severe sepsis

septic shock

 severe sepsis septic shock

Septic shock




r




on n 
n

on o

n
o




on 
invasive devices
on
n


n o o 


Septic shock
n

o




n
r o
n





o


no
on 
Septic shock
o

Systemic Inflammatory Response Syndrome ( SIRS)

on
n n




inflammatory stimuli n


n



burns
SIRS
on o
n no 
2 :
1.
2.
3.
4.

38.0 C 36.0 C
90 /
20 / PaCO2 32 .
12,000 /.. 4,000 /..
band form 10%

o oo
on onn


n o
on

Sepsis
n
n 
SIRS

Severe sepsis
sepsis n
( organ dysfunction )
( hypoperfusion )

( hypotension )
lactic acidosis o 


o 

o
Septic shock
sepsis
on
oo o o


n n n 
( hypoperfusion ) lactic acidosis
o 


o
on o
o

hypoperfusion


o 
inflammatory foci n
on 



endotoxin ,
exotoxin , peptidoglycans 
o
o
host defense system

monocyte ,
neutrophil endothelial cell o

mediator n


tumor necrosis factor (TNF), IL-1
o
n
TNF, IL-1
o o

cytokine TNF, IL-1,
IL-2 


o
complement pathway, coagulation system,platlet activating factors 
inflammatory response n
Systemic inflammation
n
no 

n o

n
microcirculation vasoconstriction, vasodilatation vascular leakage myocardial
depression
septic shock

o n n
ooxygen r 


r no

o 
mixed venous oxygen saturation(SvO2)
oxygen extraction ratio
on

 red blood cells red blood cells deformability

acidosis , mediators white cell 
arteriovenous shunting 

o
hemolysis white blood cell microcirculation

r o
endotoxin cell endothelium

enzyme



permeability
disseminated intravascular coagulation
o
coagulation cascade
microthombosis deposition fibrin
microcirculation multiorgan failure endothelium

microvascular permeability n o


o 




arteriolar
vasoconstriction vasodilation o o

Severe sepsis Septic shock

Shock SIRS n
n

3 :
1.
n
2. Intensive life support
3. o 
no 
Septic shock
1) o n
4
o n body fliud
exudate n n
on 
Septic shock hemoculture
2

 o n 
Septic schock


o
on n
n 

o nn

( grams stain, AFB ) o

on

on o
o

n



on 
febrile neutropenia
o


n
o
n



n

SIRS

1. drain infected fluid collection
2. debridement 
infected solid tissue

3.
medical device ( )
( central venous catheter)
o

4. n



n

2) Intensive life support
2.1 o 
( Fluid therapy)
2.2 vasopressure inotrope
2.3 hemodynamic monitoring
2.4 renal support
2.5 pulmonary support
2.1 o 
( Fluid therapy )
o




o
crystalloid normal
saline solution lactateds ringer solution (LRS) 500-1,000 ml 15 60
on
on
n 


intravascular volume

nnn
on o n

on

venous pressure o n 
n

on 


central venous catheter (CVP)

CVP Pulmonary artery catheter

PCWP fluid challenge
fluid challenge
Guided by

CVP

PCWP

( cmH20 )

( mmHg )

<8

< 10

200 ml/ 10 min

< 12

< 14

100 ml /10 min

12

14

50 ml/ 10 min

During infusion

Stop

After 10 min

Continue

Start

After waiting 10 min

Infusion

2 5

3 7

Wait 10 min

Stop

Still 2

Still 3

Stop

Repeat

2.2 vasopressure inotrope

2.2.1Vasopressure therapy
n
on o
n
on
n


o
o
o
hemodynamic profile

Dopamine: 1-5 ././ () 

inotropic



20 ././



: dopamine 


renal blood flow
n
o o 

renal perfusion
Norepinephrine:

n 
splanchnic blood flow
tachycardia dopamine
2.2.2 Inotropic therapy
Dobutaminne : o
on 
cardiac output 
o n o


n 
o
n o on
vasopressure

 Inotrope Vasopressure septic shock

Drug

Dose

Cardiac

(g/kg/min

Stimulation

or g/min*)
Dopamine

Vasoconstriction Vasodilatation Dopaminergic

(2)

