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Updates in Sepsis 2016

Raymundo F. Resurreccion, MD
From the PCS-MMC 34th Post Grad Course on Surgical Infections
August 16 19, 2016

Objectives
Review key concepts in sepsis
Discuss new definitions in sepsis
Highlight changes in the sepsis diagnostic criteria
Summarize findings of recent EGDT trials and their
implications in sepsis resuscitation
Demonstrate the impact of sepsis pathway in local
clinical practice

Sepsis
Harmful systemic reaction to infection
Infectious etiology + response that results in
hypofunction of uninfected organs
Incomplete understanding of pathobiology

Sepsis: what do we know


Crude estimates Mortalit
y
Sepsis
22 240/100,000
30%
Severe sepsis 13 to 300/100,000
50%
Septic shock
11/100,000
80%

Sepsis: What do we know


Contributing factor in > 200,000 deaths per year in the
US
Annual cases > 750,000 (~3 per 1000 population)

Sepsis: what do we know


Age
Underlying
comorbidities
Concurrent injuries
Medications
Mechanical devices

Early activation
of both pro- and
anti-inflammatory
responses
Major
modifications in
non-immunologic
pathways

Massive inflammation leads to organ failure.

Organ failure occurs when vital organs stop working, causing nearly half of all
deaths in the ICU, but little can be done t treat or prevent it today.

Issues with the 1991 and 2001


definitions

Poor discriminant validity

Poor convergent validity

Variability with different


scoring systems

Variability with different


clinical variables

SIRS is an appropriate response to infection or any


other stimulus that activates inflammation

JAMA. 2016; 315 (8).801810.doi.10.1001/jama.2016.0287

Sepsis-3: Issues addressed


Increased understanding of sepsis pathobiology

More than just rampant inflammation


Key role of immunosuppression
Contribution of non-immune mechanisms
Possible adaptive nature of organ dysfunction-hibernation

Sepsis-3: Definition
Sepsis is a life-threatening organ dysfunction
caused by a dysregulated host response to infection

So sepsis now = the old severe sepsis

Sepsis-3: Definition
Sepsis is a life-threatening organ dysfunction
caused by a dysregulated host response to infection
As opposed to the
regulated host response
that characterizes the non-septic response to
infection

Sepsis-3 Consensus

SEPSIS

Sepsis-3 definition
Septic shock is a subset of sepsis in which
underlying circulatory, cellular, and metabolic
abnormalities re associated with a greater risk of
mortality than sepsis alone

Sepsis-3 consensus: clinical criteria


No current clinical measure reflect the concept of a
dysregulated host response
Bedside examination + routine laboratory test results
indicative of inflammation or organ dysfunction

Task force decisions


1. Sepsis is not simply infection + two or more SIRS
criteria
2. The host response is of key importance
3. Sepsis represents bad infection where bad = infection
leading to organ dysfunction
4. Severe sepsis is not helpful and should be
eliminated

Who is septic?

How to define really sick?

There is no gold standard for sepsis

Really sick is a proxy

More common among infected patients who are septic than


those who are not

How to define really sick?

Clinical review committees

Death in the hospital

Prolonged stay in the ICU

Discharge diagnosis of sepsis

Positive microbiological cultures

Assessment of clinical criteria:


qSOFA
2 or 3 qSOFA points accounted for 70% of deaths or ICU
stays of >/+ 3 days
Predictive validity (AUROC= 0.81; 95% CI, 0.80-0.82)
similar to full SOFA score outside the ICU

Should prompt:

Further investigation for


organ dysfunction
Initiation or escalation of
therapy
Referral to critical care
Increase frequency in
monitoring

EGDT: landmark study


Timeframe
Setting
Population
Treatment
Control
Outcome

Rivers
March 1997 March 2000
Single-center
Adult with SIRS + SBP < 90 after fluid challenge OR
lactate > 4
EGDT x >/= 6 hours
Standard care
60-day in-hospital mortality

Protocoliz
ed
Managem
ent in
Sepsis
(ProMISe)
(April
2015)

Protocoliz
ed Care
for Early
Septic
Shock
(ProCESS)
(May
2014)
Resuscita
tion in
Sepsis
Evaluatio
n (ARISE)

In patients with septic shock who were identified early and


received intravenous antibiotics and adequate fluid resuscitation,
hemodynamic management according to a strict EGDT protocol did
not lead to an improvement in outcome.

In a multicenter trial conducted in the tertiary


care setting, protocol-based resuscitation of
patients in whom septic shock was diagnosed in
the emergency department did not improve
outcomes.

