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Ball L et al.
Online Supplement to: Intraoperative Ventilation Settings and Their Associations with Postoperative Pulmonary Complications in Obese Patients
Lorenzo Ball1,2, Sabrine NT Hemmes2,3, Ary Serpa Neto2,4, Thomas Bluth5, Jaume Canet6, Michael Hiesmayr7, Markus W Hollmann3, Gary H Mills8, Marcos F. Vidal Melo9, Christian Putensen10, Werner Schmid7, Paolo Severgnini11, Hermann Wrigge12, Marcelo Gama de Abreu5, Marcus J. Schultz2, Paolo Pelosi1 for the LAS VEGAS investigators*, the PROVE Network** and the Clinical Trial Network of the European Society of
Anaesthesiology
University of Genoa, Genoa, Italy, Policlinico San Martino, Genova, Italy1Department of Surgical Sciences and Integrated Diagnostics
Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands2Department of Intensive Care
3Department of AnaesthesiologyHospital Israelita Albert Einstein, São Paulo, Brazil
4Department of Critical Care MedicineUniversity Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
5Department of Anaesthesiology and Intensive Care MedicineHospital Universitari Germans Trias I Pujol, Barcelona, Spain
6Department of Anesthesiology and Postoperative CareMedical University Vienna, Vienna, Austria
7Division Cardiac, Thoracic, Vascular Anesthesia and Intensive CareSheffield Teaching Hospitals, Sheffield and University of Sheffield, United Kingdom
8Operating Services, Critical Care and AnaesthesiaMassachusetts General Hospital, Boston, U.S.A.
9Department of Anesthesia, Critical Care and Pain MedicineUniversity Hospital Bonn, Bonn, Germany
10Department of Anesthesiology and Intensive Care MedicineUniversity of Insubria, Varese, Italy
11Department of Biotechnology and Sciences of Life, ASST- Settelaghi Ospedale di Cricolo e Fondazione MacchiUniversity of Leipzig, Leipzig, Germany
12Department of Anesthesiology and Intensive Care Medicine
*LAS VEGAS (the ‘Local ASsessment of VEntilatory management during General Anesthesia for Surgery’ study)**The PROVE Network; the PROtective VEntilation Network (www.provenet.eu)
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 1
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Table of ContentsList of LAS VEGAS study Network Collaborators.................................................................................................................................................................... 3
Definitions.................................................................................................................................................................................................................................... 9eTable 1 - Definition of recruitment manoeuvres.................................................................................................................................................................. 9eTable 2 - Definition of postoperative pulmonary complications...................................................................................................................................... 10
Composite outcomes........................................................................................................................................................................................................... 10eTable 3 - Definition of intraoperative complications......................................................................................................................................................... 11
Statistics - Details on the generalized linear mixed model.................................................................................................................................................... 12
Supplementary tables............................................................................................................................................................................................................... 13eTable 4 – Patients’ characteristics..................................................................................................................................................................................... 13eTable 5 – Surgical procedures and anaesthesia technique............................................................................................................................................. 14
eTable 6 – Analysis of repeated measurements..................................................................................................................................................................... 15
Post-hoc analysis for recruitment manoeuvres..................................................................................................................................................................... 16eTable 7 - Multivariate mixed logistic regression excluding rescue recruitment manoeuvres......................................................................................16Propensity score matching for all PPC................................................................................................................................................................................ 17
eTable 8 - Efficacy of matching............................................................................................................................................................................................ 17eTable 9 - Univariate analysis.............................................................................................................................................................................................. 18eTable 10 - Multivariate mixed logistic regression for matched cohort for PPCs.................................................................................................................. 19eTable 11 - Multivariate mixed logistic regression for PPCs in surgery lasting ≥ 2 hours....................................................................................................20