(1)

1-10

++

++

+++

10-20

+++

+++

Norepinephrine

2-10*

+++

++++

Epinephrine

1-8*

++++

++++

Dobutamine

1-10

++++

2.3 Hemodynamic monitoring

resuscitrate septic shock ooo
n 

6 

Early goal-directed therapy o

hemodynamic monitoring
n :
2.3.1 Central venous pressure 8-12 mmHg
on 
o
n
12-15
mmHg
on n n
2.3.2 Mean arterial pressure ( MAP) 65 mmHg
2.3.3 Urine output > 0.5 ml/kg/hr
2.3.4 Central venous mixed venous oxygen saturation (ScvO2 SvO2) n
70% (ScvO2) 65% (SvO2)

2.4 renal support

n



n
hypercatabolic state septic
shock o




o 

optimized volume status

on o n 
renal replacement therapy
2.5 pulmonary support

n 
Acute lung injury Acute respiratory distress syndrome
Septic shock o 
low tidal volume 6 ml/kg of predicted body weight Plateau
pressure 30 cmH20 o
on 
hypercapnea Plateau pressure

( Permissive hypercapnea ) , PEEP ( Positive end expiratory pressure) o


n 
oxygen Fi02
Ventilator management

Assist control mode - volume ventilation

Reduced tidal volume to 6 mL/kg predicted body weight
Keep Ppla < 30 cm H20
Maintain Sao2/Spo2 88-95%
Anticipated PEEP setting at varius Fi02 requirements
Fi02 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0
PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 20-24
Predicted Body Weight Calculation
Male : 50 + 2.3(height (inches) 60) or 50 + 0.91(height(cm) 152.4)
Female : 45.5 + 2.3(height (inches) 60) or 45.5 + 0.91(height(cm) 152.4)


n o n

o
nn
semirecumbent o

45


o
ventilator-associated pneumonia
n
on 

on o

( spontaneous breathing trial pressure support 
n
PEEP 5 cmH20 T-piece)
o o n
n :
1.
2. ( vasopressur )
3. serious
4. ventilation end-expiratory pressure
5. Fi02 
o
mask nasal cannula

Use of spontaneous breathing trail in weaning ARDS patients

Original illness resolving : no new illness
Off vasopressure and sedative , Cough durning suctioning
PaO2/FiO2 >200 mm Hg , PEEP < 5 cm H2O
Minute ventilation < 15 L/min , F/Tv ratio < 105 durning 2-min spontaneous breathing trial
Spontaneous breathing trial ( 30-120 min)
( include: T-piece , continuous positive airway pressure 5 cm H2O ,or low-level
( 5-10cm H2O ) pressure support ventilation )
Respiratory rate > 35/min , Oxygen saturation < 90
Pluse > 140 /min or change > 20 % , SBP > 180 mm Hg or < 90 mm Hg
Agitation, diaphoresis , or anxiety
F/Tv ratio > 105
No

Yes

Cough adequate to clear secretions

Able to protect airway
Yes

Extubate

No

Return to maintenance MV

3) o

3.1 Steroid
o
on 
refractory septic shock ( adequate intravascular volume
vasopressure o
n) adrenal insufficiency 
septic
shock hydrocortisone 200-300 mg/day 3-4 

7 (
hydrocortisone 300 mg/day ) ACTH stimulation test n
serum cortisol hydrocortisone
Severe sepsis Septic shock adrenal insufficiency o
r
n :
- baseline cortisol n
10 g/dl
- cortisol o n
9 g/dl cosyntropin
- free cortisol
o nn
2 g/dl
adrenal insufficiency

cortisol 44 g/dl
Cortisol n
16.8 g/dl cosyntropin
3.2 Glucose control

oo n
150 mg/dl insulin nn
n
on
n

n
o 
o ,
insulin anti-inflammation endothelium
mitochondria
3.3 Blood product administration
red blood cell transfusion oxygen delivery
on hematocrit
< 30% , erythropoietin severe sepsis
3.4 Bicarbonate therapy
bicarbonate therapy
on 
severe metabolic acidosis septic shock
arterial PH < 7.15

