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SEPSIS

Sepsis : Definition
Sepsis = SIRS + source of infection
SIRS is defined as two or more of the following
variables:
HR > 90 beats per minute
Temperature < 36C or > 38C
Tachypnea > 20 breaths per minute or PaCO2
< 32 mmHg
WBC < 4,000 or > 12,000 cells/mm3 or 10 %
immature neutrophils (Bands)

Sepsisinducedhypotension=systolicbloodpressure(SBP)
<90mmHgormeanarterialpressure(MAP)<70mmHg
oraSBPdecrease>40mmHgorlessthantwostandard
deviationsbelownormalforageintheabsenceofother
causesofhypotension

Surviving Sepsis
Severe sepsis and septic shock - leading causes
of death among hospitalized patients ~ kills one
in four
Mortality rates attributed to severe sepsis and
septic shock are estimated at 25% or greater
EGDT publication resulted in a 10-12% drop in
mortality has been seen nationally over the last
decade
Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe
sepsis in the United States: analysis of incidence, outcome, and associated
costs of care. Crit Care Med. 2001;29:13031310.

TO BE COMPLETED WITHIN 3 HOURS:

1) Measure lactate level


2) Obtain blood cultures prior to administration of antibiotics
3) Administer broad spectrum antibiotics
4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L

Goals during the first 6 hrs

Why measure lactate?


Diagnose severe sepsis with elevated
lactate as a diagnosis of tissue
hypoperfusion
Trigger for quantitative resuscitation if
lactate is 4 mg/dL or more

Lactic Acid Can be Tricky...


during states of low perfusion when there is
cellular metabolic failure
> 2 = severe sepsis; > 4 = tissue hypoxia
Can be mildly elevated by other conditions:
Cirrhosis,lymphoma,renal failure, ketosis, short
gut syndrome, metformin, nitroprusside,
retrovirals

Blood Cultures

Diagnosis
Recommend at least two blood cultures be obtained before antimicrobial
therapy is administered , volume >10ml
As long as such cultures do not cause significant delay (>45 minutes) in
antimicrobial administration,
With at least one drawn percutaneously and one drawn through each vascular
access device, unless the device was recently (<48 hr.) inserted
Cultures of other sites (preferably quantitative where appropriate), such as
urine, cerebrospinal fluid, wounds, respiratory secretions, or other
body fluids that may be the source of infection, should also be obtained
before antimicrobial therapy if doing so does not cause significant delay in
antibiotic administration (grade 1C)

Antibiotic Therapy
We recommend that intravenous antibiotic
therapy be started as early as possible and
within the first hour of recognition of
septic shock (1B) and severe sepsis
without septic shock (1C).

Time to Antibiotics Following


Onset Septic Shock

For every hour of delay over 6 hours in IV antibiotics


administration after the diagnosis of septic shock,
mortality increases 7.6 %.

Kumar A, et al. Crit Care Med 2006; 34:1589-159

Antibiotic Therapy
Initial empiric anti-infective therapy activity against all likely
pathogens and adequate concentrations into suspected or
potential sources of infection (1B)
Reassess antibiotic regimen daily for de-escalation (1B)
For patients with severe infections associated with respiratory failure
and septic shock, combination therapy with an extended spectrum
beta-lactam and either an aminoglycoside or a fluoroquinolone is
for P. aeruginosa bacteremia (grade 2B).
A combination of beta-lactam and macrolide for patients with septic
shock from bacteremic Streptococcus pneumoniae infections (grade
2B).

Source control
A specific anatomical diagnosis of infection
requiring consideration for emergent source
control be sought and diagnosed or excluded as
rapidly as possible, and intervention be
undertaken for source control within the first 12
hr after the diagnosis is made, if feasible (grade
1C).

