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.

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.

Mechanical Ventilation, Lung-Protective Ventilation, Postoperative Pulmonary Complications, Postoperative morbidity

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)

It will not be possible to mask the assigned ventilation strategy from the treating clinicians because they have an ethical responsibility to ensure patient safety during the emergency procedures. However, procedures will be put in place to minimize the possibility of bias arising because research staff becomes aware of trial group allocation. At each participating center, patients will be followed up for primary and secondary endpoints by members of the research staff who will be unaware of the trial group allocation. Information on whether the primary and secondary outcomes occur will be collected and entered into the electronic web-based case report form (eCRF) by trial or clinical trained personal (clinical research associate), blinded to the allocation group, under the supervision of the local principal investigator (PI) or designee who will also be unaware of the trial group allocation.

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

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.

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

Hemodynamic instability ventilatory-related defined as a drop of arterial systolic pressure below 80 mmHg for more than 5 minutes not responding to treatment

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

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.

. Data can be obtained upon request from the IMPROVE-2 steering committee. Readers may contact: efutier@chu-clermontferrand.fr to request the data.

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.