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Demam Berdarah Dengue
- 1. dr.Bramantono SpPD KPTI FINASIM Divisi Tropik – Infeksi, Departemen Ilmu Penyakit Dalam FK UA – RSUD Dr. Soetomo Surabaya Demam Berdarah Dengue: Manifestasi Klinis, Diagnosis, Terapi & Tatalaksana pada Dengue Syok Sindrom
- 2. Dengue: Penyakit Arboviral yang Paling Cepat Menyebar Daerah penyebaran dengue 2008 (WHO, 2009) Jumlah insiden DD dan DBD yg dilaporkan ke WHO (WHO, 2011) 30x incidence increase in 50 yrs Surabaya (2000 - 2009): ↑ insiden: 12.04 à 48.9 per 100000 Belum ada obat/ vaksin WHO 2009: Perlu upaya yg lebih intensif untuk penelitian tentang patogenesis, perbaikan tata laksana, dan upaya penemuan obat/vaksin 2
- 3. • 2003-2005: DENV-2 • 2007-2008: DENV-2 • 2008-2010: DENV-1 • 2012: DENV-1 • 2013: DENV-1 • Further surveillance ??? 3
- 4. Infeksi virus dengue (DENV) Merupakan penyakit demam akut yang disebabkan oleh virus dengue dan ditularkan melalui gigitan nyamuk Aedes aegypty dan Aedes albopictus serta memenuhi kriteria WHO untuk Demam Berdarah Dengue (DBD) 4
- 5. Replication and transmission of 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 1 2 4 5
- 6. Replication and transmission of dengue virus (Part 2) 5. Second mosquito ingests virus with blood 6. Virus replicates in mosquito midgut and other organs, infects salivary glands 7. Virus replicates in salivary glands 6 7 5 6
- 9. Dengue infection causes capillary leak syndrome Primary target: monocytes Serotype cross- reacSve Ab Virions + non- neutralizing Ab Enhanced entry via FcR (Rothman, 2004) T cells acSvaSon Cytokines + complements acSvaSon Capillary Leak 9
- 10. DHF is not a continuum of DF 10 Dengue Virus infecSon Dengue Fever Dengue Haemorrhagic Fever Self-limited Life-threatening DHF is not DF plus bleeding Viral direct effect Secondary infecSon + Enhanced anSbodies
- 11. Manifestation of dengue virus infection 11 Dengue virus infecSon AsymtomaSc SymtomaSc UndifferenSated Fever (viral syndrome) Dengue Fever (DF) Without haemorrhage With unusual haemorrhage Dengue haemorrhaegic fever (DHF) (with plasma leakage) DHF Non-shock DHF with shock DSS Expanded dengue syndrome / isolated organopathy (unusual manifestaSon) Comprehensive Guidelines for PrevenSon and Control of Dengue and Dengue Haemorrhagic Fever, WHO-SEARO 2011
- 12. 12
- 13. 13 Course of dengue illness Dengue: Guidelines for diagnosis, treatment, prevenSon and control, TDR-WH0 2009 Shock/Bleeding
- 14. Febrile phase Febrile phase • Facial flushing • Skin erythema • Generalized body ache • Myalgia and arthralgia • Headache • Sorethroat, injected pharynx, and conjuncSval injecSon • Anorexia, nausea and vomiSng • (+) TT increases the probability of dengue • (+) hemorrhagic manifestaSons • Enlarged and tender liver • Abnormality: progressive decrease in total wbc 14 Dengue: Guidelines for diagnosis, treatment, prevenSon and control, TDR-WH0 2009
- 15. Critical phase Cri?cal phase • Temp drops to 37.5-38 (days 3-7) • (+) increase in capillary permeability with increasing hematocrit levels • Significant plasma leakage lasts for 24-48 hours • Progressive leukopenia followed by rapid decrease in platelet precedes plasma leakage • if (-) increase in capillary permeability à improve • if (+) increase in capillary permeability à pleural effusion and ascites • Degree of increase above the baseline hematocrit reflects the severity of plasma leakage • Shock: criScal volume of plasma is lost • Temperature may be subnormal • Prolonged shock à organ hypoperfusion à organ impairment, metabolic acidosis, and DIC à severe hemorrhage • Severe hepaSSs, encephaliSs or myocardiSs 15 Dengue: Guidelines for diagnosis, treatment, prevenSon and control, TDR-WH0 2009
