IT-10 Dengue in Children

Dengue Management in
Children
Blok 27 – Agustus 2018
1
Outline
Epidemiology
Etiology and Pathogenesis
Clinical manifestation
Laboratory diagnosis confirmation
Case Classification
Management
2
Etiology – Dengue Virus
Virus DEN
• Arbovirus
• Vector: (A aegypti, A albopictus, A polynesiensis, A
niveus)
– nyamuk betina yg terinfeksi, menggigit di siang hari
• Single-stranded RNA
• 4 serotypea (DEN-1, 2, 3, 4)
– Each serotype can cause fatal and severe disease
– Some genetic variants in each serotype more virulent or
have greater epidemic potency
3
Pathogenesis of DHF/DSS
• The pathogenesis of DHF and DSS still needs to be explored further

• Two basic theories, which are not mutual exclusive – were frequently cited
to explain the pathogenetic changes
– Secondary Heterologous Infection or Antibody

Dependent Enhancement (ADE) Theory
– Virus Virulence Theory
• Both theories are supported by epidemiologic and laboratory
studies/evidence, and are most probably valid
Scott B. Halstead. WHO, SEARO, New Delhi, 1993. p80-103.

Duane J. Gubler. Clinical Microbiology Reviews, 1998:480-96
Secondary Heterologous Infection
or
Antibody Dependent Enhancement (ADE)
theory
Secondary Heterologous Infection Theory
• Patients experiencing a 2nd infection with heterologous dengue virus

(DenV) serotype ð have significant higher risk to have DHF/DSS
• Prior infection, through a process ð antibody-dependent enhancement

(ADE), enhance the infection and replication of DenV in mononuclear
cells / macrophage (more receptor uptake)
• This cells, produce and secrete vasoactive mediators (particularly

cytokines) ð increase vascular permeability ð hypovolemia and shock
Halstead SB. WHO, SEARO, New Delhi 1993

Gubler DJ. Clinical Microbiology Reviews 1998
Pathogenesis of DHF - 1
• Homologous Antibodies Form Non-infectious Complexes
1
1
1
1 Dengue 1 virus
Neutralizing antibody to Dengue 1 virus
Non-neutralizing antibody
1 Complex formed by neutralizing antibody and virus
• Heterologous Antibodies Form Infectious Complexes
2 2
2
2
Dengue 2 virus
Non-neutralizing antibody to Dengue 1 virus

2
Complex formed by non-neutralizing antibody and virus
Heterologous Complexes Enter More Monocytes, Where Virus Replicates
2
2
2
2
2
2 2
2
2
2 Dengue 2 virus
Non-neutralizing antibody
2 Complex formed by non-neutralizing antibody and

Dengue 2 virus
Dengue Clinical Presentations
Dengue has a wide spectrum of clinical presentations with

often unpredictable evolution:
• Self-limiting disease in most patients
• Severe disease in a small proportion of patients,
characterized by plasma leakage with/without haemorrhage
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DENGUE EPIDEMIOLOGY
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12
Figure Trends in incidence rate of DHF cases in Indonesia from 1968 to 2013,
measured in numbers of cases per 100,000 person years.
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Figure Case fatality ratios of DHF cases in Indonesia from 1968 to 2013.
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CLINICAL COURSE OF DENGUE
15
Acknowledgements
This curriculum was developed with technical assistance from the University of Malaya Medical Centre. Materials were contributed by the
Ministry of Health, Singapore, the United States Centers for Disease Control and Prevention, and the University of Malaya Medical Centre.
16
Acknowledgements
nical assistance from the University of Malaya Medical Centre. Materials were contributed by the
Clues to diagnose dengue:
d States Centers for Disease Control and Prevention, and the University of Malaya Medical Centre.
disease progresses from
phase and evolves into

febrile phase to critical
dynamic and systemic
manifestations as the
Knowing its various
Understanding the
Dengue mimics many clinical syndromes
nature of dengue
recovery phase
Dengue
Acute abdomen
Haematological
Viral exanthem
Flu-like illness
Autoimmune
Infections
disorders
diseases
Clinical Course of Dengue
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Vignette of febrile phase
• Usually lasts 2 to 7 days
• High temperature; may be modified by antipyretics
• Common symptoms: myalgia, headache, retro-orbital pain, aches, rash
• Difficult to differentiate dengue from viral febrile illness
• Normal CBC in first 1 to 2 days of fever
Quality of life may be affected1

• Changes in behaviour and mood
• Inability to focus and concentrate on work and self-care
Children
Nausea and vomiting may be prominent
1 Lum et al. Quality of Life of Dengue Patients. Am J Trop Med Hyg, 2008.
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Febrile phase
Headache, retroorbita pain

Bleeding gums and nose
Sudden-onset fever
Exanthema
Dehydration
Vomiting
Diarrhoea Progressive leucopenia
Muscle pain Progressive
thrombocytopenia
Joint pain
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Conditions that mimic the febrile phase of dengue
Influenza, measles, rubella

