Reye Syndrome Treatment & Management

No specific treatment exists for Reye syndrome; supportive care is based on the stage of the syndrome. Continue careful monitoring. Establish and maintain the patient’s airway, breathing, and circulation. Check the glucose level, particularly if the patient is younger than 1 year and/or has altered mental status. Administer dextrose to correct hypoglycemia. Admission to the intensive care unit (ICU) is warranted for continued monitoring and treatment.

Consider consultation with a neurologist for electroencephalography (EEG). Consider consultation with a neurosurgeon for monitoring and treatment of increased intracranial pressure (ICP). Consider consultation with a gastroenterologist or surgeon for liver biopsy. Consider consultation with a metabolic disease specialist if an inborn error of metabolism (IEM) is a possibility.

Monitor and treat long-term neurologic sequelae. Prescribe outpatient anticonvulsants if ongoing seizures occur.

Reye syndrome has been successfully treated with liver transplantation. ^[19]

Supportive care is based on the clinical stage of the syndrome, with aggressive treatment provided to correct or prevent metabolic abnormalities, particularly hypoglycemia and hyperammonemia, and to prevent or control cerebral edema.

Stages 0-1

Keep the patient quiet. Frequently monitor vital signs and laboratory values. Correct fluid and electrolyte abnormalities, hypoglycemia, and acidosis. If the patient is hypoglycemic, administer dextrose 25% as an intravenous (IV) bolus in a dose of 1-2 mL/kg. The use of bicarbonate to correct acidosis is controversial because of potential paradoxical cerebrospinal fluid (CSF) acidosis. In view of the lack of data regarding the degree of acidosis for which bicarbonate should be administered and the appropriate dosage, guidelines can only be suggested. If the initial pH is less than 7.0-7.2, consider administering sodium bicarbonate 0.5-2 mEq/kg/h to correct it to 7.25-7.3, with the dosage based on the deficit, calculated as follows:

Deficit in HCO₃^– (mEq) = weight (kg) × base excess × 0.3

Avoid rapid correction or overcorrection. Recognize that administration of sodium bicarbonate results in a significant sodium load.

Maintain electrolytes, serum pH, albumin, serum osmolality, glucose, and urine output in normal ranges. Consider restricting fluids to two thirds of maintenance. Overhydration may precipitate cerebral edema. Use colloids (eg, albumin) as necessary to maintain intravascular volume. Dehydration may compromise cardiovascular volume and reduce cerebral perfusion. Glucose should be maintained in the 100-125 mg/dL range; this will require administration of D10 or D20. Place a Foley catheter to monitor urine output.

Consider giving ondansetron 1-2 mg IV every 8 hours to decrease vomiting. Antacids may also be administered for gastrointestinal (GI) protection.

Stage 2

The standard of care consists of continuous cardiorespiratory monitoring, placement of central venous lines or arterial lines to monitor hemodynamic status, urine catheters to monitor urine output, ECG to monitor cardiac function, and EEG to monitor seizure activity. Endotracheal intubation may be required at this stage to maintain the airway, control ventilation, and prevent increased ICP. Use rapid-sequence agents that minimize the chance of increasing ICP. Place a nasogastric tube to decompress the abdomen.

Hyperammonemia can contribute to cerebral edema and therefore must be corrected aggressively. The US Food and Drug Administration (FDA) has not approved any medication for treatment of hyperammonemia specifically due to Reye syndrome. However, sodium phenylacetate–sodium benzoate is FDA-approved for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle.

Administer ondansetron 1-2 mg IV during the first 15 minutes of the initial dose of sodium phenylacetate–sodium benzoate. If the ammonia level is higher than 500 µg/dL or if the patient’s condition fails to respond to the initial dose of sodium phenylacetate–sodium benzoate, start dialysis, preferably hemodialysis. (See Inborn Errors of Metabolism.)

Prevent increased ICP. Elevate the head to 30°, keep the head in a midline orientation, use isotonic rather than hypotonic fluids, avoid overhydration, and administer furosemide 1 mg/kg as often as every 4-6 hours to control fluid overload.

Stages 3-5

Continuously monitor ICP, central venous pressure, arterial pressure, or end-tidal carbon dioxide. Perform endotracheal intubation if the patient is not already intubated.

Treat increased ICP by following standard guidelines, which, in addition to correction of hyperammonemia, proper positioning of the head, and appropriate fluid management (see above), include the following:

• Ventilation to maintain the partial pressure of carbon dioxide in the normal range

• Aggressive management of fever to prevent the increased cerebral metabolism and increased cerebral blood flow resulting from hyperpyrexia

• Analgesia and sedation to alleviate agitation or prepare for painful interventions

• Paralytic agents to control shivering

• If other measures fail, mannitol 20% solution dosed at 0.25-0.5 g/kg IV infused over 10-20 minutes as often as every 6-8 hours, ^[20] or hypertonic saline 3% dosed at 3-5 mL/kg over 3-30 minutes ^[21] (For additional information, see Mannitol and ICP Monitors.)

• Induced barbiturate coma and hypothermia are controversial

Treat seizures with phenytoin 10-20 mg/kg IV as a loading dose, followed by 5 mg/kg/day IV divided every 6 hours or fosphenytoin dosed as 10-20 mg/kg phenytoin equivalents.

Correct coagulopathy (prothrombin time >16 seconds). The data on treatment of coagulopathy in Reye syndrome, like those on most etiologies of coagulopathy in children, are limited. Options include fresh frozen plasma (FFP), cryoprecipitate, platelets, vitamin K, and exchange transfusion.

FFP 10-15 mL/kg every 12-24 hours provides rapid correction and volume expansion and should be administered, particularly if active bleeding is present or if invasive procedures (eg, ICP monitoring device placement or liver biopsy) are required. If the fibrinogen level is lower than 100 mg/dL, cryoprecipitate 10 mL/kg every 6 hours should be considered instead of FFP because cryoprecipitate has a higher concentration of fibrinogen.

If invasive procedures are to be performed, platelets should also be given as needed to restore the platelet count to a value higher than 50,000/µL. Vitamin K 1-10 mg IV may be administered instead of FFP or cryoprecipitate if the need for correction is not an emergency. Exchange transfusion is rarely required. (See Consumption Coagulopathy.)

Reye syndrome has been successfully treated with liver transplantation. ^[19]

Salicylates should be avoided in children, except in those who have conditions for which salicylates are a mainstay of therapy (eg, Kawasaki disease). Of approximately 200,000 children in Japan who were treated with aspirin for Kawasaki disease, only 1 was reported to have developed Reye syndrome. In children who require long-term salicylate therapy, use of these agents should be discontinued immediately at the first signs or symptoms of Reye syndrome.

It is critical to be alert for and recognize early symptoms of Reye syndrome. It is also important to be mindful of the possibility that an IEM may be the actual cause of the symptoms and, if this is the case, to be prepared to treat the IEM. Appropriate management of IEMs dramatically decreases morbidity and mortality. (See Inborn Errors of Metabolism.)

Influenza vaccine is recommended by the Centers for Disease Control and Prevention (CDC) for everyone older than 6 months.