<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/NCT03288610</url>
  </required_header>
  <id_info>
    <org_study_id>9754</org_study_id>
    <nct_id>NCT03288610</nct_id>
  </id_info>
  <brief_title>Prediction of Inflammatory Response and Hypotensive Syndrome After Cardiac Surgery by Preoperative Copeptin Level</brief_title>
  <acronym>MicorSIRS</acronym>
  <official_title>Prognostic Value of Copeptin Level Before Cardiac Surgery and Involvement in Systemic Inflammatory Response Syndrome After Cardiopulmonary Bypass</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Thermo Fisher Scientific, Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Montpellier</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>
      The purpose of this study is to find a preoperative biomarker before cardiac surgery with&#xD;
      cardiopulmonary bypass related to severe postoperative inflammatory response and circulatory&#xD;
      complications. The investigators hypothesize that an increase of the preoperative stimulation&#xD;
      of vasopressinergic system (in response to acute or chronic conditions) could lead to a&#xD;
      microcirculatory dysfunction and favor the occurrence of vasodilatation during and after CPB&#xD;
      and increase the symptoms of an inflammatory response after CPB. By defining a high risk&#xD;
      population, a targeted strategy of monitoring and early or preventive treatment could improve&#xD;
      postoperative prognosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The occurrence of a severe systemic inflammatory response syndrome (SIRS) after elective&#xD;
      cardiac surgery with cardiopulmonary bypass (CPB) is estimated at about 20% of cases and is&#xD;
      characterized by hemodynamic changes (tachycardia, hypotension, hypovolemia). It is also&#xD;
      responsible for vasodilation with impaired microcirculation involving increased morbidity and&#xD;
      mortality associated with organ dysfunction and the risk of bacterial translocation. However,&#xD;
      the participation of vasopressinergic system in the functional impairment of microcirculation&#xD;
      is unclear.&#xD;
&#xD;
      Copeptin is considered a marker of vasopressin secretion, deriving from the same precursor,&#xD;
      being more stable and easy to dose. In a previous study of 64 patients with CPB, the&#xD;
      investigators have shown that high copeptin preoperative levels are associated with the&#xD;
      occurrence of vasodilatation syndrome after cardiac surgery (incidence 15%) with a relative&#xD;
      deficiency of postoperative vasopressin.&#xD;
&#xD;
      Microcirculatory alterations can be explored through the study of tissue oxygenation by NIRS&#xD;
      (StO2) at rest and in response to a hypoxic challenge (provided by brief vascular occlusion).&#xD;
      In septic shock, altered recovery slopes of tissue oxygenation are associated with poor&#xD;
      prognosis. The investigators could find similar impact on prognosis in cardiogenic shock if&#xD;
      first hours of care did not improve this recovery slope.&#xD;
&#xD;
      The investigators hypothesize that an increase of the preoperative stimulation of&#xD;
      vasopressinergic system (in response to acute or chronic conditions) could favor the&#xD;
      occurrence of vasodilatation during and after CPB and increase the symptoms of an&#xD;
      inflammatory response after CPB. The involvement of vasopressin in microcirculatory&#xD;
      dysfunction is unknown.&#xD;
&#xD;
      This is a validation study of a predictive test for pathophysiology and prognosis. This study&#xD;
      will be monocentric, prospective and observational in routine care.&#xD;
&#xD;
      The main end point of the study is to predict the onset of severe SIRS or postoperative&#xD;
      vasodilation syndrome after CPB by the preoperative plasma copeptin level in a cardiac&#xD;
      surgery population.&#xD;
&#xD;
      The secondary objectives are to assess the incidences of microcirculatory dysfunction, shock&#xD;
      and organs failure after CPB, to determine the postoperative copeptin kinetics for patients&#xD;
      with severe SIRS, to evaluate the prognosis with the ICU length of stay and D28 mortality.&#xD;
&#xD;
      Data are recorded prospectively on a paper case report form by ICU physicians in charge of&#xD;
      the patients on the basis of clinical observation and electronic medical records. Quality&#xD;
      assurance, monitoring and auditing are provided by the study promotor. Data will be checked&#xD;
      by the main investigator to assess the accuracy and completeness of entered data into the&#xD;
      CRF.&#xD;
&#xD;
      Patients are recruited during the preoperative period after screening of inclusion and&#xD;
      exclusion criteria, delivering information and obtaining written consent.&#xD;
&#xD;
      Considering an expected sensitivity for predicting SIRS by preoperative copeptin on the order&#xD;
      of 80%, the number of cases (subjects with severe SIRS) to be included for obtaining an&#xD;
      estimate of the sensitivity with a lower limit of 95% to 55% is placed in 42 cases.&#xD;
      Considering an incidence of severe SIRS at 20%, the total number of patients to be included&#xD;
      in the study is 200. In our center the investigators perform 700 CPB / year, 70% met the&#xD;
      criteria for inclusion.&#xD;
&#xD;
      For the primary objective, the predictive performance of preoperative copeptin for the&#xD;
      occurrence of post-CPB severe SIRS will be evaluated by the construction of a ROC curve with&#xD;
      finding an optimal threshold maximizing sensitivity and specificity (calculation of the&#xD;
      Youden index) to be then estimated with their 95% confidence interval.&#xD;
&#xD;
