Dr.

Christian A Johannes, SpAn, KIC

Tempat/ Tanggal Lahir : Jakarta, 27 November
Pendidikan : Dokter umum FK UNSRAT 1979
Anastesi logist FK UNDIP 1990
Konsultan ICU IDSAI 1996
Pekerjaan : Kepala ICU RSPAD GS Jakarta
Team Dokter Kepresidenan RI
Pathophysiology of Septic
and Septic Shock
Chris A Johannes
Head of Intensive Care Unit Central
Army Hospital Gatot Subroto
JAKARTA
ACCP/SCCM Consensus
Definitions
Infection
Inflammatory response to
microorganisms, or
Invasion of normally sterile
tissues
Systemic Inflammatory
Response Syndrome
(SIRS)
Systemic response to a variety
of processes
Sepsis
Infection plus
2 SIRS criteria

Severe Sepsis
Sepsis
Organ dysfunction
Septic shock
Sepsis
Hypotension despite fluid
resuscitation
Multiple Organ
Dysfunction Syndrome
(MODS)
Altered organ function in an
acutely ill patient
Homeostasis cannot be
maintained without
intervention

Bone RC et al. Chest. 1992;101:1644-55.

Mortality of severe sepsis in most centers
remainsunacceptable high
The speed and appropriateness of therapy
administered in the initial hours after the
syndrome develops likely influence
outcome

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
Mortality Increases in Septic Shock Patients
0
50,000
100,000
150,000
200,000
250,000
D
e
a
t
h
s
/
Y
e
a
r
Severe Sepsis:
Comparison With Other Major Diseases

National Center for Health Statistics, 2001.

American Cancer Society, 2001.

0
50
100
150
200
250
300
AIDS*
Colon Breast
Cancer

CHF

Severe
Sepsis

C
a
s
e
s
/
1
0
0
,
0
0
0

Incidence of Severe Sepsis
AIDS*

Severe
Sepsis

AMI

Breast
Cancer

*American Heart Association. 2000.
Angus DC et al. Crit Care Med. 2001 (In Press).
Mortality of Severe Sepsis
Mortality Severe Sepsis:

Angus DC et al. Crit Care Med. 2001 (In Press).

Sands KE et al. J AMA. 1997;278:234-40.

Zeni F et al. Crit Care Med. 1997;1095-100.

28%

34%

50%

0
20
40
60
M
o
r
t
a
l
i
t
y

(
%
)
2001
Brazilian Sepsis
Epidemiological Study
Mortalitas
Sepsis 33.9%
Severe sepsis 46.9%
Septic shock 52.2%
Incidence severe sepsis/1000 pop

Hospital mortality (%)
The interrelationship between SIRS, sepsis, and infection
Chest 1992;101:1645
INFECTION SIRS
SEPSIS
PANCREATITIS
BURNS
TRAUMA
OTHER
OTHER
VIREMIA
PARASITEMIA
FUNGEMIA
BACTERIEMIA
Sepsis: A Complex Disease
This Venn diagram
provides a conceptual
framework to view
the relationships
between various
components
of sepsis.
The inflammatory
changes of sepsis are
tightly linked to
disturbed hemostasis.
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Opal SM et al. Crit Care Med. 2000;28:S81-2.
SIRS: More Than Just a Systemic
Inflammatory Response
SIRS: A clinical response
arising from a nonspecific
insult manifested by
2 of the following:
Temperature
38C or 36C
HR 90 beats/min
Respirations 20/min
WBC count 12,000/mL or
4,000/mL or >10% immature
neutrophils
Recent evidence indicates
that hemostatic changes are
also involved
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Opal SM et al. Crit Care Med. 2000;28:S81-2.
Sepsis: More Than Just
Inflammation
Sepsis:
Known or suspected
infection
Two or more
SIRS criteria
A significant link
to disordered
hemostasis
Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Severe Sepsis: Acute Organ
Dysfunction and Disordered
Hemostasis
Severe Sepsis:
Sepsis with signs of
organ dysfunction in 1
of the following
systems:
Cardiovascular
Renal
Respiratory
Hepatic
Hemostasis
CNS
Unexplained metabolic
acidosis

