Dr. A .

HANAFIE, SpAn KIC

Instalasi Anestesi dan Reanimasi / ICU
FK USU/RSU. Dr. Pirngadi Medan
RSUP H. Adam Malik Medan
 Introduction – 1

DSS is a severe form of dengue viral

infection with high mortality

Endothelial dysfunction play a role in

the pathogenesis of vascular leakage,
and haemostatic disturbance in DSS
Paradigm of Activation
and Migration of PMN
 Introduction – 2

Marker of Endothelial dysfunction

in DSS Æ sICAM-1 & sVCAM-1↑
(van Gorp; 2001), PAI-1 ↑ (van
Gorp; 2001, Tattty ES; 2004),
and ↑ Endothelial microparticle
(Tatty ES; 2004)
 Introduction – 3
Initial fluid resuscitation which has a
sealing effect as well as anti-inflammatory
(reducing ICAM-1 and VCAM-1) needed in
the management of DSS Æ minimizing
vascular leakage, and bleeding
HES 200.000 MWÎ reducing ICAM-1 &
VCAM-1 ( Boldt, Zikria )
HANAFIE
HANAFIE
 H 2O

HES
Na

HES
Cl

H 2O HANAFIE
 Efficacy of Colloid
Hypovolaemia Volumetherapy Normovolaemia
Intravascular
Intravascular
Macro Volume
Volume
circulation
COLLOID
COLLOID Haemodynamic
Haemodynamic
Stabilisation
Stabilisation
Micro Non-
Non-
Circulated Circulated
Circulated
circulation Circulated
Vessels
Vessels Vessels
Vessels

Ischaemia Capillary
Capillary Perfusion
Perfusion Capillary
Capillary Perfusion
Perfusion
(tissue
(tissue perfusion)
perfusion) (improved
(improved rheological
rheological properties)
properties)

Oxygen
Oxygen Transport
Transport Oxygen
Oxygen Transport
Transport
Release
Release of
of Mediators
Mediators
Reperfusion
Reperfusion Injury
Injury
MULTIPLE ORGAN FAILURE MEDIATED BY VASCULAR DAMAGE

Leucocyte activation
A. IT, IL-2 Vascular leak

Decrease in serum albumin level Hypovolemia NO
Decrease in serum osmolarity
proteins, water, electrolytes Hypotension
Weight gain
B. Peripheral edema Tissue
Tissue edema
edema
Anasarca
Pulmonary edema

C.
Decrease in capillary circulation

      

Hypoxia
Hypoxia
D. Multiple
Multiple Organ
Organ Failure
Failure
Lungs Vessels
Kidneys Heart
Liver Gastrointestinal tract
Coagulation system Central nervous system
The relative distribution of crystalloid and colloid solutions
in the intra- and extravascular fluid space at equilibrium
(within 30 min to 1 hour of infusion)

Fluid Intravascular Extravascular

Normal capillary permeability
Crystalloid 20% 80%
Colloid 70% 30%

Increased capillary permeability

Crystalloid 15-20% 80-85%
Colloid 60-70% 30-45%

Increased capillary permeability + cell

membrane dysfunction

Crystalloid 10-15% 85-90%

Colloid 50-60% 40-50%
Fluid Therapy
in
DSS
The policy of initial fluid therapy
in DSS according to the
Department of Health and WHO
until 2003 :
Crystalloid (Ringer Lactate),
followed with colloid (Dextran)
if not responded
 Department of Health
Indonesian Intensive Care Association
Ind. Anesthesiology Ass
Ind. Paed. Ass (2004)

Review on the management of DHF

Change the protocol
Include colloid MMW-6% HES as
alternative as initial fluid
resuscitation in DSS
 Fluid Therapy in DSS

Crystalloid (RL, RA, NaCL)

Distributed to the interstitial space
Very short period in the intravascular
space
Need more fluid to maintain intravascular
volume Æ risk for interstitial edema /
pulmonary edema
 Fluid Therapy in DSS
Colloid
HES: ( MW 100.000-300.000 kD ): Sealing
effect +, good intravascular volume effect,
longer duration in the intravascular space, ↑
DO2, ↑VO2
Dextran : LMW colloid (40.000-70.000 kD)
with good preservation volume effect, no
sealing effect, increase anaphylactic reaction
 Effects of PVR solutions
on haemostasis and coagulation

Gelatins HES Dextrans

Factor VIII, vWF No effect

Platelets
• Adhesion No effect
• Aggregation
Thrombus formation No clinical effect

In emergency
Blood typing No effect situation blood typing
! prior to infusion
 Effects of colloids on kidney function
Gelatins : No negative effect ! Improved kidney
function !
Dextrans : Renal insufficiency is possible after
Dextran 40
HES : Acute renal failure after HES is possible

Decrease of glomerular
filtration

Dextran/HES Latent Enhanced

concentration increase of flow Stop of
in proximal urine resistance filtration
tubuli viscosity
 Effects of Synthetic Colloids
Retaining of fluid Oncotic
in the IVS pressure

increased IV
Hemodilution
volume

Venous flow back Improved Hematocrit

(preload) rheology

Cardiac Flow Arterial oxygen

output resistance concentration

CO DO2 CaO2
 Effect of HES on Blood
Coagulation
HMW-HES Æ more effect on blood
coagulation (vWF, factor VIII)

