DIVISI PENYAKIT TROPIK & INFEKSI

DEPARTEMEN / SMF ILMU PENYAKIT DALAM

FK USU /RS H ADAM MALIK MEDAN

Definisi :
Sepsis adalah kumpulan gejala akibat respons
sistemik terhadap inflamasi (Sistemic
Inflammatory Respons Syndrome = SIRS) akibat
infeksi.
Dikatakan sepsis bila terdapat 2 dari 4 SIRS yi :
1. Suhu tubuh > 38 atau < 36 C
2. Denyut jantung > 90 x/m
3. Pernafasan > 20 x/m atau PaCO2 < 32 mmHg
4. Lekosit > 12.000 atau < 4000 /mm3 atau
sel muda >10%
ADA BUKTI INFEKSI
atau SUSPEK INFEKSI

Hubungan antara Sepsis dan SIRS

BACTEREMIA

INFECTION

TRAUMA

SEPSIS
SEPSIS
SIRS

BURNS

PANCREATITIS

Parasite

Virus

Infection
Fungus

Severe
Sepsis
shock

SIRS

Sepsis

Severe
SIRS Trauma

Bacteria
BSI

Adapted from SCCM ACCP Consensus Guidelines

Burns

Urutan Paling Sering :

Gram Negatif
Gram Positif
Jamur
Parasit
Virus

The continuum of Sepsis

SIRS

Sepsis

Severe sepsis

Septic shock

Systemic Inflammatory Responds Syndrome

(SIRS) criteria
-Temp <36 / >38o or >100.4oF
-HR > 90
-RR >20 or PCO2 <32mmHg
-WBC <4 or >12 or bands > 10%
Bone et al. Chest 1992;101:1644

The continuum of Sepsis

SIRS

Sepsis

Severe sepsis

Septic shock

Systemic Inflammatory Responds to

Infection
-Suspected or confirmed infection
-2 or more SIRS criteria
Bone et al. Chest 1992;101:1644

The continuum of Sepsis

SIRS

Sepsis

Severe sepsis

Septic shock

Sepsis plus organ dysfunction

Bone et al. Chest 1992;101:1644

The continuum of Sepsis

SIRS

Sepsis

Severe sepsis

Septic shock

Severe sepsis and hypotension

Hypotension that does NOT
respond to fluid (30ml/kg bolus)

Bone et al. Chest 1992;101:1644

Sepsis berat
Sepsis
Gangguan fungsi organ
Hipotensi atau hipoperfusi laktik
asidosis, oliguria, perubahan status
mental akut
Septik Syok
TDS < 90 mmHg
Nadi > 100 x/m

HATI

Hiperbilirubinemia
Peningkatan transaminase
Sintesa faktor pembekuan menurun Koagulopati
GINJAL

Oliguria/ Anuria Overload volume

Imbalans Elektrolit
JANTUNG
Sitokin menekan fungsi miosit Gagal Jantung
Kerusakan sel troponin meningkat

Paru:
acute lung injury. (ALI) (PaO2/FiO2 < 300)
acute respiratory distress syndrome.(ARDS)
(PaO2/FiO2 < 200)
Otak
Encefalopati, agitasi, konfusi, koma

Salah satu penyebab kecacatan dan kematian

yang cukup tinggi di dunia.
Penyebab kematian dengan angka kejadian
tertinggi pada ICU (noncoronary)
Penyebab kematian pada urutan ke-11 secara
umum
Lebih dari 750.000 kasus sepsis berat terjadi di USA
setiap tahun
Di Amerika terjadi 500 kematian karena sepsis
setiap harinya

Dendritic

Neutrophil

Macrophage
(+/)

(+/)

(+/)

Necrotic
cell

Necrotic
cell
Apoptotic
cell

Apoptotic
cell

(+)
Anergy
(Th2) Antiinflammatory
cytokines
(Th1) Inflammatory
cytokines

CD4
(Th2) Antiinflammatory
cytokines
(Th1) Inflammatory
cytokines

Inflammatory (type 1 helper T-cell [Th1]) properties, including

TNFa
interferon gamma
Interleukin-2

Cytokines with antiinflammatory (type 2 helper T-cell [Th2]) properties

Interleukin- 4
Interleukin-10

The factors that determine whether CD4 T cells have Th1 or Th2 responses are
unknown
May be influenced by
Type of pathogen
Size of the bacterial inoculum
Site of infection.
The level of interleukin-10 is increased in patients with sepsis and that this level
predicts mortality.

