Reye’s Syndrome

An acute childhood illness, Reye’s syndrome causes fatty infiltration of the liver with concurrent hyperammonemia, encephalopathy, and increased intracranial pressure (ICP). In addition, fatty infiltration of the kidneys, brain, and myocardium may occur.
Reye’s syndrome affects children. It’s most common in patients ages 4 to 12, with a peak incidence at age 6.
The prognosis depends on the severity of central nervous system depression. Previously, mortality was as high as 90%. Today, ICP monitoring and, consequently, early treatment of increased ICP, along with other treatment measures, have cut mortality to about 20%. Death is usually a result of cerebral edema or respiratory arrest. Comatose patients who survive may have residual brain damage.

Causes
Incidence of Reye’s syndrome usually rises during influenza outbreaks and is linked to aspirin use. It almost always follows within 1 to 3 days of an acute viral infection, such as an upper respiratory tract infection, type B influenza, or varicella (chickenpox).
With Reye’s syndrome, damaged hepatic mitochondria disrupt the urea cycle, which normally changes ammonia to urea for its excretion from the body. This results in hyperammonemia, hypoglycemia, and an increase in serum short-chain fatty acids, leading to encephalopathy. Simultaneously, fatty infiltration is found in renal tubular cells, neuronal tissue, and muscle tissue, including the heart.

Signs and symptoms
Reye’s syndrome develops in five stages, but the severity of the child’s signs and symptoms varies with the degree of encephalopathy and cerebral edema. Infants may have atypical presentation.
After the initial viral infection, a brief recovery period follows when the child doesn’t seem seriously ill. A few days later, he develops intractable vomiting, lethargy, rapidly changing mental status (mild to severe agitation, confusion, irritability, delirium), hyperactive reflexes, and rising blood pressure, respiratory rate, and pulse rate.
Reye’s syndrome may progress to coma. As the coma deepens, seizures develop, followed by decreased tendon reflexes and, commonly, respiratory failure.
Increased ICP, a serious complication, results from cerebral edema. Such edema may develop as a result of acidosis, increased cerebral metabolic rate, or an impaired autoregulatory mechanism.

Diagnosis
Early diagnosis and treatment improves chances of recovery. A history of a recent viral disorder with typical signs and symptoms strongly suggests Reye’s syndrome. An increased serum ammonia level, abnormal clotting studies, and hepatic dysfunction confirm it.
Testing the serum salicylate level rules out aspirin overdose. Absence of jaundice, despite increased liver transaminase levels, rules out acute hepatic failure and hepatic encephalopathy.
Abnormal test results may include the following:

• Liver-function studies show aspartate aminotransferase and alanine aminotransferase levels elevated to twice normal; bilirubin level is usually normal.
• Liver biopsy reveals fatty droplets uniformly distributed throughout cells.
• Cerebrospinal fluid (CSF) analysis reveals a white blood cell count of less than 10; with coma, CSF pressure increases.
• Coagulation studies result in prolonged prothrombin and partial thromboplastin times.
• Blood values show elevated serum ammonia levels; normal or, in 15% of cases, low serum glucose levels; and increased serum fatty acid and lactate levels.

Stages And Management Of Reye's Syndrome

Stage I: Vomiting, lethargy, hepatic dysfunction.

Management: 

• Monitor vital signs and check level of consciousness for increasing lethargy. 
• Take vital signs more often as the patient’s condition deteriorates.
• Monitor fluid intake and output to prevent fluid overload. 
• Maintain urine output at 1 ml/kg/ hour, plasma osmolality at 290 mOsm, and blood glucose at 150 mg/dl. (Goal: Keep glucose levels high, osmolality normal to high, and ammonia levels low.) 
• Also, restrict protein.
• To decrease intracranial pressure (ICP) and brain edema, give I.V. fluids at two-thirds of the maintenance dose. 
• Also give an osmotic diuretic or furosemide.
• To treat hypoprothrombinemia, give vitamin K; if vitamin K proves unsuccessful, give fresh frozen plasma.
• Monitor serum ammonia and blood glucose levels and plasma osmolality every 4 to 8 hours to check progress.

Stage II: Hyperventilation, delirium, hepatic dysfunction, hyperactive reflexes.

Management:

• Continue baseline treatment as for Stage I.
• Maintain seizure precautions.
• Watch closely for any signs of coma that require invasive or supportive therapy such as intubation.
• Keep the head of the bed at a 30-degree angle.

Stage III: Coma, hyperventilation, decorticate rigidity, hepatic dysfunction.

Management:

• Monitor ICP (should be < 20 mm Hg before suctioning), or give a barbiturate I.V. as needed; hyperventilate the patient as necessary.
• When ventilating the patient, maintain PCO2 between 25 and 30 mm Hg and partial pressure of arterial oxygen between 80 and 100 mm Hg.
• Closely monitor cardiovascular status with a pulmonary artery catheter or central venous pressure line.
• Perform good skin and mouth care, and perform range-of-motion exercises.
• Provide endotracheal intubation and mechanical ventilation to control partial pressure of carbon dioxide (PCO2). A paralyzing agent, such as pancuronium I.V., may help maintain ventilation.
• Give mannitol I.V. or glycerol by naso-gastric tube.

Stage IV: Deepening coma; decerebrate rigidity; large, fixed pupils; minimal hepatic dysfunction

Management: 

• Check patient for loss of reflexes and signs of flaccidity.
• Give the family the extra support they need, considering their child’s poor prognosis.

Stage V: Seizures, loss of deep tendon reflexes, flaccidity, respiratory arrest, ammonia level > 300 mg/dl

• Help the family to face the patient’s impending death.