Additional figures...................................................................................................................................................................................................................... 21eFigure 1 – Data flow............................................................................................................................................................................................................. 21eFigure 2 – Tidal volume size according to different obesity classes.............................................................................................................................. 22eFigure 3 – Gas exchange in obesity classes..................................................................................................................................................................... 23eFigure 4 – Observed incidence of PPCs in patients receiving different types of recruitment manoeuvres................................................................24
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 2
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List of LAS VEGAS study Network Collaborators AustriaLKH Graz, Graz: Wolfgang Kroell, Helfried Metzler, Gerd Struber, Thomas WegscheiderAKH Linz, Linz: Hans GombotzMedical University Vienna: Michael Hiesmayr, Werner Schmid, Bernhard Urbanek
BelgiumUCL - Cliniques Universitaires Saint Luc Brussels: David Kahn, Mona Momeni, Audrey Pospiech, Fernande Lois, Patrice Forget, Irina GrosuUniversitary Hospital Brussels (UZ Brussel): Jan Poelaert, Veerle van Mossevelde, Marie-Claire van MalderenHet Ziekenhuis Oost Limburg (ZOL), Genk: Dimitri Dylst, Jeroen van Melkebeek, Maud BeranGhent University Hospital, Gent: Stefan de Hert, Luc De Baerdemaeker, Bjorn Heyse, Jurgen Van Limmen, Piet Wyffels, Tom Jacobs, Nathalie Roels, Ann De BruyneMaria Middelares, Gent: Stijn van de Velde
Bosnia and HerzegovinaGeneral Hospital “prim Dr Abdulah Nakas” Sarajevo: Marina Juros-Zovko, Dejana Djonoviċ- Omanoviċ
CroatiaGeneral Hospital Cakovec, Cakovec: Selma PernarGeneral Hospital Karlovac, Karlovac: Josip Zunic, Petar Miskovic, Antonio Zilic University Clinical Hospital Osijek, Osijek: Slavica Kvolik, Dubravka Ivic, Darija Azenic-Venzera, Sonja Skiljic, Hrvoje Vinkovic, Ivana OputricUniversity Hospital Rijeka, Rijeka: Kazimir Juricic, Vedran FrkovicGeneral Hospital Dr J Bencevic, Slavonski Brod: Jasminka Kopic, Ivan MirkovicUniversity Hospital Center Split, Split: Nenad Karanovic, Mladen Carev, Natasa DropulicUniversity Hospital Merkur, Zagreb: Jadranka Pavicic Saric, Gorjana Erceg, Matea Bogdanovic DvorscakUniversity Hospital Sveti Duh, Zagreb: Branka Mazul-Sunko, Anna Marija Pavicic, Tanja GoranovicUniversity Hospital, Medical school, “Sestre milosrdnice” (Sister of Charity), Zagreb: Branka Maldini, Tomislav Radocaj, Zeljka Gavranovic, Inga Mladic-Batinica, Mirna Sehovic
Czech RepublicUniversity Hospital Brno, Brno: Petr Stourac, Hana Harazim, Olga Smekalova, Martina Kosinova, Tomas Kolacek, Kamil Hudacek, Michal Drab University Hospital Hradec Kralove, Hradec Kralove: Jan Brujevic, Katerina Vitkova, Katerina JirmanovaUniversity Hospital Ostrava, Ostrava: Ivana Volfova, Paula Dzurnakova, Katarina LiskovaNemocnice Znojmo, Znojmo: Radovan Dudas, Radek Filipsky
EgyptEl Sahel Teaching hospital, Cairo: Samir el KafrawyKasr Al-Ainy Medical School, Cairo University: Hisham Hosny Abdelwahab, Tarek Metwally, Ahmed Abdel-Razek
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 3
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Beni Sueif University Hospital, Giza: Ahmed Mostafa El-Shaarawy, Wael Fathy Hasan, Ahmed Gouda AhmedFayoum University Hospital, Giza: Hany Yassin, Mohamed Magdy, Mahdy AbdelhadySuis medical Insurance Hospital, Suis: Mohamed Mahran
EstoniaNorth Estonia Medical Center, Tallinn: Eiko Herodes, Peeter Kivik, Juri Oganjan, Annika AunTartu University Hospital, Tartu: Alar Sormus, Kaili Sarapuu, Merilin Mall, Juri Karjagin
FranceUniversity Hospital of Clermont-Ferrand, Clermont-Ferrand: Emmanuel Futier, Antoine Petit, Adeline GerardInstitut Hospitalier Franco-Britannique, Levallois-Perret: Emmanuel Marret, Marc SolierSaint Eloi University Hospital, Montpellier: Samir Jaber, Albert Prades
GermanyFachkrankenhaus Coswig, Coswig: Jens Krassler, Simone MerzkyUniversity Hospital Carl Gustav Carus, Dresden: Marcelo Gama de Abreu, Christopher Uhlig,Thomas Kiss, Anette Bundy, Thomas Bluth, Andreas Gueldner, Peter Spieth, Martin Scharffenberg, Denny Tran Thiem, Thea KochDuesseldorf University Hospital, Heinrich-Heine University: Tanja Treschan, Maximilian Schaefer, Bea Bastin, Johann Geib, Martin Weiss, Peter Kienbaum, Benedikt PannenDiakoniekrankenhaus Friederikenstift, Hannover: Andre Gottschalk, Mirja Konrad, Diana Westerheide, Ben SchwerdtfegerUniversity of Leipzig, Leipzig: Hermann Wrigge, Philipp Simon, Andreas Reske, Christian Nestler
Greece “Alexandra” general hospital of Athens, Athens: Dimitrios Valsamidis, Konstantinos Stroumpoulis General air force hospital, Athens: Georgios Antholopoulos, Antonis Andreou, Dimitris Karapanos Aretaieion University Hospital, Athens: Kassiani Theodoraki, Georgios Gkiokas, Marios-Konstantinos TasoulisAttikon University Hospital, Athens: Tatiana Sidiropoulou, Foteini Zafeiropoulou, Panagiota Florou, Aggeliki PandaziAhepa University Hospital Thessaloniki, Thessaloniki: Georgia Tsaousi, Christos Nouris, Chryssa Pourzitaki,
IsraelThe Lady Davis Carmel Medical Center, Haifa: Dmitri Bystritski, Reuven Pizov, Arieh Eden
