Biomol Sepsis

Biologi
molekuler:
Sepsis
Sugiharto P
Euis M
Andi S
Prasetyo E
IDENTITAS :
Nama
Usia
Jenis Kelamin
Tgl Masuk
Diagnosis
perforasi
viscus
: Tn. O
: 50 tahun
: Laki-laki
: 05-06-2007
: peritonitis difus ec
hollow
K.U: nyeri seluruh perut

A.K: 3 hari smrs os mengeluh nyeri
perut seluruh perut yang diawali
dengan nyeri ulu hati yang tiba-tiba
kemudian menebar ke seluruh perut.
Keluhan disertai dengan mual,
muntah (+) demam (-). BAB (-) sejak
1 hari smrs. BAK dalam batas normal
Riwayat sakit maag (+) sejak 3 thn

smrs
Riwayat minum jamu sendi (+) sejak
3 bln smsrs
Riwayat muntah darah (-)
Riwayat BAB hitam (-)
PF:
status generalis:
Kes: CM
N: 108x T: 110/80
RR: 40x S: 36,4
conjungtiva: anemis
status lokalis:
abdomen: cembung, tegang, NT (+) seluruh
perut, DM (+), pekak hati hilang,BU (-)
RT: sfingter lemah, mukosa licin, ampulla
tidak kolaps, NT (+) seluruh lingkaran.
ST: faeces (+), darah (-)
Laboratorium:
Hb: 9,1
ureum: 114
Ht: 26 creatinine: 2,1
L: 14.900 Na: 131
T: 392.000 K: 4,7
sgot: 58
gds: 65
sgpt: 27
laktat: 1,3
Radiologis: free air (+)
Dk: peritonitis difus ec perforasi ulkus

peptikum + severe sepsis
Th: LE
DO:
Ditemukan cairan peritoneum bercampur dengan

gastric juice 1000 cc
Ditemukan fibrin-fibrin di subhepatik
subdiafragma kiri-kanan, yang masih mudah
dilepaskan
Ditemukan perforasi di antrum dengan diameter
1,5 cm tepi nekrotik
Organ solid dan hollow viscus lain intak
Diputuskan dilakukan Grahams

patch dan biopsi
Diagnosis post op:
Peritonitis difus ec perforasi ulkus
gaster + severe sepsis
Th: laparotomi eksplorasi +
grahams patch + biopsi
07/0
6
08/0
6
09/0
6
10/0
6
110 120
/60 /70
90/
60
120 120 130 125 130

/70 /70 /80 /80 /60
110 100 100 110 110 90- 100 110

- 115 150 110 115 125 115
110 120
10- 10- 20- 18- 18- 24- 20- 2224 27 45 28 32 32 30 28
36,
337,
5
37,
539,
5
U0/
jam
42c
c/ja
m
130 66c 60c 140 150 171 108

cc/j c/ja c/ja cc/j cc/j cc/j cc/j
am
m
m
am
am
am
am
lasix lasix lasix lasix lasix lasix lasix
35,
639,
0
37,
437,
5
11/0
6
34,
538,
0
12/0
6
35,
538,
5
13/0
6
37,
537,
8
14/0
6
37,
5
06/0
6
07/06
08/06
09/06 10/06
11/06
12/06
13/06
Hb
8,7
9,0
8,3
Ht
27
27
10.40
0
8700
Tr
265.0
00
SGOT
14/06
7,4
9,7
11,3
26
24
30
34
11.200
10.800
16.100
18.400
314.00
0
265.00
0
205.00
0
224.00
0
247.00
0
46
SGPT
21
Ur
75
68
98
74
73
Kr
1,3
1,1
1,4
1,5
1,0
Na
140
143
143
143
142
139
138
137
4,5
4,1
5,1
4,4
4,8
3.7
3,4
Ca
4,07
4,23
4,7
4,4
4,4
4,65
4.51
4,51
Mg
2,65
2,43
2,87
2,45
1,85
2,0
1,88
1,91
Cl
111
109
111
107
108
107
106
104
GDS
82
111
75
118
97
album
in
1,2
1,7
7/6
8/6
9/6
10/6
11/6
12/6
13/6
pH
arteri
7,44
7.27
7.269
7.261
7,285
7.249
7.378
pCO2
arteri
31,2
46,7
53,6
62
53,3
50,3
45,4
pO2
arteri
76,8
150,7
127,4
81
89,6
50,6
88,3
HCO
3
arteri
21,3
21,3
23,4
26,9
24,6
21,8
25,9
Total
CO2
arteri
22,3
22,7
24,9
28,7
26,4
23,4
27,2
Base
exces
s
arteri
-2
-5,6
-3,0
-1,2
-2,7
-6,2
0,7
Sat
O2
arteri
95,3
98,7
97.6
93.1
95.8
82,1
96,0
14/6
Permasalahan
Apa patofisiologi perforasi gaster

pasien ini?
Apakah pasien ini sudah mengalami
severe sepsis atau syok septik?
Gangguan fungsi organ apa sajakah
yang sudah terjadi?
Apakah intervensi (surgical) yang
dilakukan sudah tepat?
Bagaimana prognosis?
Pada pasien ini terjadi perforasi

gaster akibat NSAID
Pada NSAID:
Pengurangan pembentukan
prostaglandin
Lapisan gel mucous rusak, dengan
penurunan produksi mucous dan
bicarbonat
SEPSIS
Strategi Pencegahan
& Penatalaksanaan
Dr Prasetyo Edi
Dr Sugiharto P
Dr.Andi S
Dr Euis M
Pathogenesis &
Pathophysiology
Infection
Bacteremia
Sepsis
Severe Sepsis (Sepsis + MODS)
Septic Shock (Severe Sepsis + Shock)
Correlation between Insults and

Physiological Derangement with
SIRS, MODS, MOF, and Death
(Baue, 2000)
Common Pathway to Death
Pathogenesis of Sepsis
Mediated Hemodynamic
Dysfunction
NIDUS OF INFECTION
ORGANISMS
Pneumonia
Peritonitis
Cellulitis
Abscess
Other Infection Sites
EXOGENEOUS TOXINS
Organism
Structural Component
Exotoxin (TSST-1, Toxin A)
Endotoxin
Phase II Sequele
ENDOGENOUS
MEDIATORS
CYTOKINES
*Interleukin 1,2,.6
*Tumor Necrosis Factor
PLATELET ACT FACTOR
ARACHID ACID METAB
HUMORAL CASCADES
*Complement
*Kinins
*Coagulation
Severe Decrease SVR
HYPOTENSION
Depressed CO
CARDIOVASCULAR
INSUFFICIENCY
DEATH
MOSF
Multiple Organ System

Failure
RECOVERY
MYOCARDIUM
*Depression
*Dilatation
VASCULATURE
*Vasodilation
*Vasoconstriction
*Endothelial Damage
*Maldistribution of flow
Phase I Sequele
Hypothesis : micro
circulatory arrest leading to

organ failures
Activators:
Injury, Bacteria, LPS
Ischemia Reperfusion
Necrotic tissues
Microcirculatory arrest
Focal necrosis
Initiators :
Coagulation Proteins,
Platelets,
Contact activating system,
Mast cells
Complement proteins
Lingkaran
Setan
Chemoattractans
vasodilation
Increased flow &
premeability,
Edema
Phase I Sequele
Microcirculatory injury
& vasoconstriction
Margination of
Neutrophils
(Phagocytosis)
Pro-inflammatory cytokines Systemic activation
Phase II Sequele
of macrophages
(Phagocytosis)
The Sepsis Continuum

SIRS
A clinical response arising

from a nonspecific
insult, with 2 of the
following:
T >38oC or <36oC
HR >90 beats/min
RR >20/min
WBC >12,000/mm3 or
<4,000/mm3 or >10%
bands
Mortality : 0 s.d 5 %
Severe
Sepsis
Sepsis
SIRS with a
presumed
or confirmed
infectious
process
Septic
Shock
Sepsis with
organ failure
Mortality : 10 s.d 30%
Refractory
Hypotension
Mortality : 30 s.d 60%
Mortality :0 s.d 10%
SIRS =
systemic inflammatory
response syndrome
Chest 1992;101:1644.
ACCP / SCCM Consensus

Definitions of SIRS and Allied
Disorders
Critical Care Med 1992 (20):864-874)
(
SIRS
The systemic inflammatory response to a variety of severe clinical insults.
Manifested by 2 or more of the following conditions:
Temperature
HR
Respiratory Rate
WBC
>38 deg C or <36 deg C

>90 beats/min
>20 breaths/min or PaCO2 <32 torr (<4.3 kPa)
>12,000 or <4,000 cells/mm3 or >10% bands
SEPSIS
The systemic response to infection. Manifested by the same criteria as
SIRS.
ACCP / SCCM Consensus

