<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/NCT04484727</url>
  </required_header>
  <id_info>
    <org_study_id>ALF-75130-5027</org_study_id>
    <nct_id>NCT04484727</nct_id>
  </id_info>
  <brief_title>&quot;Lung Barometric Measurements in Normal And in Respiratory Distressed Lungs&quot;</brief_title>
  <acronym>LUNAR</acronym>
  <official_title>&quot;Lung Barometric Measurements in Normal And in Respiratory Distressed Lungs&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Göteborg University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sahlgrenska University Hospital, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Göteborg 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>
      Little is known about how lung mechanics are affected during the very early phase after&#xD;
      starting mechanical ventilation. Since the conventional method of measuring esophageal&#xD;
      pressure is complicated, hard to interpret and expensive, there are no studies on lung&#xD;
      mechanics on intensive care patients directly after intubation, during the first hours of&#xD;
      ventilator treatment and forward until the ventilator treatment is withdrawn. Published&#xD;
      studies have collected data using the standard methods from day 1 to 3 of ventilator&#xD;
      treatment for respiratory system mechanics, i.e. the combined mechanics of lung and chest&#xD;
      wall. Consequently, information on lung mechanical properties during the first critical hours&#xD;
      of ventilator treatment is missing and individualization of ventilator care done on the basis&#xD;
      of respiratory system mechanics, which are not representative of lung mechanics on an&#xD;
      individual patient basis. We have developed a PEEP-step method based on a change of PEEP up&#xD;
      and down in one or two steps, where the change in end-expiratory lung volume ΔEELV) is&#xD;
      determined and lung compliance calculated as ΔEELV divided by ΔPEEP (CL = ΔEELV/ΔPEEP). This&#xD;
      simple non-invasive method for separating lung and chest wall mechanics provides an&#xD;
      opportunity to enhance the knowledge of lung compliance and the transpulmonary pressure.&#xD;
      After the two-PEEP-step procedure, the PEEP level where transpulmonary driving pressure is&#xD;
      lowest can be calculated for any chosen tidal volume.&#xD;
&#xD;
      The aim of the present study in the ICU is to survey lung mechanics from start of mechanical&#xD;
      ventilation until extubation and to determine PEEP level with lowest (least injurious)&#xD;
      transpulmonary driving pressure during ventilator treatment. The aim of the study during&#xD;
      anesthesia in the OR, is to survey lung mechanics in lung healthy and identify patients with&#xD;
      lung conditions before anesthesia, which may have an increased risk of postoperative&#xD;
      complications.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Acute lung failure requiring respiratory treatment is the most common cause of intensive care&#xD;
      in Sweden and the condition has a high mortality rate; approximately 40%. To a large extent,&#xD;
      the high mortality rate is due to the patient's underlying disease, e.g. sepsis or trauma but&#xD;
      the respiratory treatment itself can also cause mechanical damage to the lungs with the risk&#xD;
      of secondary development of acute lung failure and failure in other organ systems such as the&#xD;
      liver, kidneys, heart and brain.&#xD;
&#xD;
      In order to reduce the risk and damage of ventilator treatment, it is necessary to improve&#xD;
      monitoring of lung function and to develop and evaluate methods for more gentle respiratory&#xD;
      treatment.&#xD;
&#xD;
      The studies aim to map the elastic properties of the lungs (pulmonary elastance and&#xD;
      transpulmonary drive pressure) in different patient groups, lung healthy and patients with&#xD;
      acute lung failure, using the non-invasive PEEP step method. Since the method is non-invasive&#xD;
      and is based only on a change in the end expiratory pressure in the ventilator, it can be&#xD;
      easily applied during clinical conditions, thus allowing a significant improvement in&#xD;
      monitoring and setting of ventilator therapy in both patients under general anesthesia in&#xD;
      &quot;major surgery&quot; and patients with acute pulmonary failure in intensive care units.&#xD;
&#xD;
      During general anesthesia, patients lung elasticity will be measured immediately after&#xD;
      starting the anesthesia and during surgery and before emergence. In intensive care, the&#xD;
      measurement procedure will be applied immediately after the patient has been placed on a&#xD;
      ventilator and then during respiratory care when normal intensive care measures take place,&#xD;
      such as changing the ventilator setting in terms of breath volume, respiratory rate, end&#xD;
      expiratory pressure (PEEP) and similar measures, as well as respiratory suction and&#xD;
