)</time_frame>
      <desc>regular investigator assessment</desc>
      <group_list>
        <group group_id="E1">
          <title>Midazolam</title>
          <description>Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial. The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups, patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice</description>
        </group>
        <group group_id="E2">
          <title>Midazolam&amp;Hydroxyzine Dihydrochloride</title>
          <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial. The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</description>
        </group>
        <group group_id="E3">
          <title>Midazolam&amp;Hydroxyzine dihydrochloride1/2</title>
          <description>Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial. The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.&#xD;
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.&#xD;
Midazolam: Demizolam 15mg/ml ampules, given orally with cherry juice&#xD;
Hydroxyzine Dihydrochloride: Atarax 2mg/ml syrup, given orally</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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" 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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>this current trial is not a prospective randomized study</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Ferda F. Kartufan</name_or_title>
      <organization>Yeditepe U</organization>
      <phone>+902165784000 ext 4754</phone>
      <email>ferdasozer@gmail.com</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/NCT03806270
org study id: KAEK884
nct id: NCT03806270
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Oculocardiac reflex (OCR) is usually happening in pediatric strabismus surgery and observed
      just when the surgent pulls the ocular muscles. The reflex is one of the trigemino-vagal
      reflexes, and causes bradycardia, arrhythmia, and even cardiac arrest during eye surgery.

      Premedication for relaxation with drugs like hydroxyzine dihydrochloride or midazolam before
      surgery of the pediatric population is often used in Turkey, although it is not recommended
      in foreign countries. Some recent studies showed that when midazolam and hydroxyzine
      dihydrochloride used together not only, they lessen agitation before surgery but also they
      prevent emergence agitation.

      The primary aim of this prospective observational study is to show the effect of hydroxyzine
      dihydrochloride on preventing the pediatric patient from Oculocardiac reflex related to
      strabismus surgery.
Strabismus surgery is a frequently performed surgery in the Turkish population from one year
      of age to adults. Oculocardiac reflex(OCR) is the most recent complication happens during the
      operation, and it occurs approximately 20% to 80% according to its definition, in strabismus
      surgery.

      OCR is defined as the presence of dysrhythmia or a sudden heart rate decreased by 20% after
      traction on the extraocular muscles. OCR is one of the trigemino-vagal reflexes and causes
      bradycardia, arrhythmia and even cardiac arrest during eye surgery. To prevent patients from
      this complication the operator and anesthesiologist must cooperate during the operation
      because the first treatment is to stop traction of the muscle, the second one is to use
      atropine after diagnosing bradycardia.

      Oculocardiac reflex related trials were done for decades; searching for how and when it
      happens, which ocular muscles are related mostly, or which patients are at risk of OCR( age,
      heart rate related) are the most researched ones. According to our knowledge, there is no
      research about a premedication to prevent OCR during strabismus surgery.

      Before this study has planned by the investigator, the investigator had seen many OCR
      occurrence related to strabismus surgery, treated either with pausing the surgery or with
      atropin intravenous utilization in other clinics. After started working in this university
      hospital the investigator recognized those pediatric patients whom premedicated do not need
      to treat in the strabismus surgery because the OCR incidence was decreased dramatically. The
      investigator has planned this observational research at Yeditepe University Hospital because
      in this hospital pediatric patients receive variable oral premedication for sedation before
      surgery and for the prevention of emerging agitation. In Yeditepe University Hospital oral
      premedication( with variable drugs and variable doses) is nearly always ordered by
      anesthesiologists unless there is a comorbidity or allergy anamnesis related to the drugs
      planning to use.

      This current study is planned as observational. The investigator does not allow to give any
      orders about premedications or treatments before or during strabismus surgery. The Induction
      and the maintenance of anesthesia are also variable because there is no intervening to the
      anesthetist who performs anesthesia. The anesthetist who orders the premedication and
      performs anesthesia during strabismus surgery is not related to the trial and do not know the
      aim of the trial.

