Thank you for being here, we were chatting up here and I realized that when I became a member in 1984, some of you probably weren't born, which is a little distressing, but I'm glad you're here, thank you for being here, I was also coming, there's no substitute for getting together and laughing and talking and getting to know each other and talking about research and caring for patients, I'm glad you're here and I'm glad we could finally get back together. So this is actually a pretty sensitive topic among respiratory therapists and that's the continuous use of albuterol in all mechanically ventilated patients for what seems like no reason. So I'm going to talk to you about how I think we got there and what we can do to fix it. Again so I've been a member for a long time, I'm on the editorial board, I was the chancellor of the board of regents in charge of clinical practice guidelines and have been at the university for over 40 years. These are companies that I'm either on the scientific advisory board for or do research with. So I'm going to talk about the use of aerosolized bronchodilators in ventilated patients, why do we give them, and then talk about where did this idea that albuterol helps all patients, it moves lung fluid, it improves the mucociliary escalator comes from, review the evidence for the use of bronchodilators during ARDS and hypoxemic respiratory failure, and talk about monitoring whether or not a bronchodilator is working, which is something we don't do because it's a little bit more complicated than it appears. So it appears that truthfully aerosolized bronchodilators are in fact a standard of care for patients who get intubated for asthma, which is a very small number of patients, but also with COPD where it has an effect and patients are using bronchodilators at home and when they're mechanically ventilated they receive a benefit. But aerosolized bronchodilators in ARDS and for hypoxic respiratory failure are also routinely delivered and actually have no basis in fact, and I, this is kind of that talk at the bedside, I've worked in the trauma ICU for my whole life, patient comes in, is on the ventilator after an automobile accident, oh well he's a smoker, oh well he probably needs albuterol then because he's on the ventilator, or maybe he has COPD when they look at the flow waveform. So most people will say, let's go ahead and give it because it can't hurt, it's really not that expensive, it doesn't take the therapist that much time depending on how you do it. Again, if the patient has some history, the adverse effects are minor, maybe it's a little bit of temporary tachycardia, again I haven't seen that very often, but there's a lot of discussion in the literature that it improves mucus removal and reduces lung water. So this is a really nice paper from Intensive Care Medicine that was published over almost a decade ago now, that's a French survey of how often do aerosolized treatments get given to patients who are mechanically ventilated, excuse me, and you can see, can I point at this? Yep, there you go. Here are the two most common drugs that are given, albuterol being the one that we would see most in the United States, and you can see white is they never deliver it, on exceptions they use it, it's usual treatment or it's a frequent treatment. So frequent treatment with albuterol on mechanically ventilated patients, again small response, only 15% response rate, but 95% of the respondents are giving their mechanically ventilated patients short-acting beta agonists. So interestingly enough, 43% of them use jet nebulizers, so just the ones that plug into the oxygen and blow up through the bottom, looks like one maybe somebody in your family uses at home for asthma. About half use metered dose inhalers, now this was 2013 before they switched us from CFCs to HFAs, in which case now the cost of MDIs skyrocketed. Just around 10% use vibrating mesh nebulizers, which are very popular in many places in the US because they're much more efficient, and about a quarter of the patients turn the heated humidifier off when they deliver the therapy. Now before we get into why you probably shouldn't deliver these, for sure shouldn't deliver them routinely, but could deliver them when they're indicated, the gold guidelines for care of COPD have evidence that proves albuterol short-acting beta agonists are important in patients who have a COPD exacerbation, especially if they're on mechanical ventilation. So we're not talking about COPD in ventilated patients in the medical ICU. So where does this idea come from? So this was a paper that was in the Blue Journal, or in ATS, the American Journal of Respiratory Cell and Molecular Biology, and I'm not going to read the whole thing to you, but it was based on an animal study and they concluded that beta agonists have the capacity to reduce lung edema and acute lung injury by improving lung vascular permeability and enhancing removal of alveolar fluid. And of course they said the only way we can figure this out, this is a group from here in San Francisco, is to do placebo-controlled clinical trials. So the first of those trials was published in the Blue Journal in 2006, again, based on this experimental data, but it was IV salbutamol, it was not an inhaled beta agonist. The primary endpoint was the amount of extravascular lung water, and the treatment group had lower lung waters at day seven and lower plateau pressures. But the treatment group also had a higher incidence of supraventricular arrhythmias. A number of other studies were done. So this was looking at adult