Q about Difficult Pediatric Airway (Croup vs Asthma Treatments)

[omarsaleh66]

Hey guys

When treating croup in children why is racemic epinephrine used instead of albuterol (like the formula used in acute asthma exacerbation).

Here are my thoughts: In croup, u get tachypneic, tachycardic and cyanotic so u give racemic epi cuz croup has refractory bronchospasms that albuterol cannot treat. Also does racemic epi mix better w the mist of O2/helium or whatever is used. Just wondering if I'm on the right track or if there is a deeper reason that I am missing.

THanks
Omar

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[beezar]

hmm, from what I've seen, they always use albuterol more for bronchospasm (ie: lower airway) and racemic epi is reserved for upper airway obstruction (stridor). Asthma is in the lower airways while croup is in the upper airway (subglottic stenosis usually).

 

[Adcadet]

Reasons of efficacy, perhaps? Just an MS3 guess. Buy hey, I've done 3 days of anesthesiology

 

[jetproppilot]

hmm, from what I've seen, they always use albuterol more for bronchospasm (ie: lower airway) and racemic epi is reserved for upper airway obstruction (stridor). Asthma is in the lower airways while croup is in the upper airway (subglottic stenosis usually).

exactamundo. Of course one could use epi for an asthma attack, in fact when I used to shadow an ER doc back in the mid 80s thats what he used. I'm sure it works, but with the onset of selective B2 agonists, thats where clinicians have gone with lower airway treatment.

The funny thing in medicine is as you do it longer, you see new treatments come up that everyone gravitates to. Sometimes they are better, sometimes they are not.

Hey Mil, whats your opinion on this, as far as gravitating to new, "better" treatment regimes? I mean, yeah, I know albuterol gives the bronchodilitation without all the cardiac sequelae, but in a 6 year old asthmatic, whats the difference if they get tachycardic from an epi treatment that probably costs pennies compared to all the albuterol treatments we give? Are we catering to the drug companies too much with albuterol usage when epi would work fine for most people with asthma attacks?

To the original poster,
1) Albuterol will work for an asthma attack.
2) Epi will work for an asthma attack AND upper airway edema, although epi is not "in vogue" for treating asthma attacks currently, even though it used to be used for same. I'm not sure whether this is a drug company-pressured trend or if studies have shown deleterious sequelae from using epi in asthma attacks. I'm not aware of any studies (in peer reviewed, non-drug company funded) that have poo-pooed epi's role in acute asthma exacerbation.

 

[jetproppilot]

Hey guys

Here are my thoughts: In croup, u get tachypneic, tachycardic and cyanotic so u give racemic epi cuz croup has refractory bronchospasms that albuterol cannot treat.
Omar

Croup (laryngotracheobronchitis) has nothing to do with bronchospasm...bronchospasm refers to the smallest airways spasming, down near the alveolar level, leading to profound air trapping, evident clinically by a prolonged expiratory phase and a "fight to exhale". No refractory bronchospasms with croup; croup is all "upper-airway" caused by inflammatory-induced edema in the larynx and bronchi. Look sometime at a cross section of a 2 year old's trachea...its pretty small to begin with...so add some edema and you can see where they can run into problems breathing...close off an already small trachea with some edema and you can see where the characteristic "seal-bark" cough comes from.

 

[militarymd]

exactamundo. Of course one could use epi for an asthma attack, in fact when I used to shadow an ER doc back in the mid 80s thats what he used. I'm sure it works, but with the onset of selective B2 agonists, thats where clinicians have gone with lower airway treatment.

The funny thing in medicine is as you do it longer, you see new treatments come up that everyone gravitates to. Sometimes they are better, sometimes they are not.

Hey Mil, whats your opinion on this, as far as gravitating to new, "better" treatment regimes? I mean, yeah, I know albuterol gives the bronchodilitation without all the cardiac sequelae, but in a 6 year old asthmatic, whats the difference if they get tachycardic from an epi treatment that probably costs pennies compared to all the albuterol treatments we give? Are we catering to the drug companies too much with albuterol usage when epi would work fine for most people with asthma attacks?

