09 lec - changing trends in dhf

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    Professor Siripen Kalayanarooj

    Director, WHO Collaborating Centre forCase Management of Dengue/DHF/DSS,Queen Sirikit National Institute of Child Health,

    Department of Medical Services,

    Ministry of Public Health,Bangkok, Thailand.

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    Thailand Successful Story

    DHF since 1958

    2008: 90,322 Cases with 98 deaths,

    CFR = 0.11%

    Number of cases Case Fatality Rate

    180,000 Cases

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    Dengue viruses isolates from

    The Childrens Hospital1973 - 2004

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    Asymptomatic Sympto

    Acute febrile illness Dengue fever Dengue hemorrhagic feve(Viral syndrome) (DF) (DHF)

    no shock

    Dengue viral infections

    Plasma leakage

    10,000

    50 DF, 50 DHF

    100400500

    1,0009,000

    1-248

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    Natural Course of DHF

    Fever 2 7 Days Critical Period 24 48 hrs

    Plasma leakage Abnormal hemostasis

    Convalescence 3 7 Days

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    Virus isolationMosquito inoculation (intrathoracic)

    Toxorhynchites splendensMosquito cell culture

    C6/36 (Aedes albopictus)

    Molecular techniques

    Polymerase chain reaction(PCR)

    Taqman

    NS1 Ag

    Day of Fever 2 4 6 8 10 12 14Days after infection

    Shock

    Hemorrhage

    Hemagglutination Inhibition

    Plaque Reduction Neutraliz

    IgM and IgG ELISARapid tests: Dot blot, Im

    Dipstick, Immunochromato

    Anti-dengue IgM

    Dengue Diagnosis

    Manifestations:

    ViremiaFever

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    Sensitivity in the febrile phase(First few days of fever)

    PCR: >95% - expensive, not available inmost places

    ELISA : 60% on the day of shock

    30-40% one day before shock

    100% one day after shock NS1Ag: 60-70%

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    Dengue diagnosis :

    in death case

    Armed Forces Research Institute of Medical Sciences

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    Early Diagnosis :

    simple clinical & lab. Tourniquet test

    CBC

    At least day 3 of fever

    CBC everyday if possible

    Close follow up until 24 hours ofdefervescence

    Tourniquet test positive + leucopenia*

    = Dengue infection*Leucopenia = wbc 5,000 cells/cumm.

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    Tourniquet test

    Fever day 150%

    Fever day 2 70%

    Fever day 3 > 90%False negative TT

    Obese patients

    Thin patients

    Not good technique

    During shock

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    Systolic + Diastolic

    2 = 5 mins.

    Tourniquet test

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    WBC 5,000 cells/cumm.

    Early diagnosis Indicates: no fever within

    the next 24 hours If DHF :oEntering critical stageoBeginning of plasma leakageoIf severe : aware/ prevent

    shock? Is possible

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    Duration of fever in DHF patients

    4,595 DHF patients, QSNICH

    Duration of fever(day) %

    2 2.16

    3 10.074 41.01

    5 30.946 11.51

    7 2.16

    >7 1.44

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    Prolonged shock > 10 hours untreated - Death!!!

    > 4 hours untreatedLiver failure- prognosis 50%

    Liver + Renal failure - prognosis10%3 organs failure (+respiratoryfailure) Prognosis is a miracle!!!

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    Day 1 2 3 4 5 6 7 8 9

    Fever

    WBC

    WBC 7,900 5,000

    Platelet count 230,000 100,000

    Hct 40 46 50%

    Albumin 3.5 gm%

    Cholesterol 100 mg%

    Hematocrit

    Plasma leakage Stop leakage

    Pleural effusion,Ascites

    Reabsorption

    Shock

    IV fluid: NSS, DAR, DLRColloid: 10%Dextran,

    10%Haes-sterilM+5% Deficit

    (= 4,600 ml in adult)

