Phenylephrine: A placebo you don’t need

The Pediatric Insider

© 2015 Roy Benaroch, MD

Doctors, myself included, are dismissive of placebos. “That doesn’t work,” we say, referring to countless therapies that have no benefit over fake therapies (placebos), including pediatric chiropractic, homeopathy, and acupuncture.

We need to be honest. We have our placebos, too—pushed by modern pharmaceutical companies and genuine medical doctors. Maybe we ought to spend more time cleaning up what we do rather than pointing fingers at them.

Case in point: phenylephrine, marketed as a nasal decongestant. To understand how phenylephrine (PE) became so popular, we’ll have to go backwards a bit, to 1994, when the FDA published a list of nasal decongestant products that it considered safe and effective. Anything on “the list” could be sold without further FDA review. Included on that list were two oral decongestants: phenylephrine and pseudoephedrine (commonly known by the brand name Sudafed), which was far more popular.

In the 2000’s, to combat the epidemic of methamphetamine abuse, Congress attached an amendment to the Patriot Act (yes, that Patriot Act), restricting the sale of pseudoephedrine-containing medications. You could still buy them, but in limited quantities, and you had to present your ID to the pharmacist so your purchases could be recorded and tracked. All pseudoephedrine-containing products were pulled from the shelves. And, predictably, sales suffered. People didn’t want the bother of confronting a pharmacist to buy Sudafed, and pharmacists frankly had better things to do with their time than check ID for $6 purchases.

The marketers, predictably, won: a whole slew of new products, containing PE instead of pseudoephedrine, hit the market, prominently displayed on store shelves. Names like “Sudafed PE” minimized the change in the active ingredients, relying on well-known brand names to sell the product. Within a few years, PE-containing products far outsold the hidden pseudoephedine products. And everyone was happy.

Well, almost everyone. If you had a stuffy nose, you were most certainly not happy. Because oral phenylephrine never actually worked. A 2007 review showed that the PE was no better than placebo, and the FDA considered removing it from the allowed-drugs monograph—but they were swayed by a different published analysis showing a small but positive effect of PE on one measure of nasal congestion. That study has been criticized on many grounds, including that it cherry-picked positive studies and ignored evidence that weighed against PE. Still, the FDA allowed PE to continue to be sold and advertised as effective—though they did request a solid, placebo-controlled study to settle the issue.

Now, finally, in 2015, a placebo-controlled study of PE has finally been published. It’s fairly large, using 539 adults, and it looked at multiple doses sizes of PE compared to placebo top treat seasonal allergic rhinitis. The results are unequivocal: PE, at every dose, works no better than placebo—meaning it doesn’t work at all. About 18% of study participants developed side effects, mostly headache (none were serious.)

I don’t know what the FDA is going to do with this information. They asked for it, and now they’ve got it. Perhaps they’ll pull PE from the shelves. Perhaps they’ll ask for more studies. Maybe they’ll say that the drug companies can no longer sell PE for allergies, but can continue to sell them for congestion caused by a common cold (there’s no evidence it works for that, either, but there are no big robust placebo controlled studies to cite.) For the time being, PE, the placebo, continues to be sold, and continues to be recommended by physicians. It’s hard to change habits.

If you’ve got a congested nose, there are some things that do work. Congestion can be relieved by saline washes or sprays or a steamy shower. If allergies are the culprit, a nasal steroid spray is very effective. Pseudoephedine (Sudafed) is still out there, though you have to ask for it. Topical nasal decongestant sprays (like Afrin) work, too, though should typically be used for only a few days.

Or, go with a placebo. If that’s your style, choose something safe, like a homeopathic product. It won’t relieve congestion any better than plain water, but at least it won’t hurt anything but your wallet. That’s more than I can say for phenylephrine and our other real-medicine-placebos.

A cold, the flu, or sinusitis? Part 1: Symptoms and Diagnosis

The Pediatric Insider

© 2015 Roy Benaroch, MD

 

We’re heading back into colder weather again, and along with the change in the leaves comes more people with miserable, congested noses. Today’s post is all about telling the difference. Next time, I’ll tell you how to treat them.