ItalyOspedale San. Paolo Bari, Bari: Caterina Valeria Pesce, Annamaria Campanile, Antonella MarrellaUniversity of Bari “Aldo Moro”, Bari: Salvatore Grasso, Michele De MicheleInstitute for Cancer Research and treatment, Candiolo, Turin: Francesco Bona, Gianmarco Giacoletto, Elena SardoAzienda Ospedaliera per l’emergenza Cannizzaro, Catania: Luigi Giancarlo Vicari SottosantiOspedale Melegnano, Cernuso, Milano: Maurizio SolcaAzienda Ospedaliera – Universitaria Sant’Anna, Ferrara: Carlo Alberto Volta, Savino Spadaro, Marco Verri, Riccardo Ragazzi, Roberto ZoppellariOspedali Riuniti Di Foggia - University of Foggia, Foggia: Gilda Cinnella, Pasquale Raimondo, Daniela La Bella, Lucia Mirabella, Davide D'antini
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 4
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IRCCS AOU San Martino IST Hospital, University of Genoa, Genoa: Paolo Pelosi, Alexandre Molin, Iole Brunetti, Angelo Gratarola, Giulia Pellerano, Rosanna Sileo, Stefano Pezzato, Luca MontagnaniIRCCS San Raffaele Scientific Institute, Milano: Laura Pasin, Giovanni Landoni, Alberto Zangrillo, Luigi Beretta, Ambra Licia Di Parma, Valentina Tarzia, Roberto Dossi, Marta Eugenia SassoneIstituto europeo di oncologia – ieo, Milano: Daniele Sances, Stefano Tredici, Gianluca Spano, Gianluca Castellani, Luigi Delunas, Sopio Peradze, Marco VenturinoOspedale Niguarda Ca'Granda Milano, Milano: Ines Arpino, Sara SherOspedale San Paolo - University of Milano, Milano: Concezione Tommasino, Francesca Rapido, Paola MorelliUniversity of Naples “Federico II” Naples: Maria Vargas, Giuseppe ServilloPoliclinico "P. Giaccone", Palermo: Andrea Cortegiani, Santi Maurizio Raineri, Francesca Montalto, Vincenzo Russotto, Antonino GiarratanoAzienda Ospedaliero-Universitaria, Parma: Marco Baciarello, Michela Generali, Giorgia CeratiSanta Maria degli Angeli, Pordenone: Yigal LeykinOspedale Misericordia e Dolce - Usl4 Prato, Prato: Filippo Bressan, Vittoria Bartolini, Lucia ZamideiUniversity hospital of Sassari, Sassari: Luca Brazzi, Corrado Liperi, Gabriele Sales, Laura PistiddaInsubria University, Varese: Paolo Severgnini, Elisa Brugnoni, Giuseppe Musella, Alessandro Bacuzzi
Republic of KosovoDistric hospital Gjakova, Gjakove: Dalip MuhardriUniversity Clinical Center of Kosova, Prishtina: Agreta Gecaj-Gashi, Fatos SadaRegional Hospital ”Prim.Dr. Daut Mustafa”, Prizren: Adem Bytyqi
LithuaniaMedical University Hospital, Hospital of Lithuanian University of Health Sciences, Kaunas: Aurika Karbonskiene, Ruta Aukstakalniene, Zivile Teberaite, Erika SalciuteVilnius University Hospital - Institute of Oncology, Vilnius: Renatas Tikuisis, Povilas MiliauskasVilnius University Hospital - Santariskiu Clinics, Vilnius: Sipylaite Jurate, Egle Kontrimaviciute, Gabija Tomkute
MaltaMater Dei Hospital, Msida: John Xuereb, Maureen Bezzina, Francis Joseph Borg
NetherlandsAcademic Medical Centre, University of Amsterdam: Sabrine Hemmes, Marcus Schultz, Markus Hollmann, Irene Wiersma, Jan Binnekade, Lieuwe BosVU University Medical Center, Amsterdam: Christa Boer, Anne DuvekotMC Haaglanden, Den Haag: Bas in‘t Veld, Alice Werger, Paul Dennesen, Charlotte SeverijnsWestfriesgasthuis, Hoorn: Jasper De Jong, Jens Hering, Rienk van Beek
NorwayHaukeland University Hospital, Bergen: Stefan Ivars, Ib JammerFørde Central Hospital /Førde Sentral Sykehus, Førde: Alena BreidablikMartina Hansens Hospital, Gjettum: Katharina Skirstad Hodt, Frode Fjellanger, Manuel Vico AvalosBærum Hospital, Vestre Viken, Rud: Jannicke Mellin-Olsen, Elisabeth Andersson
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 5
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Stavanger University Hospital, Stavanger: Amir Shafi-Kabiri
PanamaHospital Santo Tomás, Panama: Ruby Molina, Stanley Wutai, Erick Morais
PortugalHospital do Espírito Santo - Évora, E.P.E, Évora.: Gloria Tareco, Daniel Ferreira, Joana AmaralCentro Hospitalar de Lisboa Central, E.P.E, Lisboa.: Maria de Lurdes Goncalves Castro, Susana Cadilha, Sofia AppletonCentro Hospitalar de Lisboa Ocidental, E.P.E. Hospital de S. Francisco Xavier, Lisboa: Suzana Parente, Mariana Correia, Diogo MartinsSantarem Hospital, Santarem: Angela Monteirosa, Ana Ricardo, Sara Rodrigues
RomaniaSpital Orasenesc, Bolintin Vale: Lucian HorhotaClinical Emergency Hospital of Bucharest, Bucharest: Ioana Marina Grintescu, Liliana Mirea, Ioana Cristina GrintescuElias University Emergency Hospital, Bucharest: Dan Corneci, Silvius Negoita, Madalina Dutu, Ioana Popescu GarotescuEmergency Institute of Cardiovascular Diseases Inst. ''Prof. C. C. Iliescu'', Bucharest: Daniela Filipescu, Alexandru Bogdan ProdanFundeni Clinical institute - Anaesthesia and Intensive Care, Bucharest: Gabriela Droc, Ruxandra Fota, Mihai PopescuFundeni Clinical institute - Intensive Care Unit, Bucharest: Dana Tomescu, Ana Maria Petcu, Marian Irinel TudoroiuHospital Profesor D Gerota, Bucharest: Alida Moise, Catalin-Traian GuranConstanta County Emergency Hospital, Constanta: Iorel Gherghina, Dan Costea, Iulia CindeaUniversity Emergency County Hospital Targu Mures, Targu Mures: Sanda-Maria Copotoiu, Ruxandra Copotoiu, Victoria Barsan, Zsolt Tolcser, Magda Riciu, Moldovan Gheorghe Septimiu, Mihaly Veres
RussiaKrasnoyarsk State Medical University, Krasnoyarsk: Alexey Gritsan, Tatyana Kapkan, Galina Gritsan, Oleg KorolkovBurdenko Neurosurgery Institute, Moscow: Alexander Kulikov, Andrey LubninMoscow Regional Research Clinical Institute, Moscow: Alexey Ovezov, Pavel Prokoshev, Alexander Lugovoy, Natalia AnipchenkoMunicipal Clinical Hospital 7, Moscow: Andrey Babayants, Irina Komissarova, Karginova ZalinaReanimatology Research Institute n.a. Negovskij RAMS, Moscow: Valery Likhvantsev, Sergei Fedorov
SerbiaClinical Center of Vojvodina, Emergency Center, Novisad: Aleksandra Lazukic, Jasmina Pejakovic, Dunja Mihajlovic
SlovakiaNational Cancer Institute, Bratislava: Zuzana Kusnierikova, Maria ZelinkovaF.D. Roosevelt teaching Hospital, Banská Bystrica: Katarina Bruncakova, Lenka PolakovicovaFaculty Hospital Nové Zámky, Nové Zámky: Villiam SobonaSloveniaInstitute of Oncology Ljubljana, Ljubljana: Barbka Novak-Supe, Ana Pekle-Golez, Miroljub Jovanov, Branka Strazisar
