Postoperative Pulmonary Complications (PPC) are very common. It severely affects postoperative recovery, particularly in the abdominal surgery. Patients with laparoscopic resection of colorectal cancer generally have a higher age and decreased lung function reserve. At the same time, they prone to developing atelectasis due to the effects of pneumoperitoneum pressure. Therefore, they are a high-risk group of respiratory insufficiency and PPC.

Mechanical ventilation with a low tidal volume is a routine in clinic nowadays. However, this conventional strategy will also result in atelectasis formation. Therefore, it may deteriorate the vulnerable lung function of patients undergoing laparoscopic resection of colorectal cancer. Patients with Acute Lung Injury or Acute Respiratory Distress Syndrome (ALI/ARDS) could benefit from the "open lung approach", including the use of positive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs). Whether a lung protective mechanical ventilation strategy with medium levels of PEEP and repeated RMs, the "open lung approach", protects against respiratory insufficiency and PPC during laparoscopic resection of colorectal cancer is uncertain. The present study aims at comparing the effects of "open lung approach" mechanical ventilation strategy and conventional mechanical ventilation strategy in PPC, extra-pulmonary complications, length of hospital stay, biomarkers of lung injury and changes of respiratory function in patients undergoing general anesthesia for laparoscopic resection of colorectal cancer.

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:

   4-1. Peak inspiratory pressure limit is set at 45 cmH2O. 4-2. Tidal volume is set at 8 ml/kg PBW and respiratory rate at 6 breaths/min, while PEEP is set at 12 cmH2O.

   4-3. Inspiratory to expiratory ratio (I:E) is set at 1:2. 4-4. Tidal volumes are increased in steps of 4 ml/kg PBW until a plateau pressure of 30-35 cmH2O (if tidal volume reach the biggest volume of the ventilator and plateau pressure cannot reach 30-35 cmH2O, then PEEP is set at 16 cmH2O for a plateau pressure of 30-35 cmH2O).

   4-5. Three breaths are administered with a plateau pressure of 30-35 cmH2O. 4-6. Peak inspiratory pressure limit, respiratory rate, I: E, and tidal volume are set back to settings preceding each recruitment maneuver, while maintaining PEEP at 8 cmH2O.

5. Definitions for postoperative complications. All definitions for postoperative complications refer to the IMPROVE trial and the PROVHILO trial.

6. Composition and responsibilities of the DMSG. Members of the DMSG are the management team of anesthesia department in the research hospital. The DMSG will be responsible for safeguarding the interests of trial participants, assessing the safety and efficacy of the intervention during the trial, and for monitoring the overall conduct of the trial. To enhance the integrity of the trial, the DMSG may also formulate recommendations relating to the selection or recruitment of participants, and the procedures of data management and quality control. The DMSG will be advisory to the principal investigator. The principal investigator will be responsible for reviewing the DMSG recommendations, decide whether to continue or terminate the trial, and determine whether changes in trial conduct are required. Any DMSG members who develop significant conflicts of interest during the course of the trial should resign from the DMSG.

7. Data management. Data will be collected and recorded into case report forms (CRFs) by researchers under the supervision of DMSG members. Data manager will scan handwritten data first and then enter data into electronic database. Source data verification will be performed using a cross-check method by researchers when 7-days follow-up have successfully been completed.

   All adverse events, serious adverse events, unexpected or possibly related events will be recorded in the CRF and reported to the DMSG.

8. Statistics. Statisticians will be in blind state for data analysis. Analysis will be by intention-to-treat comparing the primary outcome measure at 7 days in the two groups by chi-squared test (or Fisher's exact test as appropriate). Continuous variables will be compared using the One-way analysis of variance or the Mann-Whitney U test. Categorical variables will be compared using the chi-square test or the Fisher's exact test. The time-to-event curves will be calculated with the use of the Kaplan-Meier method. All analyses will be conducted using the SPSS 16.0 statistical software.

Inclusion Criteria:

1. Age ≥ 40 years.
2. Undergo elective laparoscopic resection of colorectal cancer.
3. With an expected duration of pneumoperitoneum ≥1.5h.
4. With a preoperative risk index for pulmonary complications ≥ 2.
5. With no contraindication of epidural anesthesia.
6. Pulse oxygen saturation in air ≥ 92%.
7. And informed consent obtained.

Exclusion Criteria:

1. American Society of Anesthesiologists (ASA) physical status ≥ IV.
2. Body mass index ≥30kg/m2.
3. Duration of mechanical ventilation ≥ 1h within 2 weeks preceding surgery.
4. A history of acute respiratory failure within 1 month preceding surgery.
5. With a sepsis or septic shock or instable hemodynamics.
6. With a progressive neuromuscular illness such as myasthenia gravis.
7. With a epilepsy or schizophrenia or Parkinson's disease.
8. With a severe chronic obstructive pulmonary disease (COPD) or pulmonary bulla.
9. Severe organ dysfunction (acute coronary syndrome, uremia, hepatic encephalopathy, classification of function capacity of the NYHA ≥III, malignant arrhythmia and so on).
10. Coma, severe cognitive deficit, language or hearing impairment who cannot communicate.
11. Not proper controlled hypertension.
12. Involved in other clinical studies or refused to join in the research.