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Professor Siripen Kalayanarooj

Director, WHO Collaborating Centre for


Case Management of Dengue/DHF/DSS,
Queen Sirikit National Institute of Child Health,
Department of Medical Services,
Ministry of Public Health,
Bangkok, Thailand.
Thailand Successful Story
DHF since 1958
180,000 Cases

Number of cases Case Fatality Rate

2008: 90,322 Cases with 98 deaths,


CFR = 0.11%
Dengue viruses isolates from
The Children’s Hospital
1973 - 2004
Dengue viral infections
10,000
Asymptomatic Symptom
9,000 1,000

Acute febrile illness Dengue fever Dengue hemorrhagic fever


(Viral syndrome) (DF) (DHF)
500 400 100
Plasma leakage
50 DF, 50 DHF
no shock
48 1-2
Natural Course of DHF
• Fever 2 – 7 Days
• Critical Period 24 – 48 hrs
 Plasma leakage
 Abnormal hemostasis
• Convalescence 3 – 7 Days
Dengue Diagnosis

Virus isolation Hemagglutination Inhibition


Mosquito inoculation (intrathoracic) Plaque Reduction Neutraliza
Toxorhynchites splendens IgM and IgG ELISA
Mosquito cell culture Rapid tests: Dot blot, Imm
C6/36 (Aedes albopictus)
Dipstick, Immunochromatog
Molecular techniques
Polymerase chain reaction(PCR) Anti-dengue IgM
Taqman Manifestations:
Shock
NS1 Ag
Fever Hemorrhage
Viremia
Day of Fever 2 4 6 8 10 12 14
Days after infection
Sensitivity in the febrile phase
(First few days of fever)
• PCR: >95% - expensive, not available in
most places
• ELISA : 60% on the day of shock
30-40% one day before shock
100% one day after shock
• NS1Ag: 60-70%
Dengue diagnosis :
in death case

Armed Forces Research Institute of Medical Sciences


Early Diagnosis :
simple clinical & lab.
• Tourniquet test
• CBC
Tourniquet test positive + leucopenia*
= Dengue infection
*Leucopenia = wbc ≤ 5,000 cells/cumm.

• At least day 3 of fever


• CBC everyday if possible
• Close follow up until 24 hours of
defervescence
Tourniquet test

 Fever day 1
50%
 Fever day 2 70%
 Fever day 3 > 90%
False negative TT
• Obese patients
• Thin patients
• Not good technique
• During shock
Tourniquet test
Systolic + Diastolic = 5 mins.
2
WBC ≤ 5,000 cells/cumm.

• Early diagnosis
• Indicates: no fever within
the next 24 hours
• If DHF :
oEntering critical stage
oBeginning of plasma leakage
oIf severe : aware/ prevent
shock? Is possible
Duration of fever in DHF patients
4,595 DHF patients, QSNICH

Duration of fever %
(day)
2 2.16
3 10.07
4 41.01
5 30.94
6 11.51
7 2.16
>7 1.44
Prolonged shock
• > 10 hours untreated - Death!!!
• > 4 hours untreated
Liver failure- prognosis 50%
Liver + Renal failure - prognosis10%
3 organs failure (+respiratory
failure) – Prognosis is a miracle!!!
Natural course of DHF
Day 1 2 3 4 5 6 7 8 9
Shock
Fever

Pleural effusion,
Ascites
Hematocrit

Plasma leakage Stop leakage Reabsorption

IV fluid: NSS, DAR, DLR


W Colloid: 10%Dextran,
B 10%Haes-steril
C M+5% Deficit
(= 4,600 ml in adult)

WBC 7,900 ≤5,000


Platelet count 230,000 ≤100,000
Hct 40 46 50%
Albumin ≤3.5 gm%
Cholesterol ≤100 mg%
Professor Siripen Kalayanarooj
Indications for admission
• Shock
• Platelet ≤ 100,000 cells/cumm. c no
good clinical conditions; poor
appetite..
o High risk patients: Obese, infants,
bleeding, underlying diseases,
consciousness change
o No care-taker
o Live far away
o Mass-media families
Warning signs of shock

• Clinical deterioration/ not


improve when no fever/ low
grade fever
• Abdominal pain
• Vomiting
• Restless, shortness of breath,
persistent crying in infants
• Sweating, cold clamy skin
• Behavior change, drowsy
• No urine 4 – 6 hours
อาการอันตราย

• Early diagnosis of
dengue infections :
Tourniquet test and
CBC with follow-up
• Advise warning
signs of shock in
all patients with
suspected dengue
infections

