Open letter to the Executive Director of the European Medicines Agency concerning the licensing of hydroxyethyl starch solutions for fluid resuscitation
2014; Elsevier BV; Volume: 112; Issue: 3 Linguagem: Inglês
10.1093/bja/aeu025
ISSN1471-6771
AutoresRinaldo Bellomo, Julian Bion, Simon Finfer, John Myburgh, Anders Perner, Konrad Reinhart,
Tópico(s)Cardiac Arrest and Resuscitation
ResumoEditor'We have sent this letter to the Executive Director of the European Medicines Agency: we are concerned that the European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee's (PRAC) recent conclusions on the use of hydroxyethyl starch (HES)1European Medicines Agency (EMA)PRAC confirms that hydroxyethyl-starch solutions (HES) should no longer be used in patients with sepsis or burn injuries or in critically ill patients. 2013http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/10/news_detail_001917.jsp&mid=WC0b01ac058004d5c1Google Scholar will result in harm to patients. In June, the PRAC recommended the suspension of marketing authorization for HES, as the available evidence demonstrated that any possible benefits from HES no longer outweigh its risk.2European Medicines Agency (EMA)PRAC recommends suspending marketing authorisations for infusion solutions containing hydroxyethyl-starch. 2013http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/06/news_detail_001814.jsp&mid=WC0b01ac058004d5c1Google Scholar On October 11, 2013, the PRAC revised its conclusions, announcing that ‘HES must no longer be used to treat patients with sepsis or burns injuries or in critically ill patients because of an increased risk of kidney injury and mortality. HES solutions may, however, continue to be used in patients to treat hypovolaemia caused by acute blood loss, provided that appropriate measures are taken to reduce potential risks and that additional studies are carried out’.1European Medicines Agency (EMA)PRAC confirms that hydroxyethyl-starch solutions (HES) should no longer be used in patients with sepsis or burn injuries or in critically ill patients. 2013http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/10/news_detail_001917.jsp&mid=WC0b01ac058004d5c1Google Scholar Adverse effects of HES have been demonstrated in well-designed investigator-initiated clinical trials in kidney donors,3Cittanova ML Leblanc I Legendre C Mouquet C Riou B Coriat P Effect of hydroxyethylstarch in brain-dead kidney donors on renal function in kidney-transplant recipients.Lancet. 1996; 348: 1620-1622Abstract Full Text Full Text PDF PubMed Scopus (358) Google Scholar patients with sepsis,4Brunkhorst FM Engel C Bloos F et al.Intensive insulin therapy and pentastarch resuscitation in severe sepsis.N Engl J Med. 2008; 358: 125-139Crossref PubMed Scopus (2343) Google Scholar, 5Perner A Haase N Guttormsen AB et al.Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.N Engl J Med. 2012; 367: 124-134Crossref PubMed Scopus (1360) Google Scholar, 6Schortgen F Lacherade JC Bruneel F et al.Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study.Lancet. 2001; 357: 911-916Abstract Full Text Full Text PDF PubMed Scopus (599) Google Scholar and in critically ill patients.7Myburgh JA Finfer S Bellomo R et al.Hydroxyethyl starch or saline for fluid resuscitation in intensive care.N Engl J Med. 2012; 367: 1901-1911Crossref PubMed Scopus (1222) Google Scholar Experimental and clinical studies strongly suggest that toxicity of HES can be attributed to tissue storage and coagulopathy. We ask the PRAC: what assumptions or clinical data would indicate that the same pathological mechanisms do not apply in patients with hypovolaemia from blood loss? Up to one-third of applied HES dose may be stored in the body in clinical settings,8Bellmann R Feistritzer C Wiedermann CJ Effect of molecular weight and substitution on tissue uptake of hydroxyethyl starch: a meta-analysis of clinical studies.Clin Pharmacokinet. 