To the original poster,
1) Albuterol will work for an asthma attack.
2) Epi will work for an asthma attack AND upper airway edema, although epi is not "in vogue" for treating asthma attacks currently, even though it used to be used for same. I'm not sure whether this is a drug company-pressured trend or if studies have shown deleterious sequelae from using epi in asthma attacks. I'm not aware of any studies (in peer reviewed, non-drug company funded) that have poo-pooed epi's role in acute asthma exacerbation.

You're right Jet....the same is happening now with levalbuterol....same thing...just more expensive..

Do you guys remember Primatene mist.....racemic epi.

 

[Carm]

Sitting in the PICU right now and ran this by my attending. She says that there is a fair amount of older literature that shows, as in adults, the B2 specific effects of albuterol are superior to epi. She definitely said that epi works, but that it has just been accepted to use albuterol. Not sure the source of the literature, but from a pedi intensivists point of view, it is clear cut Albuterol.

Also remember that even though Epi can be used to treat asthma, albuterol is basically worthless in treating Croup.

 

[jetproppilot]

Sitting in the PICU right now and ran this by my attending. She says that there is a fair amount of older literature that shows, as in adults, the B2 specific effects of albuterol are superior to epi. She definitely said that epi works, but that it has just been accepted to use albuterol. Not sure the source of the literature, but from a pedi intensivists point of view, it is clear cut Albuterol.

Also remember that even though Epi can be used to treat asthma, albuterol is basically worthless in treating Croup.

We ALL use albuterol for bronchospasm. The question is, why dont we use epi? Drug-company-dollars-related or are selective B2 agonists truly superior to epi in the treatment of bronchospasm?

My initial visit to Pubmed.com makes me think its drug company related. Impress your attending, go to Pubmed.com, see whatcha think about some of the studies there comparing epi to a B2 agonist for pediatric bronchiolitis, print them, bring them to him/her, and say "what about these?"

 

[msumed]

Hey guys

When treating croup in children why is racemic epinephrine used instead of albuterol (like the formula used in acute asthma exacerbation).

Here are my thoughts: In croup, u get tachypneic, tachycardic and cyanotic so u give racemic epi cuz croup has refractory bronchospasms that albuterol cannot treat. Also does racemic epi mix better w the mist of O2/helium or whatever is used. Just wondering if I'm on the right track or if there is a deeper reason that I am missing.

THanks
Omar

the upper airway inflammation will respond the the alpha-1 mediated effects of racemic epi to help treat croup

 

[sdn1977]

As an "old" pharmacist...I might provide some insight. First, all epi has very short expiration dating-months rather than years that albuterol has. Racemic epi must be refrigerated and it is available as multidose vials (no longer allowed in hospitals) or very poorly labeled tiny ampules. The labeling (1:1000) was always confusing for nurses to dose properly (when it was used by them before respiratory therapists became standard). Refrigeration meant those who didn't use it all the time often couldn't find it when they needed it (injectable epi does not need refrigeration) and delayed treatment. Short dating meant replacing the racemic epi in all units where it is stored - ER, OR, ICU, cath lab, pulmonary, etc...every few months. Altho epi is cheap - so is albuterol and the cost of replacing the drug is more from the personnel required to go to each refrigerator rather than the drug itself. Albuterol rarely outdates in hospitals. Pulmonary therapists will carry a few ampules of albuterol in their pockets throughout their day and it can be easily stored and obtained from hospital dispensing modules (Pyxis, etc..) which makes it much more flexible. So, in my opinion, albuterol has replaced racemic epi not because it is that much better pharmacologically, rather it is better from a practical point of view. I think pulmonologists still use racemic epi for some diagnostic tests which is why it is still available in some hospitals.

 

[Noyac]

Wow, Thanks sdn1977.
I seem to recall somewhere in my residency that the racemic variety had less cardiovascular effects than the regular epi. Something to do with the two isomers (levo and dextro ?). Is this also true, sdn1077?

 

[sdn1977]

Good memory!! Yes, racemic epi is a combination of d & l isomers and epinephrine (injectable or topical) is only the l isomer. Generally, in drugs, the l isomer is the more potent physiologically, so you observe more stimulation of both alpha and beta receptors from epinephrine than from racemic epi because of the "dilution effect" from the mixture of isomers. But...its not predictable because altho epinephrine will cause positive inotropic & chronotropic action, it also rapidly causes vasoconstriction of the tissue - which makes its absorption variable in the bronchi, lung, etc.., which makes it unreliable for bronchodilation. I hope I explained it clearly...it was a long time ago....