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 6
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University Medical Centre Ljubljana, Ljubljana: Jasmina Markovic-Bozic, Vesna Novak-Jankovic, Minca Voje, Andriy Grynyuk, Ivan Kostadinov, Alenka Spindler-Vesel
SpainHospital Sant Pau, Barcelona: Victoria Moral, Mari Carmen Unzueta, Carlos Puigbo, Josep FavaHospital Universitari Germans Trias I Pujol, Barcelona: Jaume Canet, Enrique Moret, Monica Rodriguez Nunez, Mar Sendra, Andrea Brunelli, Frederic RodenasUniversity of Navarra, Pamplona: Pablo Monedero, Francisco Hidalgo Martinez, Maria Jose Yepes Temino, Antonio Martínez Simon, Ana de Abajo LarribaCorporacion Sanitaria Parc Tauli, Sabadell: Alberto Lisi, Gisela Perez, Raquel MartinezConsorcio Hospital General Universitario de Valencia, Valencia: Manuel Granell, Jose Tatay Vivo, Cristina Saiz Ruiz, Jose Antonio de Andrés IbanezHospital Clinico Valencia, Valencia: Ernesto Pastor, Marina Soro, Carlos Ferrando, Mario Defez Hospital Universitario Rio Hortega, Valladolid: Cesar Aldecoa Alvares-Santullano, Rocio Perez, Jesus Rico
SwedenCentral Hospital in Kristianstad: Monir Jawad, Yousif Saeed, Lars Gillberg
TurkeyUfuk University Hospital Ankara, Ankara: Zuleyha Kazak Bengisun, Baturay Kansu KazbekAkdeniz University Hospital, Antalya: Nesil Coskunfirat, Neval Boztug, Suat Sanli, Murat Yilmaz, Necmiye HadimiogluIstanbul University, Istanbul medical faculty, Istanbul: Nuzhet Mert Senturk, Emre Camci, Semra Kucukgoncu, Zerrin Sungur, Nukhet SivrikozAcibadem University, Istanbul: Serpil Ustalar Ozgen, Fevzi ToramanMaltepe University, Istanbul: Onur Selvi, Ozgur Senturk, Mine YildizDokuz Eylül Universitesi Tip Fakültesi, Izmir: Bahar Kuvaki, Ferim Gunenc, Semih Kucukguclu, Sule OzbilginSifa University Hospital, İzmir: Jale Maral, Seyda CanliSelcuk University faculty of medicine, Konya: Oguzhan Arun, Ali Saltali, Eyup AydoganFatih Sultan Mehmet Eğitim Ve Araştirma Hastanesi, Istanbul: Fatma Nur Akgun, Ceren Sanlikarip, Fatma Mine Karaman
UkraineInstitute Of Surgery And Transplantology, Kiev: Andriy MazurZaporizhzhia State Medical University, Zaporizhzhia: Sergiy Vorotyntsev
United KingdomSWARM Research Collaborative: for full list of SWARM contributors please see www.ukswarm.comNorthern Devon Healthcare NHS Trust, Barnstaple: Guy Rousseau, Colin Barrett, Lucia StancombeGolden Jubilee National Hospital, Clydebank, Scotland: Ben Shelley, Helen ScholesDarlington Memorial Hospital, County Durham and Darlington Foundation NHS Trust, Darlington: James Limb, Amir Rafi, Lisa Wayman, Jill DeaneRoyal Derby Hospital, Derby: David Rogerson, John Williams, Susan Yates, Elaine RogersDorset County Hospital, Dorchester: Mark Pulletz, Sarah Moreton, Stephanie JonesThe Princess Alexandra NHS Hospital Trust, Essex: Suresh Venkatesh, Maudrian Burton, Lucy Brown, Cait GoodallRoyal Devon and Exeter NHS Foundation Trust, Exeter: Matthew Rucklidge, Debbie Fuller, Maria Nadolski, Sandeep KusreHospital James Paget University Hospital NHS Foundation Trust, Great Yarmouth: Michael Lundberg, Lynn Everett, Helen NuttRoyal Surrey County Hospital NHS Foundation Trust, Guildford: Maka Zuleika, Peter Carvalho, Deborah Clements, Ben Creagh-Brown
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 7
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Kettering General Hospital NHS Foundation Trust, Kettering: Philip Watt, Parizade RaymodeBarts Health NHS Trust, Royal London Hospital, London: Rupert Pearse, Otto Mohr, Ashok Raj, Thais CrearyNewcastle Upon Tyne Hospitals NHS Trust The Freeman Hospital High Heaton, Newcastle upon Tyne: Ahmed Chishti, Andrea Bell, Charley Higham, Alistair Cain, Sarah Gibb, Stephen MowatDerriford Hospital Plymouth Hospitals NHS Trust, Plymouth: Danielle Franklin, Claire West, Gary Minto, Nicholas Boyd Royal Hallamshire Hospital, Sheffield: Gary Mills, Emily Calton, Rachel Walker, Felicity Mackenzie, Branwen Ellison, Helen RobertsMid Staffordshire NHS, Stafford: Moses Chikungwa, Clare JacksonMusgrove Park Hospital, Taunton: Andrew Donovan, Jayne Foot, Elizabeth HomanSouth Devon Healthcare NHS Foundation Trust /Torbay Hospital, Torquay, Torbay: Jane Montgomery, David Portch, Pauline Mercer, Janet PalmerRoyal Cornwall Hospital, Truro: Jonathan Paddle, Anna Fouracres, Amanda Datson, Alyson Andrew, Leanne WelchMid Yorkshire Hospitals NHS Trust; Pinderfields Hospital, Wakefield: Alastair Rose, Sandeep Varma, Karen Simeson Sandwell and West Birmingham NHS Trust, West Bromich: Mrutyunjaya Rambhatla, Jaysimha Susarla, Sudhakar Marri, Krishnan Kodaganallur, Ashok Das, Shivarajan Algarsamy, Julie ColleyYork Teaching Hospitals NHS Foundation Trust, York: Simon Davies, Margaret Szewczyk, Thomas Smith
United StatesUniversity of Colorado School of Medicine/University of Colorado Hospital, Aurora: Ana Fernandez- Bustamante, Elizabeth Luzier, Angela AlmagroMassachusetts General Hospital, Boston: Marcos Vidal Melo, Luiz Fernando, Demet SulemanjiMayo Clinic, Rochester: Juraj Sprung, Toby Weingarten, Daryl Kor, Federica Scavonetto, Yeo Tze
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 8
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Definitions
eTable 1 - Definition of recruitment manoeuvresType of recruitment manoeuvre Definition
Bag squeezing Sustained manual hyperinflation using balloon/bag
Ventilator Transient stepwise increase in PEEP at constant tidal volume orTransient stepwise increase in tidal volume at constant PEEP orInspiratory holds (CPAP applied for a fixed time) orAny combination of the previous three
Rescue recruitment manoeuvre Bag-squeezing or ventilator recruitment manoeuvre, and “unplanned recruitment manoeuvre” reported as intraoperative complication
In the multivariate analysis, data concerning multiple recruitment manoeuvres were aggregated for each patient, considering recruitment when any type of recruitment manoeuvre was performed at least once during the course of anaesthesia.
