INFEKSI VIRUS DENGUE

Riwayat dan Epidemiolgi

 Dinyatakan pertama sebagai `breakbone fever` (Benjamin
Rush, Philadelphia, 1780),
 Dengue pertama diterapkan pada tahun 1828 di Cuba
 Virus Dengue diisolasi pada 1944 (type 1 dan 2) dan pada
1956 (type 3 dan 4)
 Istilah `DHF` digunakan pada 1954 (previously known as P
hilippine hemorrhagic fever)
 Insiden meningkat dengan jelas sejak tahun 1960an,
Diperkirakan 100 juta kasus infeksi Virus Dengue terjadi set
iap tahun, termasuk 500,000 kasus DHF dan sekitar 30,000
meninggal.
 Satu juta orang terinfeksi di Rio de Janeiro tahun 1986
 Endemik di Asia Tenggara, Kepulauan Pacific, Afrika Timur
dan Barat, Amerika Tengah dan Selatan (> 100 countries)
Actual and potential distribution of DF and DHF (WHO, 1997)
Angka Kematian
 Indonesia
- 1968 : 41.3 %
- 1984 : 3.0 %
- 1998 : 1.9 %
- 2003 : 2.0 %
- 2004 : 1.1 %

WHO (1997) : angka kematian DSS 40-50%

Wills (2005) : angka kematian 1-5%

 Target WHO : angka kematian : <1 %

  Virus Dengue : genus Fla
vivirus, family Flavivirida
e
 4 serotypes :
DEN-1, DEN-2, DEN-3, D
EN-4
 Indonesia : DEN-3 > (3
7 %)
 Inkubation : 4 – 6 hari
(3 – 14 hari)
 Transmisi : manusia ke m
anusia malalui nyamuk
 Patogenesis : masih kont
roversy
Stegomyia aegypty (secondary heterologous
infection; Suvatt, 1977)
PATHOGENESIS
 Setelah nyamuk yang terinfeksi menghisap darah m
anusia, virus masuk ke tubuh manusia, virus berepli
kasi di limfonodi regional & menyebar melalui cairan
limfe dan darah ke jaringan
 Replication in RES & skin produce viremia
 Hallmarks of DHF-DSS :
abnormalities in capillary permeability, coagul
ation, and hemostasis
 Immune status of the host, virus genotype & sec
ondary infections determine the course of infection
& subsequent development of DHF-DSS
 Increased number of infected monocytes, elevated
TNF-a, IL-2, soluble CD8, C3a, C5a fragments
PATHOGENESIS
Antibody-dependent immune enhancement
(Halstead, 1973)
Secondary infection by different serotype

Preexisting antibody fails to neutralize, and may instead enha

nce viral uptake and replication in mononuclear phagocyte
s

Infected cells : target of immune elimination mechanism

Trigger the production of mediators with activation of comple

ment and clotting cascade

Plasma leakage, bleeding, shock

Factors influencing induction of vascular per
meability and development of shock
 presence of enhancing & non-neutralizing anti
bodies
 age : susceptibility decreases after 12 years of
age
 sex : females > males
 race & specific HLA haplotypes : caucasian >
blacks
 nutritional status : good nutrition > malnutrition
 sequence of infection : serotype-1 followed by
serotype-2 seems to be more dangerous
 infecting serotype : type-2 more dangerous
 MANIFESTATIONS OF THE DENGUE
SYNDROME
 Dengue virus infection
Asymptomatic Symptomatic

DHF
Undifferentiated fever Dengue fever
(Viral syndrome) Plasma leakage

Without haemorrhage With unusual haemorhhage No shock DSS

Dengue fever DHF

PRIMARY and SECONDARY DENGUE VIRUS INFECTION

0.007 % DSS 1.1 %

0.18 % DHF
2.0 %

Dengue Fever

PRIMARY INFECTION SECONDARY INFECTION

 DENGUE VIRUS INFECTION
FEVER BLEEDING HEPATOMEGALY INCREASE TROMBOCYTOPENIA
ANOREXIA MANIFESTATION VASCULAR
VOMITING PERMEABILITY

Plasma leakage :
Hemoconcentration
Hipoproteinemia
Dehydration Pleural effusion
Ascites

Hypovolemia

DIC Shock

G.I. bleeding Anoxia Acidosis

Death
WHO case definition of DHF

A patient with the following four criteria:

1. Acute sudden onset of high fever for 2–7 days
2. Hemorrhagic manifestations with at least a
positive tourniquet test
3. Platelet count <100,000/mm3
4. Hemoconcentration
(rising packed cell volume >20%)
or other evidence of plasma leakage—
for example, ascites, pleural effusion,
low level of serum protein/albumin
Grading of DHF

Grade I : no shock: only positive tourniquet test.

