0:03 Hey, this is Dr. Busty and we are in our
0:05 pulmonology section where we're going to
0:08 be doing a brief overview of the uh
0:11 management of acute asthma exacerbation.
0:13 I think it's important to recognize that
0:16 within this particular topic that if you
0:19 um haven't done so, it's probably worth
0:20 stopping and listening to some of the
0:24 background information or uh drug class
0:26 reviews for the different drugs or
0:27 agents because I'm not going to spend
0:29 time specifically going over the pharmarmacology
0:31 pharmarmacology
0:33 um and some of the main side effects and
0:34 those kind of things that we would
0:36 normally discuss in a drug class review.
0:38 So, those are made available. we do
0:41 provide those lecture topics and so I
0:43 just encourage you to know that
0:44 information as we move forward because
0:47 this is going to assume that you already
0:49 know some of that information and so
0:51 when somebody comes in with an acute
0:53 asthma exacerbation
0:55 um obviously they're short of breath
0:57 they're having difficulty with
1:00 oxygenation but even also some degree of
1:04 um ventilation oxygenation is getting
1:06 oxygen obviously from the air into our
1:08 blood and so it has to pass through all
1:10 the airways including the bronchules
1:12 into the alvoli so that it can exchange
1:14 and go and diffuse into the blood as
1:16 that's passing by. At the same time, the
1:18 blood is carrying endroducts of
1:21 metabolism, particularly CO2 that then
1:23 moves into the alvi and needs to be
1:26 exhaled out. That is ventilation. And so
1:28 when you start to have obstruction such
1:30 as an asthma exacerbation that can
1:34 happen, they develop these mucous plugs
1:36 um in pretty severe uh asthma attacks
1:39 that that then that plugged up area of
1:41 the airway cannot then not only get
1:44 oxygen but it also can't extract or
1:46 exhale off the CO2 and as a result of
1:49 that the patients can start to develop
1:52 um h become hypercapnic or hypercarbic
1:54 and these patients then go into
1:56 respiratory acid
1:58 as a result of it. And so our goal is to
2:01 open up those airways um to maximize
2:03 oxygenation and ventilation. And the
2:06 main stay of treatment in the acute,
2:07 right? Because there's not many drugs
2:09 that we have available that will manage
2:12 these patients acutely. But these are
2:14 the short acting broncoilators that are
2:16 listed here on this page. So we have
2:19 albuterol and epotroprium broomemide,
2:22 also known as atravent. Uh the obviously
2:24 the long acting agents aren't going to
2:25 help us. And in fact, if a patient is on
2:28 a long acting bronco dial beta aagonist,
2:30 uh, then that's actually a bad thing in
2:33 this situation. Uh, if patients are if
2:34 they haven't been on or they're already
2:36 on inhaled steroids, that's not going to
2:38 help us. You can give somebody
2:41 highdosese oral or IV steroids and we'll
2:42 talk about that here in a minute, but to
2:44 be honest with you, it's really not
2:46 going to help you in an acute setting
2:48 because those things are a delayed
2:51 onset. Um, so we have to think about how
2:52 we're going to open up those airways.
2:54 Then the first line therapy is
2:56 traditionally a combination of both
2:59 albuterol and uh epotropium or atrovent
3:02 both in pediatrics as well as adults.
3:04 Now the way you administer the
3:07 medication um is influenced by your
3:10 perception of the um literature uh and
3:11 your knowledge of the literature as well
3:14 as your own experience. Um if you look
3:16 up here you'll see that MDIs are
3:18 included in in this. So even a mendi
3:21 with a spacer four to eight puffs every
3:24 20 minutes for the next 4 hours or you
3:27 can use nebulizer solution and you see
3:30 that you give 2 to 5 milligs uh every 20
3:33 minutes for three doses. So we call that
3:35 stacking of the nebs and then you can
3:38 kind of start to taper out to every uh 1
3:39 to four hours as needed. But if you
3:42 can't get somebody to space beyond 4
3:43 hours then they usually need to be
3:45 admitted. Another option is just do it
3:48 via continuous uh usually sometimes
3:49 we'll use a positive pressure
3:52 ventilation system to uh deliver that or
3:54 you can just do it by a face mask
3:56 through nebulization. But the point here
3:59 is that MDIs or me doinators with a
4:02 spacer or nebulizer are pretty much
4:03 equally efficacious if you do them and
4:06 you implement them correctly. Um, and
4:07 the relevance of this is is that
4:10 patients outside of the hospital or
4:12 clinic environment can't carry and
4:14 generally don't carry a nebulizer
4:15 machine with them. So they need to know
4:17 how to use an MDI especially when they
4:20 get themselves in a difficult scenario.
