Let’s Talk About Dex

Dexamethasone is a long-acting steroid that can be used for a diverse range of conditions. Here is how it works and some common ED scenarios when you should consider reaching for it. 

How It Works
Dexamethasone works like other glucocorticoids. It traverses the cell membrane and binds to cytosolic glucocorticoid receptors. Bound receptors are transported into the nucleus, where they dimerize and bind to DNA, regulating transcription of a number of different mRNAs. The genes regulated have a host of different anti-inflammatory actions, reducing the activation of inflammatory cells, and reducing cytokine levels. Glucocorticoids can also reduce inflammation by lowering levels of arachidonic acid through a non-transcription-dependent mechanism. Dexamethasone’s half life is nearly twice that of other steroids, 36-72 hours compared to 16-36 hours for prednisone and prednisolone. 1mg of dexamethasone is roughly equivalent to 6.7mg of prednisone. Another advantage of dexamethasone in some circumstances, is that it does not interfere with cosyntropin stim testing. So if patients need evaluation for adrenal insufficiency, it can still be performed without waiting.

Major Emergency Medicine Indications
Asthma in kids – Multiple recent studies have shown similar outcomes, rates of return to baseline, and rates of repeat visits or hospitalization for adult patients treated with a single 0.3mg/kg or 0.6mg/kg dose of dexamethasone IM or PO compared to a three- to five-day course of 1-2mg/kg PO prednisolone [1^,2]. This is great news because it reduces the barriers of cost and compliance, and avoids the difficulty of dosing kids with a medication for several days. A dose of dexamethasone can also be given IM for kids who are vomiting or who refuse to take PO meds.

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Asthma in adults – The same is not true in adults, however. A recent non-inferiority study of adults with an acute asthma exacerbation of mild or moderate severity found that dexamethasone, a single dose of 12 mg PO was NOT non-inferior to 5 days of 60mg prednisone, meaning the prednisone was slightly better. However, the difference in outcomes was very small. So in patients who are unable or unlikely to fill a prescription for prednisone, it reinforces the fact that dexamethasone is a very good option [4].

Migraines – Migraines have the nasty habit of returning almost as soon as patients are discharged from the ED and their migraine cocktail has worn off. The return of the headache can lead to repeat ED visits and unhappy patients. Dexamethasone does not provide any immediate relief from headache symptoms, but does result in a modest reduction in rates of headache recurrence with a number needed to treat of 9 to prevent one headache recurrence [5]. 10mg IV dexamethasone is commonly used for this indication. However, given the modest benefit, and the lack of high quality evidence supporting it, the potential risks should be weighed, particularly of blood glucose elevation in diabetics, or of other complications in patients who have received many lifetime doses of steroids.

Cerebral Edema – Patients who have brain tumors or intracranial metastases with signs of vasogenic edema and are symptomatic are treated with 10mg IV dexamethasone for adults followed by 4mg every six hours. The glucocorticoids reduce intracranial pressure, with improvement in symptoms and on MRI seen within the first six hours and continuing for about 72 hours of treatment. Dexamethasone is preferred over other steroids because it has less mineralocorticoid effects, so it does not cause fluid retention. There is also potentially a lower risk of infection with dexamethasone compared to other steroids [6].

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Bacterial meningitis – An important international study published in the NEJM in 2002 showed improved outcomes for adults treated with steroids and an initial antibiotic of amoxicillin compared with those who did not receive steroids [7]. There are many differences in the patient population and treatments used in that paper compared to standard U.S. practice. A 2007 study in Africa found no benefit for steroids in patients treated with ceftriaxone for bacterial meningitis in a population with a high prevalence of HIV [8]. Finally, a 2016 study of treatment of presumptive meningitis in a resource-poor setting, found worse outcomes in patients who received steroids [9]. However, it is difficult to draw conclusions from these studies, as there are many differences in the study populations, the standard workup, and the treatment received. Currently, steroids are no longer commonly used in the US, where most patients are vaccinated. If you did decide to use it, dexamethasone is one option, with a dose of 10mg IV or 0.15mg/kg in kids, started before or within 10-20 minutes of antibiotics.

Septic Shock – Glucocorticoids were previously used more frequently for treatment of sepsis and septic shock. However, growing evidence suggests they are not as beneficial as originally thought. A 2015 Cochrane review concluded that there was low quality evidence that steroids provided a benefit in sepsis [10]. However, in patients who have other reasons for adrenal suppression, such as chronic steroid use, it is more likely to be beneficial. In these cases, for shock unresponsive to fluid therapy, the dose is 4-10mg IV.

Acute Mountain Sickness – If you find yourself practicing in or traveling to a high altitude area, be sure to stock the dexamethasone. It can be used to treat acute mountain sickness (AMS) with a dose of 4mg (or 0.15mg/kg in children) every six hours, and high altitude cerebral edema (HACE) with 8mg first, then 4mg every six hours. It can also be used to prevent AMS with 4mg every twelve hours starting on the day of ascent, and stopping after staying at the same altitude for two to three days.

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ENT Infections – Dexamethasone is a mainstay of treatment for infections and inflammation in the throat, such as croup, epiglottitis, peritonsillar abscess, uvulitis, and severe streptococal pharyngitis.

