Surviving Sepsis

Early Goal Directed Therapy

MAZEN KHERALLAH, MD, FCCP
INFECTIOUS DISEASE AND CRITICAL CARE MEDICINE

Therapy Across the Sepsis Continuum

Infection

SIRS

Microorganism
invading
sterile tissue

A clinical
response arising
from a nonspecific
insult, with 2 of
the following:
T >38oC or
<36oC
HR >90
beats/min
RR >20/min
WBC
>12,000/mm3
or <4,000/mm3
or >10% bands

Sepsis

Severe Sepsis Septic Shock

SIRS with a
presumed
or confirmed
infectious
process

Sepsis with
organ failure
Vascular collapse
Renal
Hemostasis
Lung
LA

Refractory
hypotension

Chest 1992;101:1644

Sepsis Syndromes
1992: SCCM/ACCP

Parasite

Virus
Severe
Sepsis

Infection
Fungus

Shock

Sepsis

SIRS
S ev
e
SIR re
S Trauma

BSI

Bacteria

Burns

Surviving Sepsis Campaign

Launched in Fall 2002 as a collaborative effort of

European Society of Intensive Care Medicine, the

International Sepsis Forum, and the Society of
Critical Care Medicine
Goal: reduce sepsis mortality by 25% in the next 5
years
Guidelines revealed at SCCM in Feb 2004
Critical Care Medicine March 2004 32(3):858-87.
Website: survivingsepsis . org

THE SEVERE SEPSIS BUNDLES: SSC/IHI

6 Hour Bundle

Measure serum lactate

Blood Cultures prior to antibiotics
Broad spectrum antibiotics within 3
hours of presentation, 1 hour in hospital
Initial fluid resuscitation with 20-40
mL/kg crystalloid (or equivalent
colloid) if hypotensive (SBP < 90 mmHg
or MAP < 70) or lactate > 4 mmol/L
Vasopressors
If septic shock or lactate > 4 mmol/L:
CVP and ScvO2 or SvO2 measured
CVP maintained 8-12 mm Hg
Inotropes (and/or PRBCs if Hct < 30%)
delivered for ScvO2 <70% or SvO2<65%
if CVP > 8 mmHg

24 Hour Bundle
Glucose control maintained <
150 mg/dL
Drotrecogin alfa (activated)
administered in accordance
with hospital guidelines
Steroids given for septic
shock requiring continued use
of vasopressors for > 6 hours
Lung protective strategy with
plateau pressures < 30 cm
H2O for mechanically
ventilated patients

http://www.ihi.org

SCCM 2009: Sepsis Management "Bundles" Boost

Guideline Implementation, Reduce Mortality
15,022 Patients

7% Absolute Risk Reduction

19% Relative Risk Reduction

Society of Critical Care Medicine (SCCM) 38th Critical Care Congress. Late breaker. Presented February 2, 2009

SUMMARY: SEPSIS GUIDELINES 2008

Strong Recommendation (1): Recommended
A

DVT Prophylaxis

Antibiotics within 1 hr
for Septic Shock

EGDT and Protocolized

Resuscitation

Glycemic Control

Fluid Challenge

Crystalloid = Colloid

BC prior to Abx

PPI PUD Prophylaxis

Source Control

Low VT for ALI

Dopamine or
Norepinephrine

H2 Blocker PUD
Prophylaxis
No Routine Use
of SGC
No Renal Dose
Dopamine
No High Dose
Steroids

HOB >45
Limited Transfusion
No Antithrombin II
No Erythropoietin
Intermittent =
Continuous sedation
Weaning Protocol/SBT

Avoid NMB

Limit P plateau <30

cm H2O
PEEP
De-escalation
Antibiotic Therapy
Conservative Fluid in
ALI with no Shock

D
Antibiotics within 1
hr in No septic
Shock Patients
7-10 day Antibiotic
Duration
Consider Limiting
Support

SUMMARY: SEPSIS GUIDELINES 2008

Weak Recommendation (2): Suggested
A

APC in high risk

and non-surgical

PRBCs or
Dobutamine

Wean Steroids

equivalency
of continuous
veno-veno
hemofiltration
or intermittent
hemodialysis

APC for high risk

and surgical

NIV for ALI/ARDS

mild/moderate
hypoxemia

Low dose steroids

for septic shock
ACTH test not to
be done
B/S < 150
Prone Position in
ARDS

Therapy Across the Sepsis Continuum

Infection

SIRS

Sepsis

Severe Sepsis Septic Shock

Steroids

Drotrecogin Alpha
Early Goal Directed Therapy
Antibiotics and Source Control
Insulin and Tight Glucose Control
Chest 1992;101:1644

Therapy Across the Sepsis Continuum

Infection

SIRS

Sepsis

Severe Sepsis Septic Shock

CVP > 8-12 mm Hg
MAP > 65 mm Hg
Urine Output > 0.5 ml/kg/hr
ScvO2 > 70%
SaO2 > 93%
Hct > 30%

* Early Goal Directed Therapy

Early Goal-Directed Therapy (EGDT): involves adjustments of cardiac preload, afterload, and contractility
to balance O2 delivery with O2 demand: Fluids, Blood, and Inotropes
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM 2001;345:1368.

