Every person who has ever lived has had a fever.  Like breathing, eating, and sleeping, fever is universal, and this makes it normal.

Fever under 106 degrees is harmless.   No one has ever found a lasting impact from having a temperature go above 100, even to 105.8.

The only frightening impact of fever is that in young children (ages 1 1/2- 6 years old) it can spark a febrile seizure (in 2% of all children).

Even as scary and horrible as witnessing this is, these seizures are harmless, too.  They cause no lasting impact.

So, if fever is universal and harmless, why treat it?

The clear answer is summed up in one word:  comfort.  Clearly the higher our temperature the more miserable, usually, we get.  And to watch our kids suffer is impossible.

So, we treat fever, but we should know that we treat it to help our children feel better, not because they are in any danger.

This means that the treatments for fever must be entirely safe, otherwise we are trading comfort for danger.   There is little sense to reducing fever to make someone more comfortable if it places that person in any danger.  Again, this all hinges on the fact that fever, though very miserable, is entirely safe and free of all danger.

At this time, there are two drugs used widely to treat fever:  Acetaminophen and Ibuprofen.

Acetaminophen is also called Tylenol.

Ibuprofen is also called Motrin and Advil.

Aspirin, once the only drug used for fever, is no longer used for fever since it was found, some hundreds of years after wide use, to cause the deadly Reye’s syndrome.  A reminder that just because everyone uses it, the drug is not necessarily safe.

Let’s take a look at acetaminophen and ibuprofen and talk about what they are, how they work, how well do they work, how to use them.

ACETAMINOPHEN  (aka, Tylenol)

What is it?

Acetaminonphen is one of the oldest of all modern drugs, that is chemicals purified to be used to treat symptoms and illnesses.

It was first used as a medicine in 1893 in Germany, the result of research into the finding that some chemicals in coal tar could reduce pain and fever in 1886.  Three drugs were purified from coal tar, which is the goop left over when coal is baked to form coke, the coal product used to make steel.    Those three drugs, in case you are interested, are acetanilide (the first found, and the first taken away since it was so toxic), phenacetin (widely used for decades until overdoses were found to kill one’s kidneys), and paracetamol- known in the US as acetaminophen, or Tylenol.

How does it work?

Don’t be too surprised, but the most in-depth answer to this question is:  No one knows.

It’s quite a spectacle that one of our oldest drugs (1893) is being investigated in the most cutting edge neuroscience involving all sorts of specific receptors in the brain, but no one has it solved.

Here is what we do know.  It does not do much in the body, it seems to have all its impact in the brain.

It may have an impact on a number of systems in the brain, including key compounds that organize inflammation, or the key networks activated by opiates, or the key networks activated by cannabis, or the key networks activated by serotonin.

When I see an explanation that links how a drug works across such a broad list of possibilities, linking it to pot or morphine or Prozac, or aspirin, I know we don’t have an answer yet.

But the outcome is known- it reduces fever, and it reduces pain, it does not have much impact on actual inflammation in the body, just the aspects of inflammation controlled by the brain- fever and pain (that is, not swelling, redness, or heat at an inflamed site).

How well does it work?

Overall, if a child is given acetaminophen, there is about a 44% chance they will feel all the way better with essentially no fever and no pain.

That’s good and bad news.  The good news is that nearly half get a good response.  The bad news is that over half will not.

It also turns out that acetaminophen works better the lower the fever.  The action of acetaminophen is twice as effective if the child’s fever is less than 102.0 degrees, than if it is over 102.0.

How about the size of change?  For children with a fever of 102.6, acetaminophen dropped the temperature to an average of 100.4.

However, some analyses of all studies published found little difference in the course of fever between using acetaminophen and placebo!

If used for headache management, we now know that about 40% of people taking acetaminophen will experience relief, but the chance of feeling better with placebo was 20%!

Putting it all together this means that acetaminophen does reduce fever, but half the time not so much, and on average it brings it down, but not to 98.6.  And, it works better once you are over 6 years old.  The actual chance it will treat a fever and by how much is not fully established.

Is there any harm to using acetaminophen?

As noted above, acetaminophen comes from an unlikely source, the goop left over when coal is cooked to make coke.   The other two drugs in that category are both off the market due to toxicities.  Acetaminophen appears to be a safe chemical, but once swallowed, the liver breaks it down into a toxic compound.  Usually that is present in very low levels and may not cause any harm, but if you swallow a lot of acetaminophen pills, that breakdown product accumulates and can and does destroy your liver.

The most disturbing concern with acetaminophen is preliminary evidence that it can cause a child to be more likely to have asthma, and now some say even ADHD.

One study of 320,000 children in 22 countries found that the more acetaminophen used in a country, the higher the rate of asthma   A good study from Norway in 2016 found that kids at age 7 had a 30% greater chance of having asthma if the child took acetaminophen during infancy.