4:22 Uh so the it is important to recognize
4:24 that the literature does support that if
4:26 you do it and you help the patient
4:28 through that process correctly.
4:31 Now when you consider eproprium comes
4:33 also an MDI as well as a neb and there
4:36 is duo nebs or comvent formulations
4:38 where they're formulated together. Now
4:40 when you look at these uh they're not
4:42 the same from the standpoint of their
4:44 pharmaccoinetic and dynamic profile. The
4:47 one problem with epotroprium compared to
4:49 albuterol is the epiropri has a delayed
4:51 onset maybe even up to 15 to 20 minutes
4:55 after administration but has a benefit
4:57 compared to albuterol in that epotropium
4:59 has a longer duration of action and so
5:01 that becomes somewhat relevant and we
5:03 think about it in this context here of
5:05 the pharmacocinetics. If you look at the
5:07 drug levels which then would exert some
5:11 pharmacologic effect over time here you
5:13 see that the albuterol which is the
5:16 darker uh you know line here starts
5:21 earlier usually within 5 to 15 minutes
5:23 uh but has a shorter duration of time
5:26 that it's that it's useful uh whereas
5:28 epotroprium as I said takes about 30 m
5:30 20 to 30 minutes or 15 to 20 minutes
5:33 before it actually starts to kick in uh
5:36 but lasts longer and so the duration is
5:40 longer. And so you create this overlap
5:42 uh where there's not only dual uh bronco
5:44 dilation happening but then there's a
5:46 continued bronco dilation effect
5:48 especially if somebody only got one dose
5:50 or the combo. And so the idea behind
5:51 this is that we stretch out the
5:54 broncodilatory activity from two
5:56 different mechanisms. Obviously beta
5:58 receptors and specifically the beta 2
5:59 receptors are being stimulated by the
6:03 alberol that increases cyclic AMP levels
6:05 that drives down cytoolic calcium causes
6:07 relaxation of the smooth muscle.
6:09 Epotropri is a muscerinic antagonist or
6:13 an anticolinergic um inhale uh
6:16 broncoilator and increases cyclic GMP
6:18 also driving cytolic calcium
6:20 concentrations down relaxing those
6:22 smooth muscle to broncoilate these
6:26 patients. Now steroids um are certainly
6:28 implemented but we we may give them
6:30 right when the patient comes in along
6:32 with these treatments. So treatments are
6:34 being stacked on top of each other,
6:35 right? You're doing multiple things at
6:38 the same time. But the reason that we
6:39 give them early is because there is a
6:42 delayed onset and we need to kick in the
6:44 drug as quickly as possible. Now the
6:46 problem within asthma is that there's
6:48 two phases of inflammatory response.
