Sepsis Updates The Third International

Consensus ( 2016 ) Sepsis 3

Dr. Ashraf NadeemMD , Critical Care Medicine Head of ICUHafr Elbatin Central Hospital Saudi Arabia

The Rory story !!!An infection , unnoticed , turn Unstoppable

• In March 2012, Rory Staunton, a 12-year-old boy in Queens, New York, cut his arm playing basketball in school. The next day, his parents, worried about his fever and leg pain, took him to see his pediatrician and then, the day after, to the emergency department at Langone Medical Center. He was discharged with a diagnosis of an upset stomach and dehydration but died 3 days later from sepsis

Key Concepts of Sepsis

• Sepsis is the primary cause of death from infection, especially if not recognized and treated promptly. Its recognition mandates urgent attention.

• Sepsis is a syndrome shaped by pathogen factors and host factors (eg, sex, race and other genetic determinants, age, comorbidities, environment) with characteristics that evolve over time.

• What differentiates sepsis from infection is an aberrant or dysregulated host response and the presence of organ dysfunction.

Key Concepts of Sepsis

•Sepsis-induced organ dysfunction may be occult; therefore, its presence should be considered in any patient presenting with infection. Conversely, unrecognized infection may be the cause of new-onset organ dysfunction.

•Any unexplained organ dysfunction should thus raise the possibility of underlying infection.

Key Concepts of Sepsis

•The clinical and biological phenotype of sepsis can be modified by preexisting acute illness, long-standing comorbidities, medication, and interventions.

•Specific infections may result in local organ dysfunction without generating a dysregulated systemic host response.

Why Sepsis again !!

Why new definitions !!

Why new scoring system !!

Why Sepsis is revisited again !!!

•It is still an economic burden on public health ▫$ 20 billion of total US hospital cost 2011

(Torio et al)▫Saudi Arabia ???

•Sepsis is the leading cause of death in non-coronary care intensive care units, with a mortality rate between 30-50%

Why Sepsis is revisited again !!!

•From 2007 to 2009 , over 2,047,038 patients were admitted with a sepsis-related illness

▫54% are diagnosed in the ED▫34% on the hospital wards▫13% in the ICU

Hospitalization rates

Incidence and Cost

Why Sepsis again !!

Why new definitions !!

Why new scoring system !!

The old definitions

Why new definitions•Definitions of sepsis and septic shock

were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.

Why new definitions !!•To know what distinguishes sepsis from

uncomplicated infection as simple infection (which could simply controlled by rest and cup of hot tea!! ) SIRS criteria basically could be the same

“We need to differentiate a straightforward infection from one that can cause organ dysfunction or death”

The overlap SIRS, infection, sepsis and inflammation

Why Sepsis again !!

Why new definitions !!

Why new scoring system !!

The Validity of SIRS challenged •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 1990 , but it has lost steam…..”

•Poor concurrent Validity

SIRS Criteria •Two or more of:

▫Temperature >38°C or <36°C▫Heart rate >90/min▫Respiratory rate >20/min or PaCO2 <32

mm Hg (4.3 kPa)▫White blood cell count >12 000/mm3 or

<4000/mm3 or >10% immature bands

Bone et al.Crit Care Med. 1992;20(6):864-874.

Sequential [Sepsis-Related] Organ Failure Assessment Score

"We now have a scientifically based classification that will give the clinician at the bedside new and more effective ways to recognize the septic patient and the severely septic patient so as to afford the earliest possible intervention,"

Timothy Buchman, MD, from Emory University in Atlanta

The care in sepsis is focused on prompt recognition and early treatment. “Shift of focus from inflammation to Organ Dysfunction ”

Introduction

•This is one of the largest collaborative studies ever conducted in the field of critical care medicine. It is also one of the first studies of electronic health records in field of Intensive care.

Introduction•Focused primarily on patients in the

intensive care unit who were receiving antibiotics and fluid cultures, as those were the patients who were thought to be infected.

•The team analyzed 148,907 patients with suspected infection, and evaluated how well the existing and the new criteria predicted sepsis mortality in these patients.

The Process of Developing New Definitions

The co-chairs Drs Deutschman & Singer)

• A task force of 19 critical care, infectious disease, surgical, and pulmonary specialists in January 2014.

• The group engaged in iterative discussions via face-to-face meetings between January 2014 and January 2015

The process •Definitions and clinical criteria were

generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment).

