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Updated Management of Dengue, Imrul

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Good Morning

Updated Management of
Dengue fever
DR. MD. IMRUL KAYES
Indoor Medical Officer
Department of Medicine
M Abdur Rahim Medical College Hospital
Introduction
• Dengue is a disease caused by an Arbovirus.

• Has four serotypes: DENV-1, DENV-2, DENV-3, and DENV-4

• Infection with one serotype confers life long immunity to that


serotype and cross immunity to other serotypes for 2-3 months only.

• Transmitted by Aedes mosquito.

• Regarded as the most important arthropod transmitted human viral


disease.
Current situation in Bangladesh
Pathophysiology of Dengue Infection

Antibody-dependent enhancement or ADE,

T-cell mediated immunopathology,

Complement activation by virus-antibody complexes

Cytokine abundance.
Pathophysiology of DF
Clinical course of DF
Dengue case classification by severity
New revised WHO Dengue case classification by severity

• Dengue without warning signs: Group A


(Send home)
• Dengue with warning signs: Group B
(Referred for in-hospital care)
• Severe dengue: Group C (Require emergency
management)
Clinical Presentation of Dengue
Dengue
fever

Dengue fever
Dengue
without haemorrhagic
Hemorrhage fever

Dengue fever
with Dengue shock
Hemorrhage syndrome

Expanded
dengue
syndrome
Dengue fever
Infection
Myalgia
Headache
Arthralgia

Leukopenia Platelet count GIT


(WBC <5000 ≤150,000 manifestations

Hemorrhage Rising Hct.


5-10%
Dengue Hemorrhagic Fever

Clinical
• High, continuous fever 2-7 days.
• Haemorrhagic manifestations; tourniquet test positive,
petechiae, epistaxis, haematemesis etc.
• Liver enlargement
• Shock
Dengue Hemorrhagic Fever
Laboratory: NOTE: Patients who have
• Evidence of plasma leakage definitive evidence of
• Platelet count plasma leakage,
<100,000cells/mm3. hemorrhagic manifestations,
thrombocytopenia might not
be present as the exception
Evidence of Plasma Leakage

1. Rise in Hct > 20% (eg. In children 35 42 and in


adults 40 48)
(Key
differentiating 2. Circulatory failure: Cold/cold clammy skin,
point between CRFT>2 Sec
Dengue and 3. Tachycardia, weak pulse, narrow pulse pressure
Dengue <20, hypotension.
Haemorrhagic
4. Fluid accumulation – Ascites/ Pleural effusions
Fever)
5. Albumin <3.5 gm/dl
Diagnosis

WBC ≤ 5,000 cells/cu.mm


Tourniquet test positive (positive predictive value =
83%)
Tourniquet Test

Part of the new Triage tool to


WHO case Marker of differentiate
definition for capillary fragility Dengue fever from
Probable Dengue non Dengue illness.
How to do a tourniquet test
11111
Record the patient's ≥10 petechiae/sq
blood pressure Inch area positive.

Inflate the cuff 20 petechiae per 1


midway between inch with
SBP and DBP-5 min sensitivity ≥ 90%
Release pressure for The Standard Lorem Ipsum Passage
1 min and the skin Lorem ipsum dolor sit amet, consectetur adipiscing elit,
sed do eiusmod tempor incididunt ut labore et
examined for petechiae.
How to do a tourniquet test
1. Record the patient's blood pressure
example: 100/70mmHg.
2. Inflate the cuff to a point midway
between SBP and DBP and maintain for
5 minutes (100+70)/2= 85 mm Hg
3. The pressure is released for at least one
minute and the skin below the cuff is
examined for petechiae.
4. 10 or more petechiae in one sq. inch
area considered positive.
Definite positive result when there is 20 petechiae
per 1 inch with a sensitivity of more than 90%
Capillary Refill time
Natural course of DHF

CRITICAL PHASE Convalescent


Febrile Phase Can start from D3 phase: 2-5
High fever for (Leakage phase)
2-7 days Lasts only 24-48 days longer
hours. in adults
Dengue Shock Syndrome
• Cool extremities, delayed CRT( capillary Refilling time)

