DENGUE FEVER/DENGUE HEMORRHAGIC FEVER

Dr. Harun Hudari, SpPD FINASIM

CURRICULUM VITAE

• Nama : Dr. H. Harun Hudari, SpPD, FINASIM• TTL : Palembang, 3 Mei 1970• Pendidikan :

- Dokter FK Universitas Sriwijaya 1996

- Spesialis Penyakit Dalam FK Universitas Sriwijaya 2008• Riwayat Pekerjaan :

1. Dokter PTT Puskesmas Muara Rupit 1997 – 2000

2. Dokter PNS RSUD Dr. MM Dunda Gorontalo 2001 – 2004

3. Dokter Spesialis Penyakit Dalam RSUD Banyuasin

2008 – sekarang

4. Dokter Spesialis Penyakit Dalam FK UNSRI/RSMH

Palembang 2009 – sekarang• HP : 081271621966 / 0711 7301744

About Dengue

• Dengue is one of the most important mosquito-born viral diseases affecting humans.

• Viral life cycle involves humans and the mosquito vector Aedes aegypti. – In the U.S. it has been found that the mosquito Aedes albopictus also

transmits the DEN virus.

• The disease is caused by 4 serotypes of the Dengue virus, a member of the genus Flavivirus: DEN-1, DEN-2, DEN-3, DEN-4.

• Infection with the DEN virus can result in Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS).

Dengue is a tropical febrile disease

992- Chinese Encyclopedia

1780- Philadelphia “break-bone fever”

Benjamin Rush

Dengue Fever has a long history…www.philadelphia-reflections.com/topic/17.htm

Isolated by Albert Sabin in 1944

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Manifestations of the dengue syndrome

• Spectrum of illness:

Asymptomatic

Undifferentiatedfever

No hemorrhage

Unusualhemorrhage

Dengue Fever

DHF 1& 2 DHF 3&4DSS

Dengue Hemorrhagic Fever(plasma leakage)

Symptomatic

Dengue virusInfection

Filoviridae(Ebola, Marburg)

Arenaviridae(Lassa, Junin, Machupo, Guanarito)

Bunyaviridae(CCHF, RVF,

Hantaviruses)

Viral Haemorrhagic Fevers

Flaviviridae(dengue, yellow fever, TBE encephalitides)

EnvelopedRNA viruses

Geographic distribution:

Southeast Asia, the Caribbean,

the Western Pacific Regions.

Other epidemiological features:

High incidence in rainy season;

Spread rapidly;

High mobidity;

Distribution of dengue, Eastern Hemisphere

Distribution of Aedes aegypti (red shaded areas) in the Americas in 1970,and in 1997

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Dengue Virus

• Family: Flaviviridae• ss +RNA• genome: 10 proteins• 3 Structural

– Coat, deliver RNA to target cells

• 7 Nonstructural• Enveloped• 4 serotypes:

– DEN-1, 2, 3, 4

Goodsell, David. "Dengue Virus." RCSB PDB-101. N.p., n.d. Web. 23 Oct. 2012.

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Ag

/Ab

level

Day

IgMIgG

Immune Response

SymptomNS1 AgDA

Y-7 -6 -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9

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AntibodyBite

NS1 Ag

ACUTEPHASE

CONVALES-ENCE PHASE

CRITICAL PHASE

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Dengue Fever

Febrile Phase

Critical Phase

Recovery Phase

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Clinical course of dengue infection -

Febrile Phase

Critical Phase

RecoveryPhase

Lasts for 2 – 7 daysClinical features are indistinguishable between DF and DHF

Happens often after the 3rd day of feverClinical presentation depends on the presence and degree of plasma leakageLasts for about 24-48 hours

In DHF patients – plasma leakage stops and is followed by reabsorption of extravascular fluid

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Febrile Phase• Usually lasts for 2 – 7 days• Fever is often accompanied by

– Facial flushing, skin erythema, generalised body ache, myalgia, arthalgia and headache

– Anorexia, nausea and vomiting are common• Mild hemorrhagic manifestations may be seen

– This may include positive tourniquet test, petechiae or mucosal bleeding

• Earliest abnormality in FBC is a progressive decrease in total WBC count

• These features are indistinguishable between DF and DHF

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Critical Phase - 1

• Occurs either– Towards the late febrile phase

• Often after 3rd day of fever

or– Around defervescence

• Usually between 3rd day to 5th day of fever; but may go up to the 7th day of fever.