Chikungunya, West Nile virus
Enterovirus
Viral infections Other viral haemorrhagic fever
Infectious mononucleosis
Acute HIV seroconversion illness
Leptospirosis
Bacterial infections Typhoid
Rickettsia infections (typhus, scrub typhus, etc.)
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Parasitic infections Malaria
Measles, rubella
Infectious mononucleosis, enterovirus
Chikungunya, West Nile virus,
Febrile illness with Scarlet fever, meningococcal infection
a rash Leptospirosis, typhoid
Rickettsia infections (typhus, scrub typhus, etc.)
Syphilis, acute HIV seroconversion illness
Autoimmune diseases (e.g. SLE)
Adverse drug reaction
Rotavirus
Diarrhoeal diseases Salmonellosis
Other enteric infections
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Dengue phase
Some patients
Acute febrile phase Critical phase Recovery phase
Warning signs*
No clinical improvement or worsening in afebrile phase –
abdominal pain or tenderness – persistent vomiting – refusal
Clinically of oral intake - clinical fluid accumulation – mucosal bleed –
lethargy or restlessness or irritability – liver enlargement > 2
cm – postural hypotension – oliguria
Increase in haematocrit concurrent with rapid dcrease in

Laboratory platelet count, folllowed by blood pressure and pulse changes
* WHO 2009 Dengue guideline 21

WHO 2011 Dengue guideline
Critical phase
Fever defervescene
Signs of plasma leakage
Pleural effusion Signs of shock

Increase in haematocrit
Ascites Progressive leucopenia

Progressive thrombocytopenia
Severe dengue
Severe plasma leakage
Severe bleeding
Severe organ impairment 22
Acknowledgements
Conditions that mimic the critical phase of dengue
Acute appendicitis
Acute cholecystitis
Acute abdomen
Perforated viscus
Diabetic ketoacidosis
Diabetic ketoacidosis
Acidotic breathing/ Lactic acidosis
respiratory distress Renal failure
Acute respiratory distress syndrome (ARDS)
Sepsis, septic shock

Acute gastroenteritis
Infections Leptospirosis, typhoid, typhus, malaria
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Viral hepatitis
Acute HIV seroconversion illness
Systemic lupus erythematosus

Idiopathic thrombocytopenic purpura
Autoimmune diseases Thrombotic thrombocytopenic purpura
Systemic vascultis
Acute leukaemia
Malignancies Lymphoma
Other malignancies
Liver cirrhosis with portal hypertension

Others Adverse drug reaction
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Acknowledgements
Transition from febrile phase to critical phase
• Usually day 4 to day 7 of illness
• Could be as early as day 3 or as late as day 7 or 8
• Coincides with defervescence
Development of warning signs:

Identify dengue patients already in shock or at risk of developing shock
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Clinical Warning Signs Laboratory Warning Signs
1. Severe abdominal pain 1. Leukopenia
2. Persistent vomiting 2. Rapid decrease platelet count
3. Mucosal bleed 3. Rising haematocrit
4. Lethargy; restlessness
5. Liver enlargement >2cm
6. Clinical fluid accumulation
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NOTE: Changes in haematocrit may be masked by IV fluid therapy
Pearls: laboratory warning signs
• May precede changes in blood pressure and pulse pressure

Rapid decrease in platelet count + rising trend in haematocrit
• Occurs 24 hours before rapid decrease in platelet count
• Good indicator that patient could have dengue
• Indicate an increase in vascular permeability

• Occur shortly before or at defervescence
• Not predictive of plasma leakage
Leucopenia
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What happens during the critical phase?
Increased vascular permeability How long does plasma leakage last?
24 – 48 hours
Significant plasma leakage
What could happen without treatment?
Development of warning signs Death
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Deterioration in patient’s condition
Shock occurs when critical volume of plasma is lost through leakage.

Shock is often preceded by warning signs.
Body temperature may be sub-normal when shock occurs.
The total white cell count may increase (instead of leukopenia) in patients
with severe bleeding at this stage.
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Clinical course of patient without significantly increased vascular permeability:
Do all dengue patients enter critical phase?
• Fever subsides → general condition improves and appetite recovers

NOT all patients will experience the critical phase
• Mild to moderate thrombocytopenia

• May have leukopenia
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Vignette of recovery phase
What happens in recovery phase?
Vascular permeability reverts to normal
→ Gradual reabsorption of extravascular fluid in next 48 to 72 hours
Clues to progression from critical phase to recovery phase

Clinical clues:
1. Improvement in general well-being and stable haemodynamic status
Acknowledgements
2. Diuresis
© WHO/Lucy Lum Chai See

3. Biphasic fever
4. May have bradycardia
5. Isles of white in the a sea of red
Laboratory clues:
1. HCT stabilizes.
HCT may lower due to dilutional effect of reabsorbed fluid (haemodilution).
2. WBC usually starts to rise soon after defervescence.
3. Thrombocytopenia persists longer than leucopenia.
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High fever → Neurological disturbances
Summary of clinical problems during each phase
Hypervolaemia with fluid overload because of inappropriate fluid management

Febrile seizures
Hallucination
Organ impairment to liver, kidneys and other organs

1.
2.
Plasma leakage → hypovolaemia and shock

1. Poor oral intake from anorexia and nausea
2. Insensible fluid loss from high fever
Severe haemorrhage
Recovery Phase
Critical Phase
Contributing factors:
Febrile Phase
Dehydration
Acknowledgements
Pearls and pitfalls: dengue shock
Dengue shock presents as a physiologic-time continuum
Compensated shock in the early stage Decompensated shock in the late stages
(normal or elevated blood pressure) (hypotension & unrecordable blood pressure)
Warning Compensated Hypotensive Cardiac

