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

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Pulmonary Complications
• Intervention / Treatment: Other: Preoperative Education; Procedure: Intraoperative PEEP (Positive End-Expiratory Pressure) Individualization; Other: Individualization of Neuromuscular Blockade; Procedure: Postoperative Incentive Spirometry; Behavioral: Postoperative Ambulation

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.

• Study Type: Interventional
• Enrollment (Actual): 794
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California - San Francisco
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, Anschutz Medical Campus
  • Florida
    • Miami, Florida, United States, 33125
      • South Florida Veterans Affairs Foundation for Research and Education, Inc.
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Hospital
    • Worcester, Massachusetts, United States, 01655
      • Univerisity of Massachusetts Amherst Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering
    • Rochester, New York, United States, 14642
      • University of Rochester
    • The Bronx, New York, United States, 10467
      • Montefiore Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual Care; Participants in this arm will receive usual anesthetic and postoperative care as provided in each site.
Experimental: Intervention; This arm will receive the bundle of interventions.	Other: Preoperative Education; Brochure and video about relevance of postoperative pulmonary complications, postoperative mobilization and use of incentive spirometry.; Procedure: 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.; Other: Individualization of Neuromuscular Blockade; Administration of neuromuscular blocking agents and their reversal will be done based on established protocol.; Procedure: 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.; Behavioral: Postoperative Ambulation; Participants will be encouraged to adhere to prescription of early ambulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Severity of Postoperative Pulmonary Complications Between Participant Groups	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.	Postoperative Days 0 through 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay	Number of days the participant has spent in the hospital since the day of the surgery.	Days 0 through 7, 30, and 90
Number of Participants With Grade 1 and 2 Postoperative Pulmonary Complications	Individual grade 3 and 4 postoperative pulmonary complications within 7 days after the day of the surgery.	Postoperative Days 0 through 7
Number of Participants With Grade 3 and 4 Postoperative Pulmonary Complications	Individual grade 3 and 4 postoperative pulmonary complications within 7, 30, and 90 days after the day of the surgery.	Postoperative Days 7, 30, and 90
Number of Participants With Hypoxemia by Postoperative Day 7	Presence of any hypoxemia (as defined in PPC grade 1 and 2) within 7 days after the day of the surgery.	Postoperative Days 0 through 7
Number of Participants With Atelectasis by Postoperative Day 7	Presence of atelectasis (radiological confirmation + either temperature >37.5°C or abnormal lung symptoms/signs) by day 7 after the date of surgery.	Days 0 through 7 after the day of surgery
Number of Participants With Pneumonia (Suspected and Proved) by Postoperative Day 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.	Days 0 through 7
Number of Participants With Ventilatory Dependence or Failure by Postoperative Day 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.	Days 0 through 7
Length of Postoperative Oxygen Support	Number of time (hours or days) spent in the postoperative oxygen therapy or other respiratory support	Up to 7 days post-surgery
Number of Participants With Both Intraoperative Hypoxemia and Rescue Recruitment Maneuvers	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.	Day 0
Number of Participants With Intraoperative Cardiovascular Events	Number of participants with hypotension, bradycardia, tachycardia, arrhythmias, new ST-segment changes and cardiac arrest	Day 0
Number of Participants With Other Hospital Readmission(s) After Initial Discharge	The number of participants with hospital readmission(s), other than to the Intensive Care Unit, if admitted.	After the date of discharge to day 90
Number of Participants With Any Major Extrapulmonary Complications	Number of participants with arrhythmia, paralytic ileus, surgical site infection, infection (source uncertain), acute renal failure, and systemic inflammatory response syndrome.	Days 0 to 7

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Marcos F Vidal Melo, MD, Columbia University

