“Two Decades of Managing Asthma” by Peter Cox for OPENPediatrics
25
August

By Adem Lewis / in , , , , , , , /


OK, thanks. Good morning. As many of you know, I come from the beautiful
city of Cape Town, where I was lucky to start my medical career. And what I was charged with was saying, does
experience actually count in asthma? This is the medical school I went to, and
I think few could compete with that. And shortly after spending six years at that
medical school, I entered this hospital, which is Victoria Hospital in Cape Town. I was one of six housemen employed there,
and we learned to do pretty well everything. It is also there that I gained a really healthy
respect for airway obstruction. And airway obstruction is epiglottitis and
croup, and those are pretty easily treated with a tube. But airway obstruction is also asthma. And asthma, I think, remains one of the most
terrifying diseases that I’ve ever treated. You see a kid literally running out of gas
in front of you. And I’m reminded of a 19-year-old boy. He was a very mild asthmatic. He was shopping in Foschini’s and he had an
arrest, was brought into our casualty department with a silent chest. We did what we could, which was cortisone,
aminophylline, adrenaline. We put a tube in him. And I’m sure we contributed to his poor outcome,
because we pumped his chest up really high and he ended up with a tension pneumothorax,
and he died. And that left a marked impression on me now. There’s nothing new about asthma. Asthma actually comes from the Greek word,
and those of you can understand Greek will recognize the alpha, sigma, omega, mu, and
another alpha– asthma. And it was pretty well described by a number
of ancient people. Homer, 2,700 years ago, describes a warrior
dying at the end of a battle with asthma and perspiration. Hippocrates used asthma rather loosely. He mixed it up with dyspnea, tachypnea, orthopnea. And then Aretaeus from Cappadocia described
asthma, as you can see up there– the cheeks are ruddy, the eyes protuberant, as if from
strangulation. And so, well recognized over time. And if you come more recently, 1698, John
Floyer, and then Stewart and Gibson in 1896 really talk about asthma as we know it today. And you will see from the last two how the
treatment of asthma actually evolved from treating the acute paroxysm, removing the
exciting cause, and then manage them between the cases. To remind you– and I think this is a great
slide– on your left, you can see a normal airway with a nice, patent bronchus or bronchiolus. And on the right, the components of asthma,
which are bronchospasm, mucosal edema, and mucus plugging. And our treatment is really aimed at those
three, but we can really only pharmacologically modulate the first two. There are four ways that we can do this. And I’m just going to speak very briefly about
the first three, which is anticholinergics; nonanticholinergics– and those are bronchodilators–
and then corticosteroids. Interestingly– and I’d like you to see what’s
in gray at the bottom here– is that the initial advocacy for treating asthma was to smoke
particular kinds of asthma cigarettes. Now, these were laced with belladonna, which
is one of the anticholinergics. And this will cause bronchodilatation. The belladonna comes from this particular
plant, known as the thornapple plant, and also from this, which is Solanaceae. And you can see that William Osler, the father
of medicine, Johns Hopkins, actually used hypodermic injections of pilocarpine as part
of the treatment of asthma. This is 1914. What was on the previous slide was actually
a comment also by Osler, because he was advocating smoking weed long before Justin Trudeau, and
it’s 100 years ago. For those of you in Canada know the relevance
of that. So out of this comes ipratropium bromide. And actually was surprised when I looked it
up recently that this has never been advocated for the use of asthma. There are only studies looking at the use
of Atrovent in COPD. And yet, it is very commonly used. It’s got a number of different mechanisms
of action, not really clear. But now practically every patient that comes
into our ICU is treated with Atrovent. On the nonanticholinergic side, it’s two main
groups– the methylxanthines, which is coffee, aminophylline, which is a water-soluble component
of theophylline; and then the more direct-acting bronchodilators. And again, if you look at the first line,
you can see that adrenaline was advocated for the use and treatment of asthma in 1910
by Melland. Ephedrine came in a little bit later. And a metered-dose inhaler was introduced
in the 1950s, which was associated with a sudden spike in deaths. And this was because of the size and potency
of the dose that was given. With education and change in the dose, this
peak actually dropped. This is to show you what we now commonly use,
but this is nebulized adrenaline from the 1930s. And you can see more specific B2 agonists
were developed in the ’60s and ’70s, which ended up with us using salbutamol. This is a paper by Dez and Jeff, both have
been in the audience. We initially used isoproterenol– this is
before I got there. But Jeff told me recently that he actually
smuggled four ampoules of salbutamol in from Melbourne. I don’t think there was an REB because Dez
cracked these and gave them to a number of different children. And you can see on the vertical axis is CO2,
time on the horizontal axis. And salbutamol is more effective over time
at maintaining reasonable CO2 than isopropyl was. And then next we’ll show you that its effect
on heart rate was not as bad. Steroids were introduced in the 1950s. And this is one of five patients, a young
boy of 12 years old, who had severe asthma through the summer of 1950. And at this point in time, he was given cortisone,
which, his asthma symptoms abated. They came back again. He was given another dose. And you can see how every time he got a little
exacerbation of asthma, he was given either cortisone or ACTH, and his symptoms abated. So this has now become pretty standard. And because of the risks of large doses of
steroids, inhaled aerosol steroid became the standard. So what were we doing when I got there? This is two quick papers from SickKids published
in ’89 and the early ’90s. And you can see that we were using beta-agonists
in 100% of patients. Theophylline was standard. Steroids in most of the patients. And IV salbutamol and isoproterenol were in
about 48%. Atrovent was very rarely used. The important part is that the outcome is
excellent with this management, provided optimal use of bronchodilators and steroids and judicious
