An Anesthesia-Centered Bundle to Reduce Postoperative Pulmonary Complications: The PRIME-AIR Study

Not Applicable

Completed

Conditions: Postoperative Pulmonary Complications

Registration Number: NCT04108130

Lead Sponsor: Columbia University

Brief Summary: Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality in surgical patients. National estimates suggest 1,062,000 PPCs per year, with 46,200 deaths, and 4.8 million additional days of hospitalization. The objective of the study is to develop and implement perioperative strategies to eliminate PPCs in abdominal surgery, the field with the largest absolute number of PPCs. We will conduct a randomized controlled pragmatic trial in 750 studied participants. The effectiveness of an individualized perioperative anesthesia-centered bundle will be compared to the usual anesthetic care in patients receiving open abdominal surgery. At the end of this project, the investigators expect to change clinical practice by establishing a new and clinically feasible anesthesia-centered strategy to reduce perioperative lung morbidity. The research will be conducted across 14 US academic centers, and will be funded by the National Institute of Health.

Detailed Description: Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality in surgical patients. National estimates suggest 1,062,000 PPCs per year, with 46,200 deaths, and 4.8 million additional days of hospitalization. Abdominal surgery is the field with the largest absolute number of PPCs. The long-term goal is to develop and implement perioperative strategies to eliminate PPCs. Whereas PPCs are as significant and lethal as cardiac complications, research in the field has received much less attention, and strategies to minimize PPCs are regrettably limited. Recently, the investigators and others have suggested a crucial role of anesthesia related interventions such as ventilatory strategies, and administration and reversal of neuromuscular blocking agents in reducing PPCs. These findings are consistent with the beneficial effects of lung protective ventilation during the adult respiratory distress syndrome (ARDS). While surgical patients differ substantially from ARDS patients as most have no or limited lung injury at the start of surgery, intraoperative anesthetic and abdominal surgery interventions result in lung derecruitment and predispose to or produce direct and indirect, potentially multiple-hit, lung injury. Thus, effective anesthetic strategies aiming at early lung protection in this group of patients are greatly needed. Indeed, the current lack of evidence results in wide and unexplained variability in anesthetic practices creating a major public health issue as some practices within usual care appear to be suboptimal and even potentially injurious. The investigators hypothesize that an anesthesia-centered bundle, based on recent findings and focused on perioperative lung protection, will minimize multiple and synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction and result in decreased incidence and severity of PPCs. Founded on strong preliminary data, we will leverage a network of US academic centers to study this hypothesis in two aims: Aim 1. To compare the number and severity of PPCs in participants receiving an individualized perioperative anesthesia-centered bundle to those in participants receiving usual anesthetic care during open abdominal surgery. For this, the investigators propose to conduct a prospective multicenter randomized controlled pragmatic trial with a blinded assessor in a total of 750 studied participants. The bundle will consist of optimal mechanical ventilation comprising individualized positive end-expiratory pressure to maximize respiratory system compliance and minimize driving pressures, individualized use of neuromuscular blocking agents and their reversal, and postoperative lung expansion and early mobilization; Aim 2. To assess the effect of the proposed bundle on plasma levels of lung injury biomarkers. The investigators theorize that our intervention will minimize overinflation and atelectasis reducing plasma levels of biomarkers of lung inflammatory, epithelial, and endothelial injury. Such mechanistic insights will facilitate bundle dissemination and support adoption as it has for lung protective ventilation for ARDS. At the end of this project, the investigators expect to change clinical practice by establishing a new and clinically feasible anesthesia-centered strategy to reduce perioperative lung morbidity.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 794

Inclusion Criteria

Adults (>=18 years) scheduled for elective surgery with expected duration >=2 hours
Open abdominal surgery including: gastric, biliary, pancreatic, hepatic, major bowel, ovarian, renal tract, bladder, prostatic, radical hysterectomy, and pelvic exenteration
Intermediate or high risk of PPCs defined by an ARISCAT (Assess Respiratory Risk in Surgical Patients in Catalonia Score) risk score>=26