Grade II : no shock; has spontaneous bleeding
other than a positive tourniquet test.
Grade III: shock.
Grade IV: profound shock with unmeasurable
blood pressure or/and pulse.
 fever, typical
dengue syndrome

Classic dengue
positive tourniquet
test with or without
spontaneous bleeding

thrombocytopenia
hemoconcentration Grade I DHF

spontaneous
bleeding Grade II DHF

circulatory failure
pulse pressure < 20 mm Hg
hypotension, cold, clammy skin Grade III DHF
restlessness

DSS

profound shock,
undetectable blood Grade IV DHF
pressure and pulse
Clinical features of DHF
General
High fever, intermittent.
Severe headache (especially retro-orbital).
Flushing.
Myalgia and arthralgia.
Vomiting, anorexia.
Acute abdominal pain.
Bleeding manifestations
Epistaxis.
Bleeding from gums.
Petechiae and ecchymoses.
Hematemesis and melena
Hemoptysis, hematuria
Spotting or menorrhagia in females.
Features of plasma leakage
Circulatory disturbances (low BP, tachycardia, narrow PP)
Periserositis (pleural effusions, ascites sometimes pericarditis).
Complications
Encephalopathy and encephalitis.
Liver failure.
Myocarditis.
Disseminated intravascular coagulation leading to massive bleeding.
Unusual manifestations

- Dengue encephalopathy

- Acute liver failure

- Myocarditis, cardiomyopathy
Symptoms DF (%) DHF (%)

Fever 100 100

Headache 100 96.7
Vomiting 0 47.8
Abdominal pain 0 39.1
Myalgia 27 39.1
Cough 0 39.1
Sore throat 0 21.7
Convulsion 0 17.4
Retro-orbital pain 0 13
Diarrhea 0 4.4
Differential diagnosis of dengue fever and DHF
Dengue fever
•Infectious mononucleosis.
•Chikungunya viral infections.
•Coxsackie and other enteroviral infections.
•Rickettsial infections.
•Rubella.
•Parvovirus B19 infections.
•Leptospirosis.
•Influenza.
DHF
• Leptospirosis.
• Chikungunya viral infections.
• Kawasaki disease.
• Yellow fever.
• Hanta viral infections.
• Other viral hemorrhagic fevers.
• Meningococcal septicemia.
PHYSICAL EXAMINATION
 Generalized lymphadenopathy (~ 50 % of cases)
 Relative bradycardia
 Morbiliform rash on the trunk, spreading to the face
and extremities (3rd – 5th day)
 Diffuse flushing, mottling, fleeting pinpoint erupsion
 Hemorrhagic phenomena
 Signs of plasma leakage (ascites, pleural effusion)
 Liver enlargement and tenderness
 Spleen enlargement
TEMPERATURE CURVE

defervescence phase

Critical pha convalescent

Fever phase
se
PERIOD OF DENGUE INFECTION
temp incubation acute phase critical phase recovery

5 - 9 days 1- 4 days 1 – 3 days 1- 2 days

41

40

39

38

37

0 1 2 3 4 5 6 7 8 day
 Warning Signs for Dengue Sho
ck
Four Criteria for DHF:
• Fever
• Hemorrhagic manifestations
• Excessive capillary
permeability
• 100,000/mm3 platelets
Initial Warning Signals:
• Disappearance of fever
• Drop in platelets
• Increase in hematocrite
Alarm Signals:
• Severe abdominal pain
• Prolonged vomiting
• Abrupt change from fever
to hypothermia
• Change in level of
consciousness (irritability
or somnolence)
When Patients Develop DS
S:
• 3 to 6 days after onset of
symptoms
LABORATORY EXAMINATION
Early tests
viral isolation
PCR/ RT-PCR
antigen detection
Further tests
serology test - antibody test
 LABORATORY EXAMINATIONS
 Specific
 Viral identification : viral isolation
 Serology
 detection of dengue antibody in serum
 detection of viral antigen or RNA in tissue or ser
um
 Non-specific
 WBC
 blue-plasma lymphocyte
 platelet count
 hematocrite
 albumin  blood gas
Others :
 GOT, GPT  ureum, creatinine

