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The PROtective Ventilation Using Open Lung Approach Or Not Trial

ABSTRACT: 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.

DISEASE(S): Respiratory Insufficiency,Postoperative Pulmonary Complications

PROVIDER: 2244915 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Introduction: The ideal ventilation strategy for patients with massive brain damage requires better elucidation. We hypothesized that in the presence of massive brain injury, a ventilation strategy using low (6 mL/kg) tidal volume (VT) ventilation with open lung positive end-expiratory pressure set according to the minimal static elastance of the respiratory system (LVT/OLPEEP), attenuate the impact of massive brain damage on gas-exchange, respiratory mechanics, lung histology and whole genome alterations compared with high (12 mL/kg) VT and low PEEP ventilation (HVT/LPEEP). Methods: Twenty-eight adult male Wistar rats were randomly assigned to one of four groups: 1) no brain damage (NBD) with LVT/OLPEEP; 2) NBD with HVT/LPEEP; 3) brain damage (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. All animals were mechanically ventilated for six hours. Brain damage was induced by an inflated balloon catheter into the epidural space. Hemodynamics was recorded and blood gas analysis was performed hourly. At the end of the experiment, respiratory system mechanics and lung histology were analysed. Whole genome analysis was performed using Affimetrix gene chips and confirmatory real-time PCR. Results: In NBD, both LVT/OLPEEP and HVT/LPEEP did not affect arterial blood gases, as well as whole genome expression changes and real-time PCR. In BD, LVT/OLPEEP, compared to HVT/LPEEP, reduced lung damage according to histology, genome analysis and real-time PCR with decreased interleukin (IL-6), cytokine-induced neutrophil chemoattractant (CINC)-1 and angiopoietin-4 expressions. LVT/OLPEEP compared to HVT/LPEEP improved overall survival. Conclusions: In BD, LVT/OLPEEP minimizes lung morpho-functional changes and inflammation compared to HVT/LPEEP. LVT/OLPEEP might represent a suitable ventilatory strategy in massive brain damage. 24 Wistar rats - lung samples, 4 groups, 1. non-braindamaged/braindead high tidal volume ventilation, 2. non-braindamaged/braindead best PEEP ventilation, 3. Braindamaged/braindead high tidal volume ventilation, 4. Braindamaged/braindead best PEEP ventilation

Project description:In this model of ventilator-induced lung injury (VILI), we compared the gene expression profile of whole lungs extracted from sponaneously breathing mice (control, c) or mouse submitted to 8 hours mechanical venitlation with 12 ml/kg tidal volume 2cmH2O of positive end expiratory pressure (PEEP) (ventilation, v). Spontaneously breathing NOD/shi mice were randomized to control (n=3) or ventilation (n=5) condition. In brief, mice were anesthetized with the injection of ketamine (65 mg/kg, ip), acepromazine (2 mg/kg, ip) and xylazine (13 mg/kg, ip)(Henry Schein Inc., Melville, NY). Once deep sedation was achieved, a tracheostomy was performed and a PE-10 cannula was inserted in the trachea and stabilized with silk ligature. Control animals were immediately sacrificied with a supra-physiological dose of ketamine (300 mg/kg, ip). For ventilated mice, the cannula was connected to a custom built Voltek rodent ventilator (Voltek Enterprises, Toronto, CA). We ventilated mice for 8 hours using 2cmH2O positive end expiratory pressure (PEEP), inflating the lungs every hour to 20 cmH2O pressure as we have previously described. (16). The chest muscle was paralyzed with the injection of pancurorium (1mg/kg, ip)(Sigma-Aldrich) in ventilated mice to avoid spontaneous breathing. Heart rate and respiratory rate was continuously monitored and additional anesthesia was provided if a >15% increase in these parameters was detected. The animal protocol was approved by the BWH Institutional Animal Care and Use Committee (protocol #04477). Ventilated animals At the end of the each experiment, the animals were sacrificed with a supra-physiological dose of ketamine (300 mg/kg, ip). Subsequently, the chest cavity was opened, and the right lung was isolated and ligated at the main bronchus.Lungs were harvested and snap frozen in liquid nitrogen for total RNA extraction. Total RNA was extracted from lungs of controls (n=3) and mice submitted to ventilation (n=5) and there gene expression profiles were compared.

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The PROtective Ventilation Using Open Lung Approach Or Not Trial

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