2012; 51: 225-236Crossref PubMed Scopus (75) Google Scholar contributing to kidney3Cittanova ML Leblanc I Legendre C Mouquet C Riou B Coriat P Effect of hydroxyethylstarch in brain-dead kidney donors on renal function in kidney-transplant recipients.Lancet. 1996; 348: 1620-1622Abstract Full Text Full Text PDF PubMed Scopus (358) Google Scholar, 4Brunkhorst FM Engel C Bloos F et al.Intensive insulin therapy and pentastarch resuscitation in severe sepsis.N Engl J Med. 2008; 358: 125-139Crossref PubMed Scopus (2343) Google Scholar, 5Perner A Haase N Guttormsen AB et al.Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.N Engl J Med. 2012; 367: 124-134Crossref PubMed Scopus (1360) Google Scholar, 6Schortgen F Lacherade JC Bruneel F et al.Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study.Lancet. 2001; 357: 911-916Abstract Full Text Full Text PDF PubMed Scopus (599) Google Scholar, 7Myburgh JA Finfer S Bellomo R et al.Hydroxyethyl starch or saline for fluid resuscitation in intensive care.N Engl J Med. 2012; 367: 1901-1911Crossref PubMed Scopus (1222) Google Scholar or other organ injury,9Auwerda JJ Wilson JH Sonneveld P Foamy macrophage syndrome due to hydroxyethyl starch replacement: a severe side effect in plasmapheresis.Ann Intern Med. 2002; 137: 1013-1014Crossref PubMed Scopus (30) Google Scholar, 10Schmidt-Hieber M Loddenkemper C Schwartz S Arntz G Thiel E Notter M Hydrops lysosomalis generalisatus'an underestimated side effect of hydroxyethyl starch therapy?.Eur J Haematol. 2006; 77: 83-85Crossref PubMed Scopus (41) Google Scholar, 11Ginz HF Gottschall V Schwarzkopf G Walter K Excessive tissue storage of colloids in the reticuloendothelial system.Anaesthesist. 1998; 47: 330-334Crossref PubMed Scopus (28) Google Scholar decreased survival in patients with sepsis,4Brunkhorst FM Engel C Bloos F et al.Intensive insulin therapy and pentastarch resuscitation in severe sepsis.N Engl J Med. 2008; 358: 125-139Crossref PubMed Scopus (2343) Google Scholar 5Perner A Haase N Guttormsen AB et al.Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.N Engl J Med. 2012; 367: 124-134Crossref PubMed Scopus (1360) Google Scholar and causing pruritus.12Stander S Richter L Osada N Metze D Hydroxyethyl starch-induced pruritus: clinical characteristics and influence of dose, molecular weight and substitution.Acta Derm Venereol. 2013; doi:0.2340/00015555-1639Google Scholar HES coagulopathy13Jonville-Bera AP Autret-Leca E Gruel Y Acquired type I von Willebrand's disease associated with highly substituted hydroxyethyl starch.N Engl J Med. 2001; 345: 622-623Crossref PubMed Scopus (50) Google Scholar, 14Alexander B Odake K Lawlor D Swanger M Coagulation, hemostasis, and plasma expanders: a quarter century enigma.Fed Proc. 1975; 34: 1429-1440PubMed Google Scholar, 15Sossdorf M Marx S Schaarschmidt B et al.HES 130/0.4 impairs haemostasis and stimulates pro-inflammatory blood platelet function.Crit Care. 2009; 13: R208Crossref PubMed Scopus (41) Google Scholar increases the risk of bleeding and need for blood and blood products in patients with sepsis,4Brunkhorst FM Engel C Bloos F et al.Intensive insulin therapy and pentastarch resuscitation in severe sepsis.N Engl J Med. 2008; 358: 125-139Crossref PubMed Scopus (2343) Google Scholar 5Perner A Haase N Guttormsen AB et al.Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.N Engl J Med. 2012; 367: 124-134Crossref PubMed Scopus (1360) Google Scholar 16Haase N Wetterslev J Winkel P Perner A Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc analyses of a randomized clinical trial.Intensive Care Med. 2013; doi:10.1007/s00134-013-3111-9Google Scholar intensive care patients,7Myburgh JA Finfer S Bellomo R et al.Hydroxyethyl starch or saline for fluid resuscitation in intensive care.N Engl J Med. 2012; 367: 1901-1911Crossref PubMed Scopus (1222) Google Scholar those undergoing anaesthesia for major surgery,17Hecht-Dolnik M Barkan H Taharka A Loftus J Hetastarch increases the risk of bleeding complications in patients after off-pump coronary bypass surgery: a randomized clinical trial.J Thorac Cardiovasc Surg. 2009; 138: 703-711Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 18Mittermayr M Streif W Haas T et al.Hemostatic changes after crystalloid or colloid fluid administration during major orthopedic surgery: the role of fibrinogen administration.Anesth Analg. 2007; 105: 905-917Crossref PubMed Scopus (237) Google Scholar, 19Rasmussen KC Johansson PI Hojskov M et al.Hydroxyethyl starch reduces coagulation competence and increases blood loss during major surgery: results from a randomized controlled trial.Ann Surg. 2013; doi:10.1097/SLA.0000000000000267PubMed Google Scholar and after blunt trauma.20James MF Michell WL Joubert IA Nicol AJ Navsaria PH Gillespie RS Resuscitation with hydroxyethyl starch improves renal function and lactate clearance in penetrating trauma in a randomized controlled study: the FIRST trial (Fluids in Resuscitation of Severe Trauma).Br J Anaesth. 2011; 107: 693-702Abstract Full Text Full Text PDF PubMed Scopus (203) Google Scholar The FDA issued a boxed warning for bleeding in cardiac surgical patients.21Haynes GR Havidich JE Payne KJ Why the Food and Drug Administration changed the warning label for hetastarch.Anesthesiology. 2004; 101: 560-561Crossref PubMed Scopus (42) Google Scholar It seems improbable that the PRAC recommendations ‘that HES solutions should not be used for more than 24 hours and that patients’ kidney function should be monitored for at least 90 days’ will guarantee patient safety. The adverse effects of HES appear to be generic to all HES classes22Mutter TC Ruth CA Dart AB Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function.Cochrane Database Syst Rev. 2013; 7: CD007594PubMed Google Scholar 23Zarychanski R Abou-Setta AM Turgeon AF et al.Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis.J Am Med Assoc. 2013; 309: 678-688Crossref PubMed Scopus (476) Google Scholar and dose-dependent:4Brunkhorst FM Engel C Bloos F et al.Intensive insulin therapy and pentastarch resuscitation in severe sepsis.N Engl J Med. 2008; 358: 125-139Crossref PubMed Scopus (2343) Google Scholar 5Perner A Haase N Guttormsen AB et al.Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.N Engl J Med. 2012; 367: 124-134Crossref PubMed Scopus (1360) Google Scholar 7Myburgh JA Finfer S Bellomo R et al.Hydroxyethyl starch or saline for fluid resuscitation in intensive care.N Engl J Med. 2012; 367: 1901-1911Crossref PubMed Scopus (1222) Google Scholar no safe dose for HES has been defined.22Mutter TC Ruth CA Dart AB Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function.Cochrane Database Syst Rev. 2013; 7: CD007594PubMed Google Scholar In CHEST, increased use of renal replacement therapy in intensive care patients occurred after an average dose of 5 ml kg−1 day−1, 1/10th of the maximal daily dose of 50 ml kg−1.7Myburgh JA Finfer S Bellomo R et al.Hydroxyethyl starch or saline for fluid resuscitation in intensive care.N Engl J Med. 2012; 367: 1901-1911Crossref PubMed Scopus (1222) Google Scholar Monitoring kidney function for 3 months after the use of HES seems impractical, difficult to control, and of questionable impact on patient safety. The CRISTAL trial24Annane D Siami S Jaber S et al.for the CRISTAL InvestigatorsEffects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial.J Am Med Assoc. 2013; doi:10.1001/jama.2013.280502Google Scholar that may have contributed to the EMA's new decision was not designed to assess the safety and efficacy of HES.25Seymour CW Angus DC Making a pragmatic choice for fluid resuscitation in critically ill patients.J Am Med Assoc. 