<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/NCT04455789</url>
  </required_header>
  <id_info>
    <org_study_id>AkdenizU-2</org_study_id>
    <nct_id>NCT04455789</nct_id>
  </id_info>
  <brief_title>Mechanical Ventilation Based on Driving Pressure in Lateral Position</brief_title>
  <official_title>Mechanical Ventilation in Lateral Position During Total Hip Replacement Surgery : Comparison of Driving Pressure With Conventional Ventilation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Akdeniz University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Akdeniz 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>
      Previous studies showed that, best lung protective strategies of ventilation parameters are&#xD;
      based on driving pressure in damaged lungs. But there are few studies concerning the effects&#xD;
      of different positions during different types of surgery on driving pressure with normal&#xD;
      lungs.So the investigators decided to compare mechanical ventilation based on driving&#xD;
      pressure with conventional mechanical ventilation in patients with lateral decubitus position&#xD;
      during total hip replacement surgery. The investigators hypothesised that, there will be&#xD;
      better intraoperative hemodynamic and respiratory parameters with better early postoperative&#xD;
      results in patients whom mechanical ventilation parameters are adjusted according to driving&#xD;
      pressure.&#xD;
&#xD;
      In this randomised, controlled, double blind study, 60 patients who will have total hip&#xD;
      replacement surgery will be recruited to the study. 30 patients will be ventilated by 8 ml/kg&#xD;
      tidal volume and 5 cmH20 PEEP, in conventional lung protective group. And the other 30&#xD;
      patients will be ventilated by 8 ml/kg tidal volume and PEEP level with the lowest driving&#xD;
      pressure.&#xD;
&#xD;
      The investigators primary goal in this study study is to compare the effects of conventional&#xD;
      lung protective ventilation with ventilation based on driving pressure on hemodynamic and&#xD;
      respiratory parameters. And secondly, the investigators aim to compare the effects of these&#xD;
      two techniques s on early postoperative outcome. The investigators primary result parameters&#xD;
      are intra operative fluid consumption, lactate, etC02 and mix venous oxygen saturation&#xD;
      levels.The investigators secondary result parameters are postoperative mechanical&#xD;
      ventilation, ICU stay and discharge times.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There may be physiologic and pathologic pulmonary changes because of inflammatory cytokine&#xD;
      release during total hip replacement surgery due to surgical invasivity or advanced age,&#xD;
      comorbidities, perioperative immobility of patients. Also intraoperative mechanical&#xD;
      ventilation can cause volutrauma, barotrauma or atelectrauma risk because of lateral position&#xD;
      during hip replacement surgery. All these factors can cause pulmonary complications and&#xD;
      vascular permeability increase in dependent and independent regions due to neutrophil&#xD;
      response increase. Intraoperative hypovolemia is often observed in this group patients&#xD;
      because of preoperative prolonged fasting periods, insufficient fluid intake due to&#xD;
      preoperative delirium and depression. Also mechanical ventilation with positive pressure&#xD;
      slightly decreases venous return to the heart resulting decrease in cardiac output. It is&#xD;
      more obvious in the presence of hypovolemia. Providing continuous sufficient intravascular&#xD;
      volume is necessary for prevention of tissue hypoxia and providing optimal cardiac output. It&#xD;
      is known that intra operative hemodynamic optimisation, has positive effects on mortality&#xD;
      ratio. But proper intravascular volume is not always easy to maintain, and it is not always&#xD;
      easy for anaesthetists to identify deficiency or overload of intra operative intravascular&#xD;
      volume. In recent years, intravascular volume therapies are goal directed by the reflections&#xD;
      of respiratory mechanics on arterial pressure and pulse oximetry. Plethysmographic wave&#xD;
      changes observed in pulse oximetry induced by positive pressure ventilation is accepted as&#xD;
      indicator of hypovolemia. Hemodynamic changes induced by respiratory mode can be measured by&#xD;
      invasive arterial monitorization. This dynamic variable is called as pulse pressure variation&#xD;
      index and is correlated with amplitude changes observed in pulse oximetry signals. These&#xD;
      variations are based on changes observed in pulse wavelength due to the changes in&#xD;
      intrathoracic pressure. In some pulse oximetry devices, this is done as standard function as&#xD;
      path variability index (PVI). PVI is measurement of dynamic changes of perfusion index during&#xD;
      a whole respiratory cycle. Pulse oximetry wave length changes enables the evaluate&#xD;
      hypovolemia noninvasively.&#xD;
&#xD;
      PVI is gaining importance as a dynamic parameter in evaluating fluid treatment during&#xD;
      surgery. Goal directed fluid therapy has shown positive effects on results on patient&#xD;
      survival. In a study which fluid therapy was guided by PVI changes and it was reported that,&#xD;
      goal directed fluid therapy had positive results.The investigators also, use some invasive&#xD;
      and noninvasive monitorization techniques, including PVI and CVP, to monitor static and&#xD;
      dynamic hemodynamic parameters during hip replacement surgery and we apply fluids according&#xD;
      to our fluid therapy protocols. The investigators use blood gas analysis to monitor the&#xD;
      efficiency of this treatment.&#xD;
&#xD;
      In this study, in both groups the investigators will apply fluid according to PVI values, so&#xD;
      if any difference detected is observed between groups will be because of the differences of&#xD;
      respiratory parameters between groups. And the investigators can detect, PVI stability and&#xD;
      less fluid needs differences between groups.&#xD;
&#xD;
      PETCO2 is, another parameter which will be evaluated in this study, is a factor of tissue CO2&#xD;
      production (VCO2), alveolar ventilation and cardiac output (mainly pulmonary blood flow). It&#xD;
      is known that, when CO2 produced at the tissues and formed in lungs are constant, the changes&#xD;
      of etCO2 are due to the blood flow differences and it is related to changes of cardiac&#xD;
      output. For this reason, PETCO2 is suggested as a noninvasive measure for continuous&#xD;
      assessment of cardiac output. At the same time, it is possible to comment about changes of&#xD;
      dead space by measuring arterial CO2 pressure.&#xD;
&#xD;
      Decrease of PETCO2, resulted from cardiac output decrease, can not be explained only with the&#xD;
      decrease rate of excretion of CO2, but also can be explained by the changes of production of&#xD;
