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

Postoperative Pulmonary Complications Clinical Trial

— PRIME-AIR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04108130
• Other study ID #: AAAT9106
• Secondary ID: HL140177
• Status: Recruiting
• Phase: N/A
• Start date: January 27, 2020
• Est. completion date: July 31, 2024

Study information

• Verified date: February 2023
• Source: Columbia University
• Contact: Marcos F Vidal Melo, MD
• Phone: 212 342 4799
• Email: mv2869[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: July 31, 2024
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Postoperative Pulmonary Complications

Intervention

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.

Locations

Country	Name	City	State
United States	University of Colorado, Anschutz Medical Campus	Aurora	Colorado
United States	Beth Israel Deaconess Hospital	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Duke University	Durham	North Carolina
United States	Northwestern University	Evanston	Illinois
United States	South Florida Veterans Affairs Foundation for Research and Education, Inc.	Miami	Florida
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	University of California - San Francisco	San Francisco	California
United States	Stanford University	Stanford	California
United States	Univerisity of Massachusetts Amherst Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. Erratum In: Anesth Analg. 2020 Apr;130(4):e118. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. Erratum In: JAMA. 2019 Nov 12;322(18):1829-1830. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and Severity of Postoperative Pulmonary Complications between Participant Groups	The distribution of the number and severity of post-operative pulmonary complications (PPCs) between the control and intervention groups during the first 7 days after surgery.	Postoperative Days 0 through 7
Secondary	All-Cause Postoperative Mortality	Mortality for any cause within 7, 30, and 90 days after the day of surgery.	Postoperative Days 0 through 7, 30, and 90
Secondary	Grade 3 and 4 Postoperative Pulmonary Complications	Individual grade 3 and 4 postoperative pulmonary complications within 30 and 90 days after the day of the surgery.	Postoperative Days 30 and 90
Secondary	Presence of Individual Components of Postoperative Pulmonary Complications in the Primary Endpoint	Presence of each of the individual components of the list of pulmonary complications in the primary endpoint within 7, 30, and 90 days after the day of the surgery.	Postoperative Days 0 through 7, 30, and 90
Secondary	Rate of Intraoperative Adverse Events	Rate of intraoperative adverse events (hypoxemia, hypotension during lung recruitment, need for vasoactive medications and volume replacement, muscle weakness. This will be assessed as Train Of Four scores less than 0.9 after extubation, or, in the absence of quantitative assessment, clinical assessments such as inability to generate a tidal volume above 4 mili-Liters per kilogram of predicted body weight, Predicted Body Weight (PBW), at time of extubation or to maintain sustained hand grip or 5-s head lift, presence of diplopia or ventilatory failure after extubation).	Days 0 through 7, 30, and 90
Secondary	Rate of Major Extrapulmonary Complications	Rate of extrapulmonary complications defined based on existing diagnosis in the medical chart.	Days 0, 7, 30, and 90
Secondary	Length of Stay in Post-Anesthesia Care	Length of stay in post-anesthesia care after the day of surgery until discharge.	Days 0 through 7, 30, and 90
Secondary	Length of Postoperative Oxygen Support	Number of time (hours or days) spent in the postoperative oxygen therapy or other respiratory support	Day 0
Secondary	Unexpected Readmission to ICU	The incidence of an unexpected admission to the Intensive Care Unit after the day of discharge from the surgery.	After date of discharge to day 90
Secondary	Length of ICU stay	The number of days in the Intensive Care Unit, if admitted.	After date of discharge to day 90
Secondary	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
Secondary	Incidence of Other Hospital Readmission(s) After Initial Discharge	The incidence of hospital readmission(s), other than to the Intensive Care Unit, if admitted.	After the date of discharge to day 90
Secondary	Difference in Fatigue Participant-Reported Outcomes Measurements Information System (PROMIS) scores	PROMIS is system of individual scales (e.g., Fatigue PROMIS measure, Dyspnea PROMIS measure) to quantify the physical, mental, and social health outcomes of a participant surrounding a particular health issue. The short form for both the Fatigue PROMIS measure will be used for the current study.; Items on the Fatigue PROMIS measure are rated on a 5-point Likert-type scale (1-5), where 1 most often means "not at all" and 5 most often means "very much". Some items are reverse-coded.; Total T-scores will be used in the analysis of the current study. T-scores are derived from the total raw scale scores (sum of each item on the scale). Lower values represent a better outcome and higher values represent a worse outcome.; Fatigue PROMIS T-scores will be compared at 4 time-points.	Baseline (pre-Day 0), Days 7, 30, and 90
Secondary	Difference in Dyspnea Participant-Reported Outcomes Measurements Information System (PROMIS) scores	PROMIS is system of individual scales (e.g., Fatigue PROMIS measure, Dyspnea PROMIS measure) to quantify the physical, mental, and social health outcomes of a participant surrounding a particular health issue. The short form for both the Dyspnea PROMIS measure will be used for the current study.; Items on the Dyspnea PROMIS measure are rated on a 4-point Likert-type scale (0-3), were 0 means "no difficulty" and 3 means "much difficulty". Each item also allows the participant to enter a missing value (X).; Total T-scores will be used in the analysis of the current study. T-scores are derived from the total raw scale scores (sum of each item on the scale). Lower values represent a better outcome and higher values represent a worse outcome.; Dyspnea PROMIS T-scores will be compared at 4 time-points.	Baseline (pre-Day 0), Days 7, 30, and 90