      inhalations to identify elastic properties within the range normally present in intensive&#xD;
      care patients.&#xD;
&#xD;
      Aim:&#xD;
&#xD;
      The aim of the studies is to be able to evaluate lung function during intensive care with new&#xD;
      noninvasive measurement methods such as measuring transpulmonary pressure and calculating&#xD;
      lung drive pressure, to evaluate lung function during intensive care in order to try to find&#xD;
      optimal methods for gentle but effective ventilation of critically ill patients. Studies have&#xD;
      previously shown that more gentle respiratory treatment can reduce mortality in&#xD;
      respiratory-treated intensive care patients. The development and adaptation of new methods&#xD;
      for respiratory treatment and monitoring, can offer better decision support when adjusting&#xD;
      airway pressure and volumes, which may ultimately lead to improvements in the form of shorter&#xD;
      respiratory time and reduced mortality in respiratory patients. An additional aim is to map&#xD;
      normal values of the elastance of the lung (&quot;stiffness&quot;) on a population of normal lungs in&#xD;
      lung-healthy patients who are sedated for planned surgery.&#xD;
&#xD;
      Main issues:&#xD;
&#xD;
        1. Is the measurement with the PEEP step up and down procedure sufficient to accurately&#xD;
           present the lung pressure/volume curve and the transpulmonary drive pressure in&#xD;
           respiratory-treated patient populations in surgery and ICU?&#xD;
&#xD;
        2. Is it possible to collect data on a normal population of lung-healthy patients who are&#xD;
           sedated for operative surgery as well as in intensive care patients with different&#xD;
           degrees of lung failure with the intention of mapping pulmonary elastance/transpulmonary&#xD;
           drive pressure and changes in these parameters at initiation of and during respiratory&#xD;
           treatment?&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      The PEEP-step method for determining lung elastane: The elastic properties of the lung are&#xD;
      measured by increasing PEEP from the clinical baseline level and then lowering the&#xD;
      measurement procedure by setting the breath volume to correspond to the lung volume increase&#xD;
      that occurs during the PEEP increase. PEEP and tidal volume changes are very common routine&#xD;
      measures in both general anesthesia and intensive care. So far, all analysis has been done&#xD;
      through manual calculations off-line, but now the measurement procedure and calculations must&#xD;
      be automated as far as possible and the transpulmonal drive pressure is presented breath by&#xD;
      breath in order to be used for the individualization of the ventilator treatment bedside.&#xD;
      This automation is performed in the form of software development. This work is ongoing and&#xD;
      expected to be completed in August 2020. Then the PEEP-step method can be implemented and&#xD;
      tested in the clinic.&#xD;
&#xD;
      During ten years, in two doctoral theses and four validation studies and additional lung&#xD;
      model studies, the investigators have developed an alternative method for measuring the&#xD;
      transpulmonary drive pressure, which does not require oesophageal pressure measurement, but&#xD;
      only to make a change in the end expiratory pressure (PEEP) in the ventilator and determine&#xD;
      the resulting lung volume increase (DEELV) using the ventilator's volume measurement. The&#xD;
      elastic properties of the lung (lung elastane, EL) are calculated as DPEEP/DEELV and then the&#xD;
      transpulmonary drive pressure is calculated as the volume of breath of the lung elastance, EL&#xD;
      x VT. The above additional measurement methods have been evaluated during the last 15 years.&#xD;
      Measurement methods collects data from standard monitoring equipment used in clinical&#xD;
      anesthesiological practice since the 1980s.&#xD;
&#xD;
      Protocol:&#xD;
&#xD;
      The study is a longitudinal observational study. Measurements will be performed before,&#xD;
      during and after respiratory treatment in patients in intensive care units and in surgical&#xD;
      units. The measurements take place during the respiratory care period with focus on&#xD;
      variations in lung mechanics before and after the procedures included in the clinical routine&#xD;
      regarding respiratory settings and other care. Noninvasive measurement methods will be used&#xD;
      (see above) of which no one has a negative impact on the patient. Physiological data will be&#xD;
      collected from blood gas analyses and monitoring equipment. The monitoring equipment will be&#xD;
      connected to a laptop with software that collects continuous clinical data for analysis.&#xD;
&#xD;
      Informed consent: 1) Adult patients who are about to undergo surgery will be consulted at the&#xD;
