eMedicine Specialties > Emergency Medicine > Pediatric
Pediatrics, Reye Syndrome: Treatment & Medication
Updated: Feb 3, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
- Establish and maintain the patient's airway, breathing, and circulation.
- Check the glucose level, particularly if the patient is younger than 1 year, has an altered mental status, or both.
- Administer dextrose to manage hypoglycemia.
Emergency Department Care
No specific treatment exists. Continue careful monitoring. Supportive care is based on the stage, with aggressive treatment to correct or prevent metabolic abnormalities, particularly hypoglycemia and hyperammonemia, and to prevent or control cerebral edema. Care by stage is as follows:
- 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 initially hypoglycemic, administer dextrose 25% as an intravenous (IV) bolus at a dose of 1-2 mL/kg. Use of bicarbonate to correct acidosis is controversial because of potential paradoxical CSF acidosis. Furthermore, given the lack of data regarding degree of acidosis for which bicarbonate should be administered and appropriate dose, guidelines can only be suggested. Consider administration of sodium bicarbonate (NaHCO3) 0.5-2 mEq/kg/h if the initial pH is less than 7.0-7.2 to correct to 7.25-7.3 based on deficit (deficit HCO3 in mEq = weight (kg) X base excess X 0.3); avoid rapid correction or overcorrection. Recognize that administration of sodium bicarbonate results in significant sodium load.
- Maintain fluids, electrolytes, serum pH, albumin, serum osmolality, urine output, and glucose values. Consider restriction of 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 D10 -D20. Place a Foley catheter to monitor urine output.
- Ondansetron (Zofran) 1-2 mg IV q8h may be administered to decrease vomiting. Antacids may also be administered for gastrointestinal protection.
- Stage 2
- Continuous cardiorespiratory monitoring, placement of central venous lines and/or arterial lines and urine catheters to monitor urine output, and ECG and/or EEG are standard of care.
- Endotracheal intubation may be required at this stage to maintain airway and control ventilation and to prevent increased intracranial pressure. Use rapid-sequence agents that minimize the chance of increasing intracranial pressure. Place a nasogastric tube to decompress the abdomen.
- Correct hyperammonemia. Hyperammonemia can contribute to cerebral edema. The US Food and Drug Administration (FDA) has not approved any medication to treat hyperammonemia specifically due to Reye syndrome. Sodium phenylacetate/sodium benzoate (Ammonul), a medication that treats hyperammonemia, is FDA approved for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle. Administer ondansetron during the first 15 minutes of the initial dose of sodium phenylacetate/sodium benzoate. If the ammonia level is more than 500 mcg/dL or if the patient's condition fails to respond to the initial dose of sodium phenylacetate/sodium benzoate, start dialysis, preferably hemodialysis. See eMedicine article Pediatrics, Inborn Errors of Metabolism.
- Prevent increased ICP. Elevate the head to 30 degrees, keep the head midline, use isotonic rather than hypotonic fluids, avoid overhydration, and administer furosemide (Lasix) 1 mg/kg up to every 4-6 hours to control fluid overload.
- Stages 3-5
- Continuously monitor ICP, central venous pressure, arterial pressure, and/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, positioning of the head, and appropriate fluid management, include ventilation to maintain PCO2 in the normal range, aggressive management of fever to prevent increased cerebral metabolism and increased cerebral blood flow that results from hyperpyrexia, analgesia and sedation for agitation or prior to painful interventions, paralytic agents to control shivering, and if other measures fail, mannitol 0.25-0.5 g/kg/dose IV infused over 10-20 minutes up to every 2-4 hours. Use of barbiturate coma and hypothermia are controversial.
- Treat seizures with phenytoin 10-20 mg/kg IV as a loading dose followed by 5 mg/kg/d IV divided every 6 hours or fosphenytoin dosed as 10-20 mg/kg phenytoin equivalents (PEs).
- Correct coagulopathy (PT >16 seconds).
- Data for treatment of coagulopathy in Reye syndrome, as well as for most etiologies of coagulopathy in children, are limited. Options include fresh frozen precipitate (FFP), cryoprecipitate, platelets, vitamin K, 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 invasive procedures such as intracranial pressure monitoring device placement and/or liver biopsy are required. Cryoprecipitate, 10 mL/kg every 6 hours, which has a higher concentration of fibrinogen, should be considered instead of FFP if fibrinogen is less than 100 mg/dL.
- Platelets as needed to restore platelet count to greater than 50,000/mm3 should also be given if invasive procedures are to be performed. Vitamin K 1-10 mg intravenously may be administered instead of FFP or cryoprecipitate if correction is not emergent. Exchange transfusion is rarely required. See eMedicine article Consumption Coagulopathy.
