Nama : Dr. Abbas Suherli, Sp. PKTTL : Sukabumi, 21 Jan 1967Riwayat Pendidikan : Patologi Klinik, FKUI (2001)Riwayat Pekerjaan : RSUD Kota Bekasi RS Elisabeth, Bekasi

Dr. Abas Suherli, Sp.PKRSUD Kota Bekasi

RS St Elisabeth Bekasi

Demam perlu diwaspadai!!!Demam perlu diwaspadai!!!Demam :Suhu Tubuh > 37,8 oC

Suhu Normal :36,5 - 37,2 oC

Mengapa Demam Perlu Diwaspadai ??

Menandakan adanya infeksi/penyakit yang sedang menyerang tubuh

MerangsangProduksi PIROGEN -ENDOGEN

DitangkapSEL FAGOSIT

Menggigil,pembuluh darahmenyempit

Set-pointHIPOTALAMUSmeningkat

DEMAM

BENDA ASING(Virus, bakteri, Jamur, parasitdll)

PembentukanPROSTAGLANDIN

Enzim Cyclo-oxygenase

Points PCT 9 IL-6 9 WBC 5 HLA-DR 4 Protein C 4 CRP 3 IL-10 3 IL-8 3 HMG-1 2 D-Dimer 2 e-Selectin 2

Points Tissue factor 2 TNF 2 Thrombocytes 2 Cholesterol 1 Elastase 1 C3a 1 IL-1ra 1 Thrombomodulin 1 Neopterin 1 Cortisol 1

* 80 possible sepsis biomarkers

500,000 new cases of sepsis per year in North America

Sepsis develops in approximately 1% of hospitalized patients

Sepsis mortality rate of 35% to 45% New therapeutics near approval will require

patient selection Established markers show poor differentiation

between severe sepsis and other critical conditions

PCT is the 116-amino acid prohormone of calcitonin – selectively responds to systemic and septic infections.

Early and reliable diagnosis. Increase in sepsis is not accompanied by an

increase in calcitonin levels. An increase in PCT concentration can be

detected in as little as 2 to 3 hours after the onset of septic infection.

Does not accumulate in severe renal dysfunction

Easily measured by immunoassay.

= N-ProCT

= Calcitonin

= Katacalcin= cleavage by endopeptidases

57

60

1

91

96

116

Normal subjects <0.2

Chronic inflammatory processes and autoimmune diseases

<0.5

Viral infections <0.5

Mild to moderate localized bacterial infections

<0.5

SIRS, multiple trauma, burns 0.5 – 2

Severe bacterial infections, sepsis, multiple organ failure

>2 (often 10 – 100)

PCT (ng/mL)

Monitoring patients at risk of systemic bacterial infection

Assess severity of septic processes Prognosis – response to therapy Assess Fever of Unknown Origin (FUO) Guidance for Antibiotics therapy

PCT 0.94(0.90 to 0.96)

CRP 0.89(0.85 to 0.92)

IL-6 0.78(0.71 to 0.83)

Area under ROC Curve(95% confidence interval)

Median PCT Levels

Local Bact Inf Invasive Inf Viral Inf

PCT

(ng/

mL)

0

2

4

6

8

10

12

14

16

18

n=78

n=46

n=236

IL6 stimulates hepatocytes to produce CRP; also stimulates acute phase response

Occurs in response to many stimuli (not only bacterial infection)

IL6 rises rapidly after infection, prior to CRP

IL6 10x cost of CRP assay

255 neonates investigated for suspected sepsis

IL6 at presentation and after 24 hours

Babies divided into categories of infection

0

2000

4000

6000

8000

10000

12000

None Possible Probable Definite

IL6 (0IL6(24)

IL6 (0) Sensitivity Specificity PPV NPV

< 20 pg/ml

73 56 28 90

< 50 pg / ml

59 72 33 88

Median IL-6 Levels

Local Bact Inf Invasive Inf Viral Inf

IL-6

(pg/

mL)

0

100

200

300

400

500

n=50

n=29

n=156

Good correlation between IL6 at 0 hours and CRP at 24 hours

Best prediction of infection with IL6 at 0 hours and CRP at 24 hours

IL6 not a reliable single marker Initial IL6 < 20 pg/ml may allow

antibiotics to be withheld

Acute phase reactant synthesis by liver Released at 4- 6 hours, peaks at 24- 48 hours Rise and fall correlates with infection CRP at 24 hours is a good marker of

bacterial sepsis >50mg/l distinguishes infection from

inflammation but LOW specificity CRP assay is cheap – inexpensive

SERIAL measurements of CRP Excellent negative predictive value– Rule out

sepsis Reverse is not true – non specific, poor positive

predictive value Do not treat raised CRP in isolation – rely

on clinical condition and culture results

Median CRP Levels

Local Bact Inf Invasive Inf Viral Inf

CR

P (m

g/L)

0

20

40

60

80

100

120

140

n=78

n=46

n=236