Adapted from: Bone RC et al. Chest. 1992;101:1644-55.
Identifying Acute Organ
Dysfunction as a Marker of
Severe Sepsis
Tachycardia
Hypotension
CVP
PAOP
Jaundice
Enzymes
Albumin
PT
Altered
Consciousness
Confusion
Psychosis
Tachypnea
PaO
2
<70 mm Hg
SaO
2
<90%
PaO
2
/FiO
2
300
Oliguria
Anuria
Creatinine
Platelets
PT/APTT
Protein C
D-dimer
Angus DC et al. Crit Care Med. 2001; (In Press).
Zeni F et al. Crit Care Med. 1997;25:1095-100.
Wheeler AP et al. N Engl J Med. 1999;340:207-14.
Severe Sepsis: A Complex and
Unpredictable Clinical Syndrome
High mortality rate
(28%-50%)
Heterogeneous
patient population
Unpredictable
disease progression
Unclear etiology
and pathogenesis
Systemic
Inflammation
Impaired
Fibrinolysis
Coagulation
Sepsis: Defining a Disease Continuum
Bone et al. Chest. 1992;101:1644; Wheeler and Bernard. N Engl J Med. 1999;340:207.
Sepsis SIRS
Insult Severe Sepsis
Sepsis with 1 sign of organ
failure
Cardiovascular (refractory
hypotension)
Renal
Respiratory
Hepatic
Hematologic
CNS
Metabolic acidosis
Shock
Initial Resuscitation
Diagnosis
Antibiotic therapy
Source Control
Fluid therapy
Vasopressors
Inotropic Therapy
Steroids
Recombinant Human
Activated Protein C
(rhAPC) [drotrecogin
alfa (activated)]

Blood Product Administration
Mechanical Ventilation
Sedation, Analgesia, and Neuromuscular
Blockade in Sepsis
Glucose Control
Renal Replacement
Bicarbonate Therapy
Deep Vein Thrombosis Prophylaxis
Stress Ulcer Prophylaxis
Limitation of Support

Index
Dellinger, et. al. Crit Care Med 2004, 32: 858-873.
SEPSIS
Systemic Inflammatory Response (SIRS) to
INFECTION manifested by two or > of following:
Temp > 38 or < 36 centigrade
HR > 90
RR > 20 or PaCO2 < 32
WBC > 12,000/cu mm or > 10% Bands (immature wbc)

SEPTIC SHOCK
SEPSIS WITH:
Hypotension (SBP < 90 or > 40 reduction
from baseline) &
Tissue perfusion abnormalities invasion of
the body by microorganisms & failure of
bodys defense mechanism.



Risk Factors Associated with Septic
Shock
Age

Malnutrition

General debilitation

Use of invasive
catheters

Traumatic wounds

Drug Therapy
Pathophysiology of Septic shock
Initiated by gram-negative (most common) or
gram positive bacteria, fungi, or viruses
Cell walls of organisms contain Endotoxins
Endotoxins release inflammatory mediators
(systemic inflammatory response) causes...
Vasodilation & increase capillary permeability leads
to
Shock due to alteration in peripheral circulation &
massive dilation
Pathophysiology of Septic Shock
IMMUNE / INFLAMMATORY RESPONSE
Microorganisms enter body

Mediator Release

Activation of Complement, kallikrein / kinin/ coagulation
& fibrinolytic factors platelets, neutrophils &
macrophages>>damage to endothelial cells.
ORGAN DYSFUNCTION
Sequelae of Septic Shock

The effects of the bacterias endotoxins can
continue even after the bacteria is dead!!!
ISF DEBATES:
CONTROVERSIES IN SEPSIS
Vasopressor Therapy
of Septic Shock:
Norepinephrine vs. Dopamine
Summary

Phillip Dellinger, MD
Jean-Louis Vincent, MD
No high level evidence exists to
support better clinical outcome
with either dopamine or
norepinephrine when compared to
the other drug.
Either dopamine or norepinephrine, as a
combined inotrope/vasopressor, is
preferred over alternative drugs as first
line agents to treat hypotension in septic
shock.
Non-clinical outcome physiological
studies may be used to offer potential
advantages of norepinephrine or
dopamine, one over the other.
In patients with poor contractility as a
major component of the hypotension,
dopamine may be a better initial
choice.
Some patients who do not achieve
acceptable blood pressure with dopamine
will achieve that goal with
norepinephrine.
Surviving Sepsis Campaign (SSC)
Guidelines- Vasopressors



Either norepinephrine or dopamine
(through a central line as soon as
available) is the first-choice
vasopressor agent to correct
hypotension in septic shock.