      preoperative assessment approximately 1-2 weeks before surgery about their participation. 2)&#xD;
      In adult intensive care patients treated with respiratory therapy, surrogate consent will be&#xD;
      prompted. Since it is not previously predicted which patients will be treated on a ventilator&#xD;
      in the intensive care unit, the patient's relatives will be asked for informed consent.&#xD;
&#xD;
      For key-references, se References&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 1, 2022</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2023</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>Lung-elastance, changes</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Data-collection after intubation, during interventions such as suction, inhalation, posture changes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hours/Days of ventilator treatment</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Registration of Hours/Days of ventilator treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative complications, ICU-complications</measure>
    <time_frame>Through study completion, an average of 1 year</time_frame>
    <description>Registration of the most common postoperative and ICU-complications</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Ventilator-Induced Lung Injury</condition>
  <condition>Ventilatory Failure</condition>
  <condition>Ventilator Lung</condition>
  <condition>Ventilation Therapy; Complications</condition>
  <condition>Ventilator Associated Pneumonia</condition>
  <arm_group>
    <arm_group_label>ICU-patients in ventilator treatment</arm_group_label>
    <description>Directly after intubation and start of mechanical ventilation, a two-PEEP-step up and down procedure with steps of 5-7 cmH2O each is performed and data on airway pressure and tidal volume changes collected. The data is transferred into a dedicated software for calculation of ΔEELV by cumulative difference in expiratory tidal volume before and during PEEP inflation. Consequently, the lung P/V curve from baseline clinical PEEP to end-inspiration of the highest PEEP level. The PEEP level where clinically used tidal volume has the lowest transpulmonary driving pressure is calculated.&#xD;
A one-PEEP-step procedure with a step of 5-7 cmH2O is performed when clinical events such as disconnection of the breathing circuit, posture changes, suctioning, inhalation, CO2 insufflation etc. is performed, and repeated during the whole period of ventilator treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Surgery-patients during general anaesthesia</arm_group_label>
    <description>Directly after intubation and start of mechanical ventilation, a two-PEEP-step up and down procedure with steps of 5-7 cmH2O each, is performed in the same way as described for ICU patients. Data of airway pressure and volumes are transferred into a dedicated software for calculation of ΔEELV by cumulative difference in expiratory tidal volume before and during PEEP inflation. Consequently, the lung P/V curve from baseline clinical PEEP to end-inspiration of the highest PEEP level. The PEEP level where clinically used tidal volume has the lowest transpulmonary driving pressure is calculated.&#xD;
A one-PEEP-step procedure with a step of 5-7 cmH2O is performed when clinical events such as disconnection of the breathing circuit, posture changes or suctioning is performed, and before and after implementation of pneumoperitoneum.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PEEP-step method</intervention_name>
    <description>By changing PEEP in one or two steps up and down, transpulmonary pressure and the lung P/V curve can be determined using a dedicated software collecting data on tidal-volume changes and pressure changes during the PEEP-changes from the standard monitoring equipment or ventilator.</description>
    <arm_group_label>ICU-patients in ventilator treatment</arm_group_label>
    <arm_group_label>Surgery-patients during general anaesthesia</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        ICU-patients or patients in surgery recieving invasive mechancial ventilation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients above18 years&#xD;
&#xD;
          -  ASA 1-3&#xD;
&#xD;
          -  Planned/acute ventilator treatment in ICU or OR&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients under 18 years&#xD;
&#xD;
          -  ASA 4 and above&#xD;
&#xD;
          -  severe COPD/emphysema/heart failure&#xD;
&#xD;
          -  PEEP&gt;16 and/or FiO2 &gt;80%&#xD;
&#xD;
          -  elevated intracranial pressure&#xD;
&#xD;
          -  defect coagulation&#xD;
&#xD;
          -  non-treated known or suspected pneumothorax&#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>Bengt Nellgård, Prof</last_name>
    <role>Study Chair</role>
    <affiliation>Sahlgrenska Academy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sophie Lindgren, Assoc prof</last_name>
    <phone>+46313421000</phone>
    <phone_ext>28587</phone_ext>
