<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/NCT03271905</url>
  </required_header>
  <id_info>
    <org_study_id>CibelleAndrade</org_study_id>
    <nct_id>NCT03271905</nct_id>
  </id_info>
  <brief_title>Influence of Mechanical Ventilation Modes on the Efficacy of Nebulized Bronchodilator</brief_title>
  <official_title>Influence of Mechanical Ventilation Modes on the Efficacy of Nebulized Bronchodilator in the Treatment of Patients With Obstructive Pulmonary Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal do Rio Grande do Norte</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universidade Federal do Rio Grande do Norte</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Aerosol therapy is widely used in intensive care in critically ill patients that use&#xD;
      mechanical ventilation (MV). However, there is a lack of standardization about aerosol&#xD;
      performance in this group of patients. Thus, this study aims to evaluate the effect of&#xD;
      nebulization performed in different ventilatory modes on lung function and regional pulmonary&#xD;
      distribution of critical patients with chronic obstructive pulmonary disease. It is a&#xD;
      clinical trial, crossover, randomized, controlled and blind. Three interventions with&#xD;
      bronchodilators will be performed: in the Pressure Controlled Ventilation mode (PCV) with&#xD;
      positive end expiratory pressure (PEEP) = 85% of autoPEEP, in the PCV mode with PEEP = 15&#xD;
      cmH2Oand in the Pressure Support Mode (PSV). Pulmonary function data will be evaluated&#xD;
      through Electrical Impedance Tomography to evaluate the efficacy of the bronchodilator in&#xD;
      different ventilatory modes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      2. OBJECTIVES&#xD;
&#xD;
      2.1 Primary&#xD;
&#xD;
      • To evaluate the influence of mechanical ventilation modes in the efficacy of nebulized&#xD;
      bronchodilator in ventilator dependent patients with obstructive pulmonary disease.&#xD;
&#xD;
      2.2 Secondary&#xD;
&#xD;
        -  To compare regional ventilation distribution through Ventilation Surface Area (VSA) and&#xD;
           Tidal Impedance Variation (TIV or ∆Z) by electrical impedance tomography (EIT) before,&#xD;
           immediately after, after 1hour (h), 2h and 3h of nebulized bronchodilator in pressure&#xD;
           controlled ventilation (PCV) with and without sedative drugs, and during pressure&#xD;
           support ventilation (PSV).&#xD;
&#xD;
        -  To compare the peak expiratory flow (PEF), change in End-Expiratory Lung Volume (dEELV),&#xD;
           Respiratory Compliance (Crs) and Resistance (R), before, immediately after, after 1h, 2h&#xD;
           and 3h of nebulized bronchodilator by monitoring airway pressure and EIT in ventilator&#xD;
           modes PCV, with and without sedative drugs and PSV .&#xD;
&#xD;
        -  To compare the ventilator modes on the VSA, ∆Z, PEF, dEELV and Crs after nebulized&#xD;
           bronchodilator and the duration of its effects during mechanical ventilation.&#xD;
&#xD;
        -  To compare two different level of PEEP during nebulized bronchodilator on PCV mode while&#xD;
           the patient stay with sedative drugs.&#xD;
&#xD;
           3. METHODS&#xD;
&#xD;
      3.1 Study design This is a randomized crossover, blinded clinical trial. The randomization&#xD;
      procedure will be a simple randomization by random number table. In order to improve&#xD;
      reliability, not transparent sealed envelopes for blind allocation will be used.&#xD;
&#xD;
      3.2 Local and study period This is a multicenter study that involve the following hospitals:&#xD;
      Hospital Miguel Arraes - PE and Real Hospital Português de Beneficência em Pernambuco- PE.&#xD;
      All hospitals are located in the metropolitan region of Recife, Pernambuco, Brazil and the&#xD;
      study will be conducted from February 2016 to December 2019.&#xD;
