Clinical trial NCT03107572: Predictive and Prognostic Value of Cellular Dysoxia Markers After Cardiac Surgery With Extracorporeal Circulation
Official title: Comparison of the Predictive and Prognostic Value of Cellular Dysoxia Markers in the Postoperative Period of Cardiac Surgery With Extracorporeal Circulation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiac Surgery
Cardiopulmonary Bypass
Microcirculation
Tissue Oxygenation
Postoperative Complications
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2017-04-11
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients undergoing cardiac surgery with cardiopulmonary bypass in the university hospital of Lille.

Brief summary: The study consist of evaluation in cardiac surgery with cardiopulmonary bypass (CPB) setting the ability of PCO2 derived variables (ΔPCO2, ΔPCO2/C(a-v)O2 ratio), compared to lactate and ScVO2 to predict major postoperative adverse events.

Detailed description: Cardiac surgery with cardiopulmonary bypass is associated with serious morbidity and mortality especially in moderate and high-risk patients. This procedure is associated with systemic inflammatory response as a consequence of cardiopulmonary bypass, surgical insult and genetic background of patients leading to organ injury and worse outcome. This pitfall may be worsened by hemodynamic changes with inadequate hemodynamic management.

During and after CPB, substantial changes in macrocirculation and microcirculation are observed and sustain impairment may result in reduced oxygen delivery and/or impaired oxygen extraction. The main consequence is cellular dysorexia that may trigger postoperative organ dysfunction. Rapid identification of cellular dysorexia and rapid hemodynamic management are therefore among key strategies that may reduce mortality.

In this purpose various marker can be considered. Traditionally lactatemia is considered as surrogate of anaerobic metabolism resulting from ischemia. However it interpretation may be challenging particularly in case of reduced hepatic clearance, use of epinephrine or massive blood transfusion. Venous or central venous oxygenation (S(c)VO2), a surrogate of oxygen extraction that is believed to reflect balance between oxygen delivery and consumption, is considered as an acceptable alternative as it was shown to be associated with organ dysfunction in various clinical setting. Nevertheless ScVO2 suffers from the difficulties to define adequate threshold as very high S(c)VO2 as well as low S(c)VO2 may be associated with poor outcome. Recently PCO2 derived dysorexia and perfusion markers have been shown to be predicting outcome in both septic patient and high risk surgical patient. Central venous to arterial difference in PCO2 (ΔPCO2) a global perfusion index is show to be correlated to microcirculation dysfunction and may reflect impaired tissue perfusion. In high risk non-cardiac surgical patients and in septic patient, ΔPCO2 predicted worse outcome better than S(c)VO2 and lactate. Besides this performance may be improve when using a clinically available surrogate based on ΔPCO2. When anaerobic metabolism occurred as a result of sustained hypoxia, CO2 production increases therefore the respiratory quotient (CO2 production (VCO2) and oxygen consumption (VO2) ratio) increases. VCO2/VO2 can be simplified as ΔPCO2 /Ca-vO2 ratio, where Ca-vO2 is arteriovenous O2 content difference. All these variables have never been compared in cardiac surgery setting and their association with microcirculation impaired is poorly documented. The hypotheses is that ΔPCO2, and ΔPCO2 /Ca-vO2 ratio may better predict major postoperative adverse events than blood lactate and S(c)VO2 after cardiac surgery with CPB.

Eligibility criteria: Inclusion Criteria:

* 18 years old or more
* Cardiac surgery with cardiopulmonary bypass
* Tip of a central venous catheter positioned in superior vena cava or right atria
* Arterial catheter correctly positioned

Exclusion Criteria:

* KDIGO 3 AKI prior to surgery
* Hepatic insufficiency prior to surgery
* Extracorporeal life support prior to surgery '
* Live expectancy lower than 48 hours
* pregnancy

Primary outcomes:
measure: Performances of PCO2 derived perfusion markers (ΔPCO2 and ΔPCO2/C(a-v)O2 ratio) measured 2 hours after CPB to predict major postoperative adverse events (MPAE) in the 48 hours following cardiac surgery.
timeFrame: First 2 days after surgery
Secondary outcomes:
measure: Performances of PCO2 derived perfusion marker measured ICU admission, 6 and 24 hours after CPB to predict major postoperative adverse events (MPAE) in the 2 and 7 days following cardiac surgery.
timeFrame: 2 and 7 days following cardiac surgery
measure: Performances of PCO2 derived perfusion marker measured ICU admission, 6 and 24 hours after CPB to predict organ failure (any organ failure with specific SOFA of 2 or more) in the 2 and 7 days after surgery.
timeFrame: 2 and 7 days following surgery
measure: Kinetics and relation of PCO2 derived variables, lactate and ScVO2 in the 24 hours following surgery.
timeFrame: 24 hours following surgery
measure: Association of CO2 derived variables with lactate clearance, vasopressive score and outcome variables (ICU and hospital length of stay, ICU and hospital mortality).
timeFrame: 24 hours following surgery
Other outcomes:
measure: Relation of thenar StO2 with vascular occlusion test derived variables and cellular dysorexia and perfusion markers, and their predictive value in postoperative complication after cardiac surgery.
timeFrame: 2 and 7 days following surgery
measure: Association of PCO2 derived variables, lactate, ScVO2, StO2 derived variables with VO2, VCO2 and respiratory quotient (measured using indirect calorimetry).
timeFrame: 24 hours following surgery
Locations:
city: Lille
country: France
facility: Service d'Anesthésie-Réanimation CCV Hôpital Cardiologique Centre Hospitalier et Universitaire de Lille
state: Nord
Study officials:
affiliation: University Hospital, Lille
name: Mouhamed MOUSSA, MD
role: PRINCIPAL_INVESTIGATOR
References:
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