 PT, APTT, Fibrinogen, D-dimer

Elevated liver enzymes
 Found in 90 % of dengue patients
 SGOT > 60 IU has a PPV of 80 % for the diag
nosis of dengue infections
 Usually SGPT is slightly elevated, not more t
han 200 IU and SGOT level is about 2-3 time
s that of SGPT elevation.
 LABORATORY ABNORMALITIES IN DHF
 trombocytopenia - often found
 hemoconcentration - usually on day 3,4
 leukopenia - thrombocyte < 100,000/L
- severity of hemoco
ncentration
 severity of shock

 hypoalbuminemia due to plasma leakage

 elevated liver enzymes

 prolonged PT & APTT risk of bleeding

 low F. II, V, IX dan XI
 hypofibrinogenemia
found during hypovole
  FDP mic phase
 THROMBOCYTE
THROMBOCYTOPENIA
 Suppression of hemopoetic in bone marrow
 Peripheral :
1. Destruction of thrombocyte  interaction of antibody & antig
en DV on thrombocyte surface
2. Endothel wall damage  interaction of thrombocyte with coll
agen sub endothel  agregation and lysis of thrombocyte.
3. IL-6  IgM antiplatelet antibodies  destruction of thrombocy
te
4. Increase of need
THROMBOCYTE DYSFUNCTION
Degranulation of thrombocyte  ADP (-)
1. Primary  hypoagregation
2. Secondary  no response
 LEUKOCYTE

 Normal count  leukopenia, neutropenia,

lymphocytosis and atypical lymphocyte (+
)

 Lymphocyte count in DHF higher 15 - 20%

compared with DF

 Leukocyte count becomes normal 2 – 3 da

ys after recovery phase
Leukopenia
 Leukopenia, WBC < 5,000 cells/μL, is foun
d in 70 % of dengue patients
 When WBC < 5,000, is found together with

 relative lymphocytosis (> 45 %) and

 increase in atypical lymphocyte, it

 indicates that within 24 hours the pati

ent will have no fever and he is enteri
ng the critical phase
Blue-plasma lymphocyte
WHEN HEMATOCRITE INCREASES?

Hematocrite

70

60 * *
50
*
40 *
* *
* *
30

20

10

0
1 2 3 4 5 6 7 8 day
WHEN THROMBOCYTE DECREASES ?
Thrombocyte count

200,000
* * *
*
150,000
*

100,000 *
*

50,000
* *

0
1 2 3 4 5 6 7 8 day
Thrombocytopenia
 fever phase : decreasing

 shock phase : reaches the lowest level

 convalescent : rapid increase

 in 7-10 days after onset of illness  norm

al
 DD/
Congenital thrombocytopenia
Acquired thrombocytopenia
NORMAL NORMAL

THROMBOCYTOPENIA
SEROLOGIC TESTS

 Hemaglutination inhibition test (HI)

 Complement fixation test (CF)

 Neutralization test (NT)

 ELISA and Ig M antibody-capture (MAC) ELISA

sensitivity 80 – 97 %

 Rapid test (rapid dengue immunochromatograp

hic test for specific Ig M)
ANTIBODY LEVEL

IgG

IgM IgM
IgG

Virus Virus
(day)
5 10 15 2 5
First symptom First sympto
s ms
Primary in Secondary
fection infection

immune response to dengue infection

SEROLOGIC DIAGNOSIS
Detection of Dengue virus inf
ection by Ig G and Ig M antib
odies
Immunoserology in dengue infection
 Ig M : detected since 4th day – 5th day in sec
ondary infection, and since 5th day – 10th day
in primary infection, increasing until 3rd week
, disappears after 60-90 days
 Ig G : in primary infection detected on 14th da
y, in secondary infection detected on 2nd day
INTERPRETATION OF IgM dan IgG
EXAMINATION

IgM IgG Interpretations

(+) (-)
(+) (+)
(-) (+)