&#xD;
      3.3 Sample The study population consist of patients with obstructive pulmonary disease&#xD;
      admitted to intensive care unit for MV support who meet the inclusion criteria.&#xD;
&#xD;
      3.4 Sample size Patients will be identified by a daily telephone calls to the ICUs each&#xD;
      morning for data collection. Potential candidate patients will be screened for inclusion and&#xD;
      exclusinon criteria, after the identification of eligible patients. After consent is&#xD;
      obtained, the research team goes to the ICU to start collecting data. The sample size will be&#xD;
      calculated by statistical procedures after conducting a pilot study of 10 patients.&#xD;
&#xD;
      3.5 Technical procedures and tools for data collection&#xD;
&#xD;
      Prior to starting the intervention, clinical and demographic data will be collected according&#xD;
      to the evaluation form, ( Appendix 2). After that, patients will be receive each of 4&#xD;
      interventions, with a minimum of 4 hours between bronchodilator administration to allow for&#xD;
      washout.&#xD;
&#xD;
      3.5.1. Intervention Protocol 3.5.1.1. Step 1: Nebulization during Pressure Controlled&#xD;
      Ventilation (PCV) Mode Initially the patient will be accessed when he still sedated. Two&#xD;
      intervention will be done with a PCV mode in two different ways and the order of the&#xD;
      procedures will be randomized.&#xD;
&#xD;
      One nebulization will be done with a standard PCV mode and parameters will be setted as&#xD;
      follows: sufficient Δ pressure to maintain the patient's tidal volume (vt) at 6 / kg ideal&#xD;
      weight, respiratory rate (RR) at 12 bpm, inspiratory time (Ti) up to 1 second, maintain Ti /&#xD;
      Ttot 0.3 - 0.4 without causing dynamic AutoPEEP, decreasing waveform flow and PEEP level of&#xD;
      85% from static autoPEEP.&#xD;
&#xD;
      Other nebulization will be done also in PCV mode with same parameters, but the level of PEEP&#xD;
      will be increased to 15 cmH2O. Between this two interventions will be given 4 hours for&#xD;
      washout.&#xD;
&#xD;
      After this, we will talk to the medical staff to interrupt sedation, will be given 3 hour for&#xD;
      wash out to start de Step 2.&#xD;
&#xD;
      3.5.1.2. Step 2: Nebulization During Pressure Support Ventilation (PSV) With a clinical&#xD;
      progression of the patient, a 4th evaluation will be done on the first day when the patient&#xD;
      achieve PSV mode. In this ventilation mode the patient will control the Ti, Ttot, RR and&#xD;
      inspiratory flow so it will be set only one Δ pressure for the patient to support a Vt of 6&#xD;
      ml/kg. The lowest minimum value of Δ P is 10 cmH2O and the end of inspiratory phase will be&#xD;
      determined by a decrease at 25% of the patient peak inspiratory flow.&#xD;
&#xD;
      3.5.2 Nebulization Protocol&#xD;
&#xD;
      Nebulized bronchodilator drugs will be Salbutamol Sulfate (aerolin nebulis) and ipratropium&#xD;
      bromide (atrovent) diluted in a saline solution (saline 0.9%) in 3 ml. The vibrating Mesh&#xD;
      nebulizer (Aeroneb Pro-X, Galway, Ireland) will be placed in the inspiratory circuit of the&#xD;
      MV immediately before 'Y' piece using a 22 mm T adapter. The nebulizer is operated by an&#xD;
      electric controller connected mains power. The vibrating Mesh produces aerosol with an&#xD;
      average particle size of 5 μm and will remain on continuously until the end of nebulization.&#xD;
&#xD;
      If a heat moisture exchanger (HME) is used during mechanical ventilation, it must be removed&#xD;
      from between the nebulizer and airway before nebulization so that it does not filter out and&#xD;
      reduce aerosol delivered.&#xD;
&#xD;
      3.5.3 Evaluation by Electrical Impedance Tomography. TIE is a tool of obtaining transverse&#xD;
      plane image of any section of the human body by means of low-power electric current. The&#xD;