    <email>sophie.lindgren@vgregion.se</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sophie Lindgren</name>
      <address>
        <city>Gothenburg</city>
        <state>Västra Götaland</state>
        <zip>41345</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sophie Lindgren, Ass prof</last_name>
      <phone>+46313421000</phone>
      <phone_ext>28587</phone_ext>
      <email>sophie.lindgren@vgregion.se</email>
    </contact>
    <contact_backup>
      <last_name>Ali Abdulhussein, MD</last_name>
      <phone>+46313421000</phone>
      <email>ali.abdulhussein@vgregion.se</email>
    </contact_backup>
    <investigator>
      <last_name>Ali Abdulhussein, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <link>
    <url>http://hdl.handle.net/2077/34396</url>
    <description>Grivans C., Transpulmonary pressure during mechanical ventilation. Doctoral thesis. ISBN 978-91-628-8832-9.</description>
  </link>
  <link>
    <url>http://hdl.handle.net/2077/56893</url>
    <description>Persson P. Lung and chest wall properties during mechanical ventilation. Doctoral thesis. ISBN 978-91-7833-224-3</description>
  </link>
  <reference>
    <citation>Lundin S, Grivans C, Stenqvist O. Transpulmonary pressure and lung elastance can be estimated by a PEEP-step manoeuvre. Acta Anaesthesiol Scand. 2015 Feb;59(2):185-96. doi: 10.1111/aas.12442. Epub 2014 Dec 2.</citation>
    <PMID>25443094</PMID>
  </reference>
  <reference>
    <citation>Stenqvist O, Grivans C, Andersson B, Lundin S. Lung elastance and transpulmonary pressure can be determined without using oesophageal pressure measurements. Acta Anaesthesiol Scand. 2012 Jul;56(6):738-47. doi: 10.1111/j.1399-6576.2012.02696.x. Epub 2012 Apr 23.</citation>
    <PMID>22524531</PMID>
  </reference>
  <reference>
    <citation>Persson P, Lundin S, Stenqvist O. Transpulmonary and pleural pressure in a respiratory system model with an elastic recoiling lung and an expanding chest wall. Intensive Care Med Exp. 2016 Dec;4(1):26. doi: 10.1186/s40635-016-0103-4. Epub 2016 Sep 20.</citation>
    <PMID>27645151</PMID>
  </reference>
  <reference>
    <citation>Persson P, Stenqvist O, Lundin S. Evaluation of lung and chest wall mechanics during anaesthesia using the PEEP-step method. Br J Anaesth. 2018 Apr;120(4):860-867. doi: 10.1016/j.bja.2017.11.076. Epub 2017 Dec 1.</citation>
    <PMID>29576127</PMID>
  </reference>
  <reference>
    <citation>Stenqvist O, Persson P, Stahl CA, Lundin S. Monitoring transpulmonary pressure during anaesthesia using the PEEP-step method. Br J Anaesth. 2018 Dec;121(6):1373-1375. doi: 10.1016/j.bja.2018.08.018. Epub 2018 Oct 9. No abstract available.</citation>
    <PMID>30442269</PMID>
  </reference>
  <reference>
    <citation>Stenqvist O, Persson P, Lundin S. Can we estimate transpulmonary pressure without an esophageal balloon?-yes. Ann Transl Med. 2018 Oct;6(19):392. doi: 10.21037/atm.2018.06.05.</citation>
    <PMID>30460266</PMID>
  </reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>August 15, 2022</last_update_submitted>
  <last_update_submitted_qc>August 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia, Ventilator-Associated</mesh_term>
    <mesh_term>Lung Injury</mesh_term>
    <mesh_term>Ventilator-Induced Lung Injury</mesh_term>
    <mesh_term>Hypoventilation</mesh_term>
  </condition_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/NCT04484727
org study id: ALF-75130-5027
nct id: NCT04484727
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Little is known about how lung mechanics are affected during the very early phase after
      starting mechanical ventilation. Since the conventional method of measuring esophageal
      pressure is complicated, hard to interpret and expensive, there are no studies on lung
      mechanics on intensive care patients directly after intubation, during the first hours of
      ventilator treatment and forward until the ventilator treatment is withdrawn. Published
      studies have collected data using the standard methods from day 1 to 3 of ventilator
      treatment for respiratory system mechanics, i.e. the combined mechanics of lung and chest
      wall. Consequently, information on lung mechanical properties during the first critical hours
      of ventilator treatment is missing and individualization of ventilator care done on the basis
      of respiratory system mechanics, which are not representative of lung mechanics on an
      individual patient basis. We have developed a PEEP-step method based on a change of PEEP up
      and down in one or two steps, where the change in end-expiratory lung volume ΔEELV) is
      determined and lung compliance calculated as ΔEELV divided by ΔPEEP (CL = ΔEELV/ΔPEEP). This
      simple non-invasive method for separating lung and chest wall mechanics provides an
      opportunity to enhance the knowledge of lung compliance and the transpulmonary pressure.
      After the two-PEEP-step procedure, the PEEP level where transpulmonary driving pressure is
      lowest can be calculated for any chosen tidal volume.