Tourniquet test
CBC
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
Delayed capillary refill time
Tender
Hepatomegaly
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
Chest film

Upright Right lateral decubitus


Rising Hematocrit (≥ 20%)

Problems :
• No baseline Hematocrit known
• Not done frequent enough
• Blood loss :
internal/ concealed bleeding
Hemolysis : thalassemia, G-6-PD
Ratio of Children : Adult Dengue
1997 - 2005

Child < 15 years

BoE, DDC, MOPH


Dengue CFR
Children vs Adult 2000-2007
Current situation in
Thailand
• Adult dengue 60%
• Oldest age 84 years (92 years?)
• Youngest age 16 hours (9 hours?)
IV fluid in critical period
(Platelet ≤ 100,000 cells/cumm.)

• Start Isotonic salt solution


• Amount = Maintenance + 5%Deficit in
24-48 hours
• Shock - 24 hours
• Non-shock – 48 hours
Calculation of M + 5% Deficit
Example: adult 50 kgs
Maintenance: M = (10 X 100 ml) +
• 10 kg. แรก = 100 ml/ kg
• 10 kg ต่ อมา = 50 ml/kg (10 X 50 ml) +
• > 20 kg = 20 (30 X 20 ml)
ml/kg = 1,000 + 500 + 600
5% Deficit = 50
ml/kg = 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 :
Compare adult and children
Child Adult
(ml/kg/hr) (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
Day 1 2 3 4 5 6 7 8 9
Shock
Fever

Pleural effusion,
Ascites
Hematocrit

Plasma leakage Stop leakage Reabsorption

IV fluid: NSS, DAR, DLR


W Colloid: 10%Dextran,
B 10%Haes-steril
C M+5% Deficit
(= 4,600 ml in adult)

WBC ≤5,000
Platelet count ≤100,000
Hct rising 20%
Albumin ≤3.5 gm%
Cholesterol ≤100 mg%
Professor Siripen Kalayanarooj
Monitoring parameters

clinical

Vital signs q 2 hours

Hct q 4-6 hours


Urine output
(0.5 ml/kg/hr)
High risk patients

• Infants
• Obese patients
• Prolonged shock
• Bleeding
• Encephalopathy
• Underlying diseases
Rate of IV Fluid in
Dengue Shock Syndrome

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


Rate of IV
5 ml/kg/hr (100-120 ml/hr)
10
8 3 ml/kg/hr (80-100 ml/hr)
6 3- 1 ml/kg/hr (40-80 ml/hr)
4
2
Rate
0
0 6 12 18 24 Hours after shock

Shock (Rate in adult)


When not response to
conventional IV fluid treatment

• Hct:
o Increase – use Dextran
o Decrease – Blood transfusion
• Electrolyte – Hypo Na, Hypo Ca
• Blood sugar - Hypoglycemia
• Blood gas - Acidosis
When not response to
conventional IV fluid treatment

• A – Acidosis (Prolonged
shock : LFT, BUN, Cr)
• S – Blood sugar
• C – Calcium (Na, K)
• B – Bleeding (Hct)

A Siam Commercial Bank


Indications for colloidal solution

• Signs of fluid overload : puffy


eyelids, distended abdomen, dyspnea/
tachypnea, positive lungs signs
(crepitation, rhonchi, wheezing)
• Continue rising Hct/ persistent high
Hct or cannot reduce the rate of IV
fluid in spite of adequate volume
replacement (R/O ASC and consider
concealed bleeding?) – TOO MUCH IV
FLUID AS CALCULATED as M+5% D
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)
Choice of colloidal solutions

• Plasma Substitute : (can be used as initial


fluid resuscitation but not for massive
plasma leakage)
(Iso-oncotic – 280 mosm) :
o FFP
o Hemaccel
o 6% Haes-steril
o Gelefudin
o Voluven
Colloidal solution in DHF
with massive plasma leakage

• rate 10 ml/kg/hr at a time


o Hct will drop 10
points
• Maximum dose 30 ml/kg/day
Crystalloid v.s. Colloid
Colloid
Crystalloid
15 USD/ 500 ml
1 USD/ 500
ml

Albumin
50 USD/ 50 ml
(Not recommend because
often report of acute
pulmonary edema/ heart
failure)
Rate of IV Fluid in
Dengue Shock Syndrome

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


Rate of IV
5 ml/kg/hr (100-120 ml/hr)
10
8 3 ml/kg/hr (80-100 ml/hr)
6 3- 1 ml/kg/hr (40-80 ml/hr)
4
2
Rate
0
0 6 12 18 24 Hours after shock

Shock (Rate in adult)