6:51 There's the acute uh sort of acute phase
6:53 reactions where there's the immune
6:54 system is initially spilling out all
6:56 these chemicals and mediators and then
6:58 there's the late phase which is where
7:00 there's this recruitment and the
7:01 migration of the white blood cells that
7:04 sets up the chronicity of a disease and
7:06 our goal in starting these is to try to
7:08 get a hold of that early phase and
7:10 prevent that late phase inflammatory
7:12 response from happening. So there is a
7:16 delay um but it's if by a few hours at
7:19 minimum. Okay. Now the way we administer
7:21 it is also very relevant and shows up on
7:24 Bor. There's really no difference in the
7:26 bioavailability whether you give it IV
7:30 or PO. Now here's the caveat. The caveat
7:32 is assuming that the patient isn't
7:35 nauseous and unfortunately steroids when
7:37 given by mouth especially on an empty
7:39 stomach can be irritating to the stomach
7:41 and cause nausea and vomiting. That's
7:43 not going to be helpful in a patient
7:46 who's in acute asthma exacerbation. The
7:47 other thing that's important to
7:48 recognize is that in a stressful
7:50 response, sometimes there's a
7:52 redistribution of the blood flow away
7:54 from the GI tract to more important
7:56 organ systems that are dealing with the
7:58 acute situation. And so therefore, the
8:01 the re the rate of absorption and the
8:03 overall amount that gets absorbed over a
8:07 period of a time may be affected by that
8:10 scenario. So most people in acute
8:11 situations, especially if you have
8:14 access to an IV or if you want to give
8:16 it IM cuz we do have IM steroids, then
8:18 that would be the way that some people
8:20 would do it basically to minimize
8:22 causing nausea, vomiting and or to not
8:25 worry about decreased potential GI
8:27 profusion in the context of a severe
8:30 asthma exacerbation. And one of the
8:32 other problems with aluterol is that
8:33 when you keep giving it, especially in
8:36 stack doses, that can make you also
8:38 vomit. And so we need to keep that in
8:40 mind and we don't want to cause another
8:42 problem because that certainly would
8:44 increase their risk for
8:46 aspiration. So if they're having
8:49 hypercarbia, right, retaining CO2 and
8:52 they're becoming hypercapnic or carbic,
8:54 then these patients are going to start
8:55 having an altered mental status. They
8:57 basically start getting very tired and
8:59 sleepy and they don't want to cooperate
9:01 and their mental status starts to
9:02 change. Well, you're not going to be
9:04 shoving oral medications down those
9:06 patients mouths because they're going to
9:09 be at risk for uh uh uh aspiration for
9:12 obvious reasons. Now, so predinazone or
9:14 predniscolone. Predinazone is the prod
9:17 drug prediniscolone. You can use either
9:20 one or methyl prediniscolone. If you're
9:22 going to use it IV, it needs to be the
9:24 suenate formulation. Whereas the methyl
9:26 prediniscolone acetate as a suspension,
9:29 it must be administered by IM injection.
9:32 Uh so you give it and you give it every
9:35 six hours um is typically how it's done.
9:37 Uh for pediatric p patients
9:39 prediniscolone again which is the active
9:42 form of predinazone 2 milligs per kilo
9:43 by mouth and we don't really need it for
9:45 that many days. Okay we're not looking
9:48 at chronic long-term use. Now, as I
9:49 mentioned at the beginning of this
9:51 lecture, especially in acute
9:52 exacerbation, we're trying to do
9:54 everything that we can to bronco dilate
9:56 these patients, prevent them from
9:58 obstructing and have it having mucus
9:59 plugging because then you can't
10:01 oxygenate or you can't ventilate. And
10:04 so, we really try to approach especially
10:07 in the more severe asthma attacks a
10:10 multiffactorial broncoilator properties.