      Regarding the secondary objectives, copeptin levels will be compared according to the&#xD;
      presence of postoperative microcirculatory dysfunction, hemodynamic failure, organ&#xD;
      dysfunction and preoperative factors using a reduced gap test. Univariate and multivariate&#xD;
      analysis using linear regressions will be carried out to find the preoperative factors&#xD;
      associated significantly and independently to high copeptin level. The postoperative kinetics&#xD;
      of copeptin will be modeled using mixed linear regressions with an intercept +/- a random&#xD;
      slope and taking into account the intra-individual correlation of the assays. The prognostic&#xD;
      value of preoperative copeptin and postoperative StO2 recovery slope on D28 mortality will be&#xD;
      analyzed using the ROC curve, determination of an optimal threshold using the Youden index&#xD;
      and then calculating Sensitivity and specificity with their 95% confidence interval.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">August 2017</completion_date>
  <primary_completion_date type="Actual">July 2017</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>Preoperative copeptin level</measure>
    <time_frame>Preoperative 24 hours</time_frame>
    <description>Plasmatic copeptine will be measured from routine blood sample on heparinazed tubes. The biological assay will be performed by Time-Resolved Amplified Cryptate Emission on automate Kryptor Compact plus (ThermoFisher, Clichy, France). A level above the 97° percentile of referent population will be considered pathological.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Postoperative microcirculatory impairment</measure>
    <time_frame>Within 2h of admission in intensive care unit, before weaning of sedation and mechanical ventilation</time_frame>
    <description>Tissue oxygen saturation (STO2) measured at the thenar eminence by NIRS (Inspectra 650, Hutchinson Technologies) with application of a 3 min vascular occlusion test to measure the occlusion slope, the recovery slope and the hyperemic rebound. Microcirculatory dysfunction is defined by a recovery slope below 3%/s.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of SIRS using classical definition</measure>
    <time_frame>First postoperative 24 hours</time_frame>
    <description>SIRS is classically defined when 2 of the following criteria are met together: temperature &gt;38,3 or &lt;36°C, heart rate &gt;90/min, respiratory rate &gt;20/min or PaCO2 &lt;32mmHg, GB&gt;12000 ou &lt;4000 c/mm3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative hemodynamical impairment</measure>
    <time_frame>First postoperative 24 hours</time_frame>
    <description>Occurrence of&#xD;
A postoperative vasodilation syndrome defined by the need of continuous infusion of norepinephrine (whatever the dose) to maintain the mean arterial pressure above 60 mmHg associated to a cardiac index above or egal to 2.2 L/min/m2&#xD;
a postoperative low cardiac output syndrome defined by cardiac index below 2.2 L/min/m2 without hypovolemia,&#xD;
a tissue hypoxia assessed by 2 consecutive lactate level above 2.2 mmol/l,&#xD;
an hemorrhagic shock or&#xD;
a septic shock.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perioperative copeptin kinetics</measure>
    <time_frame>24 hours before the operation until admission intensive care unit</time_frame>
    <description>Plasmatic copeptin will be measured from routine blood sample on heparinized tubes. The biological assay will be performed by Time-Resolved Amplified Cryptate Emission on automate Kryptor Compact plus (ThermoFisher, Clichy, France). A level above the 97° percentile of referent population will be considered pathological.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perioperative copeptin kinetics</measure>
    <time_frame>postoperative day</time_frame>
    <description>Plasmatic copeptin will be measured from routine blood sample on heparinized tubes. The biological assay will be performed by Time-Resolved Amplified Cryptate Emission on automate Kryptor Compact plus (ThermoFisher, Clichy, France). A level above the 97° percentile of referent population will be considered pathological.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global organs dysfunction</measure>
    <time_frame>First postoperative 24 hours</time_frame>
    <description>Assessed by the Sequencial Organ Failure Assessment (SOFA) score calculated at the postoperative day</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lengh of mechanical ventilation</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Length (hours) of postoperative invasive mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute kidney injury</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Defined and classified according to KDIGO criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal replacement therapy</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Incidence of patients requiring renal replacement therapy in ICU due to postoperative acute kidney injury</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive Care Unit stay</measure>
    <time_frame>through study completion, an average of 3 month</time_frame>
    <description>Length (days) of postoperative intensive care unit stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital stay</measure>
    <time_frame>through study completion, an average of 3 month</time_frame>
    <description>Length (days) of postoperative hospital stay before current care ward discharge (excluding rehabilitation time)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive Care Unit mortality rate</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Intensive care unit mortality rate : death before ICU discharge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Day 28 mortality rate</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Overall mortality rate at 28 days after surgery</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">200</enrollment>
