Dengue

Revised Dengue Clinical Case Management Guidelines 2011

FMIIC Martinquilla, Mae Caridad R.

Most rapidly spreading arthropod-borne viral disease of the world

All-year round disease in the Philippines

high incidence during rainy months and is more prevalent in urban areas

VIRUS• Dengue virus (DEN)- small single stranded

RNA virus

• Has 4 distinct serotypes (DEN- 1 to 4)

• “Asian” genotypes of DEN-2 and DEN-3 are frequently associated with severe disease accompanying dengue infections

VECTOR• Family of Flaviviridae

• 1) female Aedes aegypti mosquito 2) Aedes albopictus

• generally “daybiters” with 2 peaks of biting time:

a) at dawn, just before sunrise b) at dusk, just before sunset

VECTOR• Resting habit: 1. Aedes aegypti - cool, dark corners

of the house 2. Aedes albopictus - outdoors in

clearing vegetations

• Flying habits: - average light range is 50 meters

- farthest distance is only within 200- 400 meter radius from breeding places

HOST• incubation period of 4-10 days

• Primary infection:• is thought to induce lifelong protective immunity

to the infecting serotype• Individuals suffering an infection are protected

from clinical illness with a different serotype within 2-3 months of the primary infection but with no long-term cross-protective immunity

HOST• virus enters via the skin while an infected

mosquito is taking a bloodmeal

• acute phase of illness- the virus is present in the blood

• Defervescence- clearance of the virus from the blood

HOST• Humans- main amplifying host of the virus

• Dengue virus circulating in the blood ofviraemic humans is ingested by female mosquitoes during feeding

• The virus then infects the mosquito mid-gut and subsequently spreads systemically over a period of 8-12 days (extrinsic incubation)

HOST• the virus can be transmitted to other

humans during subsequent probing or feeding

1. Increased capillary fragility2. Thrombocytopenia3. Decreased Blood Coagulation Factors

1. Increased capillary fragility

• Early febrile stage• (+) tourniquet test• Hemorrhagic tendencies of a patient

2. Thrombocytopenia

• may be associated with alterations in megakaryocytopoieses by the infection of human haematopoietic cells and impaired progenitor cell growth

• Which results in platelet dysfunction (platelet activation and aggregation) and increased destruction or consumption (peripheral sequestration and consumption).

3. Decreased blood coagulation factors

• Fibrinogen and factors II, V, VII, IX

• Prolonged CT-BT, PT, PTT

Incubation period of 4-10 days

3 phases of the disease

◦FEBRILE◦CRITICAL◦RECOVERY PHASE

Usually lasts 2–7 days

Sudden high-grade fever

facial flushing, skin erythema, generalized body ache, myalgia, arthralgia, headache, sore throat, injected pharynx, conjunctival injection, anorexia, nausea and vomiting are common

Mild hemorrhagic manifestations- Petechiae- Mucosal membrane bleeding

liver is often enlarged and tender after a few days of fever

Earliest manifestation in CBC:- Progressive increase in WBC

Marks the beginning of the critical phase:• Usually on day 3-7 of the

illness • increase in capillary permeability in parallel with

increasing haematocrit levels• temperature has dropped to less than 37.5- 38 C

and remains below this level

The period of clinically significant plasma leakage usually lasts 24–48 hours

Progressive leukopenia followed by a rapid decrease in platelet count usually precedes plasma leakage

Without an increase in capillary permeability improve Dengue without warning signs

With increased capillary permeability deteriorate (result of lost plasma volume) Dengue with warning signs

Shock- occurs when a critical volume of plasma is lost through leakage; further deterioration◦ Often preceded by warning signs

Warning SignsAbdominal pain or tenderness

Persistent vomiting

Clinical signs of fluid accumulation

Mucosal bleeding

Lethargy; restlessness

Liver enlargement

Labs: ↑ in hematocrit and/or ↓ platelet

takes place in the following 48–72 hours after critical phase

What happens in recovery phase?◦ a gradual reabsorption of extravascular compartment

fluid◦ General well-being improves◦ appetite returns◦ gastrointestinal symptoms abate ◦ haemodynamic status stabilizes ◦ diuresis ensues

Hermann’s rash- “isles of white in the sea of red”

The haematocrit stabilizes or may be lower due to the dilutional effect of reabsorbed fluid

White blood cell count usually starts to rise soon after defervescence while the recovery of platelet count is typically later than that of white blood cell count.