10:12 So, this is where magnesium sulfate
10:15 infusions can be very helpful. Um again
10:18 if you think about knowing that smooth
10:20 muscle or any muscle has to have calcium
10:22 in the cytool for actinomyosin to
10:24 interact. If we can do anything to
10:27 reduce the amount of available mag uh
10:30 calcium present for actinomyosin to work
10:31 on then we're going to cause more
10:34 relaxation and more dilation. And so
10:36 when you think about that in the context
10:40 of magnesium calcium is a dvalent cation
10:43 but so is magnesium. And so what ends up
10:46 happening is they are magnesium competes
10:48 with calcium and functions kind of like
10:51 a calcium antagonist and as a result of
10:53 that magnesium can't be used by actin
10:56 andosin and so you get further
10:58 relaxation especially if patients are
11:00 not responding to initial um
11:03 broncoilatory pro uh uh medications. So
11:05 we usually give two this is adult dose
11:09 two to three grams IV over more rapid
11:12 infusion of 20 minutes. Um but you can
11:15 give it as fast as one gram per minute
11:18 um while the nebulizer treatments are
11:19 also going. So you have the ability to
11:22 do it. The point being is you want to
11:23 get them in because you don't really
11:25 don't want to intubate an asthmatic
11:26 because having them on a ventilator
11:28 causes a lot of problems in their
11:29 medical condition and it gets very
11:32 difficult to wean them off. Now what
11:35 about the use of recemic epinephrine via
11:38 uh nebulization? This drug was
11:41 historically used in the post-operative
11:45 setting to try to reduce oral like edema
11:47 uh from the endotrachial tube. Um and by
11:50 reducing the edema you could facilitate
11:52 sort of better air exchange and their
11:55 rapidity of re of recovery from the
11:57 post-operative from the operation so
11:59 that you can get them out. Well, so some
12:02 patients if they're having lurenio edema
12:04 or epiglatus that's edemmitus from the
12:07 endotracchial intubation or you have
12:09 swelling in that area recemic
12:11 epinephrine has been maybe potentially
12:14 helpful in reducing the amount of edema
12:16 and swelling in that area to maximize
12:19 movement. Why would it do that in any of
12:21 the tissue? Well, think about it.
12:24 Epinephrine works as a beta 1, beta 2,
12:27 and an alpha agonist. It stimulates all
12:29 of those receptors. And when you
12:31 stimulate the alpha receptor in
12:33 particular in this
12:36 scenario, you get vasoc constriction of
12:39 the blood vessels in that tissue. And as
12:40 a result, if you do have swelling and
12:43 you had edema and spasm and that because
12:46 of that adematus tissue, maybe that
12:48 epinephrine may constrict those vessels
12:50 and reduce the swelling. On top of that,
12:52 epinephrine stimulates the beta 2
12:55 receptors as well. And so but you know
12:57 that might add on some additional help.
13:00 So you get both broncoilatory effects as
13:02 well as the alpha 1 constricting
13:03 properties of the blood vessels in the
13:06 hopes that you reduce the swelling um
13:08 and edema around that area. Now you can
13:10 also administer it subcutaneously just
13:14 like you would for anaphylactic shock uh
13:15 for which is a type one hypersensitivity
13:18 reaction where we use the one to 1000 um
13:22 and you can administer it e or subq.
13:24 Now, if you're doing it IV, that
13:27 concentration is different, right? Uh if
13:29 you're doing it by nebulization, you you
13:32 pretty much put in.5 mls and you dilute
13:36 it up to 3 cm uh 3 mls of saline and you
13:37 administer over 15 minutes and you
13:41 repeat as needed. But that's when we
13:42 start to pull out that and this is
13:45 usually after people have already tried
13:47 epatropri and albuterol. They've already
13:48 been given magnesium. Okay, they're
13:50 still doing this. We don't want to
13:51 debate. We're trying everything we can.
13:53 And that's where maybe we start to
13:55 consider uh recemic epi knowing that
13:57 you're also going to get the beta 1
13:58 stimulation which is going to increase
14:00 your pulse which is also not sometimes
14:03 good. What about antibiotics? Should we
14:05 routinely start to use them? And the
14:07 answer is generally no unless you have
14:09 evidence for obvious infection or
14:11 pneumonia of some sort bacterial
14:13 infection in particular. And so usually
14:15 these patients are going to have a
14:17 fever. uh the white blood cell elevation
14:20 may be uh unreliable simply due to the
14:21 stress response of an asthma
14:24 exacerbation and depending on when you
14:26 draw the CBC in relationship of giving
14:29 the uh steroids. Steroids are known to
14:30 elevate the white blood cells. So you
14:32 kind of have to think about some of the
14:34 other things that would drive you to
14:36 want to use them but it should not be in
14:39 every single asthma exacerbation. But it
14:40 has some evidence in showing
14:43 improvements in symptoms and FEV1 which
14:45 is that forced expiratory volume in the
14:48 first second of exhalation and then it
14:50 may have some anti-inflammatory
14:51 properties. People tend to say that
14:54 about a zithroycin. The point being is
14:56 that you know if you reduce infection
14:58 you're going to reduce inflammation.
