<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/NCT03794271</url>
  </required_header>
  <id_info>
    <org_study_id>DCMC#6</org_study_id>
    <nct_id>NCT03794271</nct_id>
  </id_info>
  <brief_title>Effect of Pupilometer Guided Analgesia on Postoperative Pain</brief_title>
  <acronym>PUPIL_pain</acronym>
  <official_title>Effect of Pupilometer Guided Analgesia on Postoperative Pain Intensity and Perioperative Complications</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Daegu Catholic University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Daegu Catholic University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, the investigators measure a pupil size every 5 minutes during the operation in&#xD;
      patients undergoing laparoscopic cholecystectomy under general anesthesia. The investigators&#xD;
      would compare the postoperative pain intensity between the group adjusted the anesthetic drug&#xD;
      concentration based on the changes of the pupil (Pupil group) and the group based on the&#xD;
      changes of a surgical pleth index (SPI group).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 3, 2019</start_date>
  <completion_date type="Actual">May 10, 2019</completion_date>
  <primary_completion_date type="Actual">May 9, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Peak pain score assessed by numeric rating scale (NRS) in post-anesthesia care unit (PACU)</measure>
    <time_frame>During the PACU stay (Within 1 hour after the PACU admission)</time_frame>
    <description>Patients are asked to rate their pain according to the numeric rating scale (NRS, 0=no pain to 10= extreme pain imaginable) every 10 min after the PACU admission. Peak pain score is the peak NRS during PACU stay. Higher NRS represents a worse outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Intraoperative remifentanil consumption rate</measure>
    <time_frame>During the operation period (Within 2 hour after the anesthesia induction)</time_frame>
    <description>The amount of remifentanil consumption during the operation is calculated by following equation:&#xD;
Total remifentanil consumption (mcg) / body weight of the patients (kg)/ duration of anesthesia (min)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative adverse events</measure>
    <time_frame>Approximately within 1 hour after the PACU admission</time_frame>
    <description>Check the postoperative nausea and vomiting, dizziness, desaturation, urinary retention, itching sensation and bradycardia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Remnant sedation degree</measure>
    <time_frame>Approximately within 1 hour after the PACU admission</time_frame>
    <description>Remnant sedation is evaluated by Riker Sedation-Agitation (RSA) Scale every 10 minutes after the PACU admission.&#xD;
unarousable, minimal or no response to noxious stimuli, does not communicate of follow commands&#xD;
very sedate, arouse to physical stimuli but does not communicate or follow command, may move spontaneously&#xD;
sedate, difficult to arouse but awakens to verbal stimuli or gentle shaking, follows simple commands but drifts off again&#xD;
Calm and cooperative, calm and follows commands&#xD;
agitated, anxious or physically agitated and calms to verbal instructions&#xD;
very agitated, requiring restraint and frequent verbal reminding of limits, biting endotracheal tubes&#xD;
dangerous agitation, pulling at tracheal tube, trying to remove catheters or striking at staff&#xD;
RSA scale 4 means normal. If the RSA &lt;4, it means the patients are sedated. If the RSA &gt;5, it means the patients are agitated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain score assessed by numeric rating scale (NRS) 1 day after the operation</measure>
    <time_frame>On 1 day after the operation</time_frame>
    <description>Patients are asked to rate their pain according to the numeric rating scale (NRS, 0=no pain to 10= extreme pain imaginable) 1 day after the operation. Higher NRS represents a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total analgesic consumption after PACU discharge</measure>
    <time_frame>During 1 day after the operation</time_frame>
    <description>Check the analgesic consumption after PACU discharge including oral, intramuscular and intravenous administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraoperative propofol consumption</measure>
    <time_frame>During the operation period (Within 2 hour after the anesthesia induction)</time_frame>
    <description>The amount of propofol consumption during the operation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intraoperative mean SPI</measure>