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 9
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eTable 2 - Definition of postoperative pulmonary complicationsSingle PPC Definition
Unplanned need for oxygen therapy Supplemental O2 therapy administered to correct hypoxemia, defined as SpO2 < 90% in room air or PaO2 < 60 mmHg. This excludes oxygen administration given as a part of standard care, such as routine oxygen administration at the arrival in the PACU.
Respiratory failure SpO2 < 90% in room air or PaO2 < 60 mmHg with oxygen therapy, or need for non-invasive mechanical ventilation
Mechanical ventilation Need for new invasive ventilation after surgery, or unexpected prolonged invasive ventilation after discharge from the operating room
ARDS According to the Berlin definition
Pneumonia Lung infiltrates at the chest X-ray or CT, plus at least two among the following three criteria: fever > 38°C (100.4 °F), leucocytosis or leukopenia (WBC count > 12000 or <4000 cells/mm3), purulent secretions
Pneumothorax Air in the pleural space without blood presence, as confirmed by chest X-ray
Composite outcomesAll PPCs: at least one condition in eTable1
Mild PPC: Only unplanned need for oxygen therapy, as defined in eTable 1, without other PPCs
Severe PPC: at least one PPC among respiratory failure, mechanical ventilation, ARDS, pneumonia, pneumothorax, as defined in eTable1.
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 10
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eTable 3 - Definition of intraoperative complicationsIntraoperative Complication Definition
De-saturation SpO2 < 92%
Need for rescue recruitment manoeuvre Ventilation strategies aimed at restoring aeration of the lungs
Need for ventilatory pressure reduction Ventilation strategies aimed at lowering peak and/or plateau pressure
New onset of expiratory flow limitation End-expiration expiratory flow higher than zero at the visual analysis of the flow curve
Hypotension Systolic arterial pressure < 90 mmHg for at least 3 minutes
Need for vasoactive drugs Use of vasoactive drugs to correct hypotension as previously defined
Arrhythmia Defined as any new onset of atrial fibrillation, sustained ventricular tachycardia, supraventricular tachycardia, or ventricular fibrillation
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 11
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Statistics - Details on the generalized linear mixed modelA mixed logistic regression was performed with a generalized linear mixed model with logit link function. When a variable was measured at different time-
points, the median value of each patient was used.
The following parameters entered the univariate analysis for both PPCs and severe PPCs as fixed factors: intercept, sex, age, obesity class, smoking status,
obstructive sleep apnoeas, type of surgery, laparoscopic surgery, epidural analgesia, duration of anaesthesia, use of neuromuscular blocking agents, use of
neuromuscular blocking reversal agents, post-operative residual curarization defined as train-of-four below 0.9, total fluids administered per actual body weight,
use of systemic opioids, peak pressure, ventilation mode, PEEP, FiO2, tidal volume per predicted body weight, respiratory rate, routine recruitment manoeuvres,
rescue recruitment manoeuvres.
The identification number of the participating centre was included in the model as a random effect, including a random intercept.
At the multivariate analysis of PPC the following variables were entered because they had p<0.20 at the univariate: intercept, age, obesity class, obstructive
sleep apnoeas, type of surgery, duration of anaesthesia, postoperative residual curarization, use of systemic opioids, peak pressure, routine recruitment
manoeuvres, rescue recruitment manoeuvres. Tidal volume and PEEP were entered with a forced-entry strategy.
At the univariate analysis of severe PPC only rescue recruitment manoeuvres had p<0.20. Therefore, factors associated with development of all PPCs were
entered in the multivariate (obesity class, duration of anaesthesia, peak pressure, routine recruitment manoeuvres), plus tidal volume and PEEP with a forced-
entry strategy.
