DIAGNOSIS DAN

TATALAKSANA SEPSIS

Donnie Lumban Gaol

Departemen Ilmu Penyakit
Dalam
FK Universitas Kristen Indonesia

DAHULU

Sepsis the Greek

word for putrification
Denoted tissue
breakdown that
resulted in illness

SEPSIS

EPIDEMIOLOGI

MORTALITAS DAN MORBIDITAS

ETIOLOGI

DEFINISI

MANIFESTASI KLINIK

PATOGENESIS

DIAGNOSIS

PENATALAKSANAAN

EPIDEMIOLOGI

1995: 6 million records analyzed from 7 states

750,000 cases of severe sepsis occur annually

( 3/ 1000)

Mortality 28.6% or 250,000 deaths

Projected increase by 1.5% per year

Angus et al , CCM 2001, 29: 1303-13

EPIDEMIOLOGI

Faktor-faktor yang meningkatkan kejadian sepsis:1,2

1) Jumlah populasi lanjut usia

2) Jumlah pasien dengan penyakit kronik dan immunocompromised
3) Jumlah prosedur invasif
4) Penggunaan luas antimikroba

Angus DC. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs
of care. Crit Care Med. 2001.
Munford RS. Severe sepsis and septic shock. Harrisons principal of internal medicine. Edisi ke-18. 2012.

SEPSIS

EPIDEMIOLOGI

MORTALITAS DAN MORBIDITAS

ETIOLOGI

DEFINISI

MANIFESTASI KLINIK

PATOGENESIS

DIAGNOSIS

PENATALAKSANAAN

MORTALITAS DAN MORBIDITAS

Angka mortalitas secara keseluruhan
sekitar 28.6%, setara dengan 215.000
kematian tiap tahun di Amerika Serikat.
Faktor-faktor yang mempengaruhi pada
awal kematian adalah jumlah sistem organ
yang terlibat, rendahnya pH darah arteri,
dan skor SAPS, MEDS24 atau APACHE yang
tidak baik
Angus DC, et al. Crit Care
Med 2001

MORTALITAS MENINGKAT PADA PASIEN

SYOK SEPTIK
Incidence

Mortality

Sepsis
400,000

7-17%

Severe Sepsis
300,000
Septic

Approximately 200,000
patients including 70,000 Shock
Medicare patients have
septic shock annually
Balk, R.A. Crit Care Clin 2000;337:52

20-53%

53-63%

SEVERE SEPSIS:
COMPARATIVE INCIDENCE AND MORTALITY
Mortality

Deaths/Year

Cases/100,000

Incidence

Angus DC, et al. Crit Care Med 2001;

American Cancer Society

MORTALITY OF SEVERE SEPSIS BY AGE IN THE

UNITED STATES
45%
Without Co-morbidity

40%

With Co-morbidity
Overall

35%

Mortality

30%
25%
20%
15%
10%
5%
0%
0

10

15

20

25

30

35

40

45

50

55

60

Age
Angus DC, et al. Crit Care Med 2001.

65

70

75

80

85

EPIDEMIOLOGI

MORTALITAS DAN MORBIDITAS

ETIOLOGI

DEFINISI

MANIFESTASI KLINIK

PATOGENESIS

DIAGNOSIS

PENATALAKSANAAN

 60-70% penyebab sepsis adalah gram negatif

Infeksi gram negatif merupakan hal yang
predominan pada sekitar tahun 1960an dan
1970an,
akan tetapi infeksi gram positif telah
meningkat dalam 2 dekade terakhir dan
sekarang penyebab pada sebagian kasus
sepsis berat

PATHOGEN DISTRIBUTION
Fungi
Grampositives
Gramnegatives

NNIS. Crit Care Med 1999;27:887892

Microbiology of Sepsis

Martin GS, et al. NEJM 2003;348:1546

EPIDEMIOLOGI

MORTALITAS DAN MORBIDITAS

ETIOLOGI

DEFINISI

MANIFESTASI KLINIK

PATOGENESIS

DIAGNOSIS

PENATALAKSANAAN

ACCP/ SCCM CONSENSUS

CONFERENCE 1992

Systemic Inflammatory Response Syndrome

( SIRS)

Sepsis

Severe Sepsis

Septic shock

Bone RC, CHEST 1992:

101(6):1644-55

SIRS

Temperature >38 C or < 36 C

HR> 90/ min

RR> 20/ min or PaCO2< 32mmHg

WBC> 12,000 or < 4,000, or > 10% immature (bands) forms

Bone RC, CHEST 1992: 101(6):1644-55

DEFINITIONS

Sepsis
Systemic inflammatory response to known or suspected infection

Severe Sepsis
SIRS associated with organ dysfunction (failure), hypoperfusion, and perfusion abnormalities

Bone, R et al. Chest 1992;101:1644

DEFINISI (LANJUTAN)

Sepsis SIRS yang memiliki atau dicurigai ber-etiologi mikrobial1

Sepsis berat Sepsis dengan satu atau lebih tanda-tanda disfungsi

organ, misalnya:1

a) Kardiovaskular: tekanan darah arteri sistolik 90 mmHg atau tekanan

arteri rerata (mean arterial pressure/ MAP) 70 mmHg yang merespon
terhadap pemberian cairan intravena
b) Ginjal: keluaran urin <0,5 mL/kg/jam dalam 1 jam meskipun dengan
resusitasi cairan yang adekuat
c) respirasi: PaO2/FiO2 300, Acute respiratory Distress Syndrome

Munford RS. Severe sepsis and septic shock. Harrisons principal of internal medicine. Edisi ke-18. 2012.