Infection

Vasodilation

Hypotension

Inflammatory
Mediators

Microvascular Plugging

Endothelial
Dysfunction

Vasoconstriction

Maldistribution of Microvascular Blood Flow

Ischemia

Pathophysiology of
Sepsis-Induced
Ischemic Organ
Injury

Cell Death

Organ Dysfunction

Edema

Infection Source in Severe

Sepsis
10.8%
6.0%
8.0%

44.0%

2.2%
6.6%
8.6%
9.1%

Respiratory
Bacteremia
GU
Abdomen
Soft tissue
Device
CNS
Endocarditis
Other

17.3%

Angus DC et al. Crit Care Med. 2001; 29:1303

ROLE OF PROCALCITONIN
IN INITIAL SEPSIS
DIAGNOSIS & MANAGEMENT

PCT Level Increase = Increased

Significance of Bacterial Infection
2 ng/ml
0.5 ng/ml

0.05 ng/ml

Healthy
Individuals

Local
Infections

Systemic
Infections
(Sepsis)

Severe
Sepsis

Septic
Shock

In critically ill patients, PCT levels elevate in correlation to the severity of bacterial
infection
In healthy people, PCT concentration are found below 0.05ng/ml
Concentrations exceeding 0.5ng/ml can be interpreted as abnormal

PCT reflects the response of the

organism to the bacterial challenge
Elevated / rising PCT levels
Systemic response to the infection - indicates that
infection is developing or is outside the control of the
immune system
Risk for further progression
Low PCT levels despite clinical signs and symptoms
Self-limiting bacterial infection
Non-infectious cause
Early phase of infection

Table 4
Sensitivity, specificity, and negative and positive predictive value of
laboratory parameters in predicting sepsis
Parameter

CRP

TNF-

IL-2

IL-6

IL-8

PCT

58

55

63

51

68

85

58

66

55

53

57

91

Negative
predictive
value (%)

68

65

65

56

69

95

Positive
predictive
value (%)

53

54

50

42

53

89

Sensitivity
(%)
Specificity
(%)

CRP, C-reactive protein; IL, interleukin; PCT, procalcitonin; TNF,

tumour necrosis factor.

PCT results provide important information on

prognosis of CAP patients in emergency room
Mortality by PCT level
12%

10%

PCT

0.1

Mortality, %

8%

6%

4%

PCT < 0.1

2%

0%
0

10

15

20

25

30

Day

PCT can be used for Risk stratification of patients with CAP

Low PCT levels identify patients presenting in the ED with Pneumonia that have a low
risk for mortality (N=1,651).

Serial measurement of PCT provides a clearer

picture of the patients response to
antibiotic treatment.

Decreasing PCT levels in patients with sepsis indicate effective treatment of the
underlying infection

Persistently elevated PCT levels indicate a possible treatment failure

When integrated into the management of septic patients, PCT can help clinicians
to manage septic patients more efficiently

Stueber, F. University of Bonn, Lecture at ISICEM, Brussels 2001

PCT guidance in antibiotic

usage Effects on length of stay

Effect of PCT-guided management in patients with sepsis on ICU length of stay

Nobre V. et alAM Resp Crit Care Med 2008: 177:498-505

PRINSIP PENATALAKSANAAN
1. Bunuh kuman dengan Antimikrobial
2. Hilangkan sumber infeksi a.l. dengan Drainase

3. Memperbaiki Hemodinamik dan Respiratorik

4. Penatalaksanaan disfungsi Organ

ANTIMIKROBIA
Antimikroba empiris harus diberi sesegera
mungkin setelah sampel darah dan bagian lain
yang relevan sudah dikultur.
Keterlambatan 1 jam akan meningkatkan
kematian 7%
Jika hasil kultur sudah ada, regimen yang
diberikan adalah antimikrobial tunggal sesuai
hasil kultur

Menghilangkan / mendrainase sumber

infeksi
Drainase sumber kuman
Contoh : Abses, Cairan Peritoneum, Pleura, dll

Ganti Infus set Kultur Kanula

Ganti Kateter Urin
Ganti NGT
Perhatikan apakah ada sinusitis bila ada intubasi
Cegah / rawat dekubitus

Memperbaiki Hemodinamik dan Respiratorik

Pemberian cairan IV untuk mencegah udem
paru Tek.vena sentral dipertahankan 8-12
cmH2O.
Urine output harus dijaga > 0,5cc/kgBB per
jam dengan terus memberi cairan
Pertahankan MAP > 65mmHg , tek.sistolik >
90mmHg dan Cardiac Index 4L/min per m2.

Penatalaksanaan disfungsi Organ

Gagal Ginjal Hemodialisa
Gagal Nafas Ventilasi Mekanis

Intensive insulin therapy for hyperglycemia

Van den Berghe et al.
Maintained the blood glucose level at 80 to 110 mg/dL
Lower morbidity and mortality
Reduced the frequency of episodes of sepsis by 46 percent.
Reduced multiple-organ failure
The phagocytic function of neutrophils is impaired in patients
with hyperglycemia
Insulin prevents apoptotic cell death

Volume resuscitation
Early aggressive therapy that optimized cardiac preload, afterload, and contractility
in patients with improved the likelihood of survival
Colloid or crystalloid, vasoactive agents, and transfusions of red cells
increase oxygen delivery.

Corticosteroids

High doses of corticosteroids

(e.g., 30 mg of methylprednisolone /kgBW) increasing
secondary infections
Corticosteroids increase the expression of adrenergic receptors.
50-mg intravenous bolus four times per day) and fludrocortisone
(50 g per day) : 7days improved survival
Penelitian diSolo ( Guntur dkk ) memberikan 60 mg
Metilprednisolon/hari /IV selama 5 Hari memberikan hasil
yang baik.
Good for adrenal insufficiency