      The aim of the present study in the ICU is to survey lung mechanics from start of mechanical
      ventilation until extubation and to determine PEEP level with lowest (least injurious)
      transpulmonary driving pressure during ventilator treatment. The aim of the study during
      anesthesia in the OR, is to survey lung mechanics in lung healthy and identify patients with
      lung conditions before anesthesia, which may have an increased risk of postoperative
      complications.
Background:

      Acute lung failure requiring respiratory treatment is the most common cause of intensive care
      in Sweden and the condition has a high mortality rate; approximately 40%. To a large extent,
      the high mortality rate is due to the patient's underlying disease, e.g. sepsis or trauma but
      the respiratory treatment itself can also cause mechanical damage to the lungs with the risk
      of secondary development of acute lung failure and failure in other organ systems such as the
      liver, kidneys, heart and brain.

      In order to reduce the risk and damage of ventilator treatment, it is necessary to improve
      monitoring of lung function and to develop and evaluate methods for more gentle respiratory
      treatment.

      The studies aim to map the elastic properties of the lungs (pulmonary elastance and
      transpulmonary drive pressure) in different patient groups, lung healthy and patients with
      acute lung failure, using the non-invasive PEEP step method. Since the method is non-invasive
      and is based only on a change in the end expiratory pressure in the ventilator, it can be
      easily applied during clinical conditions, thus allowing a significant improvement in
      monitoring and setting of ventilator therapy in both patients under general anesthesia in
      "major surgery" and patients with acute pulmonary failure in intensive care units.

      During general anesthesia, patients lung elasticity will be measured immediately after
      starting the anesthesia and during surgery and before emergence. In intensive care, the
      measurement procedure will be applied immediately after the patient has been placed on a
      ventilator and then during respiratory care when normal intensive care measures take place,
      such as changing the ventilator setting in terms of breath volume, respiratory rate, end
      expiratory pressure (PEEP) and similar measures, as well as respiratory suction and
      inhalations to identify elastic properties within the range normally present in intensive
      care patients.

      Aim:

      The aim of the studies is to be able to evaluate lung function during intensive care with new
      noninvasive measurement methods such as measuring transpulmonary pressure and calculating
      lung drive pressure, to evaluate lung function during intensive care in order to try to find
      optimal methods for gentle but effective ventilation of critically ill patients. Studies have
      previously shown that more gentle respiratory treatment can reduce mortality in
      respiratory-treated intensive care patients. The development and adaptation of new methods
      for respiratory treatment and monitoring, can offer better decision support when adjusting
      airway pressure and volumes, which may ultimately lead to improvements in the form of shorter
      respiratory time and reduced mortality in respiratory patients. An additional aim is to map
      normal values of the elastance of the lung ("stiffness") on a population of normal lungs in
      lung-healthy patients who are sedated for planned surgery.

