DENGUE

GUIDELINES
- A REVIEW
D R . B I C H I T R O VA N U S A R K A R
D C H ( C A L ) M RC P C H ( U K ) F RC P C H ( U K )
 DR BICHITROVANU SARKAR
MBBS(CAL) DCH(CAL) MRCPCH(UK) FRCPCH(UK)
ICTPICM(UK) FELLOWSHIP IN PAEDIATRIC INTENSIVE CARE

Senior Consultant Paediatric Intensivist

Desun Institute of Women &Children, Kolkata

Accredited Teacher
IAP-ICC College of Pediatric Critical Care

Founder Member and Past President (2018)

WBAP Intensive Care Chapter / Society of Pediatric Intensive Care,
Kolkata

Member, Executive Board (2019, 2020, 2021)

West Bengal Academy of Pediatrics

Former Head of Paediatric Intensive Care Services of

AMRI Group of Hospitals, Kolkata
Fortis Hospital, Anandapur, Kolkata
Peerless Hospital & BK Roy Research Centre, Kolkata
Institute of Neurosciences, Kolkata
 CAREER HIGHLIGHTS
• MBBS – Nilratan Sircar Medical College – 1997
• DCH – Institute of Child Health, Calcutta – 2002
• Member of Royal College of Paediatrics and Child Health, UK – 2009
• Elected Fellow of Royal College of Paediatrics and Child Health, UK –
2018
• Trained in Paediatrics and Neonatology under East of England
(Cambridge) Deanery
• Trained in Paediatric Intensive Care Medicine at
• Imperial College, London
• King’s College, London
• Great Ormond Street Hospital for Children, University College London
• Royal Manchester University Children’s Hospital
• Trained in Paediatric Critical Care Transport with Europe’s elite
Children’s Acute Transport Service (CATS)
• ICTPICM(UK) Fellowship from Intercollegiate Committee for Training in
Paediatric Intensive Care Medicine – 2016
 MODULE 4: Clinical Course of
Disease

Dengue Clinical Management

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.
 Clinical course of dengue
Dengue is a systemic and dynamic disease.

Platelets

Dengue is NOT a platelet count disease

1
Lancet 2017; 389: 1611-18
 Clinical course of dengue

Viraemia:
headache, nausea, myalgia,
body ache and rash Critical
Phase
Incubation period Febrile Phase Recovery Phase

Days
0 1 2 3 4 6 8 10
After the incubation period, the illness begins abruptly.
It is characterized by 3 phases:

Febrile phase – commences at symptom onset

Critical phase – commences around time of defervescence*

* Defined as when body temperature drops to less than 38°C and remains below this level.

Recovery phase – commences when plasma leakage resolves

1
Days of illness: 0 1 2 3 4 5 6 7 8 9 10
Phases of dengue: Febrile Critical Recovery

Virology and Serology

Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 1
Days of illness: 0 1 2 3 4 5 6 7 8 9 10
Phases of dengue: Febrile Critical Recovery
6 Key features: Defervescence Bi-phasic/
40 Saddle back picture
1. Temperature
38

Subnormal
temperature

IgM/IgG
Viraemia

Virology and Serology

Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 1
Days of illness: 0 1 2 3 4 5 6 7 8 9 10
Phases of dengue: Febrile Critical Recovery
6 Key features:
40
1. Temperature
38

Laboratory
changes Platelet

4. WBC WBC
5. Platelet
Haematocrit
6. HCT

IgM/IgG
Viraemia

Virology and Serology

Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 1
Days of illness: 0 1 2 3 4 5 6 7 8 9 10
Phases of dengue: Febrile Critical Recovery
6 Key features:
40
1. Temperature
38

Potential
Dehydration Reabsorption
clinical issues Fluid overload
Shock
2. Oral intake
3. Urine output Bleeding

Capillary permeability

Organ Impairment
Laboratory
changes Platelet

4. WBC WBC
5. Platelet
Haematocrit
6. HCT

IgM/IgG
Viraemia

Virology and Serology

Adapted from WCL Yip, 1980 by Hung NT, Lum LCS, Tan LH 1
 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
Clinical Warning Signs Laboratory Warning Signs
1. Severe abdominal pain 1. Leukopenia
2. Persistent vomiting 2. Rapid decrease platelet
3. Mucosal bleed count
4. Lethargy; restlessness 3. Rising haematocrit

5. Liver enlargement >2cm

6. Clinical fluid accumulation

1
 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
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.

