The Prostaglandin E hypothesis of central apnea. How RSV and other viruses really kill babies.

posted Feb 16, 2012, 2:03 PM by Admin PEMRF

So finally for the long promised entry on the clinical implications of our recent apnea paper. First off this is about central apnea. The real deal.  Not the perfectly fine kid who scared the parents with some spit-up and laryngospasm (the vocal cords reaction to milk and stomach acid is to spasm and stay closed, sometimes long enough for the baby to turn blue). Not just ALTEs. Real, scary, the fairies and changeling have arrived, central apnea.  The kind of apnea where the brain stops telling your baby to breathe.

Normally kids respond to infection and inflammatory conditions with fever. The process is involved but the simplified version goes like this. Interleukin-1β is released in response to fever. This in turn causes the release of prostaglandin E2 (PGE2). Some is stored in the liver, some is created de-novo in the brain. This brain  PGE2  binds receptors in the medulla and causes fever.

In vulnerable infants, for example the premature neonate with RSV, instead of developing fever, the response to this PGE2 is central apnea. This knowledge has been around for a while. While animal studies demonstrate this with an elegance that human observational studies cannot, at least two human studies do show evidence of elevated PGE2 in these babies.

Acetaminophen acts to prevent the formation of PGE2 in the brain (only). This is how it prevents fever. When you give it to a kid with fever it starts working when the PGE2 already present has been used up.  That’s why it works even better at preventing fever than treating it. This is really old information.

So these divergent pieces of information when placed side by side begged the obvious questions: Could acetaminophen be used to prevent vulnerable infants from apnea?  And what about the microsomal PGE2 released peripherally that could cross the blood brain barrier?  Could we target that with ibuprofen a peripheral PGE2 inhibitor?   Next post I’ll describe how we started to answer these questions.

Or if you’re so inclined you can just read the paper!

 (Interestingly there seems to be a window period when either or both apnea and fever but with age the apnea response goes away and is replaced by fever. This explains why fever and apnea seem inversely related in bronchiolitis/RSV studies)