Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

all patients

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supportive care

Initial care begins with the basic ABCs: assure an airway, check for adequate breathing, and assess circulation. Two venous access lines are recommended.

Continued careful monitoring of vital signs along with urine output is essential. Plasma glucose levels should be measured using a rapid test device, particularly in infants and patients with altered mental status. Frequent measurement of electrolytes, serum pH, lactic acid, ammonia, albumin, and serum osmolality should be done. Treatment is guided by the clinical and biochemical response. Intravenous solutions are indicated in patients who are severely dehydrated or who have intractable vomiting. Cerebral edema may be aggravated by too rapid correction or overcorrection of volume depletion and/or acidosis.

Ondansetron may be given to decrease vomiting.

Measures to prevent raised intracranial pressure (ICP) include raising the head of the bed to 30° and careful fluid balance. Hypo-osmotic fluids should be avoided.

Primary options

ondansetron: children: 1-2 mg intravenously every 8 hours

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furosemide

Treatment recommended for ALL patients in selected patient group

May be required for fluid overload caused by overcorrection of volume depletion.

Primary options

furosemide: children: 0.5 to 2 mg/kg intramuscularly/intravenously every 6-12 hours, titrate according to response

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intensive monitoring

Treatment recommended for ALL patients in selected patient group

The National Reye Syndrome Surveillance System has described increasing stages of severity.[2]

Stage 1: lethargic, vomiting; stage 2: irritable, delirious, hyperreflexive, positive Babinski sign, dilated/sluggish pupils, responsive to pain; stage 3: decorticate posturing, obtunded, unresponsive to pain; stage 4: decerebrate posturing, comatose, fixed/dilated pupils; stage 5: areflexia, flaccid paralysis, unresponsive pupils, seizures, respiratory failure; stage 6: patient cannot be classified as he/she has been treated with curare or another medication that alters the level of consciousness.

Placement of an arterial line, urinary catheter for accurate urine output, and continuous cardiorespiratory monitoring should be performed. Periodic ECG and EEG studies may also be required.

A decision should be made when patients reach clinical stage 3 to provide continuous assessment of cerebral perfusion pressure (CPP) and monitor for raised intracranial pressure (ICP). A neurologic consultation may be necessary. Monitoring can be done by ventriculostomy, subarachnoid bolt, or intraparenchymal ICP monitor.

Indwelling arterial and central venous pressure catheters should be placed if they have not already been placed.

End-tidal carbon dioxide should also be monitored.

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intravenous fluids ± vasopressors

Treatment recommended for ALL patients in selected patient group

Isotonic crystalloid solutions (e.g., normal saline or lactated Ringer's solution) are recommended for initial volume resuscitation.

Vasopressors may also be beneficial.

Primary options

dobutamine: children: 0.5 to 2.5 micrograms/kg/minute intravenously initially, titrate according to response, maximum 40 micrograms/kg/minute

OR

dopamine: children: 1-5 micrograms/kg/minute intravenously initially, titrate according to response, maximum 50 micrograms/kg/minute

OR

norepinephrine: children: 0.1 micrograms/kg/minute intravenously initially, titrate according to response, maximum 2 micrograms/kg/minute

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intravenous dextrose

Treatment recommended for ALL patients in selected patient group

Plasma glucose levels should be measured using a rapid test device. This is particularly important in infants and in any patient with altered mental status.

Primary options

dextrose: (25%) 2 mL/kg intravenously as a single bolus

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slow intravenous bicarbonate infusion

Treatment recommended for ALL patients in selected patient group

If the pH is <7.0, consider bicarbonate administration until pH >7.0. Treatment can be repeated every 2 hours until pH >7.0. Bicarbonate treatment should be administered with caution because of the potential risk of paradoxical cerebrospinal fluid acidosis.

Bicarbonate therapy lowers serum potassium so potassium chloride should be added to isotonic bicarbonate. Sodium bicarbonate treatment also results in an additional sodium load and serum sodium levels will need to be carefully monitored. Bicarbonate deficit can be calculated using the formula: HCO₃ (mEq) = weight (kg) x base excess x 0.3.

Cerebral edema may be aggravated by too rapid correction or overcorrection of volume depletion and/or acidosis.

Primary options

sodium bicarbonate: 1mEq/kg/hour intravenously

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sodium phenylacetate/sodium benzoate

Treatment recommended for ALL patients in selected patient group

Hyperammonemia can be corrected with sodium phenylacetate/sodium benzoate. This is given as an intravenous loading dose via a central line, and followed by a slow infusion over 24 hours.

Ondansetron should be given during the first 15 minutes of initiation of sodium phenylacetate/sodium benzoate therapy to prevent vomiting and potential aspiration.

Primary options

sodium phenylacetate/sodium benzoate: children: consult specialist for guidance on dose

and

ondansetron: children: 0.15 mg/kg intravenously as a single dose

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hemodialysis

Treatment recommended for SOME patients in selected patient group

Hemodialysis corrects metabolic acidosis and electrolyte abnormalities.

If the blood ammonia concentration is >500 micrograms/dL or if there is no response to sodium phenylacetate/sodium benzoate, hemodialysis should be considered.

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ICP-lowering regimen

Treatment recommended for ALL patients in selected patient group

Raised ICP is clinically suggested by irritability and vomiting.

Monitoring can be done by ventriculostomy, subarachnoid bolt, or intraparenchymal ICP monitor.

Primary options to lower ICP include raising the head of the bed to 30° and careful fluid balance. Hypo-osmotic fluids should be avoided. Analgesics and sedation can be beneficial because pain and agitation can increase the ICP. When ventricular access is available, cerebrospinal fluid drainage should be considered.

Secondary treatment options to lower ICP include osmotic therapy with 3% hypertonic saline; osmotic diuretics such as mannitol can also be used. Neurosurgical consultation is advised.

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anticonvulsant

Treatment recommended for ALL patients in selected patient group

Patients presenting with seizures should be treated with an anticonvulsant drug.

Primary treatment options are phenytoin or fosphenytoin.

Anticonvulsants will usually be continued until patients are seizure-free; a trial off medications with the usual precautions may then be considered.

Primary options

phenytoin: children: 10-20 mg/kg intravenously as a loading dose, followed by 5 mg/kg/day given in 2 divided doses

OR

fosphenytoin: children: 10-20 mg PE/kg intravenously as a loading dose, followed by 4-6 mg PE/kg/day given in 2 divided doses

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fresh frozen plasma and/or platelet transfusion

Treatment recommended for ALL patients in selected patient group

Patients who present with or develop coagulopathy require normalization of their coagulation profile. All patients should have serial PT, PTT, INR, platelet, and fibrinogen levels followed.

If the prothrombin time is >16 seconds, coagulopathy should be corrected with replacement products. Correction of coagulopathy can include fresh frozen plasma for abnormal clotting function, and platelets for severe thrombocytopenia.

This is particularly important if an invasive procedure (e.g., intracranial bolt placement or a liver biopsy) is to be performed.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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