By Duangruethai Tunprom, MD. (Emergency physician), Phrae hospital

Incidence

Definition

Definition

Definition

MODS =Multiorgan dysfunction syndrome

Pathophysiology

Clinical

Early Hypodynamic state Peripheral

vasodilatation

Hypovolemia Global tissue

hypoxia Reversible tissue Anaerobic

metabolism Latate

Late Hyperdynamic state Perpheral

vasoconstrction Cardiac output

Global tissue hypoxia

Irreversible tissue then tissue necrosis

Organ failure

ScVO2 SvO2

ScVO2 SvO2

Warm shock Cold shock

Diagnosis

Bone’s criteria

Bone’s criteria

Diagnosis

Bone’s criteria Source of infection

H/C Sputum C/S ± G/S Pus C/S + G/S Urine C/S + G/S Synovial fluid CSF Imaging investigation

Biomarkers for diagnosis

Severity scoring system & prognostic models

CURP 65 , PSI score BISAP score, Ranson’s score Revised Atlanta Classification

APACHE II score (Acute Physiologic and Chronic Heath Evaluation II score)

SOFA score (Sepsis-related Organ Failure)

Bone’s criteria

Treatment

Get rid of source infection Intensive life support Innovative therapy

Get rid of source infection Source control Antibiotic

Source control

Antibiotics1. Intravenous antibiotic therapy should be started within the first hour of recognition of severe sepsis and septic shock

AntibioticsAntibiotics2. Broad-spectrum: one or more agents active against likely bacterial/fungal pathogens and withgood penetration into presumed source

3. The antimicrobial regimen should always be reassessed daily - The aim of using a narrow spectrum antibiotic - to prevent the development of resistance - to avoid toxicity - to reduce costs

AntibioticsAntibiotics

•suggest combination therapy for patients with known or suspected Pseudomonas infections as a cause of severe sepsis

AntibioticsAntibiotics

4. The duration should typically be 7–10 days

AntibioticsAntibiotics

5. The presenting clinical syndrome is determined to be due to a noninfectious cause

Intensive life support

Fluid Vasopressor

Fluid Therapy

1.Fluid-resuscitate using crystalloids or colloids

SAFE Study

• Indicated that albumin administration was safe andequally as effective as crystalloid .

• There was an insignificant decrease in mortalityrates with the use of colloid in a subset analysis of septic patients

SAFE Study

NEJM 2004; 350:2247

The SAFE Study Investigators, N Engl J Med 2004;350:2247-2256

Kaplan-Meier Estimates of the Probability of Survival

Primary Endpoint was 28 day mortality

Fluid TherapyFluid Therapy2. Target a CVP of 8 mm Hg (12 mm Hg if mechanically ventilated)

3. Use a fluid challenge technique while associated with a hemodynamic improvement

Give fluid challenges of 1000 mL of crystalloids or 300–500 mL of colloids over 30 mins. More

rapid and larger volumes may be required in sepsis-induced tissue hypoperfusion

VasopressorVasopressor

VasopressorVasopressor

Norepinephrine vs Dopamine+/_ Epinephrine in Septic Shock

Results of a prospective observational study

Claude, Critical Care Med 2000;28:2758

VasopressorVasopressor

VasopressorVasopressor

Inotropic therapyInotropic therapy

•.

New innovative therapy

Early goal-directed therapy Tight control of blood sugar Activated protein C

Early Goal Directed Therapy (EGDT)

Finish within 6 hr Process

Fluid resuscitation Vassopressor and inotrophic drug

Early Goal-Directed Therapy

NEJM 2001;345:1368-77.

Early goal directed therapy N=130

Standard therapy N=133

CVP > 8-12 mm HgMAP > 65 mm Hg

Urine Output > 0.5 ml/kg/hr

CVP > 8-12 mm HgMAP > 65 mm HgUrine Output > 0.5 ml/kg/hrScvO2 > 70%SaO2 > 93%Hct > 30%

Antibiotics given at discretion of

treating clinicians

As soon as possible Mean 6.2hrs

ICU MDs blinded to study treatment

NEJM 2001;345:1368-77.

At least 6 hoursof EGDTMean 8hrs

Transfer to ICU

49.2%

33.3%

0

10

20

30

40

50

60

Standard Therapy N=133

EGDTN=130

P = 0.01*

*Key difference was in sudden CV collapse, not MODS

Early Goal-Directed Therapy Results:28 Day Mortality

Sudden CV Collapse

MODS

21% vs 10%

p=0.02

22% vs 16%

P=0.27

NEJM 2001;345:1368-77.

Mo

rta

lity

Mortality 50 %30%

Glucose Control

Tight Glucose Control

Van den Berghe, NEJM 2001; 345: 1359

Intensive

>215 mg/dL

180 to 200 mg/dL (10.0 and 11.1

mmol/L)

>110 mg/dL

80 to 110 mg/dL (4.4 to 6.1 mmol/L)

Blood glucose level when insulin infusion

was started

Infusion adjusted to maintain blood

glucose

van den Berghe G, et al. NEJM 2001;345:1359-1367.

Intensive Insulin Therapy in Critically Ill Patients

39 % Received insulin 99% Received Insulin

Tight Glucose Control Improved Survival

Intensive Insulin Therapy in Critically Ill Patients: Mortality

8.0%

4.6%

0%

5%

10%

15%

10.9%

7.2%

0%

5%

10%

15%

ICU Mortality was reduced by 42%

In-Hospital Mortality was reduced by 34%

Mo

rtal

ity

(%)

p = 0.01p < 0.04 (adjusted)

N=783 N=765

Conventional IntensiveN=783 N=765

NEJM 2001;345:1359-1367.

Glucose Control

NICE-SUGAR=Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation

Recombinant HumanActivated Protein C

(rhAPC)

Recombinant HumanRecombinant HumanActivated Protein C Activated Protein C

(rhAPC)(rhAPC)

Thank youFor your attention