Understanding dexamethasone: Reviewing the risks, benefits and evidence
Is there a role for dexamethasone in the prehospital environment?
If you think corticosteroids are everywhere and given for everything, that opinion is understandable. In 2020, over 113,000,000 prescriptions for glucocorticoids were filled in the United States alone . It appears that every specialty, from oncology to obstetrics, neurology to anesthesia, uses corticosteroids – should there be a role for them in the prehospital environment as well?
Let’s look specifically at dexamethasone, a common corticosteroid in emergency medicine, and use current research to describe what the drug does and look at select situations in prehospital care where it may (or may not!) be valuable.
What are glucocorticoids?
Glucocorticoids are one of three groups of hormones (including mineralocorticoids and androgens) produced in the adrenal cortex, part of the hypothalamic-pituitary-adrenal (HPA) axis. The primary naturally occurring glucocorticoid is cortisol, which is involved in complex functions including metabolic, cardiovascular, growth and immunity.
It does this by binding to receptors inside the cell, which transport it inside the nucleus, where it interacts with DNA. In this way, it influences a number of different mediators of growth and inflammation, such as cytokines. It is this influence that causes the anti-inflammatory and immune suppressing actions of glucocorticoids .
The primary naturally occurring mineralocorticoid is aldosterone – it’s primary function is the retention of salt. This is important because at higher levels, cortisol may also bind to mineralocorticoid receptors. This may explain why many synthetic glucocorticoids have mineralocorticoid activity .
The final category, androgens, form the building blocks of testosterone and estrogen. They are of little clinical significance when administering glucocorticoids .
Dexamethasone (or just “dex”) is a synthetic glucocorticoid that is generally used for its potent anti-inflammatory effects. It is rapid acting, and is often selected because, unlike most other glucocorticoids, it has almost no mineralocorticoid properties – which means relatively fewer side effects related to fluid, sodium retention and the cardiovascular system in general.
It can be administered orally, intravenously or intramuscularly, making it very flexible.
Finally, its duration of action is longer, so it can often be prescribed once daily as opposed to drugs like hydrocortisone or methylprednisolone, which must be repeated as often as every four hours .
Corticosteroids and asthma
The role of corticosteroids in managing asthma exacerbations is well established. They have been shown to decrease time to resolution of symptoms as well as reduce the rate of relapse. The most recent guideline changes continue to recommend early (within one hour of presentation) administration in almost all presentations of asthma in patients over six years old.
Failure to respond to initial bronchodilators, exacerbations that occur while taking oral corticosteroids and a history of previous exacerbations requiring oral corticosteroids are all important indications for corticosteroids.
The route of administration (oral versus IV) should be dictated by the patient condition, as the time of onset is similar . Inhaled steroids, like budesonide, have different indications and evidence.
Should we use corticosteroids (including dexamethasone) for asthma in the prehospital setting? Yes.
Corticosteroids and croup
The use of glucocorticoids in croup is not new; the benefits appear to be the improvement in symptoms at 2 hours, with reduced rates of admission and repeat hospital visits. What is less certain is the optimal dose, agent and route of administration .
Prehospital research surrounding dex in croup is limited, but an early study suggests that it is safe and may lead to fewer nebulized epi treatments in hospital. The study did not show any effect on length of hospital stay, but these results should be viewed with caution because the study was small .
Should we use dexamethasone for croup in the prehospital setting? Probably.
Corticosteroids and COVID-19
The role of dex in COVID-19 has been extensively studied. Current recommendations suggest that COVID-19 patients with little or no oxygen requirements do not benefit from dex, however, in patients requiring oxygen, non-invasive ventilation or mechanical ventilation, dex may lower mortality and reduce ventilator days . Patients with early dex administration did not seem to benefit, however this cohort of patients had less severe symptoms . While sick COVID-19 patients benefit from dex, there is no evidence for or against its use in the prehospital environment.