      The investigator is informed about the surgery on the day of the operation. The investigator
      and the patient's encounter before the study are about having the written consent form after
      explanation of the study. The only time to discriminate the patient from the study, by the
      anamnesis of the patient that is taken (about any comorbidities) during the encounter,
      according to the trials eligibility criteria if the patient and the patient has approved for
      including the trial. The investigator has even no permission to access the demographic data
      of the patient from the clinical papers which nurses have prepared because the investigator
      is not the anesthesiologist of the patient. Therefore the demographic data of the patient and
      the premedication performed to the patient is recorded after the operation retrospectively as
      the ethical committee approved. So, this current trial is not randomized, and there is no
      placebo group also, as a control group which is needed for an interventional one. Patients
      included to this trial were grouped after the end of the operation according to the
      premedication utilized, while the patient is awake in the service room after the operation,
      by having permission to access the demographic data and the premedication that had utilized
      before operation retrospectively.

      The prospective part of this study is planned to perform in the operation theatre
      observationally without knowing which premedication is utilized to the patient. In the
      operation theatre, the investigator observes the patient coming to the operation theatre and
      records the patients Ramsey Sedation Score before the operation starts. The heart rate 1, the
      heart rate 2 and the heart rate 3 data are planned to be recorded from the EKG monitorisation
      of the patient; in cooperation with the operator( the operator warns the investigator before
      the traction of the orbital muscle and informs about the name of the orbital muscle.). The
      investigator calculates the difference between the heart rate3 and heart rate2 and records if
      OCR occurred or not. If OCR occurred, the investigator observes and records how it is treated
      by the anesthesiologist in the operation theatre and the orbital muscle name which OCR
      occurred during its traction. The investigator is also not allowed to order any treatment
      about OCR during the operation. Because it is hard to plan this kind of an observational
      study the investigator had two years of paperwork to explain the planning of this
      observational study to be approved from both "Yeditepe University Clinical Trials Ethical
      Committee," and from "The Turkish Ministry of health, Turkish Medicines and Medical Devices
      Agency." A medical doctor from another clinic is charged with the monitorisation of this
      clinical trial by the ethical committee of the Yeditepe University whose identity is not
      known by the investigator.

      The primary aim of this prospective observational trial is to compare three different
      premedication methods observationally, to see if there is any difference in the OCR
      occurrence in strabismus surgery. The secondary aim is to compare the Ramsey Sedation Scores
      of the patients before surgery, the heart rates during the operation and their effect on OCR.

