<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/NCT01716962</url>
  </required_header>
  <id_info>
    <org_study_id>CGMF IRB 100-4473A3</org_study_id>
    <nct_id>NCT01716962</nct_id>
  </id_info>
  <brief_title>Effects of Positive End-expiratory Pressure and Tidal Volume on Fluid Responsiveness of Acute Respiratory Distress Syndrome</brief_title>
  <official_title>Effects of Positive End-expiratory Pressure and Tidal Volume on Fluid Responsiveness of Acute Respiratory Distress Syndrome.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chang Gung Memorial Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fluid responsiveness (FR)refers to the ability of heart to increase its stroke volume in&#xD;
      response to volume load.Low tidal volume and high PEEP exerts contrast effect on the&#xD;
      prediction of fluid responsiveness, the aim of this study is to compare the relative&#xD;
      predicting power of the dynamic preload indicator (PPV, SVV), passive leg raising test, and&#xD;
      pleth variability index (PVI) on the fluid responsiveness of acute respiratory distress&#xD;
      syndrome ventilated with various PEEP levels or various tidal volumes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In septic critically ill mechanically ventilated patients with acute circulatory failure,&#xD;
      inadequate volume resuscitation leads to multiple organ failure. Early goal-directed therapy&#xD;
      emphasizes early and aggressive hemodynamic support in patients with severe sepsis and septic&#xD;
      shock. On the other hand, because of increased microvascular permeability and capillary&#xD;
      leakage, conservative fluid management and more aggressive restriction in fluid accumulation&#xD;
      to reduce lung water and tissue edema has been suggested by acute respiratory distress&#xD;
      syndrome net. Fluid responsiveness refers to the ability of the heart to increase its stroke&#xD;
      volume in response to volume load. Accurately predicting volume responsiveness will be&#xD;
      beneficial in obviating the need for unnecessary fluid loading, and in detecting patients who&#xD;
      may benefit from a volume load.&#xD;
&#xD;
      By inducing cyclic changes in pleural and transpulmonary pressure, mechanical ventilation&#xD;
      results in cyclic changes in the preload and afterload, and therefore, the cyclic variation&#xD;
      in systolic and pulse pressure. Recently, a systemic review concluded that dynamic preload&#xD;
      indicator [pulse pressure variation (PPV), stroke volume variation (SVV)] are highly accurate&#xD;
      in predicting volume responsiveness in critically ill patients. However, this technique is&#xD;
      limited to patients who receive controlled ventilation with adequate tidal volume (&gt; 8 ml/Kg)&#xD;
      and sedation or paralysis is needed to abolish the spontaneous ventilation.&#xD;
&#xD;
      For acute respiratory distress syndrome patients, protective ventilatory strategy suggested&#xD;
      low tidal volume to 6 ml/Kg. On the contrary, high PEEP needed for acute respiratory distress&#xD;
      syndrome to prevent VALI induces a leftward shift to the steep pat of the Frank-Starling&#xD;
      curve and increase the fluid responsiveness. Whether the dynamic preload indicators (PPV and&#xD;
      SVV) are still effective in acute respiratory distress syndrome patients for predicting fluid&#xD;
      responsiveness remain controversial.&#xD;
&#xD;
      Passive leg raising (PLR), by inducing a gravitational transfer of blood from the lower part&#xD;
      of the body toward the central circulatory compartment, can be considered as a brief &quot;self&#xD;
      volume challenge&quot;. Recently, a systemic review and meta-analysis concluded that PLR-induced&#xD;
      changes in cardiac output reliably predict fluid responsiveness regardless of ventilation&#xD;
      mode, underlying cardiac rhythm and technique of measurement and can be recommended for&#xD;
      routine assessment of fluid responsiveness in the majority of ICU population. More&#xD;
      importantly, this prediction remains very valuable in patients with cardiac arrhythmias or&#xD;
      spontaneous breathing activity.&#xD;
&#xD;
      Respiratory variations in the pulse oximeter plethysmographic waveform amplitude (ΔPOP) have&#xD;
      been shown to be able to predict fluid responsiveness in mechanically ventilated patients.&#xD;
      The main advantage of this index is that it is noninvasive, widely available, and&#xD;
      inexpensive. Perfusion index (PI), the percentage between the infrared pulsatile and&#xD;
      nonpulsatile signal, reflects the amplitude of the pulse oximeter waveform. Recently, Pleth&#xD;
      Variability Index (PVI), derived from perfusion index, affords a continuous monitoring of&#xD;
      ΔPOP. PVI has been shown to be correlated to ΔPOP and PPV and has been demonstrated to be&#xD;
      equivalent to SVV as a predictor of fluid responsiveness in ventilated patients during major&#xD;
      surgery. However, whether the PVI can predict the fluid responsiveness in acute respiratory&#xD;
      distress syndrome necessitating low tidal volume and high PEEP is not clear.&#xD;
&#xD;
      Because of the aforementioned contrasting effects of low tidal volume and high PEEP on the&#xD;
      prediction of fluid responsiveness, the aim of this study is to compare the relative&#xD;
      predicting power of the dynamic preload indicator (PPV, SVV), passive leg raising test, and&#xD;
      PVI on the fluid responsiveness of acute respiratory distress syndrome ventilated with&#xD;
      various PEEP levels or various tidal volumes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>November 2012</start_date>