3.5 Recombinant human activated ptotein C ( rhAPC )

on 
severe sepsis rhAPC



o 
o


o o

Septic shock
oo 

6
1. ( presumptive diagnosis) 1
2. Antibiotic 4 

o
n
sepsis
3. Resuscitrate o n
4. o 
MAP < 65 mmHg n o
o

5. CVP
6. PRC Central venous oxygen saturation < 70%
o


CVP > 8 mm Hg
7. n
on o nn 
o
Steroids
o 
24
1.
on
150 mg/dl
2. o
on 
Acute lung injury ARDS tidal volume 6 ml/Kg
plateau pressure 30 cmH2O

Clinical practice guideline for Severe sepsis and Septic shock

o

n 
( Early Recognition )

Criteria SIRS 2 o

n
Temp > 38.0 C < 36.0 C
Heart Rate > 90 bpm

No

Resp. Rate > 20 bpm PaCO2 < 32 mmHg

WBC > 12,000 < 4,000 Bandform Neutrophil 10%

Yes
n

No

H/C 2 specimen , Plasma glucose, Bun/Cr , Elyte, LFT, CBC

n n
Imaging Specimen n

Sepsis with hypotension or sign of hypoperfusion

-SBP < 90 mm Hg

- Change in mental status

-MAP < 65 mm Hg

- Decreased urine output

-Decreased SBP > 40 mm Hg

- Increased lactate

No

Yes
-

o
o
0.9% NSS 500-1000 ml in 30-60 min

( )

-
BP : MAP > 65, SBP > 90 mmHg

Yes

BP : MAP > 65, SBP > 90 mmHg

SBP = Systolic Blood Pressure

No

MAP = Mean Arterial Pressure

[ MAP = ( SBP+DBP)/3 + DBP ]

Notify r : Fluid challenge test ICU Early Goal Directed Therapy

( 6 . )

EARLY GOAL DIRECTED THERAPY ( 0 - 6 )

A : Invasive hemodynamic monitoring CVP monitoring
B : Broad Spectrum Antibiotic
n

Fluid challenge test Crystalloid (0.9%NSS

CVP 30 min < 8 cmH2O

or Lactate Ringer ) 20-30 ml/kg

free flow Pressure bag n

8-12 cm H2O

o
o

500 ml. 30
CVP 8-12 cmH2O

MAP < 65 mmHg ( SBP < 90 mmHg)

Yes

Vasopressors

Norepinephrine Dopamine
MAP 65-90, SBP 90-140
No

Yes
echo LV function

Adequate perfusion

Dobutamine

Adequate perfusion

Yes

Yes

MAP 65-90, SBP 90-140

No

No

n 













































Refractory septic shock
o 






























- Vasopressure 2 (

Resuscitation

Norepinephrine )
- Epinephrine Second Venous line
- Steroid ( Hydrocortisone )

- Fluid challenge ( oon)

- Hct < 30 % PRC
- Acidosis / Low SvO2 Dobutamine

 Empyrical treatment sepsis ( Antibiogram )

1) o on
oo n

n 
1
on n

Oral macrolide Oral doxycycline

n n 
DRSP

n 
2
on
n 
DRSP

Oral lactam ( high dose amoxicillin,

amoxicillic/clavulanate,cefuroxime,cefpodoxime)
oral macrolide doxycycline
Oral antipneumococcal fluoroquinolone

n 3
on o n
ICU
n 3.1
n DRSP

Intravenous advance macrolide

Intravenous antipneumococcal fluoroquinolone

n 3.2 Intravenous -lactam ( ceftriaxone, cefotaxime,

-lactam, -lactamase inhibitor, high dose
DRSP
ampicillin) macrolide doxycycline

Intravenous antipneumococcal fluoroquinolone

n 4
on 
ICU
n 4.1 n n 

Intravenous -lactam Intravenous advance

macrolide

P.aeruginosa

Intravenous antipneumococcal fluoroquinolone

n 4.2 n P.aeruginosa Antipseudomonal lactam

aminoglycoside anti-pseudomonal quinolone

Note: Antipneumococcal fluoroquinolone levofloxacin , gatifloxacin, and moxifloxacin