Exclusion Criteria

Inability or refusal to provide consent
Inability or significant difficulty to perform any study interventions, including incentive spirometry, ambulation and/or maintaining follow-up contact with study personnel for up to 90 days after the date of surgery.
Participation in any interventional research study within 30 days of the time of the study.
Previous surgery within 30 days prior to this study.
Pregnancy
Emergency surgery
Severe obesity (above Class I, BMI>=35 kg/m2)
Significant lung disease: any diagnosed or treated respiratory condition that (a) requires home oxygen therapy or non-invasive ventilation (except nocturnal treatment of sleep apnea without supplemental oxygen), (b) severely limits exercise tolerance to <4 metabolic equivalents (METs) (e.g., patients unable to do light housework, walk flat at 4 miles/h or climb one flight of stairs), (c) required previous lung surgery, or (d) includes presence of severe pulmonary emphysema or bullae
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-Turcotte-Pugh Score >9, Appendix I)
Sepsis
Malignancy or other irreversible condition for which 6-month mortality is estimated >=20%
Bone marrow transplant

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Number and Severity of Postoperative Pulmonary Complications Between Participant Groups	Postoperative Days 0 through 7	The distribution of the number and severity of accumulated post-operative pulmonary complications (PPCs) between the control and intervention groups during the first 7 days after surgery.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Grade 1 and 2 Postoperative Pulmonary Complications	Postoperative Days 0 through 7	Individual grade 3 and 4 postoperative pulmonary complications within 7 days after the day of the surgery.
Number of Participants With Grade 3 and 4 Postoperative Pulmonary Complications	Postoperative Days 7, 30, and 90	Individual grade 3 and 4 postoperative pulmonary complications within 7, 30, and 90 days after the day of the surgery.
Number of Participants With Hypoxemia by Postoperative Day 7	Postoperative Days 0 through 7	Presence of any hypoxemia (as defined in PPC grade 1 and 2) within 7 days after the day of the surgery.
Number of Participants With Atelectasis by Postoperative Day 7	Days 0 through 7 after the day of surgery	Presence of atelectasis (radiological confirmation + either temperature \>37.5°C or abnormal lung symptoms/signs) by day 7 after the date of surgery.
Number of Participants With Pneumonia (Suspected and Proved) by Postoperative Day 7	Days 0 through 7	Incidence of suspected (radiological evidence without bacteriological confirmation) and proved (radiological evidence and documentation of pathological organism) pneumonia by day 7 after the date of surgery.
Number of Participants With Ventilatory Dependence or Failure by Postoperative Day 7	Days 0 through 7	Number of participants with ventilatory dependence (Grade 3, non-invasive or invasive ventilation \< 48h) or failure (Grade 4, postoperative non-invasive or invasive ventilation dependence ≥ 48h) by day 7 after the date of surgery.
Length of Postoperative Oxygen Support	Up to 7 days post-surgery	Number of time (hours or days) spent in the postoperative oxygen therapy or other respiratory support
Number of Participants With Both Intraoperative Hypoxemia and Rescue Recruitment Maneuvers	Day 0	The incidence of both intraoperative hypoxemia (SpO2 \< 85%) and rescue recruitment maneuvers during surgery. Received unplanned RM or PEEP titrations or adjustments during surgery for oxygenation or ventilation rescue.
Number of Participants With Intraoperative Cardiovascular Events	Day 0	Number of participants with hypotension, bradycardia, tachycardia, arrhythmias, new ST-segment changes and cardiac arrest
Length of Hospital Stay	Days 0 through 7, 30, and 90	Number of days the participant has spent in the hospital since the day of the surgery.
Number of Participants With Other Hospital Readmission(s) After Initial Discharge	After the date of discharge to day 90	The number of participants with hospital readmission(s), other than to the Intensive Care Unit, if admitted.
Number of Participants With Any Major Extrapulmonary Complications	Days 0 to 7	Number of participants with arrhythmia, paralytic ileus, surgical site infection, infection (source uncertain), acute renal failure, and systemic inflammatory response syndrome.

Trial Locations

Locations (16): University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Montefiore Hospital
🇺🇸
Bronx, New York, United States
University of California - San Francisco
🇺🇸
San Francisco, California, United States
Stanford University
🇺🇸
Stanford, California, United States
University of Colorado, Anschutz Medical Campus
🇺🇸
Aurora, Colorado, United States
South Florida Veterans Affairs Foundation for Research and Education, Inc.
🇺🇸
Miami, Florida, United States
Northwestern University
🇺🇸
Evanston, Illinois, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Beth Israel Deaconess Hospital
🇺🇸
Boston, Massachusetts, United States
Scroll for more (6 remaining)
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States