• Lethargy or restlessness

• Tachypnoea or Kussmaul’s breathing

• Tachycardia, weak pulse

• Narrow pulse pressure: Pulse pressure ≤20 mmHg with increased diastolic
pressure, e.g. 100/80 mmHg

• Hypotension by age defined as SBP<80 mmHg for those aged <5 years or 80 to
90 mmHg for older children and adults
Expanded Dengue Syndrome

• Unusual manifestations with severe organ involvement such as

liver, kidneys, brain or heart associated with Dengue


infection in DHF and also in DF who do not have evidence of
plasma leakage.

• These unusual manifestations may be associated with co-


infections, co-morbidities or complications of prolonged shock
Expanded Dengue Syndrome
Expanded Dengue Syndrome
Points Dengue shock Septic shock
Type of shock Hypovolemic Vasodilatory
Condition of periphery Cold Warm
Vascular capacitance decrease Increase
Changes in BP DBP Pulse Pressure DBP Pulse pressure

Fluid management Avoid aggressive fluid aggressive Fluid may be


needed
Differential Diagnosis
points Dengue Influenza( Flu)

Causative agent Dengue virus( Aedes Influenza


species: Vector) virus( respiratory droplet)

serotypes four( DEN 1-4) Two ( A,B)

symptoms High fever, headache, Runny Nose, sore throat,


Myalgia Cough

incubation 3-14 days 1-4 days

complications Bleeding, shock Pneumonia, MOF,


Myocarditis, Encephalitis

treatment IV fluid Antiviral


Investigations
D1 5 of fever : CBC, NS1 antigen, SGOT and SGPT (Not mandatory but helpful)

After day7 : IgM and IgG Antibodies (Day 5-7 window period)

Follow up testing may be done on 1st afebrile day, but should


be done daily when DHF is suspected
Haematocrit

1. A regular haematocrit is more important for


management than the thrombocytopenia
2. In severe dengue especially with shock hourly
haematocrit is crucial for management
Investigations
• A full blood count (CBC) at the first visit (it may be normal);

• Platelet count and haematocrit daily until the critical phase is over.

• The haematocrit in the early febrile phase -patient’s own baseline.

• Decreasing white blood cell and platelet counts make the diagnosis of
dengue very likely.

• Leukopenia usually precedes the onset of the critical phase and has
been associated with severe disease.
Investigations
• Platelet count haematocrit compared to the baseline, is suggestive
of progress to the plasma leakage/critical phase of the disease.

• In the absence of the patient’s baseline, age-specific population


haematocrit levels could be used as a surrogate during the critical phase.

• If facilities for a full blood count are not available or if resources are
limited CBC or HCtshould be repeated after the 3rd day of illness and in
those with warning signs and risk factors for severe disease.
Group - A criterias
• Able to tolerate orally well, good urine output and no history of bleeding
• Absence of warning signs
• Physical examination:
• Haemodynamically stable
• No tachypnoea or acidotic breathing.
• No tender liver or abdominal tenderness
• No bleeding manifestation
• No sign of third space fluid accumulation
• No alterations in mental state
• Investigation:-Stable serial Hct.
• No other criteria for admission (i.e; co-morbidities, pregnancy, social
factors)
Management plan for Group-A Patient
• Adequate bed rest

• Adequate fluid intake (around 2500 ml or 8-10 glasses for average-sized adults)-
e.g. milk, fruit juice (caution with diabetic patients), oral rehydration solution
(ORS) or barley/rice water/coconut water

• Take paracetamol (not more than 3 grams per day for adults)

• Tepid sponging

• Advised to avoid Acetylsalicylic acid (aspirin), Mefenamic acid, Ibuprofen or other


NSAIDs, Steroids, Antibiotics
Management plan for Group-A Patient

• These patients should be immediately taken to the nearest hospital in


1st afebrile day with worsening of the situation or if any warning sign
is observed

• Observe urine output. If no urine output for 4–6 hours go


immediately to nearby hospital.
Group B criteria (patients with warning
signs)
• No clinical improvement or
worsening of situation before or
during transitions from febrile
to afebrile
• Lethargy, restlessness, giddiness
• Pale, cold ,clammy skin
• Less or no urine output for 4-6
hrs
• > 20% increase in Hematocrit
Group B criteria (patients with warning
signs)
• pregnancy
• infancy
• old age
• obesity
• diabetes mellitus
• hypertension
• heart failure
• renal failure
• chronic hemolytic disease
Fluid Management Plan for Group-B
patients
• Obtain a reference haematocrit before IV fluid therapy begins.

• Intravenous fluid therapy in DHF during the 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.
Types of Fluids used in Dengue
CRYSTALLOIDS
1. 0.9% NaCl (isotonic normal saline solution) (0.9% NS) (Preferable)
2. 0.45% half strength normal saline solution (0.45% NS) (For children <6 months)
3. 5% dextrose in Ringer's lactate solution (5% DRL)
4. 5% dextrose in acetated Ringer's solution (5% DRA)
5. Hartman solution (Preferable)
COLLOIDS
1. Dextran-based: Dextran 40, Dextran 70
2. Starch based (6% HES):Voluven, Plasmasol (6% hydroxyl ethyl ester with normal saline)
Volulyte (6% hydroxyl ethyl ester with balanced electrolyte)
3. Gelatin
4. Human Albumin
5. Plasma
6. Haemaccel
7. Blood and blood components
Fluid Requirement
• Both oral and intravenous, in critical phase (48 hours) is calculated as:

• M+ 5% (maintenance + 5% deficit)

• 5% deficit is calculated as: 50 ml/kg up to 50kg


Calculation for Maintenance intravenous
fluid:
By following method :

1. Ludan formula
2. Holliday –Segar formula
Calculation for Maintenance intravenous
fluid:
Ludan formula:
4 ml/kg/hr for first 10 kg body weight
+2 ml/kg/hr for next 10 kg body weight
+ 1 ml/kg/hr for subsequent kg body weight
Child of 20 kg
Maintenance = 4ml × 24hr ×10kg
+ 2ml ×24hr ×10kg =6 ×24 ×10= 1440 ml
Holliday -Segar formula
Fluid calculation
• A child wt 20 kg Formulla : M+ 5% (maintenance + 5% deficit)

50 ml/kg x 20 = 1000 ml.


• Deficit of 5%=

Maintenance is . Child of 20 kg
Maintenance = 4ml × 24hr ×10kg
+ 2ml ×24hr ×10kg =6 ×24 ×10= 1440 ml

2500 ml
• Hence, the total of M + 5% = 1440 ml +1000 ml= 2440 ml

• This 2500 ml is to be administered over 48 hours in non shock patients.


Fluid calculation in Obese patient
overweight/obese patients calculate normal maintenance fluid
based on ideal body weight (IBW), using the following formula:

Female: 45.5 kg + 0.91(height-152.4) cm or


45.5 + 2.3x every inch more than 5 feet
Male : 50.0 kg + 0.91(height-152.4).cm or
50.0 kg + 2.3x every inch more than 5 feet
Fluid Management Plan for Group-B patients

Hct. <20% • 1.5 mL/kg/hr ( children ) or 40 mL/hr( adults)

Hct. 20-25% • 3 ml/kg/hr ( children) or 80 mL/hour( adults)

Hct. >25% • 7-10 ml/kg/hr or 100 to 500 mL/hour for adults

Drop Calculation
(ml/h÷4 = drops/min)
• 40ml/hour = 10 drops/min
• 80ml/hour = 20 drops/min
• 100ml/hour = 25 drops/min
• 200ml/hour = 50 drops/min
Pulse pressure <20 mmHg, BP<
90/60,Fainting

• Immediate Hct, RBS, Oxygen


• IV NS 500ml/hr ( 10ml/kg/hr in child)
• If Improved then titrate the fluid
250/150/100/80/40
• If not improved the Check HcT
ABCS , vital signs

Hct falling/ deteriorates: Whole fresh blood 1unit


Hct rising/ deteriorates: Colloid 10ml/kg (500ml/hr)

Hct decreases> 10 points/ Deteriorates : Whole blood ABCS correction


Dialysis
Hct In target : titrate Fluid dose
Profound Shock(Pulse, BP Non Shock with fluid Overload
recordable) Colloid + IV frusemide

• Immediate Hct, RBS, Oxygen


• IV NS 500ml ( 10-20ml/kg in child) in 15-30 min

• If Improved : titrate the fluid


500/250/150/100/80/40
• If not improved : Repeat 2nd Bolus IV Crystalloid

Hct falling/ deteriorates/overt bleeding/concealed Hx: Whole fresh blood


1unit
Hct rising/ deteriorates: Colloid 10ml/kg (500ml/hr)

Hct decreases> 10 points/ Deteriorates : Whole blood ABCS correction


Dialysis
Hct In target : titrate Fluid dose
Fluid Overload Management
Signs of fluid Overload( Puffy face,
Abdominal swelling, Dyspnoea)
Lung: Crepitation

Oxygen, Urinary cathter, Check ABCS, Hct, Vitals


Critical phase/shock: Colloid( Dextran 40) 500ml/hr+ IV
frusemide
Reabsorption phase( Wide Pulse pressure): Stop fluid+ IV
frusemide

Improved: Stop Iv fluid Repeat IV frusemide (If


needed) ABCS correction
Hct falling/ deteriorated: whole blood Dialysis
Indications of Colloid in Dengue

Patients with massive plasma leakage

Patients with shock with rising Hct.

Those not responding to the minimum volume of crystalloid

Those with pulse pressure < 10 mm Hg, who need urgent restoration of BP
Indications for Platelet Concentrate
Very limited role of platelet transfusion
1. Very Severe Thrombocytopenia who need urgent
surgery.

2. Clinical judgement of the treating physician.


Dengue with Organopathy (Expanded
Dengue Syndrome) : Management Issue

In myocarditis with raised Troponin I and


ECG changes (Bradycardia, Tachycardia,
ST-T changes) injudicious use of
antiplatelet, anticoagulant or intervention
(e.g. pacemaker and others) should be
avoided (20% fluid is to be reduced).
Dengue with Organopathy (Expanded
Dengue Syndrome) : Management Issue

In encephalitis,
judicious use of
steroids can be given.
(Dexamethasone:
0.15 mg / kg 6-8
hourly for 3-5 days)
Dengue Encephalopathy (management)
• O2 Therapy
• Fluid: 20% fluid reduction
• Colloid Monitoring:
• Frusemide in fluid overload • Blood sugar
• Lactulose • Correction of electrolytes
• H2 receptor blocker • Bleeding episodes
• Rifaximin • I/O chart
• FFP • Any convulsion
Impact of dengue on pregnancy and delivery.

• Early Abortion (3%-13%).


• Embryopathy specially neural tube defect.
• Antepartum haemorrhage (APH) due to retro placental hemorrhage or abruptio placenta.
• Preterm birth (3%-33%).
• Low-birth weight
• Fetal Distress.
• IUD or Still birth (4.7%-13%.).
• Increased incidence of caesarean deliveries.
• Post-Partum Haemorrhage (PPH). Fetal Distress.
• IUD or Still birth (4.7%-13%.).
• Increased incidence of caesarean deliveries.
• Post-Partum Haemorrhage (PPH).
Pregnancy & Dengue Management

Medical Hospital platelet >50k/mm3


MR should not
termination is to
allow delivery Blood should be
be avoided advised available

Dengue/ Suspected Avoid elective No


patients with No
C/S & induction instrumental
pregnancy must
admit to hospital of labour episiotomy delivery
Active
In Preterm labour Injection steroid Misoprostol /
management in
advice delay in I/V to be given for Tranexamic acid can be
third stage of administered slowly
delivery Premature delivery
labour
Dengue in infancy
• Symptom: fever, runny nose, cough, loose motion, vomiting, seizures,
• Signs: high fever, sore throat, dehydration, bulged fontanel, neck rigidity,
hepatomegaly, splenomegaly
• Inv: Leukopenia unlikely, hypoglycemia, hyponatremia, hypocalcemia,
raised AST.
• USG: hepato-splenomegaly, ascites CXR: pleural effusion
• Management: Avoid Over hydration, Fluid in leakage phase
• Baby saline < 6 months infants;
• 5% dextrose in Normal saline in infants > 6 months
• Colloids (dextran 40) should be considered when high rates of
crystalloids are required
Mandatory Surgery

• Hematological and biochemical investigations should be available


immediately prior to surgery.

• Fresh blood and or platelet concentrate also has to be made


available prior to surgery.

• Platelet count should be raised up to 100000/mm3.

• Fluid replacement should be according to stage the of DHF.


Dengue in IHD
• Aspirin/clopidogrel should be avoided for certain days, until the
patient recovers from DHF.

• Patients with IHD are more prone to cardiac dysrhythmia, cardiac


failure and thrombo-embolism

• Loop diuretics should be used cautiously and in a timely way: after


achieving haemodynamic stability

• In dengue with high fever, tachycardia and increased metabolic


demands may precipitate decompensation of cardiac functions..
Hypertension & Dengue Management

Hypotension is a late sign of shock in hypertensives.

In patients with uncontrolled HTN a BP reading that is considered normal for age
may in reality be low

What is considered as “mild” hypotension may in fact be profound.

Patients with chronic hypertension should be considered to be hypotensive


(MAP) declines by 40 mmHg from the baseline, even if it still exceeds 60 mmHg.
• (For example, if the baseline MAP is 110 mmHg, a MAP reading of 65 mmHg should be considered as significant hypotension.
Diabetes Mellitus and Dengue:

• Hyperglycaemia results in osmotic diuresis and worsens


intravascular hypovolaemia.

• Not correcting the hyperglycaemic state exacerbates the shock state

• Hyperglycaemia also puts patients at risk of bacterial infection.


CKD & Dengue
Challenges in fluid management
• Narrow window of fluid tolerance.
• Urine output: Unreliable indicator
• Limited effect of diuretics.
• Patient on MHD preferably dialysis session should be deferred.

Acid base balance and electrolyte balance


• Patients with CKD are at risk of metabolic acidosis and electrolyte imbalance which
will become worse during dengue shock. If these persist after adequate fluid
replacement, dialysis may be considered after haemodynamic stability is achieved.

Platelet dysfunction
• Platelet dysfunction, well recognized in CKD together with severe thrombocytopenia
with or without coagulopathy, predispose the dengue patient to severe bleeding that
may be difficult to control.
Discharge Criteria
• No fever for at least 24 hours without antipyretic drugs
• At least two days have lapsed after recovery from shock
• Good general condition with improving appetite
• Normal HcT at baseline value or around 38 -40 % when baseline value is not known
• No distress from pleural effusions
• No ascites
• Platelet count has risen above 50,000/mm3
• No other complications
Vaccination
• One dengue vaccine has been licensed, Dengvaxia® (CYD-TDV),
developed by Sanofi Pasteur Inc.
• It was first licensed in Mexico in December 2015 for use in individuals
9-45 years of age living in endemic areas, and is now licensed in 20
countries.
• Dengvaxia® is approved in US for use in individuals 9 through 16 years
of age with laboratory confirmed previous dengue infection and living
in endemic areas.
• CYD-TDV is a live recombinant tetravalent dengue vaccine developed
by Sanofi Pasteur (CYD-TDV), given as a 3-dose series on a 0/6/12
month schedule
Reference:
1. Pocket Guideline for Dengue Clinical Case Management (2022) by
Bangladesh Society of Medicine.
2. National Guideline for Clinical Management of Dengue Syndrome;
4th Edition, 2018; DGHS.
3. www.who.int/news-room/questions-and-answers/item/dengue-vac
cines
4. www.fda.gov/vaccines-blood-biologics/dengvaxia
Thank
You

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