 

The common cold

Also called an “acute upper respiratory infection”, a “cold” is far and away the most common cause of congestion and cough. It usually starts with a vague ill feeling, followed by a sore throat and then a congested or drippy nose. Sometimes, there’s a fever at the start of the illness (that’s more common in babies and younger children.) A few days later, a cough begins. On average, the symptoms of a cold last about 10 days, though often the cough lingers for 2 or 3 weeks.

Notice: the symptoms grow or develop over several days, and the fever is really only at the beginning. By day 7-10 things are starting to improve.

 

Influenza

“The flu” is a specific viral infection, and it’s not just a bad cold. Symptoms including fever, sore throat, body aches, nasal congestion or drip, and cough all pretty much start all at the same time, or within a few hours. Sometimes there are also gastrointestinal symptoms like abdominal pain or vomiting. Fever and aches are usually the worst symptoms – you feel, pretty much, like you’ve been hit by a truck. The worst symptoms last five days, but the congestion and cough often linger for another week or so.

Notice: the symptoms are sudden and severe.

 

Sinusitis

Most common colds, of course, go away on their own, with or without any kind of treatment. But rarely a common cold can turn into a sinus infection. That occurs when the persistent mucus becomes infected with bacteria, leading to worsening symptoms 7-10 days into an ordinary cold, or persistent symptoms 2 weeks after a cold begins. Very rarely, sinusitis can start suddenly and severely, but much more typically there is first a cold that turns into a sinus infection.

Notice: a sinus infection is like a cold, but the symptoms worsen after 7-10 days. A congested nose for less than 7-10 days is unlikely to be a sinus infection, even if it feels really stuffy.

 

Next up: treating colds, the flu, and sinus infections.

The whole series:

A cold, the flu, or sinusitis? Part 1: Symptoms and Diagnosis

A cold, the flu, or sinusitis? Part 2: Treatment

A cold, the flu, or sinusitis? Part 3: Myths

 

How to treat congestion in babies

The Pediatric Insider

© 2013 Roy Benaroch, MD

Life isn’t easy for babies. You can’t talk, and to get anywhere you have to wave your arms around and hope someone carries you. Perhaps worst of all, when you’ve got a cold your little nose gets so stuffy, it’s miserable.

Face it: no matter how smart your baby is, she probably hasn’t figured out how to blow her nose. Are there any practical ways to help unstuff congested baby?

• Keep the room humid, using a cool-mist humidifier or a warm vaporizer. Moist air prevents mucus from getting stick and sticky and harder to move.

• Try using a few drops of nasal saline. You can buy a little bottle at the drug store, or make it yourself.  Squirt or drip a few drops of this up each nostril to loosen mucus. You can repeat this as often as you’d like.

• A nasal bulb aspirator can help pull out at least some of the mucus. Remember, first squeeze it, then gently press the tip against the nose opening, then let go so it sucks out the yuck.

• Gently inclining the bed can help, but it’s not a good idea to routinely let babies sleep in a car seat, bouncy seat, or other device that holds them upright.

• Vapor-rubs like “Vicks” might help some with congestion, though good studies haven’t been done, especially in young babies. If you want to try a product like this, it’s essential that your baby NOT be able to eat or lick any of the rub. It’s very toxic if ingested.

Fortunately, even the most congestion baby usually feels much better in a day or two. If your congested baby is acting ill, having trouble nursing, having any trouble breathing, or isn’t improving in a few days it’s a good idea to head to the doctor.

Great study, but wrong conclusion: The Vapo Rub fail

The Pediatric Insider

© 2010 Roy Benaroch, MD

A study due for publication in December, 2010 claims to show that Vick’s Vapo Rub can help your child fight through the common cold. Though it was funded by the manufacturer (Procter and Gamble), it’s a good study—but if you read it carefully, there are some big red flags that say “Beware!” I don’t agree with the author’s conclusions, and I don’t agree with headlines in the media extolling the virtues of Vick’s. The study was well-designed, but the authors themselves found a fatal flaw that renders their results meaningless.