2013; doi:10.1001/jama.2013.280503Google Scholar As an open-label trial that combined various colloid or crystalloid fluids in the respective study arms, it does not provide sufficiently robust evidence to contradict the accumulated signal of harm emanating from all the other trials. If HES was a new drug, data from the CRISTAL study could not be included in the regulatory process for drug approval. Given the current safety concerns, it is hard to see why IRBs and patients would give approval or informed consent for further clinical trials, unless data from animal studies strongly suggest conditions where HES might be beneficial. The revised PRAC recommendation may mean that many thousands of patients with hypovolaemia and acute blood loss will continue to receive HES which will expose them to known risks of harm and offer no proven benefit. J. B.: chair of data safety monitoring board for international study of dexmedetomidine for Orion 2008–9; honoraria paid to hospital charity. Member of scientific advisory board for Nestle; honoraria (if any) to be paid to hospital charity. Research grants from Health Foundation; NIHR Health Services Research & Delivery Programme; NIHR Research for patient Benefit Programme; EU Leonardo Programme. R.B.: consultancy fees from Gambro, Baxter, and Philips Medical. J.M.’s institution (the George Institute for Global Health, Sydney, Australia) has received travel expenses from Fresenius Kabi in relation to the development and conduct of an investigator-initiated randomized controlled trial (the Crystalloid vs. Hydroxyethyl Starch Trial) and travel expenses and honoraria from Baxter in relation to participation on advisory boards. A.P.: funding for research from Fresenius Kabi, B Braun AG, CSL Behring, Cosmed, and BioPorto A/S. Speakers fee from LBP SA. K.R.: unpaid Chairman of the Global Sepsis Alliance. B Braun AG and CSL Behring are sponsors of the Global Sepsis and of World Sepsis Day. S.F. reports receiving travel support and grant support to his institution (The George Institute for Global Health through the University of Sydney) from Fresenius Kabi, and travel support and advisory fees to his institution (The George Institute for Global Health) from Baxter and CSL Behring. All Co-signatories to Open Letter to Executive Director of European Medicines Agency Tabled 1AuthorCountryAffiliationD. AngusUSADistinguished Professor and Mitchell P. Fink Endowed Chair Department of Critical Care Medicine, University of Pittsburgh and UPMC Health System, Pittsburgh, PA, USAM. AntonelliItalyPresident of the Italian Society of Anesthesiology and Intensive Care Medicine (SIAARTI); Director of the General ICU, Institute of Anesthesiology and Intensive Care and Director of the School of Specialty in Anesthesiology and Intensive Care Medicine, University Hospital; Rome, ItalyA. ArtigasSpainDirector Critical Care Center Sabadell Hospital, Barcelona, Spain; Past President Catalan Intensive Care SocietyM. BauerGermanyProfessor of Anesthesiology and Critical Care Medicine; Chief-Executive Director Center for Sepsis Control & Care; Jena University Hospital, Jena, GermanyR.B.AustraliaMBBS, MD (Hons), FRACP, FCICM, PG Dip Echo; Professorial Fellow, Faculty of Medicine, University of Melbourne, Melbourne, Australia; Honorary Professor, Faculty of Medicine, Monash University, Melbourne, Australia; Honorary Professorial Fellow, Faculty of Medicine, The University of Sydney, Sydney, Australia; Concurrent Professor, Faculty of Medicine, University of Nanjing, Nanjing, China; Honorary Principal Research Fellow, Howard Florey Institute, University of Melbourne; Co-director, Australian and New Zealand Intensive Care Research Center; Editor, Critical Care and Resuscitation; Director of Intensive Care Research, Staff Specialist in Intensive Care, Department of Intensive