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

NCT ID: NCT04108130

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 794 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-29
• Study Completion Date: 2023-07-13

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.

Conditions

Postoperative Pulmonary Complications

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Usual Care

Participants in this arm will receive usual anesthetic and postoperative care as provided in each site.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Intervention

This arm will receive the bundle of interventions.

Group Type: EXPERIMENTAL

Preoperative Education

Intervention Type: OTHER

Brochure and video about relevance of postoperative pulmonary complications, postoperative mobilization and use of incentive spirometry.

Intraoperative PEEP (Positive End-Expiratory Pressure) Individualization

Intervention Type: PROCEDURE

PEEP will be set by maximizing respiratory system compliance along a decremental PEEP titration following an incremental recruitment maneuver.

Individualization of Neuromuscular Blockade

Intervention Type: OTHER

Administration of neuromuscular blocking agents and their reversal will be done based on established protocol.

Postoperative Incentive Spirometry

Intervention Type: PROCEDURE

Participants will be encouraged to adhere to incentive spirometry to be started 2 hours after surgery and maintained until participant freely ambulates. Supervision will be provided 3 times/day for continuous education and management of barriers to optimal performance.

Postoperative Ambulation

Intervention Type: BEHAVIORAL

Participants will be encouraged to adhere to prescription of early ambulation.

Interventions

Preoperative Education

Brochure and video about relevance of postoperative pulmonary complications, postoperative mobilization and use of incentive spirometry.

Intervention Type: OTHER

Intraoperative PEEP (Positive End-Expiratory Pressure) Individualization

PEEP will be set by maximizing respiratory system compliance along a decremental PEEP titration following an incremental recruitment maneuver.

Intervention Type: PROCEDURE

Individualization of Neuromuscular Blockade

Administration of neuromuscular blocking agents and their reversal will be done based on established protocol.

Intervention Type: OTHER

Postoperative Incentive Spirometry

Participants will be encouraged to adhere to incentive spirometry to be started 2 hours after surgery and maintained until participant freely ambulates. Supervision will be provided 3 times/day for continuous education and management of barriers to optimal performance.

Intervention Type: PROCEDURE

Postoperative Ambulation

Participants will be encouraged to adhere to prescription of early ambulation.

Intervention Type: BEHAVIORAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marcos F Vidal Melo, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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

Univerisity of Massachusetts Amherst Center

Worcester, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Columbia University Medical Center

New York, New York, United States

Memorial Sloan Kettering

New York, New York, United States

University of Rochester

Rochester, New York, United States

Montefiore Hospital

The Bronx, New York, United States

Duke University

Durham, North Carolina, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HL140177

Identifier Type: OTHER

Identifier Source: secondary_id

5UH3HL140177-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAT9106

Identifier Type: -

Identifier Source: org_study_id