      image is obtained from the electric current or potential detected on the surface of the&#xD;
      evaluated area, where each &quot;pixel&quot; image is its impedance or resistivity. Thus, when used in&#xD;
      thoracic follow-up, the EIT is able to evaluate the aeration and ventilation of the patient&#xD;
      through the following variables: distribution of regional lung ventilation by Tidal Impedance&#xD;
      Variation (ΔZ), Ventilation Surface Area (VSA), Percentage of Recruitable Lung (PRLV), Change&#xD;
      in End-Expiratory Lung Volume (dEELV) and Respiratory Compliance (Crs) .&#xD;
&#xD;
      Initially, to evaluate the acute pulmonary impact of nebulizer bronchodilator on different&#xD;
      ventilatory modes, EIT will be be performed before and immediately after the aerosol&#xD;
      administration and repeated with each ventilation mode. Furthermore, the duration of&#xD;
      nebulization effect will be evaluated by performing EIT after 1, 2 and 3h in each ventilation&#xD;
      mode. There will be a &gt; 4 hour washout between bronchodilator administrations.&#xD;
&#xD;
      An impedance tomography (ENLIGHTER, Timpel, Brazil) will be used with the patient in supine&#xD;
      position with a bed elevation of 45◦, so a belt with 32 electrodes will be applied to the&#xD;
      chest, in the position corresponding to the 4th - 5th intercostal space on a shaved skin.&#xD;
      Electrodes have to be positioned for reading electrocardiograms and a flow sensor that should&#xD;
      be attached to the endotracheal tube. After this procedures recording data starts for 3&#xD;
      minutes.&#xD;
&#xD;
      For image acquisition, harmless electrical currents (5-8 nA, 125 KHz) will be injectates&#xD;
      through electrode pairs in rotating sequence, and the potential differences Will be captured&#xD;
      in other non injetantes electrode. Variations in thoracic impedance will be evaluated through&#xD;
      a LabView software (National Instruments, USA) and the data is recorded in separate files for&#xD;
      patients for further analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">April 10, 2017</start_date>
  <completion_date type="Anticipated">December 10, 2019</completion_date>
  <primary_completion_date type="Actual">December 10, 2018</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>The participant is blind about the procedures. The investigator is blind about order of procedure and outcomes assessor is blind about procedures.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in tidal Impedance Variation</measure>
    <time_frame>change from baseline immediately after and at 1, 2, 3 hour of nebulized bronchodilator</time_frame>
    <description>compare regional ventilation distribution by electrical impedance tomography</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in compliance of respiratory sistem (cmH2O)</measure>
    <time_frame>change from baseline immediately after and at 1, 2, 3 hour of nebulized bronchodilator</time_frame>
    <description>Compare results evaluated by lung mechanics evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in peak expiratory flow (lpm)</measure>
    <time_frame>change from baseline immediately after and at 1, 2, 3 hour of nebulized bronchodilator</time_frame>
    <description>Compare results evaluated by EIT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in End-Expiratory Lung Volume</measure>
    <time_frame>change from baseline immediately after and at 1, 2, 3 hour of nebulized bronchodilator</time_frame>