Croup in kids is treated with 0.6mg/kg IV, IM, or oral dexamethasone. Epiglottitis is thankfully rare in the era of vaccines. However it can still occur from Staph, Strep, and Haemophilus Influenza (type b) in unvaccinated and rarely in vaccinated children. In adults the etiology can be bacterial or viral, often with no specific pathogen isolated. Since it is a rare and often emergent disorder, there is little evidence on the use of glucocorticoids in epiglottitis, much less a randomized controlled trial comparing different glucocorticoid options. However, in addition to airway management and epinephrine nebs, dexamethasone is typically used to help reduce airway inflammation. Peritonsillar abscesses are relatively common. The evidence for use of glucocorticoids is based largely on small trials that showed some symptomatic improvement with dexamethasone treatment [^11-13]. Doses of 6-10mg IV are commonly used in adults.

Adverse Events
Steroids have many potential side effects, though typically these occur with chronic or recurrent use. Acutely, they can cause hyperglycemia in diabetic patients. Chronically, they can cause muscle atrophy, psychiatric disorders, immunosuppression, adrenal suppression, avascular necrosis, Cushingoid appearance, weight gain, increased cardiovascular disease risk, and osteoporosis.

Dosing and Adjustments
There are no dosing changes for patients with renal or hepatic impairment.

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Special Considerations
Dexamethasone is pregnancy class C. For breastfeeding mothers, it is not known if dexamethasone transfers to breastmilk. Very little prednisone has been found to cross into the milk, so it is unlikely dexamethasone would accumulate in any significant concentration in the milk [^14].

Cost
Dexamethasone comes in many formulations. 100 4mg tablets cost about $64. By contrast, a pre-packaged 10 day DexPak of 35 1.5mg tablets costs $324! A single 10mg dose of injectable dexamethasone costs under $2. The elixirs and oral solutions cost about $63 for a total of 24mg [^15].

REFERENCES

1. Schwarz ES, Cohn BG. Is dexamethasone as effective as prednisone or prednisolone in the management of pediatric asthma exacerbations? Ann Emerg Med. 2015;65(1):81-82. doi: 10.1016/j.annemergmed.2014.05.023 [doi].
2. Keeney GE, Gray MP, Morrison AK, et al. Dexamethasone for acute asthma exacerbations in children: A meta-analysis. Pediatrics. 2014;133(3):493-499. doi: 10.1542/peds.2013-2273 [doi].
3. Levine A. Kids with asthma? reach for dexamethasone. https://epmonthly.wpengine.com/article/kids-asthma-reach-dex. Published 12/05/2016. Updated 2016. Accessed 01/19, 2017.
4. Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma. Ann Emerg Med. 2016;68(5):608-613. doi: S0196-0644(16)00215-8 [pii].
5. Orr SL, Friedman BW, Christie S, et al. Management of adults with acute migraine in the emergency department. Medscape Emergency Medicine Web site. http://www.medscape.com/viewarticle/866673_3. Updated 2016. Accessed 01/19, 2017.
6. Drappatz J, Wen PY. Management of vasogenic edema in patients with primary and metastatic brain tumors. Up to Date Web site. www.uptodate.com. Updated 2016. Accessed 01/19, 2017.
7. de Gans J, van de Beek D, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347(20):1549-1556. doi: 10.1056/NEJMoa021334 [doi].
8. Scarborough M, Gordon SB, Whitty CJ, et al. Corticosteroids for bacterial meningitis in adults in sub-saharan africa. N Engl J Med. 2007;357(24):2441-2450. doi: 357/24/2441 [pii].
9. Gudina EK, Tesfaye M, Adane A, et al. Adjunctive dexamethasone therapy in unconfirmed bacterial meningitis in resource limited settings: Is it a risk worth taking? BMC Neurol. 2016;16(1):153-016-0678-0. doi: 10.1186/s12883-016-0678-0 [doi].
10. Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Corticosteroids for treating sepsis. Cochrane Database Syst Rev. 2015;(12):CD002243. doi(12):CD002243. doi: 10.1002/14651858.CD002243.pub3 [doi].
11. Millar KR, Johnson DW, Drummond D, Kellner JD. Suspected peritonsillar abscess in children. Pediatr Emerg Care. 2007;23(7):431-438. doi: 10.1097/01.pec.0000280525.44515.72 [doi].
12. Ozbek C, Aygenc E, Tuna EU, Selcuk A, Ozdem C. Use of steroids in the treatment of peritonsillar abscess. J Laryngol Otol. 2004;118(6):439-442. doi: 10.1258/002221504323219563 [doi].
13. Chau JK, Seikaly HR, Harris JR, Villa-Roel C, Brick C, Rowe BH. Corticosteroids in peritonsillar abscess treatment: A blinded placebo-controlled clinical trial. Laryngoscope. 2014;124(1):97-103. doi: 10.1002/lary.24283 [doi].
14. Hale TW. Medications and mothers’ milk: A manual of lactational pharmacology. 12th ed. Amarillo, TX: Hale Publishing L.P.; 2012:1331.
15. Lexicomp, Lexicomp. Dexamethasone (systemic) drug information. Up to Date Web site. www.uptodate.com. Accessed 01/19, 2017.