Nursing care
Why does aspirin cause Reye syndrome in children with viral illness?
Written and reviewed by Hannah Nguyen, MSN, RN, CPN · 4 min read · Updated November 2026
Short answer
Nobody has fully proven why aspirin causes Reye syndrome, but the leading explanation is mitochondrial injury: in a child recovering from a virus such as influenza or chickenpox, salicylate appears to tip already stressed mitochondria into failure. The liver stops clearing fat and ammonia, and the brain swells. Aspirin use during viral illness raises the risk as much as 20-fold.
What the mitochondrial explanation says
Mitochondria handle fatty acid breakdown and part of the urea cycle, the pathway the liver uses to turn ammonia into urea. MSD Manuals describes Reye syndrome as mitochondrial dysfunction that disturbs fatty acid and carnitine metabolism, producing a picture that resembles inherited urea cycle and fat oxidation disorders.
When those mitochondria fail, fat builds up in liver cells and ammonia is not cleared. Ammonia and other toxic metabolites reach the brain, which swells and raises intracranial pressure. The virus seems to be the first hit and salicylate the second. MedlinePlus notes the cause is still not known, so treat the mechanism as the best current explanation rather than settled fact.
The timeline that gives it away
Reye syndrome is biphasic. The child has an ordinary viral illness, often influenza, chickenpox or an upper respiratory infection, and seems to be getting better. Then, about 5 to 7 days later per MSD Manuals, severe persistent vomiting begins along with a change in mental status that can range from mild memory problems to rapid progression toward coma.
MedlinePlus describes the child becoming confused, lethargic or hard to keep awake, and later having seizures. A stem that says a child recovering from the flu now has repeated vomiting and is unusually sleepy is pointing to this pattern, and the next question is often what medicine the parent gave for the fever.
The lab pattern, including the normal bilirubin
Expect high liver enzymes (more than three times normal), a high ammonia level and a prolonged prothrombin time. MSD Manuals also notes that glycogen depletion is common, so blood glucose can be low, which is why glucose control sits alongside intracranial pressure control in supportive care.
The detail students often miss: bilirubin is usually normal. The liver is failing at the mitochondrial level, but the child is typically not jaundiced. A pediatric stem with severe liver enzyme elevation, high ammonia and no jaundice fits Reye syndrome better than hepatitis, where yellow skin is expected.
Prevention and the age rule
The disease occurs almost exclusively in children younger than 18, and MedlinePlus calls it very rare now that aspirin is avoided in children. The teaching point is to avoid aspirin and other salicylates in children and teenagers, especially during a viral illness, unless a provider specifically prescribes it.
That exception matters on exams. MSD Manuals names Kawasaki disease as a condition where children still receive aspirin under medical supervision. Families should read labels for salicylate ingredients and use the fever reducer the provider recommends instead. The full nursing care plan for an affected child sits on the Reye syndrome page linked below.
Hypothetical practice scenario
Hypothetical scenario, not a real exam item: a 9-year-old recovering from chickenpox has vomited repeatedly since morning and is now drowsy and irritable. Which question should the nurse ask the parent first: whether the child has eaten today, whether siblings have had chickenpox, or which medicines were given for the fever?
Asking about fever medicines comes first, because salicylate exposure during a viral illness is what links this picture to Reye syndrome and changes how urgently the child is evaluated. Food intake explains the vomiting poorly and ignores the change in alertness. The siblings question concerns infection control, which can wait.
Sources and further reading
MSD Manual Professional Version: Reye Syndrome. Mitochondrial dysfunction, up to 20-fold risk with aspirin, age under 18, Kawasaki exception, biphasic course at 5 to 7 days, labs including normal bilirubin, glycogen depletion, supportive care.
MedlinePlus Medical Encyclopedia: Reye syndrome. Cause unknown but linked to aspirin in viral illness, symptoms progression, advice to avoid aspirin in children unless a provider directs it.
The next step on this is the same as on everything else here: answer questions and read the rationales. Our pediatrics practice questions are the closest set to what this page covers.
Common questions
Why does aspirin cause Reye syndrome?
The exact mechanism is unproven. The leading explanation is that salicylate, added to a recent viral infection, injures mitochondria in the liver and brain. Fat builds up in the liver, ammonia is not cleared, and the brain swells.
What age should not take aspirin?
Children and teenagers, since Reye syndrome occurs almost exclusively under age 18. Aspirin should be given to them only when a provider prescribes it, as in Kawasaki disease, and avoided especially during flu or chickenpox.
What are the signs of Reye syndrome?
Days after a viral illness seems to be improving, the child develops severe persistent vomiting, then confusion, lethargy or irritability that can progress to seizures and coma. Labs show high liver enzymes and ammonia, usually with normal bilirubin.