1. Febrile phase- dehydration- febrile seizure

2. Critical phase- shock- hemorrhage- organ impairment

3. Recovery phase- hypervolemia

Probable dengue◦ Lives in or travels to dengue-endemic area, with fever plus any

of the following: Headache Nausea Body malaise Vomiting Myalgia Arthralgia Retro-orbital pain Anorexia Diarrhea Flushed skin Rash (petechial, Hermann’s rash ) AND

CBC (leukopenia with or without thrombocypenia) and/or dengue NS1 antigen test or dengue IgM antibody test

Confirmed: viral culture isolation and PCR

Lives in or travels to dengue-endemic area, with fever lasting for 2-7days, plus any one of the following:

Confirmed: viral culture isolation and PCR

Warning Signs

Abdominal pain or tenderness

Persistent vomiting

Clinical signs of fluid accumulation

Mucosal bleeding

Lethargy; restlessness

Liver enlargement

Labs: ↑ in hematocrit and/or ↓ platelet

Lives in or travels to a dengue-endemic area with fever of 2-7 days, and any of the above clinical manifestation for dengue with/without warning signs plus any of the ff:◦ Severe plasma leakage

Shock Fluid accumulation with respiratory distress

◦ Severe bleeding◦ Severe organ impairment

Liver: AST or ALT >/= 1000 CNS: e.g. seizure, impaired consciousness Heart: e.g. myocarditis Kidneys: e.g. renal failure

Step 1: Overall Assessment◦ History◦ Physical Examination◦ Investigation

Step 2: Diagnosis, Assessment of Disease Phase and Severity

Step 3: Management◦ Group A◦ Group B◦ Group C

Treatment (by type of patient)

GROUP A- Patients who may be sent home

- Able to tolerate adequate volumes of oral fluids

- Able to pass urine at least once every 6 hours

- Do not have any warning signs particularly when fever subsides

What should be done?◦ Adequate bed rest◦ Adequate fluid intake◦ Paracetamol◦ Tepid sponging◦ Look for mosquito breeding places and eliminate

them

What shoud be avoided?◦ NSAIDs◦ Antibiotics are unecessary

If any of the ff is observed, take immediately to nearest hospital: ◦ Bleeding,vomiting, abdominal pain, drowsiness,

pale, cold and clammy hands and feet, difficulty in breathing

Warning signs

Co-existing conditions that may make dengue management more complicated such as pregnancy, infancy, and old age, obesity, diabetes mellitus, renal failure, chronic hemolytic diseases, etc

Social circumstances such as living alone or living far from health facility or without a reliable means of transport

Dengue without warning signs

Encourage oral fluids Isotonic solutions Maintenance IVF

◦ Holiday-Segar Method

Dengue without warning signs

Monitor for the ff:◦ Temperature pattern ◦ Volume of fluid intake and losses◦ Urine output- volume and frequency◦ Warning signs◦ Hematocrit◦ White blood cells◦ Platelets

Dengue with warning signs

1.Obtain a reference hematocrit

1.Give only isotonic solutions- Start with 5-7ml/kg/hour for 1-2 hours, then- Reduce to 3-5ml/kg/hour for 2-4 hours, and then- Reduce to 2-3 ml/kg/hour or less according to clinical

response

2.Reassess clinical status and repeat hematocrit

Dengue with warning signs

4. If Hct remains the same or rises only minimally, continue with the same rate (2-3 ml/kg/hour) for another 2-4 hours

5. If there are worsening vital signs and rapidly rising hematocrit, increase the rate to 5-10 ml/kg/hour for 1-2 hours

6. Reassess clinical status, repeat hematocrit and review fluid infusion rates accordingly

Dengue with warning signs

7. Reduce intravenous fluids gradually when the rate of plasma leakage decreases towards the end of the critical phase.- urine output and/or oral fluid is/are adequate or- hematocrit decreases below the baseline value in stable patient