Grade D
Initiate vasopressor therapy if appropriate fluid
challenge fails to restore adequate blood pressure
and organ perfusion
Vasopressor therapy should also be used transiently in the
face of life-threatening hypotension, even when fluid
challenge is in progress

Either norepinephrine or dopamine are first line
agents to correct hypotension in septic shock
Norepinephrine is more potent than dopamine and may be
more effective at reversing hypotension in septic shock
patients
Dopamine may be particularly useful in patients with
compromised systolic function but causes more tachycardia
and may be more arrhythmogenic

LeDoux D. Crit Care Med 2000;28:2729-2732. Regnier B. Intensive Care Med 1977;3:47-53.
Martin C. Chest 1993;103:1826-1831. Martin C. Crit Care Med 2000;28:2758-2765.
DeBacker D. Crit Care Med 2003;31:1659-1667. Hollenberg SM. Crit Care Med 1999; 27: 639-660.
Vasopressors
Grade E
Grade D
Dellinger, et. al. Crit Care Med 2004, 32: 858-873.
Low dose dopamine should not be used for
renal protection in severe sepsis

An arterial catheter should be placed as soon
as practical in all patients requiring
vasopressors
Arterial catheters provide more accurate
and reproducible measurement of arterial
pressure in shock states when compared to
using a cuff
Vasopressin may be considered in refractory
shock patients that are refractory to fluid
resuscitation and high dose vasopressors
Infusion rate of 0.01-0.04 units/min in
adults
May decrease stroke volume
Vasopressors (cont)
Grade B
Grade E
Grade E
Dellinger, et. al. Crit Care Med 2004, 32: 858-873.
Hollenberg SM. Crit Care Med 1999; 27:639-660.
Bellomo R. Lancet 2000; 356: 2139-2143.
Kellum J. Crti Care Med 2001; 29: 1526-1531.

In patients with low cardiac output despite
adequate fluid resuscitation, dobutamine may
be used to increase cardiac output
Should be combined with vasopressor therapy
in the presence of hypotension
It is not recommended to increase cardiac
index to target an arbitrarily predefined
elevated level
Patients with severe sepsis failed to benefit from
increasing oxygen delivery to supranormal levels
by use of dobutamine
Inotropic Therapy
Grade E
Grade A
Gattinoni L. N Eng J Med 1995;333:1025-1032.
Hayes MA. N Eng J Med 1994;330:1717-1722.
Dellinger, et. al. Crit Care Med 2004, 32: 858-873.
CASE REPORT
During January July 2005.
12 young men pts ( 23 38 years old ) were
evacuated to ICU RSPAD from the conflict
area.
They admitted to ICU because of severe sepsis
and septic shock e.c. gun shoot.

Location of gun shoot N
---------------------------------------------------------------
1. Abdomen 6
2. Thorax 2
3. Thoraco Abdominal 1
4. Head 2
5. Musculosceletal 1
--------------------------------------------------------------
Total 12

Clasification of Sepsis N
---------------------------------------------------------------
1. Sepsis 3
2. Severe Sepsis 4
3. Septic Shock 5
--------------------------------------------------------------
Total 12
Isolated micro organism from blood
1. Klebsiella sp ( 4 pts )
2. Enterobacter sp ( 2 pts )
3. Pseudomonas aerogenosa ( 2 pts )
4, Escheria coli ( 1 pts )


On Ventilator : 8 pts. ( e.c. ARDS )
All pts we give Fluid. ( Crystalloid an Colloid)
Antibiotic : Meropenem
Cefipime
Source Control
Vasopressors ( Noerepinephrine, Dopamine,
Dobutamine )
Glucocorticoid if there any indication.
Glucose Control
Nutrition Therapy
Polyclonal IVIG
Tight Monitoring.
- Hemodynamic monitoring.
- SaO2
- BGA
- Blood Glucose.
- Urine Output
RESULT
8 pts ( 66,6 % ) survived
4 pts ( 33,3 % ) died.
CONCLUSION
IF WE USE THE GUIDELINES FROM
SURVIVING SEPSIS CAMPAIGN, THE
MORTALITY IN SEPSIS COULD BE
DECREASED.




THANK YOU
( bertjohn27@yahoo.com )