(-) (-)
INTERPRETATION OF IgM dan IgG
EXAMINATION

IgM IgG Interpretations

(+) (-) Primary infection
(+) (+) Secondary infection
(-) (+) Suspected secondar
y infection
(-) (-) Not DV infection
Dengue NS1 antigen-capture ELISA
 One step sandwich format microplate enzyme immunoas
say (PlateliaTM Dengue NS1 AG, Bio-Rad, France) to det
ect dengue virus NS1 antigen in human serum/ plasma
 NS1 antigen is found in circulation from 1st day of fever
up to 9th day (Shu PY et al, J Clin Microbiol 2002; 40: 1840-1844)
 Sensitivity 93.4 % and specificity 100 % (Kumarasamy, et al
, J Virol Methods 2006)
 Superior to virus isolation and RT-PCR in diagnosis of a
cute dengue virus infection
 Provide early diagnosis of acute dengue infection (since
1st day of symptoms) compared with rapid test and MA
C-ELISA (4th – 5th days of illness onset in secondary infe
ction)
 The level of NS1 of Dengue-2 virus in plasma is correlat
ed with viremia levels and significantly higher in DHF pati
ents than DF patients within 72 hours of illness onset (Lib
raty et al, J Infect Dis 2002; 186: 1165-1168)
Radiology examination
 Chest X-ray : pleural effusion
 Abdomen US : ascites, thickening of gall bl
adder wall
MANAGEMENT
 Symptomatic and supportive
 Principally aimed towards replacement of plas
ma loss during the period of active leakage of a
bout 24 – 48 hours
 Treatment of complications :
bleeding, shock
metabolic acidosis, respiratory alkalosis
electrolyte disturbances
renal/ liver impairment
bacterial infections/sepsis
FLUID TREATMENT OF DF / DHF

maintenance maintenance/ modera maintenance/ stop

te dehydration
 PROTOKOL 1. PENANGANAN TERSANGKA ( PROBABLE )
DBD DEWASA TANPA SYOK

Keluhan DBD
(Kriteria WHO 1997)

Hb, Ht Hb, Ht normal Hb, Ht meningka

Hb, Ht normal
trombo normal
trombo 100.000-150.000 trombo normal/
trombo < 100.000

Observasi Observasi Rawat Rawat

Rawat jalan Rawat jalan
Periksa Hb, HtPeriksa Hb, Ht Penanganan Protokol
Leuko, Tromb/24 jam
Leuko, Rawat Inap Untuk DBD
Tromb/24 jam
( Protokol 2 )
 PROTOKOL 2. PEMBERIAN CAIRAN PADA TERSANGKA
DBD DEWASA DI RUANG RAWAT

Suspek DBD
Perdarahan Spontan dan Masif ( - )
Syok (-)

- Hb, Ht (n)
- Hb, Ht meningkat 10-20% - Hb, Ht meningkat > 20%
- Tromb < 100.000
- Tromb < 100.000 - Tromb < 100.000
- Infus Kristaloid *
- Infus Kristaloid *
- Hb, Ht, Tromb tiap 24 jam
- Hb, Ht, Tromb tiap 12 jam **
Protokol pemberian Cairan
DBD dengan Ht meningkat
> 20%

* Volume cairan kristaloid per hari yang diperlukan:

Sesuai rumus berikut 1500 + 20 x (berat badan dalam kg - 20)
Contoh volume rumatan untuk berat badan 55 kg : 1500 + 20 x (55-20) = 2200 ml
(Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention and Control.
PAHO: Washington, D.C., 1994: 67).

** Pemantauan disesuaikan dengan fase/hari perjalanan penyakit dan kondisi klinis

PROTOKOL 3. PENATALAKSANAAN DBD DENGAN
PENINGKATAN HT > 20 %

5 % defisit cairan

Terapi awal cairan intravena

Kristaloid 6-7 ml/kg/jam

Evaluasi
3-4 jam
PERBAIKAN TIDAK MEMBAIK
Ht dan frekuensi nadi turun, Ht, nadi meningkat
tekanan darah membaik, tekanan darah menurun < 20 mmHg
produksi urin meningkat produksi urin menurun

Kurangi infus TANDA VITAL DAN

kristaloid Infus kristaloid
HEMATOKRIT
5 ml/kg/jam 10 ml/kg/jam
MEMBURUK

PERBAIKAN TIDAK
PERBAIKAN MEMBAIK

Kurangi infus
kristaloid Infus kristaloid
3 ml/kg/jam 15 ml/kg/jam

PERBAIKAN
KONDISI MEMBURUK
Tanda syok
Terapi cairan
dihentikan
24-48 jam Tatalaksana sesuai
Protokol syok dan
PERBAIKAN perdarahan
 PROTOKOL 4. PENATALAKSANAAN PERDARAHAN SPONTAN
PADA DBD DEWASA