  <condition>Systemic Inflammatory Response Syndrome (SIRS)</condition>
  <condition>Postoperative Vasodilation Syndrome</condition>
  <condition>Stress Response</condition>
  <condition>Cardiac Surgery Prognosis</condition>
  <condition>Tissue Oxygenation and Post-ischemic Response</condition>
  <arm_group>
    <arm_group_label>With inflammatory response</arm_group_label>
    <description>Patients with postoperative inflammatory response as defined by the occurrence of severe SIRS and/or postoperative vasodilation syndrome.&#xD;
Severe SIRS is defined by meeting at least 2 SIRS criteria during 6 consecutive hours or at least 3 SIRS criterias. Classical SIRS criteria include: temperature &gt;38,3 or &lt;36°C, heart rate &gt;90/min, respiratory rate &gt;20/min or PaCO2 &lt;32mmHg, GB&gt;12000 ou &lt;4000 c/mm3.&#xD;
Postoperative vasodilation syndrome is defined by the need of continuous infusion of norepinephrine (whatever the dose) to maintain the mean arterial pressure above 60 mmHg associated to a cardiac index above or egal to 2.2 L/min/m2.&#xD;
Patients without postoperative severe SIRS and without postoperative vasodilation syndrome</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Preoperative copeptin level</intervention_name>
    <description>Measure of plasmatic copeptin from preoperative samples retained in a biorepository. Physicians are blinded to the result.</description>
    <arm_group_label>With inflammatory response</arm_group_label>
    <other_name>Biomarker of vasopressin secretion</other_name>
    <other_name>Systemic Inflammatory Response Syndrome (SIRS)</other_name>
    <other_name>Postoperative vasodilation syndrome</other_name>
    <other_name>Stress response</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma: preoperative, ICU admission at POD0 and POD1 samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients hospitalized and scheduled for cardiac surgery&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Elective surgery&#xD;
&#xD;
          -  Scheduled time of at least 24 hours&#xD;
&#xD;
          -  Cardiopulmonary bypass&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Urgent surgery within 24 hours of hospital admission&#xD;
&#xD;
          -  Chronic renal failure with preoperative glomerular filtration rate below 45 ml/min&#xD;
&#xD;
          -  Ongoing sepsis (ie uncontrolled endocarditis)&#xD;
&#xD;
          -  Immunosuppressive therapy (solid organ transplant recipient)&#xD;
&#xD;
          -  Previously included in this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>81 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Philippe Gaudard, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Montpellier University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of critical care, Arnaud de Villeneuve Hospital</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <results_reference>
    <citation>MacCallum NS, Finney SJ, Gordon SE, Quinlan GJ, Evans TW. Modified criteria for the systemic inflammatory response syndrome improves their utility following cardiac surgery. Chest. 2014 Jun;145(6):1197-1203. doi: 10.1378/chest.13-1023.</citation>
    <PMID>24576975</PMID>
  </results_reference>
  <results_reference>
    <citation>Colson PH, Bernard C, Struck J, Morgenthaler NG, Albat B, Guillon G. Post cardiac surgery vasoplegia is associated with high preoperative copeptin plasma concentration. Crit Care. 2011;15(5):R255. doi: 10.1186/cc10516. Epub 2011 Oct 25.</citation>
    <PMID>22026977</PMID>
  </results_reference>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>May 9, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <last_update_submitted>September 20, 2017</last_update_submitted>
  <last_update_submitted_qc>September 20, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Copeptin</keyword>
  <keyword>Vasopressin</keyword>
  <keyword>Microcirculation</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Vasodilation</keyword>
  <keyword>Cardiopulmonary bypass</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Insipidus</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Systemic Inflammatory Response Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vasopressins</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/NCT03288610
org study id: 9754
nct id: NCT03288610
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to find a preoperative biomarker before cardiac surgery with
      cardiopulmonary bypass related to severe postoperative inflammatory response and circulatory
      complications. The investigators hypothesize that an increase of the preoperative stimulation
      of vasopressinergic system (in response to acute or chronic conditions) could lead to a
      microcirculatory dysfunction and favor the occurrence of vasodilatation during and after CPB
      and increase the symptoms of an inflammatory response after CPB. By defining a high risk
      population, a targeted strategy of monitoring and early or preventive treatment could improve
      postoperative prognosis.
The occurrence of a severe systemic inflammatory response syndrome (SIRS) after elective
      cardiac surgery with cardiopulmonary bypass (CPB) is estimated at about 20% of cases and is
      characterized by hemodynamic changes (tachycardia, hypotension, hypovolemia). It is also
      responsible for vasodilation with impaired microcirculation involving increased morbidity and
      mortality associated with organ dysfunction and the risk of bacterial translocation. However,
      the participation of vasopressinergic system in the functional impairment of microcirculation
      is unclear.

