Sepsis 2016

Management
Compiled by Hul, SpAn

Sepsis
A dysregulated immune response to
infection
Local inflammation
Vasodilation, capillary leak
Systemic inflammation
SIRS

Hyperinflammatory response
Sepsis 1
Control inflammation improve outcome
Multiple studies

Steroids
Anti- TNF
Anti-IL1
Anti-IL6
Other monoclonal antibodies

At best no improvement
Often increased mortality

NEJM

Factors
Micro-organism
Virulence
Innoculation dose
Multi-drug resistance

Host
Genetic polymorphisms
Co-morbidities
Age
Chronic health status
Immuno-modulatory medications

Systemic Inflammatory Response

Syndrome (SIRS) (before 2015)

Two or more of the following:

Temperature > 38 o C or < 36 o C [>
100.4 o F or < 96.8 o F]
Heart Rate > 90 beats/min
Respiratory Rate > 20 or PaCo2 < 32
WBC > 12,000 or < 4,000

Sepsis and Severe Sepsis

SEPSIS
Known or
suspected
infection
2 or more SIRS
criteria

SEVERE SEPSIS
Sepsis plus one
or more organ
dysfunction

PATHOPHYSIOLOGY

Septic Shock
Severe sepsis with
hypotension unresponsive to
fluid resuscitation

Shapiro et al, 2014 Rosens Emergency

Medicine

Multi Organ Dysfunction Syndrome

(MODS)
Homeostasis can not be maintained
Altered organ function
Cardiovascular
Respiratory
Urinary
Hepatic
CNS
Hematological

Dysregulated?
Multi-organ dysfunction then failure
Micro necrosis

Apoptosis of the cellular immune system

Anti-inflammatory phase immunoparalysis
D4 persistent lymphopenia
Stimulate immune system improve outcome

UNDERSTANDING OF
SEPSIS PATHOPHYSIOLOGY
Sepsi
s

Coagulation

Fibrinolysis

Endotheli
al Injury

Organ

Dysfunction

Orga

Inflammation

How do we recognize the

patient?

IDENTIFYING ACUTE ORGAN

DYSFUNCTION AS A MARKER
Altered
OF SEVERE SEPSIS Tachycardi
Consciou
sness
Confusio
n
Psychosi
Tachypnea
PaOs 70
2

mm Hg
SaO2 <
90%
Jaundice

Enzymes

Albumin
PT

a
Hypotensio
n
CVP

Oliguria
Anuria

Creatinine

Platelets
PT/APTT
Protein C
D-dimer

Physiologic Response to
Sepsis
Poor tissue
oxygenation is the
core problem in
sepsis.
TIME IS TISSUE
Rapid Treatment:
Start BEFORE
arrival!

Shock
Inadequate Tissue Perfusion
Cardiovascular system fails
Alteration
Blood volume
Myocardial contractility
Blood flow
Vascular resistance

Stages of Shock
Stage I: Initiation
Hypoperfusion: inadequate delivery or
extraction of oxygen
No obvious clinical signs
May be noticed if invasive
hemodynamic monitoring in place
Early, reversible

Stages of Shock
Stage II:
Compensatory

Endocrine compensation

Sustained reduction in tissue perfusion

Initiation of compensatory mechanisms

Neural: baroreceptors and chmeoreceptors

Endocrine: ACTH and ADH
Chemical
Low oxygen tension
Hyperventilation and respiratory alkalosis

Neural Compensation

Baroreceptors : Sensitive to pressure changes

Chemoreceptors :Sensitive to chemical changes
Stimulation of the sympathetic nervous system
Increased heart rate
Increased contractility
Vasodilation of coronary arteries
Systemic vasoconstrictions
Shunting
Increased respiratory rate and depth

Response to low blood pressure Stimulates

anterior and posterior pituitary gland

Anterior pituitary
Aldosterone
Glycogenolysis/gluconeogensis
Stimulation of renin-angiotensin
response