Stable Hours Hours Hours Min
signs shock shock arrest
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Identification and treatment of early shock will improve clinical outcome.
Delayed treatment leads to a clinical course complicated by severe bleeding and
organ impairment.
Severe bleeding will exacerbate the shock state and if unrecognized will cause
refractory and irreversible shock with a very poor outcome.
Pitfall: Why is it easy to miss dengue shock?
Even in the severe shock state, the patient appears deceptively normal or “stable”
with a lucid conscious level.
A careful physical examination is critical to recognizing a patient in shock before the
stage of cardiovascular collapse.
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LABORATORY DIAGNOSIS
CONFIRMATION
31
Laboratory Diagnostic Options in a Patient
with Suspected Dengue Infection
32
Simmons CP et al. N Engl J Med 2012;366:1423-1432
Interpretation of
dengue diagnostic test
• Handbook mangement of dengue, TRD-WHO,2012
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CASE CLASSIFICATION
34
WHO Dengue Classification
WHO has proposed several guidelines
1997 2011 2009

WHO WHO-SEARO WHO 35
WHO SEARO 1997 Guidelines
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WHO 1997 Dengue Classification
DF DHF
1. Fever 2-7 days + +

2. Haemorrhagic tendencies
q Positive tourniquet test or +/- +
q Spontaneous bleeding
3. Thrombocytopenia
+/- +
q ≤ 100,000/mm³
4. Plasma leakage
q a rise or a drop in the haematocrit ≥ 20%
- +
q pleural effusion, ascites and
hypoproteinaemia
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WHO 1997 Dengue Classification
Grade Sign and Symptomps Laboratory

DF ~ DHF without plasma leakage
I Fever with non-specific constitutional symptoms; the
only hemorrhagic manifestation is a positive
tourniquet test &/or easy bruising
Thrombocytopenia
evidence of plasma leakage
(platelet count
II DHF grade I plus spontaneous bleeding £100,000/µL)
DHF
III Circulatory failure manifested by a rapid, weak pulse,
narrowing of pulse pressure, or hypotension, cold &
clammy skin, restlessness
IV Profound shock with undetectable pulse and blood
pressure
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1997 2009
• Changes in the epidemiology

– became endemic disease (expansions into other regions)
– increasing adult cases
• Clinical manifestation are more varied
• The incidence of severe cases increase
– The development of mild cases into severe cases is difficult to
detect
• Difficulties in applying the criteria for DHF in the clinical
situation, together with the increase in clinically severe
dengue cases which did not fulfil the strict criteria of DHF
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WHO TDR 2009 Dengue Classification
WHO proposed a dengue case classification system in 2009:
• Supported by set of clinical and/or laboratory parameters
• Emphasize the importance of detecting clinically significant
plasma leakage early as a feature that distinguishes severe
from non severe dengue cases
• Classification levels would help clinicians in decision making
about intensity of treatment and observation
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WHO TDR 2009 Dengue Classification
41
2009 2011
• Some cases of DF and DHF came with unusual

manifestation
• Triage system was needed for early detection
of shock and prompt management
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Manifestation of dengue virus infection
43
WHO Classification of Dengue Infection and
Grading of Severity
WHO-SEARO 2011
DF/D Grade Signs & Symptoms Laboratory
HF
DF Fever with 2 following signs Leucopenia (WBC ≤5000
• Headache cells/mm3)
• Retro-orbital pain Thrombocytopenia
• Myalgia (≤150.000 cells/mm3)
• Arthralgia/bone pain Rising hematocrit (5%-
• Rash 10%)
• Hemorrhage manifestations No evidence of plasma loss
• No evidence of plasma leakage
DHF I Fever & hemorrhagic manifestation (positive Thrombocytopenia
tourniquete test) and evidence of plasma leakage <100.000 cells/mm3
Hematocrit rising ≥20%
DHF II As grade I plus spontaneous bleeding
DHF* III As grade I or II plus circulatory failure (weak
pulse, narrow pulse pressure (≤20 mmHg),
hypotensive, restless
DHF* IV As grade III plus profound shock with
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undetectable BP & pulse
Dengue Diagnosis Classification
1997 2009 2011

• Dengue fever • Dengue without • Dengue fever
warning signs
• DHF grade I • DHF grade I
• Dengue with warning
• DHF grade II • DHF grade II
signs
• DHF grade III/DSS • DHF grade III /DSS
(dengue shock syndrome) • Severe dengue (dengue shock syndrome)
(severe plasma
• DHF grade IV (DSS with leakage, hemorrhage, • DHF grade IV
profound shock) organ involvement) • Expanded dengue
syndrome (unusual
manifestation, organ
involvement, co-morbidity
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2014 IPS Guidelines for Diagnosis and
Management of Dengue Infection in Children
✚ ✚
HARMONIZED
2009 2011 2011
WHO WHO-SEARO WHO-SEARO
IPS - Pediatric
Tropical
Infectious
Disease
Working
Group
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What is new in IPS 2014 dengue
guidelines?
• Warning signs
• Triage system in PHC/ hospital
• Determination of compensated shock and decompensated
shock as a guide for early and targeted treatment
• Concern to A-B-C-S (Acidosis, bleeding, calcium, sugar)
• Expanded dengue syndrome
• The diagnosis of dengue infection in the hospital should be
accompanied by dengue Ag detection or serological Ab tests
• High risk group
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• Electrolytes disturbance
Dengue • Fluid overload
complication
Expanded
Dengue
Syndrome
• Dengue encephalopathy
Unusual • Massive bleeding
manifestations • Dual infection
• Renal abnormality
• Miocarditis
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High risk group
The following host factors contribute to more severe disease and its complications:
• infants and the elderly,
• obesity,
• pregnant women,
• peptic ulcer disease,
• women who have menstruation or abnormal vaginal bleeding,
• haemolytic diseases such as glucose-6-phosphatase dehydrogenase (G-6PD) deficiency,
• thalassemia and other haemoglobinopathies,
• congenital heart disease,
• chronic diseases such as diabetes mellitus, hypertension, asthma, ischaemic heart disease,
chronic renal failure, liver cirrhosis,
• patients on steroid or NSAID treatment, and
• others.
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PATIENT ASSESSMENT AND
EVALUATION
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Acknowledgements
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Patient assessment: four important steps
Step 4: Diagnosis, phase of disease and

Step 2: Clinical examination
Step 3: Investigations
Step 1: History taking
severity
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How much urine output: frequency, volume and time of most
What activities could the patient do during the febrile illness?

