Early Goal-Direct Therapy in the Treatment of Severe Sepsis and Septic Shock

7/28/2019 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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Documents

Early Goal-Direct Therapy in the Treatment of Severe Sepsis and Septic Shock