Approach
Treatment is supportive, as there is no specific antiviral therapy available for the treatment of dengue infection, and is based on guidance produced by the World Health Organization (WHO) and other region-specific authorities. The only recognized treatment is maintaining adequate hydration in dengue fever and fluid replacement therapy in hemorrhagic fever (DHF) and dengue shock syndrome (DSS). In dengue-endemic regions, the triage of patients with suspected dengue infection should be carried out in a specifically designated area of the hospital.
Early diagnosis and optimal clinical management reduce the associated morbidity and mortality. Delays in diagnosis, incorrect diagnosis, use of improper treatments (e.g., nonsteroidal anti-inflammatory drugs), and surgical interventions are all considered harmful. All patients with clinically suspected dengue should receive appropriate management without waiting for diagnostic test results. Educating the public about identifying the signs and symptoms of dengue infection early, and when to seek medical advice, is the key to optimal diagnosis and treatment.
In dengue-endemic regions, suspected, probable, and confirmed cases of dengue infection should be reported to the relevant authorities as soon as possible so that appropriate measures can be instituted to prevent dengue transmission.[2]
Severity of infection
The most commonly used and practical treatment plan is produced by the WHO and is based on the severity of infection.[2] The WHO classification separates patients into 1 of 3 groups (A, B, or C), depending on the clinical presentation.
Group A
Patients with the following features are classified as group A; these patients can be managed at home:
No warning signs (particularly when fever subsides)
Able to tolerate an adequate volume of oral fluids and pass urine at least once every 6 hours
Near-normal blood counts and hematocrit.
Group B
Patients with the following features are classified as group B; these patients require hospital admission:
Developing warning signs (i.e., abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation such as ascites or pleural effusion, mucosal bleeding, lethargy/restlessness, liver enlargement >2 cm, increase in hematocrit concurrent with rapid decrease in platelet count)
Coexisting risk factors for serious infection (e.g., pregnancy, extremes of age, obesity, diabetes, renal impairment, hemolytic diseases)
Poor family or social support (e.g., patients who live alone or live far from medical facilities and do not have reliable transport)
Increasing hematocrit or a rapidly decreasing platelet count.
Group C:
Patients with the following features are classified as group C; these patients require emergency medical intervention:
Established warning signs
In the critical phase of infection, with severe plasma leakage (with or without shock), severe hemorrhage, or severe organ impairment (e.g., hepatic or renal impairment, cardiomyopathy, encephalopathy, or encephalitis).
The Centers for Disease Control and Prevention (CDC) also separate patients into 3 groups (A, B, C) for management. Group A includes patients with no warning signs, group B includes patients with warning signs or coexisting conditions, and group C includes patients with severe plasma leakage with shock and/or fluid accumulation with respiratory distress, severe bleeding, or severe organ impairment.[100]
While the WHO and CDC classify patients into 1 of 3 groups, guidelines from the Pan American Health Organization classify patients into 1 of 4 groups (A, B1, B2, C). Group B is split into groups B1 and B2. Group B1 has no warning signs and do not meet criteria for hospitalization, but do have a comorbidity or condition, or the presence of a social risk. Group B2 has warning signs, but not severe dengue.[97] The management recommendations in this topic are based on WHO guidance.
Consult your local guidelines as recommendations may differ in other countries.
Management of WHO group C patients
These patients require emergency medical intervention. Access to intensive care facilities and blood transfusion should be available. Rapid administration of intravenous crystalloids and colloids is recommended, according to algorithms produced by the WHO.[1][2] An attempt should be made to work out how long the patient has been in the critical phase and the previous fluid balance.
The total fluid quota for 48 hours should be calculated based on the following formula:[1][74]
maintenance (M) + 5% fluid deficit
M = 100 mL/kg for the first 10 kg of body weight, 50 mL/kg for the second 10 kg of body weight, and 20 mL/kg for every kilogram over 20 kg of body weight up to 50 kg; and 5% fluid deficit is calculated as 50 mL/kg of body weight up to 50 kg
For example, for an adult who weighs 50 kg or more, the total fluid quota for 48 hours would be 4600 mL.
The formula may be used for children and adults; however, the rate of administration differs between these patient groups, and local protocols should be followed. Ideal body weight should be used in the formula for children.
Other formulas for fluid replacement therapy have been reported, so local protocols should be consulted and followed. The infusion rate should be adjusted according to the usual monitoring parameters, and therapy is usually only required for 24 to 48 hours, with a gradual reduction once the rate of plasma leakage decreases toward the end of the critical phase.[2]
There is no clinical advantage to giving colloids (e.g., dextran 70) over crystalloids (e.g., 0.9% normal saline, Ringer lactate).[101][102][103] WHO guidelines clearly indicate when colloids should be used (e.g., intractable shock, resistance to crystalloid resuscitation).[1][2]
The patient should be monitored closely throughout, including vital signs, peripheral perfusion, fluid balance, hematocrit, platelet count, urine output, temperature, blood glucose, liver function tests (LFTs), renal profile, coagulation profile, and other organ function tests as indicated.
Usually the patient's condition will become stable within a few hours of fluid therapy. If the patient remains unstable, other contributory causes such as metabolic acidosis, electrolyte imbalances (e.g., hypocalcemia, hypoglycemia), myocarditis, or hepatic necrosis should be investigated and managed appropriately. If the patient is not improving and the hematocrit falls, internal bleeding should be suspected and a blood transfusion administered immediately; however, caution is advised due to the risk of fluid overload. Consensus is now for early use of colloids and blood transfusion in refractory unstable patients.