15:00 That's true for anything right? All
15:02 right. What about ventilation? So
15:03 remember I was telling you there's
15:05 oxygenation getting that oxygen down
15:07 into the alvoli so that you can exchange
15:10 and cause uh oxygenation to the blood.
15:12 Then there's the ventilation phase where
15:14 we try to exhale and get rid of
15:18 CO2. Um we tend to use or try to use
15:20 non-invasive ventilation. What I mean by
15:22 non-invasive is we're not going to do
15:24 RSI rapid sequence intubation where we
15:25 put an endotrachial tube down and
15:27 basically put them on a mechanical
15:29 ventilator. So our goal is to try to
15:32 avoid that with all cost. And so the
15:34 positive pressure ventilation or
15:36 non-invasive ventilation like BiPAP or
15:39 CPAP can be very helpful at maintaining
15:41 opening of those airways that are
15:44 spasming and trying to keep those alvei
15:47 open so that we maximize that gas
15:50 exchange. If we're going to have to
15:51 intubate the patient and undergo
15:54 invasive ventilation, then we need to
15:56 use the largest endotracchial tube
15:58 possible for that patient's age and
16:00 size. For an adult, if you can get an
16:03 eight or an 8.5 tube in, that's ideal
16:06 because again, trying to wean somebody
16:08 off of a ventilator and you're having to
16:10 breathe through a straw essentially. Uh
16:12 that's very that's very difficult. So
16:14 the bigger the straw, the easier it is
16:17 to breathe on that tube. So that's true
16:19 for any page of the patient. You always
16:21 want to try to use the largest
16:23 endotrachial tube that you can without
16:26 compromising the tissue or uh causing
16:28 trauma in the airway when you're placing
16:31 it in. We want to keep the peak plateau
16:32 pressures, that's the amount of pressure
16:35 that we're pushing in to be less than
16:37 30. And the reason for that is that we
16:38 don't want to put so much pressure in
16:41 the system to push those airways open
16:42 because then you can induce barrerow
16:46 trauma uh and that can lead to long-term
16:48 complications, remodeling of the airways
16:51 and also then start to even cause
16:54 inflammation itself. Helios is another
16:57 option that is sometimes used. There's
16:59 really no supporting evidence that it
17:02 should be used in all patients. Uh
17:04 however there are some again that just
17:06 are not responding where you again you
17:07 kind of think about it in the back of
17:09 your mind you pull it out. It is a
17:12 mixture of helium and oxygen and these
17:14 are the percents that you see here. Um
17:16 it works to replace basically the
17:19 nitrogen present in the air uh since
17:21 it's lighter in weight. So things move
17:24 around based on the density and that
17:26 makes it easier the theoretically easier
17:29 to breathe with less resistance to the
17:30 airways because remember we're trying to
17:33 maximize movement of air in and out and
17:35 so these are some of the things that are
17:39 sometimes utilized in there. Now again
17:41 through those ventilators and through
17:43 the non even the non-invasive we can
17:47 administer uh short acting uh bronco
17:50 dilators as part of this treatment. So,
17:52 you know, when we start somebody with an
17:54 acute exacerbation, we also need to be
17:56 thinking about what do we need to do to
17:58 transition them to the chronic phase
18:01 where we prevent that late phase
18:03 inflammatory response, but also try to
18:05 prevent the next asthma
18:07 exacerbation. And that's where looking
18:11 at um the adding on drugs and starting
18:13 them early in their process gets the
18:16 ball rolling. Not that they will stop
18:18 the acute exacerbation, but this
18:20 step-wise approach that's supported by
18:22 the GINA guidelines is really getting
18:24 patients geared now from an acute to
18:27 transitioning them to a chronic
18:28 maintenance phase. And you need to be
18:31 thinking about that early on. What drug
18:33 therapy do they need to be on? What were
18:35 they not on earlier that brought them
18:36 potentially in that caused that
18:38 exacerbation? So that that you can try