Care, Austin Hospital, Heidelberg, Victoria, AustraliaG. BernardUSAProfessor of Medicine; Chair, NIH NHLBI ARDS Clinical Trials Network; Melinda Owen Bass Professor of Medicine; Program Director, Vanderbilt Institute for Clinical and Translational Research; Associate Vice Chancellor for Research; Senior Associate Dean for Clinical Science Vanderbilt University Medical Center; Nashville, TN, USAJ.B.UKFRCP, FRCA, FFICM, MD, Professor of Intensive Care Medicine, University of Birmingham; Past President of the European Society of Intensive Care Medicine (ESICM); Past Foundation Chair of the European Board of Intensive Care Medicine; Past Foundation Dean of the UK Faculty of Intensive Care MedicineL. BrochardFrancePrevious (until October 2013) Head of the Medico Surgical ICU in Geneva University Hospital, Geneva, Switzerland; presently, Interdepartmental Division Director for Critical Care in the Faculty of Medicine, University of Toronto, Ontario, Canada; Full Professor, Clinician scientist in the Division of Critical Care Saint Michael's Hospital, Toronto, ON, Canada. Head of the European Clinical Research Network REVAC. Brun BuissonFranceMD, Director, Medical ICU, CHU Henri Mondor; Professor of Critical Care Medicine, Université Paris-Est Créteil; Paris, FranceF. M. BrunkhorstGermanySecretary General of the German Sepsis Society, Director of the Center of Clinical Studies, Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, GermanyV. BumbasirevicSerbiaPresident, Serbian Society of Intensive Care Medicine; Head, Department of Intensive Care Medicine; Emergency Center, Clinic of Anesthesiology, Clinical Center of Serbia; Belgrade, SerbiaH. BurchardiGermanyFRCA, Professor of Anesthesiology and Critical Care Medicine; Bovenden, Germany; Past President of the European Society of Intensive Care Medicine (ESICM)P. CaironiItalyAssistant Professor; Department of Pathophysiology and Transplantation; Policlinico Hospital of Milan; ItalyJ. CarletFrancePast President of the European Society of Intensive Care Medicine (ESICM)J. ChalmersAustraliaEmeritus Professor of Medicine, University of Sydney and George Institute for Global HealthJ. ChastreFranceProfessor of Medicine at Paris, University School of Medicine; Director of the Medical Intensive Care Unit and of the Intermediate Care Unit at the Institute of Cardiology, Groupe Hospitalier Pitié−Salpêtrière, Paris, FranceG. CiterioItalyMD; Professor; Department of Perioperative Medicine and Intensive Care, Hospital San Gerardo, Monza, ItalyD. CookCanadaCanada Research Chair in Critical Care, McMaster University, Ontario, CanadaJ. CooperAustraliaBMBS, MD, FRACP, FCICM; Professor of Intensive Care Medicine; Director, ANZICS Research Center, Monash University; Director, Center of Research Excellence for Patient Blood Management in Critical Illness and Trauma, Monash University; Director, Critical Care, School of Public Health and Preventive Medicine, Monash University; Head, The Alfred ICU Research; Melbourne, AustraliaP. DellingerUSAProfessor and Chair, Department of Medicine, Cooper Medical School of Rowan University and Chief, Medicine Service at Cooper University Hospital, Camden, NJ. Past president of the Society of Critical Care MedicineT. EvansUKProfessor of Intensive Care Medicine, Imperial College, London, UKS.F.AustraliaProfessor of Critical Care Medicine, The George Institute of Global Health, The University of Sydney, Sydney, AustraliaH. FlaattenNorwayDepartment of Anesthesia, Haukeland University Hospital (HUS); University of Bergen, NorwayR. FreebairnNew ZealandConsultant, Intensive Care Services & Clinical Director, Acute Services Hawke's Bay Hospital; Adjunct Associate Professor, Department of Anesthesia & Intensive Care, Chinese University of Hong Kong; President, College of Intensive Care Medicine, Melbourne, AustraliaC. FrenchAustraliaFCICM, FANZCA; Clinical