Intraoperative Protective Mechanical Ventilation in Patients Requiring Emergency Abdominal Surgery (IMPROVE-2)

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

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.

Study Overview

• Status: Completed
• Conditions: General Anesthesia; Mechanical Ventilation; Emergency Abdominal Surgery; Postoperative Morbidity
• Intervention / Treatment: Other: Low PEEP; Other: Driving-pressure-guided group

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.

• Study Type: Interventional
• Enrollment (Actual): 707
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France
    • University Hospital
  • Annecy, France
    • Hospital
  • Besancon, France
    • University Hospital
  • Bordeaux, France
    • University Hospital
  • Chalon-sur-Saône, France
    • Hospital
  • Clermont-Ferrand, France
    • University Hospital
  • Dijon, France
    • University Hospital
  • Grenoble, France
    • University Hospital
  • Le Mans, France
    • University Hospital
  • Lille, France
    • University Hospital
  • Lyon, France
    • University Hospital
  • Marseile, France
    • University Hospital
  • Marseille, France
    • Institut Paoli Calmette
  • Marseille, France
    • University Hospital
  • Marseille, France
    • Assistance Publique-Hôpitaux de Marseille
  • Montpellier, France
    • University Hospital
  • Nantes, France
    • University Hospital
  • Nice, France
    • University Hospital
  • Nîmes, France
    • University Hospital
  • Paris, France
    • Assistance Publique-Hopitaux de Paris
  • Point A Pitre, France
    • University Hospital
  • Périgueux, France
    • Hospital
  • Rennes, France
    • University Hospital
  • Saint-Etienne, France
    • University Hospital
  • Strasbourg, France
    • University Hospital
  • Suresnes, France
    • Hospital
  • Toulouse, France
    • University Hospital
  • Valenciennes, France
    • Hospital

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low PEEP group; Patients will receive a PEEP level ≤5 cmH2O without recruitment maneuvers	Other: Low PEEP; Patients will receive a PEEP level ≤5 cmH2O without recruitment maneuvers
Experimental: Driving-pressure-guided group; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Investigators: Principal Investigator: Emmanuel Futier, CHU de Clermont-Ferrand

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2021
• Primary Completion (Actual): July 29, 2022
• Study Completion (Actual): October 27, 2022

Study Registration Dates

• First Submitted: June 12, 2019
• First Submitted That Met QC Criteria: June 14, 2019
• First Posted (Actual): June 17, 2019

Study Record Updates

• Last Update Posted (Actual): October 31, 2022
• Last Update Submitted That Met QC Criteria: October 28, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Mechanical Ventilation; Postoperative Pulmonary Complications; Postoperative morbidity; Lung-Protective Ventilation
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Emergencies
• Other Study ID Numbers: IMPROVE-2 study; 2019-A00265-52 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

The French National Data Safety Authority (CNIL) forbids making data freely available without prior agreement. Thus, the data underlying study findings cannot be made freely available because of ethical and legal restrictions. However, individual participant data underlying the results reported in the manuscript (text, tables, figures, and appendices) can be obtained after deidentification. Data can be obtained upon request from the IMPROVE-2 steering committee. Readers may contact: efutier@chu-clermontferrand.fr to request the data.

The data cannot be freely available for the reasons mentioned above. Data access can be only possible after scientific assessment and data sharing agreement, detailing the type of data requested. This data sharing agreement has to be signed between applicants and the sponsor, Clermont-Ferrand University Hospital.

• IPD Sharing Time Frame: Beginning 6 months following article publication. No end date
• IPD Sharing Access Criteria: . Data can be obtained upon request from the IMPROVE-2 steering committee. Readers may contact: efutier@chu-clermontferrand.fr to request the data.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

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