demam berdarah dengue
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Demam Berdarah Dengue Diagnosa dan PenatalaksanaanTRANSCRIPT
Demam Berdarah Dengue
Diagnosa dan Penatalaksanaan
KURNIA F. JAMILSub-Bagian Penyakit Tropik &
Infeksi, Bagian Ilmu Penyakit Dalam
FK-UNSYIAH/RSUZABANDA ACEH
2007
Demam Berdarah Dengue
Masih merupakan masalah penyakit infeksi yang serius di Indonesia
DEPKES-RI tahun 2005
Jumlah kasus 80.837 dengan 1.099 kematian
Ledakan kasus 5 tahunan
Sejak tahun 1968 dan seterusnya
Self Limiting Diseases
Pendahuluan
Virus dengue termasuk genus Flavivirus dari family Flaviviridae
Ada 4 serotipe: Den 1- 4 Patogenesis masih
kontroversi Penelitian masih
diperlukan
Overview of the Major Viral Hemorrhagic Fever Family Genus Mortality Transmission
Cook GC, Zumla A. Manson’s Tropical Diseases, 2003
Arenaviridae Lassa West Africa 16% Rodents Junin’58* Argentina 30% Rodents Machupo’63 Bolivia 25% Rodents Sabia’90 Brazil 30% Rodents Guanarito’90 Venezuela 25% RodentsFlaviviridae Dengue 1-4 0.2-2% Mosquitos Yellow fever virus * 10-85% Mosquitos Kyasanur * India 5% Ticks Omsk Rusia 2% TicksBunyaviridae Phlebovirus- Rift Valley HF 1% Mosquitos Hantavirus - HF Renal Synd * 5-15% Rodents Nairovirus- Crimean Congo HF 20-50% Ticks Puumala 1% RodentsFiloviridae Marburg ** 20-25% Monkey Ebola ** 70-90% Monkey Alphaviridae Chikungunya # 0% MosquitosReoviridae Coltvirus <1% Ticks
* Cardiac complication** Nosocomial # Mild HF
Replication and Transmissionof Dengue Virus (Part 1)
1. Virus transmitted to human in mosquito saliva
2. Virus replicates in target organs
3. Virus infects white blood cells and lymphatic tissues
4. Virus released and circulates in blood
3
4
1
2
Patogenesis DBD
Teori virulensi virus
Teori infection enhancing antibody
Viral Risk Factorsfor DBD Pathogenesis
Virus strain (genotype)– Epidemic potential: viremia level, infectivity
Virus serotype– DBD risk is greatest for DEN-3, followed by
DEN-2, DEN-1 and DEN-4
Hypothesis on Pathogenesisof DHF (Part 1)
Persons who have experienced a dengue infection develop serum antibodies that can neutralize the dengue virus of that same (homologous) serotype
Neutralizing antibody to Dengue 1 virus
1
1
Dengue 1 virus 1
Homologous Antibodies Form Non-infectious Complexes
Non-neutralizing antibody
1
1 Complex formed by neutralizing antibody and virus
Hypothesis on Pathogenesisof DHF (Part 2)
In a subsequent infection, the pre-existing heterologous antibodies form complexes with the new infecting virus serotype, but do not neutralize the new virus
Non-neutralizing antibody to Dengue 1 virus
Dengue 2 virus
2 2
2
2
2
Heterologous Antibodies Form Infectious Complexes
Complex formed by non-neutralizing antibody and virus
2
Hypothesis on Pathogenesisof DHF (Part 3)
Antibody-dependent enhancement is the process in which certain strains of dengue virus, complexed with non-neutralizing antibodies, can enter a greater proportion of cells of the mononuclear lineage, thus increasing virus production
2
2
2
2
22
2
22
2
Heterologous Complexes Enter More Monocytes, Where Virus Replicates
