Management of dengue

1. Management of
Severe Dengue

2. Introduction
• Dengue infection is caused by dengue virus which is
a mosquito-borne flavivirus. It is transmitted by
Aedes aegypti and Aedes albopictus.
• There are four distinct serotypes, DENV-1,2,3 and 4.

3. Clinical Features
• The incubation period for dengue infection is 4-7
days (range 3-14)
• After the incubation period, the illness begins
abruptly and will be followed by three phases:
I. Febrile
II. Critical
III. Recovery phase

4. Febrile Phase
• High grade fever suddenly and usually lasting 2-7 days
• Accompanied by facial flushing, rash, generalized body
ache, vomiting and headache.
• Some patients have sore throat, injected pharynx and
conjunctival injection.
• Mild haemorrhagic manifestations like petechiae and
mucosal membrane bleed may be present during this
phase.

5. Critical Phase
• Normally occurs after third day of fever (may occur earlier) or
around defervescence.
• Indicated by rapid drop in temperature, platelet counts, increase
in capillary permeability, third space plasma leakage or organ
dysfunction.
• Critical phase lasts about 24-48 hours
• Abdominal pain, persistent vomiting and/or diarrhea,
restlessness, altered conscious level, clinical fluid accumulation,
tender liver or mucosal bleed are the clinical warning signs of
dengue infection with high possibility of rapid progression to
severe dengue.

6. Recovery Phase
• After 24-48 hours of critical phase, usually
plasma leakage stops followed by
reabsorption of extravascular fluid.
• Patient’s general well being improves,
appetite returns, gastrointestinal symptoms
improve, haemodynamic status stabilises and
diuresis ensues.
• Some patient may have a classical rash of
“isles of white in the sea of red” with
generalised pruritus.

8. Classification of Dengue

9. Investigations
• FBC :
• Decrease in WCC followed by platelet count + hemoconcentration.
• In recovery phase, WCC will normalize first followed by platelet
• Median HCT levels among Malaysians:
• Male ≤ 60 years – 46%
• Male > 60 years – 42%
• Female (all age groups) – 40%
• Other blood tests: RP, Lactate, Blood gases, Troponin, CK

11. Diagnostic Tests
1. Rapid combo test (RCT)
• Detects NS1 antigen and dengue IgM/IgG antibodies
• Generally RCT tests can be read within 15-20 minutes
• Sensitivity is 93.9% and specificity is 92%

12. 2. Dengue Antigen and Serology Tests by ELISA
I. Non-Structural Protein-1 (NS1 Antigen)
o NS1 antigen is a highly conserved glycoprotein that seems to be essential
for virus viability
o The sensitivity of NS1 antigen detection drops from day 4-5 of illness
onwards and usually becomes undetectable in the convalescence phase
o Presence after day 5 may predict severe dengue
II. Dengue IgM test
o In primary dengue, detected after D5 of illness in 80% of cases
o Almost 93%-99% of cases will have detectable IgM from day 6 through
day 10
o In the event of a negative IgM result, a repeat serum should be collected
after five days
o In secondary dengue infections, IgM appears earlier or at the same time
frame but usually at lower titres compared to primary dengue
III. Dengue IgG test
o In primary and secondary dengue infection, dengue IgG was detected in
100% of patients after day 7 of onset of fever

13. Management
• In dengue patients without co-morbidities who can tolerate orally,
adequate oral fluid intake of two to three liters daily should be
encouraged. These patients may not require intravenous (IV) fluid
therapy.
• IV fluid should be instituted in dengue patients with:
• Vomiting, unable to tolerate oral fluids or severe diarrhea
• Increasing haematocrit (with other signs of ongoing plasma leakage) despite
increased oral intake
• In patients with persistent warning signs with increasing or persistently
high HCT, the graded fluid bolus may be initiated with caution.
• Crystalloids solution should be the fluid of choice for non-shock
dengue patients.

17. Management of Bleeding
• Gastrointestinal bleeding – one of the most
common hemorrhagic manifestation in
dengue, common causes are hemorrhagic
gastritis, peptic ulcer and oesophageal ulcer
• Fluid + Transfusion of packed cells and
blood products + administration of PPI
• Endoscopic therapy indicated if having
persistent bleed despite optimum medical
therapy
• Prophylactic transfusion of packed cells /
blood components only indicated when
invasive procedure / operation is decided.

18. Management of Hepatitis
• Usually self-limiting
• Appropriate fluid management
• Monitoring of haemodynamic parameters
• Regime for IV NAC for treatment of acute liver
failure (Controversial)
• 100mg/kg/day as infusion for 5 days
• 150mg/kg infusion over 15-60 minutes, followed by
12.5mg/kg/hour for 4 hours, then 6.25mg/kg/hour

19. Management of Cardiac
Complications in Dengue Infection
• Manifests as arrhythmia, functional myocardial
impairment and myocarditis
• Investigations: ECG, Cardiac markers, Echo
• Common ECG changes: Sinus bradycardia, AV block, AF,
T wave and ST segment abnormalities
• Cautious fluid resuscitation
• No evidence to support use of beta interferon,
corticosteroids / IV immunoglobulins

20. Management of Neurological
Complications in Dengue
• Manifests in a wide spectrum of neurological
complications: Encephalitis, intracranial bleed,
meningitis, meningoencephalitis, myelitis, acute
disseminated encephalomyelitis (ADEM), Guillain-
Barre Syndrome, myositis
• Treatment mostly supportive, manage high ICP
• Adjuvant use of corticosteroids, IVIG,
plasmapheresis may be considered.

21. Management of Hemophagocytic
Syndrome
• Potentially fatal syndrome of extreme immune
activation leading to cytokine storm.
• Presents with unexplained persistent fever or
resurgence of high grade fever after defervescence.

22. • Mainstay management is mainly supportive
• For severe HPS, IV methylprednisolone or
dexamethasone (with or without IVIg) may be
helpful if started early.
• Steroids should be tapered off as patients improve
clinically and biochemically
Management of Hemophagocytic
Syndrome

24. Intensive Care Management of
Dengue Infection
• Indications for mechanical ventilation in severe dengue
• Persistent shock
• Acute respiratory failure 2’ massive pleural effusion with or without
ascites, fluid overload
• Severe metabolic acidosis
• Airway protection
• In patients with Met Acidosis, respiratory support should be
considered despite relatively normal arterial blood pH.
• When actual PaCO2 is higher than expected to compensate for
acidosis, consider intubation and mechanical ventilation

25. • IV fluid therapy as per algorithm outlined, inotrope and
vasopressors may be used as temporary measure while
resuscitating
• Cardiogenic shock – Dobutamine
• Septic shock – Noradrenaline
• If central line needed, avoid subclavian approach as not
accessible to direct compression, ultrasound guidance is
recommended.
• If platelets are to be transfused, CVC should be done
within 4 hours following transfusion.
• American Association of Blood Banks suggested for transfusion
in patients with platelet < 20 × 10^9 cells/L

26. References
• Dr Mahiran Mustafa. 2015. CPG Management Of
Dengue Infection In Adults. Putrajaya, Malaysia: Malaysia
Health Techonology Assessment Section
• Kaufman RM, Djulbegovic B, Gernsheimer T, et al.
Platelet transfusion: a clinical practice guideline from the
AABB. Ann Intern Med. 2015;162(3):205‐213.
doi:10.7326/M14-1589
• J Nicholas Brenton. 2018. Acute Disseminated
Encephalomyelitis Treatment & Management. Retrieved
from https://emedicine.medscape.com/article/1147044-
treatment