: Andvanced generation macrolide clarithromycin and azithromycin

1. Drug resistant Streptococcus pneumonia ( DRSP)

1.1 Age > 65 years
1.2 Beta-lactam therapy within 3 months
1.3 Alcoholism , exposure to child in day care
1.4 Multiple medical comorbidities

2. Enteric gram negatives

2.1 Underlying cardiopulmonary disease
2.2 Recent antibiotic therapy
2.3 Nursing home residence
2.4 Multiple medical comorbidities
3. Pseudomonas aeruginosa
3.1 Structural lung disease eg. Bronchiectasis
3.2 Broad-spectrum antibiotics for > 7 days within the past month
3.3 Corticosteroids therapy ( > 10 mg prednisolone )

3.4 Severe malnutrition

2) o on
ono

Early onset HAP/VAP , no specific risk factor

Enteric gram negative ( nonpseudomonal )

Cephalosporin

Enterobactor spp.

Second generation or

Escherichia spp.

Nonpseudomonal third generation or

Klebsiella spp.

Beta-lactam/beta-lactamase inhibitor or

Proteus spp.

Fiuoroquinolones if allergic to penicillin

Serratia marcescens
Haemophillus influenza
Methicillin sensitive Staph. Aureus
Late onset HAP/VAP
As early onset plus
Pseudomonas aeruginosa
Acinetobactor baumannii

Aminoglycoside or antipseudomonal quinolone plus

One of the followings:
Antipseudomonal penicillin
Ceftazidime
Cefoperazone/beta-lactamase inhibitor
Carbapenem groups

Methicillin resistant Staph. aureus

Vancomycin

3) o 

soft tissue
( Abcess, Cellulitis and Erysipelas )
MSSA SSTI

MRSA SSTI

Oxacillin

1-2 gm IV q 6 hr

Vancomycin

30 mg/kg/day IV q 12 hr

Cefazolin

1 gm IV q 8 hr

Clindamycin

600 mg IV q 8 hr

Clindamycin 600 mg IV q 8 hr
MSSA: methicilin-susceptible S.aureus, MRSA : methicilin-resistant S.aureus, SSTI : skin and soft-tissue infection

4) necrotizing of the skin, fascia, and muscle

First-line antimicrobial agent, by infection type

Adult dose

Mixed-infection
Ampicillin-sulbactam or

1.5-3.0 gm q 6-8 h IV

Piperacillin-tazobactam plus

3.37 gm q 6-8 h IV

Clindamycin plus

600 mg q 8 h IV

Ciprofloxacin

400 mg q 12 h IV

Imipenem/cilastin

1 gm q 6-8 h IV

Meropenem

1 gm q 8 h IV

Cefotaxime plus

2 gm q 6 h IV

Metronidazole or

500 mg q 8 h IV

Clindamycin

600 mg q 8 h IV

Streptococcus infection
Pennicillin plus
Clindamycin

2-4 MU q 4-6 h IV
600 mg q 8 h IV

S.aureus infection
Oxacillin

1-2 gm q 4 h IV

Cefazolin

1 gm q 8 h IV

Vancomycin ( for resistant )

30 mg/kg/day q 12 h IV

Clindamycin

600 mg q 8 h IV

Clostridium infection
Clindamycin

600 mg q 8 h IV

Penicillin

2-4 MU q 4-6 h IV

5) o n o o

(Community-Acquired Complicated Intra-Abdominal Infections )

Single agent
-lactam/-lactamase Ampicillin/sulbactam

Piperacillin/tazobactam

inhibitor
Combination regimens
Cephalosporin based

Cefazolin or cefuroxime plus Third/fourth- generation cephalosporin

metronidazole

(ceftriaxone,ceftazidime,cefotaxime,cefepime)
plus metronidazole

Fluoloquinolone based

Ciprofloxacin, levofloxacin
or moxifloxacin each in
combination with
metronidazole