20
MODULE 2: Epidemiology of Dengue
Dengue case classification by severity

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
WHO proposed a dengue case classification system in 2009:
• Supported by set of clinical and/or laboratory parameters
• Aim to show clear-cut difference between patients with
non-severe versus severe dengue
• Classification levels would help clinicians in decision
making about intensity of treatment and observation
Dengue case classification (2009)

Dengue Severe dengue

• 1. Severe plasma leakage

With
Without • 2. Severe haemorrhage
warning signs
• 3. Severe organ impairment
 Dengue case definition (2009)

Probable dengue
Live in and/or travelled to a dengue-endemic area
Fever and two of the following criteria:
•
Nausea, vomiting (new)
•
Rash
•
Aches and pains (combined)
•
Tourniquet test positive
•
Leucopenia
•
Any warning sign

Laboratory-confirmed dengue
(Important when there is no sign of plasma leakage)
 Dengue case classification (2009)
Dengue ± warning signs Severe dengue

• 1. Severe plasma leakage

With
Without warning signs • 2. Severe haemorrhage
• 3. Severe organ impairment

Criteria for dengue ± warning signs Criteria for severe dengue

Probable dengue Warning signs* 1. Severe plasma leakage leading to:
Live in or travelled to dengue- ·
Abdominal pain or tenderness
•
Shock (DSS)
endemic area. Fever and two of the· •
Fluid accumulation with respiratory
Persistent vomiting
following criteria: distress
·
Mucosal bleed
·
Nausea, vomiting (new)
·
Lethargy; restlessness 2. Severe bleeding
·
Rash
·
Liver enlargement >2 cm Bleeding that causes hemodynamic
·
Aches and pains (combined)
·
Clinical fluid accumulation instability and may require blood transfusion
·
Tourniquet test positive
·
Increase in HCT with rapid decrease 3. Severe organ involvement
·
Leucopenia
in platelet count Liver: AST or ALT ≥1000
·
Any warning sign •

* Requiring strict observation and medical

•
CNS: Impaired consciousness
Laboratory-confirmed dengue intervention •
Impaired cardiac function
(important when no sign of plasma leakage)
Hemodynamic Assessment - Clinical
Parameters
Parameters

Conscious
level 3a. Organ perfusion (brain)
Capillary refill
time
Extremities
(color, temp) 1. Peripheral perfusion
Peripheral
pulse volume
Heart rate
(HR)
Pulse
pressure (PP) 2. Cardiac output
Blood
pressure (BP)
Respiratory
rate (RR) 4. Respiratory compensation for tissue hypoxia
Urine output 3b. Organ perfusion (kidney)
 Hemodynamic Changes in Compensated
Shock
Blood pressure Heart rate

120 Normal or elevated systolic pressure

110 Rising diastolic pressure

100 Narrow pulse pressure – weak pulse
90 Tachycardia

80 Reduced peripheral perfusion

70 Cool/cold and pale extremities
Prolonged capillary refill time
60
“Quiet” tachypnea

LUCID conscious level

Decreased urine output

Time

LCS Lum
 Hemodynamic Changes in Hypotensive
Shock
Blood pressure Heart rate

Increasing tachycardia
120 Feeble or absent peripheral pulse
110 Systolic and diastolic pressures
100 disappear suddenly

90 Reduced peripheral perfusion

80 Very cold, clammy extremities
70 Mottled, peripheral cyanosis

60 Very prolonged capillary refill time

Kussmaul breathing

Decreased level of conscious

Oliguria or anuria

Time

LCS Lum
 Pearls in clinical examination of dengue
patients
The “5-in-1 maneuver” magic touch – CCTV-R
Hold the patient’s hand to evaluate peripheral perfusion.
Save life in 30 seconds by recognizing shock
2.
1. 3. 4.
Capillary
Colour Temperature Pulse Volume
refill

© WHO/Lucy Lum Chai See

© WHO/Lucy Lum Chai See

 Pitfalls in clinical examination of dengue
patients

Always look at the BIG picture before “zooming in”.

History: Intake/output:
When was fever onset? What was the patient’s fluid
In which phase of disease is intake and urine output?
the patient?

Big
Picture
Any warning signs? What was the patient’s pulse
volume?