Dengue with warning signs

should be monitored by health care providers until the period of risk is over

A detailed fluid balance should be maintained

Parameters that should be monitored include vital signs and peripheral perfusion, urine output, haematocrit, blood glucose, and other organ functions

severe plasma leakage leading to dengue shock and/or fluid accumulation with respiratory distress

severe haemorrhages

severe organ impairment (hepatic damage, renal impairment, cardiomyopathy, encephalopathy or encephalitis)

Patients with Compensated Shock

1. Start IVF resuscitation with isotonic fluid at 5-10 ml/kg/hr over 1 hour. Reassess patient’s condition and decide depending on the situation

2. If the patient’s condition improves, intravenous fluids should be gradually reduced to:- 5-7 ml/kg/hr for 1-2 hours, then- to 3-5 ml/kg/hr for 2-4 hours, then- to 2-3 ml/kg/hr and then- to reduce further depending on the hemodynamic status of the patient, which can be maintained for up to 24-48 hours

Patients with Compensated Shock

3. If the vital signs are still unstable, check hematocrit after the first bolus:- if Hct increases or still high (>50%) , repeat a 2nd bolus of crystalloid solution at 10ml/kg/hr for 1 hour . After this 2nd bolus, of there is improvement, then reduce the rate to 7-10ml/kg/hr for 1-2 hours, then continue to reduce as above

Patients with Compensated Shock

if hct decreases compared to the intial reference hematocrit, this indicates bleeding and the need to cross match and transfuse blood as soon as possible

Patients with Hypotensive Shock

Patients with hypotensive shock should be managed more vigorously

1. Initiate intravenous fluid resuscitation with crystalloid or colloid solution (if available) at 20 ml/kg as a bolus given over 15 minutes to bring the patient out of shock as quickly as possible

Patients with Hypotensive Shock

2. If the patient’s condition improves, give a crystalloid/colloid infusion of 10 ml/kg/hr for one hour. Then continue with crystalloid infusion and gradually reduce to 5–7ml/kg/hr for 1–2 hours, then to 3–5 ml/kg/hr for 2–4 hours, and then to 2–3 ml/kg/hr or less, which can be maintained for up to 24–48 hours

Patients with Hypotensive Shock

3. If vital signs are still unstable (i.e. shock persists), review the haematocrit obtainedbefore the first bolus. If the haematocrit was low (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to crossmatch and transfuse blood as soon as possible

Patients with Hypotensive Shock

4. If the haematocrit was high compared to the baseline value, change intravenous fluids to colloid solutions at 10–20 ml/kg as a second bolus over 30 minutes to one hour. After the second bolus, reassess the patient. If the condition improves, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, then change back to crystalloid solution and reduce the rate of infusion as mentioned above. If the condition is still unstable, repeat the haematocrit after the second bolus.

Patients with Hypotensive Shock

5. If the haematocrit decreases compared to the previous value this indicates bleeding and the need to cross-match and transfuse blood as soon as possible

Patients with Hypotensive Shock

6. If the haematocrit increases compared to the previous value or remains very high (>50%), continue colloid solutions at 10–20ml/kg as a third bolus over one hour. After this dose, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, then change back to crystalloid solution and reduce the rate of infusion as mentioned above when the patient’s condition improves

Patients with Hypotensive Shock

7. Further boluses of fluids may need to be given during the next 24 hours. The rate and volume of each bolus infusion should be titrated to the clinical response. Patients with severe dengue should be admitted to the high-dependency or intensive care area