What are important histories in dengue patients?
How much oral fluid intake: quantity and quality?

Other fluid losses: diarrhoea, vomiting

Date of onset of fever or illness
Presence of warning signs

The 3 golden questions:
Symptoms and severity
recent voiding?
•
•
5.
4.
1.
2.
3.
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What are other relevant histories?
6. Family or neighbour with dengue, or travel to dengue-endemic areas
7. Medications (including non-prescription or traditional medicine) in use?

List of medications and last time they were taken.
8. Risk Factors: infancy, pregnancy, obesity, diabetes mellitus,
Acknowledgements
hypertension, etc.
Why do we ask?
9. Jungle trekking or swimming in waterfall

Consider leptospirosis, typhus, malaria
10. Recent unprotected sexual or drug use behaviour

Consider acute HIV seroconversion illness
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Tourniquet test: repeat if negative or if there is no bleeding manifestation
Step 2: Clinical examination
Tachypnoea/acidotic breathing: indicates shock

Fluid accumulation: pleural effusion, ascites
Bleeding manifestations: mucosal bleeding
Clinical evidence of warning signs:
Haemodynamic state
Other important signs:

Abdominal tenderness
General assessment:
Liver enlargement
Hydration state
Mental state
Rash
≥15 years 60-100 80 12-18 <90
Hemodynamic Assessment
Hemodynamic Stable Compensated Hypotensive
Parameters Circulation Shock Shock
Conscious Clear and lucid Clear and lucid Restless, combative
level
Capillary refill Brisk (≤2 sec) Prolonged (>2 sec) Very prolonged, mottled skin
Extremities Warm and pink Cool peripheries Cold, clammy
Peripheral Good volume Weak and thready Feeble or absent
pulse volume
Heart rate Normal heart rate Tachycardia for age Severe tachycardia or
for age bradycardia in late shock
Blood ▶ Normal blood ▶ Normal systolic ▶ Narrow pulse pressure
pressure pressure for age pressure, but rising (≤ 20 mmHg)
▶ Normal pulse diastolic pressure ▶ Hypotension
pressure for age ▶ Narrowing pulse ▶ Unrecordable blood
pressure pressure
▶ Postural hypotension
Respiratory Normal respiratory Tachypnea Hyperpnea or Kussmaul’s

rate rate for age breathing (metabolic acidosis)
Urine output Normal Reducing trend Oliguria or anuria
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A patient with high fever (39oC) has tachycardia, cold extremities and
Pitfalls in clinical examination of dengue patients
* Reminder: Haemodynamic assessment is the foundation of dengue
A wrong interpretation could lead to a wrong decision in fluid

What other features do you need to consider?
delayed capillary refill time.
Is he or she in shock?
clinical management.
management.
•
•
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Pitfalls in clinical examination of dengue patients
What was the patient’s fluid intake
What was the patient’s pulse
Clinical features come as a “package”, not in isolation.

and urine output?
Intake/output:
volume?
Always look at the BIG picture before “zooming in”.
Picture
Big
In which phase of disease is the
When was fever onset?
Any warning signs?
Remember:
patient?
History:
Acknowledgements
Dengue investigation basics
• Complete blood count (CBC) with haematocrit (HCT) are usually all that
are necessary for monitoring
• Of special importance are:
• HCT;
• white blood cell count (WBC) and;
• platelet count
Acknowledgements
• An HCT in the first 3 days of illness suffices for the baseline HCT; in
acute cases, age-specific population HCT levels can substitute for a
patient’s baseline
• A steep drop in platelet count with a rising HCT compared to
baseline suggests progression to the plasma leakage/critical phase
of dengue
• A falling WBC followed by falling platelet count by Day 3 or 4 of
illness is almost surely dengue
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Who should get a complete blood count (CBC)?
• All patients with fever ≥3 days

• All patients with warning signs (urgently)
• All patients with shock (CBC and glucose check urgently)
o If resources are available, all febrile patients should get baseline CBC at
first visit. A normal CBC in the febrile phase does not exclude dengue.
Acknowledgements
o If resources are limited, CBC for febrile patients with poor oral intake
and/or poor urine output.
When should a patient be referred for immediate medical treatment?
• Rising HCT or high HCT

• Leucopenia and/or thrombocytopenia
• Presence of warning signs, shock
• Poor oral intake/not passing urine
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Acknowledgements
Dengue-specific diagnostic tests *
• For confirmation, e.g. NS1/IgM rapid tests or nucleic acid detection
(depending on resources of health facility)
• Not necessary for the acute management of patients but valuable in

unusual manifestations, suspected dengue deaths in the area, or for
Acknowledgements
patients who progress rapidly from mild to severe dengue or death
Other tests? *
• Blood chemistry tests (liver function, glucose, serum electrolytes, urea,
creatinine
• Should be considered in patients with risk factors and severe disease
* If available 60
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Step 4: Diagnosis, phase of disease and severity
2. Which phase of dengue (febrile/critical/recovery)?