Remember:
Clinical features come as a “package”, not in isolation.
MODULE 7: Outpatient Management
 Management of dengue

Group A Group B Group C

• Send home • Refer for in- • Require
hospital emergency
manageme treatment
nt and urgent
referral

DENCO Slide
 Outpatient management: Group A

Patients who are able to

“drink enough to pee enough”

Group A – Send home

if patient meets all of
the following 1. Give anticipatory
Intake: Getting adequate guidance before
volume of oral fluids sending home

Output: Passing urine at (see patient handout)

least once every 4 to 6
hours 2. Follow up daily
Does not have any warning 3. Do serial CBCs
signs
Has stable haematocrit 4. Identify warning signs
and hemodynamic status early
Does not have co-existing
conditions
 Outpatient Management: Group B

Group B
(any of following)
Has warning signs 1. Admit for inpatient care
Has co-existing
2. Monitor hemodynamic
condition:
status frequently
Diabetes mellitus
Renal failure 3. Use HCT to guide
Pregnancy interventions
Infant
Elderly 4. Use isotonic IV fluids
Has social judiciously
circumstances:
Living alone 5. Correct metabolic
Living far away acidosis, electrolytes as
without a reliable needed
means of transport
 Emergency management: Group C

Group C
(any of
following)
Severe plasma
leakage with shock
and/or fluid Requires emergency
accumulation with treatment and urgent
respiratory distress referral
Severe bleeding
Severe organ
impairment:
AST or ALT ≥1000
and/or impaired
consciousness
Summary of management of dengue
Group A Group B Group C
(all of following) (any of following) (any of following)
Getting adequate volume Has warning signs Severe plasma leakage
of oral fluids Has co-existing condition: with shock and/or fluid
Passing urine at least once Diabetes mellitus, renal accumulation with
every 4 to 6 hours respiratory distress
failure, pregnant, infant
No warning signs or elderly Severe bleeding
Has social circumstances:
Has stable haematocrit Severe organ impairment:
and Living alone or living far
AST or ALT ≥1000 and/or
haemodynamic status away without a reliable
impaired consciousness
means of transport
Does not have co-existing
conditions
1. Give anticipatory 1. Admit for inpatient Requires emergency
guidance before care treatment and urgent
sending home (see 2. Monitor hemodynamic referral
patient handout) status frequently
2. Follow up daily 3. Use HCT to guide
3. Do serial CBCs interventions
4. Identify warning signs 4. Use isotonic IV fluids
early judiciously
5. Correct metabolic
acidosis, electrolytes
as needed
MODULE 8A: IV Fluid Principles
 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?
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!
 Interpretation of rising or persistently high haematocrit

A rising or Active
persistently high Unstable vital signs
plasma leakage
haematocrit

Need for further fluid

replacement

A rising or Does not require extra

Stable haemodynamic intravenous fluid
persistently high
status
haematocrit

Continue to monitor closely.

HCT should start to fall within
next 24 hours as plasma
leakage stops.

DENCO Slide
 Interpretation of a decrease in haematocrit

A decrease in Unstable vital signs Major haemorrhage

haematocrit

Need for urgent

transfusion

Haemodilution and/or
A decrease in Stable haemodynamic reabsorption of
haematocrit status extravasated fluids

IV fluids should be reduced in

step-wise manner or
discontinued immediately to
avoid pulmonary oedema

DENCO Slide
 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

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.

 HOW MUCH & HOW FAST to run intravenous
fluid?
HOW MUCH & HOW FAST?
Give the minimum IVF required to maintain good perfusion and urine output of
about 0.5 ml/kg/hr
Volume based on ideal body weight if overweight
Titrate to haemodynamic state and age

What does “titrate IVF rate to haemodynamic state” mean?