  <primary_completion_date type="Anticipated">July 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>increase of cardiac output after volume expansion</measure>
    <time_frame>4 hours</time_frame>
    <description>Patients are classified to be volume expansion responders or nonresponders according to whether the volume expansion induced cardiac index increase at the end of hydroxyethyl starch infusion is ≧15% or &lt; 15% of baseline cardiac index.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Respiratory Distress Syndrome, Adult</condition>
  <arm_group>
    <arm_group_label>ARDS with acute circulatory failure</arm_group_label>
    <description>acute respiratory distress syndrome with acute circulatory failure with infusion of 6% tetrastarch for a total of 500ml</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Infusion of 6% tetrastarch for a total of 500 ml</intervention_name>
    <arm_group_label>ARDS with acute circulatory failure</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        mechanically ventilated ALL/ARDS patients conforming to the American European Consensus&#xD;
        Conference criteria with acute circulatory failure for whom the attending clinician had&#xD;
        decided to administer fluid will be enrolled.This decision was based on the presence of at&#xD;
        least one clinical sign of inadequate tissue perfusion in the absence of contraindication&#xD;
        for fluid infusion.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria: Clinical signs of inadequate tissue perfusion were defined&#xD;
&#xD;
          1. systolic blood pressure&lt; 9 mmHg(or a decrease &gt; 50 mmHg in previously hypertensive&#xD;
             patients)&#xD;
&#xD;
          2. need of vasopressive drugs(dopamine &gt; 5 ug/Kg/min or norepinephrine)&#xD;
&#xD;
          3. urine output&lt;0.5 mL/Kg/hr for at least 2 hrs&#xD;
&#xD;
          4. tachycardia (heart rate &gt;100/min)&#xD;
&#xD;
          5. presence of skin mottling.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. patient with spontaneous respiratory activity&#xD;
&#xD;
          2. cardiac arrhythmia&#xD;
&#xD;
          3. known intracardiac shunt&#xD;
&#xD;
          4. contraindication for passive leg raising(PLR),e.g.,pelvic trauma&#xD;
&#xD;
          5. unstable spine injuries or leg amputation&#xD;
&#xD;
          6. hemodynamic instability during the procedure,defined by a variation in heart rate or&#xD;
             blood pressure of&gt;10%over the 15-min period before starting the protocol&#xD;
&#xD;
          7. Patients of renal failure necessitate renal replacement therapy will be excluded also.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chung-Chi Huang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chang Gung Memorial Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>10507</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <contact>
      <last_name>Chung-Chi Huang, MD</last_name>
      <phone>033281200</phone>
      <phone_ext>2281</phone_ext>
      <email>cch4848@adm.cgmh.org.tw</email>
    </contact>
    <investigator>
      <last_name>Kuo-Chin Kao, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>November 2012</verification_date>
  <study_first_submitted>October 26, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <last_update_submitted>November 30, 2012</last_update_submitted>
  <last_update_submitted_qc>November 30, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 3, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chang Gung Memorial Hospital</investigator_affiliation>
    <investigator_full_name>Huang chung chi</investigator_full_name>
    <investigator_title>Director of Department of Respiratory Therapy, Chang Gung University</investigator_title>
  </responsible_party>
  <keyword>Acute respiratory distress syndrome, Fluid responsiveness, Pulse pressure variation</keyword>
  <keyword>Pleth variability index, Passive leg raising test</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>March 17, 2015</submitted>
    <returned>March 27, 2015</returned>
  </pending_results>
  <!-- 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/NCT01716962
org study id: CGMF IRB 100-4473A3
nct id: NCT01716962
lead sponsor: 
has dmc: No
Fluid responsiveness (FR)refers to the ability of heart to increase its stroke volume in
      response to volume load.Low tidal volume and high PEEP exerts contrast effect on the
      prediction of fluid responsiveness, the aim of this study is to compare the relative
      predicting power of the dynamic preload indicator (PPV, SVV), passive leg raising test, and
      pleth variability index (PVI) on the fluid responsiveness of acute respiratory distress
      syndrome ventilated with various PEEP levels or various tidal volumes.
In septic critically ill mechanically ventilated patients with acute circulatory failure,
      inadequate volume resuscitation leads to multiple organ failure. Early goal-directed therapy
      emphasizes early and aggressive hemodynamic support in patients with severe sepsis and septic
      shock. On the other hand, because of increased microvascular permeability and capillary
      leakage, conservative fluid management and more aggressive restriction in fluid accumulation
      to reduce lung water and tissue edema has been suggested by acute respiratory distress
      syndrome net. Fluid responsiveness refers to the ability of the heart to increase its stroke
      volume in response to volume load. Accurately predicting volume responsiveness will be
      beneficial in obviating the need for unnecessary fluid loading, and in detecting patients who
      may benefit from a volume load.