Fluid therapy
1. Crystalloids (1B)
2. Albumin (2C)
3. Avoid HES (1B)
4. Initial fluid challenge in sepsisinduced tissue hypoperfusion
(hypotension
or
elevated
lactate) with suspicion of
hypovolemia to be a minimum
of 30ml/kg of crystalloids
5. More rapid administration and
greater amounts of fluid, may
be needed in some patients
(1B)

SURVIVING SEPSIS CAMPAIGN


BUNDLES
TO BE COMPLETED WITHIN 6 HOURS:

5) Apply vasopressors (for hypotension that does not


respond to initial fluid resuscitation to maintain a
mean arterial pressure [MAP] 65 mm Hg)
6) In the event of persistent arterial hypotension despite volume resuscitation (septic
shock) or initial lactate 4 mmol/L (36 mg/dL):
- Measure central venous pressure (CVP)*
- Measure central venous oxygen saturation (ScvO2)*
7) Remeasure lactate if initial lactate was elevated*
*Targets for quantitative resuscitation included in the guidelines are CVP of 8 mm Hg,
ScvO2 of 70%, and normalization of lactate

Resuscitation of Sepsis Induced


Tissue Hypoperfusion

Requirement for vasopressors after fluid challenge


Lactate 4 mg/dL
Recommend MAP is 65 mmHg - Grade 1C

Vasopressors
(1) Norepinephrine (1B)
- Dopamine increases MAP and cardiac output - increase
in stroke volume and heart rate.
- Norepinephrine increases MAP due to its
vasoconstrictive effects, with little change in heart rate
and less increase in stroke volume compared with
dopamine.

(2) Epinephrine (2B)

Vasopressors
Dopamine, generally avoided unless
Relative or absolute bradycardia and low risk of tachyarrhythmias
(2C)
Phenylephrine, unless
Norepinephrine associated with serious arrhythmias
Cardiac output is known to be high and blood pressure target
difficult to achieve
As salvage therapy
Dobutamine
a) myocardial dysfunction as suggested by elevated cardiac filling
pressures and low cardiac output, or
(b) ongoing signs of hypoperfusion despite achieving adequate
intravascular volume and adequate mean arterial pressure

Initial Resuscitation of
Sepsis Induced Tissue
Recommend
Hypoperfusion
Insertion central venous catheter
Recommended goals :
Central venous pressure: 812 mm Hg
Higher with altered ventricular compliance or increased
intrathoracic pressure
In mechanically ventilated patients or those with known preexisting
decreased ventricular compliance, a higher target CVP of 12 to
15mm Hg should be achieved to account for the impediment in
filling
intravascular volume status and response to fluids, a low CVP
generally can be relied upon as supporting positive response to
fluid loading

Central venous oxygen


saturation (ScvO2) monitoring
The determinants of SvO2 include CO, oxygen demand, hemoglobin, and
arterial oxygen saturation
reflecting the balance between oxygen delivery (DO2) and consumption
(VO2).
Normal SvO2 is 7075%.
In sepsis SvO2 may be elevated secondary to maldistribution of flow
(blood returning to the venous circulation without opportunity for oxygen
transfer)
recent data showing that lactate clearance in sepsis is non-inferior to
continuous ScVO2 monitoring (Jones, JAMA, 2010)

2015 - ProCESS ProMISe ARISE - 3 trialsthat


do not demonstrate superiority of required
use of CVP monitoring and central venous
oxygen saturation (ScvO2) in all patients
with septic shock
esp those who have received timely
antibiotics and fluid resuscitation compared
with controls or in all patients with lactate
>4 mmol/L

Lactate Clearance
In patients with elevated lactate levels as a
marker of tissue hypoperfusion we suggest
targeting resuscitation to normalize lactate as
rapidly as possible (grade 2C).

Other Recommendations
Glucose control: commence insulin once 2 readings of
>180mg/dl
DVT prophylaxis: should receive daily VTE prophylaxis LMWH (Grade 1b) & compression stockings /
intermittent compression device
Stress ulcer prophylaxis: H2 blocker or PPI (Grade 1b)

Blood products
Red blood cell transfusion occur only when hemoglobin
concentration decreases to <7.0 g/dL to target a
hemoglobin concentration of 7.0 9.0 g/dL in adults
(grade 1B)
FFP not be used in the absence of bleeding or planned
invasive procedures (grade 2D)
Platelets prophylactically when counts are
<10,000/mm3 (10 x 109/L) in the absence of apparent
bleeding. (grade 2D)

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