title: Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition.
abstract: OBJECTIVE
  Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and neonatal intensive care (ESPNIC) experts' definition of paediatric RSS.
  
  
  METHODS
  We conducted a two-round Delphi study followed by an observational multicentre retrospective study. One hundred and fourteen paediatric intensivists answered a clinical case-based, two-round Delphi survey, identifying clinical items consistent with RSS. Multivariate analysis of these items in a development single-centre cohort (70 patients, 30 % mortality) facilitated development of RSS definitions based on either a bedside or computed severity score. Both scores were subsequently tested in a validation cohort (six centres, 424 patients, 11.6 % mortality).
  
  
  RESULTS
  From the Delphi process, the draft definition included evidence of myocardial dysfunction and high blood lactate levels despite high vasopressor treatment. When assessed in the development population, each item was independently associated with the need for extracorporeal life support (ECLS) or death. Resultant bedside and computed septic shock scores had high discriminative power against the need for ECLS or death, with areas under the receiver operating characteristics curve of 0.920 (95 % CI 0.89-0.94), and 0.956 (95 % CI 0.93-0.97), respectively. RSS defined by a bedside score equal to or higher than 2 and a computed score equal to or higher than 3.5 was associated with a significant increase in mortality.
  
  
  CONCLUSIONS
  This ESPNIC definition of RSS accurately identifies children with the most severe form of septic shock.
authors.affiliation: Paediatric Intensive Care Unit, Paris South University Hospitals, AP-HP, 78 Rue du General Leclerc, 94275, Le Kremlin-Bicêtre, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Morin
authors.affiliation: Paediatric Intensive Care Unit, Great Ormond Street Hospital NHS Foundation Trust, London, UK.
authors.forename: Samiran
authors.initials: S
authors.lastname: Ray
authors.affiliation: Paediatric Intensive Care Unit, Saint-Mary's Hospital, London, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Paediatric Intensive Care Unit, Lyon University Hospitals, Bron, France.
authors.forename: Solenn
authors.initials: S
authors.lastname: Remy
authors.affiliation: Paediatric Intensive Care Unit, Paris South University Hospitals, AP-HP, 78 Rue du General Leclerc, 94275, Le Kremlin-Bicêtre, France.
authors.forename: Mohamed Rida
authors.initials: MR
authors.lastname: Benissa
authors.affiliation: Paediatric Intensive Care Unit, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Nicolaas J G
authors.initials: NJG
authors.lastname: Jansen
authors.affiliation: Paediatric Intensive Care Unit, Lyon University Hospitals, Bron, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Javouhey
authors.affiliation: Paediatric Intensive Care Unit, Great Ormond Street Hospital NHS Foundation Trust, London, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Peters
authors.affiliation: Paediatric Intensive Care Unit, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, The Netherlands.|Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), The University of Groningen, Groningen, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Kneyber
authors.affiliation: Neonatal Intensive Care Unit, Paris South University Hospitals, AP-HP, Clamart, France.
authors.forename: Daniele
authors.initials: D
authors.lastname: De Luca
authors.affiliation: Paediatric Intensive Care Unit, Saint-Mary's Hospital, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Nadel
authors.affiliation: Paediatric Intensive Care Unit, Lady Cilento Children's Hospital, Children's Health Queensland, Brisbane, Australia.|Paediatric Critical Care Research Group, Mater Research, The University of Queensland, Brisbane, Australia.|Department of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Luregn Jan
authors.initials: LJ
authors.lastname: Schlapbach
authors.affiliation: Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Australia.|Cardiothoracic Intensive Care Unit, National University Health System, Singapore, Singapore.
authors.forename: Graeme
authors.initials: G
authors.lastname: Maclaren
authors.affiliation: Paediatric Intensive Care Unit, Paris South University Hospitals, AP-HP, 78 Rue du General Leclerc, 94275, Le Kremlin-Bicêtre, France. pierre.tissieres@aphp.fr.|Institute of Integrative Biology of the Cell, Paris Saclay University, Saint-Aubin, France. pierre.tissieres@aphp.fr.
authors.forename: Pierre
authors.identifier: http://orcid.org/0000-0001-5423-5532
authors.initials: P
authors.lastname: Tissieres
mesh_terms: D002648:Child; D002675:Child, Preschool; D032921:Consensus; D003697:Delphi Technique; D005060:Europe; D005260:Female; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D019344:Lactic Acid / Q000097:blood; D008297:Male; D012372:ROC Curve; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D009626:Terminology as Topic; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
chemical_list: D014662:Vasoconstrictor Agents; D019344:Lactic Acid
keywords: Acidosis; Cardiac; Failure; Lactic; Paediatrics; Resuscitation; Septic; Shock