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. Our 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. Recent clinical data support a crucial role for intraoperative ventilatory strategies in reducing PPCs, consistent with findings o the major effect of protective ventilation in reducing mortality in the Acute Respiratory Distress Syndrome (ARDS). Surprisingly, intraoperative ventilatory strategies are not at all included in current clinical recommendations to reduce PPCs. Surgical patients differ substantially from ARDS patients as most have no or limited lung injury at the onset of mechanical ventilation during general anesthesia. Yet, intraoperative anesthetic and surgical interventions can predispose to or produce direct and indirect lung injury. Superimposition of mechanical ventilation to these insults can facilitate the development of lung injury. Thus, ventilatory strategies aiming at lung protection in this large and underserved group of patients are greatly needed. Recent data suggest that positive end-expiratory pressure (PEEP) could be a major factor to reduce PPCs after abdominal surgery, a finding consistent with intraoperative physiological insults and experimental data. Accordingly, individualization of PEEP settings could be key to maximize outcomes. Yet, no study to date addressed methods to specifically optimize intraoperative PEEP, nor its effect on pulmonary outcomes. We hypothesize that optimal individualized intraoperative lung recruitment during abdominal surgery reduces the incidence of PPCs in patients at moderate and high-risk for them. We will leverage a collaboration among three academic US centers to study that hypothesis in the following aims:
Aim 1. To characterize usual-care practices for mechanical ventilation during abdominal surgery in major US academic centers.
Aim 2. To prospectively compare two methods to individualize PEEP settings in the operating room during abdominal surgery: (1) maximization of lung compliance during a decremental PEEP titration, and (2) prevention of negative end-expiratory transpulmonary pressures by measuring esophageal balloon pressures. With these Aims, we will determine the control (Aim 1) and intervention (Aim 2) ventilatory settings for the full-scale trial.
Aim 3. To establish the processes required for the implementation of the full- scale multi-center clinical trial. At the conclusion of these aims, we will have the necessary and sufficient data to launch a multicenter clinical trial to establish the effect of optimal PEEP settings to prevent PPCs after abdominal surgery. Accordingly, our project could result in a major change in clinical practice and paradigm on intraoperative mechanical ventilation.

Public Health Relevance

Lung problems are a major cause of illness and death after surgery. We will study methods to deliver artificial breathing during abdominal surgery individualized to each patient, and aimed at maintaining a larger amount of air in the lungs during breathing than currently used by doctors. If successful, our project will set the stage to perform a large study to establish the importance of these methods in reducing lung complications after surgery.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Planning Grant (R34)
Project #
Application #
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Reineck, Lora A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
D'Antini, Davide; Huhle, Robert; Herrmann, Jacob et al. (2018) Respiratory System Mechanics During Low Versus High Positive End-Expiratory Pressure in Open Abdominal Surgery: A Substudy of PROVHILO Randomized Controlled Trial. Anesth Analg 126:143-149
Serpa Neto, Ary; Campos, Pedro P Z A; Hemmes, Sabrine N T et al. (2017) Kinetics of plasma biomarkers of inflammation and lung injury in surgical patients with or without postoperative pulmonary complications. Eur J Anaesthesiol 34:229-238
Fernandez-Bustamante, Ana; Frendl, Gyorgy; Sprung, Juraj et al. (2017) Postoperative Pulmonary Complications, Early Mortality, and Hospital Stay Following Noncardiothoracic Surgery: A Multicenter Study by the Perioperative Research Network Investigators. JAMA Surg 152:157-166
Bagchi, A; Rudolph, M I; Ng, P Y et al. (2017) The association of postoperative pulmonary complications in 109,360 patients with pressure-controlled or volume-controlled ventilation. Anaesthesia 72:1334-1343
de Jong, Myrthe A C; Ladha, Karim S; Vidal Melo, Marcos F et al. (2016) Differential Effects of Intraoperative Positive End-expiratory Pressure (PEEP) on Respiratory Outcome in Major Abdominal Surgery Versus Craniotomy. Ann Surg 264:362-369
Wanderer, Jonathan P; Ehrenfeld, Jesse M; Epstein, Richard H et al. (2015) Temporal trends and current practice patterns for intraoperative ventilation at U.S. academic medical centers: a retrospective study. BMC Anesthesiol 15:40
Ortiz, Vilma E; Vidal-Melo, Marcos F; Walsh, John L (2015) Strategies for managing oxygenation in obese patients undergoing laparoscopic surgery. Surg Obes Relat Dis 11:721-8
PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology; Hemmes, Sabrine N T; Gama de Abreu, Marcelo et al. (2014) High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet 384:495-503