Rate
RateofofIVIVFluid
Fluidinin
Dengue
DengueHemorrhagic
HemorrhagicFever
Fevergrade
gradeI &I &II II

7 ml/kg/hr
7 ml/kg/hr(100-120 ml/hr)
8
8
6
6
1.5 ml/kg/hr (40 ml/hr) 3- 5 ml/kg/hr (80-120 ml/hr)
1.5 ml/kg/hr 3- 5 ml/kg/hr
4
4
2
2
Rate
0 Rate
00 6 12 18 24 30 36 42 48 Hours after
0 6 12 18 24 30 36 42 48 Hours after
leakage
Plt < 100,000 cells/cumm. leakage
HctPlt < 100,000 cells/cumm.
increase (Rate in adult)
Hct rising 10-20%
ICD obtained effusion
1860 ml =42 ml/kg
(maintained for 3 days)
Blood transfusion

• 10-15% of DHF cases


• Prefer whole blood (WB) if no sign of
fluid 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 5
points at a time (adult give 1 U of
WB or PRC to increase Hct by 3-4
points at a time)
Platelet (plt.) transfusion
• 0.4% in DHF cases who need blood
transfusion
• No prophylaxis plt. transfusion in
children, no matter how low is the plt.
count
• In adult age >35 years, especially those
with underlying hypertension, coronary
heart diseases give plt. tranfusion if
plt. < 10,000 cells/cumm.

Plt. 1 Unit = 50 ml
Recombinant factor VII

• 1 dose = 1,500 USD in a 10-kgs


patient
• No use in cases with prolonged shock
and multiple organs failure
• Consider in cases with bleeding causes
is not from prolonged shock: peptic
ulcer, trauma
Convalescent rash
Plasma leakage :
Natural course in sever cases
Shock

Reabsorption
Equilibrium

Start Stop

0 24 48 72 hours
Plt < 100,000 cells/cumm

Hct
Causes of death in DHF
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

Bleeding
Conclusion

• Early diagnosis - proper advice for


warning signs of shock***
• Proper IV fluid management
• Early refer/ consult
• Proper management of severe/
complicated cases (ASCB)

• Patients come early enough***


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%
Dengue hemorrhagic fever
Clinical
• High continuous fever 2 – 7 days
• Hemorrhagic manifestations :
petechiae, tourniquet test
• (hepatomegaly)
• (shock)
Lab.
• Platelet count ≤100,000 cewlls/cumm.
• Plasma leakage: rising Hct ≥ 20%,
pleural effusion,ascites, albumin<3.5
gm%, Cholesterol<100mg%
DHF severity
Plasma leakage

 Grade I - Only positive tourniquet


test
 Grade II – With spontaneous bleeding

 Grade III - Shock/ impending shock


 Grade IV – Prolonged shock (no pulse
or BP measureable)
DENCO Partners

Liverpool Heidelberg, TDR/WHO,


Germany
UK
, Geneva
Philippines


Cuba


Antwerp,
Nicaragua

Belgium

Vietnam


Thailand


Brazil


Venezuela


Malaysia


Europe

Latin America

Asia
Revised Dengue Classification
DENGUE ± Warning Signs SEVERE DENGUE

With
Without 1.Severe plasma leakage
WARNING 2.Severe haemorrhage
SIGNS 3.Severe organ impairment

Probable Dengue
Live in / travel to dengue Warning Signs* 1. Severe plasma leakage leading to
endemic area. Fever and 2 • Abdominal pain or tenderness • Shock (DSS)
of the following criteria: • Persistent vomiting • Fluid accumulation with
 Nausea, vomiting
 Rash
• Clinical fluid accumulation respiratory distress
 Aches and pains • Mucosal bleed 2. Severe bleeding
Tourniquet test +ve • Lethargy; restlessness as evaluated by clinician
 Leucopenia
• Liver enlargement >2cm 3. Severe organ involvement
Any warning sign
• Laboratory: Increase in HCT  Liver: AST or ALT>=1000
Lab. confirmed dengue concurrent with rapid decrease  CNS: Impaired consciousness
(important when no sign of plasma leakage) in platelet count  Heart and other organs
* Requiring strict observation and medical intervention
Hotline DHF:
+6689-2045522 – M.D.
+6689-2042255 – GN.
• 2008 – 200+ cases
consulted and 90%
were saved
Outcome Measures

• Decrease case fatality rate of DHF/DSS


• Decrease severity/ complications in
DHF/DSS patients
(Shock/ Fluid overload)
DHF Patient CareTeam
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Best Woman Doctor
2006

Extreme Award for


Networking 2007
Best Center of Excellence :
DHF 2006