KASUS DBD :
Perdarahan Spontan dan Masif : - Epistaksis tidak terkendali
- Hematemesis melena
- Perdarahan otak
Syok (-)

Hb, Ht, Trombo, Leuko, Pemeriksaan Hemostasis (KID)

Golongan darah, uji cocok serasi

KID (+) KID (-)

Transfusi komponen darah : Transfusi komponen darah :
* PRC (Hb<10 g/dL) * PRC (Hb<10 g %)
* FFP * FFP
* TC (Tromb.<100.000) * TC (Tromb.<100.000)
** Heparinisasi 5000-10000/24 jam drip * Pemantauan Hb, Ht, Tromb. Tiap 4-6 jam
* Pemantauan Hb, Ht, Tromb. Tiap 4-6 jam * Ulang pemeriksaan hemostasis 24 jam
* Ulang pemeriksaan hemostasis 24 jam kemudian kemudian
Cek APTT tiap hari, target 1,5-2,5 kali kontrol
 Airway
Breathing : O 2 1-2 l/menit dengan kateter nasal).
Bila lebih, dipakai sungkup muka
Circulation : cairan kristaloid * dan atau koloid **
10-20 ml/kg BB secepatnya (bila
mungkin < 10 menit)
Perhatikan : Tanda-tanda hipovolemia,
hipervolemia /overload dan TETAP SYOK
respons pemberian cairan.
PERBAIKAN ****
Kristaloid
Guyur 20-30 ml/kg BB
Kristaloid * 20-30 menit
7 ml/kg/jam dalam 1 jam
PERBURUKAN
TETAP SYOK
PERBAIKAN

Kristaloid * Ht k Ht l
5 ml/kg/jam dalam 1 jam
Koloid*** 10-20 ml/kg/BB Transfusi darah
Perhitungan nutrisi tetes cepat 10-15 menit 10 ml/kg BB dapat diulang
setelah 12 jam
sesuai kebutuhan
(destroxe 5 % bila tidak ada
kontraindikasi) PERBAIKAN****
TETAP SYOK
24-48 jam setelah syok
teratasi, tanda vital/Ht stabil,
diuresis cukup Koloid *** hingga
maksimal 30 ml/kg BB

Stop infus PERBAIKAN**** TETAP SYOK

Pasang kateter
vena sentral *****

Koloid *** bila dosis maksimal belum dicapai

atau kristaloid/gelatin (bila koloid sebelumnya

PROTOKOL 5. telah mencapai dosis maksimal) 10 ml/kg

dalam 10 menit, dapat diulang sampai 30
ml/kg; sasaran tekanan vena sentral (TVS)
TATALAKSANA SYOK 15-18 smH 2 O

PASIEN DEWASA Hipovolemik Normovolemik

TETAP SYOK

Kristaloid dipantau Koreksi gangguan

10-15 menit asam basa, elektrolit,
hipoglikemia, anemia,
PERBAIKAN**** KID, infeksi sekunder

- inotropik******
Kombinasi Perbaikan
- vasopresor
koloid kristaloid bertahap vasopresor
- vasodilator
Indication of ICU treatment

 fail to overcome shock in 1 hour

 repeated shock
 shock with severe bleeding
 shock with complications : respiratory failure
, encephalopathy, heart failure, acute renal f
ailure, convulsion
 Choice of Fluid Resuscitation
crystalloid and/or colloid

