Effects of Different Ventilation Patterns on Lung Injury

Study Overview
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Brief Summary
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In 1967, the term respirator lung was coined to describe the diffuse alveolar infiltrates and hyaline membranes that were found on postmortem examination of patients who had undergone mechanical ventilation.This mechanical ventilation can aggravate damaged lungs and damage normal lungs. In recent years, Various ventilation strategies have been used to minimize lung injury, including low tide volume, higher PEEPs, recruitment maneuvers and high-frequency oscillatory ventilation. which have been proved to reduce the occurrence of lung injury. In 2012,Needham et al. proposed a kind of lung protective mechanical ventilation, and their study showed that limited volume and pressure ventilation could significantly improve the 2-year survival rate of patients with acute lung injury.Volume controlled ventilation is the most commonly used method in clinical surgery at present.Volume controlled ventilation(VCV) is a time-cycled, volume targeted ventilation mode, ensures adequate gas exchange. Nevertheless, during VCV, airway pressure is not controlled.Pressure controlled ventilation（PCV） can ensure airway pressure,however minute ventilation is not guaranteed.Pressure controlled ventilation-volume guarantee(PCV-VG) is an innovative mode of ventilation utilizes a decelerating flow and constant pressure. Ventilator parameters are automatically changed with each patient breath to offer the target VT without increasing airway pressures. So PCV-VG has the advantages of both VCV and PCV to preserve the target minute ventilation whilst producing a low incidence of barotrauma pressure-targeted ventilation. Current studies on PCV-VG mainly focus on thoracic surgery, bariatric surgery and urological surgery, and the research indicators mainly focus on changes in airway pressure and intraoperative oxygenation index.The age of patients undergoing laparoscopic colorectal cancer resection is generally higher, the cardiopulmonary reserve function is decreased, and the influence of intraoperative pneumoperitoneum pressure and low head position increases the incidence of intraoperative and postoperative pulmonary complications.Whether PCV-VG can reduce the incidence of intraoperative lung injury and postoperative pulmonary complications in elderly patients undergoing laparoscopic colorectal cancer resection, and thereby improve postoperative recovery of these patients is still unclear.

Detailed Description
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One hundred patients undergoing elective laparoscopic colorectal cancer resection (age > 65 years old, body mass index(BMI）18-30 kg/m2, American society of anesthesiologists(ASA )grading Ⅰ - Ⅲ ) will be randomly assigned to volume control ventilation(VCV)group and pressure controlled ventilation-volume guarantee(PCV-VG)group.General anesthesia combined with epidural anesthesia will be used to both groups. Ventilation settings in both groups are VT 8 mL/kg,inspiratory/expiratory (I/E) ratio 1:2,inspired oxygen concentration (FIO2) 0.5 with air,2.0 L/min of inspiratory fresh gas flow,positive end-expiratory pressure (PEEP) 0 millimeter of mercury （mmHg）,respiratory rate (RR) was adjusted to maintain an end tidal CO2 pressure (ETCO2) of 35 -45 mmHg. In operation dates will be collected at the following time points: preanesthesia, 1 hour after pneumoperitoneum,2 hours after pneumoperitoneum ,30 minutes after admission to post-anaesthesia care unit (PACU) .The dates collected or calculated are the following:1)peak airway pressure,plate airway pressure, mean inspiratory pressure, dynamic compliance, RR,Exhaled VT andETCO2，2) Arterial blood gas analysis: arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2),power of hydrogen（PH）, and oxygen saturation (SaO2)，3) Oxygenation index (OI) calculation; PaO2/FIO2, 4) Ratio of physiologic dead-space over tidal volume(Vd/VT) (expressed in %) was calculated with Bohr's formula ; Vd/VT = (PaCO2 - ETCO2)/PaCO2,5) Hemodynamics: heart rate, mean arterial pressure (MAP),and central venous pressure （CVP），6) lung injury markers ：Interleukin 6(IL6）,Interleukin 8（IL8）,Clara cell protein 16（CC16）,Solution advanced glycation end products receptor（SRAGE）,tumor necrosis factor α(TNFα) . Investigators will collect the following dates according to following-up after surgery: the incidence of postoperation pulmonary complications(PPC) based on PPC scale within seven days , incidence of pneumonia within seven days after surgery,incidence of atelectasis within seven days after surgery,length of hospital days after surgery, the incidence of postoperative unplanned admission to ICU, the incidence of operation complications within 7 days after surgery, the incidence of postoperative systematic complications within 7 days after surgery.

