Course Management of Prevalent Infections in Children Following a Disaster

Dengue infections occur worldwide but are most prevalent in Southeast Asia, although it has become very prevalent in Central America and the Caribbean and parts of South America. In Southeast Asia, outbreaks of hemorrhagic fever occur cyclically every 4 to 5 years. It is caused by an arbovirus, usually acquired by the bite of Aedes mosquitoes. There are 4 closely related serotypes of dengue virus, all of which can cause severe disease. The underlying immunopathology of dengue infection involves host and viral factors, and possibly sequential infections with different virus serotypes. Dengue infection can have severe clinical manifestations. WHO defines severe dengue by one or more of the following: (i) plasma leakage that may lead to shock (dengue shock) and/or fluid accumulation, with or without respiratory distress, and/or (ii) severe bleeding, and/or (iii) severe organ impairment. After the incubation period, the illness begins abruptly and is followed by the three phases — febrile, critical and recovery (WHO Dengue Handbook 2009)

Febrile phase

The acute febrile phase, lasting 2-7 days, usually has a sudden onset of high fever associated with facial flushing, skin erythema, generalized body ache, myalgia, arthralgia and headache. Anorexia, nausea and vomiting are also common. Less frequently sore throat and conjunctival injection can occur. Petechiae, bleeding gums, and or nose bleeds may also occur. There may be an enlarged tender liver during this phase. It is not usually possible to clinically distinguish dengue from other febrile illnesses during this period. However, several laboratory tests are helpful; including a positive tourniquet test, a progressive decrease in the total white cell count and a falling platelet count.

Critical phase

The critical phase begins during a 24-48 hour period when there is an increase in capillary permeability, which is associated with increasing hematocrit levels. This usually occurs after the fever decreases or resolves. Leukopenia and a rapidly decreasing platelet count usually occur just before the increase in capillary permeability. Most patients recover without developing conditions caused by an increase in capillary permeability. In others the severity of the plasma leakage is quite variable. Respiratory distress may result from pleural effusions. Ascites may cause abdominal distention and tenderness. Hemoconcentration is a good indicator of the severity of plasma leakage. When plasma leakage reduces the circulating blood volume signs of shock appear. Prolonged hypoperfusion leads to poor tissue oxygenation, progressive organ failure, metabolic acidosis and disseminated intravascular coagulation (DIC). Signs of shock include a narrowed the pulse pressure (i.e. the difference between the systolic and diastolic pressures ≤20 mm Hg), poor capillary perfusion/delayed capillary refill (>3 seconds), cold extremities, and rapid pulse. Hypotension may be a late manifestation of shock.Consider major bleeding in these cases. Hemorrhage caused by DIC will decrease the hemoconcentration because of blood loss and worsen the shock and organ failure. Massive bleeding may occur without shock in instances when acetylsalicylic acid (aspirin), ibuprofen or corticosteroids have been taken.

Recovery phase

The capillary permeability gradually improves after the 24-48 hour critical phase so that patients begin to stabilize who received appropriate fluid management. There is a reabsorption of fluid and a diuresis. However, bradycardia and electrocardiographic changes are common during this stage.

Dengue Management

In an ambulatory setting where dengue is endemic all patients who have a clinical presentation consistent with the febrile phase of dengue should, if feasible, have an initial CBC to identify neutropenia and decreased platelets and possibly a tourniquet test. They should be followed daily with CBCs until afebrile for 48 hours without decreasing platelets, increasing hematocrits, or other signs of capillary permeability. Warning signs for developing severe dengue include any of the IMCI danger signs, presence of ascites or pleural effusions, increasing hematocrits, signs of shock (narrowed the pulse, poor capillary perfusion/delayed capillary refill, cold extremities, and rapid pulse), severe bleeding, or organ impairment. Make sure that the family understands the importance of returning to the clinic immediately if any of the IMCI danger signs or bleeding develop. Patients who appear to be entering the critical 24-48 phase of dengue with any warning signs should be hospitalized. The decision whether to hospitalize patients without any warning signs and stable CBCs must be individualized based on the degree of illness, access to the hospital and ability of the family to care for the child. It is important to determine if the patient can drink sufficient ORS and fluids. If the patient is unable to drink, start intravenous fluid therapy with 0.9 saline or Ringer’s lactate with or without dextrose at maintenance rate. Patients may be able to take oral fluids after a a few hours of IV therapy. The WHO recommends giving paracetamol for high fever if the patient is uncomfortable. The interval of paracetamol dosing should not be less than six hours. Tepid sponge if the patient still has high fever. Do not give acetylsalicylic acid (aspirin), ibuprofen or other non-steroidal antiinflammatory agents (NSAIDs) as these drugs may aggravate gastritis or bleeding. Acetylsalicylic acid (aspirin) may be associated with Reye’s Syndrome.

