Maintaining Mechanical Ventilation During Cardiopulmonary Bypass for Cardiac Surgery (VECAR)

Beneficial Effects on Maintaining Mechanical Ventilation During Cardiopulmonary Bypass for Cardiac Surgery on Postoperative Infections

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.

Study Overview

• Status: Completed
• Conditions: Cardiopulmonary Bypass
• Intervention / Treatment: Device: Maintaining mechanical ventilation during surgery; Device: Absence of mechanical ventilation during surgery

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.

• Study Type: Interventional
• Enrollment (Actual): 1401
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU Angers
  • Bordeaux, France
    • CHU Bordeaux
  • Lille, France
    • CHU Lille
  • Paris, France
    • Hôpital Pitié Salpetrière
  • Rennes, France
    • Chu Rennes
  • Toulouse, France
    • CHU Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mechanical ventilation group; patients with mechanical ventilation during cardiopulmonary bypass for cardiac surgery	Device: Maintaining mechanical ventilation during surgery; dead space ventilation using tidal volume of 2.5 mL/kg/pbw (predicted body weight) with 5-7 cm H2O Positive end-expiratory pressure
Active Comparator: Control group; patients without mechanical ventilation during cardiopulmonary bypass for cardiac surgery	Device: Absence of mechanical ventilation during surgery; absence of mechanical ventilation (and no Positive end-expiratory pressure) by disconnecting the tracheal tube from the ventilator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of postoperative infections	During 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Expression of human leukocyte antigen-DR antigen (HLA-DR)	At day 0, day 1 and day 7
Plasmatic concentration of interleukin 10 (IL10)	At day 0, day 1 and day 7
Indoleamine 2,3-Dioxygenase (IDO) activity	At day 0, day 1 and day 7
Proportion of myeloid-derived suppressor cells (MDSCs)	At day 0, day 1 and day 7
Plasmatic concentration of interleukin 6 (IL-6)	At day 0, day 1 and day 7
Quantity of extracellular vesicles (EV)	At day 0 and day 1
Occurrence of lymphopenia	At day 0, day 1 and day 7
Duration of antibiotic treatment	During 28 days
Mortality	During 28 days
Length of hospital stay	During 28 days
PaO2/FiO2 ratio	At day 0 and day 1
Duration of mechanical ventilation	During 28 days

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Jean-Marc TADIE, Rennes Hospital University

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2018
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): July 30, 2021

Study Registration Dates

• First Submitted: December 4, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: cardiac surgery; mechanical ventilation; postoperative infections
• Other Study ID Numbers: 35RC16_9908_VECAR; 2017-A01246-47 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No