Dengue Santika 2014

Winarko LuminturahardjoRS Panti Nirmala MalangSantika Hotel, 22 Nopember 2014

Countries/areas at risk of dengue transmission,2008

PREVALENSI DF/DHF DI DUNIA (WHO 2009)

Viral : Virulensi, Viral LoadHost : Penyakit kompleks imun Diperantarai oleh sel T ADE,Komplemen Penyakit autoimun Apoptosis Imunitas alamiah Tsunami sitokin Faktor genetikVector: Ae.aegypti, Ae.albopictusEnvironment: Artificial containerENDOTHELIALDysfunctionFAKTOR YANG BERPENGARUH

Pathogenesis

PathogenesisLeakage

Symptomatic dengue virus infections were groups: Undifferentiated fever Dengue fever (DF) Dengue haemorrhagic fever (DHF)

DHF, classified into four severity grades : Grades III and IV being defined as Dengue Shock Syndrome (DSS)

Evidence of plasma leakage manifested by at least one of the following:

a rise in the haematocrit equal or greater than 20% above average for age, sex and population

a drop in the haematocrit following volume-replacement treatment equal to or greater than 20% of baseline

signs of plasma leakage such as pleural effusion, ascites, and hypoproteinaemia. Anon S. Plasma leakage in dengue haemorrhagic fever. Thromb. Haemost. 2009; 102: 10421049

WHO,1997

Conditions that mimic the febrile phase of dengue infection Flu-like syndromes Influenza, measles, Chikungunya, infectious mononucleosis , HIV seroconversion illness Illnesses with a rash Rubella, measles, scarlet fever, meningococcal infection, Chikungunya, drug reactions Diarrhoeal diseases Rotavirus, other enteric infections Illnesses with neurological manifestations Meningo/encephalitis, Febrile seizures

Conditions that mimic the critical phase of dengue infection Infectious Acute gastroenteritis, malaria, leptospirosis, typhoid, typhus, viral hepatitis, acute HIV seroconversion illness, bacterial sepsis, septic shock Malignancies Acute leukaemia and other malignancies Other clinical pictures Acute abdomen acute appendicitis acute cholecystitis perforated viscus Diabetic ketoacidosis, Lactic acidosis Leukopenia and thrombocytopaenia bleeding Platelet disorders Renal failure Respiratory distress (Kussmauls breathing) Systemic Lupus Erythematosus

KRITERIA DENGUE (WHO 1997)Demam tinggi mendadak, berlangsung 2-7 hr, pola demam spt punggung pelana kudaKecenderungan perdarahan, dibuktikan dgn sedikitnya 1 hal sbb:1.Uji bendungan positif2.Bintik perdarahan spontan di kulit, berupa: ptekiae, atau ekimosis/purpura3.Perdarahan spontan spt: mimisan, perdarahan gusi sampai hematemesis/melena

Jumlah trombosit sp20% dibanding Ht rata2 usia, sex dan populasi yg sama2. Ht turun >20% dp Ht awal setelah pemberian cairan3. Tdp tanda2 perembesan plasma spt: efusi pleura, asites, hipoalbuminemia, dsb

DERAJAT BERAT DENGUE (WHO 1997)Derajat IDemam mendadak tinggi dg gejala lain tak jelas disertai bintik2 perdarahan pd uji bendunganDerajat IIDerajat I disertai perdarahan spontanDerajat IIIDerajat II ditambah tanda2 kegagalan sirkulasi: denyut kecil, cepat, lemah, TD rendah, kulit dinginDerajat IVSyok berat: nadi lemah+cepat,tek nadi menyempit

