Dengue Fever

HARI MUKTI U

ICU & NICU DepartmentHERMINA mother and child Hospital

Jakarta

MANIFESTATION OF DENGUE INFECTION

Symptomatic

Symptomatic


SYMPTOMATIC : Undifferentiated Fever Dengue Fever :

Without haemorrhage With unusual haemorrhage

Dengue Haemorrhagic Fever No shock DSS

PATHOGENESIS OF DENGUE FEVER AND SHOCK

The pathogenesis of DF/DHF is incompletely understood, but epidemiologic studies suggest that it is usually associated with second infections with dengue type 1-4.

Dengue virus is present in the blood in the early acute phase only, generally for 1-5 days.

The incubation periode varies between 3-10 days, with an average 4-6 days.

The major pathophysiological abnormality seen in DHF/DSS is an acute increase in vascular permeability leading to loss of plasma from the vascular compartement.

There is a loss of plasma of more than 20 % in severe cases.

No destructive or inflammatory vascular lessions are observed, suggesting that transient, functional vascular changes due to short-acting mediators occur.

Plasma leakage can lead to shock, which, if uncoreccted, leads to tissue hypoxia, metabolic acidosis and death.


The haemostatic changes in DHF include 3 components : Vascular changes Thrombocytopenia Coagulation disorders


Recogition of Dengue Fever / Dengue Haemorrhagic Fever

Pointer to the clinical diagnosis of dengue infection

1. High continuous fever of 3 days or more2. Headache, backache, retro-orbital pain3. Abdominal pain, vomiting, loose stools4. Petechial haemorrhage and / or spontaneous bleeding5. Rash – generalized flushing/maculopapular/confluent rash

with small islands or normal skin6. Hepatomegaly7. Fall in platelet caount that precedes or occurs

simultaneously with a rise in Hct8. Normal WBC or Leucopenia with relative lymphocytosis9. Normal ESR (< 20 mm/hr)10. Shock

CLASSICAL DFIs an acute febrile illness of 2-7 days duration

(sometimes with two peaks) with two or more of the following manifestations :

• Headache• Rertro-orbital pain• Myalgia/arthralgia• Rash• Haemorrhagic manifestation (petechiae and

positive tourniquet test)• leucopenia

DHFIs probable case of dengue and1. Haemorrhagic tendency evidenced by one or more of

following :– Positive tourniquet test– Petechiae, ecchymosis or purpura– Bleeding from mucosa, injection sites, or other sites– Haematemesis or melaena– thrombocytopenia

2. Evidence of plasma leakage due to increased capillary permeability manifested by one or more of the following :

• A >20 % rise in haematocrit for age and sex• A <20 % drop in Hct following treatmentwith fluids as compared to

baseline• Sign of plasma leakage (Pleural effusion, ascites or

hypoproteinaemia)

DSS

All the above criteria of DHF plus signs of circulatory failure manifested by :

1. Rapid and weak pulse

2. Narrow pulse pressure ( < or equal to 20 mmHg)

3. Hypotension for age

4. Cold and clammy skin and restlessnes

DISEASE COURSEIt is important to differentiate DF to DHF, as some

cases of DHF may progress to DSS.

DF/DHF has an unpredictable course. Most patients have a febrile phase lasting 2-7 days. This is followed by a critical phase which is of about 2-3 days duration.

During this phase, the patient is afebrile, and is at risk of developing DHF/DSS which may prove fatal if prompt and appropriate treatment is not provided.

Since haemorrhage and or shock can occur rapidly, arrangements for rapid and appropriate treatment should be always available.

GRADING THE SEVERITY OF DENGUE INFECTION

It is impoprtant to classify the severity of dengue infection for optimal treatment.

DF/DHF SYMPTOMS LABORATORY

DF fever with two Leukopenia

or more of the occasionally,

following signs Thrombocytopenia

: headache, may be present,

retro-orbital pain, No evidence of

myalgia, arthralgia plasma loss


DHF I Above signs plus Thrombocytopenia

positive tourniquet test < 100.000,

Hct rise > 20 %

DHF II Above signs plus Thrombocytopenia

spontaneous bleeding < 100.000,

Hct rise > 20 %



DHF III Above signs plus Thrombocytopenia

circulatory failure (weak < 100.000,

pulse, hypotension, Hct > 20 %

Restlessness)

DHF IV Profound shock with Thrombocytopenia

Undetectable BP and < 100.000,

Pulse Hct rise > 20 %


TREATMENT OF DENGUE INFECTIONS

Criteria for admission for suspected dengue fever (any of the following ):• Restlessness or lethargy• Cold extremities or circumoral cyanosis• Bleeding in any form• Oliguria or reluctance to drink fluids• Rapid and weak pulse• Capilarry refill time > 2 seconds• Narrowing of pulse pressure (< 20 mmHg) or hypotension• Hct of 40, or rising Hct• Platelet count of < 100.000/µL• Acute abdominal pain• Evidence of plasma leakage, e.g. pleural effusion, ascites

• Febrile Phase

In the early febrile phase, it is not possible to distinguish DF from DHF. Their treatments during the febrile phase are mainly symptomatic and supportive :– Rest– Antipyretics (paracetamol) for fever > 39 0 C– No aspirin or Brufen– No antibiotics is necessery


– ORT or IV therapy may be required for patients with moderate dehydration caused by vomiting and high temperature

– Food should be given according to appetite

Observed for complications for at least 2 days after recovery from fever. Life threatening complications often occur during this phase .

If no evidence of complications and afebrile for 2-3 days, no further observation is necessery


• Afebrile PhaseDengue FeverConstitutional symptoms in patients with DF

after the fall of fever are as during the febrile stage.

Most patients will recover without complication.

Check platelet count and Hct accordingly and provide fluids and electrolyte therapy.


TREATMENT OF DHF GRADE I AND II

The only difference between the DF and DHF grade I is the presence of thrombocytopenia and a rise in HCT (>20%).

All cases are to be admitted. Check Hct and Platelet count immediately on admission and daily subsequently.

Children with DHF grade I do not usually require IV fluid and ORT is sufficient. IV fluid may be needed when the patient is vomiting persistently or severely, or refusing to accept oral fluids.


A reduction in the platelet count to ≤ 100.000/L or less than usually precedes a rise in Hct. A rise in Hct of 20 % or more reflects a significant plasma loss and indicates the needed for IV fluid therapy.

Early volume replacement of lost plasma with crystalloid solution can reduce the severity of the disease and prevent shock. IV fluid therapy before leakage is not recommended.


If rise of Hct > 20% : initiate IV therapy 6 ml/Kg/h (for 3 hours). Check Hct/Vital signs/urine output after 3 hours.

In case of improvement, reduce IV therapy to 3 ml/kg/h (for 3 hours). If further improvement, continue IV therapy at 3 ml/kg/h (6-12 hours) and then discontinue IV therapy.

In mild or moderat cases of DHF grade II, IV therapy may be given for a period of 12-24 hours.

Patients should be monitored an hourly basis. Based on periodic Hct/platelet count determinations, vital signs, and urine output, the treatment should be reviewed and revised.

TREATMENT OF DHF GRADE III AND IV

This is an emergency, and every minute count. All cases of severe DHF and DSS should ideally be maneged in a high dependency unit.

During the afebrile phase of DHF grade IV, vital signs are unstable. The patient, in the early stage of shock, has acute abdominal pain, restleness, cold and clammy skin, rapid and weak pulse.


Immediately after hospitalization, the Hct, platelet count and vital signs should be examined to assess the patient’s condition and IV fluid therapy should be started. The patient requires regular and susteined monitoring.

If the patient has already received about 1.000 ml of IV fluid and the vital signs are still not stable, the Hct should be repeated and :– If the Hct is increasing, IV fluid should be changed to

colloidal solution, or– If the Hct is decreasing, fresh whole blood transfusion

10ml/Kg/dose should given


In case of continued or profound shock when pulse and BP are undetectable, the patient should be given colloidal fluid following the initial fluid bolus.

In the case persistent shock when, after initial fluid replacement and resuscitation with plasma or plasma expanders, the Hct continues to decline, internal bleeding should be suspected. It may be difficult to recognize and estimate the degree of internal blood loss in the presence of haemoconcentration. Fresh whole blood, 100ml/kgBw at one time can be given.

Oxygen should be given to all patients in shock.


Blood transfusion• Blood transfusion is indicated in significant clinical

bleeding, most often haematemesis and malaena.• Persistent shock with rapidly declining Hct level

despite adequte volume replacement indicates significant clinical bleeding which requires prompt treatment with blood transfusion.

• Blood products like fresh frozen plasma, platelet concentrate and cryoprecipitate may be indicated in some cases, especially when consumptive coagulopathy causes significant bleeding.

• Platelet concentrate is required if the platelet count is < 50.000µ/L with bleeding. In the absence of bleeding, prophylactic platelet concentrate is indicated when the platelet count is less than 10.000 to 20.000 µ/L

• In the presence of disseminated intravascular coagulation (DIC), supportive therapy consisting of maintaining circulatory volume, correcting acidosis with sodium bicarbonate and hypoxia with oxygen are required in addition to the use of blood products. Cryoprecipitate (1 unit/5Kgbw) followed by platelets (4 unit/m2 or 10-20 ml/Kg) within 1h and fresh frozen plasma (FFP 10-20 ml/Kg). Frequent clinical assessment and regular coagulation profile (PT, aPTT, Fibrinogen, Platelet and FDP) are mandatory as indicated

LABORATORY DIAGNOSIS

Thera are 3 approaches in the laboratory diagnosis of dengue infection :

Serology

Virus Isolation

Detection of Dengue Ribonucleic Acid

Dengue Fever

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