*PROVE Network: the PROtective Ventilation Network (www.provenet.eu) 12
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Supplementary tables
eTable 4 – Patients’ characteristicsAll patients(N = 2012)
Class I(N = 1315)
Class II(N = 449)
Class III(N=248)
Male sex 40.8% (821/2012) 46.6% (613/1315) 32.5% (146/449) 25.0% (62/248)Age (years) 56.0 [45.0 - 66.0] 57.0 [46.0 - 67.0] 55.0 [44.0 - 64.8] 51.0 [42.0 - 61.0]EthnicityCaucasian 91.9% (1840/2003) 91.5% (1200/1311) 93.0% (415/446) 91.5% (225/246)Black 1.1% (22/2003) 1.1% (15/1311) 0.7% (3/446) 1.6% (4/246)Asian 2.1% (42/2003) 2.2% (29/1311) 1.3% (6/446) 2.8% (7/246)Other 4.9% (99/2003) 5.1% (67/1311) 4.9% (22/446) 4.1% (10/246)BMI (kg/m2) 33.3 [31.3 - 36.3] 31.8 [30.9 - 33.2] 36.7 [35.7 - 38.1] 43.0 [41.1 - 46.4]Weight (kg) 95.0 [86.0 - 105.0] 90.0 [84.0 - 98.0] 100.0 [92.0 - 110.8] 117.0 [108.3 - 133.8]PBW (kg) 59.7 [52.4 - 59.7] 61.5 [54.2 - 70.6] 57.0 [51.5 - 66.1] 56.1 [50.6 - 63.3]ASA class
ASA I 14.3% (287/2009) 17.4% (229/1314) 10.5% (47/448) 4.5% (11/247)ASA II 59.3% (1192/2009) 59.9% (787/1314) 60.0% (269/448) 55.1% (136/247)ASA III 24.6% (494/2009) 21.1% (277/1314) 27.5% (123/448) 38.1% (94/247)ASA IV 1.8% (36/2009) 1.6% (21/1314) 2.0% (9/448) 2.4% (6/247)
ARISCAT score 18.0 [11.0 - 27.0] 18.0 [8.0 - 27.0] 18.0 [11.0 - 27.0] 19.0 [15.0 - 31.0]ARISCAT class
< 26 71.4% (1437/2012) 72.7% (956/1315) 71.3% (320/449) 64.9% (161/248)26 - 44 24.7% (497/2012) 23.7% (312/1315) 24.5% (110/449) 30.2% (75/248)>44 3.9% (78/2012) 3.6% (47/1315) 4.2% (19/449) 4.8% (12/248)
Preoperative SpO2 (%) 97.0 [96.0 - 98.0] 97.0 [96.0 - 98.0] 97.0 [96.0 - 98.0] 96.5 [95.0 - 98.0]Current smoker 19.7% (396/2012) 20.7% (272/1315) 16.9% (76/449) 19.3% (48/248)Chronic co-morbidity
Metastatic cancer 2.5% (50/2012) 2.7% (35/1315) 1.6% (7/449) 3.2% (8/248)Chronic kidney failure 3.0% (60/2012) 3.3% (44/1315) 2.4% (11/449) 2.0% (5/248)COPD 7.4% (148/2012) 7.5% (99/1315) 6.2% (28/449) 8.5% (21/248)Heart failure 7.6% (152/2012) 8.1% (107/1315) 7.8% (35/449) 4.0% (10/248)Obstructive sleep apnoeas 6.7% (134/2012) 3.6% (47/1315) 10.2% (46/449) 16.5% (41/248)Neuromuscular disease 0.9% (18/2012) 0.8% (11/1315) 0.9% (4/449) 1.2% (3/248)Liver dysfunction 0.9% (19/2012) 1.1% (15/1315) 0.9% (4/449) 0.0% (0/248)
Data are percent (proportion) or median [25th – 75th percentile].
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eTable 5 – Surgical procedures and anaesthesia techniqueAll patients(N = 2012)
Class I(N = 1315)
Class II(N = 449)
Class III(N=248)
Surgical procedureLower gastro-intestinal 7.5% (151/2012) 8.1% (106/1315) 6.5% (29/449) 6.5% (16/248)Upper GI, haepato-biliary, pancreas 18.3% (369/2012) 14.7% (193/1315) 18.0% (81/449) 38.3% (95/248)Vascular surgery 3.1% (63/2012) 3.5% (46/1315) 3.1% (14/449) 1.2% (3/248)Aortic surgery 1.1% (22/2012) 1.3% (17/1315) 1.1% (5/449) 0.0% (0/248)Neurosurgery, head & neck 17.6% (354/2012) 19.0% (250/1315) 17.1% (77/449) 10.9% (27/248)Urological 8.8% (178/2012) 9.7% (128/1315) 7.6% (34/449) 6.5% (16/248)Gynaecological 11.5% (231/2012) 10.8% (142/1315) 13.8% (62/449) 10.9% (27/248)Endocrine surgery 2.5% (50/2012) 2.5% (33/1315) 2.4% (11/449) 2.4% (6/248)Transplant 0.1% (3/2012) 0.2% (3/1315) 0.0% (0/449) 0.0% (0/248)Plastic, cutaneous, breast 10.4% (210/2012) 10.6% (139/1315) 10.5% (47/449) 9.7% (24/248)Bone, joint, trauma, spine 17.4% (350/2012) 18.5% (243/1315) 18.0% (81/449) 10.5% (26/248)Other procedure 5.8% (116/2012) 6.1% (80/1315) 5.1% (23/449) 5.2% (13/248)
Surgical techniqueOpen abdominal surgery 15.3% (307/2012) 14.6% (192/1315) 16.9% (76/449) 15.7% (39/248)Laparoscopic surgery 22.4% (450/2012) 19.5% (256/1315) 22.5% (101/449) 37.5% (93/248)Laparoscopic assisted surgery 2.1% (43/2012) 1.9% (25/1315) 2.9% (13/449) 2.0% (5/248)Peripheral surgery 19.5% (393/2012) 19.9% (262/1315) 21.4% (96/449) 14.1% (35/248)Other 41.3% (831/2012) 44.7% (588/1315) 37.2% (167/449) 30.6% (76/248)
UrgencyElective 93.2% (1875/2012) 93.2% (1225/1315) 93.8% (421/449) 92.3% (229/248)Urgent 10.9% (220/2012) 5.9% (78/1315) 5.3% (24/449) 47.6% (118/248)Emergency 1.7% (35/2012) 0.9% (12/1315) 0.9% (4/449) 7.7% (19/248)
Duration of surgery (min) 107.0 [70.0 - 170.0] 75.0 [40.0 - 130.0] 80.0 [46.3 - 130.0] 76.5 [50.0 - 130.0]Duration of anaesthesia (min) 75.0 [44.0 - 130.0] 105.0 [65.0 - 168.0] 113.0 [75.0 - 174.0] 111.5 [75.0 - 170.0]Antibiotic prophylaxis 70.7% (1422/2012) 69.1% (909/1315) 71.5% (321/449) 77.4% (192/248)Anaesthesia technique
Epidural anaesthesia 4.1% (82/2012) 3.7% (49/1315) 4.9% (22/449) 4.4% (11/248)Opioid 99.3% (1998/2012) 99.3% (1306/1315) 99.6% (447/449) 98.8% (245/248)
Short-acting 23.8% (476/1998) 24.2% (316/1306) 22.1% (99/447) 24.9% (61/245)Long-acting 62.9% (1256/1998) 63.2% (825/1306) 65.3% (292/447) 56.7% (139/245)Both long- and short-acting 13.3% (266/1998) 12.6% (165/1306) 12.5% (56/447) 18.4% (45/245)
Neuromuscular Blockade 86.0% (1728/2010) 84.9% (1115/1314) 87.8% (394/449) 88.7% (219/247)TIVA 14.0% (282/2009) 13.6% (179/1313) 13.1% (59/449) 17.8% (44/247)Total Fluids (mL) 1000 [850 – 1800] 1000 [800 - 1800] 1097 [1000 - 1775] 1000 [1000 - 1850]Total Fluids (mL/kg) 11.8 [8.3 - 18.7] 12.0 [8.5 - 19.6] 11.5 [8.9 - 17.7] 9.5 [7.0 - 14.8]
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Data are percent (proportion) or median [25th - 75th percentile].
