title: Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
abstract: OBJECTIVE
  The Third International Consensus Definitions Task Force defined sepsis as "life-threatening organ dysfunction due to a dysregulated host response to infection." The performance of clinical criteria for this sepsis definition is unknown.
  
  
  OBJECTIVE
  To evaluate the validity of clinical criteria to identify patients with suspected infection who are at risk of sepsis.
  Among 1.3 million electronic health record encounters from January 1, 2010, to December 31, 2012, at 12 hospitals in southwestern Pennsylvania, we identified those with suspected infection in whom to compare criteria. Confirmatory analyses were performed in 4 data sets of 706,399 out-of-hospital and hospital encounters at 165 US and non-US hospitals ranging from January 1, 2008, until December 31, 2013.
  
  
  METHODS
  Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, systemic inflammatory response syndrome (SIRS) criteria, Logistic Organ Dysfunction System (LODS) score, and a new model derived using multivariable logistic regression in a split sample, the quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score (range, 0-3 points, with 1 point each for systolic hypotension [≤100 mm Hg], tachypnea [≥22/min], or altered mentation).
  
  
  METHODS
  For construct validity, pairwise agreement was assessed. For predictive validity, the discrimination for outcomes (primary: in-hospital mortality; secondary: in-hospital mortality or intensive care unit [ICU] length of stay ≥3 days) more common in sepsis than uncomplicated infection was determined. Results were expressed as the fold change in outcome over deciles of baseline risk of death and area under the receiver operating characteristic curve (AUROC).
  
  
  RESULTS
  In the primary cohort, 148,907 encounters had suspected infection (n = 74,453 derivation; n = 74,454 validation), of whom 6347 (4%) died. Among ICU encounters in the validation cohort (n = 7932 with suspected infection, of whom 1289 [16%] died), the predictive validity for in-hospital mortality was lower for SIRS (AUROC = 0.64; 95% CI, 0.62-0.66) and qSOFA (AUROC = 0.66; 95% CI, 0.64-0.68) vs SOFA (AUROC = 0.74; 95% CI, 0.73-0.76; P < .001 for both) or LODS (AUROC = 0.75; 95% CI, 0.73-0.76; P < .001 for both). Among non-ICU encounters in the validation cohort (n = 66 522 with suspected infection, of whom 1886 [3%] died), qSOFA had predictive validity (AUROC = 0.81; 95% CI, 0.80-0.82) that was greater than SOFA (AUROC = 0.79; 95% CI, 0.78-0.80; P < .001) and SIRS (AUROC = 0.76; 95% CI, 0.75-0.77; P < .001). Relative to qSOFA scores lower than 2, encounters with qSOFA scores of 2 or higher had a 3- to 14-fold increase in hospital mortality across baseline risk deciles. Findings were similar in external data sets and for the secondary outcome.
  
  
  CONCLUSIONS
  Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis. Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis.
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania2Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Pittsburgh, Pennsylvania.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Seymour
authors.affiliation: Division of Research, Kaiser Permanente, Oakland, California.
authors.forename: Vincent X
authors.initials: VX
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor5Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan6Australia and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Iwashyna
authors.affiliation: Center for Clinical Studies, Jena University Hospital, Jena, Germany.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Brunkhorst
authors.affiliation: Division of General Internal Medicine, University of Washington, Seattle.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Rea
authors.affiliation: Research Group Clinical Epidemiology, Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.affiliation: Trauma, Emergency, and Critical Care Program, Sunnybrook Health Sciences Centre; Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Rubenfeld
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania2Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Pittsburgh, Pennsylvania.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Kahn
authors.affiliation: Critical Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, England.
authors.forename: Manu
authors.initials: M
authors.lastname: Shankar-Hari
authors.affiliation: Bloomsbury Institute of Intensive Care Medicine, University College London, London, England.
authors.forename: Mervyn
authors.initials: M
authors.lastname: Singer
authors.affiliation: Feinstein Institute for Medical Research, Hofstra-North Shore-Long Island Jewish School of Medicine, Steven and Alexandra Cohen Children's Medical Center, New Hyde Park, New York.
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Deutschman
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor5Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan6Australia and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine.
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Escobar
authors.affiliation: Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania2Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Pittsburgh, Pennsylvania.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Angus
mesh_terms: D000328:Adult; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007022:Hypotension / Q000175:diagnosis; D007239:Infections / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D007362:Intensive Care Units / Q000706:statistics & numerical data; D019344:Lactic Acid / Q000097:blood; D007902:Length of Stay; D008297:Male; D063305:Organ Dysfunction Scores; D010414:Pennsylvania / Q000453:epidemiology; D012044:Regression Analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood / Q000175:diagnosis* / Q000401:mortality*; D018746:Systemic Inflammatory Response Syndrome / Q000175:diagnosis; D059246:Tachypnea / Q000175:diagnosis
chemical_list: D019344:Lactic Acid