    Natural course of DHF

    Professor Siripen Kalayanarooj

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    Indications for admission Shock Platelet 100,000 cells/cumm. c nogood clinical conditions; poor

    appetite..o High risk patients: Obese, infants,bleeding, underlying diseases,

    consciousness changeo No care-taker

    o Live far away

    o Mass-media families

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    Warning signs of shock

    Clinical deterioration/ notimprove when no fever/ lowgrade fever

    Abdominal pain

    Vomiting Restless, shortness of breath,

    persistent crying in infants Sweating, cold clamy skin Behavior change, drowsy No urine 4 6 hours

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    Early diagnosis of

    dengue infections :

    Tourniquet test and

    CBC with follow-up

    Advise warningsigns of shock inall patients with

    suspected dengueinfections

    Tourniquet test

    CBC

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    Detection of shock : Difficult

    Good consciousness

    No fever and rapid pulse:Impending shock?

    Narrowing of pulse pressure, e.g.

    100/80, 110/90 mmHg Rapid/ weak pulse

    Delay capillary filling time (>2 sec) Restlessness/ irritable

    Speak fowl language, rude behavior

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    Delayed capillary refill time

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    Tender

    Hepatomegaly

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    A 13-year-old girl, 70 kgs

    Seen in an ER with no BP, confused,Had history of fever for a few days

    and no fever today. Mom just found

    her sleeping in her bed with cold,clammy skin.

    Diagnosis???

    Management???

    21.00 PM

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    Chest film

    Upright Right lateral decubitus

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    Rising Hematocrit ( 20%)

    Problems :

    No baseline Hematocrit known Not done frequent enough

    Blood loss :

    internal/ concealed bleeding

    Hemolysis : thalassemia, G-6-PD

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    Ratio of Children : Adult Dengue

    1997 - 2005

    BoE, DDC, MOPH

    Child < 15 years

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    C t it ti i

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    Current situation in

    Thailand Adult dengue 60%

    Oldest age 84 years (92 years?)Youngest age 16 hours (9 hours?)

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    IV fluid in critical period

    (Platelet

    100,000 cells/cumm.)

    Start Isotonic salt solution

    Amount = Maintenance + 5%Deficit in24-48 hours

    Shock - 24 hours Non-shock 48 hours

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    Calculation of M + 5% Deficit

    Maintenance: 10 kg. = 100 ml/ kg

    10 kg = 50 ml/kg > 20 kg = 20

    ml/kg5% Deficit = 50

    ml/kg

    Example: adult 50 kgs

    M = (10 X 100 ml) +

    (10 X 50 ml) +

    (30 X 20 ml)

    = 1,000 + 500 + 600

    = 2,100/day = 87 ml/hr

    5% D = 50 X 50 ml= 2,500

    M+5%D = 2,100 + 2,500

    = 4,600/day= 4,600/24 hr = 191.67 ml/hr

    = 191.67/50 kg = 3.83 ml/kg/hr

    Rate IV Fluid :

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    Rate IV Fluid :

    Compare adult and childrenChild

    (ml/kg/hr)

    Adult

    (ml/hr)

    M/2 1.5 40

    M 3 80

    M +5%D 5 100-120

    M +7%D 7 150

    M + 10%D 10 300 - 500

    Natural course of DHF

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    Day 1 2 3 4 5 6 7 8 9

    Fever

    WBC

    WBC 5,000

    Platelet count 100,000

    Hct rising 20%

    Albumin 3.5 gm%

    Cholesterol 100 mg%

    Hematocrit

    Plasma leakage Stop leakage

    Pleural effusion,Ascites

    Reabsorption

    Shock

    IV fluid: NSS, DAR, DLRColloid: 10%Dextran,

    10%Haes-sterilM+5% Deficit

    (= 4,600 ml in adult)

    Professor Siripen Kalayanarooj

    Monitoring parameters

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    Monitoring parameters

    clinical

    Vital signs q 2 hours

    Hct q 4-6 hours

    Urine output(0.5 ml/kg/hr)

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    High risk patients

    Infants

    Obese patients Prolonged shock

    Bleeding

    Encephalopathy

    Underlying diseases

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    Rate of IV Fluid in

    Dengue Shock Syndrome

    0

    2

    4

    6

    8

    10

    0 6 12 18 24

    Rate

    10- 5 ml/kg/hr (300-500 ml/hr)

    5 ml/kg/hr (100-120 ml/hr)

    3 ml/kg/hr (80-100 ml/hr)

    3- 1 ml/kg/hr (40-80 ml/hr)

    Hours after shock

    Rate of IV

    Shock (Rate in adult)

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    When not response to

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    When not response to

    conventional IV fluid treatment

    Hct:o Increase use Dextran

    oDecrease Blood transfusion

    Electrolyte Hypo Na, Hypo Ca Blood sugar - Hypoglycemia

    Blood gas - Acidosis

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    Indications for colloidal solution

    Signs of fluid overload : puffy

    eyelids, distended abdomen, dyspnea/tachypnea, positive lungs signs(crepitation, rhonchi, wheezing)

    Continue rising Hct/ persistent highHct or cannot reduce the rate of IVfluid in spite of adequate volume

    replacement (R/O ASC and considerconcealed bleeding?) TOO MUCH IVFLUID AS CALCULATED as M+5% D

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    Choice of colloidal solutions in DHF

    with massive plasma leakage

    Plasma Expander only(Hyper-oncotic->300 mosm) :

    o10% Dextran-40 in NSS (2.7 times)o10% Haes-steril (1.5 times)

    Ch f ll d l l

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    Plasma Substitute : (can be used as initial

    fluid resuscitation but not for massiveplasma leakage)

    (Iso-oncotic 280 mosm) :

    o FFPo Hemaccel

    o 6% Haes-steril

    o Gelefudin

    o Voluven

    Choice of colloidal solutions

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    Colloidal solution in DHFwith massive plasma leakage

    rate 10 ml/kg/hr at a time

    o Hct will drop 10

    points Maximum dose 30 ml/kg/day

    C t ll id C ll id

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    Colloid

    15 USD/ 500 ml

    Crystalloid

    1 USD/ 500ml

    Crystalloid v.s. Colloid

    Albumin

    50 USD/ 50 ml

    (Not recommend becauseoften report of acute

    pulmonary edema/ heart

    failure)

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    Rate of IV Fluid in

    Dengue Shock Syndrome

    0

    2

    4

    6

    8

    10

    0 6 12 18 24

    Rate

    10- 5 ml/kg/hr (300-500 ml/hr)

    5 ml/kg/hr (100-120 ml/hr)

    3 ml/kg/hr (80-100 ml/hr)

    3- 1 ml/kg/hr (40-80 ml/hr)

    Hours after shock

    Rate of IV

    Shock (Rate in adult)

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    0

    2

    4

    6

    8

    0 6 12 18 24 30 36 42 48

    Rate

    Rate of IV Fluid in

    Dengue Hemorrhagic Fever grade I & II

    Hours after

    leakage

    7 ml/kg/hr

    1.5ml/kg/hr 3- 5 ml/kg/hr

    Plt < 100,000 cells/cumm.Hct rising 10-20%

    0

    2

    4

    6

    8

    0 6 12 18 24 30 36 42 48

    Rate

    Rate of IV Fluid in

    Dengue Hemorrhagic Fever grade I & II

    Hours after

    leakage

    7 ml/kg/hr (100-120 ml/hr)

    1.5 ml/kg/hr (40 ml/hr) 3- 5 ml/kg/hr (80-120 ml/hr)

    (Rate in adult)

    Plt < 100,000 cells/cumm.

    Hct increase

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    ICD obtained effusion1860 ml =42 ml/kg(maintained for 3 days)

    Blood transfusion

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    Blood transfusion

    10-15% of DHF cases

    Prefer whole blood (WB) if no sign offluid overload and pack red cell (PRC)in cases with fluid overload

    Give equal to the amount estimated If cannot estimate: give WB 10 ml/kg

    or PRC 5 ml/kg to increase Hct by 5points at a time (adult give 1 U ofWB or PRC to increase Hct by 3-4

    points at a time)

    Platelet (plt ) transfusion

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    Platelet (plt.) transfusion

    0.4% in DHF cases who need bloodtransfusion

    No prophylaxis plt. transfusion inchildren, no matter how low is the plt.count

    In adult age >35 years, especially thosewith underlying hypertension, coronary

    heart diseases give plt. tranfusion ifplt. < 10,000 cells/cumm.

    Plt. 1 Unit = 50 ml

    Recombinant factor VII

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    Recombinant factor VII

    1 dose = 1,500 USD in a 10-kgspatient

    No use in cases with prolonged shockand multiple organs failure

    Consider in cases with bleeding causesis not from prolonged shock: pepticulcer, trauma

    Convalescent rash

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    Plasma leakage :Natural course in sever cases

    0 24 48 72 hours

    Reabsorption

    Shock

    Start

    Equilibrium

    Plt < 100,000 cells/cumm

    Hct

    Stop

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    Causes of death in DHF

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    Aug 07-Mar 08 32 cases:

    o

    Adults 18 (56.25%)o Children 14 (43.75%)

    Overweight: 19 (59.4%)

    Delayed Diagnosis: 22 (68.75%)o Fluid overload 24 (75.0%) - IPD

    o Prolonged shock 8 (25.0%) OPD

    o Massive bleeding (initially) - 0

    Major causes of death in DHF

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    Major causes of death in DHF

    Bleeding

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    Dengue Fever Headache Retro-orbital pain

    Myalgia Arthralgia/ joint pain

    Rash Bleeding manifestations: petechiae, TT+ve Leucopenia (wbc 5,000 cells.cumm.)

    Diagnosis :Tourniquet test positive +Leucopenia

    PPV 80%

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    DHF severity

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    Plasma leakage

    Grade I - Only positive tourniquettest

    Grade II With spontaneous bleeding

    Grade III - Shock/ impending shock

    Grade IV Prolonged shock (no pulseor BP measureable)

    DENCO Partners

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    Venezuela

    Antwerp,

    Belgium

    Philippines

    Heidelberg,

    Germany

    Vietnam

    Malaysia

    Thailand

    TDR/WHO,

    Geneva

    Europe

    Latin America

    Asia

    Cuba

    Liverpool

    ,UK

    Nicaragua

    Brazil

    SEVERE DENGUEDENGUE

    Revised Dengue Classification

    Warning Signs

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    SEVERE DENGUE

    1.Severe plasma leakage2.Severe haemorrhage3.Severe organ impairment

    WithoutWithWARNINGSIGNS

    Warning Signs* Abdominal pain or tenderness Persistent vomiting Clinical fluid accumulation Mucosal bleed Lethargy; restlessness Liver enlargement >2cm Laboratory:Increase in HCT

    concurrent with rapid decreasein platelet count

    1. Severe plasma leakage leading to Shock (DSS) Fluid accumulation withrespiratory distress

    2. Severe bleedingas evaluated by clinician

    3. Severe organ involvement Liver:AST or ALT>=1000

    CNS:Impaired consciousness Heart and other organs

    Probable DengueLive in / travel to dengueendemic area. Fever and 2

    of the following criteria: Nausea, vomiting RashAches and painsTourniquet test +ve LeucopeniaAny warning sign

    * Requiring strict observation and medical intervention

    g g

    Lab. confirmed dengue(important when no sign of plasma leakage)

    Hotline DHF:

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    +6689-2045522 M.D.+6689-2042255 GN.

    2008 200+ casesconsulted and 90%were saved

    Outcome Measures

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    Decrease case fatality rate of DHF/DSS

    Decrease severity/ complications inDHF/DSS patients

    (Shock/ Fluid overload)

    DHF Patient CareTeam

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    : .() .. .. .. ..() .. :

    : .() .. : : :

    ..

    International Training Course

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    MD. & GN. 2-week Course : Lectures, casediscussion & lab. practicals

    Include: visit vaccine center & one-day field trip

    29th June 10th July 2009 Apply thru WHO country office orother Institutions

    Course fee 1,200 USD perparticipants

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    Best Center of Excellence :DHF 2006

    Extreme Award forNetworking 2007

    Best Woman Doctor2006