eTable 6 – Analysis of repeated measurements The following table reports the complete results of the mixed model for the repeated measurements. The model included obesity classes as groups, time and
an interaction term time*group. Time-points between 1 and 4 hours after induction were included.
Variable p-value (Group)
p-value (Time) p-value (Interaction)
Pairwise comparisons between obesity classes
SpO2 0.032 0.380 0.701 Class III lower than I (p<0001) and II (p=0.004), class I lower than II (p=0.018)
EtCO2 <0.001 0.511 0.002 Class I lower than II (p<0.001) and III (p=0.011), other comparisons n.s.FiO2 0.779 <0.001 0.235PEEP <0.001 <0.001 0.692 All pairwise <0.001PPeak <0.001 <0.001 0.733 All pairwise <0.001TV (mL/kg PBW) <0.001 0.029 0.726 All pairwise <0.001TV (mL) 0.060 0.001 0.544PPeak-PEEP <0.001 0.002 0.647 All pairwise <0.001Respiratory Rate 0.344 0.154 0.533
Interaction terms were all non-significant, except for EtCO2, suggesting that changes over time in this variable might have a different pattern in different
obesity classes (see figure S2).
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Post-hoc analysis for recruitment manoeuvresThe following analyses were performed to test the robustness of the finding that type of recruitment manoeuvres is independently associated with the
incidence of PPC.
eTable 7 - Multivariate mixed logistic regression excluding rescue recruitment manoeuvres
Patients that underwent rescue recruitment manoeuvres (N=123) were excluded from the analysis.
Variable All PPCsOR (95% CI), p value
Severe PPCsOR (95% CI), p value
Age 1.02 [1.01 - 1.03], 0.001 Not in the modelDuration of Anaesthesia (h) 1.38 [1.25 - 1.52], <0.001 1.18 [1.04 - 1.34], 0.01Peak Pressure (cmH2O) 1.07 [1.03 - 1.11], <0.001 Not in the modelObstructive sleep apnoeas 2.34 [1.32 - 4.14], 0.004 2.22 [1.09 - 4.49], 0.027Routine Recruitment Manoeuvres
Not Performed 1 (Reference) Not in the modelVentilator 0.49 [0.16 - 1.49], 0.209Bag Squeezing 2.06 [1.14 - 3.73], 0.017
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Propensity score matching for all PPCA propensity score for PPC was calculated according to demographic characteristics, surgical procedure and known non-modifiable risk factors for PPC,
including the findings of the multivariate analysis conducted in this study: age, sex, body mass index, obstructive sleep apnoeas, duration of anaesthesia, type of
surgical procedure, type of surgical technique (laparoscopic vs. non-laparoscopic). Variables with missing values were not included in the propensity score to
maximize the use of data. A random effect to account for centre clustering was added in the regression that calculated the propensity score. Such propensity
score had an area under the curve (AUC) of 0.852 (95% CI: [0.827 - 0.877], p < 0.001) at the receiver operating characteristic (ROC) analysis.
Each patient with PPC (case) was matched with two control non-cases according to the propensity score, with a fuzzy tolerance of 10%. The matching
procedure provided 220 cases and 380 non-cases, covering 93% of the observed PPCs with an achieved matching ratio of 1:1.73.
eTable 8 - Efficacy of matchingAll cohort Matched CohortNo PPC PPC St.
Diff.p No PPC PPC St.
Diff.p
N 1776 236 380 220
Age (y) 56 [44 - 65] 59.0 [50 - 69] 29.8% <0.001
58 [48 - 68] 59 [50 - 69] 14.2% 0.109
Sex (male) 40.9% (727/1776) 39.8% (94/236) 3.2% 0.018 38.9% (148/380) 39.5% (87/220) 1.7% 0.931
BMI (kg/m2) 33.2 [31.2 - 36.2] 34.0 [31.6 - 38.7] 23.1% 0.778 33.9 [31.5 - 37.2] 33.6 [31.6 – 38.4] 2.6% 0.941
Obstructive sleep apnoeas
5.8% (103/1776) 13.1% (31/236) 30.7% <0.001
9.5% (36/380) 12.3 (27/220) 12.1% 0.333
Duration of anaesthesia (h)
1.7 [1.1 - 2.7] 2.6 [1.7 - 3.9] 55.8% <0.001
2.1 [1.2 – 3.5] 2.5 [1.7 – 3.8] 17.4% 0.003
Abdominal incision 37.7% (670/1776) 51.3% (121/236) 38.3% <0.001
41.6% (158/380) 49.1% (108/220) 21.3% 0.088
Laparoscopic surgery 24.1% (428/1776) 25.8% (61/236) 5.6% 0.572 26.1% (99/380) 25.0% (55/220) 3.4% 0.846
St. Diff: standardized difference. Data are percent (proportion) or median [25 th – 75th percentile].