subjects undergoing an esophagectomy for cancer, got either inhaled salmeterol versus placebo, it did not prevent acute lung injury. Then there was the BALTI-2 trial, which was IV salbutamol versus placebo, increased the 28-day mortality rate at the interim analysis and was stopped. Now most of you, when you hear ARDSNet, think of what is really the ARDSNet ARMA trial, which was the 6 mLs per kilo versus 12 mLs per kilo, and there's Alveoli, which was high PEEP versus low PEEP, and there's the FACT trial, which was the fluid and catheter trial, whether you get restrictive fluid therapy or did you get more aggressive therapy, and is it guided by a CVP catheter or not? But there were also a number of other studies, and one of them was a randomized placebo-controlled trial of aerosolized beta-agnes for the treatment of acute lung injury. And again, I'm not gonna go through all this data, but so a large number of patients, 152 in the albuterol group, 130 in the placebo group, looking at ventilator-free days at day 28, and there was no difference, death before discharge home at day 90, a little bit higher in the albuterol group, but none of this was statistically significant. This was a large trial, and what they concluded was the routine use of albuterol in mechanically ventilated patients with acute lung injury cannot be recommended, and I'm not sure why the interest in albuterol and reducing lung water in animal models with the IV has seemed to overcome this thought. There's a lot to giving an aerosolized bronchodilator to a mechanically ventilated patient. There are things related to the ventilator, there are issues related to the circuit, which device you use, you know, meter dose inhalers have become expensive in mechanically ventilated patients. You end up throwing away about 75% of the dose most of the time, so people have tried to move to common canister using the same MDI adapter, going from patient to patient, which of course got killed by COVID and probably will never come back. Now we see them making smaller meter dose inhalers that have fewer doses in them to reduce the cost. Nebulizers again, the updraft nebulizers are very inefficient, the circuit and the endotracheal tube are impediments to bronchodilator delivery. The mesh nebulizers are much more efficient, but I have to be honest here, from my standpoint, there are a lot of studies that are done looking at which nebulizer is the best. There's breath-actuated nebulizers that only fire during inspiration. The standard jet nebulizer, which is really cheap, I mean, on the order of dollars and basically gets purchased as a commodity at the hospital. And then there are the mesh nebulizers, which are much more expensive. But we put so much drug into the nebulizers that it probably doesn't matter which one you use. One of them is more efficient, so you give a longer treatment with the jet nebulizer. There's some disagreement about that, but for the most part, we don't have too much trouble delivering aerosolized bronchodilators to ventilated patients. And that's not the purpose of my talk. So this is one of the things that you'll see. This is probably a little bit different, I turned it upside down. This is a pressure or a flow volume curve in a mechanically ventilated patient. And going down is inspiration. This is expiration. And then this is on a mechanically ventilated patient. And then you come down here. And this is this very slow return to zero flow. And this is the place where the respiratory therapist will look and say, this patient appears to me to have expiratory flow limitation. Now this is pretty interesting, I always point this out. Why is the flow so high at the beginning? When you ventilate a patient, the circuit itself is very stiff. It has a compliance of about two milliliters per centimeter of water pressure. So the circuit stretches during inspiration. And at the very beginning of expiration, the circuit exhales. So you get this, what looks like a very high peak expiratory flow. But this is because of the ventilator circuit, not to the patient. This is where you have to look to see what's going on. You can monitor pressure volume and flow volume loops before and after delivery of a bronchodilator to determine if there's been a change. So here there are a number of ways to measure resistance. The ventilator usually will measure it for you. But be careful, because there's inspiratory resistance, the peak pressure minus the plateau divided by the flow. Then there's expiratory resistance, the plateau minus the total peak divided by the flow. And the question becomes, what flow? The peak flow? The mid-expiratory flow? The last 10%, that's actually where all the resistance is. Dean Hess and Ted Tabor, both respiratory therapists, wrote a paper in the Journal of Clinical Monitoring over 30 years ago. There are six methods, calculations for measuring airway resistance in mechanically ventilated patients. And if you use them, they all, six, give you a different value. So you have to be consistent. And expiratory resistance is what matters. The other thing that you can look at is the presence of auto-peep. And that's usually seen by what we call missed triggers. So this is a patient with COPD. And whenever you see the flow go up and then back down with no delivery of a ventilator breath, and if you happen to have esophageal pressure, you can see that. This is indicative of somebody with obstructive lung disease who requires aerosol therapy. This is a paper published in Restoricare from Georgopoulos' group from Greece. Looking at this, and this is a