Intraoperative Protective Ventilation and Postoperative Pulmonary Complications

Study Overview
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Brief Summary
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The purpose of this pilot study is to identify the optimal way to ventilate patients during abdominal surgery in order to reduce the amount of post-operative pulmonary complications in patients at moderate and high-risk for them.

Detailed Description
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The investigators plan to prospectively compare two methods to individualize Positive End Expiratory Pressure (PEEP) settings in the operating room during abdominal surgery: (1) Maximization of respiratory compliance during a decremental PEEP titration, and (2) Prevention of negative end-expiratory transpulmonary pressures. The investigators will exploit the usual intraoperative requirement for a naso/orogastric tube to assess transpulmonary pressures,and respiratory mechanics measurements from anesthesia machines to titrate PEEP. The investigators will measure biomarkers of lung injury and lung function to compare those methods between themselves and to the control group. In the process, the investigators will assess the ease and reliability of anesthesia teams in implementing the methods. These data will allow us to determine the PEEP strategy best suited for the full-scale trial, and to estimate the degree of separation the experimental lung protective approach will have from the protocolized usual care control settings.

Official Title
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Intraoperative Protective Ventilation and Postoperative Pulmonary Complications

Conditions
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Complication of Ventilation Therapy, Postoperative Respiratory Complications

Intervention / Treatment
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* Other: Maximal Compliance
* Other: Transpulmonary Pressure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ( 18 years) scheduled for elective surgery expected to last 2 h, elective intraperitoneal abdominal or pelvic surgery including: gastric; biliary; pancreatic; hepatic; major bowel, ovarian, renal tract, bladder, and prostatic; radical hysterectomy; and pelvic exenteration; at least intermediate risk of PPCs defined by a risk score 26 Exclusion Criteria: Inability or refusal to provide consent Refusal of clinicians caring for patient to follow the protocol Participation in interventional investigation within 30 days of the time of the study Pregnancy Emergency surgery Severe obesity (above Class I, BMI 35) Significant lung disease: any diagnosed or treated respiratory condition that (a) requires home oxygen therapy or non-invasive ventilation, (b) severely limits exercise tolerance to <4 METs (e.g. patients unable to do light housework, walk flat at 4 miles/h or climb one flight of stairs), or (c) required previous lung surgery80 Significant heart disease: cardiac conditions that limit exercise tolerance to <4 METs Renal failure: peritoneal or hemodialysis requirement or preoperative creatinine 2 mg/dL; Neuromuscular disease that impairs ability to ventilate without assistance Severe chronic liver disease (Child-Pugh Score of 10 -15) Sepsis Malignancy or other irreversible condition for which 6-month mortality is estimated 50% Bone marrow transplant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional Strategy<br>Patients will receive usual and prudent PEEP and tidal volume settings. | |
| Experimental: Maximal Compliance Strategy<br>PEEP will be set at the maximum static respiratory system compliance during a descending PEEP titration curve. | Other: Maximal Compliance<br>* PEEP will be set at the maximum static respiratory system compliance during a descending PEEP titration curve.<br>|
| Experimental: Transpulmonary Pressure Strategy<br>Personal PEEP titration using transpulmonary pressures obtained from a naso/orogastric tube containing an esophageal balloon port | Other: Transpulmonary Pressure<br>* We will use transpulmonary pressure values obtained using an naso/orogastric tube during the operative procedure to titrate PEEP intraoperatively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative driving pressure | We will assess intraoperative driving pressure to evaluate respiratory mechanics during surgery. | During abdominal surgery | 
| Intraoperative transpulmonary pressure | We will assess intraoperative transpulmonary pressure to evaluate respiratory mechanics during surgery. | During abdominal surgery | 
| Intraoperative respiratory system compliance | We will assess intraoperative respiratory system compliance to evaluate respiratory mechanics during surgery. | During abdominal surgery | 
| Intraoperative positive end-expiratory pressure (PEEP) levels | We will assess intraoperative PEEP values and their variability between patients and during surgery. | During abdominal surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraoperative gas exchange | We will assess intraoperative oxygenation and carbon dioxide elimination. | During abdominal surgery | 
| Plasma levels of biomarkers of lung injury | We will assess plasma concentrations of biomarkers of lung injury before and after surgery, including biomarkers of inflammation (interleukin-6, IL-6, interleukin-8, IL-8), epithelial injury (soluble form of the receptor for advanced glycation end-products, sRAGE, Club Cell protein-16, CC16), endothelial injury (angiopoietin-2, Ang-2), and endothelial-derived coagulation activation (plasminogen activator inhibitor-1, PAI-1). | During abdominal surgery | 
| Postoperative Pulmonary Complications | We will assess the incidence and absolute number of postoperative pulmonary complications within the first 7 postoperative days. | Within the first 7 postoperative days. |