LMW (HES 70/0.5/4)/MMW(HES 200/0.5/6)

Æ did not affect on blood coagulation

Possible dilutional coagulation effect : PT,

aPTT (significant prolongation after HMW-
HES 480)
Hydroxyethyl Starch (HES)
Effective and safe plasma substitute
HMW-HES Æ bleeding complication
LMW/MMW-HES Æ less/rare bleeding
complication
Bleeding complication : effects on factor VIII
and von Willebrand Factor
Sealing effect : HES with 100.000 – 300.000
D MW
Evidence (Boldt, Zikria) : HES–Solution

Reduced : ELAM–1, ICAM, VCAM

Reduced : Endothelial damage & MOD

Sealing effect MMW HES
Animal studies:

Zikria HES 200.000/0.5 & MW

100.000-300.000 : Sealing effect
(Animal studies) in burns

Webb ( peritonitis), Traber (sepsis),

Tanaka (lung edema)
Fluid Resuscitation in DSS

Primary importance in the management

of hypoperfusion state

Goal of therapy
↑ Tissue DO2
HES MMW
↑ Blood Pressure
↑ VO2
Reversing Lactic Acidosis
Study on DSS using colloid ( HES )
as initial fluid resuscitation

Tatty E. Setiati Different

(2000) RESULT
Different
Herminia L. Cifra method of
(2001) study
Tatty E. Setiati ( 2000 )
Randomized Control Trial
60 DSS Æ 30 RL (control)
30 HES (MMW)
Diagnosis DSS : WHO 1997, Rapid dengue
blot, and HI test
Location : Department of Child health
(PICU; HND) Dr. Kariadi Hospital /
Diponegoro University
 OBJECTIVES
Compare
Duration of shock
Intravascular volume preservation
Evaluate
Plugging effect on endothelial cell
Organ dysfunction
ICU lengths of stay
Ventilator day
Mortality rate
Æ Between 6% HAES–sterile and lactate ringer
solution
Procedure DSS - WHO Criteria
- Dengue Blot IgM/IgG

Organ Dysfunction : Proloux (1997)

Control Group I Protocol Group II

(standard therapy DSS) HAES – 6% 10 – 30 cc / kgBW
RL 20 – 60 cc / kgBW or more (10’ – 30’)
(10’ – 30’) FFP 15 – 20 cc / kgBW
FFP 15 – 20 ml / kgBW (if needed)
CVP 12 – 15 cmH2O CVP 15 – 18 cmH2O

Blood Component
are given according to the indication of both groups

Evaluate :
Inotropic : Tissue Perfusion
Dopamine, Dobutamine Plugging effect
Organ dysfunction
Monitoring was done :
a. At the time shock diagnosed
b. Recovery from shock
c. 48 hours after admission
d. Discharge from the HND/PICU to the
ward or a moment before death.
 Comparison between Control
and Protocol Group

Control Protocol p value

Age 6.62 ± 2 6.9 ± 2 > 0.05

Duration of shock 4.9 ± 2.8 2.3 ± 1.3 < 0.001

PICU length of stay 7.20 ±
14 ± 2.05 0.000
(days) 1.28
4.00 ±
Ventilators (days) 8 ± 1.10 < 0.05
0.71
Mortality rate (%) 26.07 6.67

Blood component need 30 7

 Evaluation of CVP and MAP
60
57
56 56 56 56
55 55 56 56 56

50
47
45 46

43

40

CVP Group I (control)

30 CVP Group II (protocol)
MAP Group I (control)
MAP Group II (protocol)

20
17 17
16
15 15
12 13
10 10
10 8
6
4
3
2

0
On admission 2 hours 4 hours 6 hours 8 hours 12 hours 24 hours
 Lung Dysfunction

Control Protocol

ALI 4 (0.13%) 1 (0.04%)

ARDS 6 (0. 2% ) 2 (0.07%)

Chi-square p < 0.05

 Hematology Dysfunction

Control Protocol

Severe DIC 8 (0.27%) 2 (0.07%)

Moderate DIC 12 (0.4%) 9 (0.3%)

Mild DIC 10 (0.33%) 19 (0.63%)

Chi-square p < 0.05

Herminia L. Cifra, Jesus Nazareno J.
Velasco (2001)

27 patients with DSS : 16 RL group and

11 HES group by systematic allocation of
subjects

The two groups were compared according

to the duration of shock, frequency of
recurrent shock, and length of ICU stay
 Herminia L. Cifra, Jesus Nazareno J.
Velasco (2001)

Results
• Duration of control of shock by HES
group significantly longer than RL
• Lesser frequency of recurrent Shock in
HES group than RL
• Length of ICU stay were not different
 Summary

Evidenced showed that endothelial

dysfunction lead to vascular leakage and
hemostatic disturbances occurred in DSS

MMW which has a sealing effect could

minimizing vascular leakage, good
preservation volume effect, and lowering
mortality
 Summary
MMW HES can be used as alternative for
initial fluid resuscitation in DSS

Another study of using MMW HES in DSS

as alternative for initial fluid resuscitation
should be made, with a more samples and
good methodology to have a good
conclusion
A. Hanafie ‘05
Activation of inflammation

HANAFIE
HANAFIE