AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
Page 1 of 51
Global epidemiology of pediatric severe sepsis: the Sepsis PRevalence, OUtcomes, and Therapies study
Scott L. Weiss, MD, MSCE1*, Julie C. Fitzgerald, MD, PhD1*, John Pappachan, MBBChir FRCA2, Derek Wheeler, MD, MMM3, Juan C. Jaramillo-Bustamante, MD4, Asma Salloo, MBBCh, FCPaed(SA), FSCC(SA)Paed5, Sunit C. Singhi, MBBS, MD6, Simon Erickson, MBBS7, Jason A. Roy, PhD8, Jenny L. Bush, RNC, BSN1, Vinay M. Nadkarni, MD, MS1, Neal J. Thomas, MD, MSc1,9, for the SPROUT Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
*These two authors contributed equally to the manuscript. 1
Division of Critical Care Medicine, Department of Anesthesia and Critical Care, The Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; [email protected]; [email protected]; [email protected]; [email protected]
2
Paediatric Intensive Care Unit, NIHR Respiratory Biomedical Research Unit and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust and Faculty of Medicine, University of Southampton, Southampton, UK; [email protected] 3
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center; Department of Pediatrics, University of Cincinnati College of Medicine; Cincinnati, OH, USA; [email protected]
Copyright © 2015 by the American Thoracic Society
AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
4
Division of Pediatric Critical Care, Hospital General de Medellín, Medellin, Colombia; [email protected]
5
Chris Hani Baragwanath Academic Hospital, University of Witwatersrand, Johannesburg, South Africa; [email protected]
6
Department of Pediatrics and Pediatric Emergency and Intensive care, Advanced Pediatrics
Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India; [email protected] 7
Department of Intensive Care, Princess Margaret Hospital for Children, University of Western Australia, Perth, Australia; [email protected]
8
Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; [email protected]
9
Division of Pediatric Critical Care Medicine, Penn State Hershey Children’s Hospital, Penn State University College of Medicine, Hershey, PA, USA; [email protected]
Running Title: SPROUT Pediatric Severe Sepsis Study Word Count: 3716 Descriptor: 4.12 Sepsis/Multiple Organ Failure This article has an online data supplement, which is accessible from this issue's table of content online at www.atsjournals.org.
Corresponding Author: Julie C. Fitzgerald, MD, PhD
Copyright © 2015 by the American Thoracic Society
Page 2 of 51
AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
Page 3 of 51
Assistant Professor of Critical Care and Pediatrics Department of Anesthesia and Critical Care University of Pennsylvania Perelman School of Medicine The Children’s Hospital of Philadelphia 8th Floor Main Hospital, Room 8571 34th St. & Civic Center Blvd. Philadelphia, PA 19104 Phone: (215) 590-4879 Fax: (215) 590-4327 Email: [email protected]
AUTHOR COMMENTS SL Weiss and JC Fitzgerald had full access to all of the data in the study and take complete responsibility for the integrity of the data and the accuracy of the data analysis. SL Weiss, JC Fitzgerald, VM Nadkarni, JA Roy, and NJ Thomas conducted and are responsible for the data analysis. Study concept and design: Weiss, Fitzgerald, Nadkarni, Thomas Acquisition, analysis, or interpretation of data: Weiss, Fitzgerald, Pappachan, Wheeler, Jaramillo-Bustamante, Salloo, Singhi, Erickson, Roy, Bush, Nadkarni, Thomas Drafting of the manuscript: Weiss, Fitzgerald, Nadkarni, Thomas Critical revision of the manuscript for important intellectual content: Weiss, Fitzgerald, Pappachan, Wheeler, Jaramillo-Bustamante, Salloo, Singhi, Erickson, Roy, Bush, Nadkarni, Thomas
Copyright © 2015 by the American Thoracic Society
AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
Statistical analysis: Weiss, Fitzgerald, Roy, Nadkarni, Thomas Obtained funding: Weiss, Fitzgerald, Nadkarni Administrative, technical, or material support: Bush Study supervision: Weiss, Fitzgerald, Nadkarni, Thomas
FUNDING/SUPPORT Financial support was provided by the Endowed Chair, Department of Anesthesia and Critical Care, University of Pennsylvania Perelman School of Medicine and the Center for Pediatric Clinical Effectiveness at The Children’s Hospital of Philadelphia. Dr. Weiss is also supported by NIH K12HD047349-10. Financial support for data collection in all UK centers was provided by the UK National Institute of Health (NIHR) Clinical Research Network and in Southampton by the Southampton NIHR Wellcome Trust Clinical Research Facility. None of the funders participated in the design and conduct of study; collection, management, analysis, and interpretation of the data; or preparation, review or approval of the manuscript.