    <description>Compare results evaluated by EIT</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>COPD</condition>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Pressure-controled-ventilation (PCV)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nebulization during mechanical ventilation on a pressure controled ventilation mode.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PCV and high PEEP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nebulization during mechanical ventilation on a pressure controled ventilation mode and PEEP = 15 cmH2O.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pressure suport ventilation (PSV)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nebulization during mechanical ventilation on a pressure suport ventilation mode.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>salbutamol sulfate and ipratropium bromide</intervention_name>
    <description>Nebulization with salbutamol sulfate and ipratropium bromide during mechanical ventilation.</description>
    <arm_group_label>PCV and high PEEP</arm_group_label>
    <arm_group_label>Pressure suport ventilation (PSV)</arm_group_label>
    <arm_group_label>Pressure-controled-ventilation (PCV)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Mesh nebulization</intervention_name>
    <description>Nebulization with Mesh device.</description>
    <arm_group_label>PCV and high PEEP</arm_group_label>
    <arm_group_label>Pressure suport ventilation (PSV)</arm_group_label>
    <arm_group_label>Pressure-controled-ventilation (PCV)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients with asthma or chronic obstructive pulmonary disease (COPD) Invasive mechanical&#xD;
        ventilation Hemodynamically stable&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Prescribed metered dose inhaler (MDI) or intravenous bronchodilators Undrained pneumothorax&#xD;
        Bronchopleural fistula Chest trauma Tracheoesophageal fistula Tracheal granulomas Tracheal&#xD;
        stenosis PEEP dependence&#xD;
&#xD;
        Contraindicated disconnection of the MV&#xD;
&#xD;
        Endotracheal tube diameter less than 7.5&#xD;
&#xD;
        Do not make part of the protocol of daily sedation&#xD;
&#xD;
        No regular ventilatory drive when with out sedation&#xD;
&#xD;
        Do not reach a minimum tidal volume 6 ml/kg with a maximum peak pressure (PIP) of 35 cmH2O&#xD;
        (centimeter of water) during MV.&#xD;
&#xD;
        Do not use the same MV modes that will be tested in this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Cibelle Andrade Lima</name>
      <address>
        <city>Recife</city>
        <state>Pernambuco</state>
        <zip>50610060</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>June 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>May 18, 2019</last_update_submitted>
  <last_update_submitted_qc>May 18, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Federal do Rio Grande do Norte</investigator_affiliation>
    <investigator_full_name>Cibelle Andrade Lima</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bromides</mesh_term>
    <mesh_term>Albuterol</mesh_term>
    <mesh_term>Ipratropium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03271905
org study id: CibelleAndrade
nct id: NCT03271905
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Aerosol therapy is widely used in intensive care in critically ill patients that use
      mechanical ventilation (MV). However, there is a lack of standardization about aerosol
      performance in this group of patients. Thus, this study aims to evaluate the effect of
      nebulization performed in different ventilatory modes on lung function and regional pulmonary
      distribution of critical patients with chronic obstructive pulmonary disease. It is a
      clinical trial, crossover, randomized, controlled and blind. Three interventions with
      bronchodilators will be performed: in the Pressure Controlled Ventilation mode (PCV) with
      positive end expiratory pressure (PEEP) = 85% of autoPEEP, in the PCV mode with PEEP = 15
      cmH2Oand in the Pressure Support Mode (PSV). Pulmonary function data will be evaluated
      through Electrical Impedance Tomography to evaluate the efficacy of the bronchodilator in
      different ventilatory modes.
2. OBJECTIVES