Ciprofloxacin in combination with

metronidazole

6) o

o 
E.coli, Klebsiella spp.,Proteus spp.,S. aureus
First-line antimicrobial agent

Adult dose

Gentamicin

7 mg/kg day 5 mg/kg/day IV

Cefotaxime

1 gm IV q 6 hr

Ceftriaxone

2 gm oo
1 gm IV q 12 hr

Amikacin

1 gm 15 mg/kg/day IV

Neltilmycin

300 mg ( 6 mg/kg/day) 4 mg/kg/day IV

Imipenem

1 gm 
oo
500 mg IV q 6 hr

7) o

o 
Klebsiella spp., Enterobacte spp., Pseudomonas aeruginosa, Acinetobactor spp.

o n

Antimicrobial agent

Adult dose

Beta-lactam group
- Ceftazidime/Cefepime

2 gm IV q 8 hr

- Cefoperazone/sulbactam

1.5 2 gm 
oo
1.5 1 gm IV q 8-12 hr

- Imipenem

1gm 0.5 gm IV q 6-8 hr

- Meropenem

2gm 1 gm IV q 8 hr

- Piperacillin+tazobactam

4.5gm IV q 8 hr

- Colistin

3 on 
oo
1.0-1.5 IV q 8 hr

Amikacin

1 gm 15 mg/kg/day IV

Neltilmycin

6 mg/kg/day 4 mg/kg/day IV

Levofloxacin

750 mg IV OD

Ciprofloxacin

400 mg IV q 12 hr

8) Primary bacteremia/sepsis
n

rickettsia leptospira
Antimicrobial agent
- Ceftriaxone 2gm IV 
o
1 gm IV q 12 hr Doxycycline 200 mg oral
100 mg q 12 hr
- Ceftriaxone 2gm IV 
o
1 gm IV q 12 hr azithromycin(
doxycycline) 2 gm 
oo
500 mg IV q 12 hr 3-5

Severe sepsis Septic shock
nno o




n
o o 


n oo o



o 
1-6

o 




o


n n



o
o

n 
o 


on 

o



n



o

o 


o



no n o o o



sepsis o
o o n
o
ro

1. R.Phillip Dellinger,Jean M.Carlet et al; Surviving Sepsis Campaign guidelines for management of
severe sepsis and septic shock. Crit Care Med 2004 ;32: 859-872.
2. River E , Nyugen B, Havstad S et al; Early goal directed therapy in the treatment of severe
sepsis and septic shock. N Eng J Med 2001;345:1368-77.
3. ; Septic shock :an Update 2007. Best Practices in Critical Care
2006;227-246.
4. MacArthur RD, Miller M,Albertson T et al; Adequacy of early empiric antibiotic treatment and
survival in severe sepsis:experience from the MONARCS trial. Clin Infect Dis 2004;38:284-8.
5. Annanae D, Maxime V, Ibrahim F,Alvarez JC,Abe E. Diagnosis of adrenal insufficiency in
severe sepsis in severe sepsis and septic shock . Amer J Respir Crit Care Med 2006;174:1319-26.
6. .. ; Septic shock :More Than Just Antibiotic. Update on Infectious Diseases:An
Evidence-Based Approach to Patient Care 2008;56-103.
7. Lionel A. Mandell et al; Guidelines on the management of Community-Acquired Pneumonia in
Adults. Clin Infect Dis 2007;44:22-72.
8. Michael S. Niederman et al; Guidelines for the Management of Adults with HospitalAcquired,Ventilator-associated, and Health-care associated Pneumonia.Am J Respire Care
Med2005;171:388-416.
9. Dennis L.Stevens et al; Guidelines for Skin and Soft-tissue infections. Clin Infect Dis
2005;41:1373-1408.
10. Joseph S.Solomkin; Guideline for the Selection of Anti-infective Agents for Complicated Intraabdominal Infections. Clin Infect Dis 2003;37:997-1005.