      CO2 caused by dependency to oxygen supply. On the contrary, when cardiac output is high,&#xD;
      pulmonary blood flow is no longer a limiting factor for PETCO2 formation, and PETCO2 is&#xD;
      related to sufficiency of alveolar ventilation.&#xD;
&#xD;
      As a result, etCO2 measurement has some advantages; it is simple noninvasive and does not&#xD;
      require a invasive hemodynamic measurement.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2019</start_date>
  <completion_date type="Anticipated">August 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>volume of intraoperative fluid administration</measure>
    <time_frame>during intraoperative period</time_frame>
    <description>the patients will receive intraoperative fluids according to a protocol based on PVI.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>intraoperative etCO2 levels</measure>
    <time_frame>during mechanical ventilation</time_frame>
    <description>et CO2 levels will be recorded form the anesthesia machine monitor</description>
  </primary_outcome>
  <primary_outcome>
    <measure>lactate levels</measure>
    <time_frame>during intraoperative period</time_frame>
    <description>lactate levels will be obtained from the serial blood gas analysis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>postoperative mechanical ventilation duration</measure>
    <time_frame>From end of surgery to the end of mechanical ventilation duration in the intensive care unit until the patient is extubated, up to 3 days</time_frame>
    <description>The patient's need for mechanical ventilation, after the surgery, will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>postoperative intensive care stay</measure>
    <time_frame>From end of operation to the end of intensive care stay, up to 1 week</time_frame>
    <description>after the end of surgery the patients need for intensive care will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>length of hospital stay after the operation</measure>
    <time_frame>form end of surgery to the end of hospital stay, up to 10 days</time_frame>
    <description>the effects of mechanical ventilation on the days of hospital stay will be assessed</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Fracture of Hip</condition>
  <condition>Osteoarthritis, Hip</condition>
  <condition>Congenital Hip Deformity</condition>
  <arm_group>
    <arm_group_label>conventional mechanical ventilation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>routine mechanical ventilation will be adjusted based on conventional mechanical ventilation settings with tidal volume of 8 ml/kg and PEEP level of 5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>mechanical ventilation adjusted according to driving pressure</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>routine mechanical ventilation adjusted based on driving pressure during lateral position. After patients are put to lateral position incremental increase in PEEP will be applied and the driving pressures will be recorded for each PEEP level and the patients will be ventilated with this PEEP during anesthesia. the other setting will be same with conventional group. tidal volume of 8 ml/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>routine lung protective, conventional mechanical ventilation</intervention_name>
    <description>routine lung protective, conventional mechanical ventilation with stabil PEEP</description>
    <arm_group_label>conventional mechanical ventilation</arm_group_label>
    <arm_group_label>mechanical ventilation adjusted according to driving pressure</arm_group_label>
    <other_name>routine lung protective, conventional mechanical ventilation with PEEP adjusted to the lowest Driving Pressure level</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients planned to have total hip replacement&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        High intracranial pressure Bronchopleural fistula Hypovolemic shock Right ventricular&#xD;
        failure Left ventricular failure(Ejection fraction lower than 50%) Arrythmia&#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>Zekiye Bigat, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Akdeniz University Medical School Anesthesiology and Reanimation Department</affiliation>
  </overall_official>
  <overall_official>
    <last_name>İlker O Aycan, Ass Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Akdeniz University Medical school Anesthesiology and Reanimation Departmnet</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nesil coskunfırat, Ass Prof</last_name>
    <phone>00902422496257</phone>
    <phone_ext>6260</phone_ext>
    <email>nesildgr@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yesim Cetintas, specialist</last_name>
    <phone>00902422496257</phone>
    <phone_ext>6260</phone_ext>
    <email>yesimcetintas@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Akdeniz University Hospital</name>
      <address>
        <city>Antalya</city>
        <zip>07070</zip>
        <country>Turkey</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nesil Coskunfırat, Ass. Prof</last_name>
      <phone>00902422496257</phone>
      <phone_ext>6260</phone_ext>
      <email>nesildgr@yahoo.com</email>
    </contact>
    <contact_backup>
      <last_name>Yesim Cetintas, Specialist</last_name>
      <phone>00902422496257</phone>
      <phone_ext>6260</phone_ext>
      <email>yesimcetintas@yahoo.com</email>
    </contact_backup>
    <investigator>
      <last_name>Zekiye Bigat, Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ilker O Aycan, Ass.Prof</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>July 26, 2022</last_update_submitted>
  <last_update_submitted_qc>July 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Akdeniz University</investigator_affiliation>
    <investigator_full_name>Nesil Coskunfirat</investigator_full_name>
    <investigator_title>associate professor</investigator_title>
  </responsible_party>
  <keyword>Driving Pressure</keyword>
  <keyword>lung protective ventilation</keyword>
  <keyword>PEEP</keyword>
  <keyword>total hip replacement</keyword>
  <keyword>lateral position</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis, Hip</mesh_term>
    <mesh_term>Hip Fractures</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/NCT04455789
org study id: AkdenizU-2
nct id: NCT04455789
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Previous studies showed that, best lung protective strategies of ventilation parameters are
      based on driving pressure in damaged lungs. But there are few studies concerning the effects
      of different positions during different types of surgery on driving pressure with normal
      lungs.So the investigators decided to compare mechanical ventilation based on driving
      pressure with conventional mechanical ventilation in patients with lateral decubitus position
      during total hip replacement surgery. The investigators hypothesised that, there will be
      better intraoperative hemodynamic and respiratory parameters with better early postoperative
      results in patients whom mechanical ventilation parameters are adjusted according to driving
      pressure.