    <time_frame>Approximately during 2 hour after the anesthesia induction</time_frame>
    <description>Check the SPI value throughout the operation using the vital recorder program.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>PACU stay time</measure>
    <time_frame>Approximately within 1 hour after the PACU admission</time_frame>
    <description>Duration of time interval from PACU admission to discharge.</description>
  </other_outcome>
  <other_outcome>
    <measure>Intraoperative vasopressor or vasodilator consumption</measure>
    <time_frame>During the operation period (Within 2 hour after the anesthesia induction)</time_frame>
    <description>The amount of ephedrine and nicardipine consumption during the operation</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Cholecystectomy, Laparoscopic</condition>
  <condition>Anesthesia, General</condition>
  <condition>Reflex, Pupillary</condition>
  <arm_group>
    <arm_group_label>Pupilometer group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this group, intraoperative analgesia is performed using pupilometer guided anesthesia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPI group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In this group, intraoperative analgesia is performed using SPI guided anesthesia</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Pupilometer guided anesthesia</intervention_name>
    <description>At least 10 min after anesthesia induction by target-controlled infusion of propofol and remifentanil, baseline values for pupillary diameter is recorded before any surgical procedure.&#xD;
During the operation, propofol effect-site target concentration (Ce) is adjusted to maintain the bispectral index (BIS) value between 40 and 60. Remifentanil Ce is adapted every 5 min based on the changes of pupillary diameter. If the pupillary diameter is increased by more than 30% compared to baseline value, remifentanil concentration is increased by 0.5 ng/ml. If the pupillary diameter is maintained between 5 and 30 % change compared with baseline, remifentanil is not modified. In a case of pupillary diameter is decreased less than 5 % change of baseline, remifentanil concentration is decreased by 0.5 ng/ml.</description>
    <arm_group_label>Pupilometer group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>SPI guided anesthesia</intervention_name>
    <description>During the operation, SPI value should be maintained between 20 and 50 by changing the infusion rate of remifentanil. Even if the SPI is maintained within the target range, the remifentanil infusion rate is increased by 0.5 ng/ml in a case of the SPI value suddenly arises by more than 10.</description>
    <arm_group_label>SPI group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 20 to 65 yr, American Society of Anesthesiologist Physical status(ASA&#xD;
             PS) I to II, scheduled for a laparoscopic cholecystectomy under general anesthesia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of ophthalmologic diseases such as Horner's syndrome or Sjogren's disease.&#xD;
&#xD;
          -  Presence of neurologic or metabolic diseases&#xD;
&#xD;
          -  Medicated that could interfere with the autonomous nervous system (e.g., b- blockers,&#xD;
             anticholinergics)&#xD;
&#xD;
          -  History of substance abuse or psychiatric disease with chronic pain or preoperative&#xD;
             analgesics with pacemaker or arrhythmia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eugene Kim, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Assistant professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Eugene Kim</name>
      <address>
        <city>Daegu</city>
        <state>Nam-gu</state>
        <zip>42472</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <reference>
    <citation>Larson MD, Behrends M. Portable infrared pupillometry: a review. Anesth Analg. 2015 Jun;120(6):1242-53. doi: 10.1213/ANE.0000000000000314.</citation>
    <PMID>25988634</PMID>
  </reference>
  <reference>
    <citation>Huybrechts I, Barvais L, Ducart A, Engelman E, Schmartz D, Koch M. Assessment of thoracic epidural analgesia during general anesthesia using pupillary reflex dilation: a preliminary study. J Cardiothorac Vasc Anesth. 2006 Oct;20(5):664-7. doi: 10.1053/j.jvca.2006.04.004. Epub 2006 Aug 8.</citation>
    <PMID>17023285</PMID>
  </reference>
  <reference>
    <citation>Sabourdin N, Barrois J, Louvet N, Rigouzzo A, Guye ML, Dadure C, Constant I. Pupillometry-guided Intraoperative Remifentanil Administration versus Standard Practice Influences Opioid Use: A Randomized Study. Anesthesiology. 2017 Aug;127(2):284-292. doi: 10.1097/ALN.0000000000001705.</citation>