• This phase lasts for 24- 48 hours

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Critical Phase - 2During this phase if,

• Minimal or no plasma leakage occurs– Patient feels better as the

temperature subsides

• Dengue fever

• Critical volume of plasma leakage occurs– Patient develops DHF– Varying degrees of

circulatory disturbances occur depending on the degree of plasma leakage

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Critical Phase -3

• In more severe form of plasma leakage– Patients may sweat, become restless, have cool

extremities and prolonged capillary filling time– The pulse rate increases, diastolic BP increases

and the pulse pressure narrows

12011010090807060

Blood pressure, pulse pressure, heart rate in hypovolemic shock

Time

Compensated shock Decompensated shock

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Critical Phase - 3Clinical warning signs of severe dengue or

high possibility of rapid progression to shock

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Critical phase - 4• Thrombocytopenia and hemoconcentration are

usually detectable before the onset of shock• HCT level correlates well with plasma volume

loss and disease severity.• However HCT values may be equivocal and hence

unhelpful when there is frank hemorrhage or with untimely HCT determinations

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Recovery Phase• Plasma leakage stops after 24-48 hours of

defervescence• This followed by reabsorption of extravascular fluid• Patients’ general well being improves, appetite

returns, gastrointestinal symptoms abate, hemodynamic status stabilises and diuresis ensues.

• Recovery of platelet count is typically preceded by the recovery of WCC count

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WHO classification - DHF• Grade 1

In the presence of haemoconcentration, fever and symptoms, a positive TT and/or easy bruising

• Grade 2spontaneous bleeding in addition to the manifestation from Grade 1

• Grade 3*circulatory failure – rapid, week pulse and narrowing of pulse pressure or

hypotension with the presence of cold, clammy skin and restlessness.• Grade 4*

profound shock – with undetectable blood pressure or pulse.

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• Grade 1 & 2 – Non-shock DHF• Grade 3 & 4 – DSS

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Pathophysiology of DHF - 1• Primary pathophysiological abnormality in DHF

and DSS is an acute increase in vascular permeability

• Plasma leakage results in hemoconcentration and hypovolemia or shock

• Hypovolemia leads to reflex tachycardia and generalised vasoconstriction

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Clinical manifestations of vasoconstriction in various systems are;– Skin

• coolness, pallor and delayed capillary refill time– Cardiovascular system

• raised diastolic blood pressure and a narrowing pulse pressure – Renal system

• reducing urine output – Gastrointestinal system

• vomiting and abdominal pain– Central nervous system

• lethargy, restlessness, apprehension, reduced level of consciousness– Respiratory system

• tachypnoea (respiratory rate >20/min)

Pathophysiology of DHF - 2

Kasus DBD

1.Demam akut 2-7 hari, bersifat bifasik.

2. Manifestasi perdarahan

• uji tourniquet positif

• petekia, ekimosis, atau purpura

• Perdarahan mukosa, saluran cerna, dan tempat bekas suntikan

• Hematemesis atau melena

3. Trombositopenia < 100.00/pl

4. Kebocoran plasma yang ditandai dengan

•Peningkatan nilai hematrokrit >_ 20 % dari nilai baku sesuai umur dan jenis kelamin.

• Penurunan nilai hematokrit >_ 20 % setelah pemberian cairan yang adekuat

• Efusi pleura, asites, hipoproteinemi39

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TATALAKSANA• 1. Demam dengue

Pasien DD dapat berobat jalan, tidak perlu dirawat.

Pada fase demam pasien dianjurkan

• Tirah baring, selama demam.

• Obat antipiretik atau kompres hangat

Asetosal tidak dianjurkan gastritis, perdarahan, /asidosis.

• cairan dan elektrolit per oral, jus buah, sirop, susu, disamping air putih, paling sedikit diberikan selama 2 hari.

• Monitor suhu, jumlah trombosit dan hematokrit sampai fase konvalesen.

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• 2. DBDJenis Cairan (rekomendasi WHO)

Kristaloid. • Larutan ringer laktat (RL) ,

Larutan ringer asetat (RA), Larutan garam faali (GF)• Dekstrosa 5% dalam larutan ringer laktat (D5/RL)• Dekstrosa 5% dalam larutan ringer asetat (D5/RA)• Dekstrosa 5% dalam 1/2 larutan garam faali (D5/1/2LGF)• (Catatan:Untuk resusitasi syok dipergunakan larutan RL atau

RA tidak boleh larutan yang mengandung dekstran)

Koloid.• Dekstran 40• Plasma• Albumin

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• Monitoring tanda vital• Koreksi Gangguan Metabolik dan Elektrolit• Pemberian Oksigen• Transfusi Darah

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Volume Therapy Fluid replacement : renal, enteral or dermal loss (interstitial space)

Crystalloids distributes in the intravasuclar and interstitial space filling thereby the extravascular space up

Volume replacement : acute or subacute loss from the intravasuclar - Colloids contain oncotic substances- Ideally the volume stays intravasal

General Fluid Replacement Crystalloids : Compensation extracellular fluid losses

Plasma Volume Replacement Colloids : Compensation of acute or subacute intravascular fluid losses

Perbedaan Terapi berdasarkan kompartemen cairan

Terapi kasus dehidrasi

penggantian kehilangan cairan di semua ruang extracellular

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Terapi kasus hypovolemia

penggantian kehilangan

cairan di ruang intravascular (= kehilangan darah)

fluid replacement volume replacement

Kristaloid Koloid

Efek osmolarity cairan pada sel

Saat menderita DBD, cairan tubuh banyak hilang karena:

KEBOCORAN SEL

DEMAM PERDARAHAN

MUAL & MUNTAH

BAHAYA DEHIDRASI PADA PASIEN DBD :• Demam lambat turunnya • Pematangan trombosit terhambat perdarahan sulit

dihentikan• Kekentalan darah meningkat supply oksigen dan

nutrisi ke seluruh tubuh melambat • Tekanan darah tidak stabil• Kekuatan otot berkurang

KENAPA SAAT DBD PERLU CAIRAN?

