The Leftovers

The breathing treatment hall of shame

It’s a bright new year, and some of you probably spent yesterday regretting a few of the chemicals you chose to ingest the night before. What better time to go over breathing treatments other than the ubiquitous albuterol? Go ahead, sit down, fill up a neb, and puff-puff away. It might make you feel better …

I said in my first post that most of the other drugs we nebulize are typically useless. There’s a big proviso I have to attach to that, right off the bat: I haven’t worked with every single kind of breathing treatment. In particular, there are long-acting forms of albuterol—formoterol and arformoterol, among others—which can be put in a nebulizer. They last much longer than albuterol’s four to six hours, but they’re expensive and at least some of them have to be kept in the fridge. So I’ve never had a cause to work with them, at least in that form¹, and can’t assess.

So I’ll start with good old Xopenex, AKA levalbuterol. If you know a bit of chemistry, you might be aware that many molecules show chirality—the same set of atoms can be arranged in a “left-handed” or “right-handed” way². Standard albuterol is a racemic mixture, with both left- and right-handed forms. Levalbuterol is just the one form—I don’t recall if it’s “left” or “right”—which happens to be more selective for receptors in the lungs as opposed to the heart. What that means is that Xopenex is less likely to trigger tachycardia in sensitive patients. Not incapable, mind you, just less likely. It’s also more expensive, and gets over-ordered on every patient who has a heart condition even if that heart condition doesn’t make them prone to tachycardia³. Beyond that, yeah, it works well enough.

But then there’s Atrovent, which has been generic ipratropium for ages, but “Atrovent” is easier to say and type. As I said in All-Better-All, the majority of patients are going to be on (generic) Duoneb, which combines albuterol⁴ and ipratropium in one dose. In practice, it doesn’t really matter which the patient is on, because Atrovent is an anticholinergic which only works as an indirect bronchodilator; it discourages the muscle rings around your airway from tightening rather than tell them to open up. It’s kind of inoffensively useless, TBH. I’m sure it’s been found to be better than albuterol alone in studies. If a patient is so tachycardic they can’t even tolerate Xopenex, the doc may order Atrovent. In which case I’ll shrug and do it, but it’s probably not helping.

95% of the time, if you see Atrovent, it’s in combination with Xopenex. Like I said, Duoneb is the standard. If a patient can’t be on Duoneb, which is albuterol and ipratropium, what’s the next best thing? Clearly, levalbuterol and ipratropium! Which is a combination that you apparently can’t get premade, or if you can it’s not generic yet so my hospital doesn’t stock it⁵. So I go in, I squirt in some Xop, I squirt in some Atro, and the breathing treatment runs twice as long because there’s twice as much fluid in the little cup, and half of it’s kinda useless. This makes cardiac floors a real drag to mind, but it happens often enough that we just say “yeah, they’re on Xop-and-Atro q6” in shift-change report.

Passing from the merely annoying to the actively harmful: Pulmicort. Pulmicort, or budesonide⁶, is an inhaled corticosteroid (ICS) which works long-term to control symptoms of COPD. GOLD, the body responsible for making recommendations for COPD management, emphatically does not recommend starting every COPDer with ICS therapy; you adopt it in addition to other therapies if the others aren’t enough by themselves. Steroids reduce symptoms of COPD, but also increase your chance of developing pneumonia, which is extremely bad and a chronic issue in hospitals. And ventilator patients already have an elevated risk of pneumonia, so it’s presumably even worse for them.

Now, the average non-specialist hospitalist doctor doesn’t know all that, or what GOLD is for that matter, so he’ll order it on top of DuoNeb for an asthmatic COPDer if he looks kinda bad, or if a coin-flip comes up heads, or if the cafeteria was out of fries and he’s in a bad mood, or whatever. And in practice I imagine the risk of pneumonia is small, because—this is the funny part—studies show that budesonide takes a couple of weeks of regular dosing to build up to full strength. I don’t know if the pneumonia risk builds up faster than the benefits, but I’m inclined to doubt it. Most patients don’t stay in the hospital for more than two weeks, so in all likelihood Pulmicort is just another do-nothing drug. Probably you just have to worry about the thrush.