    <PMID>28719527</PMID>
  </reference>
  <reference>
    <citation>Neice AE, Behrends M, Bokoch MP, Seligman KM, Conrad NM, Larson MD. Prediction of Opioid Analgesic Efficacy by Measurement of Pupillary Unrest. Anesth Analg. 2017 Mar;124(3):915-921. doi: 10.1213/ANE.0000000000001728.</citation>
    <PMID>27941575</PMID>
  </reference>
  <reference>
    <citation>Ledowski T, Burke J, Hruby J. Surgical pleth index: prediction of postoperative pain and influence of arousal. Br J Anaesth. 2016 Sep;117(3):371-4. doi: 10.1093/bja/aew226.</citation>
    <PMID>27543532</PMID>
  </reference>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>January 3, 2019</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>August 9, 2019</last_update_submitted>
  <last_update_submitted_qc>August 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Daegu Catholic University Medical Center</investigator_affiliation>
    <investigator_full_name>JongHae Kim</investigator_full_name>
    <investigator_title>Associate professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anesthetics</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03794271
org study id: DCMC#6
nct id: NCT03794271
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this study, the investigators measure a pupil size every 5 minutes during the operation in
      patients undergoing laparoscopic cholecystectomy under general anesthesia. The investigators
      would compare the postoperative pain intensity between the group adjusted the anesthetic drug
      concentration based on the changes of the pupil (Pupil group) and the group based on the
      changes of a surgical pleth index (SPI group).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Peak pain score assessed by numeric rating scale (NRS) in post-anesthesia care unit (PACU)
time frame: During the PACU stay (Within 1 hour after the PACU admission)
description: Patients are asked to rate their pain according to the numeric rating scale (NRS, 0=no pain to 10= extreme pain imaginable) every 10 min after the PACU admission. Peak pain score is the peak NRS during PACU stay. Higher NRS represents a worse outcome.
measure: Intraoperative remifentanil consumption rate
time frame: During the operation period (Within 2 hour after the anesthesia induction)
description: The amount of remifentanil consumption during the operation is calculated by following equation:
Total remifentanil consumption (mcg) / body weight of the patients (kg)/ duration of anesthesia (min)
measure: Postoperative adverse events
time frame: Approximately within 1 hour after the PACU admission
description: Check the postoperative nausea and vomiting, dizziness, desaturation, urinary retention, itching sensation and bradycardia
measure: Remnant sedation degree
time frame: Approximately within 1 hour after the PACU admission
description: Remnant sedation is evaluated by Riker Sedation-Agitation (RSA) Scale every 10 minutes after the PACU admission.
unarousable, minimal or no response to noxious stimuli, does not communicate of follow commands
very sedate, arouse to physical stimuli but does not communicate or follow command, may move spontaneously
sedate, difficult to arouse but awakens to verbal stimuli or gentle shaking, follows simple commands but drifts off again
Calm and cooperative, calm and follows commands
agitated, anxious or physically agitated and calms to verbal instructions
very agitated, requiring restraint and frequent verbal reminding of limits, biting endotracheal tubes
dangerous agitation, pulling at tracheal tube, trying to remove catheters or striking at staff
RSA scale 4 means normal. If the RSA <4, it means the patients are sedated. If the RSA >5, it means the patients are agitated.
measure: Pain score assessed by numeric rating scale (NRS) 1 day after the operation
time frame: On 1 day after the operation
description: Patients are asked to rate their pain according to the numeric rating scale (NRS, 0=no pain to 10= extreme pain imaginable) 1 day after the operation. Higher NRS represents a worse outcome.
measure: Total analgesic consumption after PACU discharge
time frame: During 1 day after the operation
description: Check the analgesic consumption after PACU discharge including oral, intramuscular and intravenous administration.
measure: Intraoperative propofol consumption
time frame: During the operation period (Within 2 hour after the anesthesia induction)
description: The amount of propofol consumption during the operation
measure: Intraoperative mean SPI
time frame: Approximately during 2 hour after the anesthesia induction
description: Check the SPI value throughout the operation using the vital recorder program.