      By inducing cyclic changes in pleural and transpulmonary pressure, mechanical ventilation
      results in cyclic changes in the preload and afterload, and therefore, the cyclic variation
      in systolic and pulse pressure. Recently, a systemic review concluded that dynamic preload
      indicator [pulse pressure variation (PPV), stroke volume variation (SVV)] are highly accurate
      in predicting volume responsiveness in critically ill patients. However, this technique is
      limited to patients who receive controlled ventilation with adequate tidal volume (> 8 ml/Kg)
      and sedation or paralysis is needed to abolish the spontaneous ventilation.

      For acute respiratory distress syndrome patients, protective ventilatory strategy suggested
      low tidal volume to 6 ml/Kg. On the contrary, high PEEP needed for acute respiratory distress
      syndrome to prevent VALI induces a leftward shift to the steep pat of the Frank-Starling
      curve and increase the fluid responsiveness. Whether the dynamic preload indicators (PPV and
      SVV) are still effective in acute respiratory distress syndrome patients for predicting fluid
      responsiveness remain controversial.

      Passive leg raising (PLR), by inducing a gravitational transfer of blood from the lower part
      of the body toward the central circulatory compartment, can be considered as a brief "self
      volume challenge". Recently, a systemic review and meta-analysis concluded that PLR-induced
      changes in cardiac output reliably predict fluid responsiveness regardless of ventilation
      mode, underlying cardiac rhythm and technique of measurement and can be recommended for
      routine assessment of fluid responsiveness in the majority of ICU population. More
      importantly, this prediction remains very valuable in patients with cardiac arrhythmias or
      spontaneous breathing activity.

      Respiratory variations in the pulse oximeter plethysmographic waveform amplitude (ΔPOP) have
      been shown to be able to predict fluid responsiveness in mechanically ventilated patients.
      The main advantage of this index is that it is noninvasive, widely available, and
      inexpensive. Perfusion index (PI), the percentage between the infrared pulsatile and
      nonpulsatile signal, reflects the amplitude of the pulse oximeter waveform. Recently, Pleth
      Variability Index (PVI), derived from perfusion index, affords a continuous monitoring of
      ΔPOP. PVI has been shown to be correlated to ΔPOP and PPV and has been demonstrated to be
      equivalent to SVV as a predictor of fluid responsiveness in ventilated patients during major
      surgery. However, whether the PVI can predict the fluid responsiveness in acute respiratory
      distress syndrome necessitating low tidal volume and high PEEP is not clear.

      Because of the aforementioned contrasting effects of low tidal volume and high PEEP on the
      prediction of fluid responsiveness, the aim of this study is to compare the relative
      predicting power of the dynamic preload indicator (PPV, SVV), passive leg raising test, and
      PVI on the fluid responsiveness of acute respiratory distress syndrome ventilated with
      various PEEP levels or various tidal volumes.
observational model: Cohort
time perspective: Prospective
measure: increase of cardiac output after volume expansion
time frame: 4 hours
description: Patients are classified to be volume expansion responders or nonresponders according to whether the volume expansion induced cardiac index increase at the end of hydroxyethyl starch infusion is ≧15% or < 15% of baseline cardiac index.
arm group label: ARDS with acute circulatory failure
description: acute respiratory distress syndrome with acute circulatory failure with infusion of 6% tetrastarch for a total of 500ml
intervention type: Other
intervention name: Infusion of 6% tetrastarch for a total of 500 ml
arm group label: ARDS with acute circulatory failure
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chung-Chi Huang, MD
role: Principal Investigator
affiliation: Chang Gung Memorial Hospital
facility: 
contact: 
investigator: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: Chang Gung Memorial Hospital
investigator full name: Huang chung chi
investigator title: Director of Department of Respiratory Therapy, Chang Gung University
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Syndrome
submitted: March 17, 2015
returned: March 27, 2015