Official Title
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Effects of Different Ventilation Modes on Intraoperative Lung Injury and Postoperative Pulmonary Complications in Elderly Patients Undergoing Laparoscopic Colorectal Cancer Resection

Conditions
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Lung Injury

Intervention / Treatment
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* Procedure: pressure-controlled ventilation-volume guaranteed
* Procedure: volume controlled ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: scheduled for Laparoscopic colorectal cancer resection age >65 years body mass index(BMI) 18-30kg / m2 ASA gradingⅠ-Ⅲ Exclusion Criteria: history of lung surgery severe restrictive or obstructive pulmonary disease (preoperative lung function test: forced vital capacity(FVC)< 50% predictive value of FVC,forced expiratory volume at one second(FEV1)< 50% predictive value of FEV1 Acute respiratory failure, pulmonary infection, ALI/ARDS, and acute stage of asthmaAcute respiratory failure, pulmonary infection, acute lung injury(ALI),acute respiratory distress syndrome(ARDS), and acute stage of asthma (bronchodilators were needed for treatment) were found within 1 month before surgery Patients at risk of preoperative reflux aspiration Preoperative positive pressure ventilation (as obstructive sleep apnea hypopnea syndrome patients) or long-term home oxygen therapy were performed Serious heart, liver and kidney diseases: heart function class more than 3, severe arrhythmia (sinus bradycardia (ventricular rate < 60 times/min), atrial fibrillation, atrial flutter, atrioventricular block, frequent premature ventricular and polyphyly ventricular early, early to R on T, ventricular fibrillation and ventricular flutter), acute coronary syndrome, liver failure, kidney failure Neuromuscular diseases affect respiratory function, such as Parkinson's disease, myasthenia gravis and cerebral infarction affect normal breathing Mental illness, speech impairment, hearing impairment Contraindications for spinal anesthesia puncture Refuse to participate in this study or participate in other studies -