1. Does the patient have dengue or other illnesses?
6. What is the best medical plan for the patient?

4. Are dengue warning signs present?
5. What is the haemodynamic state?

3. What is the hydration state?
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Acknowledgements
Group C
• Require
Management of dengue
Step 4: Diagnosis with dengue phase and severity

Step 2: Clinical examination: 5-in-1 magic touch
Group B
Step 5: Management decision
• Refer for in-

Group A
• Send home
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Acknowledgements
urgent referral
treatment and
Group C
emergency
• Require
Management of dengue
Step 4: Diagnosis with dengue phase and severity

Step 2: Clinical examination: 5-in-1 magic touch
management
Group B
Step 5: Management decision
• Refer for in-

hospital
Group A
• Send home
DENCO Slide
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1. Give anticipatory guidance
3. Identify warning signs

(see patient handout)
before sending home
Outpatient management: Group A
1. Follow up daily
2. Do serial CBCs
“drink enough to pee enough”
Patients who are able to
early
Group A – Send home if
patient meets all of the
Output: Passing urine at least
Has stable haematocrit and

Does not have any warning
Does not have co-existing

Intake: Getting adequate
once every 4 to 6 hours

following
hemodynamic status
volume of oral fluids
conditions
signs
Acknowledgements
Keys to good home care
1. Bed rest
2. Encourage oral intake

What is adequate oral intake?
6 to 8 glasses of fluid for adults and accordingly in children
What types of fluid?

Milk, coconut water, fruit juice (caution with diabetes patient), oral rehydration
Acknowledgements
solution, barley water, rice water, clear soup
Water alone may cause electrolyte imbalance.
3. Manage fever
Give paracetamol if fever is higher than 38°C
Adult - not more than 4 g per day
Child - 10 mg/kg/dose, not more than 4 times a day
Tepid (lukewarm water) sponging
Do not give ibuprofen or aspirin (or other non-steroidal anti-inflammatory drugs)
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Keys to good home care (cont.)
4. Reduce breeding habitats around the home and kill adult mosquitoes
5. Return to hospital IMMEDIATELY if no improvement or warning signs

appear
Frequent vomiting, unable to drink or scanty urine

Severe abdominal pain
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Severe tiredness, drowsiness, mental confusion or seizures
Bleeding:
Red spots or patches on the skin
Bleeding from nose or gums
Vomiting blood
Black coloured stools
Heavy menstruation or vaginal bleeding
Pale, cold or clammy hands and feet
Breathing difficulty
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2. Monitor hemodynamic status
5. Correct metabolic acidosis,

1. Admit for inpatient care
Outpatient Management: Group B
electrolytes as needed
4. Use isotonic IV fluids
3. Use HCT to guide
interventions
judiciously
frequently
Has co-existing condition:
Has social circumstances:
a reliable means of
Living far away without
(any of following)
Group B
Has warning signs
Diabetes mellitus
transport
Living alone
Renal failure
Pregnancy
Elderly
Infant
Acknowledgements
Haematocrit should not be interpreted on its own
Haematocrit should always be interpreted in the context of and “in
phase” with:
1. Haemodynamic evaluation at time of sampling
2. Before or after IV fluid therapy?
3. Before or after transfusion with whole blood or packed cells?
Acknowledgements
4. Phase of disease, where in the clinical course is the patient: day 2 vs day 5
IMPORTANT REMINDER:
Haemodynamic state should be the principal driver of IV fluid therapy
Haematocrit level should only be a guide
NOT the other way around!
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within next 24 hours as
Continue to monitor closely.
HCT should start to fall
Does not require extra
Interpretation of rising or persistently high haematocrit
Need for further fluid
intravenous fluid
plasma leakage
plasma leakage stops.

replacement
Active
Stable haemodynamic
Unstable vital signs
status
persistently high
persistently high
haematocrit
haematocrit
A rising or
A rising or
DENCO Slide
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Acknowledgements
Requires emergency treatment
Emergency management: Group C
and urgent referral

(any of following)
with shock and/or fluid

Severe plasma leakage
respiratory distress
AST or ALT ≥1000

accumulation with
Group C
and/or impaired
Severe bleeding
consciousness
Severe organ
impairment:
When to start and stop intravenous fluid therapy
Febrile phase
Limit IV fluids (refer to later slides for oral fluid advice)

Early IV therapy may lead to fluid overload especially with non-isotonic IV fluid
Critical phase
IV fluids are usually required for 24–48 hours

NOTE: For patients who present with shock, IV therapy should be <48 hours
Recovery phase
IV fluids should be stopped so that extravasated fluids can be reabsorbed
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Intravenous fluid therapy in DHF during critical period
Indications for IV fluid:

• when the patient cannot have adequate oral fluid intake or is
vomiting.
• when HCT continues to rise 10%–20% despite oral
rehydration.
• impending shock/shock.
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What type of intravenous fluid therapy should we use?
Use isotonic solutions (normal saline, Ringer’s lactate)
Colloids are preferred if the blood pressure has to be restored urgently

(e.g. Group C patients)1,2,3
Na K Cl Lactate Ca Osm
Solution mEq/L
Normal saline (NS) 154 154 292
D5% NS 154 154 565
Ringer’s lactate 130 4 109 28 3 274
Hartmann’s solution 131 5 111 29 2 278
1 Dung NM, Day NP, Tam DT. Clin Infect Dis, 1999, 29:787–794;
2 Ngo NT, Cao XT, Kneen R. Clin Infect Dis, 2001, 32:204–213.
3 Wills BA et al. N Engl J Med, 2005, 353:877–889.
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Calculations for normal maintenance of intravenous
fluid infusion
Normal IV fluid maintenance per hour by Holliday-Segar formula:
4 mL/kg/h for first 10 kg body weight