Definitions of SIRS and Allied
Disorders
(Critical Care Med 1992 (20):864-874)
SEVERE SEPSIS
Sepsis associated with organ dysfunction, hypoperfusion, or hypotension.
Perfusion abnormalities include but are not limited to:
lactic acidosis
oliguria
mental status
SEPTIC SHOCK
Sepsis with hypotension (SBP<90), despite adequate fluid resuscitation and
perfusion abnormalities as listed for severe sepsis. Patients on inotropic/
vasopressor agents may not be hypotensive.
Severe Sepsis Criteria
SIRS -Plus- 1 Organ Failure

1.
Cardiovascular:
SBP 90 or MAP 70 despite of fluid resuscitation of at least 20 ml/kg
or- continuing need for vasopressors following above fluid challenge
2.
Respiratory:
PaO2/FiO2 200*
3.
Renal:
UO < o.5 mL/kg despite above fluid challenge* -or- S. Creatinine > 2.0
4.
Hematologic:
Platelet count < 80000 or- decrease by 50% in past 3 days
5.
Acidosis:
Lactate > 1.5 or pH < 7.30 with base deficit > 5 mmol/L*
6.
Hepatic:
Acute bilirubin elevation > 3.0
7.
Brain:
Acute alteration in mental status
* Modified from Bone at al. Chest 1992;101:1644-1655
Septic Shock Criteria

1.
2.
3.
Severe Sepsis Criteria

Plus
Cardiovascular
SBP 90 or MAP 70 for 1 hour despite
fluid resuscitation of at least 20mL/kg or
continuing need of vasopressors
And/or
Serum lactate 4.0
Pencegahan dan
Penangganan
Sepsis
Introduction
The Management of Sepsis & Trauma
Source Control
1. Remove / Treat Infection
2. Remove / Treat Inflammation
3. Remove Dead Tissue
4. Stabilization Injured Tissue
Nutrition / Metabolic
Support
Resuscitation &
Physiologic Support
1. Minimize flow-dependent
oxygen consumption
2. Minimize flow-dependent
lactate clearance
3. Restore Microcirculation
Pencegahan :
Diagnosis Dini dan Penangganan

Tepat
SIRS
Sepsis
A clinical response arising

from a nonspecific
insult, with 2 of the
following:
SIRS with a
presumed
or confirmed
infectious
process
T >38oC or <36oC
HR >90 beats/min
RR >20/min
WBC >12,000/mm3 or
<4,000/mm3 or >10%
bands
Mortality :0 s.d 10%
Mortality : 0
Upayakan Agar SIRS & Sepsis tidak menjadi Severe Sepsis & Septic Shock
Background
The Surviving Sepsis Campaigns mission is

to increase awareness and improve outcome
in severe sepsis
Guidelines developed by a group of
international experts representing 11
organizations
Developed under unrestricted industry
educational grants
Published in March 3, 2004 issue of Critical
Care Medicine
Dellinger, et. al. Crit Care Med 2004, 32: 858-873.
Mission
To develop guidelines that the bedside
clinician can use to improve outcome
in severe sepsis and septic shock
These recommendations are intended to
provide guidance for the clinicians
caring for a patient with severe sepsis
or septic shock, but they are not
applicable for all patients
Sponsoring Organizations
American Association of Critical-Care Nurses

American College of Chest Physicians
American College of Emergency Physicians
American Thoracic Society
Australian and New Zealand Intensive Care Society
European Society of Clinical Microbiology
and Infectious Diseases
European Society of Intensive Care Medicine
European Respiratory Society
International Sepsis Forum
Society of Critical Care Medicine
Surgical Infection Society
Grading System
Grading of Recommendations
A. Supported by at least two level I investigations
B. Supported by one level I investigation
C. Supported by level II investigations only
D. Supported by at least one level III investigation
E. Support by level IV or V evidence
Grading System
Grading of Evidence
I.
II.
III.
IV.
V.
Large randomized trials with clear-cut results; low risk of

false-positive (alpha) error or false-negative (beta) error
Small randomized trials with uncertain results; moderate-tohigh risk of false-positive (alpha) and/or false-negative (beta)
error
Nonrandomized, contemporaneous controls
Nonrandomized, historical controls and expert opinion
Case series, uncontrolled studies, and expert opinion
Index
Initial
Resuscitation
Diagnosis
Antibiotic therapy
Source Control
Fluid therapy
Vasopressors
Inotropic Therapy
Steroids
Recombinant Huma
n Activated Prot
ein C (rhAPC)
[drotrecogin alfa
(activated)]
Blood Product Administration