Over-enthusiastic treatment and too rapid hydration can lead to fluid overload, causing pulmonary edema, facial congestion, elevated jugular venous pressure, pleural effusion, or ascites. These complications should be treated with restriction of intravenous fluid therapy and bolus doses of intravenous furosemide until the patient is stable.
Management of WHO group B patients
These patients require hospital admission. The severity of infection should be assessed. If the patient is not in the early critical phase (i.e., with plasma leakage), then he or she is encouraged to take fluids orally (e.g., approximately 2500 mL/24 hours for an adult, or age-appropriate maintenance fluid requirement for children). If this is not possible, or the patient enters the critical phase (indicated by rising hematocrit, hypoalbuminemia, progressive leukopenia, thrombocytopenia, third space fluid loss, and narrowing of pulse pressure with postural drop), intravenous fluid replacement therapy with 0.9% saline (or Ringer lactate) should be started using the maintenance (M) + 5% fluid deficit formula.[1][74] There is no clinical advantage to giving colloids (e.g., dextran 70) over crystalloids (e.g., 0.9% normal saline, Ringer lactate).[101][102][103] WHO guidelines clearly indicate when colloids should be used (e.g., intractable shock, resistance to crystalloid resuscitation).[1][2]
The patient should be monitored closely throughout, including vital signs, peripheral perfusion, fluid balance, hematocrit, platelet count, urine output, temperature, blood glucose, LFTs, renal profile, and coagulation profile.
Management of WHO group A patients
These patients can be managed at home. The patient should be encouraged to take oral fluids (e.g., approximately 2500 mL/24 hours for an adult, or age-appropriate maintenance fluid requirement for children).[1] Oral rehydration products, fruit juices, and clear soups are better than water; however, it is recommended that red- or brown-colored fluids be avoided, as these may lead to confusion about the presence of hematemesis if the patient vomits.
The patient should be advised to rest. Tepid sponging may be used for fever. Acetaminophen may be used in normal doses for pain or fever; however, nonsteroidal anti-inflammatory drugs should be avoided as they increase bleeding tendency.[2]
An instruction pamphlet outlining the warning signs should be given to the patient and the patient advised to return to the hospital immediately if any of the signs develop. Blood counts should be performed on a daily basis.[2]
Pregnancy
Pregnancy is a risk factor for higher maternal mortality and poor prenatal outcomes. There is also a higher incidence of cesarean sections, preeclampsia, preterm deliveries, reduced birth weight, and perinatal transmission of the infection.[44][45] However, one meta-analysis of 14 studies found that current evidence did not suggest that maternal infection increases the risk of premature birth, low birthweight, miscarriage, and stillbirth.[47] Close observation and meticulous management is important in this patient group. Fluid administration is the same as for nonpregnant adults; however, prepregnancy body weight should be used in the formula.[1][99]
As pregnancy is associated with various physiologic changes such as high pulse rate, low blood pressure, wider pulse pressure, decreased hemoglobin and hematocrit, and decreased platelet count, baseline parameters should be noted on the first day of infection and subsequent results interpreted with caution. Also, it should be remembered that other conditions that occur in pregnancy, such as preeclampsia and HELLP syndrome, may also alter laboratory parameters.[1][99]
Detection of plasma leakage (e.g., ascites, pleural effusion) is difficult in pregnant women, and so the early use of ultrasound is recommended.[1][99]
It is imperative to differentiate dengue fever from Zika virus infection in pregnancy as the latter is known to be associated with microcephaly in newborns.[82]
Children
The WHO guidelines are mainly based on studies performed in the pediatric population; therefore, the management approach to children is similar to adults, with fluid calculations based on ideal body weight.
As the tendency for children to develop DHF or DSS is increased, laboratory parameters such as hematocrit, platelet count, and urine output should be monitored regularly.
Assessment of the severity of symptoms in very young children is very difficult compared to older children and adults. Infants have less respiratory reserve and are more susceptible to electrolyte imbalances and hepatic impairment. The plasma leakage that occurs in children may be shorter and respond faster to fluid resuscitation.[1]
Convalescence and discharge
Convalescence can be recognized by the improvement in clinical parameters as well as the patient's appetite and well-being. The patient may develop a diuresis where hypokalemia may develop. If this occurs, intravenous fluids should be discontinued and a potassium-rich fluid given. Patients may also develop a rash or generalized pruritus during recovery. Once well-being is achieved and the patient remains afebrile for 48 hours with a rising platelet count and stable hematocrit, the patient can be discharged.[2]
Adjunctive therapies
Prophylactic platelet transfusions are rarely required (even with very low platelet counts) and are not recommended except in situations where there is active bleeding. The clinical value of fresh frozen plasma, corticosteroids, intravenous immunoglobulin, and antibiotics are controversial and require more evidence before they are recommended.[1][104]
One multicenter, open-label, randomized trial found that prophylactic platelet transfusion plus supportive care was not superior to supportive care alone in preventing bleeding in adults with dengue and thrombocytopenia, and may actually be associated with adverse events (e.g., urticaria, anaphylaxis, transfusion-related acute lung injury, fluid overload).[105]
How to insert a peripheral intravascular catheter into the dorsum of the hand.
Ultrasound-guided insertion of a non-tunnelled central venous catheter (CVC) into the right internal jugular vein using the Seldinger insertion technique.
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