      The hypothesis is that; the pediatric patients premedicated with hydroxyzine dihydrochloride
      would be prevented from OCR during strabismus surgery because of the drug's side-effect of
      tachycardia while they are sedated before surgery as a positive effect.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Heart Rate-1
time frame: 1 minute, at the "time out", through study completion an average of 6 months
description: The lowest heart rate observed from EKG monitorization at the "time-out" after the anesthesia induction, and just before the surgery starts. Heart rate-1 is a data, not an assessing change, which is recoded during the "time-out". "The time-out" is when the patient's name, the procedure, the surgent name is repeated before the operation starts.
measure: Heart Rate-2
time frame: 1 minute, at the strabismus surgery operation, through study completion an average of 6 months
description: The heart rate observed from EKG monitorization at the time operator warns the investigator just before the traction of the orbital muscle. Heart rate-2 is a data, not an assessing change, which is recorded during the operation at the time operator warns. The heart rate observed from EKG monitorization, before every orbital muscle traction at the time the operator's warning before traction.
measure: Heart Rate-3
time frame: within 120 seconds after the orbital muscle traction, at the strabismus surgery operation, through study completion an average of 6 months
description: The lowest heart rate observed from EKG monitorization, after every orbital muscle traction within 120 seconds. Heart rate-3 is a data, not an assessing change, which is recorded within 120 seconds after traction applied.
measure: Number of Observed Oculocardiac Reflex(OCR)
time frame: 2 minutes, at the strabismus surgery operation after recording Heart Rate-3, through study completion an average of 6 months
description: The OCR is a heartbeat anomaly(bradycardia, any arrhythmia, or cardiac arrest) associated with traction applied to the extraocular muscles during strabismus surgery. The specific criteria were as follows: the lowest heart rate observed within 120 seconds from EKG monitorization, after every orbital muscle traction, was less than 20% of the heart rate observed directly preceding traction of the orbital muscle. Additionally, any kind of arrhythmia or cardiac arrest occurrence within 120 seconds after orbital muscle traction was also defined as an OCR.
measure: Ramsay Sedation Score
time frame: After patient transferred into the operation theatre and before anesthesia induction, through study completion an average of 6 months
description: If Awake; Ramsay 1: Anxious, agitated, restless; Ramsay 2: Cooperative, oriented, tranquil; Ramsay 3: Responsive to commands only If Asleep; Ramsay 4: Brisk response to a light glabellar tap or loud auditory stimulus;
Ramsay 5: Sluggish response to a light glabellar tap or loud auditory stimulus; Ramsay 6:
No response to a light glabellar tap or loud auditory stimulus
measure: Number of Orbital Muscles of the Participants With Different Considerations Taken With Respect to the Treatment of OCR
time frame: within 5 minutes after defining the OCR occurrence, at the strabismus surgery operation, through study completion an average of 6 months
description: The investigator records every OCR treatment like; pausing surgery, atropin 20mcg/kg intravenous treatment or cardiac resuscitation.
measure: The Orbital Muscle Name Which OCR Occurred During it's Traction
time frame: within 5 minutes after defining the OCR occurrence, at the strabismus surgery operation, through study completion an average of 6 months
description: The investigator records the orbital muscle name which OCR occurred during its traction; like Right eye medial rectus muscle, Right eye inferior oblique muscle, Right eye lateral rectus muscle, Left eye medial rectus muscle, Left eye inferior oblique muscle, Left eye lateral rectus muscle.
arm group label: Midazolam
description: Demizolam, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with cherry juice of maximum 5 ml. in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.
In all groups patients are not selected to the groups and premedication and doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.
arm group label: Midazolam&Hydroxyzine dihydrochloride1/2
description: Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with hydroxyzine dihydrochloride (dose of 0.5 mg/kg) in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.
arm group label: Midazolam&Hydroxyzine dihydrochloride
description: Midazolam and Hydroxyzine dihydrochloride, once on the operation day, usually ordered 15 minutes before strabismus operation by another anesthesiologist who is charged to perform anesthesia who is not related with the trial.The maximum dose of 0.5 mg/kg midazolam is given orally with the maximum dose of 1mg/kg hydroxyzine dihydrochloride in Yeditepe University Hospital to the pediatric patients by the anesthesiologists.
In all groups patients are not selected to the groups and premedication doses are not given by the investigator, they grouped according to the premedication given by the anesthesiologists, after the operation retrospectively.
intervention type: Drug
intervention name: Midazolam
description: Demizolam 15mg/ml ampules, given orally with cherry juice
arm group label: Midazolam
arm group label: Midazolam&Hydroxyzine dihydrochloride
arm group label: Midazolam&Hydroxyzine dihydrochloride1/2
other name: Dormicum,8699505751689,N05CD08
other name: Demizolam,8699769750077,N05CD08
other name: Zolamide,8680184750025,N05CD08
intervention type: Drug
intervention name: Hydroxyzine Dihydrochloride
description: Atarax 2mg/ml syrup, given orally
arm group label: Midazolam&Hydroxyzine dihydrochloride
arm group label: Midazolam&Hydroxyzine dihydrochloride1/2
other name: ATARAX 200 ml syrup,8699624570062,N05BB01
other name: VALIDOL,8699705590019,N05BB01
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Year
maximum age: 10 Years
healthy volunteers: No
last name: Ferda F Kartufan, Assist.Prof
role: Principal Investigator
affiliation: Yeditepe University Hospital
facility: 
facility: 
country: Turkey
citation: Oh JN, Lee SY, Lee JH, Choi SR, Chin YJ. Effect of ketamine and midazolam on oculocardiac reflex in pediatric strabismus surgery. Korean J Anesthesiol. 2013 Jun;64(6):500-4. doi: 10.4097/kjae.2013.64.6.500. Epub 2013 Jun 24.
PMID: 23814649
citation: Koner O, Ture H, Mercan A, Menda F, Sozubir S. Effects of hydroxyzine-midazolam premedication on sevoflurane-induced paediatric emergence agitation: a prospective randomised clinical trial. Eur J Anaesthesiol. 2011 Sep;28(9):640-5. doi: 10.1097/EJA.0b013e328344db1a.
PMID: 21822077
responsible party type: Principal Investigator
investigator affiliation: Yeditepe University
investigator full name: Fatma Ferda Kartufan
investigator title: Assistant Professor
mesh term: Strabismus
mesh term: Bradycardia
mesh term: Midazolam
mesh term: Hydroxyzine
sharing ipd: No
ipd description: No individual data will be shared.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: this current trial is not a prospective randomized study
point of contact: 