Mechanical Ventilation
Sedation, Analgesia, and Neuromuscular Blo
ckade in Sepsis
Glucose Control
Renal Replacement
Bicarbonate Therapy
Deep Vein Thrombosis Prophylaxis
Stress Ulcer Prophylaxis
Limitation of Support
Initial Resuscitation
Resuscitation should begin as soon as severe sepsis or sepsis

induced tissue hypoperfusion is recognized
Elevated Serum lactate identifies tissue hypoperfusion in

patients at risk who are not hypotensive
Goals of therapy within first 6 hours are

-
Grade B
Central Venous Pressure 8-12 mm Hg (12-15 in ventilator pts)

Mean arterial pressure > 65 mm Hg
Urine output > 0.5 mL/kg/hr
- 2 70%;
ScvO2 or SvO
if not achieved with fluid resuscitation during first 6 hours:
- Transfuse PRBC to hematocrit > 30% and/or
- Administer dobutamine (max 20 mcg/kg/min) to goal
Rivers E. N Engl J Med 2001;345:1368-77.
Early Goal-Directed
Therapy Results
28-day Mortality
60
50
49.2%
40
P = 0.01*
33.3%
30
20
10
0
Standard Therapy
EGDT
n=133
n=130
*Key difference was in sudden CV collapse, not MODS
Rivers E. N Engl J Med 2001;345:1368-77.
Diagnosis
Before the initiation of antimicrobial therapy, at least

two blood cultures should be obtained
At least one drawn percutaneously

At least one drawn through each vascular
access device if inserted longer than 48 hours
Other cultures such as urine, cerebrospinal fluid,

wounds, respiratory secretions or other body fluids
should be obtained as the clinical situation dictates
Other diagnostic studies such as imaging and
sampling should be performed promptly to determine
the source and causative organism of the infection
Grade D
Grade D
Grade E
may be limited by patient stability
Weinstein MP. Rev Infect Dis 1983;5:35-53

Blot F. J Clin Microbiol 1999; 36: 105-109.
Antibiotic Therapy
Start intravenous antibiotic therapy within the
first hour of recognition of severe sepsis after

obtaining appropriate cultures
Empirical choice of antimicrobials should
include one or more drugs with activity against
likely pathogens, both bacterial or fungal
Penetrate presumed source of infection
Guided by susceptibility patterns in the

community and hospital
Continue broad spectrum therapy until

the causative organism and its
susceptibilities are defined
Grade E
Grade D
Kreger BE. Am J Med 1980;68:344-355.

Ibrahim EH. Chest 2000;118:146-155.
2000;118:146-155.
Hatala R. Ann Intern Med 1996;124-717-725.
Antibiotic Therapy
Reassess after 48-72 hours to

narrow the spectrum of antibiotic
therapy
Duration of therapy should typically
be 7-10 days and guided by clinical
response
Some experts prefer combination
therapy for Pseudomonas infections
or neutropenic patients
Stop antimicrobials promptly if
clinical syndrome is determined to be
noninfectious
Grade E
Grade E
Grade E
Grade E
Ali MZ. Clin Infect Dis 1997;24:796-809

Source Control
Evaluate patients for focus of infection

amenable to source control measures
Drainage of an abscess or local focus of
infection
Debridement of infected necrotic tissue
Removal of a potentially infected device
Definitive control of a source of ongoing

microbial contamination
Source control methods must weigh benefits
and risks of the specific intervention
Grade E
Grade E
Jimenez MF. Intensive Care Med 2001;27:S49-S62.

Bufalari A. Acta Chir Belg 1996;96:197-200.
Source Control (cont)
Once a focus of infection has been identified, source

control should be implemented as soon as possible
following initial resuscitation
Especially important for patients with necrotizing
soft tissue infection or intestinal ischemia
If intravascular access devices are suspected to be
the source of infection, remove them promptly after
establishing other vascular access
It may be reasonable to leave access devices in
place when patients develop sepsis of unknown
source, until the source of infection is determined
Grade E
Grade E
Moss RL. J Pediatr Surg 1996;31:1142-1146.

