Intraoperative Protective Ventilation and Postoperative Pulmonary Complications

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Respiratory Complications; Complication of Ventilation Therapy
• Intervention / Treatment: Other: Maximal Compliance; Other: Transpulmonary Pressure

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: University of Colorado, Denver; Mayo Clinic

Publications and helpful links

General Publications

• Fernandez-Bustamante A, Sprung J, Parker RA, Bartels K, Weingarten TN, Kosour C, Thompson BT, Vidal Melo MF. Individualized PEEP to optimise respiratory mechanics during abdominal surgery: a pilot randomised controlled trial. Br J Anaesth. 2020 Sep;125(3):383-392. doi: 10.1016/j.bja.2020.06.030. Epub 2020 Jul 16.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: January 30, 2016
• First Submitted That Met QC Criteria: January 30, 2016
• First Posted (Estimate): February 2, 2016

Study Record Updates

• Last Update Posted (Actual): February 8, 2019
• Last Update Submitted That Met QC Criteria: February 6, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 2015P001613

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No