The study design was solid, and cleverly tried to prevent parents from being able to skew the results. 138 kids from age 2-11 years with at least moderate coughs were recruited. Children with more-specific causes of cough, like asthma, were excluded; and the children were not allowed to take other kinds of medication that might suppress a cough. The group was divided into thirds: one group received no treatment at all, one group received plain petrolatum (similar to Vaseline), and one group received Vick’s Vapo Rub. The parents were given a glass jar in an opaque bag with their study drug (or an empty jar, if they were in the no treatment group), along with a second jar that contained Vapo Rub in all three groups. When the families began treatment, they were instructed to first rub Vapo Rub under their own noses—then rub the study medication on their child’s chest. By putting Vapo Rub on the parents, the hope was that parents would not be able to tell whether they had put plain petrolatum or Vapo Rub on their child’s chest.

The next day, parents filled out a questionnaire, recording how well, or how poorly, their child did. The kids who received Vapo Rub did the best, especially when their ability to sleep was judged. That’s what the mainstream and medical press are reporting. But sometimes it pays to read the study a little bit further.

Thought the authors tried to prevent the parents from knowing what treatment group they were in, 90% of the parents correctly “guessed” what their child had been treated with the night before. I don’t know if the parents were able to smell past the Vick’s on their own noses, or if they didn’t follow directions, or if the approximately 50% of children in the Vapo Rub group who developed skin irritation gave it away—but in any case, this was essentially an unblinded study. Almost all of the parents knew whether their child was treated with Vick’s or the placebo—and that could certainly account for the observed differences in how the children did.

It’s human nature. The placebo effect has been documented in almost every clinical study that’s been done. People who are given what they think is medicine expect to get better, or expect their kids to get better, and will honestly judge that they did get better. Even if the “medicine” is itself just a placebo. Our own expectations influence our perceptions. If study participants are aware of whether they’re taking placebo or the study drug, clinical studies of medications are worthless.

There are other reasons to think twice before using Vick’s Vapo Rub. It can be quite toxic—according to the discussion section of this new study, an 8 tsp dose can kill a child. Much smaller doses are probably safe, but have occasionally been linked to seizures (children with seizures were excluded from the study.) In children less than two, Vick’s can cause serious lung irritation and breathing troubles.

When deciding whether to try a treatment, parents and physicians ought to weight the risks and the benefits. This study, in which the participants were inadvertently unblinded, allows us to draw no conclusions about whether Vick’s actually works. We do know that there are genuine risks. I’d stay away from Vicks, especially in younger children, until there is better proof that it actually works.

If you do want to try Vick’s Vapo Rub, follow the directions carefully. Do not put any near your child’s mouth, and do not use it in children less than two. Keep it way out of the reach of children and pets.

Too many colds

The Pediatric Insider

© 2010 Roy Benaroch, MD

Claire wanted to know why her kids get sick so much. So many colds, so much snot. Is there any way to stop this?

Colds are called “upper respiratory infections” in doctor-talk. They’re caused by one of hundreds of viruses that invade the tissues of your nose, sinuses, and throat. Typically symptoms begin with a sore throat, move into a stuffy nose, and then cause a lingering cough as a good-bye present.

Normal kids get a lot of upper respiratory infections, about twelve per year for pre-schoolers and nine per year for kindergarteners. They tend to occur more frequently once school starts in the fall, and last all through the winter. So from September through March you can expect what will seem like at least one cold a month. Since ordinary colds last at least 10 days, for the winter it seems like many kids are sick more days than they’re well.

What about those kids who really do get more than their share of colds, or the kids whose colds linger for weeks and turn into sinus infections or other problems? Think about these kids in three groups:

1. Otherwise completely healthy kids who just get a lot of colds. They get better on their own, but seem to get “frequent colds” one after another in a string of isolated episodes. There’s no history of other infections, unusual infections, or anything else about these children that seems unhealthy.  They’re often in day care or school, and sometimes get extra exposures to cold viruses from helpful siblings. This is the largest of the three groups.

1. Kids who “keep a cold.” These children get many colds, but don’t get better on their own. The cold symptoms linger and last “forever.” Often their colds will turn into ear infections or sinus infections, and won’t get better until an antibiotic is prescribed. Other than the lingering colds, these kids are not otherwise unwell. They don’t get lots of infections other than these respiratory problems, they’re growing well, they’re doing fine. They just have persistent snotty noses.

1. Kids who are genuinely unwell. By far, this is the smallest of the three groups. These are children who are often not growing well, and suffer from many other frequent infections including chronic diarrhea, thrush, and other unusual or chronic, hard-to-treat infections. Kids in this group should be aggressively evaluated for an immune deficiency, and should be seen by a specialist in pediatric immunology.

