Reducing Mortality from Severe Sepsis and Septic Shock: A ...
Early Goal-Direct Therapy in the Treatment of Severe Sepsis and Septic Shock
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Transcript of Early Goal-Direct Therapy in the Treatment of Severe Sepsis and Septic Shock
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Early Goal-Direct Therapy in the Treatmentof Severe Sepsis and Septic Shock
Rivers E, Nguyen B, Havstad S.
N Engl J M 2001; 345: 1368-1377
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Background
SIRS
Self
Limited
Severe
Sepsis
Septic
Shock
Circulatory Abnormalities
Intravascularvolume depletion
Peripheraldilatation
Myocardialdepression
Increasemetabolism
Imbalance between DO2 and VO2
Global
Tissue Hypoxia
MOF &
Death
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Background
Cardiac
preload
Cardiac
after load
Cardiac
contractility
Balance between DO2 and VO2
SvO2 Lactate Base deficit pH
Resuscitation end points
Target forhemodynamic
Surrogate forcardiac index
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Value of SvO2
Mixed venous oxygen saturation (SvO2)
Global Tissue Oxygenation
VO2 DO2
O2 remaining in venous bloodafter extracting by tissue
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Tissue Oxygenation
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Value of SvO2
Venous O2 Saturation(SvO2)
Right atrium
Superior vena cava
Pulmonary artery
Hyperdynamic state SvO2 < 65% (Rare)
Centralvenous O2saturation(ScvO2)
Mixed venous O2saturation (SvO2)
5-13% lower
Splanchnic O2saturation (SspO2)
15% lower
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Value of SvO2
SvO2
Normal SvO2 (70 75%)
Doesnt assure a normal
metabolism
O2 kinetic is normal
or compensated
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Value of SvO2
SvO2
Low SvO2
SvO2 < 50%
Poor tolerated
Below 30%
Anaerobic Metabolism
Lactic Acidosis
Emergency !!!
High SvO2
Have enough O2
available to the cells butthe cells cannot extract it
Shunt, intracardiac or
systemic vascular shunt
Hb failed to unload O2
(leftward shift in ODC)
Interstitial edema
Toxic, Dying or Necrotic
Tissue hypoxia
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Clinical application of SvO2
Hemodynamic monitoring
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Clinical application of SvO2
Hemodynamic monitoring
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SvO2low
SaO2 NSaO2low
Hypoxemia O2ER
CardiacOutput
CardiacOutput
VO2 VO2 N
Obstruction
HeartFailure
Hypovolemia
AnemiaStressInfectionAnxiety
PAOP
PAOP
PAOP
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Objective
Early goal-directed therapy before admission to the ICU
Reduce of multi organ dysfunction
Reduce incidence of mortality
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Study designSIRS criteria
SBP < 90 mmHgLactate > 4 mmol/L
Assessment and consent
Randomization (n=263)Standard Therapy
in ED (n=130)Early goal-directedtherapy (n=133)
Vital sign, Lab data, cardiacmonitoring, pulse oximetry,
Urinary catheterization,
arterial and venouscatheterization
Continuous SvO2monitoring and
EGDT for 6 hours
CVP 8-12 mmHg
MAP 65 mmHg
Urine 0.5 cc/kg/min
ScvO2 70%
SaO2 93%
Hematocrit 30%
Cardiac index
VO2
CVP 8-12 mmHg
MAP 65 mmHg
Urine 0.5cc/kg/min
Standard care
Hospital admission
Vital sign, lab data,obtained every 12 hour
for 72 hour
Follow upDid not complete6 hour (n=13)
Did not complete6 hour (n=14)
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Study design
Exclusion
Criteria
< 18 yrs old
Pregnancy
Acute cerebral vascular event
Acute coronary syndrome
Acute pulmonary oedemContra indication to CVC
Cardiac dysrhythmia (primer)
Status asthmaticus
Requirement for immediate surgery
Active GI tract hemorrhage
Drug overdoses
Trauma
Burn injury
DNAR
Uncured Cancer (chemotherapyImmunosuppressant therapy
(transplantation/systemic disease)
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Protocol for Early Goal-Directed Therapy
Supplement O2Endotracheal intubations
Mechanical ventilation
Central venous andarterial catheterization
Sedation, Paralysis(if intubated), or both
CVP
MAP
ScvO2
Crystalloid
Colloid
< 8 mmHg
Vasoactive agents< 65 mmHg
> 90 mmHg
8 12 mmHg
65 90 mmHg
70%
Goalachieved
Transfusion of RCuntil Ht 30%
70%
< 70%
Inotropic agents
Hospital admissionYesNo
< 70%
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Early Goal Directed Therapy
in Emergency Department
Standard
Therapy
Early Goal
Directed Therapy
Hospital mortality
42,3%56,8%
Rivers et all. N Engl J Med 2001; 345: 1368-77
25%
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Supra normal value of survivors as therapeutic
goals in high risk surgical patients
mortality
Shoemaker et all. Chest 1988; 94: 1176-86
CI > 4,5; DO2 >600; VO2 > 170
post operative
complication
post operative
organ failure
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Effects of deliberate perioperative increase of DO2
on mortality in 107 high risk surgical patients
mortality at 28 days
by 75%
Byod et all. JAMA 1993; 270: 2699-707
DO2 >600
post operative
complication by 50%
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Elevation of CO and DO2 in septic shock
No significant
difference in mortality
Tuchchmidt J et all. Chest 1992; 102: 216-20
CI up to 6; DO2 >600
ICU LoS
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Aggressive Hemodynamic
Optimization in ICU
Control Treatment
Hospital mortality
71%52%
Hayes et all. N Engl J Med 1994; 330: 1717-22
36,5%
CI > 4,5; DO2 >600; VO2 . 170
Di i
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Discussion
Early
identification
Abrupt transition of
severe disease
Sudden
Cardiovascular collapse
Discussion
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Discussion
Aggressive fluidresuscitation
Reperfusion Injury ?
Discussion
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Discussion
Early
identification
Global
tissue hypoxia
Early implementation
of goal-direct therapy
Endothelial
activation
Disruption of
hemostaticcoagulation
Vascular
permeability
Vascular
tone
Microcirculatoryfailure
Refractory
tissue hypoxia
Organ
dysfunction
T t t f S i
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Treatment of Sepsis
Ventilator
EGDT
Tight control glycemia
Low dose corticosteroid
Activated Protein C
Conclusion
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Conclusion
Goal-directed therapy at earliest stage
of severe sepsis and septic shock
Significant short term and long termbenefits
Identification at
high risk forcardiovascularcollapse
Therapeutic
intervention
Balance betweenDO2 and VO2
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