      2.1 Primary

      • To evaluate the influence of mechanical ventilation modes in the efficacy of nebulized
      bronchodilator in ventilator dependent patients with obstructive pulmonary disease.

      2.2 Secondary

        -  To compare regional ventilation distribution through Ventilation Surface Area (VSA) and
           Tidal Impedance Variation (TIV or ∆Z) by electrical impedance tomography (EIT) before,
           immediately after, after 1hour (h), 2h and 3h of nebulized bronchodilator in pressure
           controlled ventilation (PCV) with and without sedative drugs, and during pressure
           support ventilation (PSV).

        -  To compare the peak expiratory flow (PEF), change in End-Expiratory Lung Volume (dEELV),
           Respiratory Compliance (Crs) and Resistance (R), before, immediately after, after 1h, 2h
           and 3h of nebulized bronchodilator by monitoring airway pressure and EIT in ventilator
           modes PCV, with and without sedative drugs and PSV .

        -  To compare the ventilator modes on the VSA, ∆Z, PEF, dEELV and Crs after nebulized
           bronchodilator and the duration of its effects during mechanical ventilation.

        -  To compare two different level of PEEP during nebulized bronchodilator on PCV mode while
           the patient stay with sedative drugs.

           3. METHODS

      3.1 Study design This is a randomized crossover, blinded clinical trial. The randomization
      procedure will be a simple randomization by random number table. In order to improve
      reliability, not transparent sealed envelopes for blind allocation will be used.

      3.2 Local and study period This is a multicenter study that involve the following hospitals:
      Hospital Miguel Arraes - PE and Real Hospital Português de Beneficência em Pernambuco- PE.
      All hospitals are located in the metropolitan region of Recife, Pernambuco, Brazil and the
      study will be conducted from February 2016 to December 2019.

      3.3 Sample The study population consist of patients with obstructive pulmonary disease
      admitted to intensive care unit for MV support who meet the inclusion criteria.

      3.4 Sample size Patients will be identified by a daily telephone calls to the ICUs each
      morning for data collection. Potential candidate patients will be screened for inclusion and
      exclusinon criteria, after the identification of eligible patients. After consent is
      obtained, the research team goes to the ICU to start collecting data. The sample size will be
      calculated by statistical procedures after conducting a pilot study of 10 patients.

      3.5 Technical procedures and tools for data collection

      Prior to starting the intervention, clinical and demographic data will be collected according
      to the evaluation form, ( Appendix 2). After that, patients will be receive each of 4
      interventions, with a minimum of 4 hours between bronchodilator administration to allow for
      washout.

      3.5.1. Intervention Protocol 3.5.1.1. Step 1: Nebulization during Pressure Controlled
      Ventilation (PCV) Mode Initially the patient will be accessed when he still sedated. Two
      intervention will be done with a PCV mode in two different ways and the order of the
      procedures will be randomized.

      One nebulization will be done with a standard PCV mode and parameters will be setted as
      follows: sufficient Δ pressure to maintain the patient's tidal volume (vt) at 6 / kg ideal
      weight, respiratory rate (RR) at 12 bpm, inspiratory time (Ti) up to 1 second, maintain Ti /
      Ttot 0.3 - 0.4 without causing dynamic AutoPEEP, decreasing waveform flow and PEEP level of
      85% from static autoPEEP.

      Other nebulization will be done also in PCV mode with same parameters, but the level of PEEP
      will be increased to 15 cmH2O. Between this two interventions will be given 4 hours for
      washout.

      After this, we will talk to the medical staff to interrupt sedation, will be given 3 hour for
      wash out to start de Step 2.

      3.5.1.2. Step 2: Nebulization During Pressure Support Ventilation (PSV) With a clinical
      progression of the patient, a 4th evaluation will be done on the first day when the patient
      achieve PSV mode. In this ventilation mode the patient will control the Ti, Ttot, RR and
      inspiratory flow so it will be set only one Δ pressure for the patient to support a Vt of 6
      ml/kg. The lowest minimum value of Δ P is 10 cmH2O and the end of inspiratory phase will be
      determined by a decrease at 25% of the patient peak inspiratory flow.

      3.5.2 Nebulization Protocol

      Nebulized bronchodilator drugs will be Salbutamol Sulfate (aerolin nebulis) and ipratropium
      bromide (atrovent) diluted in a saline solution (saline 0.9%) in 3 ml. The vibrating Mesh
      nebulizer (Aeroneb Pro-X, Galway, Ireland) will be placed in the inspiratory circuit of the
      MV immediately before 'Y' piece using a 22 mm T adapter. The nebulizer is operated by an
      electric controller connected mains power. The vibrating Mesh produces aerosol with an
      average particle size of 5 μm and will remain on continuously until the end of nebulization.

      If a heat moisture exchanger (HME) is used during mechanical ventilation, it must be removed
      from between the nebulizer and airway before nebulization so that it does not filter out and
      reduce aerosol delivered.

