Clinical trial NCT04108130: An Anesthesia-Centered Bundle to Reduce Postoperative Pulmonary Complications: The PRIME-AIR Study
Official title: An Anesthesia-Centered Bundle to Reduce Postoperative Pulmonary Complications: The PRIME-AIR Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Postoperative Pulmonary Complications
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2019-09-27
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number and Severity of Postoperative Pulmonary Complications between Participant Groups
timeFrame: Postoperative Days 0 through 7
Secondary outcomes:
measure: All-Cause Postoperative Mortality
timeFrame: Postoperative Days 0 through 7, 30, and 90
measure: Grade 3 and 4 Postoperative Pulmonary Complications
timeFrame: Postoperative Days 30 and 90
measure: Presence of Individual Components of Postoperative Pulmonary Complications in the Primary Endpoint
timeFrame: Postoperative Days 0 through 7, 30, and 90
measure: Rate of Intraoperative Adverse Events
timeFrame: Days 0 through 7, 30, and 90
measure: Rate of Major Extrapulmonary Complications
timeFrame: Days 0, 7, 30, and 90
measure: Length of Stay in Post-Anesthesia Care
timeFrame: Days 0 through 7, 30, and 90
measure: Length of Postoperative Oxygen Support
timeFrame: Day 0
measure: Unexpected Readmission to ICU
timeFrame: After date of discharge to day 90
measure: Length of ICU stay
timeFrame: After date of discharge to day 90
measure: Length of Hospital Stay
timeFrame: Days 0 through 7, 30, and 90
measure: Incidence of Other Hospital Readmission(s) After Initial Discharge
timeFrame: After the date of discharge to day 90
measure: Difference in Fatigue Participant-Reported Outcomes Measurements Information System (PROMIS) scores
timeFrame: Baseline (pre-Day 0), Days 7, 30, and 90
measure: Difference in Dyspnea Participant-Reported Outcomes Measurements Information System (PROMIS) scores
timeFrame: Baseline (pre-Day 0), Days 7, 30, and 90
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado, Anschutz Medical Campus
state: Colorado
city: Miami
country: United States
facility: South Florida Veterans Affairs Foundation for Research and Education, Inc.
state: Florida
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Hospital
state: Massachusetts
city: Worcester
country: United States
facility: Univerisity of Massachusetts Amherst Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Columbia University
name: Marcos F Vidal Melo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.