<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/NCT03788707</url>
  </required_header>
  <id_info>
    <org_study_id>1368341</org_study_id>
    <nct_id>NCT03788707</nct_id>
  </id_info>
  <brief_title>Capnogram and Fluid Responsiveness</brief_title>
  <official_title>Performance of CO2 Changes to Predict Fluid Responsiveness in Spontaneously Breathing Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Augusta University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Augusta University</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>
      Predicting fluid responsiveness in critically ill patients is of paramount importance. It can&#xD;
      help define an adequate fluid balance. Overzealous fluid administration is poorly tolerated&#xD;
      and has been associated with poor outcomes but so has insufficient administration. Currently&#xD;
      available predictors of fluid responsiveness rely on invasive monitors and require patients&#xD;
      to be on mechanical ventilation. It is thus important to develop non invasive novel methods&#xD;
      to assess fluid responsiveness to provide an accurate management for a favorable outcome. We&#xD;
      propose a readily available non-invasive method that relies on improvement of the ventilation&#xD;
      perfusion mismatch as recorded by end tidal CO2.&#xD;
&#xD;
      Ventilation of physiologic dead space is part of a spectrum of mismatch between ventilation&#xD;
      and perfusion of the lungs. The extent of pulmonary dead space varies depending on factors&#xD;
      affecting pulmonary perfusion (e.g. pulmonary capillary hydrostatic pressure) and alveolar&#xD;
      pressure (e.g. positive pressure ventilation). Compromised pulmonary capillary perfusion can&#xD;
      lead to ventilation-perfusion mismatch in a patient with clear conductive airway and adequate&#xD;
      alveolar oxygen pressure. Alveolar dead space results in decreased CO2 exchange that&#xD;
      translates into lower levels of expired CO2.&#xD;
&#xD;
      Stroke volume of the right ventricle is a major determinant of the pulmonary capillary&#xD;
      perfusion. Right ventricular cardiac output can be increased by passive lower limb elevation&#xD;
      maneuver, which ultimately results in improvement of the ventilation to perfusion ratio. This&#xD;
      effect leads to a higher participation of perfused (and ventilated) alveolar units in gas&#xD;
      exchange and narrowing of the gradient between arterial and expired CO2 concentration.&#xD;
      Performing a passive leg raising (PLR) maneuver leads to stroke volume enhancement in both&#xD;
      healthy patients and in those experiencing hemodynamic instability. Responsiveness to PLR can&#xD;
      be assessed by different methods including echocardiography and pulse pressure variation.&#xD;
      Left ventricular cardiac output (LVCO) can be easily measured by transthoracic echo and be&#xD;
      used as a surrogate of right ventricular preload changes. LVCO can thus be used to assess the&#xD;
      fluid responsiveness of PLR and the effects of on end tidal CO2 that ensue.&#xD;
&#xD;
      We propose this study to test the hypothesis that expired CO2 is a reliable predictor of&#xD;
      fluid responsiveness after performance of the PLR maneuver, based on the assumption that&#xD;
      increasing right ventricular output causes a reduction of the ventilation to perfusion ratio,&#xD;
      leading to increased levels of expired CO2. T&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Due to COVID-19. The study was never started.&#xD;
  </why_stopped>
  <start_date type="Actual">May 1, 2019</start_date>
  <completion_date type="Anticipated">December 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Volunteers will lay flat with a face mask breathing room air while expired CO2 is measured. After 30 seconds, legs will be passively raised for 3 minutes. Changes in expired CO2 before and after leg raising will be compared.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Expired CO2</measure>
    <time_frame>10 minutes</time_frame>
    <description>Area under the curve of a capnogram tracing will be measured in milimiters</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean arterial pressure</measure>
    <time_frame>10 minutes</time_frame>
    <description>Mean arterial pressure in mmHg measured by non invasive oscillometer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>10 minutes</time_frame>
    <description>beats per minute measured by non invasive plethysmography</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Healthy</condition>
  <condition>Blood Pressure</condition>
  <arm_group>
    <arm_group_label>Passive leg raising</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Passive leg raising for 3 minutes after 20 seconds of lying flat</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Passive leg raising</intervention_name>
    <description>After 30 seconds of lying flat, volunteers will have passive leg raising to 45 degrees. Expired CO2 will be measured via a face mask before and after leg raising.</description>
    <arm_group_label>Passive leg raising</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age older than 18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiovascular and respiratory disease reported by the participant&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Augusta University</name>
      <address>
        <city>Augusta</city>
        <state>Georgia</state>
        <zip>30912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>July 21, 2021</last_update_submitted>
  <last_update_submitted_qc>July 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Augusta University</investigator_affiliation>
    <investigator_full_name>Efrain Riveros Perez, MD</investigator_full_name>
    <investigator_title>Assistant Professor. Department of Anesthesiology</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03788707
org study id: 1368341
nct id: NCT03788707
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Predicting fluid responsiveness in critically ill patients is of paramount importance. It can
      help define an adequate fluid balance. Overzealous fluid administration is poorly tolerated
      and has been associated with poor outcomes but so has insufficient administration. Currently
      available predictors of fluid responsiveness rely on invasive monitors and require patients
      to be on mechanical ventilation. It is thus important to develop non invasive novel methods
      to assess fluid responsiveness to provide an accurate management for a favorable outcome. We
      propose a readily available non-invasive method that relies on improvement of the ventilation
      perfusion mismatch as recorded by end tidal CO2.