Kids in group 3 are rare, but characteristic, and it’s easy to tell that these children are different. It’s sometimes tricky to separate group 1 from group 2, especially if the group 1 kids get so many colds that one just immediately follows another. The best “test” to tell if your child is in group 1 or group 2 is for parents to keep a “snot calendar.” Group 1 children, the “frequent colds,” really should get completely better, at least briefly, in between individual cold episodes. Group 2 kids, the “keep a colds,” have symptoms that get better and worse, but are never completely free of cold symptoms.

“Frequent colds” versus “keep a cold” kids are different. Though they might both benefit from strategies to prevent colds in the first place (more about that later), the children who “keep a cold” very often develop complications of viral respiratory infections: bacterial sinusitis or ear infections. Snot that stays in one place for too long is very inviting to bacteria– like a sticky, inviting swimming pool– and eventually, kids who “keep a cold” are going to be infected with bacteria. To help avoid these secondary infections, families with “keep a cold” kids need to get very aggressive about clearing out mucus. Use a humidifier, long steamy showers, and saline nose drops. Anything that physically clears out mucus will make secondary infections less likely. The children will feel better, and will need fewer antibiotics. Families who get good at mucus control might even be able to avoid a trip to the ENT for sinus surgery or ear tubes.

“Keep a cold” kids tend to run in families, probably because their parents share their same small sinuses and ear anatomy that makes clearance of mucus difficult. Some of these kids might also have allergies that trigger very similar symptoms. If your child who keeps a cold has symptoms of allergy (itchy nose, itchy eyes, sneezing) or a strong family history of allergy, further testing or treatment of possible allergies might be worthwhile.

Whether your child is in the “frequent colds” of group 1 or the “keep a cold” of group two, strategies to avoid infections are a good idea. Many, many respiratory virus exposures occur in day care. Can you move your child out of group care, at least for the winter? Children can be taught not to rub or touch their own face, which prevents viruses on their hands from invading their usual ports of entry, the nose, eyes, and mouth. Avoid playing with toys in common areas like doctor waiting rooms, and stay out of little gym classes and fast food play areas. Get into the habit of washing hands frequently or using an alcohol-based hand sanitizer to prevent not only upper respiratory infections, but common “tummy bugs” as well.

There are plenty of herbal products and supplements that claim to protect your child from colds. They’re quackery. Save your money for something else.

Some vaccines can help prevent at least some respiratory infections, and even some complications. Influenza vaccines should be given to all children each winter. Very recently, the Prevnar (pneumococcal) vaccine was improved to include several more strains of this common bacterial cause of ear infections and sinus infections. These vaccines will not prevent all or even most of these infections, but they can make an important difference.

What about medicines to treat Junior when he has a cold? Though they’re marketed very heavily, they’re not very effective. Your best bets for symptom relief during a cold are acetaminophen or ibuprofen for aches, nasal saline washes for congestion, honey for cough (over age 12 months), throat drops for sore throat, and ice cream for the child and the parents. There. Doesn’t that feel better?

Out, damn’d snot

“Out, damn’d snot! out, I say!—One; two: why, then ’tis time to do’t.—Hell is murky.—Fie, my lord, fie, a soldier, and afeard? What need we fear who knows it, when none can call our pow’r to accompt?—Yet who would have thought the child to have had so much snot in him?”

Macbeth Act 5, scene 1, 26–40. Adapted.

One of the joys of being a pediatrician is that I can still make jokes about snot. I get all serious sometimes during the physical exam, asking a six year old to turn up their nose for a careful look. Then I make a concerned “Hmmmmm noise”—you know, create some comedic tension—then, a pause, followed by one of my best one-liners: “Ewww! Boogers!”

It cracks them up. Really.

Shannon asked me to write about whether the fancy-pants new high-tech nasal aspirators are any better than the old fashioned ones at de-snotting kids. The truth is, I have no idea. But there are plenty of other booger-tidbits I’d be happy to share—so join me for what promises to be the most revolting post of 2009, a journey of mucus and fun!