Less effective for severe DSS

Need large volume
CRYSTALLOID: Pro-coagulant effect
RL DVT/ emboli effect
COLLOID:
RA DEXTRAN
NS 0.9% GELATINE
Effective for iv filling
HES
HES: Sealing Albumin
HES: Macro and
Microcirculation
Plasma not used as replacement of fluid loss !
NS in large volume can cause hyperchloremic acidosis
RL/RA in large volume not cause metabolic acidosis
RA used if there is severe liver dysfunction
Colloids
 HES MW 130,000, HES MW 200,000,
HES MW 40,000, gelatine, dextran
 Maximum dose of synthetic colloids :
HES (pentastarch) 6 % : 30 ml/ kg BW/ day
HES (pentastarch) 10 % : 20 ml/ kg BW/ day
HES (tetrastarch) : 50 ml/ kg BW/ day
dextran : 1.5 g/ kg BW/ day
 Choice of colloids :
1. HES MW 130,000, substitution level 0.4 (tetrastarch)
2. HES MW 200,000
3. HES MW 40,000
4. Gelatine, dextran 6 %, dextran 10 %
Colloids
 HES MW 130,000 : Voluven®
 HES MW 200,000 : Haes Steril 6 %®,
Haes Steril 10 %® ,
FIMA HES®, Wida Hes®
 HES MW 40,000 : Expafusin®
 Gelatine : Haemacel®, Gelafusin®
 Dextran : Dextran L®, Dextran 70®,
Plasmafusin®
rapid infusion 10-20 ml/ kg BW, evaluated after 1
0-30 minutes, maximum dose 30 ml/ kg BW/ day
 Blood Component
 PRC: Hb maintained 10 g/dl to increase DO2
 D02= CI x (1.36 x Hb% x SaO2 )+PaO2x 0.003
 FFP : bleeding, prolonged PT & APTT (> 1.5 x N)
 Cryoprecipitate: low fibrinogen < 100 mg/dl
 Thrombocyte concentrate :
(1). Active bleeding or at high risk: post surgery, pre-
procedure with platelet 5000-30,000.
(2). Platelet <5000/mm3 regardless of apparent blee
ding.
WHO (1997): platelet < 20,000/mm3,
or < 40,000/mm3 with significant bleeding
 Fresh blood
internal bleeding with decreased hematocrite, transfu
sion 10 ml/ kg BW and can be repeated if necessary
 Inotropics/ vasopressors
(patients should be in normovolemic condition)
- dopamine 5 – 10 μg/ kg/ minute with target
MAP > 60 mmHg
- if MAP still < 60, dopamine substituted by
dobutamine 5 – 20 μg/ kg/ minute in combination with
norepinephrine 0,05 – 0,1 μg/ kg/ minute - 1 μg/ kg/ minute
- if MAP remains < 60, regiment changed with epinephrine
0,1 μg/ kg/ minute titrated up to 2 μg/ kg/ minute
Heparin
if clinical and laboratory findings support th
e presence of DIC,
dose of 5,000 – 10,000 unit/ 24 hours conti
nuing infusion
Disseminated Intravascular Coagulation (DIC)
 Screening tests
platelet count, PT, aPTT,
thrombine time, fibrinogen
 Confirmed tests
soluble fibrin monomer, D-Dimer, FDP, AT (antithr
ombin)

Minimum criteria for diagnosis of DIC :

( National Consensus of Management of DIC, 2001)
 Clinical features or conditions that can cause DIC

 Manifestations of bleeding, thromboemboli or both

 Thrombocytopenia and Burr cell (+) or D-Dimer (+)

DIC Score
(Scientific and Standardization Committee of International Society on Throm
bosis and Haemostasis)

Score

Platelet count : > 100,000 0

50,000-100,000 1
< 50,000 2
sFM/ FDP/ D-Dimer : not increased (D-D < 500) 0
moderately increased (D-D 500-1000) 2
very high increase (D-D > 1000) 3
Prolongation of PT : < 3 seconds 0
4- 6 seconds 1
> 6 seconds 2
Fibrinogen : > 100 mg/dL 0
< 100 mg/dL 1
Score ≥ 5 : DIC, score repeated every day
Score < 5 : suggestive of DIC, score repeated in 1-2 days
IVIG in DSS: Decrease cytokine release; anti-auto antibody

Frias MV (1999). The use of intravenous immunoglobulin in d

engue shock syndrome: a randomized double-blind placebo-
controlled trial [dissertation]. Manila, The Philippines
216 children, IVIG 400 mg/kg once daily for 3 days significan
tly reduced mortality