Associate Professor, The University of Melbourne; Adjunct Associate Professor, The University of Notre Dame; Director of Intensive Care Western Health; Vice Chair Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS); Melbourne, AustraliaD. GattasAustraliaClinical Associate Professor, Sydney Medical School, University of Sydney; Executive Committee, Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS); Honorary Fellow, Critical Care & Trauma Division, The George Institute for Global Health; Senior Staff Intensivist, Royal Prince Alfred Hospital, Sydney, AustraliaL. GattinoniItalyMD, FRCP; Professor in Anesthesia and Intensive Care, University of Milan; Chairman of the Department of Pathophysiology and Transplantation, University of Milan; Chief of the Department of Emergency and Intensive Care, Policlinico Hospital of Milan, Italy; Past President of the World Federation Societies of Intensive and Critical Care Medicine (WFSICCM)H. GerlachGermanyDirector, Department of Anesthesiology, Operative Intensive Care and Pain Management, Vivantes-Klinikum Neukoelln, Berlin, Germany; Past Secretary ESICM; Past Treasurer ESICM; Past Chair of the Section Systemic Inflammation and Sepsis; President of the German Sepsis SocietyE. J. Giamarellos-BourboulisGreece4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece; Co-ordinator Hellenic Sepsis Study Group (www.sepsis.gr)C. HartogGermanyMD, Senior lecturer; Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, GermanyC. HindsUKProfessor of Intensive Care Medicine; Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UKU. KaisersGermanyProfessor of Anesthesia and Intensive Care Medicine; Director of the Department for Anesthesiology and Intensive Care, University of Leipzig, Medical Faculty, Leipzig, GermanyM. LevyUSAProfessor of Medicine, Brown University, School of Medicine, Providence RI, USA; Past President of the Society of Critical Care Medicine (SCCM)J. LipmanAustraliaMBBCH, DA, FFA (Crit Care), FCICM, MD Professor and Head; Anesthesiology and Critical Care, The University of Queensland, Queensland, AustraliaS. MacMahonAustralia/UKPrincipal Director, The George Institute for Global Health; Executive Director, The George Institute for Global Health UK at the Oxford University, UK; Professor of Medicine, University of Sydney, Australia; Professor of Medicine and James Martin Professorial Fellow, Oxford University, UKD. McAuleyUKProfessor of Intensive Care Medicine Center for Infection and Immunity, Queen's University of Belfast and Royal Victoria Hospital, Belfast; Co-Director of Research, UK Intensive Care Society; Chair, Irish Critical Care Trials Group; Director Northern Ireland Clinical Trials Unit; Belfast, UKS. McGuinnessNew ZealandFRCA, FANZCA, FFICM; Specialist, Cardiothoracic & Vascular ICU, Auckland City Hospital; Auckland, New ZealandL. McIntyreCanadaMD, MSc, FRCPC, Assistant Professor, Department of Medicine (Critical Care), Ottawa Hospital; Scientist, Ottawa Hospital Research Institute; Center for Transfusion and Critical Care Research; Adjunct Scientist, Canadian Blood Services; Ottawa, Ontario, CanadaM. MaggoriniSwitzerlandProfessor; Medical Intensive Care Unit, University Hospital Zurich; Zurich, Switzerland; Chair of the Division of Professional Development ESICM 2010–3J. ManceboSpainMD, Director Intensive Care Medicine at University Hospital Sant Pau, Barcelona, SpainJ. MarshallCanadaMD, FRCSC, Professor of Surgery, University of Toronto, Senior lnvestigator, Li Ka Shing Knowledge Institute, St Michael's Hospital; Chairman International Forum for Acute Care Trialists and past-chair, Canadian Critical Care Trials Group; Toronto, Ontario, CanadaR. MorenoPortugalMD, PhD, Director, UCINC Hospital de São José Centro Hospitalar de Lisboa Central Lisbon, Portugal; Past President Portuguese Society of Intensive Care