Snot is nasal mucus, made by specialized cells lining the nose, sinuses, and the entire respiratory tree. It’s mostly water, plus specialized proteins called mucins that help create its wonderfully sticky character. Mucus also contains disease-fighting antibodies and chemicals that can tear apart infectious particles. Not only does it help prevent and treat infections, but it also keeps the nasal linings happy and moist, and humidifies inhaled air. Its sticky surface traps pollens, infectious particles, and airborne pollutants, sort of like built-in fly paper. Under ordinary circumstances, a person makes—and swallows– about a quart of it a day.

The most common “chief complaint” for visits to a pediatric office is nasal congestion, most often caused by an upper respiratory infection, or “the common cold.” The snot, especially early on in the cold when it’s clear and watery, is loaded with infectious viral particles. That’s why colds are so common: they make your nose runny and irritated, so you rub it, then touch a doorknob, and then the virus can easily spread to the rest of the family and everyone else in the classroom. Towards the end of a cold, snot will get thick and dark and lovely yellow-green (especially the stuff in that first morning tissue.) By then, the mucus isn’t infectious anymore. Rather than being loaded with virus, it’s filled with dead and dying infection-fighting cells and sloughed debris from your nose. It’s a misconception (unfortunately perpetuated by many doctors, I know) that green snot at the end of a cold means that there’s some kind of infection that needs antibiotics. ‘Taint true, though if thick persistent all-day mucus lasts longer than 10-14 days at the end of a cold, you might have a sinus infection brewing. It’s the duration of symptoms that helps distinguish a cold from sinusitis, not the color of the boogers. And no, you don’t need to bring in a sample for your pediatrician to examine. Really. Thanks.

Excessive snot could be caused by other things. Allergies can make your nose run, though more commonly allergies cause swelling of the lining of the nose, causing a congested feeling without much actual extra mucus. When you cry or have irritated, teary eyes, the tears drain into your nose through little ducts, which makes your nose run too. And a three year old who shoves a lego up her nose is going to get one heck of a snotty discharge in a few days. About once a year I see a toddler with a “cold”—but a cold that oddly enough only leads to nasal discharge from one nostril. If your child has two nostrils, but only one of them is runny, take a look up there. You might just find a toy you thought was missing.

Too much snot causes a few problems. In the short-run, it might make it hard for your child to get comfortable, and can interfere with sleep. More importantly, nasal mucus that just sits there in the nasal cavity is a warm and inviting media for bacteria, and can eventually lead to secondary bacterial infections like ear infections and sinusitis. So both for symptom relief and for the prevention of these infections, it’s a good idea to at least try to get the boogers out of there.

What about cold medicines? The short answer: they don’t work. Some contain antihistamines that may make your child sleepy—that’s not a bad thing, as long as it’s safe—but none actually decrease mucus accumulation . Topical decongestants like Afrin do work, but are potentially addictive and shouldn’t routinely be used in children.

So a more creative approach is needed. Traditional, effective advice includes giving the child extra fluids, humidifying the air, and sitting in a steamy bathroom. These will all keep the mucus nice and runny rather than thick and sticky. You can also put a few drops of saline solution in the nostrils, or even better use a nasal saline irrigator to wash out the boogies. Loose, watery mucus can also be sucked out with a traditional bulb aspirator.

You say you want something fancy, something high-tech, something to casually whip out to the oooohs and aaaaahs of the envious playgroup crowd? This electronic marvel boasts twelve different tunes it can play to distract your honey while her nose is sucked out. (Got to be at least 12. Junior would certainly complain if the same tedious song were played during each episode of nose-sucking. I’m surprised there isn’t a built-in MP3 player.) Or the Nosefrida, manufactured in Sweden, which apparently lets you inflate your baby’s head much like a carnival balloon. I can’t believe I’m raising three kids without it!

I have no experience with these newer nose-suckers, so please, if you get one, post a review. Anyone who posts gets double points if you include a photo—of the kid, not the snot. I really can live without seeing that!

A cold lasts longer than you think

Here’s a simple question: how long should symptoms of a common cold last? Three days? How about five? Maybe a week?

A study published in January, 2008 sought to answer that question. School-age children were followed for several months, and kept records of the onset and duration of common cold symptoms like fever, congestion, cough, sneezing, and runny nose. During the study period, 81 colds occurred. The investigators also collected mucus from the kids during their colds to test it for viruses and bacteria.