What’s that? Thrush? Oh, it’s a fungal infection in your mouth. You get it after using budesonide or other ICS drugs, especially if you neglect to rinse your mouth out after every dose. Which most RTs don’t bother to do, since they’re in a hurry. I can’t count the number of times I’ve had a patient rinse and had them tell me, “You’re the first person who’s asked me to do that.” Nor can I count the number of patients who told me, typically after the Pulmicort was delivered, that their tongue was really sore. When that happens, I notify the provider, who usually d/c’s⁷ it and orders the “magic mouthwash” antifungal compound to treat their patient who now has athlete’s foot in their mouth.

I think it’s a good idea to use budesonide on patients who use it routinely at home to treat COPD, to avoid disruption of therapy. The rest of the time, it’s basically just an invitation to thrush. But it gets ordered too frequently to fight every single time; I only make a fuss when it comes to, say, immune-compromised patients, who I suspect are going to be more vulnerable to both the thrush and the pneumonia.

Moving on: mucolytics. Drugs which are intended to break up mucus to make it easier to cough up. The best-known of these is MucoMyst, or acetylcysteine. Acetylcysteine is a terrific drug. It neutralizes the toxic metabolites your body produces when you ingest too much Tylenol, potentially saving your liver and thus your life if you get it quickly enough. Unfortunately, that’s what happens if you swallow it. If you breathe it, it makes the room smell like rotten eggs⁸ and irritates your airway to the point where you may start coughing violently or even go into bronchial constriction, even if you don’t have asthma or COPD. Which is why it is absolutely out of the question to nebulize a mucolytic without a bronchodilator like albuterol to counteract it.

So, why do we nebulize this stuff? Because the doctor believes it will make your mucus thinner. The body of scientific evidence for this belief is notoriously poor, so it’s basically witchcraft. Supposedly the sulfur atom in the compound bonds with sulfur in your lung secretions to break it up and make it easier to expectorate. In practice, I think it “works” to a very limited extent because it makes the patient cough much harder than they would normally cough of their own free will, for as long as they’re taking it. I’ve known a few oddball patients who swear by it and use it at home, perhaps for that reason. I can’t recall ever seeing a patient do much better from regular mucolytic use. But they all complain about it, unless they’re sedated.

There’s also hypertonic saline, which is to say saline which is more than 0.9% salt, saltier than your body’s tissues. This is supposed to work because the extra salt sucks the moisture out of your lung tissues into your mucus, thinning it out. Again, I can’t say I ever noticed a great difference. Patients can improve after days or weeks on this stuff⁹, but patients often get better naturally, from a variety of conditions.

As to hypertonic specifically, well, it’s not as stinky as MucoMyst. It’s still a noxious irritant. It doesn’t have the same bad reputation. But note that it works by being hypertonic, ie extra-salty. All nebs contain some amount of saline, and if a doctor is feeling zealous they’ll order the same patient to have, oh, Xopenex, Atrovent, Pulmicort, and add some 7% hypertonic alternating with MucoMyst every six hours. Look at me, I’m ordering all the stuff, I’m taking care of my patient, whoop-de-do.

But, aside from making the one visit take half an hour from all those treatments stacked end-to-end—and the patient will start to get quite testy past the twenty-minute mark, especially if they want to use the bathroom or eat—it’s common practice to just squirt everything in the cup together, cramming in as much as you can. I believe you’re supposed to do the bronchodilator first, wait for it to run out, then run the hypertonic by itself. However, as a famous internet sage reminds us, “Ain’t nobody got time for that.” Overworked RTs commonly dump in every drop they can, start the neb, move on to the next patient, start them, etc., and circle back to the original patient to take off the dry nebulizer¹⁰. A standard small-volume nebulizer might be able to fit in three drugs at once, and everything but the hypertonic will be 0.9%, soooo … how hypertonic is that neb treatment? A bit less than 3%, assuming the RT squeezed in the full dose of 7% with the other two instead of carelessly leaving a drop or two at the bottom. But the doc doesn’t know that.