Non-neutralizing antibody
Dengue 2 virus 2
Complex formed by non-neutralizing antibody and Dengue 2 virus
2
Hypothesis on Pathogenesisof DHF (Part 4)
Infected monocytes release vasoactive mediators, resulting in increased vascular permeability and hemorrhagic manifestations that characterize DHF and DSS
Replikasi
2 – 3 hari
Sirkulasi & Jaringan
Infeksi : Macrofag
Monosit
Limfosit
ANTIBODI
Trombosit
KompleksAg-Ab
• Trombosit dihancurkan
• Agregasi terganggu
Perdarahan
DemamPermeabilitas
Kapiler
Mediator
SSD
Sitokin Menstimulasi
Sistem Koagulasi
FibrinogenFaktor V,VII,
VIII,X,XII
Perdarahan
KID
Temp
Trombosit
Bifasik
DEMAM & TROMBOSITOPENIA
Kompleks Imun
Manifestations of dengue infection
Dengue virus infection
Asymptomatic Symptomatic
Undifferentiated fever
Dengue fever syndrome
Without haemorrhage
With unusual haemorrhage
Dengue haemorrhagi
c fever
No shock Dengue shock
syndrome
Dengue fever
Dengue haemorrhagic
fever
Non-specific constitutional symptoms observed in haemorrhagic fever patients with dengue
Criteria DHF(%)
Injected pharynx 96.8Vomiting 57.9Constipation 53.5Abdominal pain 50.0Headache 44.6Generalized lymphadenopathy 40.5Conjunctival injection 32.8Cough 21.5Rhinitis 12.8Maculopapular rash 12.1Myalgia/arthralgia 12.0Enanthema 8.3Abnormal reflex 6.7Diarrhea 6.4Palpable spleen 6.3Coma 3.0
The following classifications are proposed :• Probable-an acute febrile illness with two or more of the following manifestations :
– headache
– retro-orbital pain
– myalgia
– arthralgia
– rash
– haemorrhagic manifestations
– leukopenia
– serology (+) or DF occurrence at the same location /
time
Kriteria Diagnosis DBD (WHO 1997)• Demam, atau riwayat demam akut, antara 2-7 hari biasanya
bifasik, • Trombositopenia (< 100.000/mm3)• Terdapat minimal satu dari manifestasi perdarahan berikut ini: Uji tourniquet positif Petekie, ekimosis, atau purpura Perdarahan mukosa, saluran cerna, bekas suntikan atau di tempat lain Hematemesis atau melena• Terdapat minimal satu dari tanda-tanda plasma leakage oleh
karena peningkatan permeabilitas kapiler berikut:
۵
۵
۵
۵
Hematokrit meningkat > 20% dibandingkan hematokrit rata-rata pada usia, jenis kelamin, dan populasi yang sama
Hematokrit turun hingga > 20% dari hematokrit awal, setelah pemberian cairan
Terdapat efusi pleura, asites , hiponatremia, hipoalbuminemia
I VIV VII VIIIIIIII IV
36 oC
39 oC
40 oC
38 oC
37 oC
Pola panas Demam DenguePola panas Demam Dengue
Ruam primerRuam primer Ruam sekunderRuam sekunder
Warning Signs for Dengue Shock
When Patients Develop DSS:• 3 to 6 days after onset of
symptoms
When Patients Develop DSS:• 3 to 6 days after onset of
symptoms
Initial Warning Signals:• Disappearance of fever• Drop in platelets• Increase in hematocrit
Initial Warning Signals:• Disappearance of fever• Drop in platelets• Increase in hematocrit
Alarm Signals:• Severe abdominal pain• Prolonged vomiting• Abrupt change from
fever
to hypothermia• Change in level of consciousness (irritability or somnolence)
Alarm Signals:• Severe abdominal pain• Prolonged vomiting• Abrupt change from
