2. Outline
1. Pathophysiology of dengue fever
2. Revised dengue classification
3. Phases in dengue
4. Patient assessment and evaluation
5. Fluid therapy in dengue fever
3. Introduction
• Dengue infection is a multi-systemic and
dynamic disease
• The profile changes from day to day; and
accelerates to the hour during critical phase
• Fluid therapy – mainstay of treatment; prompt
and judicious
• Failure to recognize the dynamic changes à
delay in institution of fluid therapy à
intractable shock and death
4. Pathophysiology of Dengue Fever
Leakage of proteins especially albumin and essential
coagulation proteins
Decompensated plasma leakage
Pathological loss of vascular integrity (vasculopathy)
Release vasoactive mediators ie chymase, leukotrienes
Activation of mast cells and extracellular granules
Dengue virus in vivo (dengue infection)
5. Pathophysiology of Dengue Fever
Massive bleeding eg DIVC / multi-organ failure
If prolonged shock
Inadequate tissue perfusion (tissue hypoperfusion)
Reflex tachycardia + generalized vasoconstriction
Hypovolaemia or shock
Haemoconcentration ( HCT ↑)
Plasma leakage into extravascular space
↑ in vascular permeability (vasculopathy)
6. Risk factors for development of severe dengue1-4
• Obesity - higher risk of developing AKI and severe hepatitis à acute
liver failure
• NSAIDS/ Aspirin use à significantly higher risk of GI bleeding (due to
hemorrhagic gastric erosions, and thrombocytopenia)
• Co-infection with bacteremia
• Pregnancy
• Underlying co-morbids – diabetes, hypertension, cardiac disorders,
end stage renal failure, asthma, immunosuppressive states
• Duration of shock on presentation – prolonged shock
• Bleeding tendencies
• Severe vomiting
• Abdominal pain
• Platelet of less than 50 x 109 cells/L on presentation
• Lactate > 2 on presentation
• Clinical fluid accumulation – pleural effusion, ascites
7.
8. Warning
Signs
Abdominal pain, persistent vomiting,
persistent diarrhea, and spontaneous bleeding
tendency
Raised HCT with
rapid drop in
platelet
Abdominal tenderness, hepatomegaly
>2cm, tender liver, restlessness/
lethargy, clinical fluid accumulation
9. The Phases of Dengue Fever
Febrile
Phase
Critical
Phase
Recovery
Phase
10. Features of Febrile Phase
• Last from 2 - 7 days
• Development of high temperature
• Symptoms – body ache, headache, poor oral
intake, mood changes
• Poor self care and inability to focus on work
• FBC usually normal in the first 2 days
• Symptoms, signs and hematological changes
are difficult to differentiate from other viral
febrile illness
11. Transition from febrile to critical phase
Increased vascular
permeability
Significant plasma
leakage
Development of
warning signs
Deterioration of
patient’s condition
ü Usually at Day 4 to Day 7 of illness
ü Coincides with defervescence
ü Development of warning signs
ü At risk of shock or already in shock
ü Shock is often preceded by warning signs
ü Shock occurs when critical plasma volume is lost through leakage
ü Total WCC may be increased – in patients with severe bleeding at
this stage/ concomitant bacterial infection
12. Do all dengue patients enter the critical phase?
Clinical course of patient without significantly
increased vascular permeability:
