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BackgroundBiological phenotypes have been identified within several heterogeneous pulmonary diseases, with potential therapeutic consequences.ObjectiveTo assess whether distinct biological phenotypes exist within surgical patients, and whether development of postoperative pulmonary complications (PPCs) and subsequent dependence of intra-operative positive end-expiratory pressure (PEEP) differ between such phenotypes.SettingOperating rooms of six hospitals in Europe and USA.DesignSecondary analysis of the 'PROtective Ventilation with HIgh or LOw PEEP' trial.PatientsAdult patients scheduled for abdominal surgery who are at risk of PPCs.InterventionsMeasurement of pre-operative concentrations of seven plasma biomarkers associated with inflammation and lung injury.Main outcome measuresWe applied unbiased cluster analysis to identify biological phenotypes. We then compared the proportion of patients developing PPCs within each phenotype, and associations between intra-operative PEEP levels and development of PPCs among phenotypes.ResultsIn total, 242 patients were included. Unbiased cluster analysis clustered the patients within two biological phenotypes. Patients with phenotype 1 had lower plasma concentrations of TNF-α (3.8 [2.4 to 5.9] vs. 10.2 [8.0 to 12.1] pg ml; P ConclusionPatients at risk of PPCs and undergoing open abdominal surgery can be clustered based on pre-operative plasma biomarker concentrations. The two identified phenotypes have different incidences of PPCs. Biologic phenotyping could be useful in future randomised controlled trials of intra-operative ventilation.Trial registrationThe PROtective Ventilation with HIgh or LOw PEEP trial, including the substudy from which data were used for the present analysis, was registered at (NCT01441791).

Original publication




Journal article


European journal of anaesthesiology

Publication Date





702 - 709


From the Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil (ASN, PPZAC), Department of Intensive Care, Academic Medical Center (ASN, LDB, PPZAC, SNTH, MJS), Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center (LDB, MJS), Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (SNTH, MWH, AMT-dB), Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (TB, AG, TK, MGdA), Division of Pulmonary and Critical Care Medicine, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, California, USA (CSC), Interdisciplinary Center for Clinical Trials (IZKS), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany (MF), Department of Anaesthesiology, Hospital de Sant Pau, Barcelona, Spain (II), Department of Anaesthesiology, University Hospital Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany (RL-F), Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota (JS, TNW), Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA (DS, MFVM), Department of Surgical Sciences and Integrated Diagnostics, IRCCS San Martino IST, University of Genoa, Genoa, Italy (PP) and Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand (MJS). PROVHILO = PROtective Ventilation with HIgh or LOw PEEP-trial. PROVE = PROtective VEntilation (


PROVHILO* and the PROVE** investigators, Humans, Lung Diseases, Postoperative Complications, Inflammation Mediators, Preoperative Care, Positive-Pressure Respiration, Cluster Analysis, Phenotype, Internationality, Aged, Middle Aged, Female, Male, Biomarkers