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pressure-controlled ventilation-volume guaranteed<br>patients will be allocated to pressure-controlled ventilation volume guaranteed in operation | Procedure: pressure-controlled ventilation-volume guaranteed<br>* patients will be allocated to pressure-controlled ventilation-volume guaranteed in operation<br>|
| Placebo Comparator: volume controlled ventilation<br>patients will be allocated to volume controlled ventilation in operation | Procedure: volume controlled ventilation<br>* patients will be allocated to pressure-controlled ventilation volume guaranteed in operation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence rate of Oxygenation index≤300mmHg | Oxygenation index(OI)=PaO2/FiO2 | 10minutes before anesthesia,1 hour after pneumoperitoneum,2 hour after pneumoperitoneum,30 minutes after after extubation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence rate of pulmonary complications | Pulmonary complications were assessed using the Postoperation Pulmonary complication ( PPC) scale,The scale is divided into four grades, with 0 indicating no pulmonary complications and 1 to 4 indicating increasingly severe pulmonary complications. | Day 0 to 7 after surgery | 
| incidence of pneumonia | record the occurrence rate of pneumonia after surgery | Day 0 to 7 after surgery | 
| incidence of pulmonary atelectasis | record the occurrence rate of pulmonary atelectasis after surgery | Day 0 to 7 after surgery | 
| peak airway pressure | Peak airway Pressure（Ppeak, cm H2O) | through mechanical ventilation,average of 3 hours | 
| Plateau airway pressure | Plateau airway pressure（Pplat, cm H2O） | through mechanical ventilation,average of 3 hours | 
| Static lung compliance | Static lung compliance (Csta, ml/cm H2O) = Vt/ (Pplat-PEEP) | through mechanical ventilation,average of 3 hours | 
| Dynamic lung compliance | Dynamic lung compliance (Cdyn , ml/cm H2O)= Vt/ (Ppeak-PEEP) | through mechanical ventilation,average of 3 hours | 
| Arterial partial pressure of oxygen | Arterial partial pressure of oxygen (PaO2, mmHg） | 10 minutes before anesthesia, 1 hour after pneumoperitoneum, 2 hours after pneumoperitoneum, 30 minutes after extubation | 
| assessing change of Alveolar-arterial oxygen tension difference | Alveolar-arterial oxygen tension difference (mmHg） | 10 minutes before anesthesia, 1 hour after pneumoperitoneum, 2 hours after pneumoperitoneum, 30 minutes after extubation | 
| assessing change of Respiratory index | Fraction of inspired oxygen (FiO2); Respiratory index (RI) =Ratio of alveolar-arterial oxygen tension difference to FiO2 | 10 minutes before anesthesia, 1 hour after pneumoperitoneum, 2 hours after pneumoperitoneum, 30 minutes after extubation | 
| assessing change of Alveolar dead space fraction | Arterial carbon dioxide partial pressure (PaCO2); partial pressure of carbon dioxide in endexpiratory gas (PetCO2); Alveolar dead space fraction (Vd/Vt）=(PaCO2-PetCO2)/ PaCO2; | 10 minutes before anesthesia, 1 hour after pneumoperitoneum, 2 hours after pneumoperitoneum,30 minutes after extubation | 
| assessing change of lactic acid | lactate ( LAC), mmol/L | 10 minutes before anesthesia, 1 hour after pneumoperitoneum, 2 hours after pneumoperitoneum, 30 minutes after extubation | 
| assessing change of Advanced glycation end products receptor | Advanced glycation end products receptor (RAGE, pg/ml) | 10 minutes before anesthesia,30 minutes after extubation | 
| assessing change of Tumor Necrosis Factor alpha | Tumor Necrosis Factor alpha (TNF-α, pg/ml) | 10 minutes before anesthesia,30 minutes after extubation | 
| assessing change of Interleukin 6 | Interleukin 6 (IL-6, pg/ml) | 10 minutes before anesthesia,30 minutes after extubation | 
| assessing change of Interleukin 8 | Interleukin 8 (IL-8, pg/ml) | 10 minutes before anesthesia,30 minutes after extubation | 
| assessing change of Clara cell protein 16, | Clara cell protein 16, | 10 minutes before anesthesia,30 minutes after extubation | 
| The occurrence rate of hypoxemia in PACU | The occurrence rate of hypoxemia (SPO2<90% or PaO2<60 mmHg) in PACU | 30 minutes after extubation | 
| Occurrence rate of operation complications | abdominal abscess, anastomotic fistula, bleeding and the incidence of reoperation within 7 days | within 7 days after operation | 
| Occurrence rate of Systemic complications | Systemic complications including sepsis and septic shock | within 7 days after surgery | 
| Antibiotic dosages | record the Antibiotic dosages within 7 days after surgery | within 7 days after surgery | 
| incidence of Unplanned admission to ICU | Unplanned admission to ICU within 30 days after surgery | within 30 days after surgery | 
| Length of ICU stay within 30 days after surgery | Length of ICU stay within 30 days after surgery | within 30 days after surgery | 
| Length of hospital stay within 30 days after surgery | Length of hospital stay within 30 days after surgery | within 30 days after surgery | 
| Death from any cause | Death from any cause 30 days after surgery | within 30 days after surgery | 
| The occurrence rate of hypoxemia after surgery | The occurrence rate of hypoxemia (SPO2<90% or PaO2<60 mmHg) after surgery | within 7 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aged, mechanical ventilation,