In critically ill patients presenting to the


emergency department with early septic shock,
EGDT did not reduce all-cause mortality at 90
days.

Is EGDT obsolete?
Conclusion:
In-hospital survival with usual care = EGDT
Continuous ScvO2 monitoring and strict protocolization do not
improve outcomes

The usual care comparator in theses trials are of high


quality
Front-end interventions, specifically antibiotics and
intravenous fluids, perhaps contributed most to the
survival rates observed.

Updated Bundles in
Response to New Evidence
With publication of 3 trials (2, 3, 4) that do not demonstrate
superiority of required use of a central venous catheter (CVC) to
monitor central venous pressure (CVP) and central venous oxygen
saturation (ScvO2) in all patients with septic shock who have
received timely antibiotics and fluid resuscitation compared with
controls or in all patients with lactate > 4 mmol/L, the SSC
Executive Committee has revised the improvement bundles as
follows:
To be completed within 3 hours of time of presentation:

Measure lactate level


Obtain blood cultures prior to administration of antibiotics
Administer broad spectrum antibiotics
Administer 30 ml/kg crystalloid for hypotension or lactate >/= 4 mmol/L

* Time of presentation is defined as the time of triage in the emergency department or, if presenting from another care venue, from the earliest
chart annotation consistent with all elements of severe sepsis or septic shock entertained through chart review.

Updated Bundles in
Response to New Evidence
With publication of 3 trials (2, 3, 4) that do not demonstrate
superiority of required use of a central venous catheter (CVC) to
monitor central venous pressure (CVP) and central venous oxygen
saturation (ScvO2) in all patients with septic shock who have received
timely antibiotics and fluid resuscitation compared with controls or in
all patients with lactate > 4 mmol/L, the SSC Executive Committee
has revised the improvement bundles as follows:
To be completed within 6 hours of time of presentation:
Apply vasopressors (for hypotension that does not respond to initial fluid
resuscitation) to maintain a mean arterial pressure (MAP) >/= 65 mmHg
In the event of persistent hypotension after initial fluid resuscitation (MAP < 65
mmHg) or if initial lactate was >/= 4 mmol/L, re-assess volume status and tissue
perfusion and document findings according to Table 1.
Re-measure lactate if initial lactate elevated.

When should you suspect sepsis?


Think: could this be sepsis?
If a person presents with signs or symptoms that
indicate possible infection
Take into account that people with sepsis may have nonspecific, non-localized presentations
Feeling very unwell
May not have a high temperature

Pay particular attention to concerns expressed by the


person and their family or caregivers
Changes from usual behavior

International
Guidelines for
Management of
Severe Sepsis and
Septic Shock: 2012

Fluid therapy
Initial fluid challenge in
sepsis-induced
hypoperfusion with
hypovolemia to achieve a
minimum of 30 ml/kg of
crystalloid [1C]
More rapid administration
and greater amounts of
fluid may be needed in
some patients [1C]

Diagnosis
Obtain appropriate cultures before starting antibiotics.
[1C]
Perform imaging studies promptly in order to confirm
and sample any source of infection. [UG]

Antibiotic therapy
Administer IV antibiotics within the first hour of
recognizing severe shock [1B] and severe sepsis without
shock [1C].
Broad spectrum: one or more agents active against
likely bacterial/fungal pathogens, and with good
penetration into presumed source.[1B]

Source control
A specific anatomical diagnosis of infection should be
established as rapidly as possible. [1C]
Formally evaluate patient for a focus of infection
amenable to emergent source control measures [1C]
Undertake intervention for source control within the first
12 hours after diagnosis is made, if feasible. [1C]

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.

Key concepts of sepsis


Sepsis is a syndrome shaped by pathogen factors and
host factors 9eg. Sex, race, and other genetic
determinants, 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.
An 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 pre-existing acute illness, long-standing comorbidities, medication and interventions.
Specific infections may result in local organ dysfunction
without generating a dysregulated systemic host
response.

Fundamental principles of sepsis


management
1. Early recognition
2. Control of the source of infection
3. Appropriate and timely administration of antibiotics
4. Resuscitation with intravenous fluids and vasoactive
drugs

qSOFA implications
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 (HAT)
Hypotension: SBP less than or equal to 100 mmHg
Altered mental status (any GCS less than 15)
Tachypnea: RR >/= 22

References
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GJ, Angus DC. 2016. Assessment of clinical criteria for sepsis for the Third International Consensus Definitions for Sepsis and Septic
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(16): 1496-1506
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Thank you!