Intraoperative Protective Mechanical Ventilation in Patients Requiring Emergency Abdominal Surgery

Study Overview
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Brief Summary
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The aim of this study is to compare the effects of a strategy aimed at increasing alveolar recruitment (high PEEP levels adjusted according to driving pressure and recruitment maneuvers) with that of a strategy aimed at minimizing alveolar distension (low PEEP level without recruitment maneuver) on postoperative respiratory failure and mortality in patients receiving low VT ventilation during emergency abdominal surgery.

Detailed Description
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Emergency abdominal surgery is associated with a high risk of morbidity and mortality. Postoperative pulmonary complications (PPCs) are the second most common surgical complication and adversely influence surgical morbidity. Postoperative respiratory failure (PRF) is one of the most serious pulmonary complication. Two hypotheses can be forward by the literature. First, a low VT lung protective ventilation in combination with a strategy aimed at minimizing alveolar distension by using low PEEP level (and without recruitment maneuver) could improve postoperative outcome while reducing the risk of hemodynamic alterations or, second, could increase the risk of PRF compared with a strategy aimed at increasing alveolar recruitment using higher PEEP level adjusted according to driving pressure in combination with recruitment maneuvers in adult patients undergoing emergency abdominal surgery. Given the uncertainties, and in order to determine the impact of lung protective ventilation strategies on clinical outcomes of high-risk surgical patients, a randomized trial is needed. Our primary hypothesis is that, during low VT ventilation, a strategy aimed at increasing alveolar recruitment by using high PEEP levels adjusted according to driving pressure in combination with recruitment maneuvers could be more effective at reducing PRF and mortality after emergency abdominal surgery than a strategy aimed at minimizing alveolar distension by using lower PEEP without recruitment maneuver. Given the number of patients for whom the question applies, the prevalence and the burden of PPCs, the study can have significant clinical importance and public health implications.

Official Title
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Intraoperative Protective Mechanical Ventilation in Patients Requiring Emergency Abdominal Surgery: IMPROVE-2 Multicenter Prospective Randomized Trial

Conditions
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Emergency Abdominal Surgery, Mechanical Ventilation, General Anesthesia, Postoperative Morbidity

Intervention / Treatment
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* Other: Driving-pressure-guided group
* Other: Low PEEP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥18 years) Patients requiring emergency (defined by the need to proceed to surgery within a few hours after diagnosis) Laparoscopic or non-laparoscopic abdominal surgery under general anesthesia and with an expected duration of at least two hours Exclusion Criteria: Patients already receiving mechanical ventilation for more than 12 hours before enrollment Intracranial hypertension Chronic respiratory disease requiring oxygen therapy or mechanical ventilation at home Undrained pneumothorax or subcutaneous emphysema Patients for which death is deemed imminent and inevitable or patients with an underlying disease process with a life expectancy of less than 3 month Body mass index (BMI) >40 kg/m2 Pregnant or breastfeeding women Patients already enrolled in the IMPROVE-2 trial Participation in a confounding trial with mortality or PRF as the main endpoint Patient's or relative's refusal to participate Guardianship or trusteeship patient No affiliation to the Social Security system

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, prospective, randomized, stratified, parallel-group clinical trial with blinded outcome assessment and concealed allocation of patients undergoing emergency abdominal surgery using low VT lung-protective ventilation to a strategy of minimal alveolar distension using low PEEP level or to a strategy aimed at increasing alveolar recruitment (higher PEEP level individually titrated to minimize the driving pressure in addition to recruitment maneuvers)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low PEEP group<br>Patients will receive a PEEP level ≤5 cmH2O without recruitment maneuvers | Other: Low PEEP<br>* Patients will receive a PEEP level ≤5 cmH2O without recruitment maneuvers<br>|
| Experimental: Driving-pressure-guided group<br>Patients will receive PEEP levels individually set at the highest possible value (up to 15 cmH2O) providing a driving pressure (airway plateau pressure minus PEEP) lower than 13 cmH2O, in addition to recruitment maneuvers | Other: Driving-pressure-guided group<br>* Patients will receive PEEP levels individually set at the highest possible value (up to 15 cmH2O) providing a driving pressure (airway plateau pressure minus PEEP) lower than 13 cmH2O, in addition to recruitment maneuvers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative respiratory failure | Composite criteria : - Failure to wean from the ventilator after surgery (Yes or No) - Requiring unplanned reintubation (Yes or No) - Curative non-invasive ventilation once extubated postoperatively (Yes or No) - Death (all cause of mortality) (Yes or No) If at least one of these 4 criteria is answered yes, the composite criterion (i.e. the primary outcome) will be answered yes | Hospital discharge - Up to day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pulmonary complications | Hypoxemia, pneumonia? development of acute respiratory distress syndrome (ARDS) | Day 30 | 
| Postoperative extra-pulmonary complications | sepsis and septic shock, renal dysfunction | Day 30 | 
| SOFA | Sequential-related Organ Failure Assessment | Day 1 | 
| SOFA | Sequential-related Organ Failure Assessment | Day 2 | 
| SOFA | Sequential-related Organ Failure Assessment | Day 3 | 
| SOFA | Sequential-related Organ Failure Assessment | Day 4 | 
| SOFA | Sequential-related Organ Failure Assessment | Day 5 | 
| SOFA | Sequential-related Organ Failure Assessment | Day 6 | 
| SOFA | Sequential-related Organ Failure Assessment | Day 7 | 
| Ventilator-free days | The number of days alive and with unassisted breathing | Day 30 | 
| Duration of invasive mechanical ventilation | Duration of invasive mechanical ventilation from randomization to first tracheal extubation | Up to Day 30 | 
| Total duration of mechanical ventilation | Total duration of mechanical ventilation (additive, for all épisodes) | Up to Day 30 | 
| Time to successful tracheal extubation | Absence of ventilatory support during the first 48 hours after extubation | 48 hours | 
| Total volume of intraoperative fluids | Total volume of intraoperative fluids (crystalloids and colloids) | Day 1 | 
| Median norepinephrine doses during surgery | µg/kg/min | Day 1 | 
| Median phenylephrine doses during surgery | µg/kg/min | Day 1 | 
| Median ephedrine doses during surgery | µg/kg/min | Day 1 | 
| Intensive care unit (ICU)-free days | Intensive care unit (ICU)-free days | Day 30 | 
| Duration of ICU stay | Duration of ICU stay | Up to day 90 | 
| Duration of hospital stay | Duration of hospital stay | Up to day 90 | 
| All-cause mortality | All-cause mortality | Day 30 | 
| All-cause mortality | All-cause mortality | Day 90 | 
| Time to death | Time to death (Days) | Up to 90 days | 
| Hemodynamic instability | Hemodynamic instability ventilatory-related defined as a drop of arterial systolic pressure below 80 mmHg for more than 5 minutes not responding to treatment | Up to day 30 | 
| Pneumothorax | Pneumothorax ventilatory-related | Up to day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mechanical Ventilation, Lung-Protective Ventilation, Postoperative Pulmonary Complications, Postoperative morbidity