fever
to hypothermia• Change in level of consciousness (irritability or somnolence)
Four Criteria for DHF:• Fever• Hemorrhagic manifestations• Excessive capillary permeability• 100,000/mm3 platelets
Four Criteria for DHF:• Fever• Hemorrhagic manifestations• Excessive capillary permeability• 100,000/mm3 platelets
CENTERS FOR DISEASE CONTROLAND PREVENTION
Four Grades of DHF Grade 1
• Fever and nonspecific constitutional symptoms• Positive tourniquet test is only hemorrhagic manifestation
Grade 2• Grade 1 manifestations + spontaneous bleeding
Grade 3• Signs of circulatory failure (rapid/weak pulse, narrow
pulse pressure, hypotension, cold/clammy skin) Grade 4
• Profound shock (undetectable pulse and BP)
CENTERS FOR DISEASE CONTROLAND PREVENTION
Problem in Dengue Fever/Dengue Hemorrhagic Fever in Indonesia
High viral transmission Economical impact : Cost of treatment Lost of productivity Mortality especially in children about 2 % Not effective prevention: vector eradication no effective vaccine
CENTERS FOR DISEASE CONTROLAND PREVENTION
years
1996
1994
1992
1990
1988
1986
1984
1982
1980
1978
1976
1974
1972
1970
1968
Me
an
ca
ses
70000
60000
50000
40000
30000
20000
10000
0
Incidence of Dengue Hemorrhagic Fever in Indonesia 1968-1996
Ministry of Health, Rep of Indonesia
CENTERS FOR DISEASE CONTROLAND PREVENTION
years
1996
1994
1992
1990
1988
1986
1984
1982
1980
1978
1976
1974
1972
1970
1968
Me
an
ca
se f
ata
lity
rate
(%
)50
40
30
20
10
0
Mortality of Dengue Hemorrhagic Feverin Indonesia 1968-1997
Ministry of Health, Rep of Indonesia
Treatment of Dengue Haemorrhagic Fever
Fluids Rest Antipyretics (avoid aspirin and non-steroidal
anti-inflammatory drugs) Monitor blood pressure, hematocrit, platelet
count, level of consciousness
Tatalaksana DBD pada Dewasa
Protokol 1Penanganan Tersangka ( Probable ) DD/DBD dewasa tanpa syok
Protokol 2Pemberian cairan pada tersangka DBD dewasa di ruang rawat
Protokol 3Penatalaksanaan DBD dengan peningkatan Ht > 20 %
Protokol 4
Penatalaksanaan Perdarahan Spontan pada DBD dewasa
Protokol 5 Tatalaksana sindroma syok Dengue pada dewasa
Keluhan DBD (Kriteria WHO 1997)
Hb, Ht Normal Tromb > 100.000/mm³
Observasi Rawat jalanPeriksa Hb, Ht dan leuko, tromb/ 24 jam
Hb, Ht normalTrombo < 100.000
Hb, Ht meningkatTrombo N / turun
Protokol 1. Penanganan Tersangka ( Probable )
DD / DBD Dewasa tanpa syok
Rawat Inap
( Protokol 2 )
Protokol 2. Pemberian cairan pada tersangka DBD dewasa di ruang rawat
Suspek DBDPerdarahan Spontan dan Masif (-)Syok (-)
Hb,Ht (n)Tromb. <100.000
Hb,Ht 10-20% Tromb. <100.000
Hb,Ht > 20% Tromb.<100.000
◘Infus Kristaloid ◘Hb,Ht,Tromb. tiap 24 jam
Infus Kristaloid Hb,Ht,Tromb. tiap 12 jam
Protokol 3
Volume cairan kristaloid per hari yang diperlukan :
1500 + 20 X ( BB dalam kg – 20 )
Contoh :
BB 50 kg : 1500 + 20 X ( 50 – 20) = 1500 + (20 x 30) = 1500 + 600 = 2100 ml
(Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever: Guidelines for Prevention and Control. PAHO: Washington,D.C,1994:67).
Awasi kadar elektrolit darah jika memungkinkan.