- 16. Recovery phase Recovery phase • Gradual reabsorpSon of extravascular compartment fluid (48-72 hours) • General well-being improves, appeSte returns, GI symptoms abate, hemodynamic status stabilizes and diuresis ensues • (+) rash: “isles of white in the sea of red” • Hematocrit stabilizes or may be lower due to diluSonal effect of reabsorbed fluid • Wbc starts to rise • Recovery of platelet count occurs later 16 Dengue: Guidelines for diagnosis, treatment, prevenSon and control, TDR-WH0 2009
- 17. Pemeriksaan penunjang • Pemeriksaan darah serta serologi • DL, LFT, RFT, BG, CoagulaSon profile, BGA, Electrolyte, lactate, NS1, Igm/IgG anS-dengue • EKG • Pemeriksaan Radiologis • Foto Thoraks • USG • Penunjang lainnya sesuai indikasi 17
- 18. Diagnosis of dengue • AnSbody detecSon • HemaggluSnaSon InhibiSon (HAI) • IgM & IgG • AnSgen detecSon • NS1 • RNA detecSon • RT-PCR • Viral isolaSon 18
- 20. Approximate timeline of primary and secondary dengue virus infections and the diagnostic methods that can be used to detect infection 20 O.D O.D -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16-20 21-40 41-60 61-80 90 >90 Days Onset of symptoms IgG secondary IgM secondary IgM primary >25 60 80 0 HIA Viraemia NS1 detec?on Virus isola?on RNA detec?on IgG primary infec?on
- 21. Differential diagnoses of dengue • Arboviruses: Chikungunya virus (terutama di Asia Tenggara) • Other viral diseases: Measles; rubella; Epstein-Barr Virus (EBV) • Enteroviruses; influenza; hepaSSs A; Hantavirus • Bacterial diseases: Meningococcaemia, leptospirosis, typhoid, melioidosis, rickemsial diseases, scarlet fever • ParasiSc diseases: Malaria 21
- 22. WHO Guidelines on dengue 22 1997 2009 2011
- 23. Criteria for clinical diagnosis of DHF (2011) • Clinical manifestaSons • Fever: acute onset, high and conSnuous, lasSng two to seven days in most cases • Any of the following haemorrhagic manifestaSons including a posiSve tourniquet test (the most common), petechiae, purpura, ecchymosis, epistaxis, gum bleeding, and haematemesis and/or melena • Laboratory findings • Thrombocytopenia (100 000 cells per mm 3 or less) • HaemoconcentraSon; haematocrit increase of ≥20% from the baseline, plasma leakage : pleura effusion, ascites, hypoproteinemia / hypoalbuminemia 23
- 24. Classifications 1997 2009 2011 Dengue Fever Dengue without warning signs Dengue Fever DHF grade I Dengue with warning signs DHF grade I DHF grade II DHF grade II DHF grade III Severe dengue: § With compensated shock § With hypotensive shock DHF grade III DHF grade IV DHF grade IV EXPANDED DENGUE SYNDROME
- 25. 25 25 DF/DHF Grade Symptoms Laboratory DF Fever with two of the following: Headache, etro-orbital pain, Myalgia, Arthtralgia/bone pain, Rash,Haemorrhagic manifestations, No evidence of plasma leakage. Leucopenia (wbc ≤5000 cells/mm 3 ), Thrombocytopenia (Platelet count <150 000 cells/ mm 3 ), Rising haematocrit (5% – 10% ), No evidence of plasma loss DHF I Fever and haemorrhagic manifestation (positive tourniquet test) and evidence of plasma leakage Thrombocytopenia <100,000, Hct rise >20% DHF II As in Grade I plus Spontaneous bleeding. Thrombocytopenia <100,000, Hct rise >20% DHF III As in Grade I or II plus Circulatory Failure (weak pulse, narrow pulse pressure(≤20 mmHg), hypotension,restlessness). Thrombocytopenia <100,000, Hct rise >20% DHF IV As in Grade III plus profound shock with undetectable BP and pulse Thrombocytopenia <100,000, Hct rise >20% WHO 2011 Classification of Dengue Infections and Grading of Severity of DHF
