Clinical trial NCT03987789: Intraoperative Protective Mechanical Ventilation in Patients Requiring Emergency Abdominal Surgery
Official title: Intraoperative Protective Mechanical Ventilation in Patients Requiring Emergency Abdominal Surgery: IMPROVE-2 Multicenter Prospective Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Emergency Abdominal Surgery
Mechanical Ventilation
General Anesthesia
Postoperative Morbidity
Keywords: Mechanical Ventilation
Lung-Protective Ventilation
Postoperative Pulmonary Complications
Postoperative morbidity
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2019-06-17
Enrollment: 707
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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)
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Postoperative respiratory failure
timeFrame: Hospital discharge - Up to day 30
Secondary outcomes:
measure: Postoperative pulmonary complications
timeFrame: Day 30
measure: Postoperative extra-pulmonary complications
timeFrame: Day 30
measure: SOFA
timeFrame: Day 1
measure: SOFA
timeFrame: Day 2
measure: SOFA
timeFrame: Day 3
measure: SOFA
timeFrame: Day 4
measure: SOFA
timeFrame: Day 5
measure: SOFA
timeFrame: Day 6
measure: SOFA
timeFrame: Day 7
measure: Ventilator-free days
timeFrame: Day 30
measure: Duration of invasive mechanical ventilation
timeFrame: Up to Day 30
measure: Total duration of mechanical ventilation
timeFrame: Up to Day 30
measure: Time to successful tracheal extubation
timeFrame: 48 hours
measure: Total volume of intraoperative fluids
timeFrame: Day 1
measure: Median norepinephrine doses during surgery
timeFrame: Day 1
measure: Median phenylephrine doses during surgery
timeFrame: Day 1
measure: Median ephedrine doses during surgery
timeFrame: Day 1
measure: Intensive care unit (ICU)-free days
timeFrame: Day 30
measure: Duration of ICU stay
timeFrame: Up to day 90
measure: Duration of hospital stay
timeFrame: Up to day 90
measure: All-cause mortality
timeFrame: Day 30
measure: All-cause mortality
timeFrame: Day 90
measure: Time to death
timeFrame: Up to 90 days
measure: Hemodynamic instability
timeFrame: Up to day 30
measure: Pneumothorax
timeFrame: Up to day 30
Other outcomes:
Locations:
city: Angers
country: France
facility: University hospital
city: Annecy
country: France
facility: Hospital
city: Besancon
country: France
facility: University hospital
city: Bordeaux
country: France
facility: University Hospital
city: Chalon-sur-Saône
country: France
facility: Hospital
city: Clermont-Ferrand
country: France
facility: University hospital
city: Dijon
country: France
facility: University hospital
city: Grenoble
country: France
facility: University hospital
city: Le Mans
country: France
facility: University hospital
city: Lille
country: France
facility: University hospital
city: Lyon
country: France
facility: University hospital
city: Marseile
country: France
facility: University hospital
city: Marseille
country: France
facility: Assistance Publique-Hôpitaux de Marseille
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Marseille
country: France
facility: University hospital
city: Montpellier
country: France
facility: University hospital
city: Nantes
country: France
facility: University Hospital
city: Nice
country: France
facility: University hospital
city: Nîmes
country: France
facility: University hospital
city: Paris
country: France
facility: Assistance Publique-Hôpitaux de Paris
city: Point A Pitre
country: France
facility: University hospital
city: Périgueux
country: France
facility: Hospital
city: Rennes
country: France
facility: University hospital
city: Saint-Etienne
country: France
facility: University hospital
city: Strasbourg
country: France
facility: University hospital
city: Suresnes
country: France
facility: Hospital
city: Toulouse
country: France
facility: University hospital
city: Valenciennes
country: France
facility: Hospital
Study officials:
affiliation: CHU de Clermont-Ferrand
name: Emmanuel Futier
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khaled L, Godet T, Jaber S, Chanques G, Asehnoune K, Bourdier J, Araujo L, Futier E, Pereira B. Intraoperative protective mechanical ventilation in patients requiring emergency abdominal surgery: the multicentre prospective randomised IMPROVE-2 study protocol. BMJ Open. 2022 May 6;12(5):e054823. doi: 10.1136/bmjopen-2021-054823.