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Tissue Hypoxia
Sun Sunatrio
Department of Anesthesiology , Faculty of Medicine,
University of Indonesia, Jakarta
Tissue Hypoxia (TH)
Some limitation
Not yet widely utilized
PH and Lactate
a common abnormality in pts with TH is a
metabolic acidosis often due to lactic acidosis
the major reasons to measure arterial lactate
are to assess TH and to investigate metabolic
acidosis
Plasma arterial lactate is a goal prognostic
indicator and can be followed sequentially to
assess the pts response to th/ designed to
reverse TH
Glucose Metabolism
Glucose
CYTOPLASM
Glucose
Cori MITOCHONDRIA
Cycle
Pyruvate Pyruvate Krebs
Cycle ATP
AcetylCoA
Lactate
Lactate
Lieberman MA, Vester JW. Carbohydrates. In: Nutrition and Metabolism in the Surgical Patient.
Boston, MA: Little, Brown and Company;1996:203-236.
Inflammatory Response
Glucose CYTOPLASM
Glucose
Cori MITOCHONDRIA
Cycle Pyruvate
Pyruvate TNF
Krebs
IL1X Cycle ATP
IL6
Acetyl CoA
Lactate
Lactate
BLOCKAGE
DO2 VO2 Relationship
100 torr
Hb
Cytosol +
H H+ H
+
c Hb 50 torr
III IV
I Q bc1 aa3
DH II Fo
TMPD
NADH FADH ADP ATP
+
Substrates Succinate H H
+ 1-10 torr
Matrix
DO2 = CO x CaO2
= 5000 x 20/100
BW 70 kg Hb 15 g %
Normal basal O2 demand = 280 mL
Aorta
CvO2 = 12-15 vol %
SvO2 = 60-80%
DO2 = 750 ml/min
ScvO2
= 60-80%
80
% Mortality
60
40
20
0
0 - 8.5 9.0 - 12.9 3.0 - 16.9 17.0 - 20.9 21.0 - 24.9 25 +
Oxygen Delivery (ml/kg/min)
Anemia, hemorrhage
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 renal protection
in severe sepsis
Grade B
Sedation,paralysis
(if intubated) Minimize VO2
Or both
crystalloid
Volume load
CVP
8-12 mmHg
colloid
MAP
<65mmHg
Vasoactive agents Vasoactive drugs
>90mmHg
>65 and<90mmHg
<70% Transfusion of red cells >70% O2 carrying
ScvO2
Until hematocrit>30% capacity
<70%
>70%
No Inotropic agents Inotrope
Goals
achieved
Yes
ICU admission Rivers E, et al. NEJM 2001;345:1368-1377
BPs often Yet, the patients
normal are sick
Pathophysiology Septic Shock
1. Hypoxia
2. Hypovolemia
3. afterload
4. Possible anemia
5. contractility
Contractility inotrope 5
Early Goal-Directed Therapy (EGDT)
yields significant reductions in sepsis
related mortality
Standard Therapy (n=133) Early Goal-Directed Therapy (n=130)
60 56.9
49.2
50 46.5
44.3
40
33.3
30.5
30
20
10
0
In-hospital Mortality 28-day Mortality 60-day Mortality
P Value 0.009 0.01 0.03
A negative or positive value indicates how the control group therapy compares with the treatment group.
a P<0.001 , b P=0.01, c P= 0.02, d P =0.03, e P=0.04.
ventilation!
Less fluid : more aggressive (0-6 hrs) less
complications!
Why was cardiovascular collapse a
significant cause of death in the control
group?
Blood pressures: N/
ScvO2
cardiac indices
tissue hypoxia
Prevention of acute cardiovascular collapse
Comorbidity Time
Genetics Therapy
Microcirculatory dysfunction
ESR CRP
ESR CRP
hari
pekan
MATI MOF
CEDERA
INFLAMASI
PATOGENESIS MOF
INFLAMASI & GAGAL ORGAN
Serum C reactive protein mg/L
KAPILER BOCOR :
PLASMA PROT
EDEMA ELEKTROLIT
AIR
Sindroma kebocoran kapiler klinis
INJURY MULTIPLE
ORGAN FAILURE
Histamine INJURY TO:
[V] Polymorphs/Cytokines LUNGS
KIDNEY
LIVER
LEAK BOWEL
ALBUMIN
CAPILLARY INTERSTI. CELL
SPACE
WATER
OEDEMA
Histamin.
