Prediction of Inflammatory Response and Hypotensive Syndrome After Cardiac Surgery by Preoperative Copeptin Level

NCT ID: NCT03288610

Last Updated: 2017-09-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2017-08-31

Brief 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.

Conditions

Systemic Inflammatory Response Syndrome (SIRS); Postoperative Vasodilation Syndrome; Stress Response; Cardiac Surgery Prognosis; Tissue Oxygenation and Post-ischemic Response

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

With inflammatory response

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

Preoperative copeptin level

Intervention Type: DIAGNOSTIC_TEST

Measure of plasmatic copeptin from preoperative samples retained in a biorepository. Physicians are blinded to the result.

Interventions

Preoperative copeptin level

Measure of plasmatic copeptin from preoperative samples retained in a biorepository. Physicians are blinded to the result.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Biomarker of vasopressin secretion; Systemic Inflammatory Response Syndrome (SIRS); Postoperative vasodilation syndrome; Stress response

Eligibility Criteria

Inclusion Criteria

• Elective surgery
• Scheduled time of at least 24 hours
• Cardiopulmonary bypass

Exclusion Criteria

• Urgent surgery within 24 hours of hospital admission
• Chronic renal failure with preoperative glomerular filtration rate below 45 ml/min
• Ongoing sepsis (ie uncontrolled endocarditis)
• Immunosuppressive therapy (solid organ transplant recipient)
• Previously included in this study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 81 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thermo Fisher Scientific, Inc

INDUSTRY

Sponsor Role: collaborator

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe Gaudard, MD

Role: PRINCIPAL_INVESTIGATOR

Montpellier University Hospital

Locations

Department of critical care, Arnaud de Villeneuve Hospital

Montpellier, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 24576975 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22026977 (View on PubMed)

Other Identifiers

9754

Identifier Type: -

Identifier Source: org_study_id