Protokol 3. Penatalaksanaan DBD dengan peningkatan Ht > 20 %
5 % defisit cairan
Kristaloid 6 – 7 ml/kg/jam
PERBAIKAN TIDAK MEMBAIK
Kristaloid 5 ml/kg/jam Kristaloid 10 ml/kg/jam
TIDAK MEMBAIK
Kristaloid 15 ml/kg/jam
MEMBURUK SYOK
PROTOKOL 4 / 5
PERBAIKAN
Kristaloid 3 ml/kg/jam
PERBAIKAN
STOP CAIRAN
PERBAIKAN
PERBAIKAN
3-4 jam
2 jam
3 jam
24-48 jam
Protokol 4. Penatalaksanaan Perdarahan Spontan pada
DBD dewasaKASUS DBD :Perdarahan Spontan dan Masif : - Epistaksis tidak terkendali
- Hematemesis melena- Perdarahan otakSyok (-)
Hb, Ht, Trombo, Leuko, Pemeriksaan Hemostasis (KID)
Golongan darah, uji cocok serasi
Transfusi komponen darah :* PRC (Hb<10 g %)* FFP (APTT > 1,5 X normal )* TC (Tromb.<100.000)
* Pemantauan Hb, Ht, Tromb. Tiap 4-6 jam* Ulang pemeriksaan hemostasis 24 jam kemudian
KID +:
HEPARINISASI
5000 – 10.000 / 24J
Protokol 5. Tatalaksana Syok pasien Dewasa
AIRWAY
BRAETHING : O2 1 – 4 l/menit
CIRCULATION : 10 – 20 ml/kgBB
20 – 30 MENITPERBAIKAN TETAP SYOK
Kristaloid 20-30 ml/kgBB20-30 menit
TETAP SYOK
Ht k
Koloid 10-20 ml/kg/BB tetes
cepat 10-15 menit
Transfusi PRC10 ml/kgBB
Ht k
TETAP SYOKKoloid hinggamaksimal 30
ml/kgBB
TETAP SYOK
Pasang CVP
Hipovolemik
Normovolemik
KRISTALOID TETAP SYOK
Inotropik , Vasoaktif
Koreksi : As/Bs, Electr,Glikemia, Anemia, KID, Infeksi Sekunder
PERBURUKAN
AIRWAY
BREATHING : O2 1 – 4 l/menit
CIRCULATION : 10 – 20 ml/kgBB
Protokol 5. Tatalaksana Syok pasien Dewasa
20 – 30 MNTPERBAIKAN
Kristaloid 7 ml/kg/jam dalam 1 jam
PERBAIKAN
Kristaloid 5 ml/kg/jam dalam 1 jam
PERBAIKAN
Kristaloid 3 ml/kg/jam dalam 1 jam
STABIL 24 – 48 JAM
PERBURUKAN
TETAP SYOK
Protokol pemberian zat inotropik / zat vasoaktif
Dopamin 5 mg/kg/mnt dititrasikan sampai 10 mg/kg/mnt Sasaran : MAP > 60 mmHg.
Gagal
Dobutamin 5 mg/kg/mnt + Norepinefrin 0,05 – 0,1 mg/kg/mnt
10 mg/kg/mnt 1 mg/kg/mnt
Epinefrin 0,1 mg/kg/mnt
Dititrasikan setiap 0,1 mg/kg/mnt
Max 2 mg/kg/mnt
GAGAL ?
Indikasi masuk ICU :
Syok yang tidak dapat teratasi maksimal 2 jam
Syok berulang
Syok dengan perdarahan hebat
Syok dengan penyulit seperti : kegagalan pernafasan,
ensefalopati, gagal jantung, dll.
Penatalaksanaan Sindrom Renjatan Dengue
Kriteria Pemulangan pasien DBD
1. Tidak demam selama 24 jam tanpa antipiretik2. Nafsu makan membaik3. Klinis tampak perbaikan4. Hematokrit stabil5. Tiga hari setelah renjatan teratasi6. Jumlah trombosit > 50.0007. Tidak dijumpai distres pernafasan
KESIMPULAN Indonesia merupakan negara tropis dengan risiko
kemungkinan terjadinya DBD cukup tinggi Menegakkan diagnosis serta penatalaksanaan
Dengue tidaklah mudah Penanganan pasien DBD melalui pedoman
tatalaksana yang ada, di sarana pelayanan kesehatan Pedoman ini perlu disosialisasikan ke semua
petugas kesehatan, pemantauan, evaluasi implementasinya agar penanganan DBD dapat maksimal
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