How is Sepsis Defined?

Although sepsis was described over 2,000

years ago, clinicians still struggle to define it,
and there is no 'gold standard.'

http://journals.lww.com/ccmjournal/Abstract/2016/03000 A_Framework_for_the_Development_and_Interpretation.35.aspx

• http://www.qsofa.org
  A conceptual framework for how one might approach
defining sepsis is described by Angus and colleagues

 The proposed framework intends to aid in the

understanding of the multiple current sepsis
definitions and guide the development of useful
criteria that may serve different purposes

Derek C. Angus, M.D., M.P.H.

• http://www.qsofa.org
 sepsis has been defined for clinical care
several time

1991

https://www.ncbi.nlm.nih.gov/pubmed/1303622

2001

https://www.ncbi.nlm.nih.gov/pubmed/12682500

2016

http://jamanetwork.com/journals/jama/fullarticle/2492875

• http://www.qsofa.org
 Most recently, the 2016 Third International Consensus Definitions
for Sepsis and Septic Shock defined sepsis as:

A life-threatening organ dysfunction due to a dysregulated

host response to infection.

This is similiar to the lay definition of sepsis derived at the

Merinoff Symposium in 2010

Sepsis is a life threatening condition that arises when the

body's response to an infection injures its own tissues and
organs

• Singer, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
JAMA February 23, 2016 Volume 315, Number 8
• http://www.qsofa.org
 SIRS (Systemic Inflammatory Response Syndrome)

 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 >12000/mm3 or

<4000/mm3 or >10% immature bands

• Singer, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
JAMA February 23, 2016 Volume 315, Number 8
 Key Concepts of Sepsis

 Sepsis-induced organ dysfunction may be occult

 Conversely, unrecognized infection may be the
cause of new-onset organ dysfunction.
 Any unexplained organ dysfunction should thus
raise the possibility of underlying infection.
 The clinical and biological phenotype of sepsis
 Specific infections may result in local organ
dysfunction without generating a dysregulated
systemic host response.

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 Key Concepts of Sepsis

 Organ dysfunction can be identified as an

acute change in total SOFA score >2 points
consequent to the infection.
 The baseline SOFA score can be assumed
to be zero in patients not known to have
preexisting organ dysfunction.
 A SOFA score >2 reflects an overall
mortality risk of approximately 10% in a
general hospital population with suspected
infection.
• Singer, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
JAMA February 23, 2016 Volume 315, Number 8
What is SOFA & qSOFA
  For clinical operationalization, organ dysfunction can
be represented by an increase in the Sequential
[Sepsis-related] Organ Failure Assessment (SOFA)

 adult patients with suspected infection can be rapidly

identified as being more likely to have poor outcomes
typical of sepsis if they have at least 2 of the following
clinical criteria that together constitute a new bedside
clinical score termed quickSOFA (qSOFA)

• Singer, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).
JAMA February 23, 2016 Volume 315, Number 8
 http://jamanetwork.com/journals/jama/fullarticle/2492881

• http://www.qsofa.org
  The diagnosis of infection was left to the clinician,
while the TF recommended that an acute change
of more than 2 sepsis-related organ dysfunction
assessment (SOFA) points would identify sepsis.

 SOFA score requires multiple laboratory tests and

may not be available in a timely manner.

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  Seymour and colleagues tested the construct and
criterion validity of qSOFA compared to other criteria
like the SOFA score, change in SOFA score,
logisticorgan dysfunction score (LODS), and systemic
inflammatory response syndrome (SIRS) criteria near
the onset of infection.

 They found that mortality increased among patients

with suspected infection with each point.

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 What about lactate?
 Lactate is a well-studied prognostic marker in patients with sepsis.
 During statistical model building, lactate was excluded from qSOFA.
 Seymour and colleagues tested how serum lactate would improve
qSOFA post hoc, using a variety of serum lactate thresholds.
 They found that the criterion validity was statistically improved
(p<0.01) comparing qSOFA plus lactate versus qSOFA alone, but
actual changes in classification were minimal.
 More work is forthcoming to test how lactate can substitute for or
improve qSOFA in centers where testing is both affordable and
available.

http://jamanetwork.com/journals/jama/article-abstract/2089333
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SOFA
SOFA Score
score
  To facilitate simple recognition in
prehospital, ward, and the emergency
department, the Task Force recommended
a prompt called "qSOFA" for quick sepsis-
related organ dysfunction assessment
score

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 qSOFA
Altered mentation

Respiratory rate 22/min

Systolic blood pressure 100 mm Hg

• http://www.qsofa.org
  They found that 24% of infected patients with 2 or 3 qSOFA
points accounted for 70% of deaths.
 Outside the ICU, there was a 3- to 14-fold increase in the
rate of in-hospital mortality across a range of baseline risk
comparing those with ≥2 vs. <2 qSOFA points (where
baseline risk determined by demographics and co-morbidity).
 The simple qSOFA model performed similarly to more
complex models like SOFA or LODS outside the ICU.

• http://www.qsofa.org
Qsofa Calculator
Is the patient in the ICU? Yes No
Altered Mentation Yes No
Respiratory rate (breaths per minute) (0 to 60)
Systolic blood pressure (mmHg) qSOFA Calculat
(0 to 300) or

Submit

Is the patient in the ICU? No

Altered Mentation No
Respiratory rate (breaths per minute) 32
Systolic blood pressure (mmHg) 90

Tot al Scor e 2
‹ 2. How is qSOFA defined?

Your patient with suspected infection not in the intensiv e care unit has a 6% r isk of a bad outcome.
This is a prompt to consider that sepsis is likely
likely.

http://www.qsofa.org/calc.php
‹ 2. How is qSOFA defined?
Qsofa Calculator mobile app
Qsofa Calculator mobile app
 Managing Infection

 Antibiotics: Administer broad-spectrum intravenous

antimicrobials for all likely pathogens within 1 hour after
sepsis recognition (strong recommendation; moderate
quality of evidence
 •Source control: Obtain anatomic source control as rapidly
as is practical (best practice statement [BPS]).
 •Antibiotic stewardship: Assess patients daily for
deescalation of antimicrobials; narrow therapy based on
cultures and/or clinical improvement

• Howell, MD, Davis, M. Management of Sepsis and Septic Shock. JAMA Published online January 19, 2017
 Managing Resuscitation
 Fluids: For patients with sepsis-induced hypoperfusion, provide 30
mL/kg of intravenous crystalloid within 3 hours (strong
recommendation; low QOE) with additional fluid based on frequent
reassessment (BPS), preferentially using dynamic variables to
assess fluid responsiveness

 Resuscitation targets: For patients with septic shock requiring

vasopressors, target a mean arterial pressure (MAP) 65 mmHg
(strong recommendation; moderate QOE).

 • Vasopressors: Use norepinephrine as a first-choice vasopressor

(strong recommendation; moderate QOE)

• Howell, MD, Davis, M. Management of Sepsis and Septic Shock. JAMA Published online January 19, 2017
 Mechanical ventilation in patients with sepsis-
related ARDS:

 Target a tidal volume of 6 mL/kg of predicted body

weight (strong recommendation; high QOE) and a
plateau pressure of 30 cm H2O (strong
recommendation; moderate QOE).

• Howell, MD, Davis, M. Management of Sepsis and Septic Shock. JAMA Published online January 19, 2017
 Formal improvement programs

 Hospitals and health systems should implement

programs to improve sepsis care that include sepsis
screening (BPS)

• Howell, MD, Davis, M. Management of Sepsis and Septic Shock. JAMA Published online January 19, 2017
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