      Copeptin is considered a marker of vasopressin secretion, deriving from the same precursor,
      being more stable and easy to dose. In a previous study of 64 patients with CPB, the
      investigators have shown that high copeptin preoperative levels are associated with the
      occurrence of vasodilatation syndrome after cardiac surgery (incidence 15%) with a relative
      deficiency of postoperative vasopressin.

      Microcirculatory alterations can be explored through the study of tissue oxygenation by NIRS
      (StO2) at rest and in response to a hypoxic challenge (provided by brief vascular occlusion).
      In septic shock, altered recovery slopes of tissue oxygenation are associated with poor
      prognosis. The investigators could find similar impact on prognosis in cardiogenic shock if
      first hours of care did not improve this recovery slope.

      The investigators hypothesize that an increase of the preoperative stimulation of
      vasopressinergic system (in response to acute or chronic conditions) could favor the
      occurrence of vasodilatation during and after CPB and increase the symptoms of an
      inflammatory response after CPB. The involvement of vasopressin in microcirculatory
      dysfunction is unknown.

      This is a validation study of a predictive test for pathophysiology and prognosis. This study
      will be monocentric, prospective and observational in routine care.

      The main end point of the study is to predict the onset of severe SIRS or postoperative
      vasodilation syndrome after CPB by the preoperative plasma copeptin level in a cardiac
      surgery population.