Reassess haemodynamic responses immediately after every IV bolus

AFTER correction of shock:
REDUCE IV infusion rate in step-wise manner whenever:
• Haemodynamic state is stable
• Rate of plasma leakage decreases towards end of critical phase
indicated by:
Improving haemodynamic signs
Increasing urine output
Adequate oral fluid intake
Haematocrit decreases below baseline value in a stable
patient
 Summary of IV fluid therapy in dengue

Inadequate Excessive
Adequate

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
MODULE 8B: Management of Group B – Dengue with
Warning Signs or Dengue with Co-existing Conditions
Group B: Dengue with warning signs (not in shock)
– Inpatient fluid management
Obtain reference HCT before starting IVF
therapy
Start with isotonic * Reassess haemodynamic state
crystalloids
5–7 ml/kg/hr for 1–2 1. Vital signs
hours 2. “5-in-1 magic touch”: CCTV-R
Colour
Improved *REASSESS Capillary refill time
Temperature
Volume of pulse
IV isotonic crystalloids^
3–5 ml/kg/hr for 2–4 hours Rate
3. Urine volume

IV isotonic crystalloids^
2–3 mL/kg/hr for 2–4 hours If improvement in oral intake,
HCT remains same or minimal
high:
Clinical improvement or 1. Step-wise reduction in IVF
improved oral intake,
reduce IVF accordingly 2. Consider glucose-electrolyte
for children
Continue to monitor patient until
Stop IVF therapy within
24–48 hours out of critical period
Stop IVF within 24–48 hours
Group B: Dengue with warning signs (not in shock)
– No improvement after first bolus
Obtain reference HCT before
starting IVF therapy

Start IV isotonic
crystalloids
5–7 ml/kg/hr for 1–2 hours

* Reassess haemodynamic *REASSESS Not improved

state:
• Vital signs
Check haematocrit
• “5-in-1 magic touch” –
CCTV-R
• Urine volume Increasing
If there is NO improvement, or high HCT
check HCT

If HCT is increasing or high,

Increase IV crystalloids to
increase IV crystalloids to 5– 5–10 ml/kg/hr for 1–2 hours
10 ml/kg/hr for 1–2 hours

* Reassess
Group B: Dengue with warning signs (not in shock)
– No improvement after first bolus (cont.)
Obtain reference HCT before starting
IVF

Start IV isotonic
crystalloids
5–7 ml/kg/hr for 1–2 hours

Improved *REASSESS Not improved

IV crystalloids Check haematocrit

3–5 mL/kg/hr for 2–4 hours

Increasing Decreasing
IV crystalloids Or high HCT HCT
2–3 mL/kg/hr for 2–4 hours

Increase IV Bleeding?
Clinical improvement or crystalloids Consider "Severe
improved oral intake, 5–10 ml/kg/hr for 1–2 Dengue"
reduce IVF accordingly hours algorithm

Stop IV fluids at 48 hours

* Reassess the patient’s clinical condition (vital signs, 5-in-1 magic touch – CCTV-R and urine output) and
decide on the situation.
MODULE 8C: Management of Group C –
Severe Dengue
 Group C: Emergency treatment – Summary
Compensated shock (systolic pressure maintained + reduced
perfusion)
Start isotonic crystalloid therapy Try to obtain CBC, HCT,
5–10 ml/kg/hr (adult) or GXM & other bloods
10–20 ml/kg/hr (child) for 1 hour before fluid resuscitation

Not improved
Improved *REASSESS

Start step-wise reduction Increasing

Check haematocrit Decreasing HCT
of isotonic crystalloid Or high HCT
therapy:
5–7 ml/kg/hr for 1–2 hours
3–5 ml/kg/hr for 2–4 hours Severe overt bleed
2–3 ml/kg/hr for 2–4 hours Crystalloid (2nd bolus) or
colloid** Yes No
10–20 ml/kg/hr for 1 hour
Further boluses may be
Urgent
• Colloid 10-20
required
blood ml/kg over 1 hr
transfusion • Evaluate to
consider blood
Clinical improvement or transfusion if
If improved no clinical
improved oral intake, •Reduce IV
reduce fluids step-wise improvement
crystalloid
therapy to
7–10 ml/kg/hr
for 1–2 hours
If not improved,
Stop IV fluids in 24–48 •Continue recheck haematocrit
hours
step-wise
reduction ofIVF

* Reassess the patient’s clinical condition: vital signs, peripheral perfusion - 5-in-1 magic touch, urine output; and decide on the situation.
** Colloid is preferable if the patient has already received several boluses of crystalloid
 Summary of management of dengue
Group A – Sent home Group B Group C
(all of following) (any of following) (any of following)

1. Give anticipatory 1. Admit for inpatient care As Group B PLUS:

guidance before
sending home (see 2. Monitor haemodynamic 1. Larger initial volume at
patient handout) status frequently a faster rate

2. Follow up daily 3. Use HCT to guide 2. Use colloids if several

interventions boluses of crystalloids
3. Do serial CBCs already given
4. Use isotonic IVF
4. Identify warning signs judiciously 3. After improvement, a
early further resuscitation
5. Titrate fluid precedes step-wise IVF
resuscitation to reduction
haemodynamic state
4. Monitor for occult
6. Correct metabolic bleeding
acidosis, electrolytes as
needed 5. Prophylactic platelet
transfusions not
indicated
 Group C: Emergency treatment – Summary
Try to obtain CBC, HCT, Hypotensive
GXM and other blood
readings before fluid
shock
resuscitation Start isotonic crystalloid or colloid therapy
10–20 ml/kg (adult) or
20 ml/kg (child) over 15–30 minutes

Not improved *REASSESS Improved

Check haematocrit Increasing

Or high HCT IV crystalloid or colloid
10 ml/kg/hr for 1 hour

Decreasing HCT
Colloid**
10 ml/kg/hr Step-wise reduction of
for 30–60 IV crystalloids
Severe overt bleed minutes 5–7 ml/kg/hr for 1–2
Yes No hours
3–5 ml/kg/hr for 2–4
Urgent
• Colloid (10–20 hours
blood ml/kg/hr) 2–3 ml/kg/hr for 2–4
transfusion • Evaluate to If improved hours
consider •Reduce IV
Further boluses may be
blood crystalloids Clinical improvement or
required
transfusion if 7–10 ml/kg/hr improved oral intake,
no clinical for 1–2 hours reduce fluids step-wise
improvement •Continue step-

wise reduction
If not improved, with
recheck haematocrit Stop IV fluids at 24–48
crystalloids
hours

* Reassess the patient’s clinical condition: vital signs, peripheral perfusion (CCTV-R) & urine output and decide on the situation.
** Colloid is preferable if the patient has already received several boluses of crystalloid
IV: intravenous, HCT: hematocrit, IVF: intravenous fluids
 Group C: Emergency treatment – Summary
Compensated shock Hypotensive shock
(systolic pressure maintained + reduced
perfusion)
Try to obtain CBC, HCT,
Start isotonic crystalloid GXM & other bloods Start isotonic crystalloid or colloid
therapy before fluid therapy
5–10 ml/kg/hr (adult) or 10–20 ml/kg (adult) or
resuscitation
10–20 ml/kg (child) for 1 hour 20 ml/kg (child) over 15–30 min

Improved *REASSESS Not improved *REASSESS Improved

Step-wise reduction Increasing Increasing

Check haematocrit IV crystalloid or colloid
of IV crystalloids or high HCT Or high HCT 10 ml/kg/hr for 1 hours
5–7 ml/kg/hr for 1–2 hours
3–5 ml/kg/hr for 2–4 hours
2–3 ml/kg/hr for 2–4 hours
Crystalloids (2nd
Decreasing HCT
Colloids**
bolus) or colloids** 10 ml/kg Step-wise reduction
10–20 ml/kg/hr for 1 hr for 30–60 min of IV crystalloids
Further boluses may be Severe overt bleed 5–7 ml/kg/hr for 1–2 hours
required
3–5 ml/kg/hr for 2–4 hours
Yes No 2–3 ml/kg/hr for 2–4 hours
• Colloid 10–20 Further boluses may be
Clinical improvement or Urgent
If improved ml/kg/hr required
improved oral intake, •Reduce IV blood • Evaluate to If Improved
reduce fluids step-wise crystalloids to transfusion consider blood •Reduce IV
7–10 ml/kg/hr transfusion if crystalloids to
for 1–2 hours no clinical 7–10 ml/kg/hr for Clinical improvement
•Continue
improvement 1–2 hours or improved oral
Stop IV fluids at
step-wise •Continue step- intake, reduce fluids
24–48 hours
reduction of IVF wise reduction step-wise

If not improved, with crystalloids

recheck haematocrit Stop IV fluids at 24–48

hours

* Reassess the patient’s clinical condition: vital signs, pulse volume, capillary refill time and temperature of extremities; decide on the situation.
** Colloids are preferable if the patient has already received several boluses of crystalloid.
How to avoid the trap?

Keep the focus

1. Priority: Haemodynamic evaluation

Vital signs + perfusion + urine output

Acid-base balance

Is the patient STABLE?

2. Consult HCT only when the patient is

UNSTABLE