Intraoperative Mechanical Ventilation and Postoperative Pulmonary Complications After On-pump Cardiac Surgery in High-risk Patients

Study Overview
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Brief Summary
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Controversies remain concerning the best intraoperative mechanical ventilation regimen for major cardiac surgery. While the use of intra operative low tidal volumes is now standard practice, the optimal level of positive end-expiratory pressure (PEEP) and the use of recruitment maneuvers (RM) remain controversial. The aim of this study is to compare two regimens of intraoperative mechanical ventilation on postoperative outcomes in cardiac surgery patients at risk of postoperative pulmonary complications

Detailed Description
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In this randomized controlled trial, cardiac surgery patients at risk of postoperative pulmonary complications will be assigned to intraoperative ventilation with high PEEP and RM or intraoperative mechanical ventilation with low PEEP and without RM. The primary endpoint will be a composite endpoint including major postoperative complications within the first postoperative week and death within the 28 days after surgery

Official Title
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Effect of IntraoperatiVe High Positive End-ExpirAtory Pressure (PEEP) With ReCruitment MAneuveRs vs Low PEEP on Major Postoperative Pulmonary Complications and Death After On-pump Cardiac Surgery in High-risk Patients: the VACARM Study

Conditions
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Postoperative Pulmonary Complications

Intervention / Treatment
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* Procedure: Intervention group_MRA
* Procedure: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years-old, Evaluated before cardiopulmonary bypass for any cardiac surgical procedure (e.g. coronary artery bypass grafting, valve, aorta, or combined procedures), With a pulmonary risk score ≥ 2 Who gave written informed consent affiliated to a social security system Exclusion Criteria: BMI > 40kg/m2 ; Left Ventricular Ejection Fraction < 35% ; Preoperative shock ; Aortic surgery with planned circulatory arrest ; Minimally invasive cardiac surgery ; Emergency surgery with patient unable to give written informed consent Heart transplantation Mechanical circulatory support surgery Pregnant or lactating women Adults legally protected (under judicial protection, guardianship, or supervision), persons deprived of their liberty

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, randomized, comparative, parallel-group trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group_MRA<br>Recruitment maneuvers and high PEEP | Procedure: Intervention group_MRA<br>* Tidal Volume (Vt) =6-8 mL/kg of predicted body weight (PBW), Peep=8 cmH2O, recruitment maneuvers=30cm H2O every 30 min after intubation (except during CPB), after any disconnection and at the admission in ICU. Recruitment maneuvers are performed in accordance with the surgical team an if SAP≥90 mmHg or MAP≥65 mmHg. Ventilation is maintained during CPB Vt=2.5 mL/kg, Peep= 5 cmH2O<br>* Other names: recruitment maneuvers;|
| Active Comparator: Control group<br>No recruitment maneuvers and low PEEP | Procedure: Control group<br>* Vt=6-8 mL/kg of PBW, Peep=5 cmH2O , No recruitment maneuvers. Ventilation maintained during CPB Vt=2.5 mL/kg, Peep= 5 cmH2O.<br>* Other names: NO recruitment maneuvers;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of major pulmonary complications and death | Major pulmonary complications, defined as prolonged mechanical ventilation >24h post-operatively, pneumonia (defined according to the 2017 French guidelines) or reintubation for any cause within 7 post-operative days, or death | 28 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with hypotension | Hypotension lasting more than 60 seconds after the end of the recruitment maneuvers | intraoperative period | 
| Evaluate the postoperative blood gases | Measure of PaO2 (mmHg) | 30 minutes after extubation | 
| Evaluate the postoperative blood gases | Measure of HCO3 (mmol/l) | 30 minutes after extubation | 
| Evaluate the postoperative blood gases | Measure of PaCO2 (mmHg) | 30 minutes after extubation | 
| Evaluate the postoperative blood gases | Measure of SaO2 (%) | 30 minutes after extubation | 
| Evaluate the postoperative blood gases | Measure of PaO2 (mmHg) | Day 1 | 
| Evaluate the postoperative blood gases | Measure of HCO3 (mmol/l) | Day 1 | 
| Evaluate the postoperative blood gases | Measure of PaCO2 (mmHg) | Day 1 | 
| Evaluate the postoperative blood gases | Measure of SaO2 (%) | Day 1 | 
| Evaluate the postoperative blood gases | Measure of PaO2 (mmHg) | Day 2 | 
| Evaluate the postoperative blood gases | Measure of HCO3 (mmol/l) | Day 2 | 
| Evaluate the postoperative blood gases | Measure of PaCO2 (mmHg) | Day 2 | 
| Evaluate the postoperative blood gases | Measure of SaO2 (%) | Day 2 | 
| Pulmonary function tests | Measure of vital capacity (CV) and maximum expiratory volume by second (VEMS) by spirometry | Day 0 | 
| Pulmonary function tests | Measure of vital capacity (CV) and maximum expiratory volume by second (VEMS) by spirometry | Day 3 | 
| Pulmonary function tests | Measure of vital capacity (CV) and maximum expiratory volume by second (VEMS) by spirometry | Day 5 | 
| Daily evaluation of organ failure | SOFA score | Up to 7 days | 
| Daily evaluation of delirium | CAM-ICU scale | Up to 7 days | 
| Rate of Postoperative pulmonary complications (PPC) | Pneumonia (defined according to the 2017 French guidelines), re-intubation within 7 days, mechanical ventilation >24h, pneumothorax, Atelectasis, Acute Respiratory Distress Syndrome. PPC grade (according to Huzelbos et al; JAMA) | within the 28 days after surgery | 
| Rate of Postoperative non pulmonary complications | Re intervention for acute bleeding, Pericardial Tamponade, Sternal wound infection, Ventricular Arrhythmia, Atrial fibrillation, Myocardial infarction, Mesenteric ischemia, Sepsis/septic shock, Acute kidney injury with renal replacement | within the 28 days after surgery | 
| Ventilation duration, length of stay in ICU and in the study hospital and death | Number of Ventilatory-free days, vasopressor-free days, ICU-free days and hospital-free days | Day 28 | 
| Mortality rate |  | Day 28 | 
| Mortality rate |  | Day 90 | 
| Mortality rate |  | Day 180 | 
| Biomarkers of systemic inflammation and of epithelial and endothelial aggression | Plasma levels of TNFα, IL1β, IL6, IL8 et IL10, Angiopoeitin 2 and soluble form of receptor for advanced glycation end products (sRAGE) | Day 0 | 
| Biomarkers of systemic inflammation and of epithelial and endothelial aggression | Plasma levels of TNFα, IL1β, IL6, IL8 et IL10, Angiopoeitin 2 and soluble form of receptor for advanced glycation end products (sRAGE) | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recruitment maneuvers, Postoperative pulmonary complications, Peep, Cardiac surgery, Mortality