      The secondary objectives are to assess the incidences of microcirculatory dysfunction, shock
      and organs failure after CPB, to determine the postoperative copeptin kinetics for patients
      with severe SIRS, to evaluate the prognosis with the ICU length of stay and D28 mortality.

      Data are recorded prospectively on a paper case report form by ICU physicians in charge of
      the patients on the basis of clinical observation and electronic medical records. Quality
      assurance, monitoring and auditing are provided by the study promotor. Data will be checked
      by the main investigator to assess the accuracy and completeness of entered data into the
      CRF.

      Patients are recruited during the preoperative period after screening of inclusion and
      exclusion criteria, delivering information and obtaining written consent.

      Considering an expected sensitivity for predicting SIRS by preoperative copeptin on the order
      of 80%, the number of cases (subjects with severe SIRS) to be included for obtaining an
      estimate of the sensitivity with a lower limit of 95% to 55% is placed in 42 cases.
      Considering an incidence of severe SIRS at 20%, the total number of patients to be included
      in the study is 200. In our center the investigators perform 700 CPB / year, 70% met the
      criteria for inclusion.

      For the primary objective, the predictive performance of preoperative copeptin for the
      occurrence of post-CPB severe SIRS will be evaluated by the construction of a ROC curve with
      finding an optimal threshold maximizing sensitivity and specificity (calculation of the
      Youden index) to be then estimated with their 95% confidence interval.

