Staten Island Corner: Asthma: Enough with the Prednisone, make it Dex…

WELCOME to this month’s edition of Staten Island Corner.  For this month we have a guest appearance from the Staten Island Chief himself Dr. Caputo.

…So without further adieu please read the following written by Billy:

Asthma is one of the most common reasons for patients to present for acute evaluation. Some exacerbations warrant admission for inpatient care, but many can be managed effectively on an outpatient basis with a combination of avoiding environmental triggers, inhaled β-agonists, a short course of oral steroids, and close follow-up.

It is well proven that a short course of steroids is beneficial in acute asthma and this will not address the EBM behind this.  The issue that will be addressed is whether we are using the right steroid.  You cannot walk passed an asthma room without getting 60mg of prednisone and multiple nebs thrown in our face, even if we are not patients.

Background

Things to look at in terms of a medication in general or more specifically a steroid in asthma is: effectiveness, cost, patient compliance, and side effect profile.

Each steroid is differentiated based upon their glucocorticoid and mineralocorticoid activity, in addition to their half life.  This is based around hydrocortisone.  Below is the chart of this:

As you can see, the half-life of Dexamethasone is the longest and can be double that of Prednsione and Solu-medrol.

Second, Dexamethasone is generally thought to have 5 times the anti-inflammatory potency of prednisone.  It by far has the most anti-inflammatory potential.  It does not affect the adrenal glands at all, as compared to Prednsione where roughly 1/7^th of the drug is aimed at mineralocorticoid activity.

Pediatric EBM

Few trials compare oral dexamethasone head-to-head with oral prednisone. In 2001, Qureshi et al compared 2 days of dexamethasone (0.6 mg/kg daily; maximum 16 mg/d) to 5 days of prednisone (1 mg/kg daily; maximum 60 mg/d). Dexamethasone had a similar efficacy as measured by relapse rates (7.4% vs 6.9%, P = .84), hospitalization rates (11% vs 12%), and the persistence of symptoms at 10 days (22% vs 21%). The patients treated with dexamethasone had increased compliance (99.6% vs 96%, P = .004) and fewer side effects, such as vomiting (0.3% vs 3%, P = .008). Part of the increased compliance in the dexamethasone group was believed to be owing to patients being discharged from EDs with the medication, whereas prednisone required a prescription to be filled at a pharmacy. Another study, which had 89 children, also noted no significant difference in 10-day relapse rates between the 2 groups (P = .27) and no significant difference in vomiting (5 of 51 with dexamethasone vs 7 of 38 with prednisone, P = .24).

Because dexamethasone has a long half-life, Altamimi et al attempted to determine if a single dose of dexamethasone (0.6 mg/kg) was equal to 5 days of prednisolone (2 mg/kg daily). The single dose of dexamethasone demonstrated no difference in any of the following: hospital admission rates (13.4% dexamethasone vs 14.9% prednisolone), additional β-agonist therapy, return to baseline of patient self-assessment scores (5.21 days vs 5.22 days, respectively, mean difference −0.01; 95% CI −0.70 to 0.68), and mean pulmonary index scores (0.4 vs 0.3, mean difference 0.1; 95% CI −0.25 to 0.45) in children 2 to 16 years of age with mild to moderate asthma.

In summary, these studies showed that slight differences exist in vomiting and compliance favoring dexamethasone; however, more studies are needed to further investigate these effects. To date, studies support using either prednisone or dexamethasone.

Intramuscular single dose of Dexamethasone

Three studies reported the use of a single dose of intramuscular (IM) dexamethasone. Klig et al conducted a pilot study with 42 children, half of whom received 0.3 mg/kg of IM dexamethasone (maximum 15 mg) once and half of whom received 2 mg/kg of oral prednisone (maximum 100 mg) for 3 days. The primary outcome measure was parental report of a lack of symptomatic improvement or the need for urgent care or hospital visits during the 5 days after enrolment, which occurred in only 2 of 21 dexamethasone patients versus 0 of 21 prednisone patients (P = .49). In a second study, Gries et al found similar improvements in clinical asthma scores within the first 5 days of therapy. This study contained a group of 15 children receiving a single dose of IM dexamethasone (1.7 mg/kg) and a group of 17 children receiving 5 doses of oral prednisone (2 mg/kg). In a third randomized trial, Gordon et al found similar asthma scores at 4 and 14 days among 126 children receiving either 1 dose of IM dexamethasone (0.6 mg/kg, maximum 15 mg) or 5 daily doses of prednisone (2 mg/kg, maximum 50 mg). Furthermore, a recent abstract described better parental satisfaction after a single dose of 0.6 mg/kg IM dexamethasone (maximum 15 mg) compared with 5 days of 2 mg/kg of oral prednisolone (maximum 60 mg).

In these studies of mild-to-moderate pediatric asthma, IM dexamethasone appears to be as effective as 3 to 5 days of oral prednisone or prednisolone.  I personally do not feel as though every child with asthma needs and IM injection.