      Main issues:

        1. Is the measurement with the PEEP step up and down procedure sufficient to accurately
           present the lung pressure/volume curve and the transpulmonary drive pressure in
           respiratory-treated patient populations in surgery and ICU?

        2. Is it possible to collect data on a normal population of lung-healthy patients who are
           sedated for operative surgery as well as in intensive care patients with different
           degrees of lung failure with the intention of mapping pulmonary elastance/transpulmonary
           drive pressure and changes in these parameters at initiation of and during respiratory
           treatment?

      Methods:

      The PEEP-step method for determining lung elastane: The elastic properties of the lung are
      measured by increasing PEEP from the clinical baseline level and then lowering the
      measurement procedure by setting the breath volume to correspond to the lung volume increase
      that occurs during the PEEP increase. PEEP and tidal volume changes are very common routine
      measures in both general anesthesia and intensive care. So far, all analysis has been done
      through manual calculations off-line, but now the measurement procedure and calculations must
      be automated as far as possible and the transpulmonal drive pressure is presented breath by
      breath in order to be used for the individualization of the ventilator treatment bedside.
      This automation is performed in the form of software development. This work is ongoing and
      expected to be completed in August 2020. Then the PEEP-step method can be implemented and
      tested in the clinic.

      During ten years, in two doctoral theses and four validation studies and additional lung
      model studies, the investigators have developed an alternative method for measuring the
      transpulmonary drive pressure, which does not require oesophageal pressure measurement, but
      only to make a change in the end expiratory pressure (PEEP) in the ventilator and determine
      the resulting lung volume increase (DEELV) using the ventilator's volume measurement. The
      elastic properties of the lung (lung elastane, EL) are calculated as DPEEP/DEELV and then the
      transpulmonary drive pressure is calculated as the volume of breath of the lung elastance, EL
      x VT. The above additional measurement methods have been evaluated during the last 15 years.
      Measurement methods collects data from standard monitoring equipment used in clinical
      anesthesiological practice since the 1980s.

      Protocol:

      The study is a longitudinal observational study. Measurements will be performed before,
      during and after respiratory treatment in patients in intensive care units and in surgical
      units. The measurements take place during the respiratory care period with focus on
      variations in lung mechanics before and after the procedures included in the clinical routine
      regarding respiratory settings and other care. Noninvasive measurement methods will be used
      (see above) of which no one has a negative impact on the patient. Physiological data will be
      collected from blood gas analyses and monitoring equipment. The monitoring equipment will be
      connected to a laptop with software that collects continuous clinical data for analysis.

      Informed consent: 1) Adult patients who are about to undergo surgery will be consulted at the
      preoperative assessment approximately 1-2 weeks before surgery about their participation. 2)
      In adult intensive care patients treated with respiratory therapy, surrogate consent will be
      prompted. Since it is not previously predicted which patients will be treated on a ventilator
      in the intensive care unit, the patient's relatives will be asked for informed consent.

