jama. 2016;315(8):801-810. doi:10.1001/jama.2016 7/01... · 2018-01-19 · septic shock definition...
TRANSCRIPT
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