      In this randomised, controlled, double blind study, 60 patients who will have total hip
      replacement surgery will be recruited to the study. 30 patients will be ventilated by 8 ml/kg
      tidal volume and 5 cmH20 PEEP, in conventional lung protective group. And the other 30
      patients will be ventilated by 8 ml/kg tidal volume and PEEP level with the lowest driving
      pressure.

      The investigators primary goal in this study study is to compare the effects of conventional
      lung protective ventilation with ventilation based on driving pressure on hemodynamic and
      respiratory parameters. And secondly, the investigators aim to compare the effects of these
      two techniques s on early postoperative outcome. The investigators primary result parameters
      are intra operative fluid consumption, lactate, etC02 and mix venous oxygen saturation
      levels.The investigators secondary result parameters are postoperative mechanical
      ventilation, ICU stay and discharge times.
There may be physiologic and pathologic pulmonary changes because of inflammatory cytokine
      release during total hip replacement surgery due to surgical invasivity or advanced age,
      comorbidities, perioperative immobility of patients. Also intraoperative mechanical
      ventilation can cause volutrauma, barotrauma or atelectrauma risk because of lateral position
      during hip replacement surgery. All these factors can cause pulmonary complications and
      vascular permeability increase in dependent and independent regions due to neutrophil
      response increase. Intraoperative hypovolemia is often observed in this group patients
      because of preoperative prolonged fasting periods, insufficient fluid intake due to
      preoperative delirium and depression. Also mechanical ventilation with positive pressure
      slightly decreases venous return to the heart resulting decrease in cardiac output. It is
      more obvious in the presence of hypovolemia. Providing continuous sufficient intravascular
      volume is necessary for prevention of tissue hypoxia and providing optimal cardiac output. It
      is known that intra operative hemodynamic optimisation, has positive effects on mortality
      ratio. But proper intravascular volume is not always easy to maintain, and it is not always
      easy for anaesthetists to identify deficiency or overload of intra operative intravascular
      volume. In recent years, intravascular volume therapies are goal directed by the reflections
      of respiratory mechanics on arterial pressure and pulse oximetry. Plethysmographic wave
      changes observed in pulse oximetry induced by positive pressure ventilation is accepted as
      indicator of hypovolemia. Hemodynamic changes induced by respiratory mode can be measured by
      invasive arterial monitorization. This dynamic variable is called as pulse pressure variation
      index and is correlated with amplitude changes observed in pulse oximetry signals. These
      variations are based on changes observed in pulse wavelength due to the changes in
      intrathoracic pressure. In some pulse oximetry devices, this is done as standard function as
      path variability index (PVI). PVI is measurement of dynamic changes of perfusion index during
      a whole respiratory cycle. Pulse oximetry wave length changes enables the evaluate
      hypovolemia noninvasively.