      For key-references, se References
observational model: Cohort
time perspective: Prospective
measure: Lung-elastance, changes
time frame: Through study completion, an average of 1 year
description: Data-collection after intubation, during interventions such as suction, inhalation, posture changes
measure: Hours/Days of ventilator treatment
time frame: Through study completion, an average of 1 year
description: Registration of Hours/Days of ventilator treatment
measure: Postoperative complications, ICU-complications
time frame: Through study completion, an average of 1 year
description: Registration of the most common postoperative and ICU-complications
arm group label: ICU-patients in ventilator treatment
description: Directly after intubation and start of mechanical ventilation, a two-PEEP-step up and down procedure with steps of 5-7 cmH2O each is performed and data on airway pressure and tidal volume changes collected. The data is transferred into a dedicated software for calculation of ΔEELV by cumulative difference in expiratory tidal volume before and during PEEP inflation. Consequently, the lung P/V curve from baseline clinical PEEP to end-inspiration of the highest PEEP level. The PEEP level where clinically used tidal volume has the lowest transpulmonary driving pressure is calculated.
A one-PEEP-step procedure with a step of 5-7 cmH2O is performed when clinical events such as disconnection of the breathing circuit, posture changes, suctioning, inhalation, CO2 insufflation etc. is performed, and repeated during the whole period of ventilator treatment.
arm group label: Surgery-patients during general anaesthesia
description: Directly after intubation and start of mechanical ventilation, a two-PEEP-step up and down procedure with steps of 5-7 cmH2O each, is performed in the same way as described for ICU patients. Data of airway pressure and volumes are transferred into a dedicated software for calculation of ΔEELV by cumulative difference in expiratory tidal volume before and during PEEP inflation. Consequently, the lung P/V curve from baseline clinical PEEP to end-inspiration of the highest PEEP level. The PEEP level where clinically used tidal volume has the lowest transpulmonary driving pressure is calculated.
A one-PEEP-step procedure with a step of 5-7 cmH2O is performed when clinical events such as disconnection of the breathing circuit, posture changes or suctioning is performed, and before and after implementation of pneumoperitoneum.
intervention type: Other
intervention name: PEEP-step method
description: By changing PEEP in one or two steps up and down, transpulmonary pressure and the lung P/V curve can be determined using a dedicated software collecting data on tidal-volume changes and pressure changes during the PEEP-changes from the standard monitoring equipment or ventilator.
arm group label: ICU-patients in ventilator treatment
arm group label: Surgery-patients during general anaesthesia
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bengt Nellgård, Prof
role: Study Chair
affiliation: Sahlgrenska Academy
last name: Sophie Lindgren, Assoc prof
phone: +46313421000
phone ext: 28587
email: sophie.lindgren@vgregion.se
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Sweden
url: http://hdl.handle.net/2077/34396
description: Grivans C., Transpulmonary pressure during mechanical ventilation. Doctoral thesis. ISBN 978-91-628-8832-9.
url: http://hdl.handle.net/2077/56893
description: Persson P. Lung and chest wall properties during mechanical ventilation. Doctoral thesis. ISBN 978-91-7833-224-3
citation: Lundin S, Grivans C, Stenqvist O. Transpulmonary pressure and lung elastance can be estimated by a PEEP-step manoeuvre. Acta Anaesthesiol Scand. 2015 Feb;59(2):185-96. doi: 10.1111/aas.12442. Epub 2014 Dec 2.
PMID: 25443094
citation: Stenqvist O, Grivans C, Andersson B, Lundin S. Lung elastance and transpulmonary pressure can be determined without using oesophageal pressure measurements. Acta Anaesthesiol Scand. 2012 Jul;56(6):738-47. doi: 10.1111/j.1399-6576.2012.02696.x. Epub 2012 Apr 23.
PMID: 22524531
citation: Persson P, Lundin S, Stenqvist O. Transpulmonary and pleural pressure in a respiratory system model with an elastic recoiling lung and an expanding chest wall. Intensive Care Med Exp. 2016 Dec;4(1):26. doi: 10.1186/s40635-016-0103-4. Epub 2016 Sep 20.
PMID: 27645151
citation: Persson P, Stenqvist O, Lundin S. Evaluation of lung and chest wall mechanics during anaesthesia using the PEEP-step method. Br J Anaesth. 2018 Apr;120(4):860-867. doi: 10.1016/j.bja.2017.11.076. Epub 2017 Dec 1.
PMID: 29576127
citation: Stenqvist O, Persson P, Stahl CA, Lundin S. Monitoring transpulmonary pressure during anaesthesia using the PEEP-step method. Br J Anaesth. 2018 Dec;121(6):1373-1375. doi: 10.1016/j.bja.2018.08.018. Epub 2018 Oct 9. No abstract available.
PMID: 30442269
citation: Stenqvist O, Persson P, Lundin S. Can we estimate transpulmonary pressure without an esophageal balloon?-yes. Ann Transl Med. 2018 Oct;6(19):392. doi: 10.21037/atm.2018.06.05.
PMID: 30460266
responsible party type: Sponsor
mesh term: Pneumonia, Ventilator-Associated
mesh term: Lung Injury
mesh term: Ventilator-Induced Lung Injury
mesh term: Hypoventilation
sharing ipd: No