Adult EBM

Kravitz et al randomized adult emergency department patients (aged 18 to 45 years) with acute exacerbations of asthma (peak expiratory flow rate less than 80% of ideal) to receive either 50 mg of daily oral prednisone for 5 days or 16 mg of daily oral dexamethasone for 2 days.  They compared the time needed to return to normal activity and the frequency of relapse after acute exacerbation in adults receiving either 5 days of prednisone or 2 days of dexamethasone.  The results were that Ninety-six prednisone and 104 dexamethasone subjects completed the study regimen and follow-up. More patients in the dexamethasone group reported a return to normal activities within 3 days compared with the prednisone group (90% versus 80%; difference 10%; 95% confidence interval 0% to 20%; P=.049). Relapse was similar between groups (13% versus 11%; difference 2%; 95% confidence interval -7% to 11%, P=.67).

Therefore from very limited adult data, you can see that dexamethasone has the potential to be as effective or better than prednsione.

Compliance

The compliance rates following emergency department visits for both general pediatric prescriptions and asthma-control medications are suboptimal. Single-dose treatment given in the ambulatory care setting might improve compliance.

For the pediatric population, dexamethasone is given at a smaller volume and can be mixed with better-tasting syrups to allow for better palatability and therefore compliance.  In a single-blind taste test among 39 children 5 to 12 years old, the palatability of dexamethasone was significantly better than that of prednisolone (8.2 cm vs 5.0 cm on a 10-cm visual analogue scale; P = .03).  This makes sense because in contrast to the frequent emesis seen with prednisolone, dexamethasone is considered to have an antiemetic effect. Anesthesiologists use it frequently as a postoperative antiemetic, and oncologists sometimes use it to minimize chemotherapy-related vomiting

Cost

Dexamethasone is not a new drug and is by far not expensive.  An estimation of drug cost at drugstore.com showed the following costs:

DEXAMETHASONE 4 MG X 90 FOR $22.99

PREDNISONE 20 MG 30 FOR $ 11.99

For adults taking either, the numbers work out to around $1 per dose per day (60 mg prednisone vs 16 mg Dexamethasone).  Being that you can likely take less days of dexamethasone, it has the potential to be more cost effective.

Adrenal Issue

We are taught that short courses of steroids have minimal affect on the adrenal glands and there should be no issue with giving our asthma patients 5 days of 60 mg of Prednisone.  It is also known that for longer courses, this needs to be tapered to avoid abruptly stopping prednisone and causing renal insufficiency.  However, we have all met the person that has a home supply of prednisone and self medicates on it.

There are reports that pharmacologic doses of glucocorticoids administered orally, intramuscularly, intranasally, inhalationally, transdermally, or intraorbitally may result in suppression of the hypothalamic-pituitary-adrenal axis. We do not know prevalence of secondary adrenal insuffiency, but do know that exogenous steroids are a big player.

My concern is for the patients that come multiple times a year with an asthma exacerbation.  Do the adrenals not take any hit with 5 days of prednisone or only take a small hit and recover every time? I think it would be safer in the long run to give a 1 or 2 day prescription for dexamethasone.  You also know that dexamethasone isn’t hitting every part of your adrenal gland like prednisone is, since it does not have any mineralocorticoid activity.

Conclusion

Growing evidence, which is still limited, in the adult and pediatric population suggest that dexamethasone is as effective as prednisone regimens for outpatient asthma treatment.  Dexamethasone is cost effective, tastes better and will likely have a better compliance, and has a longer half life (which can lead to shorter courses of treatment).  In addition, I think that making the switch away from prednisone will potentially help the adrenal glands of the future.  It makes sense that it would be a better asthma medication than prednisone for the disease process.

Larger-scale studies, including those to determine the safest and most effective dose, are still needed to prove its effectiveness and make us more confident (Especially Dr. Sinert and Dr. Zehtabchi)

References:

• Kravitz J., Dominici P, Ufberg J. Two      days of dexamethasone versus 5 days of      prednisone in the treatment of acute asthma:      a randomized controlled trial.Can Fam Physician. 2009 July; 55(7):      704–706.
• Altamimi      S, Robertson G, Jastaniah W, Davey A, Dehghani N, Chen R, Leung K, Colbourne      M. Single-dose oral dexamethasone in the emergency management of children      with exacerbations of mild to moderate asthma. Pediatr Emerg Care. 2006      Dec;22(12):786-93.
• Cross K, Paul R, Goldman R. Single-dose      dexamethasone for mild-to-moderate asthma exacerbations:Effective, easy, and acceptable.      Canadian Family Physician October      2011 vol. 57 no.      10 1134-1136
• Qureshi      F, Zaritsky A, Poirier MP. Comparative efficacy of oral dexamethasone      versus oral prednisone in acute pediatric asthma. J Pediatr. 2001      Jul;139(1):20-6.

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