Should we use dexamethasone for COVID in the prehospital setting? Probably not.
Corticosteroids and anaphylaxis
Historically, steroids have been used in anaphylaxis with positive results and outcomes. This was largely based on the experience with asthma and the assumption that the immunosuppressant and anti-inflammatory effects would be equally useful in anaphylaxis. When the evidence is examined, steroids do not improve outcomes or resolve shock and may increase the risk of a biphasic reaction. For this reason, they are no longer recommended in the routine treatment of anaphylaxis .
The prehospital data is also not supportive of dexamethasone in anaphylaxis. A large database review established a relationship between corticosteroid administration and increased likelihood of ICU admission .
Should we use corticosteroids (including dexamethasone) for anaphylaxis in the prehospital setting? No.
How to administer dexamethasone
The effects of dex are dose dependent and recommendations vary widely; a good practice is to use the minimal dose required to achieved the desired effect. Evidence from asthma and croup suggest that oral and IV routes have similar onset times, so this decision should be patient condition [4,5].
A long list of adverse reactions, including GI, skin, neurological, musculoskeletal and ophthalmological complications can occur with long-term use. In the acute setting, adverse reactions to be aware of are related to fluid and electrolyte imbalance, specifically related to fluid retention (such as hypertension and CHF) and loss of potassium. Anaphylactoid reactions have been reported very rarely [2,3].
Dexamethasone is contraindicated in systemic fungal infections
The overall profile of dex is safe and could be an important addition to your prehospital practice.
Understanding prehospital ketamine: Dosing to drawbacks
In the right patient, with a solid understanding of the pharmacology and a plan to address potential side effects, ketamine can be an incredibly useful tool for EMS
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- Katzung BG, Trevor AJ, editors. Basic & clinical pharmacology. 14th edition. McGraw-Hill 2018.
- Fresenius Kabi. Dexamethasone Sodium Phosphate Product Monograph. Drugs@ FDA Database. May 2014. Retrieved December 28, 2022 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/40572s002lbledt.pdf
- Global initiative for asthma. Global Strategy for Asthma Management and Prevention, 2022. Retrieved from https://ginasthma.org/wp-content/uploads/2022/07/GINA-Main-Report-2022-FINAL-22-07-01-WMS.pdf
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- COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed [December 28, 2022].
- Swaminathan, L., Kaatz, S., Chubb, H. et al. Impact of Early Corticosteroids on Preventing Clinical Deterioration in Non-critically Ill Patients Hospitalized with COVID-19: A Multi-hospital Cohort Study. Infect Dis Ther 11, 887–898 (2022). https://doi.org/10.1007/s40121-022-00615-x
- Shaker MS, Wallace DV, Golden DB, Oppenheimer J, Bernstein JA, Campbell RL, Dinakar C, Ellis A, Greenhawt M, Khan DA, Lang DM. Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. Journal of Allergy and Clinical Immunology. 2020 Apr 1;145(4):1082-123.
- Gabrielli S, Clarke A, Morris J, Eisman H, Gravel J, Enarson P, Chan ES, O’Keefe A, Porter R, Lim R, Yanishevsky Y. Evaluation of prehospital management in a Canadian emergency department anaphylaxis cohort. The Journal of Allergy and Clinical Immunology: In Practice. 2019 Sep 1;7(7):2232-8.
- Williams DM. Clinical pharmacology of corticosteroids. Respiratory care. 2018 Jun 1;63(6):655-70. DOI: https://doi.org/10.4187/respcare.06314
- Batzlaff CM, Limper AH. When to consider the possibility of a fungal infection: an overview of clinical diagnosis and laboratory approaches. Clinics in chest medicine. 2017 Sep 1;38(3):385-91.
- Paramythiotou E, Frantzeskaki F, Flevari A, Armaganidis A, Dimopoulos G. Invasive fungal infections in the ICU: how to approach, how to treat. Molecules. 2014 Jan 17;19(1):1085-119.