- 26. Expanded dengue syndrome 26 NEUROLOGICAL Febrile seizures in young children. Encephalopathy. Encephalitis/aseptic meningitis. Intracranial haemorrhages/thrombosis. Subdural effusions. Mononeuropathies/polyneuropathies/GBS Transverse myelitis. GASTROINTESTINAL/HEPATIC Hepatitis/fulminant hepatic failure. Acalculous cholecystitis. Acute pancreatitis. Hyperplasia of Peyer’s patches. Acute parotitis. RENAL Acute renal failure. Hemolytic uremic syndrome. CARDIAC Conduction abnormalities. Myocarditis. Pericarditis. Maheshwari A. Atypical manifestaSons of dengue. Trop Med Int Health. 2007 Sep.; 12(9):1087 – 95 RESPIRATORY Acute respiratory distress syndrome. Pulmonary haemorrhage. MUSCULOSKELETAL Myositis with raise CPK Rabdomyolysis OTHERS
- 27. Warning signs (2009) • Abdominal pain or tenderness • Persistent vomiSng • Clinical fluid accumulaSon • Mucosal bleed • Lethargy, restlessness • Liver enlargment >2 cm • Laboratory: increase in HCT concurrent with rapid decrease in platelet count 27
- 28. High-risk patients (2011) The following host factors contribute to more severe disease and its complicaSons: • Infants and the elderly • Obesity • Pregnant women • PepSc ulcer disease • Women who have menstruaSon or abnormal vaginal bleeding • HaemolySc diseases • Thalassemia and other haemoglobinopathies • Congenital heart disease • Chronic diseases such as diabetes mellitus, hypertension, asthma, ischaemic heart disease • Chronic renal failure, liver cirrhosis • PaSents on steroid or NSAID treatment 28
- 29. Clinical management • Complex pathogenesis and manifestaSons à BUT, relaSvely simple and inexpensive treatment • No spesific treatment à rely on fluid management • The most effecSve way to reduce incidence and morbidity à vector control • PotenSal manegement: vaccine and anS-viral drugs 29
- 30. 30 DF & DHF in Febrile Phase • Parcetamole • Physical methods of controlling fever • Don’t use Aspirin and NSAID • Fluid to maintain nutriSon and hydraSon Recognize the Time of Entry to the Critical Phase ( when blood vessels become leaky) • Dropping platelet count below 100 000/dl • Rising HCT & Evidence of plasma leakage
- 31. Choice of fluids • Suspected dengue fever - Isotonic crystalloid : normal saline, Ringer’s lactate, Ringer’s acetate, Ringer’s dextrose • Dengue hemorrhagic fever (DHF I and II) - Isotonic crystalloid : glucose contained soluSon? • DSS Crystalloid vs colloid ? 31 Crystalloid Colloid Ringer’s lactate Ringer’s acetate 0.9% saline 5% dextrose 0,9% 5% dextrose 1/2 saline Dextran 40 in saline Hydroxyethyl strach (HES) GelaSn soluSons
- 32. The general principles of fluid therapy in DHF • Isotonic crystalloid soluSons should be used throughout the criScal period • Hyper-oncoSc colloid soluSons (osmolarity of >300 mOsm/l) such as dextran 40 or starch soluSons may be used in paSents with massive plasma leakage, and those not responding to crystalloid • A volume of about maintenance +5% dehydraSon 32
- 33. Fluid management in DHF gr I & II 33 Kalayanarooj S. and Nimmannitya S. In: Guidelines for Dengue and Dengue Haemorrhagic Fever Management. Bangkok Medical Publisher, Bangkok 2003.