DEFINITIONS CONTINUED
Septic shock
A subset of severe sepsis, where patients experience combined
decreased systemic vascular resistance and the presence of
reduced myocardial performance

Bone, et al. CHEST , 1992;101:1644

Sepsis: Defining a Disease

Continuum
Infection/
Trauma

SIRS

A clinical response
arising from a nonspecific
insult, including 2 of the
following:
Temperature 38oC or
36oC
HR 90 beats/min
Respirations 20/min
WBC count
12,000/mm3 or
4,000/mm3 or >10%
immature neutrophils

Bone RC, et al. Chest 1992;101:1644

Opal SM, et al. Crit Care Med 2000;28:S81

Sepsis

Severe
Sepsis

SIRS with a presumed

or confirmed
infectious process
SIRS = Systemic Inflammatory Response
Syndrome

Sepsis: Defining a
Disease Continuum
Infection/
Trauma

SIRS

Sepsis

Severe
Sepsis
Sepsis with 1 sign of organ
failure
Cardiovascular (refractory
hypotension)
Renal
Respiratory
Hepatic
Hematologic
CNS
Metabolic acidosis

Shock

Bone et al. Chest 1992;101:1644;

Wheeler and Bernard. N Engl J Med 1999;340:207

RELATIONSHIP OF INFECTION, SIRS,

SEPSIS SEVERE SEPSIS AND SEPTIC
SHOCK
SEPSIS

PANCREATITIS

SEVERE
SEPSIS

INFECTION

SEPTIC
SHOCK

SIRS

BURNS

TRAUMA
OTHER
Bone et al. Chest 1992;101:1644

EPIDEMIOLOGI

MORTALITAS DAN MORBIDITAS

ETIOLOGI

DEFINISI

MANIFESTASI KLINIK

PATOGENESIS

DIAGNOSIS

PENATALAKSANAAN

SEVERE SEPSIS: PRIMARY SOURCE

Pulmonary: 50%

Abdomen/Pelvis: ~25%

Primary bacteremia: ~15%

Urosepsis: 10%

Skin: 5%

Vascular: 5%

Other: ~15%

Martin GS, et al. NEJM 2003;348:1546

MANIFESTASI KLINIK

Vital Sign
Fever, Chills/Rigors, Hypotermia
Tachycardia
Tachypnea

Central Nervous System

Encephalopathy

Cardiopulmonary
Increased Cardiac output
Decreased systemic vascular resistance
Hypotension
Metabolic asidosis hyperlactatemia
Acute Lung injury, Hypoxemia
Vincent LJ.et.al. The Sepsis Text. Kluwer Academic
Publisher 2002

MANIFESTASI KLINIK

Renal
Decreased urinary output
Elevated BUN and creatinine
Gastrointestinal
Ileus
Elevated Bilirubin, predominantly direct fraction
Dermatology
Ecthyma gangrenosum
Rash-maculopapular, vesicular, Bullous
Toxic erythema
Metabolic
Hyperglicemia, hypoglicemia
Hematologic
Leukocytosis, leukopenia, thrombocytopenia, DIC

Vincent LJ.et.al. The Sepsis Text. Kluwer Academic Publisher 2002

MANIFESTASI KLINIK
Gejala klinik non spesifik demam, menggigil.1
Gejala konstitutif lelah, malaise, gelisah,
kebingungan.1
Gejala-gejala sepsis lebih berat penderita usia lanjut,
diabetes, kanker, gagal organ utama, dan pasien
dengan granulositopenia.1

1.

Hermawan AG. Sepsis. Buku ajar ilmu penyakit dalam. Jilid III. Edisi ke-5.2009.

MANIFESTASI KLINIK (LANJUTAN)

Pasien dengan sepsis dapat normotermia atau hipotermia tidak

adanya demam sebagai gejala sepsis neonatus, lanjut usia, dan
pasien dengan uremia atau alkoholisme.1

36% pasien sepsis berat memiliki temperature normal2

40% memiliki frekuensi nafas normal2

10% memiliki denyut jantung normal2

33% memiliki hitung leukosit normal2

1.
2.

Munford RS. Severe sepsis and septic shock. Harrisons principal of internal medicine. Edisi ke-18. 2012.
Pohan HT. Diagnosis dan penatalaksanaan sepsis. Bunga rampai penyakit infeksi .2004.

MANIFESTASI KLINIK (LANJUTAN)

Respon awal sepsis hiperventilasi, disorientasi, kebingungan dan

ensefalopati.1

Akrosianosis, nekrosis iskemik jaringan perifer, selulitis, pustul,

bula dan lesi hemoragik.1

Mual, muntah, diare, ileus, perdarahan saluran cerna bagian atas.