ü Fever subsides à general condition improves
and appetite recovers
ü May have leukopenia
ü Mild to moderate thrombocytopenia
13. Features of Recovery phase
• Normalization of vascular permeability à
resorption of extravascular fluid to
intravascular compartment over next 48-72
hours
• Symptoms/signs: Improvement of general
well being, hemodynamically stable, diuresis,
biphasic fever, rashes
• Laboratory: HCT stable, increasing WCC trend,
thrombocytopenia usually persist longer than
leucopenia
14. Summary of clinical problems during each phase
Febrile
Phase
• Dehydration – poor oral intake, insensible fluid loss
from high fever
• High fever à neurological disturbances à
hallucination, febrile
Critical
Phase
• Plasma leakage à hypovolemia and shock
• Severe haemorrhage
• Organ impairment – liver, kidneys and other organs
Recovery
Phase
• Hypervolemia with fluid overload à inappropriate
fluid management
15. Patient Assessment and Evaluation
History Taking
Clinical Examination
Investigations
Diagnosis, phase of disease
and severity
16. What are the other important histories?
ü Date of onset of illness/ fever
ü What are symptoms and severity – ask for warning symptoms
ü How much oral fluids can she take? – quantity and quality
ü How much of urine output? – frequency, volume, and last voiding
time
ü What can she do during the febrile illness?
ü Recent fogging? Family/ neighbour with dengue?
ü Travel history – to endemic areas
ü Medication history – NSAIDs, Aspirin, other OTCs, traditional
medications?
ü Any co-morbids? – asthma, cardiac disorders, CKD, etc
ü Any high risk behaviours – acute HIV seroconversion illness
ü Any jungle trekking/ swimming in waterfalls – leptospirosis/
malaria
17. What to assess in Clinical Examination?
üHaemodynamic assessment – cardiac output
and peripheral perfusion – BP, pulse
pressure, pulse rate, pulse volume, capillary
refill time
üMental state – restless, combative, blunted
response, confused
üHydration state
üClinical evidence of plasma leakage –
especially pleural effusion, ascites
üAny respiratory distress? – complication of
plasma leakage
20. INVESTIGATIONS
• Full blood count (FBC)
– All febrile patient should get baseline FBC during their first visit, if
resources available
– All patients with fever ≥ 3 days, warning signs and/or in shock
MUST have a FBC
– A normal FBC DOES NOT exclude dengue fever
– Platelet should not be interpreted in isolation; its rapid decrease
marks the onset of plasma leakage BUT have no bearing on fluid
management
– FBC at the first 3 days of illness suffices for baseline HCT in acute
cases and serial FBC should be monitored as disease progresses
– Rising HCT with steep drop in platelet suggest progression to
plasma leakage, ie in critical phase of dengue
– A reducing WCC followed by falling platelet count by Day 3 or 4 of
illness is almost suggestive of dengue
21. INVESTIGATIONS (2)
• Dengue-specific diagnostic tests
– NSI/IgM rapid tests or nucleic acid detection –
for confirmation
– Dengue PCR (Molecular testing) – identification
of serotype
• Other tests
– Blood chemistry tests – liver function, glucose,
serum electrolytes and urea and creatinine,
– lactate, acid-bases (pH and HCO3)
– Serum ferritin level, serum fibrinogen,
coagulation profile
22. Making an appropriate diagnosis
1. Day of illness – fever onset?
2. Classification of dengue – dengue fever with
warning signs or severe dengue?
3. Phase of dengue fever – febrile/ critical/
recovery
4. Severity – hepatitis, carditis, encephalitis,
plasma leakage, acute kidney injury,
compensated/ decompensated shock, bleeding
and other organs involvement
5. Does it fulfill criteria for severe dengue? –
severe plasma leakage, severe bleeding and
severe organ involvement
23. Fluid Therapy in Dengue Fever
Principles and Practice
Based on the 3rd Clinical Practice Guidelines for the
Management of Dengue Infection in Adults (2015)
26. Fluid Therapy Principles (5)
• Used for NON-SHOCK dengue patients with
persistent warning signs, increasing or persistently
high HCT
Graded Fluid Bolus Regime
Graded Fluid Bolus Regime
1. Obtain a baseline HCT before fluid therapy
2. Give crystalloids solution (ie. 0.9% saline)
3. Start with 5ml/kg/hr for 1-2 hours, then reduced to 3ml/kg/hr for 2 – 4
hours, and then reduce to 2ml/kg/hr or less according to clinical response
4. If the clinical parameters are worsening and HCT rising, increase the
rate of infusion
5. Reassess the clinical status, repeat the HCT and review fluid infusion
rates accordingly
27. Fluid Therapy Principles (6)
Fluid Responsiveness Parameters
A. Clinical response parameters
ü Improvement of general well being/ mental state
ü Warm peripheries
ü Capillary refill time < 2 secs
ü Stable blood pressure
ü Improving pulse pressure
ü Pulse: Improving volume, reducing tachycardia
ü Improving urine output (aim urine output 0.5ml – 1.0ml/kg/hr)
ü Reducing tachypnoea
B. Laboratory parameters
ü Appropriate decrease in HCT
ü Improvement in metabolic acidosis and lactate clearance
Dengue WITH warning signs – What do you monitor?