CDC. MMWR 2002;51:1-29.
Source Control: Examples of

Drainage
Potential Sites
-
Intra-abdominal abscess
Thoracic empyema
cholangitis
- Septic arthritis
- Pyelonephritis,
Debridement
-
Necrotizing fasciitis
Infected pancreatic necrosis
Device
-
Removal
Infected vascular catheter

Urinary catheter
Colonized endotracheal tube
Definitive
-
- Mediastinitis
- Intestinal infarction
Control
Sigmoid resection for diverticulitis

Amputation for clostridial myonecrosis
Cholecystectomy for gangrenous cholecystitis
Fluid Therapy: Choice of

Fluid
Fluid resuscitation may consist of

natural or artificial colloids or
crystalloids
Grade C
No evidenced-based support for one type

of fluid over another
Crystalloids have a much larger volume of

distribution compared to colloids
Crystalloid resuscitation requires more fluid to
achieve the same endpoints as colloid
Crystalloids result in more edema
Choi PTL. Crit Care Med 1999;27:200-210.
Cook D. Ann Intern Med 2001;135:205-208.
Schierhout G. BMJ 1998;316:961-964.
Fluid Therapy: Fluid

Challenge
Fluid challenge in patients with

suspected hypovolemia may be given
500 - 1000 mL of crystalloids over 30 mins

300 - 500 mL of colloids over 30 mins
Repeat based on response and tolerance
Input is typically greater than output due
to venodilation and capillary leak
Most patients require continuing
aggressive fluid resuscitation during the
first 24 hours of management
Grade E
Vasopressors
Initiate vasopressor therapy if appropriate fluid

challenge fails to restore adequate blood
pressure and organ perfusion
Grade E
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 Grade D

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 (cont)
Low dose dopamine should not be used for

Grade B
renal protection in severe sepsis
An arterial catheter should be placed as soon as
Grade E
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 cuf
Vasopressin may be considered in refractory
Grade E
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
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.
Inotropic Therapy
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
Grade E
Grade A
It is not recommended to increase cardiac

index to target an arbitrarily predefined
elevated level
Patients with severe sepsis failed to benefit from

L. N Eng J Med 1995;333:1025-1032.
increasing oxygen delivery toGattinoni
supranormal
levels
Hayes MA. N Eng J Med 1994;330:1717-1722.
by use of dobutamine
Steroids
Grade C
Intravenous corticosteroids are
recommended in patients with septic
shock who require vasopressor
therapy to maintain blood pressure
Administer intravenous hydrocortisone

200-300 mg/day for 7 days in three or
four divided doses or by continuous
infusion
Shown to reduce mortality rate in
patients with relative adrenal
Annane, D. JAMA, 2002; 288 (7): 868
insuficiency
Steroids
May use 250 mcg ACTH stimulation test to identify

Grade E
responders and discontinue therapy in these patients
Responders can be defined as >9 mcg/dL increase
in cortisol 30-60 minutes post ACTH
administration
Clinicians should not wait for ACTH stimulation
test results to administer corticosteroids
After the resolution of septic shock, may decrease
dosage of steroids
Consider tapering the dose of corticosteroids at
the end of therapy
May add fludrocortisone to the hydrocortisone
regimen
Annane, D. JAMA, 2002; 288 (7): 868
Steroids
Low-Dose Steroids: 28-day Mortality
Patients with Relative Adrenal
Insufficiency (ACTH Test Nonresponders) (77%)
Patients Without Relative Adrenal

Insufficiency (ACTH Test
Responders) (23%)
28-day Mortality
P=0.04
N=114
P=0.96
N=115
Low-dose Steroids
Annane, D. JAMA, 2002; 288 (7): 868
N=36
Placebo
N=34
Steroids
Doses of hydrocortisone >300

mg daily should NOT be used
in septic shock or severe
sepsis for the purpose of
treating shock
In the absence of shock,
corticosteroids should not be
used for treatment of sepsis
Grade A
Grade E
Bone RC. N Engl J Med 1987;653-658.

VA Systemic Sepsis Cooperative Study Group. N Engl J Med 1987;317:659-665.
Recombinant human
Activated Protein C
Recombinant human Activated Protein C

[Drotrecogin alfa (activated)] is recommended in
patients at a high risk of death
APACHE II score 25, or
Sepsis-induced multiple organ failure, or
Septic shock, or
Sepsis induced acute respiratory distress
syndrome
Treatment with drotrecogin alfa (activated)
should begin as soon as possible once a patient
has been identified as being at high risk of death
Patients should have no absolute or relative
contraindication related to bleeding risk that
outweighs the potential benefit of rhAPC
Grade B
Bernard GR. N Eng J Med 2001;344:699-709.