+ 2 mL/kg/h for next 10 kg body weight
+ 1 mL/kg/h for subsequent kg body weight
For overweight/obese patients, calculations for normal maintenance

of IV fluid should be based on ideal body weight (IBW)
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Skema 1. Tatalaksana Tersangka DBD derajat I & II (tanpa syok)
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Skema 2. Tatalaksana DBD Derajat I dan II
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Box 15: Volume Skema 3. Tatalaksana
replacement flow chart for DBD Derajat
patients IIIs
with DSS
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Management of prolonged/profound shock:
DHF Grade 4
• The scheme is similar with Skema 3 (Tatalaksana DBD derajat III) but
the initial fluid resuscitation in Grade 4 DHF is more vigorous
– 10-20 ml/kg of bolus fluid should be given as fast as possible, ideally
within 10 to 15 minutes. When the blood pressure is restored, further
intravenous fluid may be given as in Grade 3.
– If shock is not reversible after the first 10 ml/ kg, a repeat bolus of 10
ml/kg and laboratory results should be pursued and corrected as
soon as possible.
• Laboratory investigations should be done as soon as possible for
ABCS as well as organ involvement.
• Urgent blood transfusion should be considered as the next step
(after reviewing the pre- resuscitation HCT) and followed up by
closer monitoring
78
A–B–C-S
• Profound shock A-Acidosis

B-Bleeding
• Complication Blood gas
Haematocrit
• Adequate volume LFT, BUN, Cr
replacement à no
improvement S-Blood
C-Calcium
sugar
à ABCS Electrolyte,
BS
Ca++
(dextrostick)
Tatalaksana Fase Kritis

Hematocrit
Summary of Monitoring AndinDengue
IV fluid therapy dengue
Inadequate Adequate Excessive
Hypovolaemia Improved circulation Fluid overload:

and tissue perfusion • Pulmonary oedema
Compensated shock • Respiratory distress
•Worsening pleural effusion
• Capillary refill <2 seconds
Hypotensive • Normal heart rate and ascites
shock • Normal blood pressure • Clinical deterioration
• Normal pulse pressure
• Urine 0.5ml/kg/hr
• Bleeding
• ↓ HCT to normal
• DIC • Improving acid-base
• Multi-organ failure
80
Acknowledgements
Summary of management of dengue
Group A Group B Group C
(all of following) (any of following) (any of following)
Getting adequate volume of Has warning signs Severe plasma leakage with
oral fluids shock and/or fluid
Has co-existing condition:
Passing urine at least once accumulation with
Diabetes mellitus, renal
every 4 to 6 hours respiratory distress
failure, pregnant, infant or
No warning signs elderly Severe bleeding
Has stable haematocrit and Has social circumstances: Severe organ impairment:
haemodynamic status Living alone or living far
AST or ALT ≥1000 and/or
away without a reliable
Does not have co-existing impaired consciousness
Acknowledgements
means of transport
conditions
1. Give anticipatory 1. Admit for inpatient care Requires emergency

guidance before sending 2. Monitor hemodynamic treatment and urgent referral
home (see patient status frequently
handout)
3. Use HCT to guide
2. Follow up daily interventions
3. Do serial CBCs 4. Use isotonic IV fluids
4. Identify warning signs judiciously
early 5. Correct metabolic
acidosis, electrolytes as
needed
81
Acknowledgements
Saving lives with simple steps
Lives can be saved with simple steps
1. Successful patient–physician clinical encounter*
Very sensitive step:
Dengue patient feels vulnerable and perhaps fearful
Acknowledgements
Outpatient department, emergency department and general
practitioners have only one window of opportunity to form a
solid connection with outpatients.
Clinical encounters affect trust, patient understanding and

follow-up, all vital for a positive clinical outcome.
As doctors and nurses we are in control of this step
* James T. The Patient-Physician Clinical Encounter. 2007 82

Acknowledgements
Saving lives with simple steps (cont.)
2. Fast-track patient follow-up.
3. Monitor disease progression daily.
For every visit:

Ask the 3 golden questions:
• How much oral fluid intake (in the last 12-24 hours)?
• How much urine output? Other fluid losses?
Acknowledgements
• What activities can the patient do?
Monitor disease progression:
• Fever or defervescence?
• Development of warning signs?
Assess hemodynamic state: 5-in-1 magic touch
Conduct serial CBCs until patient is out of the critical phase:
• Decreasing WBC
• Rising HCT with concurrent rapid fall in platelet count
83
Dengue WITH warning signs – What do you monitor?
Document disease progression and defervescence
• Monitor until risk period is over (24 to 48 hrs after defervescence).