28. Fluid Therapy Principles (7)
Other aspects of monitoring
ü Documenting disease progression and defervescence - monitor
until period of 24 – 48 hours after defervescence
ü Monitoring for signs of plasma leakage, shock and bleeding à if
patient progresses to shock à proceed to Algorithm A & B
ü Detailed fluid balance – oral and IV fluids and urine output
ü Blood glucose – every 6 – 12 hours or as indicated
ü Electrolytes and organ functions as indicated by clinical status –
liver function test, acid-bases, renal function, coagulation profile
Dengue WITH warning signs – What do you monitor?
29. Fluid Therapy Principles (8)
Non-obese patients
Maintenance fluid can be calculated based on the following formula :
- 1.2 to 1.5 ml/kg/hour
Adapted : National Clinical Guideline Centre (UK). Intravenous Fluid Therapy:
Intravenous Fluid Therapy in Adults in Hospital. London: Royal College of Physicians
(UK); 2013 Dec. Available from http://www.ncbi.nlm.nih.gov/books/NBK247761/
Overweight and obese patients (BMI >27.5 kg/m2)
Maintenance fluid can be calculated based on adjusted body weight
Adjusted bodyweight (ABW) can be calculated using the formula.
ABW = IBW + 0.4 (actual weight - IBW)**
Ideal bodyweight (IBW) can be estimated based on the following formula.
Female: 45.5 kg + 0.91(height -152.4) cm
Male: 50.0 kg + 0.91(height -152.4) cm
CAUTION : Fluid intake and urine output must be reviewed and adjusted according to
clinical response. Use of volumetric pumps is encouraged, especially in patients
requiring close fluid monitoring.
The normal maintenance requirement for IV fluid therapy
30. Fluid Therapy Principles (9)
• Use isotonic solutions (normal saline, Ringer’s
lactate) – in non-shock patients
• Colloids (albumin and gelatin solution) is
preferred if the blood pressure have to be
restored urgently:
– Hypotensive shock patients
– Repeated shocks – 2nd or 3rd shocks onwards
– After 20-30ml/kg crystalloids and still in shock state
– HCT does not decrease after crystalloid
administration in shock state
What type of IV fluids should we use
31. Fluid therapy Principles (10)
• Step-wise reduction (usually after 24 – 48
hours after defervescence) of IV fluids when:
– signs of recovery (clinical and laboratory
parameters) and/or
– appropriate reduction of HCT WITH stable
hemodynamic state
• Stop immediately when (when approaching
recovery/ in recovery):
– there are features of intravascular compartment
overload à pulmonary edema and respiratory
distress, hypertension with good pulse
When to reduce or stop IV fluid therapy
32. Fluid Therapy Principles (5)
SUMMARY
Febrile phase
1. Limit IV fluids and encourage oral fluids (how much?)
2. Indicated in patients who have severe vomiting, severe
diarrhoea and unable to tolerate orally adequately
Critical phase
1. IV fluids are usually needed for 24 – 48 hours
2. Indicated in patients with increasing/ persistently high HCT
with evidence of plasma leakage despite adequate oral
intake or poor oral intake
Recovery phase
1. IV fluids should be reduced gradually or stopped
2. Continuation of IV fluids can lead to hypervolemia à
pulmonary oedema à respiratory distress
35. Algorithm A – If Clinical Improvement - YES
1) Compensated shock à Initial IV fluid isotonic
crystalloids bolus of 10ml/kg/hr over 1 hour.
2) FBC, HCT, before and after fluid resuscitation, BUSE,
LFT, RBS, PT/APTT, Lactate/HCO3, GXM
1) If improvement à IV fluids isotonic crystalloids
5-7ml/kg/hr for 1-2h
2) Reassess the patient’s clinical condition, vital signs,
pulse volume, capillary refill time, urine output and
temperature of extremities.
3) Monitor FBC, HCT Lactate/HCO3
1) If further improvement, fluid can be reduced further :
3-5ml/kg/hr for 2 - 4 hours
2-3ml/kg/hr for 2 - 4 hours
2) Monitoring of HCT 4 – 6 hourly
36. Algorithm A – If Clinical Improvement - NO
1. If HIGH/ INCREASING HCT à proceed w/ second bolus colloid 10-
20ml/kg/hr for 1 hour and reassess
2. If LOW HCT à Consider significant occult/ overt bleeding. Initiate
blood transfusion.
If clinical improvement after second bolus colloid, reduce IV fluids
further to 7 – 10ml/kg/hr for 1 – 2 hours
1) If further clinical improvement, IV fluids can be reduced further:
5-7ml/kg/hr for 1 -2 hours à 3-5ml/kg/hr for 2 - 4 hours à
2-3ml/kg/hr for 2 - 4 hours
2) Monitor HCT 4 – 6 hourly
38. Algorithm B – If Clinical Improvement - YES
1) Decompensated shock à Initial IV fluid colloids
bolus of 20ml/kg/hr over 15 – 30 minutes
2) FBC, HCT, before and after fluid resuscitation, BUSE,
creatinine, LFT, RBS, PT/APTT, Lactate/HCO3, GXM
1) IV fluids colloids/ crystalloids 10ml/kg/hr for 1 hour
2) Reassess the patient’s clinical condition, vital signs,
pulse volume, capillary refill time, urine output and
temperature of extremities.
3) Monitor FBC, HCT Lactate/HCO3 before and after
fluid resuscitation
1) If further improvement, fluid can be reduced further:
5-7ml/kg/hr for 1 -2 hours
3-5ml/kg/hr for 2 - 4 hours
2-3ml/kg/hr for 2 - 4 hours
2) Monitor HCT 4 – 6 hourly
39. Algorithm B – If Clinical Improvement - NO
1. If HIGH/ INCREASING HCT à 2nd bolus colloid 10-20ml/kg/hr for 30 – 60 minutes and
reassess à if still HIGH/ INCREASING HCT à 3rd bolus colloid 10 – 20 ml/kg/hr over 1 hour
2. If LOW HCT à Consider significant occult/ overt bleeding. Initiate blood transfusion with
fresh blood/ blood products
3. If HCT UNCHANGED à Proceed to Algorithm C (suspect bleeding + leaking; or other causes
of shock)
If improvement after 2nd bolus colloid, reduce IV fluids to
crystalloids/colloids 10ml/kg/hr over 1 hour and reassess
1) If further improvement, IV fluids can be reduced further:
5-7ml/kg/hr for 1 -2 hours à 3-5ml/kg/hr for 2 - 4 hours à
2-3ml/kg/hr for 2 - 4 hours
2) Monitor HCT 4 – 6 hourly
40. Dengue Fever
Non Shock
Without warning
signs
Outpatient
management
With warning
signs
Graded fluid
bolus regime
Maintenance
fluid regime
With Shock (Compensated/
Decompensated)
Compensated
Shock
Algorithm A
Decompensated
Shock
Algorithm B
Decompensated shock
with unchanged HCT
Algorithm C
