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
Philippine hemorrhagic fever)
 Insiden meningkat dengan jelas sejak tahun 1960an,
Diperkirakan 100 juta kasus infeksi Virus Dengue terjadi
setiap 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 %

Target WHO : angka kematian : <1 %

WHO (1997) : angka kematian DSS 40-50%
Wills (2005) : angka kematian 1-5%
  Virus Dengue : genus
Flavivirus, family
Flaviviridae
 4 serotypes :
DEN-1, DEN-2, DEN-3,
DEN-4
 Indonesia : DEN-3 >
(37 %)
 Inkubation : 4 – 6 hari
(3 – 14 hari)
 Transmisi : manusia ke
manusia malalui nyamuk
 Patogenesis : masih
kontroversy
Stegomyia aegypty (secondary heterologous
infection; Suvatt, 1977)
PATHOGENESIS
 Setelah nyamuk yang terinfeksi menghisap darah
manusia, virus masuk ke tubuh manusia, virus
bereplikasi 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,
coagulation, and hemostasis
 Immune status of the host, virus genotype &
secondary infections determine the course of
infection & subsequent development of DHF-DSS
 Increased number of infected monocytes, elevated
TNF-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

enhance viral uptake and replication in mononuclear
phagocytes

Infected cells : target of immune elimination mechanism

Trigger the production of mediators with activation of

complement and clotting cascade

Plasma leakage, bleeding, shock

Factors influencing induction of vascular
permeability and development of shock
 presence of enhancing & non-neutralizing
antibodies
 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
Dengue encephalopathy
encephalopathy

- Acute
Acute liver
liver failure
failure

- Myocarditis,
Myocarditis, cardiomyopathy
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 convalescent
Fever phase
phase
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
Shock
AlarmSignals:
Alarm Signals:
•• Severe
Severeabdominal
abdominalpain
pain
•• Prolonged
Prolongedvomiting
vomiting
Four
FourCriteria
Criteriafor
forDHF:
DHF: •• Abrupt
Abruptchange
changefrom
fromfever
fever
•• Fever
Fever
•• Hemorrhagic
Hemorrhagicmanifestations
manifestations
•• Excessive
Excessivecapillary
capillary
permeability
permeability
••100,000/mm
100,000/mm3platelets
3
platelets
tohypothermia
to hypothermia
Initial
InitialWarning
WarningSignals:
Signals: • Change
Change inlevel
level of
•• Disappearance •When
When in
Patients of
Develop
Patients Develop
Disappearanceof offever
fever consciousness
consciousness (irritability
(irritability
•• Drop DSS:
DSS:
Dropininplatelets
platelets
•• Increase
Increaseininhematocrite
hematocrite •• 33to
to66days
daysafter
afteronset
onsetof of

or somnolence)
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

serum
 Non-specific
 WBC
 blue-plasma lymphocyte

 platelet count

 hematocrite

 albumin  blood gas

Others :  ureum, creatinine
 GOT, GPT
 PT, APTT, Fibrinogen, D-dimer
Elevated liver enzymes
 Found in 90 % of dengue patients
 SGOT > 60 IU has a PPV of 80 % for the
diagnosis of dengue infections
 Usually SGPT is slightly elevated, not more
than 200 IU and SGOT level is about 2-3
times that of SGPT elevation.
 LABORATORY ABNORMALITIES IN DHF
 trombocytopenia - often found
 hemoconcentration - usually on day 3,4
 leukopenia - thrombocyte < 100,000/L
- severity of
hemoconcentration
 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
  FDP hypovolemic phase
 THROMBOCYTE
THROMBOCYTOPENIA
 Suppression of hemopoetic in bone marrow
 Peripheral :
1. Destruction of thrombocyte  interaction of antibody &
antigen DV on thrombocyte surface
2. Endothel wall damage  interaction of thrombocyte with
collagen sub endothel  agregation and lysis of thrombocyte.
3. IL-6  IgM antiplatelet antibodies  destruction of
thrombocyte
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

days after recovery phase
Leukopenia
 Leukopenia, WBC < 5,000 cells/μL, is
found 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

patient will have no fever and he is
entering 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 

normal
 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
immunochromatographic test for specific Ig M)
ANTIBODY LEVEL

