Approach

Primary approach to management is optimal support in an intensive care unit. Because the major lethal factor is increased intracranial pressure (ICP) secondary to cerebral oedema, control of ICP is critical for patients with more advanced stages of disease.

Clinical stages (modified from Hurwitz)

The US National Reye's Syndrome Surveillance System has described increasing stages of severity:[2]

  • Stage 1: Lethargic, vomiting

  • Stage 2: Irritable, delirious, hyper-reflexive, positive Babinski's 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.

Initial supportive care and monitoring

Patients with stage 1 disease

  • Assessment and treatment should proceed alongside each other. Initial care should include 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. This is particularly important in infants and in any patient with altered mental status. Frequent measurement of laboratory metabolic parameters should include: electrolytes, serum pH, lactic acid, ammonia, albumin, and serum osmolality.

  • Intravenous solutions are indicated in patients who are severely dehydrated or who have intractable vomiting. Maintenance fluids should be calculated and given, with the caveat that cerebral oedema 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 increased ICP should be undertaken. These should include elevation of the head of the bed and careful fluid balance. Hypo-osmotic fluids should be avoided. Furosemide may be required for fluid overload.

Patients with stage 2-5 disease

  • Once stabilised, 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 to monitor for raised ICP. A neurosurgical 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.

Management of metabolic abnormalities

Hypotension

  • Isotonic crystalloid solutions (e.g., normal saline or lactated Ringer's solution) are recommended for initial volume resuscitation to treat hypotension and maintain intravascular volume.[24] Vasopressors may also be beneficial. See Volume depletion in children (Management approach).

Hypoglycaemia

  • Hypoglycaemia should be corrected with intravenous glucose as soon as possible.

Acidosis

  • If the pH is <7.0, consider bicarbonate administration. Treatment can be repeated every 2 hours until pH is >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 is 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.

Hyperammonaemia

  • Hyperammonaemia can be corrected with sodium phenylacetate/sodium benzoate. This is given as an intravenous loading dose via a central line, and is followed by a slow intravenous 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.

  • If the blood ammonia concentration is >357 micromol/L (>500 micrograms/dL), or if there is no response to phenylacetate/sodium benzoate, haemodialysis should be considered. Haemodialysis corrects metabolic acidosis and electrolyte abnormalities.

Raised ICP

Primary options that can be used to lower ICP to below 20 mmHg and maintain the cerebral perfusion pressure above 50 mmHg include raising the head of the bed to 30°, and continued careful fluid balance. Hypo-osmotic fluids should be avoided. Analgesics and sedation can be beneficial because pain and agitation can increase the ICP. Forced hyperventilation may be of value. When ventricular access is available, cerebrospinal fluid drainage should be considered. Secondary treatment options include osmotic therapy with 3% hypertonic saline, and osmotic diuretics such as mannitol. Neurosurgical consultation is advised.

Seizures

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.

Coagulopathy

Patients should have serial PT, PTT, INR, platelet, and fibrinogen levels monitored. Any coagulopathy should be corrected for those patients with active bleeding or if an invasive procedure (e.g., intracranial bolt placement or a liver biopsy) is to be performed.[25] Correction of coagulopathy can include fresh frozen plasma for abnormal clotting function (PTT, PT, and fibrinogen) and platelets for severe thrombocytopenia.[26]

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