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eTable 9 - Univariate analysisThe table resumes the univariate comparison between cases and matched controls.
No PPC PPC pPEEP (cmH2O) 4.0 (2.0 - 5.0) 5.0 (2.0 - 5.0) 0.219Tidal Volume (mL/kg PBW) 8.8 (7.8 - 10.0) 8.8 (7.8 - 10.1) 0.814Peak Pressure (cmH2O) 21.0 (18.0 - 24.0) 22.0 (19.0 - 27.0) <0.001FiO2 (%) 51.3 (46.1 - 70.0) 55.0 (47.0 - 67.0) 0.980Obstructive sleep apnoeas 9.5% (36/380) 12.3 (27/220) 0.333Routine Recruitment Manoeuvres
Not Performed 95.1% (350/380) 89.5% (197/220)
0.028Ventilator 3.4% (13/380) 1.4% (3/220)Bag Squeezing 4.4% (17/380) 9.1% (20/220)
Rescue Recruitment ManoeuvresNot Performed 94.9% (361/380) 86.4% (190/220)
0.001Ventilator 2.2% (8/380) 6.8% (15/220)Bag Squeezing 2.9% (11/380) 6.8% (15/220)
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eTable 10 - Multivariate mixed logistic regression for matched cohort for PPCsVariable All PPCs
OR (95% CI), p valuePEEP Not in the modelTidal Volume Not in the modelFiO2 Not in the modelDuration of anaesthesia Not in the modelPeak Pressure (cmH2O) 1.06 [1.02 - 1.10], 0.003
Obstructive sleep apnoeas Not in the modelRoutine Recruitment Manoeuvres
Not Performed 1 (Reference)Ventilator 0.27 [0.07 - 1.08], 0.064Bag Squeezing 2.34 [1.11 - 5.16], 0.027
Rescue Recruitment ManoeuvresNot Performed 1 (Reference)Ventilator 2.73 [1.03 - 7.24], 0.043Bag Squeezing 2.41 [0.99 - 5.86], 0.053
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eTable 11 - Multivariate mixed logistic regression for PPCs in surgery lasting ≥ 2 hoursVariable All PPCs
OR (95% CI), p valueSevere PPCsOR (95% CI), p value
Age Not in the model (p=0.052) Not in the modelObesity WHO Class Not in the model Not in the model (Class III p=0.05)Obstructive sleep apnoeas 1.06 [1.02 - 1.10], 0.003 Not in the modelDuration of anaesthesia 1.06 [1.02 - 1.10], 0.003 1.21 [1.02 - 1.43], 0.028Peak Pressure (cmH2O) Not in the model (p=0.077) Not in the model
Routine Recruitment ManoeuvresNot Performed 1 (Reference)
Not in the modelVentilator 0.64 [0.16 - 2.55], 0.525Bag Squeezing 3.39 [1.27 - 9.07], 0.015
Rescue Recruitment ManoeuvresNot Performed 1 (Reference) 1 (Reference)Ventilator 3.26 [1.28 - 8.29], 0.013 3.69 [1.29 – 10.57], 0.015Bag Squeezing 2.01 [0.73 - 5.52], 0.175 3.14 [1.02 – 9.64], 0.046
Multivariate mixed logistic regression including a random effect to account for centre clustering restricted to surgical procedures lasting 2 hours or more
(N=630 patients). The following variables were entered in the univariate model: sex, age, obesity class, smoking status, obstructive sleep apnoeas, type of
surgery, type of surgical incision, epidural analgesia, duration of anaesthesia, use of neuromuscular blocking agents, neuromuscular blockade reversal, presence
of residual curarization, fluids per kg body weight, use of opiates, peak pressure, ventilation mode, positive end-expiratory pressure, fraction of inspired oxygen,
tidal volume per kg predicted body weight, type of routine recruitment manoeuvres, type of rescue recruitment manoeuvres. WHO: World Health Organisation;
PPC: Postoperative Pulmonary Complication; OR: Odds Ratio; CI: Confidence Interval.
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Additional figures
eFigure 1 – Data flow
Patients’ inclusion flow.
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eFigure 2 – Tidal volume size according to different obesity classes
Tidal volume size according to different obesity classes. Boxes are interquartile ranges, whiskers the 5th and 95th percentile, line the median. PBW:
predicted body weight, ABW: actual body weight. *Between-classes difference significant at p<0.001.
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eFigure 3 – Gas exchange in obesity classes
Gas exchange over time. T 0 h represents the induction of general anaesthesia. P-values refers to the obesity class effect in a mixed model including obesity
class, time and an interaction term. Only the time-points highlighted in grey are included in the mixed model. Data are plotted as mean SEM.
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eFigure 4 – Observed incidence of PPCs in patients receiving different types of recruitment manoeuvres
Observed incidence of mild (blue) and severe (green) PPCs in the different categories of recruitment manoeuvres. *Independently associated with PPC at the
multivariate mixed logistic regression analysis. § Independently associated with severe PPC at the multivariable regression analysis. “Not recruited” is the
reference category, error bars are symmetric 95% CI of proportions. Mild PPC: patients that required only oxygen therapy, not as part of the standard of care,
without other PPCs. Severe PPC: patients that developed at least one of the following PPCs: acute respiratory failure, need for mechanical ventilation, ARDS,
pneumonia, pneumothorax.
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