Donnie Lumban Gaol

Departemen Ilmu Penyakit Dalam

FK Universitas Kristen Indonesia

DIAGNOSIS DAN
TATALAKSANA SEPSIS

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: 1303-1310
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
Mortality
Septic
Shock
53-63%
20-53%
Severe Sepsis
300,000
7-17%
Sepsis
400,000
Incidence
Balk, R.A. Crit Care Clin 2000;337:52
MORTALITAS MENINGKAT PADA PASIEN
SYOK SEPTIK
Approximately 200,000
patients including 70,000
Medicare patients have
septic shock annually

SEVERE SEPSIS:
COMPARATIVE INCIDENCE AND
MORTALITY
Angus DC, et al. Crit Care Med 2001;
American Cancer Society
0
50
100
150
200
250
300
AIDS Breast
Cancer
1st MI Severe
Sepsis
Incidence
C
a
s
e
s
/
1
0
0
,
0
0
0

0
50000
100000
150000
200000
250000
AIDS Breast
Cancer
AMI Severe
Sepsis
Mortality
D
e
a
t
h
s
/
Y
e
a
r

MORTALITY OF SEVERE SEPSIS BY AGE IN THE
UNITED STATES
Angus DC, et al. Crit Care Med 2001.
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
0 1 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85
Age
M
o
r
t
a
l
i
t
y

Without Co-morbidity
With Co-morbidity
Overall
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
Gram-
positives
Gram-
negatives
Fungi
NNIS. Crit Care Med 1999;27:887892
Microbiology of Sepsis
Martin GS, et al. NEJ M 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 PaCO
2
< 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 mikrobial
1

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
A clinical response arising from a
nonspecific insult, including 2 of
the following:
Temperature 38
o
C or 36
o
C
HR 90 beats/min
Respirations 20/min
WBC count 12,000/mm
3
or
4,000/mm
3
or >10% immature
neutrophils
SIRS = Systemic Inflammatory Response
Syndrome
SIRS with a presumed
or confirmed
infectious process
Sepsis
SIRS
Infection/
Trauma
Severe Sepsis
Bone RC, et al. Chest 1992;101:1644
Opal SM, et al. Crit Care Med 2000;28:S81
Sepsis: Defining a Disease
Continuum
Bone et al. Chest 1992;101:1644;
Wheeler and Bernard. N Engl J Med 1999;340:207
Sepsis SIRS
Infection/
Trauma
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
RELATIONSHIP OF INFECTION, SIRS,
SEPSIS SEVERE SEPSIS AND SEPTIC
SHOCK
SIRS
INFECTION
PANCREATITIS
BURNS
TRAUMA
OTHER
SEPSIS
SEVERE
SEPSIS
SEPTIC
SHOCK
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. NEJ M 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
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
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 normal
2

40% memiliki frekuensi nafas normal
2

10% memiliki denyut jantung normal
2

33% memiliki hitung leukosit normal
2
1. Munford RS. Severe sepsis and septic shock. Harrisons principal of internal medicine. Edisi ke-18. 2012.
2. 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
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.
1

Kardiovaskular syok, depresi miokardium.
1

Respiratorik gagal napas, PaO
2
, compliance paru ,
ARDS, PCWP > 18 mmHg.
1, 2

Ginjal gagal ginjal, nekrosis tubular akut.
1
1. Cilliers H. Serious complication of sepsis. ABC of sepsis. 2010.
2. 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. Cilliers H. Serious complication of sepsis. ABC of sepsis. 2010.
2. 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
Oxidases
Platelet
Activation
Kinins
Complement
Coagulopathy/DIC
Vascular/Organ System Injury
Multi-Organ Failure
Death
Coagulation
Activation
Cytokines
TNF, IL-1, IL-6




BIOLOGIC EFFECTS OF PROINFLAMMATORY
CYTOKINES SUCH AS TNF AND IL-1


Fever
Hypotension
Acute phase protein response
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 (1
ST
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