Rivers E, Nguyen B, Havstad S, et al 2001;345:1368-1377.

Early Goal-Directed Therapy Results:

28 Day Mortality
60
50

49.2%

P = 0.01*

40
Mortality %

Vascular
Collapse

33.3%

p=0.02

30

MODS

20

22% vs 16%

10
0

21% vs 10%

P=0.27

Standard Therapy
N=133

EGDT
N=130

*Key difference was in sudden CV collapse, not MODS

NEJM 2001;345:1368-77.

The Importance of Early Goal-Directed

Therapy for Sepsis-induced Hypoperfusion

60

Mortality (%)

50

NNT to prevent 1 event (death) = 6 - 8

Standard therapy
EGDT

40
30
20
10
0

In-hospital
mortality
(all patients)

28-day
mortality

Rivers E, Nguyen B, Havstad S, et al. 2001;345:1368-1377.

60-day
mortality

 If venous O2 saturation target not achieved: (2C)

Consider further fluid
Tansfuse packed red blood cells if required to

hematocrit of 30% and/or

Dobutamine infusion max 20 g.kg1 .min1

Rivers E, Nguyen B, Havstad S, et al. 2001;345:1368-1377.

SIRS Screen
First section screens for SIRS

SIRS includes objective vital signs data:

Temperature 100.4 or 96.8 F

Heart Rate 90
Respiratory Rate 20
WBC count 12,000 or 4,000, or greater than 0.5K/uL
bands

If the patient has 2 or more of the above, they screen

positive for SIRS

Infection Screen
Second section screens for infection

The patient is screened for infection if they have

SIRS
Does the patient have suspected or documented
infection?
Has the patient received antibiotics (not
prophylaxis)?
If one of the above is confirmed, the patient is
screened for organ dysfunction

Severe Sepsis Screen

Third section screens for Organ Dysfunction

Respiratory: SaO2 < 90 %

Cardiovascular: SBP < 90
Renal: urine output < 0.5ml/hr; creatinine
increase > 0.5mg/dl from baseline
CNS: altered LOC, Glascow coma scale 5

Any one of the above, in addition to positive

results from sections 1 and 2, indicates severe

sepsis.

SBAR
The RN should approache the MD, informing
him using SBAR technique, that the patient has
screened positive for severe sepsis.

SBAR Communication Technique

Situation:
RN

caring for John Smith

Screened positive for severe sepsis
Background:
Positive

for SIRS (describe)

Known or suspected infection
Organ dysfunction (describe)
Assessment:
Share

complete VS and SaO2

SBAR Communication Technique

Recommendation:
I

need you to come and evaluate the patient

to confirm if they have severe sepsis.
It is recommended that I get an ABG, lactate,
and CBC, Can I proceed and get these?
Any other labs you would like me to obtain?
If the pt is hypotensive: Can I start an IV and
give a bolus of NS 20 ml/kg?

Resuscitation Goals (Grade 1C)

Central venous pressure (CVP): 812mm

Hg
Mean arterial pressure (MAP) 65mm Hg
Urine output 0.5mL.kg1.hr 1
Central venous (superior vena cava) or
mixed Venous oxygen saturation 70% or
65%, respectively
Hemoglobin >10 mg/dL
Rivers E, Nguyen B, Havstad S, et al. 2001;345:1368-1377.

Initiation of Resuscitation (1C)

Begin resuscitation immediately in

patients with CVP < 8, hypotension or

elevated serum lactate >4mmol/l;
Do not delay pending ICU admission.

Rivers E, Nguyen B, Havstad S, et al. 2001;345:1368-1377.

CVP <8 mmHg

Central line placement and CVP

monitoring
500 mL 0.9% NaCl bolus every 15
minutes to maintain a CVP goal
Colloids if CVP <4
Transfuse 1 unit of PRBCs if Hg <10

A higher target CVP of 1215 mmHg is

recommended in the presence of
Mechanical ventilation
Pre-existing decreased ventricular

compliance
Increased intra-abdominal pressure

MAP <65 mmHg

Arterial line placement
Norepinephrine 2-20 mcg/min
Vasopressin 0.04 Unit/min
Phenylephrine 40-200 mcg/min
Hydrocortisone 50 mg IV every 6

hours

ScvO2 <70%
Arterial line placement
Transfuse 1 PRBCs if Hg level <10 mg/dL
Start Dobutamine 2.5-20 mcg/kg/min IV

infusion
Intubation and ventilation

If you are admitted to our ICU with severe

sepsis we will:
Obtain blood cultures and lactic acid level
Start antibiotics within one hour
Target a central venous pressure target to 8

mmHg
Target a mean arterial blood pressure target of 65
mmHg
Target a central venous O2 saturation of 70%
Target your urine output to >0.5 mL/Kg/Hour

Thank You