Brazilian study in adult DHF: IVIG 500 mg/kg daily (5 days) in

only 5 patients: rapid decrease in bleeding and rapid increas
e in number of platelets (Ostronoff M, Ostronoff F, Florencio R et al: Serio
us thrombocytopenia due to dengue hemorrhagic fever treated with high dosages
of immunoglobulin. Clin Infect Dis 2004;36:1623-1624)
Bicarbonate therapy
Bicarbonate not recommended for correcting acidemia due to
hypoperfusion with pH > 7.15
Bicarbonate not improve hemodynamic or response to cathe
colamin administration
More useful to manage its etiology
OTHERS
Carbazochrome not useful in preventing plasma leakage and shock i
n DSS (Tassniyom S et al, 1997)
Antacida : no reference of the use of antacida in DSS
Pleural effusion & ascites not need drainage because of risk of ble
eding, except cause severe dysfunction of cardiorespiration system
Insertion of CVP catheter, higher risk compared with its benefits (S
hann, 2005)
Plasma exchange (if not available : whole blood exchange) can be giv
en for severe DHF , (especially before given IVIG) (Shann, 2005)
Benefits from Colloids
 Attenuate inflammatory response, res
tore vascular integrity and improve mi
crocirculation
 Restore intravascular volume more ra
pidly regardless of vascular permeabi
lity
 Reduce tissue and pulmonary edema
 Improve oxygenation in adult respirat
ory distress syndrome
 Reduce mortality in severe sepsis
HES
 Downregulate the production of pro-inflammatory cytokin
es TNF-alfa, IL-1, IL-6 and inhibit production of inflammat
ory mediators by suppressing the activation of NFkb, AP-
1
 Reduce leucocyte endothelial interaction by downregulati
on of cellular adhesion molecules on neutrophil and endo
thelium
 Reduce pulmonary capillary permeability and prevent me
senteric ischemia better than crystalloids
 Restore intravascular volume & tissue perfusion more ra
pidly than crystalloids (greater volume expansion per unit
infused)
 Restore intravascular volume & cardiac output without wo
rsening pulmonary edema & oxygenation
 Sealing the endothelium
 SEALING EFFECT
HES 200/0.5 is better than :
 ALBUMIN 5%
 RINGER LACTATE
 HES w MW < 50,000
 HES w MW > 300,000
Zikria BA et al. A biophysical approach to
capillary permeability. Surgery 1989; 105;625.
Adverse effects of HES
 Negative effect on kidney function (none r
equires dialysis)
 Coagulopathy
newer HES up to 2500 ml has no negative
effect on platelet function and coagulation
 Very rare :
anaphylactoid reaction (bradycardia, tachycardia
, bronchospasm, non-cardiac pulmonary edema)
increased serum amylase
itching
Contraindications
 Fluid overload (hyperhydration) including pulmonary
edema
 Renal failure with oliguria or anuria
 Patients receiving dialysis treatment
 Intracranial bleeding
 Severe hypernatremia or severe hyperchloremia
 Known hypersensitivity to HES
 Use in children, pregnancy, lactating women  care
ful evaluation of risk and benefit
 Hazards from Crystalloids
 No beneficial effect on microcirculation an
d organ perfusion
 Up to three times more volume and longer
infusion periods is required to achieve com
parable hemodynamic end points
 Tissue and lung edema
 Hyperchloremic acidosis
 Hypercoagulability
 Advantages of Colloid
 Refilling IVF faster than crystalloids
 Shock time becomes shorter
 Remains in IVF longer than crystalloids
 No interstitial edema
 Preserves oncotic pressure effect
 No interstitial edema
THINGS TO REMEMBER (1)

 Keys of successful management are early cli

nical recognition and careful/ close monitorin
g of clinical presentations, laboratory finding
s/ other examinations
 Volume substitution IS NOT fluid replacemen
t
 Fluid balance must be checked carefully
 Crystalloids have always to be given in additi
on
 THINGS TO REMEMBER (2)

• Early recognition of sign of shock can modify

the severity of DHF patients
• The period of plasma leakage/shock is short :
24 - 48 hours
• DSS can be successfully resuscitated by using
crystalloid only : + 60%
plus colloids : 20%
need blood/component transfusion: + 15%
Pitfalls in management

• Use hypotonic solution and delay to use colloids

during critical period of plasma leakage
• Failure to monitor the rate/volume of replacement
fluid:  massive pleural effusion/ ascites
 pulmonary edema
• Failure to recognize concealed internal bleeding
 prolonged shock, fluid overload, death
• Over use of platelet transfusion as prophylaxis
for bleeding in all shock cases
PROGNOSIS
 After recovery from dengue infection, convales
cent may be prolonged for several weeks by w
eakness, depression, occasional palpitation, br
adycardia, ventricular extrasystole
 Case fatality rate of DHF-DSS that NOT treate
d promptly and properly ~ 50 %
 With good medical management : mortali
ty < 1 %