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The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D et al.

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA.2016 Feb 23;315(8):801-10.



  • To evaluate and, as needed, update definitions for sepsis and septic shock.
  • To evaluated which clinical criteria best identified infected patients with sepsis from the patients without sepsis.



Development of Definitions and clinical criteria –

  • Society of Critical Care Medicine and the European Society of Intensive Care Medicine proposed a task force of 19 critical care, infectious disease, surgical & pulmonary specialists. Existing definitions were re-evaluated by these specialists. They utilized a large electronic health record database and patient cohorts (44 studies reporting septic shock outcomes (total of 166 479 patients) from a total of 92 sepsis epidemiology studies), and appreciated the role of pathobiology in defining sepsis and septic shock. Following this, updated definition and criteria for sepsis were proposed.
  • Then the definition and criteria were applied to multiple large electronic health record databases (Surviving Sepsis Campaign [n = 28 150]; University of Pittsburgh Medical Center [n = 1309 025], and Kaiser Permanente Northern California [n = 1 847 165]).


New Definition

  • Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection.
  • Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.

New Clinical criteria

  • Sepsis is suspected or documented infection and
an acute increase of ≥2 SOFA points (a proxy for organ dysfunction).
  • Septic shock is sepsis
vasopressor therapy needed to elevate MAP ≥65 mm Hg
lactate >2 mmol/L (18 mg/dL) despite adequate fluid resuscitation


  • The investigators tried to evaluate which clinical criteria best identified infected patients most likely to have sepsis. It was done by analyzing a large dataset of hospitalized patients with presumed infection. Various scores i.e. Systemic inflammatory response (SIRS), Sequential organ failure assessment (SOFA) score and Logistic Organ Dysfunction System were compared (construct validity) and their correlation with subsequent outcomes were determined (predictive validity). Also, 21 bedside and laboratory criteria proposed by the 2001 task force were evaluated by multivariable regression method.



When evaluated in ICU patients for hospital mortality with SOFA (AUROC = 0.74; 95% CI, 0.73-0.76) and the Logistic Organ Dysfunction System (AUROC = 0.75; 95% CI, 0.72-0.76) were found to be superior to SIRS (AUROC = 0.64; 95% CI, 0.62-0.66). The predictive validity of a change in SOFA score of 2 or greater was similar (AUROC = 0.72; 95% CI, 0.70-0.73).

In contrast, when they evaluated patients with suspected infection outside the ICU, discrimination of hospital mortality with SOFA (AUROC = 0.79; 95% CI, 0.78-0.80) or change in SOFA score (AUROC = 0.79; 95% CI, 0.78-0.79) was similar to that with SIRS (AUROC = 0.76; 95% CI, 0.75-0.77).

A change in SOFA of 2 or more points was designated to represent organ dysfunction. SOFA was preferred over Logistic Organ Dysfunction System as it is well conversant and simpler to use. Patients with presumed infection and a SOFA score of 2 or more had an overall mortality of 10%.

The multivariate logistic regression also identified that 2 of 3 clinical variables— Glasgow Coma Scale score of 13 or less, systolic blood pressure of 100 mm Hg or less, and respiratory rate 22/min or greater (Quick SOFA- qSOFA) offered predictive validity (AUROC = 0.81; 95% CI, 0.80-0.82) similar to that of the full SOFA score outside the ICU but lagged behind SOFA when analysed for patients in ICU (SOFA score had predictive validity (AUROC = 0.74; 95% CI, 0.73-0.76) superior to q SOFA(AUROC = 0.66; 95% CI, 0.64-0.68). The investigators proposed that “qSOFA” provides simple bedside criteria to identify adult patients with suspected infection who are likely to have poor outcomes.



New definition and criteria for sepsis and septic shock were proposed. Use of SIRS for diagnosis sepsis is not recommended. Severe sepsis definition is obsolete. The SOFA score was the most promising scoring system in ICU patients. A new bed side evaluation tool called “qSOFA” (Glasgow Coma Scale score of 13 or less, systolic blood pressure of 100 mm Hg or less, and respiratory rate 22/min or greater) was proposed as screen tool for patient at risk of sepsis and consequent deterioration.



  1. The study data did not involve low/ middle income countries. The aim should be to detect early and raise awareness in these left out countries
  2. qSOFA was only been validated retrospectively, based on data from the USA and Germany.
  3. With ongoing widespread use of survival sepsis campaign definition, the outcome in sepsis is encouraging and improving. It seems unwise to change our practices when the current practice is rewarding. It can be a setback for years of hard work that has yielded good results.
  4. SIRS concept is not helpful?? The supporting evidence cited is a recent study demonstrating that SIRS is absent in 1 of 8 patients with infection and organ dysfunction. This could be restated that 7 of 8 patients (87.9%) with life threatening organ dysfunction have SIRS, making SIRS a highly sensitive indicator for organ dysfunction.
  5. Limited use of SOFA score worldwide.


Take home message


  1. Putting the line between definition and objective criteria for sepsis and septic shock is encouraging. It will help to eliminate the selection bias in further clinical studies.
  2. Severe sepsis is eliminated in the definition, implication of which is not entirely clear.
  3. Though still to validated, “qSOFA” can be used as a screening tool for patients with infection in and out of ICU. Though patient not fitting to this cohort can have sepsis. The clinical judgment and use of SIRS criteria cannot be neglected any time.
  4. “qSOFA” can be thought of an added tool for early diagnosis but should be be replace the existing methodology for now.





DR Sananta K Dash


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