      Regarding the secondary objectives, copeptin levels will be compared according to the
      presence of postoperative microcirculatory dysfunction, hemodynamic failure, organ
      dysfunction and preoperative factors using a reduced gap test. Univariate and multivariate
      analysis using linear regressions will be carried out to find the preoperative factors
      associated significantly and independently to high copeptin level. The postoperative kinetics
      of copeptin will be modeled using mixed linear regressions with an intercept +/- a random
      slope and taking into account the intra-individual correlation of the assays. The prognostic
      value of preoperative copeptin and postoperative StO2 recovery slope on D28 mortality will be
      analyzed using the ROC curve, determination of an optimal threshold using the Youden index
      and then calculating Sensitivity and specificity with their 95% confidence interval.
observational model: Cohort
time perspective: Prospective
measure: Preoperative copeptin level
time frame: Preoperative 24 hours
description: Plasmatic copeptine will be measured from routine blood sample on heparinazed tubes. The biological assay will be performed by Time-Resolved Amplified Cryptate Emission on automate Kryptor Compact plus (ThermoFisher, Clichy, France). A level above the 97° percentile of referent population will be considered pathological.
measure: Postoperative microcirculatory impairment
time frame: Within 2h of admission in intensive care unit, before weaning of sedation and mechanical ventilation
description: Tissue oxygen saturation (STO2) measured at the thenar eminence by NIRS (Inspectra 650, Hutchinson Technologies) with application of a 3 min vascular occlusion test to measure the occlusion slope, the recovery slope and the hyperemic rebound. Microcirculatory dysfunction is defined by a recovery slope below 3%/s.
measure: Occurrence of SIRS using classical definition
time frame: First postoperative 24 hours
description: SIRS is classically defined when 2 of the following criteria are met together: temperature >38,3 or <36°C, heart rate >90/min, respiratory rate >20/min or PaCO2 <32mmHg, GB>12000 ou <4000 c/mm3.
measure: Postoperative hemodynamical impairment
time frame: First postoperative 24 hours
description: Occurrence of
A postoperative vasodilation syndrome defined by the need of continuous infusion of norepinephrine (whatever the dose) to maintain the mean arterial pressure above 60 mmHg associated to a cardiac index above or egal to 2.2 L/min/m2
a postoperative low cardiac output syndrome defined by cardiac index below 2.2 L/min/m2 without hypovolemia,
a tissue hypoxia assessed by 2 consecutive lactate level above 2.2 mmol/l,
an hemorrhagic shock or
a septic shock.
measure: Perioperative copeptin kinetics
time frame: 24 hours before the operation until admission intensive care unit
description: Plasmatic copeptin will be measured from routine blood sample on heparinized tubes. The biological assay will be performed by Time-Resolved Amplified Cryptate Emission on automate Kryptor Compact plus (ThermoFisher, Clichy, France). A level above the 97° percentile of referent population will be considered pathological.
measure: Perioperative copeptin kinetics
time frame: postoperative day
description: Plasmatic copeptin will be measured from routine blood sample on heparinized tubes. The biological assay will be performed by Time-Resolved Amplified Cryptate Emission on automate Kryptor Compact plus (ThermoFisher, Clichy, France). A level above the 97° percentile of referent population will be considered pathological.
measure: Global organs dysfunction
time frame: First postoperative 24 hours
description: Assessed by the Sequencial Organ Failure Assessment (SOFA) score calculated at the postoperative day
measure: Lengh of mechanical ventilation
time frame: Up to 28 days
description: Length (hours) of postoperative invasive mechanical ventilation
measure: Acute kidney injury
time frame: Up to 28 days
description: Defined and classified according to KDIGO criteria
measure: Renal replacement therapy
time frame: Up to 28 days
description: Incidence of patients requiring renal replacement therapy in ICU due to postoperative acute kidney injury
measure: Intensive Care Unit stay
time frame: through study completion, an average of 3 month
description: Length (days) of postoperative intensive care unit stay
measure: Hospital stay
time frame: through study completion, an average of 3 month
description: Length (days) of postoperative hospital stay before current care ward discharge (excluding rehabilitation time)
measure: Intensive Care Unit mortality rate
time frame: Up to 28 days
description: Intensive care unit mortality rate : death before ICU discharge
measure: Day 28 mortality rate
time frame: Up to 28 days
description: Overall mortality rate at 28 days after surgery
arm group label: With inflammatory response
description: Patients with postoperative inflammatory response as defined by the occurrence of severe SIRS and/or postoperative vasodilation syndrome.
Severe SIRS is defined by meeting at least 2 SIRS criteria during 6 consecutive hours or at least 3 SIRS criterias. Classical SIRS criteria include: temperature >38,3 or <36°C, heart rate >90/min, respiratory rate >20/min or PaCO2 <32mmHg, GB>12000 ou <4000 c/mm3.
Postoperative vasodilation syndrome is defined by the need of continuous infusion of norepinephrine (whatever the dose) to maintain the mean arterial pressure above 60 mmHg associated to a cardiac index above or egal to 2.2 L/min/m2.
Patients without postoperative severe SIRS and without postoperative vasodilation syndrome
intervention type: Diagnostic Test
intervention name: Preoperative copeptin level
description: Measure of plasmatic copeptin from preoperative samples retained in a biorepository. Physicians are blinded to the result.
arm group label: With inflammatory response
other name: Biomarker of vasopressin secretion
other name: Systemic Inflammatory Response Syndrome (SIRS)
other name: Postoperative vasodilation syndrome
other name: Stress response
Plasma: preoperative, ICU admission at POD0 and POD1 samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 81 Years
healthy volunteers: No
last name: Philippe Gaudard, MD
role: Principal Investigator
affiliation: Montpellier University Hospital
facility: 
country: France
citation: MacCallum NS, Finney SJ, Gordon SE, Quinlan GJ, Evans TW. Modified criteria for the systemic inflammatory response syndrome improves their utility following cardiac surgery. Chest. 2014 Jun;145(6):1197-1203. doi: 10.1378/chest.13-1023.
PMID: 24576975
citation: Colson PH, Bernard C, Struck J, Morgenthaler NG, Albat B, Guillon G. Post cardiac surgery vasoplegia is associated with high preoperative copeptin plasma concentration. Crit Care. 2011;15(5):R255. doi: 10.1186/cc10516. Epub 2011 Oct 25.
PMID: 22026977
responsible party type: Sponsor
mesh term: Diabetes Insipidus
mesh term: Syndrome
mesh term: Systemic Inflammatory Response Syndrome
mesh term: Vasopressins
sharing ipd: No