• Watch for signs of plasma leakage, shock and bleeding
Maintain detailed fluid balance – oral fluids, IV fluids and urine volume
• Empower patients or parents to document intake and output
Monitor parameters including:
• vital signs and peripheral perfusion (every 1 to 2 hours until out of critical
phase)
• HCT (before and after IVF therapy, then every 6 to 8 hours)
• blood glucose (every 6 to 12 hours or as indicated, consider glucose-
electrolyte solutions for children)
• electrolytes and organ functions as indicated by clinical status (LFT, acid
base)
DENCO Slide
84
Group B: Dengue WITH co-existing conditions
but without warning signs
If patients are/have:
Pregnant
Infants
Elderly
Diabetes mellitus
Hypertension
Ischaemic heart disease/heart failure
Liver cirrhosis
Chronic renal failure
Chronic lung disease
Haemolytic disease – G6PD deficiency, thalassaemia
Poor social conditions – living alone, no transport
Admit early (in febrile phase)

Monitor baseline HCT
Monitor glucose and blood pressure
85
Criteria for discharging patients
• Absence of fever for at least 24 hours without the use of anti-
fever therapy.
• Return of appetite.
• Visible clinical improvement.
• Satisfactory urine output.
• A minimum of 2–3 days have elapsed after recovery from shock.
• No respiratory distress from pleural effusion and no ascites.
• Platelet count of more than 50 000/mm3. If not, patients can be
recommended to avoid traumatic activities for at least 1–2
weeks for platelet count to become normal. In most
uncomplicated cases, platelet rises to normal within 3–5 days.
86
87
Your child or family member may have dengue fever
according to their clinical history and physical examination.
If it is dengue, serious complications of the disease can develop. If the complications are recognized
early, and a doctor is consulted, it may save the patient’s life. Your doctor can order more tests to see
if the patient needs to be hospitalized. The doctor can also order specific tests for dengue, but those
tests will take longer than a week for the results to come back.
How to Care for the Patient While They Have a Fever:

✔ Bed rest. Let patient rest as much as possible.
Your child or family member may have dengue fever

DO WHILE THE PATIENT HAS FEVER
✔ Control the fever.
● Give acetaminophen or paracetamol (Tylenol) every 6 hours (maximum 4 doses per day).
Do not give ibuprofen (Motrin, Advil) aspirin, or aspirin containing drugs.

● Sponge patient’s skin with cool water if fever stays high.
✔ Prevent dehydration which occurs when a person loses too much fluid (from high fevers, vomiting,
or poor oral intake). Give plenty of fluids and watch for signs of dehydration. Bring patient to clinic
or emergency room if any of the following signs develop:
● Decrease in urination (check number of wet diapers or trips to the bathroom)
● Few or no tears when child cries

● Dry mouth, tongue or lips
● Sunken eyes
● Listlessness or overly agitated or confused

● Fast heart beat (more than 100/min)
● Cold or clammy fingers and toes
● Sunken fontanel in infant

✔ Prevent spread of dengue within your house.

● Place patient under bed net or use insect repellent on the patient while they have a fever.
Mosquitoes that bite the patient can go on to bite and infect others.
How to Care for the Patient While They Have a Fever: ● KILL all mosquitoes in house and empty containers that carry water on patio.
● Put screens on windows and doors to prevent mosquitoes from coming into house.
How to Care for the Patient While Fever is Going Away:

DO WHEN FEVER GOING AWAY
✔ Watch for warning signs as temperature declines 3 to 7 days after symptoms began.
Return IMMEDIATELY to clinic or emergency department if any of the following
warning signs appear:
● Severe abdominal pain or persistent vomiting
● Red spots or patches on the skin
● Bleeding from nose or gums

● Vomiting blood
● Black, tarry stools
Sponge patient’s skin with cool water if fever stays high.

● ● Drowsiness or irritability
● Pale, cold, or clammy skin
● Difficulty breathing
✔ Prevent dehydration which occurs when a person loses too much fluid (from high fevers, vomiting, 88
or poor oral intake).YouGive plenty of fluids and watch for signs of dehydration. Bring patient to clinic
should have available the name and telephone number of your doctor and ask for clarifications if needed. CS205910
How to Care for the Patient While They Have a Fever:

DO WHILE THE PATIENT HAS FEVER

● Sponge patient’s skin with cool water if fever stays high.
✔ Prevent dehydration which occurs when a person loses too much fluid (from high fevers, vomiting,
or poor oral intake). Give plenty of fluids and watch for signs of dehydration. Bring patient to clinic
or emergency room if any of the following signs develop:
● Decrease in urination (check number of wet diapers or trips to the bathroom)
● Dry mouth, tongue or lips
● Sunken eyes

● KILL all mosquitoes in house and empty containers that carry water on patio.

OING AWAY
warning signs appear: 89

Dry mouth, tongue or lips
DO WHILE THE
●
● Sunken eyes

● KILL all mosquitoes in house and empty containers that carry water on patio.

DO WHEN FEVER GOING AWAY
warning signs appear:
● Bleeding from nose or gums
● Vomiting blood
● Black, tarry stools
● Drowsiness or irritability
● Pale, cold, or clammy skin
● Difficulty breathing
You should have available the name and telephone number of your doctor and ask for clarifications if needed. CS205910
90
Dengue Management DO’s and DON’Ts
X DON’T use corticosteroids. They are not indicated and can increase the risk of GI
bleeding, hyperglycemia, and immunosuppression.
X DON’T give platelet transfusions for a low platelet count. Platelet transfusions do
not decrease the risk of severe bleeding and may instead lead to fluid overload and
prolonged hospitalization.
X DON’T give half normal (0.45%) saline. Half normal saline should not be given, even
as a maintenance fluid, because it leaks into third spaces and may lead to worsening
of ascites and pleural effusions.
X DON’T assume that IV fluids are necessary. First check if the patient can take fluids
orally. Use only the minimum amount of IV fluid to keep the patient well-perfused.
Decrease IV fluid rate as hemodynamic status improves or urine output increases.
✓ DO tell outpatients when to return. Teach them about warning signs and their
timing, and the critical period that follows defervescence.
✓ DO recognize the critical period. The critical period begins with defervescence and
lasts for 24–48 hours. During this period, some patients may rapidly deteriorate. 91
X DON’T give half normal (0.45%) saline. Half normal saline should not be given, even
as a maintenance fluid, because it leaks into third spaces and may lead to worsening
of ascites and pleural effusions.
X DON’T assume that IV fluids are necessary. First check if the patient can take fluids
Decrease IV fluid rate as hemodynamic status improves or urine output increases.
Dengue Management DO’s and DON’Ts
X DON’T
timing, use andcorticosteroids.
the critical period thatare
They follows defervescence.
not indicated and can increase the risk of GI
✓ bleeding, hyperglycemia, and immunosuppression.