WithoutWarning SignWithRevised Dengue Classification (WHO 2009)Dengue Warning SignSevere DengueSevere plasma leakage2. Severe hemorrhage3. Severe organ impairmentProbable Dengue :Live in /travel to dengue endemic area. Fever and 2 of the following criteria:Nausea, vomitingRashAches and painsTourniquet test positiveLeukopeniaAny warning signWarning signs*Abdominal pain or tendernessPersistent vomitingClinical fluid accumulationMucosal bleedLethargy, restlessnessLiver enlargment >2 cmLaboratory: increase in HCT concurrent with rapid decrease in platelet count*(requiring strict observation and medical intervention)- Severe plasma leakage leading to: * Shock (DSS) * Fluid accumulation with respiratory distress- Severe bleeding as evaluated by clinician- Severe organ involvement: * Liver: AST or ALT 1000 * CNS: Impaired consciousness * Heart and other organsLaboratory-confirmed dengue (important when no sign of plasma leakage)

KLASIFIKASI (WHO 2011)

199720092011Dengue FeverDengue without warning signDengue FeverDHF grade IDengue with warning signDHF grade IDHF grade IIDHF grade IIDHF grade IIISevere dengue : without hypovolemic shock with hypovolemic shockDHF grade IIIDHF grade IV DHF grade IV EXPANDED DENGUE SYNDROME

Laboratory Investigation

Laboratory Investigation

Step I. Overall assessment

I.1 History, including information on symptoms, past medical and family historyI.2 Physical examination, including full physical and mental assessmentI.3 Investigation, including routine laboratory and dengue-specific laboratory

Step II. Diagnosis, assessment of disease phase and severity

Step III. Management

III.1 Disease notificationIII.2 Management decisions. Depending on the clinical manifestations and other circumstances, patients may: be sent home (Group A); be referred for in-hospital management (Group B); require emergency treatment and urgent referral (Group C).

Referral Criteria : early presentation 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 hepatic damage, cardiomyopathy, encephalopathy, encephalitis and other unusual complications). Referral centres

Admission criteria :

Warning signs Any of the warning signs

Signs and symptoms Dehydrated patient, unable to tolerate oral fluids related to hypotension Postural Hypotension, Profuse perpsiration, fainting, (possible plasma leakage) prostration during defervescence, hypotension or cold extremities

Bleeding Spontaneous bleeding, independent of the platelet count

Organ impairment Renal, hepatic, neurological or cardiac enlarged, tender liver, although not yet in shock chest pain or respiratory distress, cyanosis

Findings through Rising haematocrit, pleural effusion,ascites or further investighation asymptomatic gall-bladder thickening

Co-existing conditions Pregnancy,Co-morbid conditions, such as diabetes mellitus, hypertension, peptic ulcer, haemolitic anemias and others Overweight or obese (rapid venous access difficult in emergency) Infancy or old age

Social circumstances Living alone, Living far from health facility Without reliable means of transport

HIGH RISK PATIENTS (2011)Infants and the elderlyObesityPregnant womanPeptic ulcer diseaseWoman who have menstrual or abnormal bleedingHemolytic diseaseThalassemia and other hemoglobinopathiesCongenital heart diseaseChronic disease (DM, hypertension, asthma, ischemic heart disease, etc)Chronic renal failure, liver cirrhosis

Treatment of Dengue FeverContinue monitoring after defervescenceIf any doubt, provide intravenous fluids, guided by serial hematocrits, blood pressure, and urine outputThe volume of fluid needed is similar to the treatment of diarrhea with mild to moderate isotonic dehydration (5%-8% deficit)Pan American Health Organization: Dengue and Dengue Hemorrhagic Fever : Guidelines for Prevention and Control. PAHO: Washington, D.C., 1994: 67.

Rehydrating Patients Over 40 kgVolume required for rehydration is twice the recommended maintenance requirementFormula for calculating maintenance volume: 1500 + 20 x (weight in kg - 20)For example, maintenance volume for 55 kg patient is: 1500 + 20 x (55-20) = 2200 mlFor this patient, the rehydration volume would be 2 x 2200, or 4400 mlPan American Health Organization: Dengue and Dengue Hemorrhagic Fever : Guidelines for Prevention and Control. PAHO: Washington, D.C., 1994: 67.