little bit different. Here's that exhalation part of the circuit compressible volume. And then you see there are different parts of the flow volume curve. And as you look at them, the pressure drop at that volume is a lot different. And there are significant differences in where you measure resistance. And this is before and after salbutamol and that salbutarol in that paper, looking at the plateau pressures, the intrinsic peep, and the trapped tidal volume, which is basically the compliance times the intrinsic peep. So there is a way to monitor bronchodilator delivery to see if it's valuable, but it's not done very often because it's a little bit difficult. Again, this is a little bit more time here looking at the resistance, the time constant of the respiratory system, which is just the compliance times the resistance. And these are those five different slices. And I really just want to show you how different the resistance is at the beginning of the breath versus at the end of the breath. It almost doubles. So in mechanically ventilated patients with COPD exacerbation, hailed salbutarol significantly decreases expiratory resistance and increases the rate of lung emptying, reduces auto-peep, reduces missed triggers. Expiratory resistance is several fold higher than end-inspiratory resistance. So inspiratory resistance is always less than expiratory resistance because during inspiration, you use positive pressure to help widen the airway. In expiratory measurements, you don't. There's no correlation between albuterol-induced changes in the expiratory and inspiratory resistance. I would encourage you this expiratory is the way to go. And these changes in the flow volume relationship are only accurately predicted the corresponding changes at the end of expiration. So what can we do about all this? Again, the data suggests that there's no real value. Who knows? How many of you, every mechanically ventilated patient gets albuterol? A number of you. It's not inexpensive. It takes therapist's time. Depending on how they do it, they might break the circuit, which we're all trying to avoid. But the use of albuterol based on could it improve mucociliary clearance or would it improve lung clearance of fluid just doesn't hold any water, quite frankly. So I wanted to show you this. This is a paper that's coming out in a couple months in respiratory care, and it's from a group in Wisconsin. And now this isn't specifically with bronchodilators, but they looked and said there are 9,000 aerosol treatments across our health system, and about 4,600 of them are not evidence-based. Most of them included 3% hypertonic saline as well as mucamyst, which I still in 40-something years of being a respiratory therapist am not sure if there's a good role of mucamyst unless you're going to drink it. It's the equivalent of almost seven full-time equivalents to give all this therapy. So again, this nebulous bronchodilator therapy is not without cost. So they did a study where they empowered the respiratory therapist to educate the physicians. And then after that educational component, they decided they would empower the therapist to discontinue the orders for these. And I see a lot of patients now in the surgical ICU are starting to get hypertonic saline aerosols to improve mucus clearance. Again, it's great for inducing a sputum in a patient who's not intubated. And they were able to reduce 90% of these treatments in a very short period of time. And here's their data looking at the baseline. And it's really interesting educating the physicians, meeting with them, providing them with the information that shows that these aerosols have no value, resulted in a slight fall in how much aerosol therapy was being delivered. But then once the post-policy activation went into place, it made a huge difference in how many of these treatments were in. It's a huge savings for the respiratory care budget line, savings for the hospital, and probably reduced unnecessary therapy and potentially complications in those patients. When I was a young respiratory therapist and worked at a children's hospital, we used to give all the cystic fibrosis patients got aerosol mucumus. And aside from being pretty bad smelling in the room, it's very caustic. It causes a lot of bronchospasm and airway edema. The important thing about it is it didn't cause the therapies like albuterol therapy for patients with chronic lung disease to fall at all. Now, these are not mechanically ventilated patients. So I think what this shows is that there is a way for us to implement a process to reduce unnecessary therapy related to aerosol therapy, both to the financial advantage of the health system as well as to the advantage of the patients not receiving therapies that have no value. But I think it's really important to see that just educating people has an advantage, but there needs to be a place where somebody can come in and discontinue these treatments that are unnecessary. So in the absence of airway reactivity, asthma, or COPD, beta agonists have no impact on ARDS physiology or outcomes, only negative outcomes. So if you're a physician in the room, please stop ordering it. Respiratory therapists make fun of people who order albuterol on everybody in the break room and think that everybody has to have albuterol no matter what happens. So it really is an issue, and it's an important issue, and I think it's very easily solved. It's just educating people and changing their attitudes. Thank you.

albuterol

mechanically ventilated patients

effectiveness

aerosolized bronchodilators

asthma