Consultations
- Consider consultation with a neurologist for EEG.
- Consider consultation with a neurosurgeon for monitoring and treatment of increased ICP.
- Consider consultation with a gastroenterologist or surgeon for liver biopsy.
- Consider consultation with a metabolic disease specialist if IEM is possible.
Medication
No specific treatment is available. Supportive care to reduce hyperammonemia with sodium phenylacetate/sodium benzoate may be required. For highly elevated levels of ammonia, hemodialysis may be the appropriate initial treatment if it is readily available, and it is also recommended for patients whose condition fails to respond to initial course of sodium phenylacetate/sodium benzoate. Continuing the administration of sodium phenylacetate/sodium benzoate with hemodialysis may be considered.
In terms of managing increased ICP, steroids are of no proven benefit, they may be harmful, and they are not indicated.
Ammonia detoxicants
Treatment of hyperammonemia; enhances elimination of nitrogen. Sodium phenylacetate/sodium benzoate is FDA approved for treatment of hyperammonemia due to urea-cycle defects and is available only from a specialty wholesaler, Ucyclyd Pharma, Inc (in the United States and Canada, 24-hour toll-free number: 888-829-2593; 8125 N. Hayden Road, Scottsdale, AZ 85258). For more information, see Ammonul prescribing information.
Sodium phenylacetate and sodium benzoate (Ammonul)
May be effective to treat hyperammonemia. For levels >500-600 mcg/dL, hemodialysis preferred. Can be used until dialysis started or with dialysis. Benzoate combines with glycine to form hippurate (excreted in urine). One mole of benzoate removes 1 mole of nitrogen. Phenylacetate conjugates (by acetylation) with glutamine in liver and kidneys to form phenylacetylglutamine (excreted by kidneys). Nitrogen content of phenylacetylglutamine per mole identical to that of urea (2 mol). Preparation contains 100 mg/mL each of sodium phenylacetate and sodium benzoate; supplied as 50-mL vials. Must dilute IV dose in at least 25 mL/kg of dextrose 10% up to 600 mL. Do not directly mix with other medications; may be piggybacked. Give in addition to daily fluid requirement.
Adult
Loading: 55 mL (5.5 g)/m2 IV over 90-120 min through central line
Maintenance: 55 mL (5.5 g)/m2/d IV over 24 h through central line
Pediatric
<20 kg:
Loading: 2.5 mL (250 mg)/kg IV over 90-120 min through central line
Maintenance: 2.5 mL (250 mg)/kg/d IV over 24 h through central line
>20 kg: Administer as in adults
Penicillin may decrease effects; probenecid may inhibit renal excretion of products; valproate may antagonize efficacy
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Closely monitor patients with hepatic or renal impairment; caution in neonatal hyperbilirubinemia (competes for bilirubin-bindings sites on albumin); because of sodium content, caution in congestive heart failure, severe renal dysfunction, or sodium retention with edema; common adverse effects include nausea, vomiting, tinnitus, and visual disturbance; may cause hyperglycemia or hypokalemia; if needed, may be given with furosemide for edema, insulin to maintain euglycemia, or ondansetron 0.15 mg/kg (not to exceed 8 mg q8h) during initial 15 min of priming infusion to offset GI effects; overdose may result in death
Antiemetic agents
Administer ondansetron to decrease vomiting and during initiation of sodium phenylacetate and sodium benzoate.
Ondansetron (Zofran)
Controls nausea and vomiting associated with Reye syndrome and with IV administration of sodium benzoate and phenylacetate.
Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally. Prevents nausea and vomiting associated with IV administration of sodium benzoate and phenylacetate.
Adult
32 mg IV infused over 15 min beginning 30 min before start of IV sodium benzoate and phenylacetate infusion
Pediatric
1-2 mg IV q8h
Although there is potential for cytochrome P-450 inducers (barbiturates, rifampin, carbamazepine, and phenytoin) to change half-life and clearance of ondansetron, dosage adjustment is not usually required
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause headache
More on Pediatrics, Reye Syndrome |
| Overview: Pediatrics, Reye Syndrome |
| Differential Diagnoses & Workup: Pediatrics, Reye Syndrome |
 Treatment & Medication: Pediatrics, Reye Syndrome |
| Follow-up: Pediatrics, Reye Syndrome |
| References |
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References
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Further Reading
Keywords
Reye's syndrome, Reye syndrome, acute noninflammatory encephalopathy, inborn error of metabolism, IEM, Reye syndrome in children, hepatic failure, upper respiratory tract infection, URTI, influenza, varicella, gastroenteritis, use of aspirin, aspirin use in children
