Module of

SEPSIS
Pediatric Critical Care
Diponegoro University/Kariadi Hospital
Semarang - 2011

Learning Objectives
1. How to diagnose pediatric sepsis
2. How to manage pediatric sepsis
3. How to understand early detection
in pediatric sepsis
How to prevent sepsis

Must to know key points

to diagnose sepsis

Definition
Differential diagnosis
Classification
from clinical
Etiology
manifestations
Epidemiology Laboratory
interpretation:
Pathogenesis
hematology, serology
Diagnosis
and microbiology
(bacteriology)

Must to know key points

to manage sepsis

Procedure of : fluid resuscitation, Infection

control, Nutrition and Bed rest
Medical treatment : empirical antibiotic
deescalating system
Nonsurgical critical care management :
electrolyte disturbance, acid-base
imbalance, multiorgan dysfunction
Source of infection detection

Must to know key points

to do early detection

Communication skill
Correlation between predisposing factors
and onset of sepsis

SEPSIS

Introduction
Consensus for pediatric sepsis was done (2005),
according to the age (Goldstein et al. Pediatr Crit Care
2005, 6 : 1) Update in 2007 (Crit Care Med 2009 vol
37 no 2)
The changes recommended were few
There was no change in emphasis (continued emphasis)
There are some new recommendations in the 2007
update

Epidemiology
Incidence of severe sepsis : 2-11% PICU
admission
Mortality rate of sepsis in developing country
still high
(50-70%);
in developed country decreased from 97% to
9% (DuPont HL. Medicine 1968;48:307-332) (Stoll
BJ, Holman RC, Shuchat A. Pediatrics 1998;102:E18)
Mortality rate for septic shock / MOF : 80%

Definition

SIRS : At least 2 of the following (temp. or leukocyte abnormality should be

present):

Core temperature > 38.5C or < 36C

Tachycardia, a mean HR > 2SD above normal for age
Mean Respiratory Rate > 2SD above normal for age
Leukocyte count or for age or >10% immature neutrophils

INFECTION:
Suspected or proven infection by any pathogen or a clinical syndrome assoc. with
a high probability of infection
Evidence of infection : positive findings on clinical exam, imaging, laboratory test,
pneumonia (chest radiograph), petechial or purpuric rash, or purpura fulminans)
SEPSIS SIRS in the presence of or as a result of suspected or proven infection

SEVERE SEPSIS Sepsis plus one of the following : cardiovascular organ

dysfunction or ARDS or two or more other organ dysfunctions

SEPTIC SHOCK Sepsis and cardiovascular organ dysfunction

(Goldstein et al. Pediatr Crit Care 2005, 6 : 1)

Correlation between
SIRS, Infection and Sepsis
Bacteria
Major surgery
Fungi
Trauma

Infection
Parasite

SEPSIS

SIRS
(non
infectio
n)

Burn
Transplant
rejection

Pancreatitis

Virus
Other

Myocard infarct

Pathophysiology of Sepsis
Infection
Initiations

LPS, Exotoxins

Primary Mediators

TNF, IL-1, IFN, etc

Primary Sites

WBCS, Vascular Coagulation

Secondary
Mediators

O2 Radicals, NO, PAF, TXA2,

ILS, etc
Endothelium, Organs

Secondary Sites
Shock MODS

New Concept about

SIRS, SEPSIS, CARS, MARS
Pro-inflammatory
response

Initial insult
(bacterial, viral,
traumatic, thermal)

Anti-inflammatory
response

Systemic spillover of
antiinflammatory
Systemic reaction
mediators
SIRS (pro-inflammatory)
CARS (anti-inflammatory)
MARS (mixed)

Systemic spillover of
proinflammatory mediators

Cardiovascular Homeostasis
compromise
CARS
shock, SIRS
and SIRS
predominates
balanced

Apoptosis (cell
death) Death
with minimal
inflammation

Organ
dysfunction

SIRS
predominates
CARS : Compensatory Antiinflammatory Response Syndrome
MARS : Mixed Antiinflammatory Response Syndrome

Suppression of
the immune
system CARS
predominates

The Pathophysiological and

Clinical Process of MODS

The Inflammatory Cascade

Leading to MODS

Intestinal Ischemia / Reperfusion Injury

Humoral Mediators
Complemen
t
Endotoxin
Cytokines
PAF
Eicosanoids
Others
Pulmonary
Microvascular
Endothelial
Endothelial Dysfunction
Microvascular
Thrombosis
Ec Blebbing, Focal Necrosis
Increased
microvascular permeability
Interstitial Edema
Alveolar
Hemorrhage / Edema

Cellular Mediators
PMNS (acute)
Macrophages
(chronic)
Selectin
s
Integrin
s
Cel
l
Oxidants
protease
s

PMN

Intestinal Ischemia / Reperfusion Injury

(contd)
Systemic Circulation

Splanchnic Bed

Activated Complement
TNF, IL-1, IL-6, LPS, PAF
ODFRS
TxA2
LTB4

Neutrophils

PAF
TNF

TXA2
LTC4

PGI2

NO
Microcirculatory
Plugging

Activated
Neutrophils

TXA2
Vasoconstriction

IL-2
Reduced Splanchnic Perfusion

Definition of MODS
Occurrence of 2 or more organ
dysfunction for minimum 24 48 hours.
Criteria by:
Marshall
Leteurte or Fischer & Fancony
(Pediatrics)
Goldstein (2005)

Marshall Descriptors
for MODS Outcome
Respiratory system: PO2 / FiO2 ratio.
Renal system: serum creatinine
concentration.
Hepatic system: serum bil.
concentration.
Haematological system: platelet count.
CNS: Glasgow Coma Scale

MODS
Main caused of death in the critically ill
patients in PICU.
The more MODS highest mortality.
1 organ failure 30 40 % mortality.
2 organ failure 50 60 % mortality.
3 organ failure 80 100 % mortality.

Diagnosis approach

P
I
R
O

:
:
:
:

Predisposition of infection
Infection (insult)
Respons of inflammatory
Organ dysfunction

Diagnosis of Septic Shock

Sepsis with signs of shock
Altered consciousness
Low Systolic BP < 5 percentile and low
MAP according to age
Decreased peripheral perfusion: cold
extremities, prolong capillary refill time
> 2 second, increase serum lactate,
urine output < 1 ml/kgBW, core-toe
temperature different > 2 C

Management

BUNDLE DEFINITION
A "bundle" is a group of interventions related
to a disease process that, when executed
together, result in better outcomes than
when implemented individually.
1. Sepsis Resuscitation Bundle
(To be accomplished as soon as possible and scored over first
6 hours):
2. Sepsis Management Bundle
(To be accomplished as soon as possible and scored over
first 24 hours):

6 Hours
Resuscitation Bundle
Early Identification
Early Antibiotics and Cultures
Early Goal Directed Therapy

6 - hour Severe Sepsis/Septic Shock Bundle

1. Early Detection:
Obtain serum lactate.

2. Early Blood
Cx/Antibiotics:
within 3 hours of
presentation.

3. EGDT:
Hypotension
or lactate > 4 mmol/L:
initial fluid bolus
20-40 ml of crystalloid (or
colloid equivalent) per kg of
body weight.

Vasopressors:

Hypotension not
responding to fluid
Titrate to MAP according
to age.

Septic shock or
lactate > 4 mmol/L:

CVP and ScvO2 measured.

CVP maintain >8 mmHg.
MAP maintain >65 mmHg.

ScvO2<70% with
CVP > 8 mmHg,
MAP > 65 mmHg:

PRBCs if Ht < 30%.

Inotropes.

24 - hour Severe Sepsis and

Septic Shock Bundle

Glucose control (insulin):

maintained on average <150 mg/dL (8.3 mmol/L)

Steroids:
for septic shock requiring continued use of
vasopressors for equal to or greater than 6 hours.

Lung protective strategy:

Maintain plateau pressures < 30 cm H2O for
mechanically ventilated patients

Early Antibiotic/Culture
Within the first hour
Culture should be made before
antibiotic
Empirical AB/ De-escalation of one
or more drugs that active against all
likely pathogen and that penetrate in
the presumed source of infection

Graph: Blood culture

30

20

Count

10

Jenis kelamin
perempuan

laki-laki

Jenis kuman darah ?

Graph: Urine culture

Jenis kelamin

Count

perempuan
0

laki-laki
Enterob. aerogenes

Pseudomonas aerugino

Staphylococcus epide

Jenis kuman urine ?

E. coli

Graph: ETT culture

7

Count

Jenis kelamin

perempuan

laki-laki
Enterob. aerogenes

Pseudomonas aerugino

Staphylococcus epide

Jenis kuman kultur ET ?

E. coli

Graph: Ampicillin sensitivity

40

30

20

Kultur darah sensiti

Count

10

tidak
0

ya

Jenis kuman darah ?

Graph: Chloramphenicol sensitivity

20

10

Count

Kultur darah sensiti

tidak
0

ya

Jenis kuman darah ?

Graph: Gentamycin sensitivity

30

20

Count

10

Kulturdarah sensitif
tidak

ya

Jenis kuman darah ?

Graph: Amikacin sensitivity

30

20

Count

10

Kultur darah sensiti

tidak

ya

Jenis kuman darah ?

Graph: Cefotaxime sensitivity

30

20

Count

10

Kultur darah sensiti

tidak

ya

Jenis kuman darah ?

Graph: Ceftazidime sensitivity

20

10

Count

Kultur darah sensiti

tidak
0

ya

Jenis kuman darah ?

Graph: Cefepime sensitivity

30

20

Count

10

Kultur darah sensiti

tidak

ya

Jenis kuman darah ?

Graph: Fosfomycin sensitivity

30

20

Count

10

Kultur darah sensiti

tidak

ya

Jenis kuman darah ?

Graph: Meropenem sensitivity

30

20

Count

10

Kultur darah sensiti

tidak

ya

Jenis kuman darah ?

Empirical Antibiotic Therapy

Started within 1 hour of recognition of severe
sepsis after cultures have been obtained
Initial empirical antibiotic therapy: one or more
drugs that have activity against likely pathogen
and penetrate into the presumed source of
infection ( 48-72 hrs )
Guided by susceptibility pattern of microorganism
in the community/hospital

Source of infection

Skin and integument

Respiratory tract
GI tract
Genitourinary tract

Common bugs

55% polymicrobial

JAMA 1995;274:639644

The causative micro-organisms most commonly

isolated from patients with PICU-acquired infections
Dr Kariadi Hospital
January December 2006

2005

2006

No.

Microorganisms

Rank

Rank

E.coli

28

19

K.pneum.

23

20

S.aureus/MRSA

17

21

P.aeruginosa

19

23

E.aerogenes

18

27

S.epid./MRSE

20

29

Proteus spp.

15

11

Candida

12

15

Acinetobac. spp

14

apted from Nosocomial Surveillance System Data , Dr Kariadi Hospital 1998-2006

Antibiotics
Full- loading dose
AB/ regimen should be reassessed
daily to optimize activity, prevent
resistance, reduced toxicity, and cost
Combination th/ if known/suggest
pseudomonas

Most Common Pathogens in Childhood

Bacterial Sepsis
Age Group

0 1 months

Pathogens

(Pending culture)

Initial
dose
(mg/kg)

Group B Strept. Enterobacteriaceae

Ampiciline +

50

Staph. Aureus

Gentamicin

2.5

Listeria meningtides

Cefotaxime

5-0

Cefotaxime

50

S. aureus, Neisseria meningtidis

Ampiciline +

50

Group B Streptococcus

Chlorampenicol

25

S. Pneumoniae

Cefotaxime

50

H. Influenzae

Cefriaxone

50

S. Aureus

Ampiciline +

50

N. Meningtidis

Chlorampenicol

25

S. aureus, Proteus

Vancomycin +

25

Pseudomonas

Ceftazidime +

50

Enterobacteriaceae

Ticarcillin

75

1 24 months H. influenzae, Strept. Pneumoniae

> 24 months

Immuno
compromised

Antimicrobial

Antibiotic
Combination AB/ in neutropenic
patients
Empirical AB/ not more than 3 5
days
Duration of AB: 7 10 days

Negative cultured
Sepsis occurred
In > 50%
Decision to : continue,
Narrow, stop of AB
On the basis 0f
Clinical judgment
&
Clinical information

4 basic principles of empirical

Antibiotic Therapy
Adequate and accurate antibiotic therapy
Therapeutic effect of antibiotic
Antibiotic effect and negative effect of
antibiotic
Accurate time of antibiotic therapy

Stepwise management of hemodynamic support with goals of normal perfusion and perfusion pressure (MAP-CVP)
in infants and children with septic shock. Proceed to next step if shock persists.

Recognize
Recognize decreased
decreased mental
mental status
status and
and perfusion.
perfusion.
Maintain
Maintain airway
airway and
and establish
establish access
access according
according to
to PALS
PALS guidelines.
guidelines.

0 min
5 min

Push
Push 20cc/kg
20cc/kg isotonic
isotonic saline
saline or
or colloid
colloid boluses
boluses up
up to
to and
and over
over 60
60 cc/kg
cc/kg
Correct
Correct hypoglycemia
hypoglycemia and
and hypocalcemia
hypocalcemia
Fluid refractory shock

15 min
Fluid responsive

Establish
Establish central
central venous
venous access,
access, begin
begin
dopamine
dopamine therapy
therapy and
and establish
establish arterial
arterial monitoring
monitoring ..
Fluid refractory-dopamine resistant shock

Observe
Observe in
in PICU
PICU

Titrate
Titrate epinephrine
epinephrine for
for cold
cold shock,
shock, norepinephrine
norepinephrine for
for warm
warm
shock
shock to
to normal
normal MAP-CVP
MAP-CVP and
and SVC
SVC O2
O2 saturation
saturation >
> 70%
70%

At Risk of Adrenal Insufficiency?

60 min

Give
Give hydrocortisone
hydrocortisone
Normal Blood Pressure
Cold Shock
SVC O2 sat < 70%
Add vasodilator or Type III PDE inhibitor
with volume loading

Catecholamine -resistant shock

Not at
Risk?
Do
Do not
not give
give hydrocortisone
hydrocortisone
Low Blood Pressure
Cold Shock
SVC O2 sat < 70%
Volume and Epinephrine

Low Blood Pressure

Warm Shock
Volume and Norepinephrine
(?vasopressin or angiotensin)

Persistent Catecholamine-resistant shock

Place
Place pulmonary
pulmonary artery
artery catheter
catheter and
and direct
direct fluid,
fluid,
inotrope,vasopressor,vasodilator,
inotrope,vasopressor,vasodilator, and
and hormonal
hormonal therapies
therapies to
to
22
attain
normal
MAP-CVP
and
CI
>
3.3
and
<
6.0
L/min/m
attain normal MAP-CVP and CI > 3.3 and < 6.0 L/min/m

Refractory shock
Consider
Consider ECMO
ECMO

k
g
n
e
r
a
r
a
T
iu ana
y
a
d
sa

Soal latihan MCQ

1. Pernyataan yang benar tentang sepsis :
a. Sindrom klinis akibat respons proinflamasi
sistemik masif terhadap infeksi
b. Tidak terjadi pada penderita imunodefisiensi
c. Disebabkan oleh bakteri gram negatif tetapi
tidak oleh bakteri gram positif
d. Bukan disebabkan oleh virus ataupun parasit

2. Metronidazole perlu diberikan dalam

terapi antibiotik empiris pada penderita
sepsis dengan dugaan fokus infeksi di
daerah :
a. Rongga mulut
b. Muskuloskeletal
c. Rongga abdomen
d. Paru-paru

3.

Seorang bayi berusia 7 bulan dengan sepsis

disertai adanya tanda inflamasi dan hematoma
di kedua kelopak mata dan jaringan
muskulokutaneus. Mikroorganisme yang paling
mungkin sebagai penyebab :
a. Staphylococcus
b. Streptococcus hemoliticus
c. Pseudomonas aerogenosa
d. Haemophilus influenzae

4. Pemberian cairan initial pada penderita sepsis

berat adalah :
a. Cairan 20 ml/kgBB/jam
b. Cairan rumatan
c. Cairan 20-40 ml/kgBB/jam
d. Cairan 20-60 ml/kgBB/secepatnya

5. Pada penderita HIV, penyebab sepsis tersering

adalah :
a. Trepanoma pallidum
b. Streptococcus pneumoniae
c. Mycobacterium tuberculosis
d. Pneumocystis jiroveci

6. Seorang anak dengan sepsis disertai adanya

hipotensi dan penurunan kesadaran, memberikan
respons hemodinamik yang baik setelah inisiasi
cairan resusitasi, diklasifikasikan sebagai
penderita :
a. Sepsis
b. Sepsis berat
c. Syok sepsis
d. Kegagalan organ multipel

7. Pemberian kortikosteroid pada penderita sepsis

menunjukkan manfaat yang baik bila diberikan pada :
a. Syok septik
b. Acute Respiratory Distress Syndrome
c. Sepsis dini disertai perdarahan korteks adrenal
d. Kegagalan organ multipel disertai pankreatitis
akut