Summary of Data Sets

Accrual of Encounters for Primary Cohort

What clinical criteria to study

New definitions ( the screening tool )•Patients with suspected infection who are

likely to have a prolonged ICU stay or to die in the hospital can be promptly identified at the bedside with qSOFA, ▫Respiratory rate ≥22/min▫Altered mentation▫Systolic blood pressure ≤ 100mmHg

The presence of at least two of these criteria strongly predicts the likelihood of poor outcome in out-of-ICU patients with clinical suspicion of sepsis.

New definitions •Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.

• NB:▫ The SIRS criteria have been removed▫It may present in simple, non-complicated infection,

or in response to non infectious-triggers (i.e. trauma, pancreatitis, post-cardiac arrest syndrome),

▫Or may even be absent in critically ill patients with obvious evidence of a life-threatening infection.

New definitions •Organ dysfunction can be identified as an

acute change in total SOFA score> 2 points consequent to the infection.

•A SOFA score > 2 reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection

•The baseline SOFA score can be assumed to be zero or in patients not known to have preexisting organ dysfunction.

New definitions •Septic shock is a subset of sepsis in which

underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.

▫ Clinical criteria identifying such condition include the need for vasopressors to obtain a MAP≥ 65mmHg and an increase in lactate concentration > 2 mmol/L, despite adequate fluid resuscitation.

Terms like Severe Sepsis/Septicemia has been removed

Organ Failure Check Best in the ICU, Quick Score Better Elsewhere

•In the old criteria for sepsis, the systemic inflammatory response syndrome score was a measure of respiratory rate, white blood cell count, heart rate, and fever.

•The sequential organ failure assessment score ( SOFA ) and the logistic organ dysfunction system score ( LODS ) are more recent criteria.

How well these existing scores for inflammation and organ dysfunction predicted mortality compared with the quick score…!!!

Analysis of electronic records•The receiver operating characteristic

curve (AUROC) has been assessed to predict the validity of the different scores.

•The quick score was a better predictor of hospital mortality for patients with suspected infection who were not in the ICU than for those in the ICU.

Predictive Validity for Death

Area Under the Receiver Operating Characteristic Curve and 95%Confidence Intervals for In-Hospital Mortality of Candidate Criteria(SIRS, SOFA, LODS, and qSOFA) Among Suspected Infection Encounters in the UPMC Validation Cohort (N = 74 454)

Which score to use !!•"The SOFA score found patients more

likely to be septic both in and out of the ICU. But it involves the use of many lab tests and is a bit complex.

•For patients not in the ICU, the performance of Quick SOFA score was similar to that of the sequential organ failure assessment score.

Recommendation

•Infection plus two or more sequential organ failure assessment points, and the use of quick sepsis-related organ failure assessment score as a prompt to identify patients likely to be septic early on,.

A Need for Sepsis Definitions for the Public and for Health Care Practitioners•A life-threatening condition that arises

when the body’s response to infection injures its own tissue.

•Finally, all these new definitions are recommended for coding and research purposes. 

Terminology and international classification of disease Coding

Recommended primary ICD codes

Sepsis Septic shock

Controversies and limitations•Most data extracted from US database •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

Operationalization of clinical Criteria identifying patients with sepsis & septic shock

Fostering future updates.•Despite the unavoidable limits affecting any

definition of syndromes that do not have any specific diagnostic clinical, imaging, laboratory or biochemical marker, this new classification includes the most recent deep understanding of sepsis biology and stresses the clinical relevance of organ dysfunction. In addition, similarly to software updates, the Sepsis-3 definition has been established with the aim of fostering future updates.

Conclusions

• Among ICU encounters with suspected infection, the predictive validity for in-hospital mortality of SOFA was not significantly different than the more complex LODS but was statistically greater than SIRS and qSOFA, supporting its use in clinical criteria for sepsis.

• Among encounters with suspected infection outside of the ICU, the predictive validity for in-hospital mortality of qSOFA was statistically greater than SOFA and SIRS, supporting its use as a prompt to consider possible sepsis.

Take Home Message

• New definitions of sepsis and septic shock are now available. These rely on the importance of recognizing when an adaptive and protective host response becomes maladaptive, impairing organ function.

• SIRS criteria may still guide clinicians toward identifying an ongoing infectious process, but ‘severe sepsis’ is no longer a part of the new classification.

• Hypotension and lactate level are key points underpinning the new septic shock criteria, as they reflect metabolic and cellular abnormalities characterizing the pathobiology of sepsis.

Finally “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 ”

Julie A. Jacob, MA JAMA. 2016;315(8):739-740. doi:10.1001/jama.2016.0736.

Thank you