 

[sdn1977]

An interesting addtion to the albuterol topic - drug companies responded to an appeal from an international environmental group a number of years ago when they were requested to eliminate propellants in their metered dose inhalers. Thats when the "branded" MDI's started changing (Serevent became Serevent Discus, Flovent became Flovent HFA, etc...)-these new delivery systems don't have propellants. The branded ones were the first because their patents weren't going to expire soon (drug patents are 17 years) so they could afford to make the changes - these are complicated and expensive delivery devices actually! But...the problem is with the albuterol MDI - it has been available generically so long, is so inexpensive, and is used so much it becomes an economic hardship to all (patients, hospitals, insurance) to change to these new delivery systems. At this point, it is my understanding there is no timetable for changing this drug. All others must change by a certain year.....I can't remember when though.

 

[jetproppilot]

As an "old" pharmacist...I might provide some insight. First, all epi has very short expiration dating-months rather than years that albuterol has. Racemic epi must be refrigerated and it is available as multidose vials (no longer allowed in hospitals) or very poorly labeled tiny ampules. The labeling (1:1000) was always confusing for nurses to dose properly (when it was used by them before respiratory therapists became standard). Refrigeration meant those who didn't use it all the time often couldn't find it when they needed it (injectable epi does not need refrigeration) and delayed treatment. Short dating meant replacing the racemic epi in all units where it is stored - ER, OR, ICU, cath lab, pulmonary, etc...every few months. Altho epi is cheap - so is albuterol and the cost of replacing the drug is more from the personnel required to go to each refrigerator rather than the drug itself. Albuterol rarely outdates in hospitals. Pulmonary therapists will carry a few ampules of albuterol in their pockets throughout their day and it can be easily stored and obtained from hospital dispensing modules (Pyxis, etc..) which makes it much more flexible. So, in my opinion, albuterol has replaced racemic epi not because it is that much better pharmacologically, rather it is better from a practical point of view. I think pulmonologists still use racemic epi for some diagnostic tests which is why it is still available in some hospitals.

GREAT, GREAT post. Thanks alot for your post.

 

[sublimazerules]

You're right Jet....the same is happening now with levalbuterol....same thing...just more expensive..

I'd disagree with you that levalbuterol (R-albuterol) is just a more expensive version of racemic albuterol (50% R-, 50% S-albuterol) that has no therapeutic advantage. It may turn out to be the case, but I think the jury is still out. There are a handful of articles published that suggest 1.25mg nebs of levalbuterol are more effective in increasing FEV1 in asthmatics than 2.5mg nebs of albuterol (a fair comparison, in my opinion, because you are comparing the same quantity of R-albuterol). There are a handful of studies that show no advantage to levalbuterol vs. albuterol, but at least a couple of these are comparing 5mg of racemic albuterol to 1.25mg levalbuterol, and a couple others are adding ipratropium to the racemic albuterol, but not to the levalbuterol, which makes for an unfair comparison in my opinion.

The big issue is, what is the effect, if any, of S-albuterol (the other half of racemic albuterol)? There seems to be some misconception that there is less tachycardia and other side effects with levalbuterol than with racemic albuterol, but this isn't supported in in vivo or in vitro studies. Most evidence sugests that R-albuterol is the compound responsible for both the therapeutic efect and the undesirable side effects. However, there are not many studies published as to what S-albuterol does.

There are some in vitro and some in vivo mice studies that suggest that S-albuterol actually can cause bronchoconstriction. S-albuterol also has a half-life 10X greater than R-albuterol, so this effect can persist long after the bronchodilatory effect of R-albuterol has worn off.

The fact is, racemic albuterol is actually two drugs, R-albuterol and S-albuterol, and we can't just assume that the S isomer is just an inactive compound. It may have very undesirable effects, but we don't know because it has not been fully studied by itself. The FDA is now requiring all new drugs to be pure isomers and not racemic mixtures, and I think this is due to the realization that different isomers of the same compound can have drastically different effects.

Some food for thought....R-carvone is perceived by olfactory receptors as spearmint, while S-carvone is perceived as dill. (bad pun, I know)

 

[omarsaleh66]

This is great, I learned alot thanks to everyone for your help.

peace
Omar