Download - New definition of sepsis... sepsis 3
Changing Definition of Sepsis- New Inroads
Dr Neisevilie Nisa
All India Institute of Medical Sciences
Why sepsis again..?• Its magnitude on public health
• $20 billion of total US hospital cost 2011 (Torio et al)
• $2000 crore = Rs 1,33,944 crores
• 3.97 % of GDP 2013 = Rs 33,150 crore
• AIIMS budget = Rs 1,340 crore (2013-14)
The need to upgrade definitions…
“To know what distinguishes sepsis from an
uncomplicated infection”
“…. We need to differentiate a straight forward
infection from one that can cause organ
dysfunction or death…….”
Old definition and its limitation
1991 consensus conference (Sepsis-1)
• Introduced SIRS (Systemic Inflammatory
response syndrome)
• Sepsis complicated by organ dysfunction= severe
sepsis
• Septic shock= Sepsis induced hypotension
persistent despite adequate fluid resuscitation
2001 Task Force (Sepsis-2)
• Expanded the list of diagnostic criteria
• No other alternatives offered due to lack of
evidence
• Definitions have remained unchanged for more
than 2 decades
The validity of SIRS challenged…
• Are all infection sepsis…?
• Which kind of infection leads to sepsis…?
• Uncertain pathobiology
• No gold standard diagnostic test
• Poor Discriminant Validity
• Poor Concurrent Validity
• SIRS criteria have been used to diagnose sepsis for
more than 20 years.
• “SIRS no longer has any legs….. it sounded like a
good idea in 1992, but it has lost steam….”
Developing new definitions
• European Society of Intensive Care Medicine
• Society of Critical Care Medicine
“ Shift of focus from Inflamation to Organ
Dysfunction”
New definitions• Sepsis: A life-threatening organ dysfunction caused by a
dysregulated host response to infection.
• Septic shock: Sepsis in which underlying circulatory and
cellular/metabolic abnormalities are profound enough to
substantially increase mortality.
• Terms like severe sepsis/ septicemia removed
Criteria for new definitions
• SOFA score ≥ 2 points consequent to the infection.
• Baseline SOFA score is assumed to be zero
• SOFA score ≥ 2 overall mortality risk 10%
Evidence behind SOFA score
Two outcomes:
1) Hospital mortality
2) ICU stay of 3 days or longer
Consort diagram
ICU encounters (n=7932)
Non-ICU encounters (n=66522)
SOFA and LODS superior to SIRS with higher
Predictive Validity to represent organ dysfunction
Limitations of SOFA
• Cumbersome due to multiple variables
• Not well known outside ICU setting
• Variables and cutoff values were developed by
consensus
Quick SOFA( q SOFA) Seymor et al
Early Screening for Performance Improvement
Parameters Criteria
Respiratory rate ≥22/min
Altered mentation GCS <13
Systolic blood pressure ≤100mmHg
q SOFA ≥ 2 Predictive validity outside ICU setting = 81 %
Evidence of q SOFA• Poor man’s SOFA
• Quick and repeat bedside test
• No laboratory test required
– Outside ICU settings
– Emergency
– Wards
Predictive validity outside ICU setting = 81 %
Remarkable 3 vital signs model returning results with a
model that has multiple lab test (SOFA)
Changing definition of Septic Shock• First Consensus Definitions in 1991 and revisited
in 2001 Septic shock defined as a state of cardiovascular
dysfunction associated with infection and unexplained by
other causes
• No differentiation between Septic Shock and Cardiovascular Dysfunction
• To recognize the importance of Cellular Abnormalities
• Meta-analysis and systemic reviews from January 1, 1992- December 25,2015• 44 septic shock studies• 166,479 patients
Three variables identified
• Hypotension
• Elevated serum lactate level
• Sustained need for vasopressor therapy
Mortality significantly higher (p< .001) in patients with fluid resistant hypotension requiring vasopressors and hyperlactatemia (42.3 %)
‘VS’
Hyperlactatemia alone “or”
Fluid resistant hypotension requiring vasopressors
but Lactate level ≤ 2 mmol/L (30.1%)
Lactate > 2 mmol/L for predicting mortality in Septic Shock
Sensitivity = 82.5 %
Specificity = 22.4 %
New definition of Septic shock
• A clinical construct of sepsis with persisting
hypotension requiring vasopressors to maintain MAP
65mmHg and having a serum lactate level >2 mmol/L
(18mg/dL) despite adequate volume resuscitation
• With these criteria, hospital mortality is in excess of 40%
A subset of sepsis in which underlying circulatory and
cellular metabolism abnormalities are profound enough to
substantially increase mortality
How it differs from old definition..??
• Both serum lactate level and vasopressor-
dependent hypotension instead of either alone
• Lower serum lactate level cutoff of 2 mmol/L vs 4
mmol/L as currently used in the SSC definitions
• Fewer patients will be diagnosed, but a more robust
characterization
• More precise diagnosis
• Better epidemiological tracking
Summary
• Sepsis: A life-threatening organ dysfunction caused by a
dysregulated host response to infection.
• SOFA score ≥ 2 points = Organ Dysfunction
• SOFA score to evaluate sepsis in ICU settings
• q SOFA score to evaluate sepsis outside the ICU
• Septic shock: Sepsis in which underlying circulatory and
cellular/metabolic abnormalities are profound enough to
substantially increase mortality.
• Terms like severe sepsis/ septicemia removed
Operationalization of Clinical Criteria
Controversies and limitations• Most data extracted from US databases
• q SOFA and SOFA can miss occult organ dysfunction
• Specific infections can cause local organ dysfunction
without dysregulated systemic host response
• Non-availability of lactate measurements in resource
poor settings
• Task force focused on adult patients
Conclusion It took us more than 10 years to understand sepsis, now we
will have to change it all….
“…. Is it the final word in sepsis..?... Or the starting point of
discussion and additional research into this deadly
condition……”
Thank you
References • Torio CM, Andrews RM. National inpatient hospital costs: the most expensive conditions
by payer, 2011. Statistical Brief #160. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs.August 2013.Accessed October 31, 2015
• Bone RC, Balk RA, Cerra FB, et al. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med.1992;20(6):864-874.
• Levy MM, Fink MP, Marshall JC, et al;International Sepsis Definitions Conference. 2001
SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care
Med. 2003;29(4):530-538.• Seymour CW, Liu V, Iwashyna TJ, et al Assessment of clinical criteria for sepsis. JAMA. Doi:
10.1001/jama.2016.0288.• 13. Shankar-HariM, Phillips G, LevyML, et al Assessment of definition and clinical criteria
for septic shock. JAMA.doi:10.1001/jama.2016.0289• Singer M, Deutschman CS, Seymour CW, et al.The Third International Consensus
Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA.doi:10.1001/jama.2016.0287.