new definition of sepsis... sepsis 3

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Changing Definition of Sepsis- New Inroads

Dr Neisevilie NisaAll 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 sepsisSeptic shock= Sepsis induced hypotension persistent despite adequate fluid resuscitation

2001 Task Force (Sepsis-2)

Expanded the list of diagnostic criteriaNo other alternatives offered due to lack of evidenceDefinitions 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 ValiditySIRS 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 definitionsSepsis: 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:

Hospital mortality

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 rate22/min

Altered mentationGCS 2 mmol/L for predicting mortality in Septic ShockSensitivity = 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 resuscitationWith 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 aloneLower serum lactate level cutoff of 2 mmol/L vs 4 mmol/L as currently used in the SSC definitionsFewer patients will be diagnosed, but a more robust characterization More precise diagnosis Better epidemiological tracking

SummarySepsis: A life-threatening organ dysfunction caused by a dysregulated host response to infection.SOFA score 2 points = Organ DysfunctionSOFA score to evaluate sepsis in ICU settingsq 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 limitationsMost data extracted from US databasesq SOFA and SOFA can miss occult organ dysfunctionSpecific infections can cause local organ dysfunction without dysregulated systemic host response Non-availability of lactate measurements in resource poor settingsTask 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, 2015Bone 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.

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