Various studies of pregnant women have found that use of acetaminophen in pregnancy leads to higher risks of asthma in the child by age 7, but others say it does not.  The study from Norway in 2016 found that kids at age 7 had a 13% greater chance of having asthma if their mothers took acetaminophen during their pregnancy.

A recent study (2016) found that kids with asthma have no worsening of their symptoms if they take acetaminophen which is reassuring.

IBUPROFEN (aka Motrin or Advil)

What is it?

Ibuprofen was created in the early 1960’s during work on simple organic acids.  Its first use was by its inventor in 1961 to treat his hangover.

It is part of a broad group of related anti-inflammatory drugs, including naproxen, indomethacin, toradol, and even aspirin.  Aspirin helps keep blood from clotting, none of the others, including ibuprofen do.

They all work by blocking the action of a key set of chemicals that cause inflammation, the prostaglandins, and they all block the production of prostaglandins in all the body.  Remember, acetaminophen works in the brain, ibuprofen works across the body.

How does it work?

Ibuprofen, like all the drugs in its category work by blocking the action of a key set of chemicals that cause inflammation, the prostaglandins, and they all block the production of prostaglandins in all the body.  Remember, acetaminophen works in the brain, ibuprofen works across the body.

How well does it work?

Overall, if a child is given ibuprofen, there is about a 70% chance they will feel all the way better with essentially no fever and no pain.

Ibuprofen too works better the lower the fever.  The action of ibuprofen is also twice as effective if the child’s fever is less than 102.0 degrees, than if it is over 102.0.

How about the size of change?  For children with a fever of 102.4, ibuprofen dropped the temperature to an average of 99.7

Putting it all together this means that ibuprofen does reduce fever, about 2/3 of the time, so more often than acetaminophen works, and drops the temp further.

Is there any harm to using ibuprofen?

In small doses it appears ibuprofen is pretty safe.

But, all the drugs in this class have two side effects worth keeping in mind when used in large doses for extended periods of time:

Bleeding from the gut, and increased risk of heart attacks and stroke.

More common side effects seen with infrequent use, such as for treating a few days of fever could include stomach ache, headache, and changes in stool.

USING ACETAMINOPHEN AND IBUPROFEN TOGETHER

The question often comes up, if you are giving your child ibuprofen and they are one of the 30% of fevers it doesn’t work for, is there any help gained from adding acetaminophen?   This is often done as the so-called “alternating course” where a dose of acetaminophen is given in between doses of ibuprofen.

So does that work better than using one of them?

The short answer is no.

That may come as a surprise to the 2/3 of families that use this technique, many of whom see their child’s fever drop when they do alternate use of ibuprofen and acetaminophen, but keep in mind the one essential property of fever- it goes up and down, and always goes down and away.  That means whatever you do, including nothing, it will appear that your plan worked, because all fevers drop and eventually cease.

There are not one, but many, studies that show that using ibuprofen and acetaminophen together offer no better drops in fever than using just one of these drugs.

Further, there are safety concerns about exposing our children to double the medication that they would be exposed to if only one is used.

Putting all the evidence together, the American Academy of Pediatrics recommends families do not alternate such therapies, a recommendation supported in pediatric societies across the world as well.

BOTTOM LINES

1. The only problem with fever is a real problem, it is terrifically uncomfortable and creates misery.
2.   BUT- FEVER IS AN EXPERIENCE EVERYONE HAS AND TURNS OUT TO BE COMPLETELY HARMLESS
3. The normal range of fever is 100.4-105.8.  This means temperatures in this range are to be expected and cause no harm.  Only if the temperature goes up to and beyond 106 does it begin to hurt.  Fortunately, it is exceedingly rare to see anyone’s temperature go to 106 or beyond.
4. The drugs most commonly used to treat fever don’t work all the time.  Acetaminophen (Tylenol) only works about half the time, and about a third of the time ibuprofen (Advil, Motrin) fails too.
5. Acetaminophen use during pregnancy and childhood may be associated with an increased risk of developing asthma, some studies link prenatal exposure to altered cognitive functions such as ADHD as well.  These concerns are not yet settled and proven, but until firm proof is set we recommend not using acetaminophen.
6. Ibuprofen is associated with the main side effects of gut bleeding and increased heart attacks, but only with prolonged use at high dose later in life.  Use for a few days to treat childhood fevers is likely safe.
7. The popular notion of alternating use of acetaminophen and ibuprofen, doesn’t work.  Ironically, it is popular because both drugs often fail as noted above.  If your child has a fever and the ibuprofen doesn’t work, it is tempting to add acetaminophen.  We do not recommend it.

The good news is that fever is not harmful, there is no actual urgency to treat it, but it’s nice to to reduce your child’s discomfort.  Neither of the drugs used work all the time, so do not be dismayed or surprised if you try them and they don’t work.

If you do choose to use a medicine to reduce fever, we prefer the use of ibuprofen until we know for sure of acetaminophen is safe to use.

To your health,
Dr. Arthur Lavin

http://www.nytimes.com/2016/09/25/opinion/sunday/the-trouble-with-tylenol-and-pregnancy.html