An anesthesia-centered bundle to reduce postoperative pulmonary complications: The PRIME-AIR study protocol

PLOS ONE STUDY PROTOCOL An anesthesia-centered bundle to reduce postoperative pulmonary complications: The PRIME-AIR study protocol Ana Fernandez-Bustamante ID1*, Robert A. Parker2, Juraj Sprung3, Matthias Eikermann4, Marcelo Gama de Abreu ID5,6, Carlos Ferrando ID7,8, B. Taylor Thompson9, Marcos F. Vidal Melo10 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Anesthesiology, University of Colorado School of Medicine, Aurora, CO, United States of America, 2 Biostatistics Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA, United States of America, 3 Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, United States of America, 4 Department of Anesthesiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, United States of America, 5 Department of Intensive Care and Resuscitation, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, United States of America, 6 Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, United States of America, 7 Department of Anesthesiology and Intensive Care, Hospital Clı́nic Institut D’investigació August Pi i Sunyer, Barcelona, Spain, 8 CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain, 9 Division of Pulmonary and Critical Care, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America, 10 Department of Anesthesiology, Columbia University Irving Medical Center, New York, NY, United States of America OPEN ACCESS Citation: Fernandez-Bustamante A, Parker RA, Sprung J, Eikermann M, Gama de Abreu M, Ferrando C, et al. (2023) An anesthesia-centered bundle to reduce postoperative pulmonary complications: The PRIME-AIR study protocol. PLoS ONE 18(4): e0283748. https://doi.org/ 10.1371/journal.pone.0283748 Editor: Johannes Stortz, GERMANY Received: February 16, 2023 Accepted: March 5, 2023 Published: April 6, 2023 Copyright: © 2023 Fernandez-Bustamante et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion. Funding: NIH/NHLBI #UH3HL140177 (AFB, MFVM) https://www.nhlbi.nih.gov The Sponsor has no role in the data collection, analysis, and interpretation; preparation, review, or approval of any manuscripts submitted for publication. NIH/ NHLBI #U24HL140109 (RAP) https://www.nhlbi. * Abstract Background Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may minimize the synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction. This ongoing study will assess whether an anesthesia-centered bundle focused on perioperative lung expansion results in decreased incidence and severity of PPCs after open abdominal surgery. Methods Prospective multicenter randomized controlled pragmatic trial in 750 adult patients with at least moderate risk for PPCs undergoing prolonged (�2 hour) open abdominal surgery. Participants are randomized to receive either a bundle intervention focused on perioperative lung expansion or usual care. The bundle intervention includes preoperative patient education, intraoperative protective ventilation with individualized positive end-expiratory pressure to maximize respiratory system compliance, optimized neuromuscular blockade and reversal management, and postoperative incentive spirometry and early mobilization. Primary outcome is the distribution of the highest PPC severity by postoperative day 7. Secondary outcomes include the proportion of participants with: PPC grades 1–2 through POD 7; PPC grades 3–4 through POD 7, 30 and 90; intraoperative hypoxemia, rescue recruitment maneuvers, or cardiovascular events; and any major extrapulmonary postoperative PLOS ONE | https://doi.org/10.1371/journal.pone.0283748 April 6, 2023 1 / 20 PLOS ONE nih.gov The Sponsor has no role in the data collection, analysis, and interpretation; preparation, review, or approval of any manuscripts submitted for publication. Competing interests: AFB reports additional research funding from the US Department of Defense, the Merck Investigator-initiated Studies Program and the Institute for Healthcare Quality, Safety and Efficiency for projects unrelated to the discussed work. The rest of authors report no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The PRIME-AIR study protocol complications. Additional secondary and exploratory outcomes include individual PPCs by POD 7, length of postoperative oxygen therapy or other respiratory support, hospital resource use parameters, Patient-Reported Outcomes Measurements (PROMIS®) questionnaires for dyspnea and fatigue collected before and at days 7, 30 and 90 after surgery, and plasma concentrations of lung injury biomarkers (IL6, IL-8, RAGE, CC16, Ang-2) analyzed from samples obtained before, end of, and 24 hours after surgery. Discussion Participant recruitment for this study started January 2020; results are expected in 2024. At the conclusion of this trial, we will determine if this anesthesia-centered strategy focused on perioperative lung expansion reduces lung morbidity and healthcare utilization after open abdominal surgery. Trial registration ClinicalTrial.gov NCT04108130. Introduction Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality for patients undergoing the estimated 51 million annual inpatient surgeries in the US [1–3]. National estimates in 2011 suggested 1,062,000 PPCs per year, with 46,200 additional deaths, and 4.8 million additional days of hospitalization [2]. Abdominal surgery is associated with the largest absolute number of PPCs [4]. Whereas PPCs are as significant and lethal as cardiac surgical complications [1, 5], research in the field has received much less attention, and strategies to reduce perioperative lung morbidity are limited [5, 6]. Prior individual approaches to optimize specific aspects of care have been pursued to reduce PPCs, mostly focused on mechanical ventilation strategies during surgery [7–10], and the optimization of the reversal of neuromuscular blockade [11–13]. During abdominal surgery, Futier et al. [7] demonstrated a reduced incidence of a composite of pulmonary complications of repeated intraoperative recruitment maneuvers, higher positive end-expiratory pressure (PEEP) 6–8 cmH2O and lower tidal volume (VT) 6–8 ml/kg of predicted body weight (PBW) vs. a strategy of no lung recruitments, PEEP 0 c (...truncated)