Posterior pituitary
Antidiuretic hormone

Provides body with glucose

Increases intravascular blood volume

Chemical Compensation

Ventilation-perfusion imbalances

Chemoreceptors in aorta and carotids

React to low oxygen tension
Respiratory rate and depth increase
Patient hyperventilates Respiratory
alkalosis occurs
Cause vasoconstriction of cerebral blood
vesselsAttempt to increase oxygen supply
Negative effects on cerebral perfusion

Stages of Shock
Stage III: Progressive
Increased capillary hydrostatic pressure
Intravascular fluid shifts
Interstitial edema
Decreased circulating intravascular volume

Decreased coronary perfusion

MDF released
Decreased myocardial contractility

Stages of Shock
Stage IV: Refractory
Prolonged inadequate tissue
perfusion
Unresponsive to therapy
Contributes to multiple organ
dysfunction

Definition Changes in
2016
A task force of 19 leaders in the field of sepsis was convened
by SCCM and the European Society of Intensive Care
Medicine (ESICM)
Changes categories to sepsis and septic shock
The new diagnostic tool for sepsis : quickSOFA qSOFA, 2 of
3 indicators below
An alteration in mental status
A decrease in systolic blood pressure of less than 100
mm Hg
A respiration rate greater than 22 breaths/min

Septic Shock Definitions

Persisting hypotension requiring vasopressors to maintain MAP
65 mm Hg
Blood lactate >2 mmol/L despite adequate volume resuscitation

Singer M, Deutschman CS, Seymour C, et al. The Third

International Consensus Definitions for Sepsis and Septic
Shock (Sepsis-3).JAMA.2016;315(8):801-810.
doi:10.1001/jama.2016.0287

Definition Changes in 2016

Concerns with Definition Changes
Later diagnosis
Based decisions on retrospective review of
data
Consensus was of 2 organizations
Using the new definitions the denominator of
hospital cases with expected mortality
decreases (sepsis terminology would be used
instead of severe sepsis or septic shock).
This gives the potential appearance that the
organization is treating pateints poorly as the
observed mortality is high in comparison.

Sepsis-3: A life threatening organ

dysfunction caused by a dysregulated host
response to infection

qSOFA

RR> 22, Altered Mental status, SBP <100

1o outcome: increased specificity in predicting
Mortality > 10%; ICU LOS > 3 days

SOFA score

Respiration: PaO2/FiO2 or SaO2/FiO2

Coagulation: Platelets
Liver: Bilirubin
Cardiovascular: Hypotension or vasopressor
CNS: GCS
Renal: Creatinine or urinary output

SOFA Score
RESPIRATORY

CARDIO VASCULAR

PaO2/FiO2 (mmHg)

SOFA score

<400
<300

1
2

<200andmechanically
ventilated

<100andmechanically
ventilated

Mean arterial pressure OR administration of

vasopressors required
MAP<70mm/Hg
dop5ordob(anydose)
dop>5ORepi;0.1ORnor0.1
dop>15ORepi>0.1ORnor>0.1
(vasopressor drug doses are in
g/kg/min)

SOFA score
1
2
3
4

COAGULATION

NERVOUS SYSTEM
Glasgow coma scale
1314

SOFA score
1

1012
69
<6

2
3
4

LIVER SYSTEM

Platelets103/l
<150

SOFA score
1

<100
<50

2
3

<20

KIDNEY SYSTEM

Bilirubin (mg/dl) [mol/L]

1.21.9[>20-32]

SOFA score
1

Creatinine (mg/dl) [mol/L] (or

urine output)

SOFA score

2.05.9[33-101]
6.011.9[102-204]

2
3

1.21.9[110-170]
2.03.4[171-299]

1
2

>12.0[>204]

3.54.9[300-440](or<500ml/d)
>5.0[>440](or<200ml/d)

3
4

Diagnostic criteria for sepsis

SIRS

Sepsis

Infectious &
non
infectious
causes
Clinical
response
arising from
a non
specific
insult