None of the authors have potential conflicts of interests to report.
Copyright © 2015 by the American Thoracic Society
Page 4 of 51
AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
Page 5 of 51
ABSTRACT Rationale: Limited data exist about the international burden of severe sepsis in critically ill children. Objectives: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. Methods: Point prevalence study conducted on 5 days throughout 2013-2014 in 128 sites from 26 countries. Patients 5 mcg/kg/min, or any dose of epinephrine, norepinephrine, vasopressin, phenylephrine, milrinone, levosimendan, or vasodilator. ‡Denominator is the number of patients on any vasoactive infusion (n=314) §Vasodilators include nitroprusside, nitroglycerin, and nicardipine ǁIncludes PRBCs, platelets, FFP, cryoprecipitate, granulocytes, and whole blood **Includes intravenous insulin by continuous infusion only ††Includes hemodialysis, all continuous renal replacement modalities, and peritoneal dialysis
32
Copyright © 2015 by the American Thoracic Society
AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
Page 37 of 51
Table 4: Outcomes for total cohort and by age category
Age Categories Total
0-28 days
29 d to < 1 yr
1 to
Page 1 of 51
Global epidemiology of pediatric severe sepsis: the Sepsis PRevalence, OUtcomes, and Therapies study
Scott L. Weiss, MD, MSCE1*, Julie C. Fitzgerald, MD, PhD1*, John Pappachan, MBBChir FRCA2, Derek Wheeler, MD, MMM3, Juan C. Jaramillo-Bustamante, MD4, Asma Salloo, MBBCh, FCPaed(SA), FSCC(SA)Paed5, Sunit C. Singhi, MBBS, MD6, Simon Erickson, MBBS7, Jason A. Roy, PhD8, Jenny L. Bush, RNC, BSN1, Vinay M. Nadkarni, MD, MS1, Neal J. Thomas, MD, MSc1,9, for the SPROUT Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
*These two authors contributed equally to the manuscript. 1
Division of Critical Care Medicine, Department of Anesthesia and Critical Care, The Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; [email protected]; [email protected]; [email protected]; [email protected]
2
Paediatric Intensive Care Unit, NIHR Respiratory Biomedical Research Unit and NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust and Faculty of Medicine, University of Southampton, Southampton, UK; [email protected] 3
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center; Department of Pediatrics, University of Cincinnati College of Medicine; Cincinnati, OH, USA; [email protected]
Copyright © 2015 by the American Thoracic Society
AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
4
Division of Pediatric Critical Care, Hospital General de Medellín, Medellin, Colombia; [email protected]
5
Chris Hani Baragwanath Academic Hospital, University of Witwatersrand, Johannesburg, South Africa; [email protected]
6
Department of Pediatrics and Pediatric Emergency and Intensive care, Advanced Pediatrics
Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India; [email protected] 7
Department of Intensive Care, Princess Margaret Hospital for Children, University of Western Australia, Perth, Australia; [email protected]
8
Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; [email protected]
9
Division of Pediatric Critical Care Medicine, Penn State Hershey Children’s Hospital, Penn State University College of Medicine, Hershey, PA, USA; [email protected]
Running Title: SPROUT Pediatric Severe Sepsis Study Word Count: 3716 Descriptor: 4.12 Sepsis/Multiple Organ Failure This article has an online data supplement, which is accessible from this issue's table of content online at www.atsjournals.org.
