Effects of Open Lung Approach on Intraoperative Respiratory Function and Postoperative Recovery of Patients With Laparoscopic Colorectal Resection

1. Sample size calculation, randomization and patients safety. The required sample size is calculated from previous studies on the incidence of postoperative pulmonary complications. A two group chi-square test with a 0.05 two-sided significance level will have 80% power to detect the difference (in primary outcome) between conventional mechanical ventilation strategy (25%) and open lung approach mechanical ventilation strategy (12.5%) when the sample size in each group is 126. In consideration of a 10% loss rate, 280 cases to be included in this trial.

Research will be carried out in two stages. Completely-randomized design was used in the first stage, and randomized block design in the second stage. The interim analysis will be performed when 100 patients (first stage) have successfully been included and followed-up. The Data Monitoring and Safety Group (DMSG) will provide recommendations about stopping or continuing the trial to the principal investigator. The DMSG will recommend stopping the trial, if significant group-difference in adverse events is found at the interim analysis (p<0.025), or if postoperative pulmonary complications occur more frequently in the intervention group (p<0.025). If the intervention has a strong trend for improving postoperative pulmonary complications (p<0.018) at the first stage, termination of the study is considered. 2. Protocol drop-out. Anesthesiologists are allowed to change the ventilation protocol if there is any concern about patient's safety. The level of PEEP can be modified according to the anesthesiologist in charge if the systolic arterial pressure (SBP)< 80 mmHg and SBP drop ≥30% baseline values for more than 3 minutes despite intravenous fluid infusion and/or start of vasopressors, if dosages of vasopressors are at the highest level tolerated, if new arrhythmias develop which are unresponsive to treatment suggested by the Advanced Cardiac Life Support Guidelines. If there is pneumothorax or hypoxemia (SpO2 < 90% for more than 3 minutes）, if there is need of massive transfusion (>8 units packed red blood cell) to maintain hemoglobin >7 mg/dl, if the duration of pneumoperitoneum is less then 1h or mechanical ventilation time is less then 2h, if there is a surgical complication (such as severe hypercapnia, unexpected conversion to open surgery, unplanned reoperation in 24h after surgery, unplanned ICU admission for surgical reasons) or if patient die during operation, then the patient will be dropped out of the study. All drop-out cases will be included in the safety analysis. 3. Trial settings for intraoperative ventilation. Patients in the conventional mechanical ventilation strategy group will have a tidal volume of 6 to 8 ml per kilogram Predicted Body Weight (PBW), zero PEEP and no recruitment maneuver. Patients in the open lung approach mechanical ventilation strategy group will have a tidal volume of 6 to 8 ml per kilogram PBW, a PEEP level of 6 to 8 cm of water and recruitment maneuvers. Recruitment maneuvers consist of a stepwise increase of tidal volume （as detailed below） and will be applied immediately after tracheal intubation and every 30 min thereafter until the end of surgery.

In each group, anesthesiologists will be advised to use an inspired oxygen fraction (FIO2) between 0.4 to 0.5 and to maintain oxygen saturation ≥ 92%. The inspiratory to expiratory time ratio will be set at 1:2, with a respiratory rate adjusted to maintain normocapnia (end-tidal carbon dioxide concentration of 30-50 mmHg).

PBW is calculated according to a predefined formula with: 50 + 0.91 x (centimeters of height - 152.4) for males and 45.5 + 0.91 x (centimeters of height - 152.4) for females. In each group, patients will be ventilated using the volume-controlled ventilation strategy using an anesthesia ventilator: 1. Avance® (Datex-Ohmeda, General Electric, Helsinki, Finland) 2. Tiro® (Dräger, Lübeck, Germany) 4. Recruitment maneuvers.

Stepwise increase of tidal volume will be used as a method of recruitment maneuvers in this trial. Recruitment maneuvers should not be performed when patients are hemodynamic unstable, as judged by the attending anesthesiologist. Recruitment maneuvers will be performed as follows: