Dengue Shock with Severe Plasama Leakage Management

Severe dengue occurs as a result of secondary infection with a different virus serotype.
The onset of shock in dengue can be dramatic, and its progression relentless.

The pathogenesis of shock 

It is known that endothelial dysfunction induced by cytokines and chemical mediators occurs.

Dengue viruses are transmitted to humans by infected mosquitoes :Aedes aegypti and Aedes albopictus. There are four serotypes (species) of the dengue virus: types 1, 2, 3, and 4.
DEN-1 infection, followed by DEN-2 infection, has been reported to be associated with worse outcome

Two Theories :

• One theory, DHF/DSS is caused by more virulent strains of the dengue virus. 
• The other theory suggests that DHF/DSS results from abnormal and exaggerated host immune responses – in particular, the production of dengue virus cross-reactive antibodies – which augments the infection. 

In primary infection with the dengue virus, cross-reactive antibodies that lack neutralizing activity are produced.
During secondary infection by a different serotype, the dengue virus and non-neutralizing antibodies form virus–antibody complexes.


Patients with severe dengue die of progressively worsening shock and multiorgan failure.
The exact mechanism as also occurs in severe sepsis.

3 Hari pertama : yang tinggi adalah Sitokin tipe Th1 (TNF-α, IL-2, IL-6, and IFN-γ)
Hari berikutnya :Sitokin tipe Th2 (IL-10, IL-5, and IL-4)

Yang terinfeksi adalah :  monocytes and endothelial cells
Monosit mengeluarkan TNF-α yang merupakan biang penyebab plasma leakage.
Basophils and mast cells yang terinfeksi menghasilkan IL-1 and IL-6
Lymphocytes yang terinfeksi menghasilkan IFN-α and IFN-γ

IFN-α levels tinggi pada pasien DF dan DHF
The cytokines TNF-α, IL-6, IL-8, IL-13, IL-18, and cytotoxic factor are significantly elevated in DHF as compared with DF.
Levels of IL-13, IL-18, and IL-8 correlate positively with increasing grades of DHF.

The dengue virus is also known to infect endothelial cells and cause direct damage through apoptosis
Increased endothelial cell expression of VCAM-1 and ICAM-1 occurs, and TNF-α is a key intermediary in this process.
Dengue infections are associated with reduced numbers of CD4+ T-cells, CD8+ T-cells, and natural killer cells.

Clinical Features

1. Increased vascular permeability results in third space fluid loss, leading to pleural effusions, pericardial effusions, ascites, non-cardiogenic pulmonary edema and, subsequently, hypotension. 
2. Right hypochondrial pain -->  acalculous cholecystitis is a characteristic feature of DHF.
3. Myocarditis can result in heart block and can be severe enough to result in acute heart failure with global hypokinesia and acute cardiac dilatation.
4. Lactic acidosis, a result of the sluggish circulation, possibly contributes to myocardial depression in severe cases. 
5. Acute hepatic derangement can occur though fulminant liver failure is rare.
6. Acute renal failure is usually secondary to hypotension in shock syndrome and is associated with increased mortality.

Management

The only known effective treatment in DSS is timely and aggressive fluid resuscitation.
Fluids used for volume expansion include normal saline, Ringer lactate, 5% glucose diluted 1:2 or 1:1 in normal saline, plasma, plasma substitutes, or 5% albumin.
There is no evidence that colloids are superior to crystalloids for resuscitation.
No difference was seen between the fluid requirements of crystalloids or colloids.

In the case of shock, fluids should be administered as a rapid (over less than 20 min) intravenous bolus of 10–20 ml/kg body weight.
If shock persists, and the hematocrit is rising, plasma, plasma substitutes, or albumin should be given as a rapid bolus and repeated if necessary to a total dose or 20–30 ml/kg of colloid.
If shock persists, and particularly if the hematocrit decreases, fresh whole-blood transfusion may be required (10 ml/kg).
Platelet transfusions are usually given to patients who develop serious hemorrhagic manifestations or have very low platelet counts.
Blood transfusion is required in patients with severe hemorrhage.

In patients with ARDS, high-dose corticosteroids have been shown to reduce the levels of the cytokines TNF-α, interleukin (IL)-1β, IL-6, and IL-8. However,

Replacement doses of corticosteroids are thought to improve mortality and duration of shock in patients with septic shock who showed a blunted adrenocortical response to the ACTH stimulation test.Cortisol levels are low in a subgroup of patients with septic shock, and a blunted cortisol response to ACTH stimulation is associated with poor prognosis.
In contrast, cortisol levels are high in DHF during both the acute and convalescent phases. Although some clinicians use steroids in treatment, there is currently no clear evidence to justify the use of corticosteroids in the treatment of DSS.