Bradikinin. TNF.
Platelet activiting Activated
factor. complement.
Proteasis (lepas dr Leukotrien B4.
PMN). Tromboksan.
Radikal bebas O2.
IMBANG CAIRAN YG MELEWATI
ENDOTELIUM KAPILER
900 900
800 800
700 700
600 600
500 500
400 400
300 300
200 200
100 100
0 0
0 500 1000 1500 2000 2500 3000 3500 4000 4500 0 500 1000 1500 2000 2500 3000 3500 4000 4500
8 to 96 hours
1000
900
800
700
Cum ulative ACR
600
500
400
300
200
100
0
0 500 1000 1500 2000 2500 3000 3500 4000 4500
Fluid Balance m L
Kebocoran albumin kumulatif dinyatakan sebagai rasio albumin kreatinin (ACR) dibandingkan
dengan imbang cairan untuk 4 pasien trauma. Pasien di ujung paling kanan mati akibat MOF
Penyesuaian macam cairan iv thd
permeab kapiler.
ANTIOKSIDAN
INHIBITOR ENZIM
ZAT-ZAT FARMAKOLOGIS
masih dlm tahap
ANTIBODI eksperimental
Sindroma kebocoran kapiler klinis
Sealling effect of HES 200/0.5
DO2
VO2
Waxman K et al. Hemodynamic and oxygen tranport effects
of pentastarch in burn resuscitation. Ann Surg 1989; 209:
341-5.
Managing the Inflammatory Response
to Critical Illness and Injury
Managing the Inflammatory Response to
Critical Illness and Injury
Proinflammatory Anti-inflammatory
Mediators Mediators
Eicosanoids Eicosanoids
TBXA2 TBXA3
LTB2 LTB5
Prostaglandins Prostaglandins
PGE2 PGE1
PGE3
Cytokines Cytokines
IL-1 IL-1 Receptor Antagonist
IL-6 IL-4
IL-8 IL-10
Tumor Necrosis Factor (TNF) TNF Receptor
TBX = Thromboxane
LT = Leukotriene
PG = Prostaglandin
Bone RC: Ann Intern Med 1991;115:457-469 IL = Interleukin
The Inflammatory Response
Pro-inflammatory Mediators
Anti-inflammatory Mediators
Immune Suppression
Anti-inflammatory
mediators predominate
Immune Suppression
(Risk for infection)
Conceptual Model of Normal
Immune Response
As the body fights off infection, the immune response increases.
However, in normal health, this response must decline in order for
healing & repair to take place.
Change in Immune Response
Fighting Healing
Time
Infection
Balance of Infection and Inflammation
Pro-inflammatory
mediators predominate
Patients at risk
Trauma
Surgery
Wounds
More trauma patients develop infection than surgical
patients
Infection occurs in 34% of ICU patients
Glutamine
Conditionally essential
Fuels GI and immune cells
20-30g free glutamine/day
Inherent glutamine glutamate
free glutamine
SIRS
Response
Fighting Healing
Infection
Time
Uncontrolled Inflammation
(SIRS)
Uncontrolled Inflammation
SIRS
Uncontrolled inflammatory response
Death
Arachidonic Acid
Borage Oil
Fish Oil
GLA EPA
Cyclooxygenase
Lipoxygenase
DGLA
Replacing AA with
Replacing AA with
GLA results in X EPA results in
E012373A 17
SIRS: Inflammation- Modulating Nutrients
Cyclooxygenase
Produces
Proinflammatory Eicosanoids
Antioxidants Interrupt the Cycle
Nutritional Therapy for SIRS
Immunomodulation with n-3 fatty acids (EPA, fish oil) and n-6
fatty acids (GLA, borage oil)
Injury SIRS
Change in Immune
Immunomodulation
with EPA & GLA
Response
Fighting Healing
Infection
EPA and GLA Do They Work?
These therapies are selected according to the patients condition to accomplish the
following basic therapeutic goals: