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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