Medicine; Past President of the European Society of Intensive Care Medicine (ESICM); Past President European Board of Intensive Care MedicineJ. MorganAustraliaFellow of the College of Intensive Care Medicine of Australia and New Zealand; Intensive Care Specialist, Mater Health Services; Senior Lecturer, University of Queensland; Brisbane, AustraliaJ.M.AustraliaMBBCh, PhD, FCICM; Professor of Critical Care Medicine, University of New South Wales; Director, George Institute for Global Health; Honorary Professor, University of Sydney; Honorary Professor, Monash University, Melbourne; Senior Physician, Department of Intensive Care Medicine, St George Hospital, Sydney, Australia; Past President, College of Intensive Care Medicine; Past Chairman, Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS); Lead investigator, Crystalloid vs. Hydroxyethyl Starch Trial (CHEST)C. NatansonUSASenior investigator and chief of the Anesthesia Section, Clinical Center's Critical Care Medicine Department at the National Institutes of Health (NIH); Professor of Anesthesia at University of Maryland and at Johns Hopkins University, Baltimore, MD; Clinical Professor of Medicine at George Washington University; Washington, DC, USAR. NortonUK/AustraliaMA, MPH, PhD; Professor of Global Health & James Martin Professorial Fellow, University of Oxford; Professor of Public Health, The University of Sydney; Sydney, Australia; Co-Principal Director of The George Institute for Global Health; Sydney, AustraliaD. PayenFranceProfessor of Medicine; Director, Department of Anesthesiology and Intensive Care, Lariboisiere University Hospital; University Paris 7 Denis Diderot, Paris, FranceA.P.DenmarkProfessor in Intensive Care Medicine, University of Copenhagen; Chair Scandinavian Critical Care Trials Group; Senior staff specialist, Rigshospitalet, Copenhagen, Denmark; Principal investigator, The TRISS trialV. PerkovicAustraliaMBBS, PhD, FRACP FASN Executive Director, The George Institute Australia; Professor of Medicine, University of Sydney, Sydney, AustraliaA. PesentiItalyProfessor of Anesthesia and Intensive Care, University of Milano Bicocca, Chief Anesthesia and Critical Care; Director, Department of Emergency Medicine, Ospedale San Gerardo, Monza, Italy; Coordinator of the Emergency Medical Services of Milan Metropolitan Area, Regional Emergency Systems Agency (AREU), Regione Lombardia, ItalyV. PettilaFinlandMD, Professor, Helsinki University Central Hospital, Helsinki, FinlandC. PutensenGermanyProfessor of Intensive Care Medicine, University Hospital of Bonn; Past Chairman of the ESICM Acute Respiratory Failure Section, Bonn, GermanyM. QuintelGermanyDirector, Center for Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Göttingen, Germany; Past President Interdisciplinary Society of Intensive Care Medicine (DIVI)M. RanieriItalyProfessor of Anesthesia and Critical Care Medicine; Department of Anesthesia and Intensive Care Medicine, University of Turin, Italy; Past President of the European Society of Intensive Care Medicine (ESICM)K.R.GermanyProfessor of Anesthesia and Critical Care Medicine, Jena University Hospital, Jena, Germany; Chairman Global Sepsis Alliance; Member of the German National Academy of Science LeopoldinaA. RhodesUKFRCP, FRCA, FFICM, MD(Res); Hon. Reader in Anesthesia and Intensive Care Medicine St George's Healthcare NHS; Trust and St George's University of London, London, UK; Past President of the European Society of Intensive Care Medicine (ESICM)C. RichardFranceProfessor of Critical Care Medicine; Head of Medical Intensive Care Unit; Bicetre Hospital; Risk and Quality Coordinator; Assistance Publique'Hôpitaux de Paris, Paris, France; Past President of the Société de Réanimation de Langue Française (SRLF)N.C. RiedemannGermanyVice Director Intensive Care Medicine, Jena University