Prediction of Inflammatory Response and Hypotensive Syndrome After Cardiac Surgery by Preoperative Copeptin Level
Condition: Systemic Inflammatory Response Syndrome (SIRS); Postoperative Vasodilation Syndrome; Stress Response; Cardiac Surgery Prognosis; Tissue Oxygenation and Post-ischemic Response
MeSH terms: Diabetes Insipidus; Syndrome; Systemic Inflammatory Response Syndrome
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Preoperative copeptin level
Intervention type(s): Diagnostic Test
Intervention description(s): Measure of plasmatic copeptin from preoperative samples retained in a biorepository. Physicians are blinded to the result.
Other intervention name(s): Biomarker of vasopressin secretion; Systemic Inflammatory Response Syndrome (SIRS); Postoperative vasodilation syndrome; Stress response
Intervention MeSH terms: Vasopressins
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients hospitalized and scheduled for cardiac surgery
      
Biospecimen description: 
      Plasma: preoperative, ICU admission at POD0 and POD1 samples
    
Keywords: Copeptin; Vasopressin; Microcirculation; Inflammation; Vasodilation; Cardiopulmonary bypass