SIRS plus
Presume
d or
confirmed
infection

Severe
Sepsis

Septic
Shock

Sepsis plus
Sepsisinduced
organ
dysfunction
or tissue
hypoperfusio
n

Sepsisinduced hypoperfusion or
hypotension
persisting
despite 30
mls/kg fluid
rescusitation

Sources of sepsis

Respiratory
Urinary tract
Intra-abdominal
CRBSI
Device
CNS
Others

38%
21%
16.5%
2.3%
1.3%
0.8%
11.3%

Pathway of care

Rapid Recognition
Rapid Initiation of Treatment
3 Hour Bundle
6 Hour Bundle
Reassessment parameters
Critical Monitoring and Targeted Therapies

TREATMENT INITIATION
3 hour bundle
1.
2.
3.

1 2
4
3

4.

Serum lactate measured

Blood culture obtained
prior to antibiotics
Broad-spectrum
antibiotics within 3 hour
of presentation to the
ED, or within 1 hour in
currently hospitalized
patients
Deliver an initial
minimum of 30 ml/kg of
crystalloid if
hypotensive or elevated
lactate > 4 mmol/L

How much can we push?

Sepsis Kit
Blood Cultures
2 grams Ceftriaxone
IVF Administration

Therapy initiated if sepsis

suspected by the physician in the
ambulance/helicopter
Median time to IVF/ABX: 19 min
(18-24)
Median transport time: 56 min (4667)
Sepsis Diagnosis confirmed in
87.5%
46.4% Severe Sepsis/Septic Shock

Correct ABX: 69%

Median IVF Prior to ED: 2.5 L (1.5-3)

6 Hour Bundle

1.
2.
3.

Vasopressors for MAP less than 65 mmHg after fluid resuscitation

Reassess volume status and tissues perfusion if persistent
hypotension (MAP < 65) after initial fluid resuscitation or lactate > 4
mmol/L
Remeasure lactate if initial level elevated

Fluid balance
Initial aggressive fluid resuscitation is gold
standard
Prospective study to determine if fluid
balance had an impact on mortality rate in
patients with severe sepsis or septic shock
Daily and accumulated fluid balance at 24,
48, 72 and 96 hours with 28-day mortality
Non-survivors demonstrated higher
accumulated positive fluid balance at 48, 72
and 96 hours
Higher SOFA scores in the non-survivor
group

Give 3

Take 3

1.OXYGEN: Titrate O2 to
1. CULTURES: Take blood
saturations of 94 -98% or 92% in cultures before giving
antimicrobials (if no significant
chronic lung disease.
delay i.e. >45 minutes) and
consider source control.
2. FLUIDS: Start IV fluid
resuscitation if evidence of
hypovolaemia. 500ml bolus of
isotonic crystalloid over 15mins
& give up to 30ml/kg,
reassessing for signs of
hypovolaemia, euvolaemia, or
fluid overload.

2.BLOODS: Check point of care

lactate & full blood count.Other
tests and investigations as per
history and examination.

3. ANTIMICROBIALS: Give IV
3. URINE OUTPUT: Assess
antimicrobials according to local urine output and consider
antimicrobial guidelines.
urinary catheterisation for
accurate measurement in

Fluid resuscitation and

Mortality

Figure 3. Mean hospital mortality among patients with decreased lactate within 8 hours of index test, stratified by total fluid received in increments of
7.5 ml/kg based on medication administration record.
Annals ATS, 2013
http://www.atsjournals.org/doi/abs/10.1513/AnnalsATS.201304-099OC

Summary
Rapid early recognition- at home, in the clinic, in
the ED or on the inpatient unit q SOFA, SOFA
Early screening: lactate, SIRS
Early source identification (source cultures) and
management (IV abx, broad spectrum, source
control)
Rapid IV fluids (30mL/kg IVF bolus challenge)
Vasopressors/Intubation/Critical Care
management for persistent shock
Family/Patient Education for at risk conditions