selection for those requiring ventilation. Another paper from SickKids– and this is
from Robin Cox, about the same era, using a very similar medication strategy– looked
at 19 ventilated patients, who were all muscular– paralyzed, and you can see that what was considered
permissive hypercapnia– CO2 was very high and was brought down to 45. That’s a big change from earlier on where
you aimed for more normal gases, but a much more aggressive approach than we would use
today. And you can see that pH goes up over time. Ventilator pressures– this is about 45 centimeters
of water. So that was what was happening when I arrived
there. The principles of ventilation were to avoid
all air trapping, allow the lungs to deflate, correct the hypoxemia, and try and avoid hyperinflation. What’s happened since then? So a couple of things I’ve learned. And this is from an Australian, and this isn’t
Mountain Equipment Co-op. If you remember what happens with this in
a normal lung, at the end of expiration, your alveolar pressure’s zero centimeters of water. If you look in the patient with airflow obstruction,
asthma, you can get gas trapping. And as you get gas trapping, your lung volume
increases. And as your lung volume increases, instead
of having a nice, compliant lung, you become very noncompliant. And the mechanics of the movement of your
diaphragm and chest wall are inhibited because everything is really overinflated. So I walked into a room one day, and I saw
one of our fellows, Margaret Schindler from Australia, straddling a patient and compressing
the chest. And what she was doing was trying to move
that very flat part of the PV curve to a point where you could actually get gas in and out
of the patient’s chest again. So rather than having a silent chest, we were
once again able to ventilate it. I’ve seen that happen a couple of times. And Malcolm Fisher was the principal all through
this paper. And for those of you from Australia, I’m told
that this is still a mechanism that’s commonly used by paramedics in the field. When I started, we wouldn’t have thought of
it, about using bronchoscopy. But if you think about what you’re dealing
with, you’re dealing with plugs in the major airways. And if you can get rid of them, putting a
bronchoscope in, using DNAs, you actually get patients to improve. And I don’t know if Sam’s in the audience,
but he will remember a couple of patients that we avoided ECMO by bronchoscoping them
and using DNAs. So that’s what’s changed there. I’ve never really understood why magnesium’s
good for asthma, so I tried to find some reason. And there were two papers published in The
Lancet in 2013. And there’s a very good editorial that goes
with those– this is by Rowe– that says that magnesium seems efficacious in children with
severe acute asthma. It’s not effective in adults, and basically
it should be reserved for those with very severe asthma. Again, if you come to our unit today, 100%
of our patients will have had magnesium in our emergency room. I’m grateful to Ivor Berkowitz for these slides. This is something you always talk about but
I’ve never done, and that’s the use of a volatile agent. And Ivor showed that in seven of the 18 patients
in his unit that were on mechanical ventilation, they used isoflurane. And with that, they had a very rapid change
in both CO2 and pH and were able to get these patients extubated much quicker than they
anticipated. So this is something that I’ve not used, but,
again, if you’re going to use it, in our situation, we would have to do it in the operating room,
because we don’t have the ability to scavenge volatile agents. ECMO– if you think about ECMO and asthma,
asthma is probably the ideal disease for ECMO. You’ve got a single system failure that you
know is going to reverse over time, and you just have to get them from one point to another. You have to balance that against the risks
of ECMO. And this is data that Anne Marie Guerguerian
kindly got for me, and you can see there are about 500 ECMO runs for asthma over the last–
oh, since 1984. And as anticipated, like many things, the
rate of use is increasing quite dramatically. And the outcomes, as shown in the previous
slide, had been about a 75% to 80% survival. So ECMO is certainly something to use. How are we doing? There are two papers published in 2012 that
you can look at. 13,500 patients– this is by Susan Bratton. And you can see there’s huge variability in
the way that medications are used to treat asthma. This is an important fact, is that 60% of
the patients in this study were intubated before a PICU admission. Complications are rare, and death is even
more rare. Kit Newth, an ex-SickKids fellow, also published
in the same year, 2012, a review of 261 children requiring ventilation. And again, 178, or 70% of them, were intubated
prior to admission to the ICU. And what I’d like to point out to you is this,
that there were 11 deaths in this cohort, of which 10 were prehospital. So if you come to us today, what’ll happen? This is what we gave you before. What we’ve added is magnesium; ipratroprium–
that’s about 100%. Here, we had permissive hypercapnia, 45. Here, we have permissive hypercapnia of 90
or more. We used muscle relaxation, which you never
see anymore. Now we use quite a lot of noninvasive ventilation. And I try to get my colleagues to remember
when last we intubated a patient for asthma in the unit, and I think there’s been one
in the last 10 years. So our practice has changed quite dramatically. What’s important, though, is that despite
the variability in practice, the majority of patients who come into an ICU with severe
asthma do pretty well. Most deaths, like the patient I described
in the beginning, happen outside of an intensive care unit. And so this is an article, or the editorial
that went with Kit Newth’s paper, and the statement is made, “an ounce of prevention
may be worth more than a pound of cure.” And I think what our role as intensivists
is, is to make sure that our patients are all referred to chest services, because what
happens outside of the ICU to all of these patients is the only thing that’s going to
really change the outcome. And so, experience counts, and I think it
does. I’ve learned to sit on my hands. And I know that, that’s very difficult when
you’re starting intensive care. But the older you get, the more you recognize
that this is what you should be doing, and you just keep your eyes open to watch what’s
going on. Thank you very much. Please help us improve the content by providing
us with some feedback.


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