1.

Munford RS. Severe sepsis and septic shock. Harrisons principal of internal medicine. Edisi ke-18. 2012.

MANIFESTASI KLINIK (LANJUTAN)

Sumber infeksi determinan penting dalam
menentukan berat atau tidaknya gejala sepsis.1
Tempat infeksi yang paling sering adalah paru-paru,
traktus digestivus, traktus urinarius, kulit, jaringan
lunak, dan saraf pusat.1

1.

Hermawan AG. Sepsis. Buku ajar ilmu penyakit dalam. Jilid III. Edisi ke-5.2009.

KOMPLIKASI
Sepsis berat dan renjatan sepsis gangguan atau
komplikasi pada berbagai sistem organ.

Kardiovaskular syok, depresi miokardium.1

Respiratorik gagal napas, PaO2

, compliance paru

, ARDS, PCWP > 18 mmHg.1, 2

Ginjal gagal ginjal, nekrosis tubular akut.1

1.
2.

Cilliers H. Serious complication of sepsis. ABC of sepsis. 2010.

Hermawan AG. Sepsis. Buku ajar ilmu penyakit dalam. Jilid III. Edisi ke-5.2009.

KOMPLIKASI (LANJUTAN)

Koagulasi hipoperfusi relatif, DIC.1

Sistem Saraf Pusat ensefalopati.1

Gastrointestinal iskemia hepatik, peningkatan permeabilitas

intestinal dan translokasi bakteri, perdarahan saluran cerna bagian
atas.1

Kulit & tungkai purpura fulminan, autoamputasi.1

Psikologis depresi, anxietas, PTSD, serangan panik.1

1.
2.

Cilliers H. Serious complication of sepsis. ABC of sepsis. 2010.

Hermawan AG. Sepsis. Buku ajar ilmu penyakit dalam. Jilid III. Edisi ke-5.2009.

EPIDEMIOLOGI

MORTALITAS DAN MORBIDITAS

ETIOLOGI

DEFINISI

MANIFESTASI KLINIK

PATOGENESIS

DIAGNOSIS

PENATALAKSANAAN

Bone, RC, Crit Care Med 1996; 24:1125

.

Sepsis Battlefield: Cells and Mediators

Hotchkiss RS, Karl IE, NEJM 2003;348:138

INFLAMMATORY RESPONSES TO SEPSIS

Russel JA. Management of Sepsis. N Eng J Med 2006;355:1699-713

PATHOGENESIS OF SEVERE SEPSIS

Infection
Microbial Products
(exotoxin/endotoxin)
Cellular Responses
Platelet
Activation

Coagulation
Activation

Oxidases

Kinins
Complement

Cytokines
TNF, IL-1, IL-6

Coagulopathy/DIC
Vascular/Organ System Injury

mage
a
d
l
a
i
l
e
h
Endot

Endothelial d
amage

Multi-Organ Failure
Death

 Fever
Hypotension
BIOLOGIC
EFFECTS OF PROINFLAMMATORY
Acute phase protein response
CYTOKINES
SUCH AS TNF AND IL-1
Induction of IL-6 and IL-8
Coagulation activation
Fibrinolytic activation
Leukocytosis
Neutrophil degranulation and augmented antigen expression (TNF)
Increased endothelial permeability (TNF)
Stress hormone response
Enhanced gluconeogenesis (TNF)
Enhanced lipolysis (TNF)

Uptodate 2008

Marshall J ,Curr Op Crit Care 2004; 10(4):250-264

PENATALAKSANAAN
DIAGNOSIS

SURVIVING SEPSIS CAMPAIGN

2012 UPDATE

International effort to increase awareness and improve outcomes in

severe sepsis

Endorsed by various organizations including SCCM, ACCP, ACEP, SHM,

AACCN, and ESICM

Crit Care Med 2013

CRITICAL CARE MEDICINE 2013;41:580

SEVERE SEPSIS:
INITIAL RESUSCITATION (1ST 6 HOURS)

Should begin as soon as the syndrome is recognized and should not

be delayed pending ICU admission.

Elevated serum lactate concentration identifies tissue hypoperfusion

in patients at risk who are not hypotensive.

RESUSCITATION GOALS
Goals in the first 6 hours:

CVP: 8-12 mm Hg
MAP > 65 mm Hg
Urine output > 0.5 ml/kg/hr
Central venous (SVC) or mixed
venous oxygen (SvO2) saturation >
70%

Early Goal Directed

Therapy

EGDT IN SEVERE SEPSIS AND SEPTIC SHOCK

Rivers et al, NEJM 2001;345:1368

RECOMMENDATIONS: HEMODYNAMIC SUPPORT

AND ADJUNCTIVE THERAPY

RECOMMENDATIONS: HEMODYNAMIC SUPPORT

AND ADJUNCTIVE THERAPY

RECOMMENDATIONS: HEMODYNAMIC SUPPORT

AND ADJUNCTIVE THERAPY

HATUR NUHUN