Mucosal bleeding Profound thrombocytopenia- ensure strict

bedrest and protection from trauma to reduce the risk of bleeding

No IM injections If major bleeding occurs- usu from GIT or

per vagina in females; internal bleeding- may not become apparent for many hours until the first black stool is passed

Who are at risk for bleeding?◦ prolonged or refractory shock◦ hypotensive shock and renal or liver failure and or

severe metabolic acidosis◦ given with NSAIDs◦ existing peptic ulcer disease◦ on anticoagulant therapy◦ any form of trauma, including IM injections

How do you recognize severe bleeding?◦ Persistent or severe/overt bleeding in the

presence of unstable hemodynamic status, regardless of the hematocrit level

◦ A decrease in hematocrit after fluid resuscitation together with unstable vital signs

◦ Refractory shock that fail to respond to consecutive fluid resuscitation of 40-60ml/kg

◦ Hypotensive shock with low/normal hematocrit before fluid resuscitation

◦ Persistent or worsening met.acidosis +/- well maintained SBP esp. in those with severe abdominal tenderness and distention.

ACTION PLAN

Give 5–10ml/kg of fresh-packed red cells or 10–20 ml/kg of fresh whole blood at an appropriate rate and observe the clinical response. It is important that

A good clinical response includes improving haemodynamic status and acid-base balance

ACTION PLAN

Consider repeating the blood transfusion if there is further blood loss or no appropriate rise in haematocrit after blood transfusion

Great care should be taken when inserting a naso-gastric tube which may cause severe haemorrhage and may block the airway. It should be lubricated.

ACTION PLAN

Insertion of central venous catheters should be done with ultra-sound guidance or by a very experienced person.

Causes of fluid overload are

– excessive and/or too rapid intravenous fluids– incorrect use of hypotonic rather than isotonic crystalloid solutions– inappropriate use of large volumes of intravenous fluids in patients with unrecognized severe bleeding

– inappropriate transfusion of fresh-frozen plasma, platelet concentrates and cryoprecipitates

– continuation of intravenous fluids after plasma leakage has resolved (24–48 hours from defervescence);

– co-morbid conditions such as congenital or ischaemic heart disease, chronic lung and renal diseases.

Early clinical features of fluid overload are:– respiratory distress, difficulty in breathing– rapid breathing– chest wall in-drawing– wheezing (rather than crepitations)– large pleural effusions– tense ascites– increased jugular venous pressure (JVP)

Late clinical features are:– pulmonary oedema (cough with pink or frothy sputum ± crepitations, cyanosis)– irreversible shock (heart failure, often in combination with ongoing hypovolaemia)

ACTION PLAN

Oxygen therapy should be given immediately

Stopping intravenous fluid therapy during the recovery phase will allow fluid in the pleural and peritoneal cavities to return to the intravascular compartment

ACTION PLAN

If the patient has stable haemodynamic status and is out of the critical phase (> 24–48 hours of defervescence), stop intravenous fluids but continue close monitoring. If necessary, give oral or intravenous furosemide 0.1–0.5 mg/kg/dose once or twice daily, or a continuous infusion of furosemide 0.1 mg/kg/hour

Monitor serum potassium and correct the ensuing hypokalaemia

ACTION PLAN

If the patient has stable haemodynamic status but is still within the critical phase, reduce the intravenous fluid accordingly. Avoid diuretics during the plasma leakage phase because they may lead to intravascular volume depletion

ACTION PLAN

Patients who remain in shock with low or normal haematocrit levels but show signs of fluid overload may have occult haemorrhage

Careful fresh whole blood transfusion should be initiated as soon as possible

If the patient remains in shock and the haematocrit is elevated, repeated small boluses of a colloid solution may help

Based on 7 Parameters1. mental status2. heart rate3. blood pressure4. respiratory rate5. capillary refill time6. peripheral blood volume7. extremities

All of the following conditions must be present:

Clinical- No fever for 48 hours- Improvement in clinical status

Labortory- Increasing trend of the platelet count- Stable hematocrit without IVF

Thank you!