DO recognize the critical period. The critical period begins with defervescence and
X DON’T
lasts forgive24–48 hours.transfusions
platelet During this period,
for a lowsome patients
platelet may
count. rapidlytransfusions
Platelet deteriorate.do
✓ not decrease the risk of severe bleeding and may instead lead to fluid overload and
DO closely monitor fluid intake and output, vital signs, and hematocrit levels. Ins
prolonged hospitalization.
and outs should be measured at least every shift and vitals at least every 4 hours.
X DON’T
Hematocrits should
give half be measured
normal (0.45%)every 6–12
saline. hours
Half at minimum
normal duringnot
saline should thebe
critical
given,period.
even
✓ asofDOa maintenance fluid, because it leaks into third spaces and may lead to worsening
recognize and treat early shock. Early shock (also known as compensated or
ascites and pleural effusions.
normotensive shock) is characterized by narrowing pulse pressure (systolic minus
X DON’T
diastolic
refill or
BP approaching
assume
cool
20 mmHg),
that IV fluids
extremities.
increasing
are necessary. Firstheart
check rate, and
if the delayed
patient
cancapillary
take fluids
✓ Decrease IV fluid rate as hemodynamic status improves or urine output increases.

DO administer colloids (such as albumin) for refractory shock. Patients who do not
respond to 2–3 boluses of isotonic saline should be given colloids instead of more
saline.
✓ timing,
DO giveand the critical
PRBCs or whole period
bloodthat
forfollows defervescence.
clinically significant bleeding. If hematocrit is
dropping with unstable vital signs or significant bleeding is apparent, immediately
✓ DO recognize
transfuse the critical period. The critical period begins with defervescence and
blood.
lasts for 24–48 hours. During this period, some patients may rapidly deteriorate.
✓ DO closely monitor fluid intake and output, vital signs, and hematocrit levels. Ins
and outs should be measured at least every shift and vitals at least every 4 hours. 92
Hematocrits should be measured every 6–12 hours at minimum during the critical period.

IT-10 Dengue in Children

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Dengue Management in

Etiology and Pathogenesis

Laboratory diagnosis confirmation

• The pathogenesis of DHF and DSS still needs to be explored further

– Secondary Heterologous Infection or Antibody

Scott B. Halstead. WHO, SEARO, New Delhi, 1993. p80-103.

• Patients experiencing a 2nd infection with heterologous dengue virus

• Prior infection, through a process ð antibody-dependent enhancement

• This cells, produce and secrete vasoactive mediators (particularly

Halstead SB. WHO, SEARO, New Delhi 1993

• Homologous Antibodies Form Non-infectious Complexes

• Heterologous Antibodies Form Infectious Complexes

Non-neutralizing antibody to Dengue 1 virus

 Heterologous Complexes Enter More Monocytes, Where Virus Replicates

2 Complex formed by non-neutralizing antibody and

Dengue has a wide spectrum of clinical presentations with

phase and evolves into

Quality of life may be affected1

Headache, retroorbita pain

Influenza, measles, rubella

Acute febrile phase Critical phase Recovery phase

Increase in haematocrit concurrent with rapid dcrease in

* WHO 2009 Dengue guideline 21

Pleural effusion Signs of shock

Ascites Progressive leucopenia

Sepsis, septic shock

Systemic lupus erythematosus

Liver cirrhosis with portal hypertension

Development of warning signs:

• May precede changes in blood pressure and pulse pressure

• Good indicator that patient could have dengue

• Indicate an increase in vascular permeability

Shock occurs when critical volume of plasma is lost through leakage.

• Fever subsides → general condition improves and appetite recovers

• Mild to moderate thrombocytopenia

Clues to progression from critical phase to recovery phase

© WHO/Lucy Lum Chai See

Hypervolaemia with fluid overload because of inappropriate fluid management

Organ impairment to liver, kidneys and other organs

Plasma leakage → hypovolaemia and shock

Warning Compensated Hypotensive Cardiac

• Handbook mangement of dengue, TRD-WHO,2012

WHO has proposed several guidelines

1997 2011 2009

1. Fever 2-7 days + +

Grade Sign and Symptomps Laboratory

• Changes in the epidemiology

• Some cases of DF and DHF came with unusual

1997 2009 2011

Step 4: Diagnosis, phase of disease and

What activities could the patient do during the febrile illness?

How much oral fluid intake: quantity and quality?

Other fluid losses: diarrhoea, vomiting

Presence of warning signs

What are other relevant histories?

7. Medications (including non-prescription or traditional medicine) in use?

8. Risk Factors: infancy, pregnancy, obesity, diabetes mellitus,

9. Jungle trekking or swimming in waterfall

10. Recent unprotected sexual or drug use behaviour

Tachypnoea/acidotic breathing: indicates shock

Other important signs:

Respiratory Normal respiratory Tachypnea Hyperpnea or Kussmaul’s

* Reminder: Haemodynamic assessment is the foundation of dengue

Heterologous Complexes Enter More Monocytes, Where Virus Replicates