Divisi Penyakit Tropik Dan Infeksi Departemen Ilmu Penyakit Dalam

FK UNS / RSUD Dr. Moewardi Surakarta

CURICULUM VITAE
Nama : dr. Arifin, SpPD, KIC, FINASIM
Tempat/tanggal lahir : Jombang, 8 Januari 1972
Agama : ISLAM
Alamat kantor : SMF Ilmu Penyakit Dalam RSUD Dr. Moewardi Surakarta
Jl. Kolonel Sutarto 132 Surakarta
Alamat rumah : Jl. Tarumanegara III No. 39 Banyuanyar Banjarsari
Surakarta
Handphone : +62813 2751 2014, +6281 7946 9272
Email : cakipin.as@gmail.com
Spesialis : Penyakit Dalam FK UNS 2008
Konsultan : Konsultan Intensive Care FK UI/RSCM Jakarta 2015
Jabatan : Kepala medical ICU RSUD Dr Moewardi
 History of Sepsis Definition
Infection/trauma SIRS Sepsis Severe Sepsis
1991
SIRS + presumed or
confirmed infectious process

≧2 of the following: ≧1 organ dysfunction

•BT >38℃ or <36℃ •Cardiovascular (Refractory low BP)
•HR > 90bpm •Adrenal
•RR > 20bpm or PaCO2 <32mmHg •Hematologic
•WBC >12,000, <4,000, or >10% bands •Coagulation
•Renal
•Respiratory Septic shock
•Hepatic
•CNS
Bone RC, et al. Chest 1992;101:1644
•Unexplained metabolic acidosis
History of Sepsis Definition

2001 Expanded General

List Criteria
Parameters
Diagnostic
Limitations Inflammatory Parameters
sepsis definition
in 1991
Did Not offer alternatives
Haemodynamic Parameters

because lack
Tissueof evidence
Perfusion Parameters
Levy et al. Intensive Care Med. 2003;29(4):530-538
New Definition of Sepsis

2016

SCORE ≥ 2
Sepsis is defined as life-threatening organ dysfunction
caused by a dysregulated host response to infection
New Definition of Septic Shock
Septic shock is a subset of sepsis in which underlying circulatory and
cellular/metabolic abnormalities are profound enough to substantially
increase mortality.

Need Vassopressor to
Persisting hypotension maintain MAP ≥ 65 mmHg
despite adequate fluids
Serum lactat level > 2
resuscitation mmol/L (18 mg/dL)
qSOFA (quick SOFA)

Respiration rate ≥ 22/min

Altered Mentation Clinical Tool

Systolic Blood Pressure ≤
100 mmHg
Screening patients likely to have sepsis

Sepsis
 EPIDEMIOLOGY
Incidence Septic Shock

Data collected over an 8-year period from 22 hospitals (Annane et al Am J Respir Crit Care Med 2003;
168:165-72)

1
2
3 Source of Septic
Shock

Kumar et al, Crit Care Med 2010; 38:1773–85)

Sepsis Resuscitation Bundle (2015)
TO BE COMPLETED WITHIN 3 HOURS OF TIME OF PRESENTATION*:
1. Measure lactate level
2. Obtain blood cultures prior to administration of antibiotics
3. Administer broad spectrum antibiotics
4. Administer 30ml/kg crystalloid for hypotension or lactate ≥4mmol/L
TO BE COMPLETED WITHIN 6 HOURS OF TIME OF PRESENTATION:
5. Apply vasopressors (for hypotension that does not respond to initial fluid
resuscitation) to maintain a mean arterial pressure (MAP) ≥65mmHg
6. In the event of persistent hypotension after initial fluid administration (MAP <
65 mm Hg) or if initial lactate was ≥4 mmol/L, re-assess volume status and
tissue perfusion and document findings (see below).
7. Re-measure lactate if initial lactate elevated.
 Sepsis Resuscitation Bundle (2017)