Corresponding Author: Julie C. Fitzgerald, MD, PhD
Copyright © 2015 by the American Thoracic Society
Page 2 of 51
AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
Page 3 of 51
Assistant Professor of Critical Care and Pediatrics Department of Anesthesia and Critical Care University of Pennsylvania Perelman School of Medicine The Children’s Hospital of Philadelphia 8th Floor Main Hospital, Room 8571 34th St. & Civic Center Blvd. Philadelphia, PA 19104 Phone: (215) 590-4879 Fax: (215) 590-4327 Email: [email protected]
AUTHOR COMMENTS SL Weiss and JC Fitzgerald had full access to all of the data in the study and take complete responsibility for the integrity of the data and the accuracy of the data analysis. SL Weiss, JC Fitzgerald, VM Nadkarni, JA Roy, and NJ Thomas conducted and are responsible for the data analysis. Study concept and design: Weiss, Fitzgerald, Nadkarni, Thomas Acquisition, analysis, or interpretation of data: Weiss, Fitzgerald, Pappachan, Wheeler, Jaramillo-Bustamante, Salloo, Singhi, Erickson, Roy, Bush, Nadkarni, Thomas Drafting of the manuscript: Weiss, Fitzgerald, Nadkarni, Thomas Critical revision of the manuscript for important intellectual content: Weiss, Fitzgerald, Pappachan, Wheeler, Jaramillo-Bustamante, Salloo, Singhi, Erickson, Roy, Bush, Nadkarni, Thomas
Copyright © 2015 by the American Thoracic Society
AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
Statistical analysis: Weiss, Fitzgerald, Roy, Nadkarni, Thomas Obtained funding: Weiss, Fitzgerald, Nadkarni Administrative, technical, or material support: Bush Study supervision: Weiss, Fitzgerald, Nadkarni, Thomas
FUNDING/SUPPORT Financial support was provided by the Endowed Chair, Department of Anesthesia and Critical Care, University of Pennsylvania Perelman School of Medicine and the Center for Pediatric Clinical Effectiveness at The Children’s Hospital of Philadelphia. Dr. Weiss is also supported by NIH K12HD047349-10. Financial support for data collection in all UK centers was provided by the UK National Institute of Health (NIHR) Clinical Research Network and in Southampton by the Southampton NIHR Wellcome Trust Clinical Research Facility. None of the funders participated in the design and conduct of study; collection, management, analysis, and interpretation of the data; or preparation, review or approval of the manuscript.
None of the authors have potential conflicts of interests to report.
Copyright © 2015 by the American Thoracic Society
Page 4 of 51
AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
Page 5 of 51
ABSTRACT Rationale: Limited data exist about the international burden of severe sepsis in critically ill children. Objectives: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. Methods: Point prevalence study conducted on 5 days throughout 2013-2014 in 128 sites from 26 countries. Patients 5 mcg/kg/min, or any dose of epinephrine, norepinephrine, vasopressin, phenylephrine, milrinone, levosimendan, or vasodilator. ‡Denominator is the number of patients on any vasoactive infusion (n=314) §Vasodilators include nitroprusside, nitroglycerin, and nicardipine ǁIncludes PRBCs, platelets, FFP, cryoprecipitate, granulocytes, and whole blood **Includes intravenous insulin by continuous infusion only ††Includes hemodialysis, all continuous renal replacement modalities, and peritoneal dialysis
32
Copyright © 2015 by the American Thoracic Society
AJRCCM Articles in Press. Published on 03-March-2015 as 10.1164/rccm.201412-2323OC
Page 37 of 51
Table 4: Outcomes for total cohort and by age category
Age Categories Total
0-28 days
29 d to < 1 yr
1 to