All patients with warning signs or severe dengue should be admitted to a hospital with access to intensive care facilities and blood transfusion. Hospital emergency rooms where dengue is endemic should have triage protocols in place to identify severe dengue patients and start fluid management as soon as possible. Triage should classify cases into 3 categories: severe cases needing immediate fluid resuscitation, cases with warning signs who need to be given priority, and non urgent cases. Before beginning IV fluids obtain a reference hematocrit. According to the WHO Dengue handbook avoid administering free water by giving only isotonic solutions such as 0.9% saline, Ringer’s lactate, or Hartmann’s solution. These guidelines are taken directly from the handbook. Start with 5-7 ml/kg/hour for 1-2 hours, then reduce to 3-5 ml/kg/hr for 2-4 hours, and then reduce to 2-3 ml/kg/hr or less according to the clinical response. Reassess the clinical status and repeat the hematocrit. If the hematocrit remains the same or rises only minimally, continue with the same rate (2-3 ml/kg/hr) for another 2-4 hours. If the vital signs are worsening and hematocrit is rising rapidly, increase the rate to 5-10 ml/ kg/hour for 1-2 hours. Reassess the clinical status, repeat the hematocrit and review fluid infusion rates accordingly. Give the minimum intravenous fluid volume required to maintain good perfusion and urine output of about 0.5 ml/kg/hr. Intravenous fluids are usually needed for only 24-48 hours. Reduce intravenous fluids gradually when the rate of plasma leakage decreases towards the end of the critical phase. This is indicated by urine output and/or oral fluid intake that is/are adequate, or hematocrit decreasing below the baseline value in a stable patient. Maintain a detailed fluid balance record and monitor vital signs and peripheral perfusion (1-4 hourly until the patient is out of the critical phase), urine output (4-6 hourly),hematocrit (before and after fluid replacement, then 6-12 hourly), blood glucose, and other organ functions (such as renal profile, liver profile, coagulation profile, as indicated). Care must be taken to avoid excessive fluid administration during the critical phase of capillary permeability to avoid pulmonary edema and congestive heart failure.

The action plan for treating patients with compensated shock in the WHO dengue handbook follows:

• Start intravenous fluid resuscitation with isotonic crystalloid solutions at 5-10 ml/kg/hour over one hour. Then reassess the patient’s condition (vital signs, capillary refill time, hematocrit, urine output). The next steps depend on the situation.
• 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 further depending on hemodynamic status, which can be maintained for up to 24-48 hours.
• If vital signs are still unstable (i.e. shock persists), check the hematocrit after the first bolus. If the hematocrit increases or is still high (>50%), repeat a second bolus of crystalloid solution at 10–20 ml/kg/hr for one hour. After this second bolus, if there is improvement, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, and then continue to reduce as above. If hematocrit decreases compared to the initial reference hematocrit (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to cross-match and transfuse blood as soon as possible.
• Further boluses of crystalloid or colloidal solutions may need to be given during the next 24–48 hours.

Avoid fluid overload while ensuring adequate volume replacement. If resources are available, a patient with severe dengue should have an arterial line placed as soon as practical. The reason for this is that in shock states, estimation of blood pressure using a cuff is commonly inaccurate. The use of an indwelling arterial catheter allows for continuous and reproducible blood pressure measurements and frequent blood sampling on which decisions regarding therapy can be based. Monitoring of ECG and pulse oximetry should be available in the intensive care unit. Urine output should be checked regularly (hourly till the patient is out of shock, then 1-2 hourly). A continuous bladder catheter enables close monitoring of urine output. An acceptable urine output would be about 0.5 ml/kg/ hour. Hematocrit should be monitored (before and after fluid boluses until stable, then 4-6 hourly). In addition, there should be monitoring of arterial or venous blood gases, lactate, total carbon dioxide/bicarbonate (every 30 minutes to one hour until stable, then as indicated), blood glucose (before fluid resuscitation and repeat as indicated), and other organ functions (such as renal profile, liver profile, coagulation profile, before resuscitation and as indicated).

Severe bleeding can be recognized by:

The action plan for the treatment of hemorrhagic complications is as follows:

• Give 5-10 ml/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 fresh whole blood or fresh red cells are given. Oxygen delivery at tissue level is optimal with high levels of 2,3 di-phosphoglycerate (2,3 DPG). Stored blood loses 2,3 DPG, low levels of which impede the oxygen-releasing capacity of haemoglobin, resulting in functional tissue hypoxia. A good clinical response includes improving hemodynamic status and acid-base balance.
• Consider repeating the blood transfusion if there is further blood loss or no appropriate rise in hematocrit after blood transfusion. There is little evidence to support the practice of transfusing platelet concentrates and/or fresh-frozen plasma for severe bleeding.