Recombinant human
Activated Protein C*
PROWESS 28-day Mortality High Risk of Death Patients*
Mortality Rate
Absolute Risk = 13%

Reduction
Placebo
*rhAPC is drotrecogin alfa (activated)
Drotrecogin
alfa
(activated)
* as defined by
APACHE II 25
Contraindications to use
of rhAPC
rhAPC
(drotrecogin alfa [activated]) increases the risk of

bleeding. rhAPC is contraindicated in patients with the
following clinical situations in which bleeding could be
associated with a high risk of death or significant morbidity:
-
Active internal bleeding

Recent (within 3 months) hemorrhagic stroke
Recent (within 2 months) intracranial or intraspinal surgery, or severe head
trauma
Trauma with increased risk of life-threatening bleeding
Presence of an epidural catheter
Intracranial neoplasm or mass lesion or evidence of cerebral herniation
See
labeling instructions for relative contraindications (i.e.

warnings)
The committee recommends that platelet count be maintained
at 30,000 during infusion of rhAPC
Blood Product
Administration
Red blood transfusion should occur only when Grade B

hemoglobin decreases to < 7 g/dL
Once tissue hypoperfusion has resolved and
in the absence of extenuating circumstances
such as significant coronary artery disease,
acute hemorrhage or lactic acidosis
Target hemoglobin of 7 9 g/dL
Erythropoietin is not recommended for specific Grade B
treatment of anemia associated with severe
sepsis
Unless septic patients have other accepted
reasons for administration of erythropoietin
Grade E
Routine use of fresh frozen plasma to correct
laboratory clotting abnormalities in the
absence of bleeding or planned invasive
procedures is not recommended
Corwin HL. JAMA 2002;288:2827-2835.
Blood Product
Administration (cont)
It is NOT recommended to use antithrombin for

Grade B
the treatment of severe sepsis or septic shock
High dose antithrombin in a phase III trial did
not demonstrate a beneficial efect on 28-day
mortality and was associated with increased risk
of bleeding when administered with heparin
Platelets should be administered when platelet
Grade E
counts are < 5000/mm3 regardless of apparent
bleeding
Platelet transfusion may be considered when
counts are 5000 - 30,000/mm3 and there is a
significant risk of bleeding
Platelet counts 50,000/ mm3 are typically
required for surgery or invasive procedures
Warren BL. JAMA 2001;286:1869-1878.
Mechanical Ventilation of
Sepsis-Induced Acute Lung
Injury (ALI)/ARDS
Grade B
High tidal volumes, > 6 ml/kg, coupled
with high plateau pressures, > 30 cm H2O,
should be avoided
Grade C
Hypercapnia can be tolerated in patients
with ALI/ARDS if required to minimize
plateau pressures and tidal volumes
Grade E
A minimum amount of positive end
expiratory pressure should be set to
prevent lung collapse at end-expiration
ARDSNet. N Eng J Med 2000;342:1301-1308.
Injury (ALI)/ARDS
Mortality* - Low vs Traditional Tidal Volume
P=0.007
* death before
discharge home
and breathing without
assistance
Low Tidal
Volume
ARDSNet. N Eng J Med 2000;342:1301-1308.
Traditional
Tidal
Volume
Injury (ALI)/ARDS
In experienced facilities, prone positioning

should be considered in ARDS patients
requiring potentially injurious levels of FiO 2 or
plateau pressure who are not at high risk for
adverse consequences to positioning changes
Unless contraindicated, mechanically ventilated
patients should be maintained semirecumbent
with the head of the bed raised to 45 to
prevent ventilator associated pneumonia
Drakulovic M. Lancet 1999;354:1851-1858.
Grade E
Grade C
Injury (ALI)/ARDS
A weaning protocol should be in place and

Grade A
mechanically ventilated patients should undergo
spontaneous breathing trial when they satisfy the
following criteria:
- Arousable
- Low ventilatory and end expiratory pressure
requirements
- No new potentially serious conditions
- Hemodynamically stable without vasopressors
- Requiring levels of FiO2 that could be delivered
with a face mask or nasal cannula
Esteban A. Am J Respir Crit Care Med 1999;159:512-518.
Ely EW. N Engl J Med 1996;335:1864-1869.
Esteban A. Am J Respir Crit Care Med 1997;156:459-465.
Sedation, Analgesia, and