      3.5.3 Evaluation by Electrical Impedance Tomography. TIE is a tool of obtaining transverse
      plane image of any section of the human body by means of low-power electric current. The
      image is obtained from the electric current or potential detected on the surface of the
      evaluated area, where each "pixel" image is its impedance or resistivity. Thus, when used in
      thoracic follow-up, the EIT is able to evaluate the aeration and ventilation of the patient
      through the following variables: distribution of regional lung ventilation by Tidal Impedance
      Variation (ΔZ), Ventilation Surface Area (VSA), Percentage of Recruitable Lung (PRLV), Change
      in End-Expiratory Lung Volume (dEELV) and Respiratory Compliance (Crs) .

      Initially, to evaluate the acute pulmonary impact of nebulizer bronchodilator on different
      ventilatory modes, EIT will be be performed before and immediately after the aerosol
      administration and repeated with each ventilation mode. Furthermore, the duration of
      nebulization effect will be evaluated by performing EIT after 1, 2 and 3h in each ventilation
      mode. There will be a > 4 hour washout between bronchodilator administrations.

      An impedance tomography (ENLIGHTER, Timpel, Brazil) will be used with the patient in supine
      position with a bed elevation of 45◦, so a belt with 32 electrodes will be applied to the
      chest, in the position corresponding to the 4th - 5th intercostal space on a shaved skin.
      Electrodes have to be positioned for reading electrocardiograms and a flow sensor that should
      be attached to the endotracheal tube. After this procedures recording data starts for 3
      minutes.

      For image acquisition, harmless electrical currents (5-8 nA, 125 KHz) will be injectates
      through electrode pairs in rotating sequence, and the potential differences Will be captured
      in other non injetantes electrode. Variations in thoracic impedance will be evaluated through
      a LabView software (National Instruments, USA) and the data is recorded in separate files for
      patients for further analysis.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: The participant is blind about the procedures. The investigator is blind about order of procedure and outcomes assessor is blind about procedures.
measure: Change in tidal Impedance Variation
time frame: change from baseline immediately after and at 1, 2, 3 hour of nebulized bronchodilator
description: compare regional ventilation distribution by electrical impedance tomography
measure: Change in compliance of respiratory sistem (cmH2O)
time frame: change from baseline immediately after and at 1, 2, 3 hour of nebulized bronchodilator
description: Compare results evaluated by lung mechanics evaluation
measure: Change in peak expiratory flow (lpm)
time frame: change from baseline immediately after and at 1, 2, 3 hour of nebulized bronchodilator
description: Compare results evaluated by EIT
measure: Change in End-Expiratory Lung Volume
time frame: change from baseline immediately after and at 1, 2, 3 hour of nebulized bronchodilator
description: Compare results evaluated by EIT
arm group label: Pressure-controled-ventilation (PCV)
arm group type: Experimental
description: Nebulization during mechanical ventilation on a pressure controled ventilation mode.
arm group label: PCV and high PEEP
arm group type: Experimental
description: Nebulization during mechanical ventilation on a pressure controled ventilation mode and PEEP = 15 cmH2O.
arm group label: Pressure suport ventilation (PSV)
arm group type: Experimental
description: Nebulization during mechanical ventilation on a pressure suport ventilation mode.
intervention type: Drug
intervention name: salbutamol sulfate and ipratropium bromide
description: Nebulization with salbutamol sulfate and ipratropium bromide during mechanical ventilation.
arm group label: PCV and high PEEP
arm group label: Pressure suport ventilation (PSV)
arm group label: Pressure-controled-ventilation (PCV)
intervention type: Device
intervention name: Mesh nebulization
description: Nebulization with Mesh device.
arm group label: PCV and high PEEP
arm group label: Pressure suport ventilation (PSV)
arm group label: Pressure-controled-ventilation (PCV)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Universidade Federal do Rio Grande do Norte
investigator full name: Cibelle Andrade Lima
investigator title: Principal Investigator
mesh term: Bromides
mesh term: Albuterol
mesh term: Ipratropium
sharing ipd: No