Kristaloid

Colloid

TATALAKSANA KASUS DBD DERAJAT III & IV (SSD) (EIMED 2012)

There is evidence of plasma leakage, such as: high or progressively rising haematocrit; pleural effusions or ascites; circulatory compromise or shock (tachycardia, cold and clammy extremities, capillary refill time > 3, weak or undetectable pulse, narrow pulse pressure or, in late shock, unrecordable blood pressure).

There is significant bleeding.

There is an altered level of consciousness (lethargy or restlessness,coma, convulsions).

There is severe gastrointestinal involvement (persistent vomiting, increasing or intense abdominal pain, jaundice).

There is severe organ impairment (acute liver failure, acute renal failure, cardiomyopathy,encephalopathy or encephalitis, or other unusual manifestation) Problems in Dengue Infection Mild to Severe Clinical ManifestationOnly Fluids !!!!

What are the effects of supportive treatments for dengue haemorrhagic fever or dengue shock syndrome in adult? Clinical Evident BJM

Colloid (DepKes RI) 1. Gelatin ( Gelofusin, Gelafudin, Haemaccel ) 2. HES BM 130,000 Da (Tetrastarch, Voluven)3. HES BM 200,000 Da (Haes Steril 6% / 10%, Firma Hes, Hemo Hes, Wida Hes)4. HES BM 40,000 Da (Expafusin)5. Dextran 6% (Dextral)6. Dextran 10%

There are 4 types of colloid products available for clinical use: albumin, dextrans, starches and gelatinsSamuel A, Samson G, Richard I, Greg F, Chi E, Charles RJC N et al. Colloid Study in Kenya. 2004

Colloid NatureDextransStarches Gelatins Markets Albumin Dextran 40 Dextran 70 Hetastarch (6%) Pentastarch Haemacel Molecular weight (KD) 70 40 70 450 260 35 Plasma volume expansion (ml/500ml infused) 500 500-1000500-700 500-700 600-800 500 Cost (US $) per litre (in ) 360 200 150 130 150 15-20* Incidence of allergic reactions 0.011 1.1 1.1 0.09Not available 0.06 Effect on clottingv. mild, dilutionalDecreases in von Willebrands factorIncrease in PT and APTTv. mild, dilutional CommentDecreases blood viscosity Increases blood viscosity Prolongs bleeding time

Characteristics of various different colloids used for plasma volume support.

Colloid Initial volume Duration of volume Adverse effect Allergic Other significant expansion (%)* effect (hours) on coagulation potential side effects

3% Gelatin 6080 34 +/ +(MW = 35,000)10% Dextran 40 170180 46 ++ + Renal failure in(MW = 40,000) hypovolaemic patients6% Dextran70 100140 68 ++ +(MW = 70,000)6% HES (Wida HES)100140 68 + +/(MW = 200,000/0.5) 6% HES 80100 1224 ++ +(MW = 400,000)HES=HydroxyethylstarchScott B H. Dengue. 2008

Supportive care and adjuvant therapy in severe dengue.

Renal Replacement Therapy, with a preference to continuous veno- venous haemodialysis (CVVH), since peritoneal dialysis has a risk of bleeding Vasopressor and inotropic therapies as temporary measures to prevent life-threatening hypotension in dengue shock and during induction for intubation, while correction of intravascular volume is being vigorously carried out Treatment of organ impairment, such as severe hepatic involvement or encephalopathy or encephalitis; Treatment of cardiac abnormalities, such as conduction abnormalities, may occur (the latter usually not requiring interventions).

Clinical No fever for 48 hours. Improvement in clinical status (general well- being, appetite, haemodynamic status, urine output, no respiratory distress). Laboratory Increasing trend of platelet count( >50000/mm3) Stable haematocrit without intravenous fluids.Discard creteria

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