Clinical trial NCT03372174: Maintaining Mechanical Ventilation During Cardiopulmonary Bypass for Cardiac Surgery
Official title: Beneficial Effects on Maintaining Mechanical Ventilation During Cardiopulmonary Bypass for Cardiac Surgery on Postoperative Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiopulmonary Bypass
Keywords: cardiac surgery
mechanical ventilation
postoperative infections
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2017-12-13
Enrollment: 1401
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The main objective of this study is to measure the incidence of postoperative infections in 2 groups of patients: one group of patients ventilated and one group of patients without mechanical ventilation during cardiopulmonary bypass for cardiac surgery, and demonstrate that the incidence of postoperative infections is significantly lower in patients ventilated during cardiopulmonary bypass.

Detailed description: Cardiopulmonary bypass (CBP) during cardiac surgery induces a systemic inflammatory response associated with an immune dysregulation and a significant pulmonary dysfunction. First, the inflammatory response, usually attributed to surgical trauma, contact of blood with artificial surfaces, and ischemia reperfusion injury, is responsible for a postoperative immunodepression. For instance, an early impairment of lung cellular immune response after CPB, which could promote the development of postoperative pneumonia, has been found. Along these lines, a downregulation of human leukocyte antigen-DR antigen (HLA-DR) expression on monocytes and an increase in plasma interleukin 10 (IL-10) associated with the occurrence of nosocomial infections have been reported. Second, CPB induces a pulmonary dysfunction, which ranges from a temporary and clinically insignificant reduction in arterial oxygenation to a life-threatening injury manifested as acute respiratory distress syndrome (ARDS). This phenomenon is of multifactorial sources, but one of the main mechanisms is the occurrence of atelectasis during surgery. Atelectasis has been associated with lung injury and release of cytokines by shear forces on alveoli and small airways. However, it is not clear whether this injury is due to a recruitment/derecruitment phenomenon (i.e., atelectrauma) or whether it might by itself lead to the release of cytokine. Since CPB mechanically circulates and oxygenates blood bypassing the heart and lungs, usual procedure during CPB is to stop mechanical ventilation (MV) (apnea). Nevertheless, maintaining MV with positive expiratory pressure (PEEP) during CPB diminished the occurrence of atelectasis and the postoperative inflammatory response. Thus, we investigated the effects of maintaining MV during CPB for cardiac surgery on postoperative immunodepression and found that maintaining MV during CPB decreased postoperative immune dysfunction and could be an interesting strategy to diminish the occurrence of postoperative infection (nosocomial infection) without hampering the surgical procedure. However, these findings have to be confirmed in a clinical trial using the incidence of nosocomial infection as an endpoint.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old;
* Scheduled for any cardiac surgery (elective surgery) with cardio-pulmonary bypass, aortic clamp and cardioplegia, with median sternotomy and bi-pulmonary ventilation (cardiac valvular surgery (valve replacement or repair), coronary artery surgery, ascending aortic surgery and/or combined);
* Written informed consent.

Exclusion Criteria:

* Emergency surgery ;
* Planned thoracotomy with one lung ventilation ;
* Patients with known respiratory diseases (current respiratory infections, asthma, chronic obstructive or restrictive pulmonary disease, obstructive apnea syndrome) ;
* Patients already intubated in the peri-operative period ;
* Immunodepression defined by proven humoral or cellular deficiency, by continuous administration of steroids at any dose for more than one month prior to hospitalization, high-dose steroids (\> 15 mg / kg / day of methylprednisolone or Equivalent), radiotherapy or chemotherapy in the previous year;;
* Need for vasopressor or inotropic agents before surgery ;
* Any acute infection in the last month before surgery ;
* Hematological disorder, autoimmune disease, immunodeficiency, immunosuppressive therapy ;
* Heart failure with an left ventricular ejection fraction\<35% ;
* Protected person (adults legally protected (under judicial protection, guardianship, or supervision), person deprived of their liberty.

Primary outcomes:
measure: Incidence of postoperative infections
timeFrame: During 28 days
Secondary outcomes:
measure: Expression of human leukocyte antigen-DR antigen (HLA-DR)
timeFrame: At day 0, day 1 and day 7
measure: Plasmatic concentration of interleukin 10 (IL10)
timeFrame: At day 0, day 1 and day 7
measure: Indoleamine 2,3-Dioxygenase (IDO) activity
timeFrame: At day 0, day 1 and day 7
measure: Proportion of myeloid-derived suppressor cells (MDSCs)
timeFrame: At day 0, day 1 and day 7
measure: Plasmatic concentration of interleukin 6 (IL-6)
timeFrame: At day 0, day 1 and day 7
measure: Quantity of extracellular vesicles (EV)
timeFrame: At day 0 and day 1
measure: Occurrence of lymphopenia
timeFrame: At day 0, day 1 and day 7
measure: Duration of antibiotic treatment
timeFrame: During 28 days
measure: Mortality
timeFrame: During 28 days
measure: Length of hospital stay
timeFrame: During 28 days
measure: PaO2/FiO2 ratio
timeFrame: At day 0 and day 1
measure: Duration of mechanical ventilation
timeFrame: During 28 days
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Lille
country: France
facility: CHU Lille
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière
city: Rennes
country: France
facility: CHU Rennes
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: Rennes Hospital University
name: Jean-Marc TADIE
role: PRINCIPAL_INVESTIGATOR
References: