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
Pathogenesis interpretation:
Diagnosis hematology, serology
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
SIRS Burn
Parasite SEPSIS (non
infectio
Transplant
n)
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 O2 Radicals, NO, PAF, TXA2,

Mediators ILS, etc
Secondary Sites Endothelium, Organs

Shock MODS
 New Concept about
SIRS, SEPSIS, CARS, MARS
Pro-inflammatory Anti-inflammatory
response response
Initial insult
(bacterial, viral,
traumatic, thermal)
Systemic spillover of Systemic spillover of
pro- anti-
inflammatory mediators Systemic reaction inflammatory
SIRS (pro-inflammatory) mediators
CARS (anti-inflammatory)
MARS (mixed)

Cardiovascular Homeostasis Apoptosis (cell Organ Suppression of

compromise CARS death) Death dysfunction the immune
shock, SIRS and SIRS with minimal system CARS
predominates balanced inflammation SIRS
predominates
CARS : Compensatory Antiinflammatory Response Syndrome predominates
MARS : Mixed Antiinflammatory Response Syndrome
The Pathophysiological and
Clinical Process of MODS
The Inflammatory Cascade
Leading to MODS
Intestinal Ischemia / Reperfusion Injury

Humoral Mediators Cellular Mediators

Complemen
t PMNS (acute)
Endotoxin Macrophages
(chronic)
Cytokines Selectin
PAF s
Integrin
Eicosanoids s
Others
Pulmonary Microvascular Cel
Endothelial l PMN
Endothelial Dysfunction
Microvascular Oxidants
Thrombosis protease
Ec Blebbing, Focal Necrosis s
Increased
microvascular permeability
Interstitial Edema
Alveolar
Hemorrhage / Edema
 Intestinal Ischemia / Reperfusion Injury
(contd)
Splanchnic Bed Systemic Circulation
Activated Complement
TNF, IL-1, IL-6, LPS, PAF

ODFRS PGI2
TxA2
NO
LTB4 Neutrophils Microcirculatory Activated
Plugging Neutrophils
PAF
TXA2 TXA2
TNF LTC4
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 : Predisposition of infection
I : Infection (insult)
R : Respons of inflammatory
O : 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: Vasopressors:

Obtain serum lactate. Hypotension not
responding to fluid
Titrate to MAP according
2. Early Blood to age.
Cx/Antibiotics:
within 3 hours of Septic shock or
presentation. lactate > 4 mmol/L:
CVP and ScvO2 measured.
3. EGDT: CVP maintain >8 mmHg.
Hypotension MAP maintain >65 mmHg.

or lactate > 4 mmol/L: ScvO2<70% with

initial fluid bolus CVP > 8 mmHg,
20-40 ml of crystalloid (or MAP > 65 mmHg:
colloid equivalent) per kg of PRBCs if Ht < 30%.
body weight. 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

10
Jenis kelamin

perempuan
Count

0 laki-laki

Jenis kuman darah ?

 Graph: Urine culture

Jenis kelamin
1

perempuan
Count

0 laki-laki
Enterob. aerogenes Pseudomonas aerugino
Staphylococcus epide E. coli

Jenis kuman urine ?

Graph: ETT culture

2
Jenis kelamin
1
perempuan
Count

0 laki-laki
Enterob. aerogenes Pseudomonas aerugino
Staphylococcus epide E. coli

Jenis kuman kultur ET ?

Graph: Ampicillin sensitivity

40

30

20

Kultur darah sensiti

10

tidak
Count

0 ya

Jenis kuman darah ?

Graph: Chloramphenicol sensitivity

20

10

Kultur darah sensiti

tidak
Count

0 ya

Jenis kuman darah ?

Graph: Gentamycin sensitivity

30

20

10
Kulturdarah sensitif

tidak
Count

0 ya

Jenis kuman darah ?

Graph: Amikacin sensitivity

30

20

10
Kultur darah sensiti

tidak
Count

0 ya

Jenis kuman darah ?

Graph: Cefotaxime sensitivity

30

20

10
Kultur darah sensiti

tidak
Count

0 ya

Jenis kuman darah ?

Graph: Ceftazidime sensitivity

20

10

Kultur darah sensiti

tidak
Count

0 ya

Jenis kuman darah ?

Graph: Cefepime sensitivity

30

20

10
Kultur darah sensiti

tidak
Count

0 ya

Jenis kuman darah ?

Graph: Fosfomycin sensitivity

30

20

10
Kultur darah sensiti

tidak
Count

0 ya

Jenis kuman darah ?

Graph: Meropenem sensitivity

30

20

10
Kultur darah sensiti

tidak
Count

0 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
1 E.coli 28 1 19 6
2 K.pneum. 23 2 20 5
3 S.aureus/MRSA 17 6 21 4
4 P.aeruginosa 19 4 23 3
5 E.aerogenes 18 5 27 2
6 S.epid./MRSE 20 3 29 1
7 Proteus spp. 15 7 11 8
8 Candida 12 9 15 7
9 Acinetobac. spp 14 8 9 9

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 Pathogens Antimicrobial Initial
(Pending culture) dose
(mg/kg)
0 1 months Group B Strept. Enterobacteriaceae Ampiciline + 50
Staph. Aureus Gentamicin 2.5
Listeria meningtides Cefotaxime 5-0
1 24 months H. influenzae, Strept. Pneumoniae Cefotaxime 50
S. aureus, Neisseria meningtidis Ampiciline + 50
Group B Streptococcus Chlorampenicol 25
> 24 months S. Pneumoniae Cefotaxime 50
H. Influenzae Cefriaxone 50
S. Aureus Ampiciline + 50
N. Meningtidis Chlorampenicol 25

Immuno S. aureus, Proteus Vancomycin + 25

compromised Pseudomonas Ceftazidime + 50
Enterobacteriaceae Ticarcillin 75
 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.
0 min Maintain
Maintain airway
airway and
and establish
establish access
access according
according to
to PALS
PALS guidelines.
guidelines.
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 andand hypocalcemia
hypocalcemia

15 min Fluid refractory shock

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? Catecholamine -resistant shock Not at

Risk?
60 min
Give
Give hydrocortisone
hydrocortisone Do
Do not
not give
give hydrocortisone
hydrocortisone

Normal Blood Pressure Low Blood Pressure Low Blood Pressure

Cold Shock Cold Shock Warm Shock
SVC O2 sat < 70% SVC O2 sat < 70%
Add vasodilator or Type III PDE inhibitor Volume and Epinephrine Volume and Norepinephrine
with volume loading (?vasopressin or angiotensin)
Persistent Catecholamine-resistant shock
Place
Place pulmonary
pulmonary artery
artery catheter
catheter and
and direct
direct fluid,
fluid, Refractory shock
inotrope,vasopressor,vasodilator,
inotrope,vasopressor,vasodilator, and
and hormonal
hormonal therapies
therapies toto
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 22
Consider
Consider ECMO
ECMO
 gk
en
r a r
Ta iu ana
ay
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