- 35. Pemeriksaan laboratorium syok berat atau tidak ada perbaikan dengan resusitasi cairan 35 Comprehensive Guidelines for PrevenSon and Control of Dengue and Dengue Haemorrhagic Fever, WHO-SEARO 2011 Singkatan Pemeriksaan Laboratorium Kepen?ngan A-Asidosis Analisa gas darah (kapiler dan vena) Menandakan syok yang sedang berlangsung. Keterlibatan organ juga harus dievaluasi ; fungsi haS, BUN dan kreaSnin B-Bleeding Hematokrit Jika terjadi penurunan nilai HCT dibandingkan dengan nilai sebelumnya atau jika Sdak berubah, lakukan cross-match untuk transfusi darah secepatnya C-Calsium Elektrolit, Ca++ Hipokalsemia terjadi pada kebanyakan DBD namun tanpa gejala. Pemberian suplementasi kalsium pada kondisi yang lebih berat/kompleks dapat diindikasikan. Dosis yang dianjurkan 1 ml/kg maksimal 10cc kalsium glukonas, dilarutkan dengan perbandingan 1:2, diberikan secara IV perlahan (dapat diulang Sap 6 jam jika diperlukan) S-Blood Sugar Kadar gula darah (fingersGck) Kebanyakan kasus DBD disertai penurunan selera makan dan muntah. Hipoglikemia dapat terjadi pada pasien dengan gangguan fungsi haS, namun pada kondisi lain dapat terjadi hiperglikemia
- 36. Dengue shock sydrome Kriteria DHF dengan tanda tanda syok • Takikardia, ekstremitas dingin, waktu pengisian kapiler memanjang, nadi lemah, lesu atau gelisah, yang mungkin merupakan tanda dari penurunan perfusi otak • Tekanan nadi ≤20 mmHg dengan peningkatan tekanan diastolik , misalnya 100/80 mmHg • Hipotensi yang disesuaikan dengan usia, yakni tekanan sistolik < 80 mmHg untuk mereka yang berusia < 5 tahun atau 80 - 90 mmHg untuk anak-anak dan orang dewasa 36
- 37. 37 Fluid management in DSS Fluid bolus 10- 20 ml/kg crystalloid/ 15 mt NO IMPROVEMENT If HCT is dropping < 40 for Children and female < 45 for adult male Blood transfusion whole blood 10 -20 ml/kg Packed RBC 5-10 ml/kg Rising HCT 2nd bolus - Colloids 10 – 20 ml/kg/1 hr Check HCT before fluid bolus or awer fluid bolus 3rd bolus - Colloids 10 – 20 ml/kg/1 hr IMPROVEMENT DHF gr III A B C S Dengue: Guidelines for diagnosis, treatment, prevenSon and control, TDR-WH0 2009
- 39. Fluid management in DSS 39 1 Kalayanarooj S. and Nimmannitya S. In: Guidelines for Dengue and Dengue Haemorrhagic Fever Management. Bangkok Medical Publisher, Bangkok 2003.79 Hour 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Time Type IV Intake Urine (mL) Hct (%) 10 9 8 7 6 5 4 3 2 1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Rate of KV fluid for children (Rate for adults) shock hour 24 hrs…….cc 18 hrs…….cc 6 hrs…….cc 8 hrs…….cc 5-3 ml/kg/hr (120-80 ml/hr) 3-1.5 ml/kg/hr (80-40 ml/hr) 1.5 ml/kg/hr-KVO (40 ml/hr-KVO) 10-5 ml/kg/hr (200-120 ml/hr) IV Transfusion (ml/kg/hr) IV Adjust on shock grade III, IV Name…………………..BW……………….kg. M=………….CC/days………..cc/hr M+5%=……….….CC/days………..cc/hr
- 40. Tatalaksana perdarahan masif • Sumber pedarahan diidenSfikasi, mis : epitaxis dikontrol dgn nasal packing • Perdarahan saluran cerna diberikan H-2 antagonis atau PPI, monitor HCT • Tranfusi darah segera diberikan, 10 ml/kg WB atau PRC • Trombosit konsentrat / fresh frozen plasma (FFP) meningkatkan resiko kelebihan cairan 40
- 41. Fase pemulihan • Perbaikan parameter klinis serta hemodinamik • HCT kembali ke base line atau lebih rendah • Cairan intravena dihenSkan cegah overload • Pada pasien dengan efusi masif dan ascites, hypervolemia dapat terjadi dan terapi diureSk dapat diperSmbang untuk mencegah edema paru 41
- 42. Criteria for transfer IGD Soetomo • Early presentaSon with shock (on days 2 or 3 of illness) • Severe plasma leakage and/or shock • Undetectable pulse and blood pressure • Severe bleeding • Fluid overload • Organ impairment (such as hepaSc damage, cardiomyopathy, encephalopathy, encephaliSs and other unusual complicaSons) Expanded dengue syndrome 42
- 43. Kriteria KRS • Tidak ada demam dalam 24 jam terakhir, tanpa anSpireSk • Kembalinya nafsu makan • Perbaikan klinis yang nyata • Produksi urin yang baik • SeSdaknya 2-3 hari setelah sembuh dari syok • Tidak ada distres nafas • Tidak ada asites • Trombosit lebih dari 50000 sel/mm3 43
- 44. TERIMA KASIH