IgG

IgM IgM
IgG

Virus Virus
(day)
5 10 15 2 5
First First
symptoms symptoms
Primary Secondary
infection infection

immune response to dengue infection

SEROLOGIC DIAGNOSIS
Detection of Dengue virus
infection by Ig G and Ig M
antibodies
Immunoserology in dengue infection
 Ig M : detected since 4th day – 5th day in
secondary 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
day, 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
secondary infection
(-) (-) Not DV infection
Dengue NS1 antigen-capture ELISA
 One step sandwich format microplate enzyme
immunoassay (PlateliaTM Dengue NS1 AG, Bio-Rad,
France) to detect 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
acute dengue virus infection
 Provide early diagnosis of acute dengue infection (since
1st day of symptoms) compared with rapid test and
MAC-ELISA (4th – 5th days of illness onset in secondary
infection)
 The level of NS1 of Dengue-2 virus in plasma is
correlated with viremia levels and significantly higher in
DHF patients than DF patients within 72 hours of illness
onset (Libraty et al, J Infect Dis 2002; 186: 1165-1168)
Radiology examination
 Chest X-ray : pleural effusion
 Abdomen US : ascites, thickening of gall
bladder wall
MANAGEMENT
 Symptomatic and supportive
 Principally aimed towards replacement of
plasma loss during the period of active leakage
of about 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/ maintenance/ stop

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

Keluhan DBD
(Kriteria WHO 1997)

Hb, Ht Hb, Ht normal Hb, Ht normal Hb, Ht meningkat

trombo normal trombo 100.000-150.000 trombo < 100.000 trombo normal/turun

Observasi Observasi Rawat Rawat

Rawat jalan Rawat jalan
Periksa Hb, Ht Periksa Hb, Ht Penanganan Protokol
Leuko, Tromb/24 jam Leuko, Tromb/24 jam Rawat Inap Untuk DBD
( 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  Ht 
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 failure, 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
10-30 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
bleeding.
WHO (1997): platelet < 20,000/mm3,
or < 40,000/mm3 with significant bleeding
 Fresh blood
internal bleeding with decreased hematocrite,
transfusion 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
the presence of DIC,
dose of 5,000 – 10,000 unit/ 24 hours
continuing infusion
Disseminated Intravascular Coagulation (DIC)
 Screening tests
platelet count, PT, aPTT,
thrombine time, fibrinogen
 Confirmed tests
soluble fibrin monomer, D-Dimer, FDP, AT
(antithrombin)

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
Thrombosis 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

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

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

only 5 patients: rapid decrease in bleeding and rapid
increase in number of platelets (Ostronoff M, Ostronoff F, Florencio R
et al: Serious 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
cathecolamin administration
More useful to manage its etiology
OTHERS
Carbazochrome not useful in preventing plasma leakage and shock
in 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
bleeding, except cause severe dysfunction of cardiorespiration system
Insertion of CVP catheter, higher risk compared with its benefits
(Shann, 2005)
Plasma exchange (if not available : whole blood exchange) can be
given for severe DHF , (especially before given IVIG) (Shann, 2005)
Benefits from Colloids
 Attenuate inflammatory response,
restore vascular integrity and improve
microcirculation
 Restore intravascular volume more
rapidly regardless of vascular
permeability
 Reduce tissue and pulmonary edema
 Improve oxygenation in adult
respiratory distress syndrome
 Reduce mortality in severe sepsis
HES
 Downregulate the production of pro-inflammatory
cytokines TNF-alfa, IL-1, IL-6 and inhibit production of
inflammatory mediators by suppressing the activation of
NF, AP-1
 Reduce leucocyte endothelial interaction by
downregulation of cellular adhesion molecules on
neutrophil and endothelium
 Reduce pulmonary capillary permeability and prevent
mesenteric ischemia better than crystalloids
 Restore intravascular volume & tissue perfusion more
rapidly than crystalloids (greater volume expansion per
unit infused)
 Restore intravascular volume & cardiac output without
worsening 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
requires 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 
careful evaluation of risk and benefit
 Hazards from Crystalloids
 No beneficial effect on microcirculation
and organ perfusion
 Up to three times more volume and longer
infusion periods is required to achieve
comparable 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

clinical recognition and careful/ close
monitoring of clinical presentations,
laboratory findings/ other examinations
 Volume substitution IS NOT fluid
replacement
 Fluid balance must be checked carefully
 Crystalloids have always to be given in
addition
 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,
convalescent may be prolonged for several
weeks by weakness, depression, occasional
palpitation, bradycardia, ventricular
extrasystole
 Case fatality rate of DHF-DSS that NOT
treated promptly and properly ~ 50 %
 With good medical management :
mortality < 1 %