Neuromuscular Blockade in
Sepsis
Grade B
Protocols should be used when sedation of
critically ill mechanically ventilated patients is
required
The protocol should include the use of a
sedation goal, measured by a standardized
subjective sedation scale
Grade B
Intermittent bolus or continuous infusion
sedation are recommended to predetermined
end points
With daily interruptions/lightening of
continuous infusion sedation with
Brook AD. Crit Care Med 1999;27:2609-2615.
awakening and retitration, if necessary
Sedation, Analgesia, and

Neuromuscular Blockade in
Sepsis
Neuromuscular blockers should be

avoided in the septic patient due to
the risk of prolonged neuromuscular
blockade
If needed for more than the first
hour of mechanical ventilation,
either intermittent bolus as required
or continuous infusion with
monitoring of depth of block with
train of four monitoring should be
used
Grade E
Glucose Control
Following initial stabilization of patients with

severe sepsis, maintain blood glucose to < 150
mg/dL
Best results obtained when blood glucose was
maintained between 80 and 110 mg/dL
Glycemic control strategy should include a nutrition

protocol with the preferential use of the enteral
route
Grade D
Grade E
Minimize the risk of hypoglycemia by providing

a continuous supply of glucose substrate
Accomplished by using 5% or 10% dextrose IV
infusion and followed by initiation of feeding
preferably by enteral route
van den Berghe G. N Engl J Med 2001;345:1359-1367.
Glucose Control
Intensive Insulin
Mortality During Intensive
Care
p = 0.01
Mortality (%)
p < 0.04 (adjusted)
In-Hospital Mortality
n=783
n=765
Conventional
van den Berghe G. N Engl J Med 2001;345:1359-1367.
n=783
Intensive Insulin
n=765
Renal Replacement
Continuous venovenous hemofiltration and intermittent Grade B
hemodialysis are considered equivalent in acute renal
failure (in the absence of hemodynamic instability)
Continuous hemofiltration ofers easier

management of fluid balance in
hemodynamically unstable septic patients
Mehta RL. Kidney Int 2001;60:1154-1163

Kellum J. Intensive Care Med 2002;28:29-37.
Bicarbonate Therapy
Bicarbonate is not recommended for the purpose of
improving hemodynamics or reducing vasopressor
requirements for the treatment of hypoperfusion
induced lactic acidemia with pH 7.15
Grade C
No diference revealed in vasopressor

requirements or hemodynamic variables between
bicarbonate and normal saline for treating
hypoperfusion-induced acidemia
Efects of bicarbonate therapy at pH levels < 7.13
have not been studied
Cooper DJ. Ann Intern Med 1990;112:492-498.
Mathieu D. Crit Care Med 1991;19:1352-1356.
Deep Vein Thrombosis

(DVT) Prophylaxis
DVT prophylaxis with either low-dose unfractionated
heparin or low molecular weight heparin should be
used in severe sepsis patients
Grade A
Use a mechanical prophylactic device or

intermittent compression in patients
with contraindications to heparin
Use a combination of pharmacological

and mechanical therapy in very high risk
Belchand
JJ, Scotthistory
Med J 1981;26:115-117
patients (eg, severe sepsis
of
Samama MM, N Engl J Med 1999;341:793-800
DVT)
Stress Ulcer Prophylaxis

Stress ulcer prophylaxis should be given to all patients
with severe sepsis
Grade A
H2 receptor blockers are more

eficacious than sucralfate and are the
preferred agents
Proton pump inhibitors compared to H2
blockers have not been assessed
Bresalier RS et al. Am J Med 1987;83:110-116

Borrero et al. Am J Med 1985;79:62-64
Consideration for
Limitation of Support
Advance care planning, including the communication of
likely outcomes and realistic goals of treatment, should
be discussed with patients and families
Decisions for less aggressive

support or withdrawal of support
may be in the patients best
interest
Grade E
Keadaan Umum
(KU) :
KU pasien sepsis yg akan dioperasi, perlu
KU pasien sepsis yg akan dioperasi, perlu
disiapkan secara baik
Bila disertai syok hipovolemik, koreksi Dehidrasi

setelahnya Tetapkan Tingkatan Sepsis
Cara Koreksi :
Penilaian Tingkat KU : (R), Sedang (S), Buruk (B),

