JAMA. 2016;315(8): doi: /jama

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2 JAMA. 2016;315(8): doi: /jama

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11 SEPSIS 3 life-threatening organ dysfunction caused by a dysregulated host response to infection organ dysfunction: an increase in the SOFA score of 2 points or more associated with an in-hospital mortality greater than 10%

12 SOFA SCORE Vincent et al Intensive Care Med 1996;22:707-10

13 SOFA SCORE AND MORTALITY Vincent et al Intensive Care Med 1996;22:707-10

14 KEY CONCEPTS OF SEPSIS

15 KEY CONCEPTS OF SEPSIS primary cause of death from infection syndrome shaped by pathogen and host factors characteristics evolve over time differs from infection: aberrant/dysregulated host response organ dysfunction organ dysfunction may be occult infection may go unrecognized preexisting acute illness, comorbidities, medications, and interventions may modify clinical presentation («phenotype») specific infections may cause local organ dysfunction without sepsis (dysregulated host response)

16 EARLY ACTIVATION OF BOTH PRO- AND ANTI-INFLAMMATORY RESPONSES vs PROGRESSIVE SYSTEMIC INFLAMMATORY RESPONSE

17 SEPSIS DEFINITION FOR LAY PUBLIC sepsis is a life-threatening condition that arises when the body s response to infection injures its own tissues

18 SEPTIC SHOCK DEFINITION

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20 MULTIPLE SEPTIC SHOCK DEFINITIONS heterogeneity in outcomes due to varying cutoffs for systolic or mean blood pressure diverse levels of hyperlactatemia vasopressor use concurrent new organ dysfunction defined fluid resuscitation volume/target the data source and coding methods enrollment dates

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22 SEPTIC SHOCK DEFINITION (3): three sets of studies a systematic review and meta-analysis observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; a Delphi study to achieve consensus on a new septic shock definition and clinical criteria 3 surveys and discussions of results from the systematic review, surveys, and cohort studies cohort studies to test variables identified by the Delphi process Surviving Sepsis Campaign (SSC) ( ; n=28 150) University of Pittsburgh Medical Center (UPMC) ( ; n= ) and Kaiser Permanente Northern California (KPNC) ( ; n= ) electronic health record (EHR) data sets

23 SEPTIC SHOCK DEFINITION (3): cohort studies Surviving Sepsis Campaign (SSC) ( ; n=28 150) adequate fluid resuscitation as judged by the collecting sites, 2 or more systemic inflammatory response syndrome criteria 1 or more organ dysfunction criteria lactate: in 84% of patients (in 71% within first 6 hrs), 67% included electronic health record (EHR) data sets hypotension, highest serum lactate level, and vasopressor therapy as a binary variable [yes/no]) during the 24-hour period after infection was suspected hypotension: systolic blood pressure was 100mmHg or less for any single measurement during the 24-hour period after infection was suspected lactate: in 9% of infected patients at UPMC and in 57% at KPNC.

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25 SEPTIC SHOCK (3) a subset of sepsis: particularly profound circulatory, cellular, and metabolic abnormalities, associated with a greater risk of mortality vasopressors to maintain a mean arterial pressure >65mmHg serum lactate >2 mmol/l in the absence of hypovolemia associated with hospital mortality rates greater than 40%

26 SEPTIC SHOCK DEFINITION (3) «hypotension» «need for vasopressor therapy» «adequate fluid resuscitation» «elevated blood lactate»

27 SEPTIC SHOCK DEFINITION (3) clinical criteria for septic shock : hypotension and hyperlactatemia in combination rather than either alone encompasses both cellular dysfunction and cardiovascular compromise associated with higher risk-adjusted mortality approved by a majority (13/18) of voting members

28 SEPTIC SHOCK DEFINITION (3) Delphi process and voting by 17 experts «hypotension» MAP <65mmHg (14/17 agreed) «need for vasopressor therapy» could not be explicitly specified «adequate fluid resuscitation» could not be explicitly specified «elevated blood lactate» (11/17 agreed) > 2 mmol/l tested in combination with «fluid resistant hypotension requiring vasopressors»

29 agree neither disagree

30 agree neither disagree

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32 OPEN QUESTIONS/ MAJOR CONTROVERSIES «need for vasopressors» definition of blood pressure targets «adequate fluid resuscitation»

33 «On page 1647, under the definition of "septic shock," the phrase "despite adequate fluid resuscitation" is used without any qualification...» correspondence in CHEST from 1992

34 WHY ARE THESE QUESTIONS IMPORTANT? interventions to achieve the desired blood pressure may influence outcome vasopressor load fluid load fluid resuscitation strategy may influence outcome association of positive fluid balance with increased risk of death «need for vasopressors» and «adequate fluid resuscitation» context and interpretation highly variable effects unknown

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36 identification of patients with infection evaluation of 4 different severity scores for construct validity and outcome prediction (sepsis vs uncomplicated infection)

37 qsofa: assessment of organ dysfunction outside the ICU risk of poor outcome in patients with suspected infection and any 2 of GCS<15 systolic blood pressure < 100 mmhg respiratory rate > 22 breaths/min (multivariable logistic regression modeling; GCS<14 in original model) prompt to search organ dysfunction and/or infection

38 WORSENING ORGAN FUNCTION IN PATIENTS WITH SUSPECTED INFECTION IS AN EARLY WARNING FOR RISK OF DEATH

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