• Hour One Bundle : initial resuscitation in sepsis and septic

shock ( start immidiately)
1. Measure lactate level*
2. Obtain blood cultures prior to administration of antibiotics
3. Administer broad spectrum antibiotics
4. Administer 30ml/kg crystalloid for hypotension or lactate
≥4mmol/L
5. Apply vasopressors during or after initial fluid resuscitation
to maintain a mean arterial pressure (MAP) ≥65mmHg

* Re-measure lactate if initial lactate elevated (> 2mmol/L)

 Treatment of Septic
Shock

Hemodynamic Infection Control

Stabilization

Vasoactive Source
Fluids Antibiotics
agents control

Modulation of the
septic response

Steroid .....
 Management of Sepsis

EARLY
1 3
Save lives
2

Hemodynamic Infection
Recognition restoration control
• q SOFA • Fluids • Antibiotics
• SOFA • Vasopressors • Source control
Why should we give fluids in sepsis?

Vasoplegia Capillary leak

SEPTIC SHOCK
Vasodilatory
shock
Distributive
shock

No volume loss !!!

 Treatment of Septic
Shock

Hemodynamic Infection Control

Stabilization

Vasoactive Source
Fluids Antibiotics
agents control

Modulation of the
septic response

Steroid .....
Steroid .....
How to use
We suggest against using IV hydrocortisone to
treat septic shock patients if adequate fluid
resuscitation and vasopressor therapy are able to
restore hemodynamic stability. If this is not
achievable, we suggest IV hydrocortisone at a
dose of 200 mg per day (weak recommendation,
low quality of evidence).
 Role of Response
Immune in Sepsis

Proinflammatory Response Anti-inflammatory Response

IL-1, IL-6, TNF-a IL-10, IL-4, IL-1ra

MARS
Mixed Antagonist Response Syndrome

Hyperinflammatory
Status Anti-inflammatory
Status
SIRS
Systemic Inflamatory Response Syndrome CARS
Compensatory Anti-inflammatory
Cardiovascular compromise (shock) Response Syndrome
Apoptosis - Necrosis
Organ dysfunction (MODS/MOF) Suppression of the Immune System
 IMUNOPATOGENESIS

C3a, C5a LPS APC SUPER ANTIGEN

IMUNO.COM
LPS bp

C7a CD 4+ TCR
CD 14
TLR 4 IL - 10
IFN - g IL - 4
TLR2 TH - 1 TH - 2 IL - 5 B cell
IL - 6
CSF Ig
IL 8
SEPSIS
IL 6 IL-2
IL -1 NÆ
Compl.
TNF - a CD 8+
MOD
NK
TF-VIIA ↑
PaI-1↑ PGE 2 NO ICAM -1

SHOCK
SEPTIC (Guntur, 2000)
 HPA AKSIS

normal sepsis Syok septik

CRH CRH CRH

corticosteroid
pituitary pituitary pituitary

Corticotropin Corticotropin Corticotropin

Cytokines
Anesthetics
Antiinfective agents
adrenal adrenal adrenal Hemorrhage
infection

Mineralocorticotropin Mineralocorticotropin Mineralocorticotropin

Epinephrine Epinephrine Epinephrine
Nor-epinephrine Nor-epinephrine Nor-epinephrine
cortisol cortisol cortisol
 Route of Cytokine Releases
LPS
ENDOTOKSIN
TLR4
CD14 MD-2
Corticosteroid
PPRg
My D88 Herbal
IRAK
TRAF6

NF-KB M
Target Genes

CYTOKINES
TNF-
 Cytokine Release Inhibition
LPS bp
ENDOTOKSIN
TLR4

CD14 MD-2
Insulin Treatment
Anti Oxidant
My D88 (ALA)
IRAK
TRAF6

NIK/MKK
M Steroid
IKK Curcumin

NF-KB IVIG
NO
Hemofiltrasi
Target Genes Antimediator

TNF- IL-12
IL-1 IL-8
IL-6 Guntur,2008;Sepsis Forum
Terapi kortikosteroid dibandingkan dengan perawatan
suportif standar atau plasebo secara signifikan
menurunkan mortalitas pada pasien dengan sepsis.