SEPSIS

dr. Donnie Lumban Gaol, SpPD

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

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

Sepsis is a common condition. In the US, the incidence of sepsis per

100,000 exceeds AIDS, breast cancer, and first myocardial infarctions.
Concerted public awareness campaigns have emphasized the importance of
coronary heart disease, AIDS, and breast cancer. Yet, as shown on this slide,
the mortality of severe sepsis exceeds AIDS, breast cancer and is only
DC, et al. Crit Care
Med 2001;
American Cancer
slightly less that thatAngus
of patients
dying
suddenly
of anSociety
acute myocardial

Mortality of Severe Sepsis by Age in the

United States

45%

40%
35%

30%

Mortality

25%

20%

15%

10%

5%

0%

10

15

20

25

30

35

40

Without Co-morbidity

With Co-morbidity

Overall

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

From 1979 through 1987, gram neg bacteria were the predominant
organisms causing sepsis. From 1988 onwards, gram pos bacteria have
become the predominant organisms. In 2001, gram (+) bacteria accounted
for 52% of cases with gram (-) accounting for 38%, polymicrobial infections
5%, anaerobes 1%, and fungi 5%.
Martin
GS, etare
al. NEJM
2003;348:1546
** In 1/3 of cases, no
organisms
recovered.

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

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

This conceptual framework shows the

interrelationships between infection, noninfectious disorders, SIRS, sepsis and severe
sepsis. Components of the process not discussed
on the following slides include:
Infection: a microbial phenomenon characterized
by an inflammatory response to the presence of
microorganisms or the invasion of normally
sterile host tissue by those organisms
Bacteremia: the presence of viable bacteria in
the bloodstream
Septic shock: sepsis-induced hypotension despite
adequate fluid resuscitation along with the
presence of perfusion abnormalities that may
include, but are not limited to, lactic acidosis,

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

Patogenesis

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

Sepsis Battlefield: Cells and Mediators

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

The pathophysiology of sepsis depends on a complex

interaction and cooperation between a whole host of
cells, including neutrophils, macrophages and
structural cells such as endothelial cells, epithelial
cells, and dendritic cells.
This slide illustrates the response to pathogens,
involving cross-talk among many immune cells,
including macrophages, dendritic cells and CD4 T
cells.
Macrophages and dendritic cells are activated by the
ingestion of bacteria and by stimulation through
cytokines secreted by CD4 T cells.
These cells secrete a variety of cytokines, chemokines
and lipid mediators which can attract further immune
cells into the battlefield.
The concept has emerged that although initially sepsis
may be characterized by increases in inflammatory
mediators, as the sepsis persists, there is a shift

The factors that determine whether CD4 T cells

have Th1 (inflammatory) or Th2 (antiinflammatory) responses are unknown but
appear to be influenced by the type of pathogen,
size of the bacterial inoculum and the site of
infection.
Casualties in this battle are the host cells:
endothelial cells, epithelial cells in organs such
as the lung, kidney and gut and parenchymal
cells such as cardiac myocytes.
It also has become clear that during sepsis, T
cells become anergic or lose their ability to
proliferate or secrete cytokines in response to
specific antigens. This sepsis-induced anergy
seems to be triggered by apoptotic or
programmed cell death. Basically, the cells

Inflammatory Responses to Sepsis

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

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

Coagulation
Activation

Oxidases

Kinins
Complement

Coagulopathy/DIC
Vascular/Organ System Injury

Multi-Organ Failure

Death

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

Penatalaksanaan

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%

6 Hour Resuscitation Bundle

Early Identification
Early Antibiotics
and Cultures
Early Goal Directed
Therapy

6 - hour Severe Sepsis/

Septic Shock Bundle

Early Detection:
Obtain serum
lactate level.

Vasopressors:
Hypotension not responding
to fluid
Titrate to MAP > 65 mmHg.

Septic shock or lactate > 4 mmol/L:

CVP and ScvO2

measured.
CVP maintained >8
mmHg.
MAP maintain > 65
mmHg.

Early Blood
Cx/Antibiotics:
within 3 hours of
presentation.
Early EGDT:
Hypotension (SBP <
90, MAP < 65) or
lactate > 4 mmol/L:

initial fluid bolus 20-40 ml

of crystalloid (or colloid
equivalent) per kg of body

ScvO2<70%with CVP > 8 mmHg, MAP >

65 mmHg:

PRBCs if hematocrit <

30%.
Inotropes.

Early Goal Directed Therapy

EGDT in Severe Sepsis and Septic Shock

Rivers et al, NEJM 2001;345:1368