      Ventilation of physiologic dead space is part of a spectrum of mismatch between ventilation
      and perfusion of the lungs. The extent of pulmonary dead space varies depending on factors
      affecting pulmonary perfusion (e.g. pulmonary capillary hydrostatic pressure) and alveolar
      pressure (e.g. positive pressure ventilation). Compromised pulmonary capillary perfusion can
      lead to ventilation-perfusion mismatch in a patient with clear conductive airway and adequate
      alveolar oxygen pressure. Alveolar dead space results in decreased CO2 exchange that
      translates into lower levels of expired CO2.

      Stroke volume of the right ventricle is a major determinant of the pulmonary capillary
      perfusion. Right ventricular cardiac output can be increased by passive lower limb elevation
      maneuver, which ultimately results in improvement of the ventilation to perfusion ratio. This
      effect leads to a higher participation of perfused (and ventilated) alveolar units in gas
      exchange and narrowing of the gradient between arterial and expired CO2 concentration.
      Performing a passive leg raising (PLR) maneuver leads to stroke volume enhancement in both
      healthy patients and in those experiencing hemodynamic instability. Responsiveness to PLR can
      be assessed by different methods including echocardiography and pulse pressure variation.
      Left ventricular cardiac output (LVCO) can be easily measured by transthoracic echo and be
      used as a surrogate of right ventricular preload changes. LVCO can thus be used to assess the
      fluid responsiveness of PLR and the effects of on end tidal CO2 that ensue.

      We propose this study to test the hypothesis that expired CO2 is a reliable predictor of
      fluid responsiveness after performance of the PLR maneuver, based on the assumption that
      increasing right ventricular output causes a reduction of the ventilation to perfusion ratio,
      leading to increased levels of expired CO2. T
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Volunteers will lay flat with a face mask breathing room air while expired CO2 is measured. After 30 seconds, legs will be passively raised for 3 minutes. Changes in expired CO2 before and after leg raising will be compared.
primary purpose: Diagnostic
masking: None (Open Label)
measure: Expired CO2
time frame: 10 minutes
description: Area under the curve of a capnogram tracing will be measured in milimiters
measure: Mean arterial pressure
time frame: 10 minutes
description: Mean arterial pressure in mmHg measured by non invasive oscillometer
measure: Heart rate
time frame: 10 minutes
description: beats per minute measured by non invasive plethysmography
arm group label: Passive leg raising
arm group type: Experimental
description: Passive leg raising for 3 minutes after 20 seconds of lying flat
intervention type: Other
intervention name: Passive leg raising
description: After 30 seconds of lying flat, volunteers will have passive leg raising to 45 degrees. Expired CO2 will be measured via a face mask before and after leg raising.
arm group label: Passive leg raising
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Augusta University
investigator full name: Efrain Riveros Perez, MD
investigator title: Assistant Professor. Department of Anesthesiology
sharing ipd: Undecided