Publications and helpful links

General Publications

• Futier E, Constantin JM, Paugam-Burtz C, Pascal J, Eurin M, Neuschwander A, Marret E, Beaussier M, Gutton C, Lefrant JY, Allaouchiche B, Verzilli D, Leone M, De Jong A, Bazin JE, Pereira B, Jaber S; IMPROVE Study Group. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013 Aug 1;369(5):428-37. doi: 10.1056/NEJMoa1301082.
• de Jong MAC, Ladha KS, Vidal Melo MF, Staehr-Rye AK, Bittner EA, Kurth T, Eikermann M. Differential Effects of Intraoperative Positive End-expiratory Pressure (PEEP) on Respiratory Outcome in Major Abdominal Surgery Versus Craniotomy. Ann Surg. 2016 Aug;264(2):362-369. doi: 10.1097/SLA.0000000000001499.
• Ladha K, Vidal Melo MF, McLean DJ, Wanderer JP, Grabitz SD, Kurth T, Eikermann M. Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study. BMJ. 2015 Jul 14;351:h3646. doi: 10.1136/bmj.h3646.
• Ferrando C, Soro M, Unzueta C, Suarez-Sipmann F, Canet J, Librero J, Pozo N, Peiro S, Llombart A, Leon I, India I, Aldecoa C, Diaz-Cambronero O, Pestana D, Redondo FJ, Garutti I, Balust J, Garcia JI, Ibanez M, Granell M, Rodriguez A, Gallego L, de la Matta M, Gonzalez R, Brunelli A, Garcia J, Rovira L, Barrios F, Torres V, Hernandez S, Gracia E, Gine M, Garcia M, Garcia N, Miguel L, Sanchez S, Pineiro P, Pujol R, Garcia-Del-Valle S, Valdivia J, Hernandez MJ, Padron O, Colas A, Puig J, Azparren G, Tusman G, Villar J, Belda J; Individualized PeRioperative Open-lung VEntilation (iPROVE) Network. Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial. Lancet Respir Med. 2018 Mar;6(3):193-203. doi: 10.1016/S2213-2600(18)30024-9. Epub 2018 Jan 19.
• Williams EC, Motta-Ribeiro GC, Vidal Melo MF. Driving Pressure and Transpulmonary Pressure: How Do We Guide Safe Mechanical Ventilation? Anesthesiology. 2019 Jul;131(1):155-163. doi: 10.1097/ALN.0000000000002731.
• PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology; Hemmes SN, Gama de Abreu M, Pelosi P, Schultz MJ. High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet. 2014 Aug 9;384(9942):495-503. doi: 10.1016/S0140-6736(14)60416-5. Epub 2014 Jun 2.
• Writing Committee for the PROBESE Collaborative Group of the PROtective VEntilation Network (PROVEnet) for the Clinical Trial Network of the European Society of Anaesthesiology; Bluth T, Serpa Neto A, Schultz MJ, Pelosi P, Gama de Abreu M; PROBESE Collaborative Group; Bluth T, Bobek I, Canet JC, Cinnella G, de Baerdemaeker L, Gama de Abreu M, Gregoretti C, Hedenstierna G, Hemmes SNT, Hiesmayr M, Hollmann MW, Jaber S, Laffey J, Licker MJ, Markstaller K, Matot I, Mills GH, Mulier JP, Pelosi P, Putensen C, Rossaint R, Schmitt J, Schultz MJ, Senturk M, Serpa Neto A, Severgnini P, Sprung J, Vidal Melo MF, Wrigge H. Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial. JAMA. 2019 Jun 18;321(23):2292-2305. doi: 10.1001/jama.2019.7505.
• Wanderer JP, Ehrenfeld JM, Epstein RH, Kor DJ, Bartz RR, Fernandez-Bustamante A, Vidal Melo MF, Blum JM. Temporal trends and current practice patterns for intraoperative ventilation at U.S. academic medical centers: a retrospective study. BMC Anesthesiol. 2015 Mar 28;15:40. doi: 10.1186/s12871-015-0010-3. eCollection 2015.
• Brandao JC, Lessa MA, Motta-Ribeiro G, Hashimoto S, Paula LF, Torsani V, Le L, Bao X, Eikermann M, Dahl DM, Deng H, Tabatabaei S, Amato MBP, Vidal Melo MF. Global and Regional Respiratory Mechanics During Robotic-Assisted Laparoscopic Surgery: A Randomized Study. Anesth Analg. 2019 Dec;129(6):1564-1573. doi: 10.1213/ANE.0000000000004289.
• Fernandez-Bustamante A, Parker RA, Frendl G, Lee JW, Nagrebetsky A, Grecu L, Amar D, Tanaka P, Sprung J, Gupta RA, Subramanian B, Giquel J, Eikermann M, Musch G, Nadler JW, Gama de Abreu M, Bartels K, Grover M, Chen LL, Sparling J, Douin DJ, Weingarten T, Wagener G, Thompson BT, Vidal Melo MF; Perioperative Research Network (PRN) Investigators. Perioperative lung expansion and pulmonary outcomes after open abdominal surgery versus usual care in the USA (PRIME-AIR): a multicentre, randomised, controlled, phase 3 trial. Lancet Respir Med. 2025 May;13(5):447-459. doi: 10.1016/S2213-2600(25)00040-2. Epub 2025 Feb 25.
• Fernandez-Bustamante A, Parker RA, Sprung J, Eikermann M, Gama de Abreu M, Ferrando C, Thompson BT, Vidal Melo MF. An anesthesia-centered bundle to reduce postoperative pulmonary complications: The PRIME-AIR study protocol. PLoS One. 2023 Apr 6;18(4):e0283748. doi: 10.1371/journal.pone.0283748. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2020
• Primary Completion (Actual): July 13, 2023
• Study Completion (Actual): July 13, 2023

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: September 26, 2019
• First Posted (Actual): September 27, 2019

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Airway Management; Respiratory Therapy; Respiration, Artificial; Positive-Pressure Respiration
• Other Study ID Numbers: AAAT9106; HL140177 (Other Identifier: MGH); 5UH3HL140177-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In compliance with with the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information (Notice Number NOT-OD-16-149) and NIH/NHLBI guidelines, we will submit data and specimens to the NHLBI BioLINCC (The Biologic Specimen and Data Repository Information Coordinating Center) repository, and follow procedures specified in the BioLINCC Handbook. First, list of materials to be submitted including the specimens for the NHLBI biorepository will be created. Then a data redaction plan removing personal identifiers and administrative data will be prepared, recoding low-frequency data values for subject privacy protection. The data set documentation, summary of changes made during redaction, and a summary report will be submitted to the BioLINCC repository following the standard procedures. We will comply with any modifications identified during the BioLINCC repository review, and submit the final material acceptable to the repository.
• IPD Sharing Time Frame: After conclusion of the study, planned for 5 years.
• IPD Sharing Access Criteria: According to the NIH/NHLBI access policies.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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