That was quite a lengthy aside. But we’re nearing the end, where common stuff is concerned¹¹. Let’s end on a bright note: racemic ephinephrine. This is a genuine life-saver, under the right circumstances. You see, it sometimes happens that you extubate a patient who’s been on the ventilator for a bit, and their throat reacts to the sudden absence of a tube by trying to swell shut. Which, as you might imagine, can be fatal. This usually causes a noise known as “stridor,” which sounds kind of like a pig being strangled. Just a pathetic, unpleasant squeal, sometimes audible from the door. Racemic epi is the treatment for that. It doesn’t always work, but when it does, racemic epi can get inflamed vocal cords to relax and settle down, eliminating the need for emergency reintubations or tracheostomies. I keep a dose of racemic epi in my pocket, every day, just in case I need it, because if I need it I might need it very quickly, and the medicine cabinet might be a long way away. Its main side effect is, like albuterol’s, tachycardia. Totally worth it.

However—you did realize there would be a “however” here, didn’t you?—a lot of doctors don’t really have much experience with stridor or upper airway compromise, and they lean highly conservative. It doesn’t happen too often, but every now and then I’ll get called to a room for a stat racemic epi treatment, and … uh, that ain’t stridor, boss. It’s a weird upper-airway wheeze, and the patient is clearly not in any kind of respiratory distress. But I’m there, and doctors are not about to take your peon word for it on something this potentially serious, so you give the neb to treat the scary noise. Which persists after treatment, because it’s not actually the condition the drug was made to treat.

Nothing you can do but shrug and move on. Lots more nebs to do. Busy busy.

1. Many maintenance inhalers like Symbicort or Advair contain similar long-acting beta agonists (LABAs). I’ve used Advair myself, back in the day, since I used to have mildly serious problems with my asthma. My memory is that Advair worked okay, and we do use similar inhalers at my hospital. The ups and downs of those are too much for even one of my voluminous footnotes to handle.

2. Don’t ask me to elaborate on that. I don’t know what it means. I’m not a chemist, I just parrot what they tell me. Rawk! Got a cracker?

3. Elevated/rapid heart rate, if you’ve forgotten.

4. Brand names include Proventil, Ventolin, and ProAir, depending on form and manufacturer, but in this case we usually just say albuterol amongst ourselves.

5. I just looked it up, and apparently there’s an inhaler called Combimist? There’s an inhaler or neb for every conceivable combination of drugs, since every combination can be patented separately, and some sunny day they will all go off-patent and I’ll be slinging them too. For now, nope.

6. It’s at least easier to type than “ipratropium.” Real PITA remembering where the R’s go in that made-up drug name.

7. This medical abbreviation can mean you’re discontinuing a medicine or discharging a patient. Context is key.

8. Or farts/feces/sewage gas/something else horrible, depending who you ask.

9. I don’t think you’re supposed to be on it for weeks; I think you’re supposed to be on it for something like three days, tops, and you stop if the patient develops bronchial constriction or starts coughing up blood, etc. But it’s easy for a busy doctor to forget that they ordered a drug for a patient, and thus for the treatment to outlast the disease it’s meant to treat.

10. Are they supposed to do this? Hell no. The rules say you stay with the patient the whole time, in case of adverse reaction. But serious adverse reactions are quite rare, most of these patients have had this stuff multiple times before, and the workload at a facility may be high enough that doing it the right way would make a single round of treatments take three hours or more—you finish your morning rounds and immediately segue to your mid-morning rounds, then to your one-o’-clocks, etc. You’d run yourself ragged. So RTs have been doing the round-robin of the floors for ages. I try to avoid it, personally, but I’m not going to claim to be without sin. If the right way is impossible to execute in practice, you get the wrong way instead.

11. You can also neb tobramycin, lidocaine, tranexamic acid, morphine, epoprostenol, and probably a lot of other little oddball drugs I just haven’t been exposed to or have forgotten since respiratory school. Ask if you care; this post is getting lengthy.