      PVI is gaining importance as a dynamic parameter in evaluating fluid treatment during
      surgery. Goal directed fluid therapy has shown positive effects on results on patient
      survival. In a study which fluid therapy was guided by PVI changes and it was reported that,
      goal directed fluid therapy had positive results.The investigators also, use some invasive
      and noninvasive monitorization techniques, including PVI and CVP, to monitor static and
      dynamic hemodynamic parameters during hip replacement surgery and we apply fluids according
      to our fluid therapy protocols. The investigators use blood gas analysis to monitor the
      efficiency of this treatment.

      In this study, in both groups the investigators will apply fluid according to PVI values, so
      if any difference detected is observed between groups will be because of the differences of
      respiratory parameters between groups. And the investigators can detect, PVI stability and
      less fluid needs differences between groups.

      PETCO2 is, another parameter which will be evaluated in this study, is a factor of tissue CO2
      production (VCO2), alveolar ventilation and cardiac output (mainly pulmonary blood flow). It
      is known that, when CO2 produced at the tissues and formed in lungs are constant, the changes
      of etCO2 are due to the blood flow differences and it is related to changes of cardiac
      output. For this reason, PETCO2 is suggested as a noninvasive measure for continuous
      assessment of cardiac output. At the same time, it is possible to comment about changes of
      dead space by measuring arterial CO2 pressure.

      Decrease of PETCO2, resulted from cardiac output decrease, can not be explained only with the
      decrease rate of excretion of CO2, but also can be explained by the changes of production of
      CO2 caused by dependency to oxygen supply. On the contrary, when cardiac output is high,
      pulmonary blood flow is no longer a limiting factor for PETCO2 formation, and PETCO2 is
      related to sufficiency of alveolar ventilation.

      As a result, etCO2 measurement has some advantages; it is simple noninvasive and does not
      require a invasive hemodynamic measurement.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: volume of intraoperative fluid administration
time frame: during intraoperative period
description: the patients will receive intraoperative fluids according to a protocol based on PVI.
measure: intraoperative etCO2 levels
time frame: during mechanical ventilation
description: et CO2 levels will be recorded form the anesthesia machine monitor
measure: lactate levels
time frame: during intraoperative period
description: lactate levels will be obtained from the serial blood gas analysis
measure: postoperative mechanical ventilation duration
time frame: From end of surgery to the end of mechanical ventilation duration in the intensive care unit until the patient is extubated, up to 3 days
description: The patient's need for mechanical ventilation, after the surgery, will be assessed
measure: postoperative intensive care stay
time frame: From end of operation to the end of intensive care stay, up to 1 week
description: after the end of surgery the patients need for intensive care will be assessed
measure: length of hospital stay after the operation
time frame: form end of surgery to the end of hospital stay, up to 10 days
description: the effects of mechanical ventilation on the days of hospital stay will be assessed
arm group label: conventional mechanical ventilation
arm group type: Experimental
description: routine mechanical ventilation will be adjusted based on conventional mechanical ventilation settings with tidal volume of 8 ml/kg and PEEP level of 5
arm group label: mechanical ventilation adjusted according to driving pressure
arm group type: Experimental
description: routine mechanical ventilation adjusted based on driving pressure during lateral position. After patients are put to lateral position incremental increase in PEEP will be applied and the driving pressures will be recorded for each PEEP level and the patients will be ventilated with this PEEP during anesthesia. the other setting will be same with conventional group. tidal volume of 8 ml/kg
intervention type: Procedure
intervention name: routine lung protective, conventional mechanical ventilation
description: routine lung protective, conventional mechanical ventilation with stabil PEEP
arm group label: conventional mechanical ventilation
arm group label: mechanical ventilation adjusted according to driving pressure
other name: routine lung protective, conventional mechanical ventilation with PEEP adjusted to the lowest Driving Pressure level
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Zekiye Bigat, Prof
role: Principal Investigator
affiliation: Akdeniz University Medical School Anesthesiology and Reanimation Department
last name: İlker O Aycan, Ass Prof
role: Principal Investigator
affiliation: Akdeniz University Medical school Anesthesiology and Reanimation Departmnet
last name: Nesil coskunfırat, Ass Prof
phone: 00902422496257
phone ext: 6260
email: nesildgr@yahoo.com
last name: Yesim Cetintas, specialist
phone: 00902422496257
phone ext: 6260
email: yesimcetintas@yahoo.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Akdeniz University
investigator full name: Nesil Coskunfirat
investigator title: associate professor
mesh term: Osteoarthritis, Hip
mesh term: Hip Fractures
sharing ipd: No