measure: PACU stay time
time frame: Approximately within 1 hour after the PACU admission
description: Duration of time interval from PACU admission to discharge.
measure: Intraoperative vasopressor or vasodilator consumption
time frame: During the operation period (Within 2 hour after the anesthesia induction)
description: The amount of ephedrine and nicardipine consumption during the operation
arm group label: Pupilometer group
arm group type: Experimental
description: In this group, intraoperative analgesia is performed using pupilometer guided anesthesia.
arm group label: SPI group
arm group type: Active Comparator
description: In this group, intraoperative analgesia is performed using SPI guided anesthesia
intervention type: Procedure
intervention name: Pupilometer guided anesthesia
description: At least 10 min after anesthesia induction by target-controlled infusion of propofol and remifentanil, baseline values for pupillary diameter is recorded before any surgical procedure.
During the operation, propofol effect-site target concentration (Ce) is adjusted to maintain the bispectral index (BIS) value between 40 and 60. Remifentanil Ce is adapted every 5 min based on the changes of pupillary diameter. If the pupillary diameter is increased by more than 30% compared to baseline value, remifentanil concentration is increased by 0.5 ng/ml. If the pupillary diameter is maintained between 5 and 30 % change compared with baseline, remifentanil is not modified. In a case of pupillary diameter is decreased less than 5 % change of baseline, remifentanil concentration is decreased by 0.5 ng/ml.
arm group label: Pupilometer group
intervention type: Procedure
intervention name: SPI guided anesthesia
description: During the operation, SPI value should be maintained between 20 and 50 by changing the infusion rate of remifentanil. Even if the SPI is maintained within the target range, the remifentanil infusion rate is increased by 0.5 ng/ml in a case of the SPI value suddenly arises by more than 10.
arm group label: SPI group
criteria: 
gender: All
minimum age: 20 Years
maximum age: 65 Years
healthy volunteers: No
last name: Eugene Kim, MD, PhD
role: Study Chair
affiliation: Assistant professor
facility: 
country: Korea, Republic of
citation: Larson MD, Behrends M. Portable infrared pupillometry: a review. Anesth Analg. 2015 Jun;120(6):1242-53. doi: 10.1213/ANE.0000000000000314.
PMID: 25988634
citation: Huybrechts I, Barvais L, Ducart A, Engelman E, Schmartz D, Koch M. Assessment of thoracic epidural analgesia during general anesthesia using pupillary reflex dilation: a preliminary study. J Cardiothorac Vasc Anesth. 2006 Oct;20(5):664-7. doi: 10.1053/j.jvca.2006.04.004. Epub 2006 Aug 8.
PMID: 17023285
citation: Sabourdin N, Barrois J, Louvet N, Rigouzzo A, Guye ML, Dadure C, Constant I. Pupillometry-guided Intraoperative Remifentanil Administration versus Standard Practice Influences Opioid Use: A Randomized Study. Anesthesiology. 2017 Aug;127(2):284-292. doi: 10.1097/ALN.0000000000001705.
PMID: 28719527
citation: Neice AE, Behrends M, Bokoch MP, Seligman KM, Conrad NM, Larson MD. Prediction of Opioid Analgesic Efficacy by Measurement of Pupillary Unrest. Anesth Analg. 2017 Mar;124(3):915-921. doi: 10.1213/ANE.0000000000001728.
PMID: 27941575
citation: Ledowski T, Burke J, Hruby J. Surgical pleth index: prediction of postoperative pain and influence of arousal. Br J Anaesth. 2016 Sep;117(3):371-4. doi: 10.1093/bja/aew226.
PMID: 27543532
responsible party type: Principal Investigator
investigator affiliation: Daegu Catholic University Medical Center
investigator full name: JongHae Kim
investigator title: Associate professor
mesh term: Pain, Postoperative
mesh term: Anesthetics