JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287

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%

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

SOFA SCORE

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

KEY CONCEPTS OF SEPSIS

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)

EARLY ACTIVATION OF BOTH PRO- AND ANTI-INFLAMMATORY RESPONSES

vs

PROGRESSIVE SYSTEMIC INFLAMMATORY RESPONSE

SEPSIS DEFINITION FOR LAY PUBLIC

“sepsis is a life-threatening condition that arises when the

body’s response to infection injures its own tissues”

SEPTIC SHOCK DEFINITION

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

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) (2005-2010; n=28 150)

University of Pittsburgh Medical Center (UPMC) (2010-2012; n=1 309 025)

and Kaiser Permanente Northern California (KPNC) (2009-2013; n=1 847

165) electronic health record (EHR) data sets

SEPTIC SHOCK DEFINITION (3): cohort studies

• Surviving Sepsis Campaign (SSC) (2005-2010; 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.

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%

SEPTIC SHOCK DEFINITION (3)

• «hypotension»

• «need for vasopressor therapy»

• «adequate fluid resuscitation»

• «elevated blood lactate»

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

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»

agree disagree neither

agree disagree neither

OPEN QUESTIONS/ MAJOR CONTROVERSIES

• «need for vasopressors»

definition of blood pressure targets

• «adequate fluid resuscitation»

«…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

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

identification of patients with infection

evaluation of 4 different severity scores for construct validity and

outcome prediction (sepsis vs uncomplicated infection)

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

WORSENING ORGAN FUNCTION IN

PATIENTS WITH SUSPECTED INFECTION

IS AN EARLY WARNING FOR RISK OF DEATH