Hospital, Jena, GermanyI. RobertsUKEditor, Cochrane Injuries Group; Director, Clinical Trials Unit, London School of Hygiene & Tropical Medicine, Keppel Street, London, UKG. RubenfeldCanadaMD, MSc, FRCPC; Chief, Trauma, Emergency and Critical Care Program, Sunnybrook Health Sciences Center; Professor of Medicine, Interdepartmental Division of Critical Care Medicine, University of Toronto; Senior Scientist, Sunnybrook Research Institute; Toronto, Ontario, CanadaF. SchortgenFranceMD, PhD; Department of Medical Intensive Care, Henri Mondor University Hospital, University Paris-Est, Créteil, FranceG. SigurdssonIcelandChairman of University Hospital Research Council; Professor & Faculty Chairman; Department of Anaesthesia & Intensive Care Medicine, Landspitali University Hospital, Reykjavik, Iceland; Director, Scandinavian Postgraduate Program in Intensive Care Medicine; Editor, Acta Anaesthesiologica ScandinavicaC. SprungIsraelDirector, General Intensive Care Unit; Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel; Past Treasurer of European Society of Intensive Care Medicine (ESICM)N. StochettiItalyProfessor of Anesthesia and Intensive Care, Milan University, Department of Physiopathology and Transplants, Milan, ItalyP. SuterSwitzerlandHonorary Professor, University of Geneva; Genva, Switzerland; Past President of Swiss Academie of Science and European Society of Intensive Care Medicine (ESICM)J. TakalaSwitzerlandMD, PhD, Professor of Intensive Care Medicine; Director and Chief Physician, Department of Intensive Care Medicine; University Hospital Bern (Inselspital); Bern, Switzerland; Past President of the European Society of Intensive Care Medicine (ESICM)T. ThompsonUSAMD, Director of Translational Research; Pulmonary Critical Care Unit; Massachusetts General Hospital; Professor of Medicine; Harvard Medical School; Boston, MA, USAA. TurnerAustraliaPresident Australian and New Zealand Intensive Care SocietyT. WalshUKProfessor of Critical Care, Edinburgh University; Chair UK National Institute of Healthcare Research Critical Care Network, Edinburgh, UKS. WebbAustraliaSenior Staff Specialist, Intensive Care Unit, Royal Perth Hospital; Clinical Professor, School of Medicine and Pharmacology and School of Population Health, University of Western Australia; Perth, WA, Australia; Immediate Past Chair, Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS)N. WebsterUKProfessor of Anesthesia and Intensive Care, University of Aberdeen; Aberdeen, UKT. WelteGermanyDirector, Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; President of the German Society of Pneumology (DGP); Past President of the German Sepsis Society; Member of the Executive Board of the German Interdisciplinary Society of Intensive Care Medicine (DIVI); Spokesman of the Fachkolleg I (Inflammation) of the German Research Council (DFG)M. WhiteAustraliaMB BCh, BAO, FFARCSI; Associate Professor, Discipline of Acute Care Medicine, University of Adelaide; Adelaide, Australia; Immediate Past President, Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS)C. WiedermannItalyAssociate Professor of Internal Medicine, Medical University of Innbruck; Past President of the Austrian Society of General and Medical Intensive Care Medicine; Co-Editor of ‘Pharmainformation'Unabhängige Information für Ärzte/innen’ by The Austrian Chamber of Physicians (Member of the International Society of Drug Bulletins, ISDB)D. YoungUKSenior Clinical Lecturer in Intensive Care, University of Oxford; Oxford, UK; Chair, CHEST study DMECR. ZarychanskiCanadaMD, MSc, University of Manitoba, Department of Internal Medicine, Sections of Critical Care and of Hematology and Medical Oncology, University of Manitoba, Winnipeg, Canada Open table in a new tab Download .zip (.01 MB) Help with zip files Download .zip (.0 MB) Help with zip files Download .zip (.01 MB) Help with zip files
Referência(s)