Sangat Buruk (SB)
Parameternya :
i.
ii.
iii.
iv.
Tingkat Kesadaran
Tensi
Nadi
Diuresis/menit
Diketahui Tingkat KU : Ringan/Sedang/Buruk/Sangat

Buruk
Prognosis Peritonitis
Umum e.c Perforasi
Ileum demam tifoid
(Hanafi, 1979)
Faktor Penentu Prognosis :

1. Perforasi-operasi Interval
i.
ii.
iii.
iv.
Interval < 24 jam, Mortality

4%
Interval 24-48 jam, Mortality 25%
Interval 49-72 jam, Mortality 50%
Interval >72 jam, Mortality > 75%
Prognosis Peritonitis
Umum e.c Perforasi
Ileum demam tifoid
2.
i.
ii.
iii.
(Hanafi,
1979)
Keadaan Umum
Pre Op (Setelah
Resusitasi)
KU baik,
Mortality < 5 %
KU sedang
Mortality 25 %
KU buruk pasca Resusitasi, Mortality mendekati 100
%
Upayakan KU Baik, EGDT Pola Kita Sejak

1979
Oxygen Transport &

Consumption Parameter
DO2I
= CI x 10 Hgb x SaO2 x 1.34

VO2I =CI x C(a-v)O2
C(a-v)O2 = Hb x (SaO2 SvO2) x 1
Note :
VO2 : global oxygen consumpton index

(ml/min/m2)
C(a-v)O2 : extracted O2 content (ml/L)
SaO2 * 1.34
CI = SI * HR
chronotropy
SI @ MAP
Sepsis Guideline
Initial Resuscitation
Resuscitation should begin as soon as severe
sepsis or sepsis induced tissue hypoperfusion is
recognized
Elevated Serum lactate identifies tissue
hypoperfusion in patients at risk who are not
hypotensive
TERIMA KASIH
HATUR NUHUN

Biomol Sepsis

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Biologi

K.U: nyeri seluruh perut

Riwayat sakit maag (+) sejak 3 thn

Dk: peritonitis difus ec perforasi ulkus

Ditemukan cairan peritoneum bercampur dengan

Diputuskan dilakukan Grahams

120 120 130 125 130

110 100 100 110 110 90- 100 110

10- 10- 20- 18- 18- 24- 20- 2224 27 45 28 32 32 30 28

130 66c 60c 140 150 171 108

Apa patofisiologi perforasi gaster

Pada pasien ini terjadi perforasi

Correlation between Insults and

Severe Decrease SVR

Multiple Organ System

circulatory arrest leading to

Pro-inflammatory cytokines Systemic activation

The Sepsis Continuum

A clinical response arising

Mortality :0 s.d 10%

ACCP / SCCM Consensus

>38 deg C or <36 deg C

ACCP / SCCM Consensus

Severe Sepsis Criteria

SIRS -Plus- 1 Organ Failure

* Modified from Bone at al. Chest 1992;101:1644-1655

Septic Shock Criteria

Severe Sepsis Criteria

Diagnosis Dini dan Penangganan

A clinical response arising

Mortality :0 s.d 10%

The Surviving Sepsis Campaigns mission is

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

American Association of Critical-Care Nurses

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Large randomized trials with clear-cut results; low risk of

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Blood Product Administration

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Resuscitation should begin as soon as severe sepsis or sepsis

Elevated Serum lactate identifies tissue hypoperfusion in

Goals of therapy within first 6 hours are

Central Venous Pressure 8-12 mm Hg (12-15 in ventilator pts)

Dellinger, et. al. Crit Care Med 2004, 32: 858-873.

Rivers E. N Engl J Med 2001;345:1368-77.

Before the initiation of antimicrobial therapy, at least

At least one drawn percutaneously

Other cultures such as urine, cerebrospinal fluid,

may be limited by patient stability

Weinstein MP. Rev Infect Dis 1983;5:35-53

first hour of recognition of severe sepsis after

Penetrate presumed source of infection

Guided by susceptibility patterns in the

Continue broad spectrum therapy until

Kreger BE. Am J Med 1980;68:344-355.

Reassess after 48-72 hours to

Ali MZ. Clin Infect Dis 1997;24:796-809

Evaluate patients for focus of infection

Debridement of infected necrotic tissue

Removal of a potentially infected device

Definitive control of a source of ongoing

Jimenez MF. Intensive Care Med 2001;27:S49-S62.