Cairan tubuh (air + ION) berkurang.POTENSI

DEHIDRASI

Approach to the Management

Groups A• may be sent

home• tolerate

adequate volumes of oral fluids and pass urine at least once every 6 hours

• no warning signs

Groups B• referred for in-

hospital management

• with warning signs, co-existing conditions,

• with certain social circumstances

Groups C• require

emergency treatment and urgent referral

• severe dengue (in critical phase)

Management Decisions

Group A Action Plan

• Encourage intake of ORS, fruit juice and other fluids• Paracetamol and tepid sponge for fever• Advise to come back if with

no clinical improvement severe abdominal pain persistent vomiting cold and clammy extremities,lethargy or irritability or restlessness, bleeding

not passing urine for more than 4–6 hours.

monitor: temperature pattern, volume of fluid intake and losses, urine output, warning signs, signs of plasma leakage and bleeding, haematocrit, and white blood cell and platelet counts

Group B (with warning signs) Action Plan

• reference hematocrit before fluid therapy• isotonic solutions

5–7 ml/kg/hour for 1–2 hours, then reduce to 3–5 ml/kg/hr for 2–4 hours, and then reduce to 2–3 ml/kg/hr or less according to the clinical response

reassess:• haematocrit remains the same or rises only minimally 2–3 ml/kg/hr for

another 2–4 hours • worsening vital signs and rising haematocrit rising 5–10 ml/kg/hour for 1–2

hours

Group B (with warning signs) Action Plan

Give minimum intravenous fluid volume: maintain good perfusion and urine output of about 0.5 ml/kg/hr• Intravenous fluids are usually needed for only 24–48 hours. • Reduce intravenous fluids gradually when the rate of plasma

leakage decreases towards the end of the critical phase.

monitor: • vital signs and peripheral perfusion (1–4 hourly until the patient is

out of the critical phase)• urine output (4–6 hourly)• hematocrit (before and after fluid replacement, then 6–12 hourly) • blood glucose • organ functions (renal profile, liver profile, coagulation profile)

Group B (without warning signs) Action Plan

• Encourage oral fluids

• If not tolerated, start intravenous fluid therapy of 0.9% saline or Ringer’s lactate with or without dextrose at maintenance rate

Patients may be able to take oral fluids after a few hours of intravenous fluid therapy.

• Give the minimum volume required to maintain good perfusion and urine output.

• Intravenous fluids are usually needed only for 24–48 hours.

• Close monitoring

Group C Action Plan

• admit to a hospital with access to intensive care facilities and blood transfusion

• plasma losses should be replaced immediately and rapidly with isotonic crystalloid solution or, in the case of hypotensive shock, colloid solutions

• blood transfusion: with suspected/severe bleeding

• judicious intravenous fluid resuscitation: sole intervention required

Group C Action Plan

Goals of fluid resuscitation:• improving central and peripheral circulation

(decreasing tachycardia, improving BP, warm and pinkextremities, and capillary refill time <2 seconds)

• improving end-organ perfusion– i.e. stable conscious level (more alert or less restless), urine output ≥ 0.5 ml/kg/hour,decreasing metabolic acidosis.

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TATALAKSANA ENSEFALOPATI DENGUE• udem otak dan alkalosis,• syok teratasi ganti cairan dengan tidak mengandung HC03-

dan cairan dikurangi.• Edem otak dexametason 0,5 mg/kg BB/kali / 8 jam,• Perdarahan saluran cerna , kortikosteroid (-)• Disfungsi hati, vitamin K intravena 3-10 mg selama 3 hari, • BSS > 80 mg. Mencegah peningkatan tekanan intrakrani kurangi

jumlah cairan ( diuretik), koreksi asidosis dan elektrolit. • Mengurangi produksi amoniak neomisin dan laktulosa. • Transfusi darah • Masa penyembuhan , diberikan asam amino rantai pendek.

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Kriteria Memulangkan Pasien

memenuhi semua keadaan dibawah ini

1.Tampak perbaikan secara klinis

2.Tidak demam selaina 24 jam tanpa antipiretik

3.Tidak dijumpai distres pernafasan (disebabkan oleh efusi pleura atau asidosis)

4. Hematokrit stabil

5. Jumlah trombosit cenderung naik > 50.000/pl

6. Tiga hari setelah syok teratasi

7. Nafsu makan membaik

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Thank you

Arigatou

Terima kasih

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