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Dexamethasone


Dexamethasone

Article Author:
Donavon Johnson
Article Author:
Michael Lopez
Article Editor:
Brendan Kelley
Updated:
9/5/2020 7:15:57 PM
For CME on this topic:
Dexamethasone CME
PubMed Link:
Dexamethasone

Indications

Dexamethasone has a wide variety of uses in the medical field. As a treatment, dexamethasone has been useful in the treatment of acute exacerbations of multiple sclerosis, allergies, cerebral edema, inflammation, and shock. Patients with conditions such as asthma, atopic and contact dermatitis, and drug hypersensitivity reactions have benefited from the use of dexamethasone.[1]

In endocrinology, dexamethasone has been found useful as a test for Cushing syndrome.[2] This test begins with a low dose test. There are two versions of this test: the standard two-day test and the overnight test. With the standard test, 0.5 mg oral dose of dexamethasone is given every 6 hours for two days. Six hours after giving the final dose, serum cortisol levels are measured. The overnight test begins with a 1 mg oral dose of dexamethasone at 11:00 PM with a second 1 mg oral dose at midnight. The following morning, serum cortisol levels are tested between 8:00 AM and 9:00 AM. The test is read as a positive screening test for Cushing syndrome if the final cortisol reading is high, signaling that the more specific confirmative high dose dexamethasone suppression test should follow. The high dose dexamethasone suppression test has three forms: the standard 2-day test, the overnight test, and the intravenous (IV) test. With all three versions of the test, baseline serum cortisol levels need to be determined before commencing with the test. Baseline serum is measurable with a 24-hour urinary free cortisol test.[3] The standard 2-day test uses 2 mg of oral dexamethasone given every 6 hours for two days. During the 2-day exam, urine is collected and tested for free cortisol and 6 hours after the final dose of dexamethasone; blood is drawn to measure the serum cortisol level. The overnight test begins with an 8 mg oral dose of dexamethasone at 11:00 PM. The following morning between 8:00 AM, and 9:00 AM, serum cortisol is measured. The IV test is the shortest of the tests. The patient receives one milligram of dexamethasone via continuous intravenous infusion per hour for 7 hours. Serum cortisol is measured at the end of 7 hours.

Off-label indications are as follows. Dexamethasone is useful in the treatment of chemotherapy-induced nausea and vomiting. It is also used in the prevention and treatment of altitude sickness. It has also seen use in the treatment of spinal cord compression due to metastases in oncological cases.[4]

Mechanism of Action

Dexamethasone is a potent glucocorticoid with very little, if any, mineralocorticoid activity.[5] Dexamethasone’s effect on the body occurs in a variety of ways. It works by suppressing the migration of neutrophils and decreasing lymphocyte colony proliferation. The capillary membrane becomes less permeable, as well. Lysosomal membranes have increased stability. There are higher concentrations of vitamin A compounds in the serum, and prostaglandin and some cytokines (interleukin-1, interleukin-12, interleukin-18, tumor necrosis factor, interferon-gamma, and granulocyte-macrophage colony-stimulating factor) become inhibited. Increased levels of surfactant and improved pulmonary circulation have also been shown with dexamethasone use. Dexamethasone is metabolized by the liver and excreted in the urine mainly. Dexamethasone has a half-life of approximately 3 hours.

Administration

Dexamethasone is available in various formulations. As a tablet, it is available in strengths ranging from 0.5 mg to 6 mg. Other forms of administration are as an injectable suspension or as an oral solution.[6]

  • In the treatment of inflammation, it is advisable to start with low doses of 0.75 mg/day, which may titrate to 9 mg/day, with dosing divided into 2 to 4 doses throughout the day. This applies to intravenous, intramuscular, and oral administrations. Less may be used when directly administered to the lesion or tissue with dosing ranging from 0.2 to 6 mg per day.[7]
  • As therapy for acute multiple sclerosis exacerbations, 30 mg oral daily doses taken for seven days is the recommended regimen followed by one month of 4 to 12 mg oral daily doses.
  • As cerebral edema may be a life-threatening condition, aggressive treatment is necessary. The recommendation is for 10 mg of intravenous dexamethasone, followed by 4 mg of intramuscular administration given every 6 hours. In this instance, it is necessary to titrate down over 7 days to discontinue dexamethasone therapy.[8]
  • In the treatment of circulatory shock, the regimen is 1 to 6 mg/kg of intravenous dexamethasone as a one-time bolus. This regimen may be substituted with 40 mg given intravenously every 2 to 6 hours as needed. Treatment with high dose dexamethasone is not recommended beyond 2 to 3 days.
  • Research has shown that allergic reactions improve with a 6-day regiment beginning with 4 to 8 mg intramuscular injection on the first day. This dose is followed by oral doses on days 2 to 6 beginning with 1.5 mg every 12 hours for days 2 and 3, 0.75 mg every 12 hours for the third day, and finally 0.75 mg daily for days 5 and 6. The patient should appropriately be titrated down by day 7 with no dosing necessary on day 7.

Adverse Effects

Although dexamethasone is generally well tolerated, it does have its drawbacks as a medication. The most frequently reported adverse effect by patients is the presence of insomnia after use. Some other frequent adverse effects reported by patients include acne, indigestion, weight gain, increased appetite, anorexia, nausea, vomiting, acne, agitation, and depression. There have been reports of adrenal suppression, arrhythmias, spermatogenic changes, glaucoma, hypokalemia, pulmonary edema, pseudotumor cerebri, and increased intracranial pressure.[9]

Contraindications

Dexamethasone use is contraindicated if patients have systemic fungal infections, hypersensitivity to dexamethasone, or cerebral malaria. Another contraindicated to administer live or live-attenuated vaccines during the use of dexamethasone as the immune system is being suppressed and will less like form a strong enough immune response placing the patient at risk. It is still permissible to administer killed or inactivated vaccines, although it bears mentioning that immune response may be attenuated, and it is unpredictable if immunity with developing as a result.[10]

In patients with cirrhosis, diverticulitis, myasthenia gravis, renal insufficiency, or ulcerative diseases such as peptic ulcer disease or ulcerative colitis, it is important to use caution when prescribing dexamethasone. Recommendations include using dexamethasone cautiously during pregnancy as there is an increased risk of oral cleft formations. Clinical experience has shown that large doses can increase blood pressure. In patients with recent myocardial infarction, it is advised to proceed with caution as an increase in free wall rupture of the left ventricle has been reported with the use of dexamethasone. Suppression of the hypothalamus-pituitary-adrenal axis (HPA axis) occurs with use, and therefore the rapid withdrawal of dexamethasone is not recommended. It is important to gradually increase and/or decrease any corticosteroid due to its effect on the HPA axis.

Latent diseases such as fungal (Candida, Cryptococcus, Pneumocystis), parasitic (Toxoplasmosis, Amebiasis, Strongyloides), and bacterial (Mycobacterium, Nocardia) infections may become active due to suppression of the immune system.[11]

Steroid use may inhibit bone formation and may lead to the formation of osteoporosis. Caution is necessary when prescribing dexamethasone to populations at higher risk for osteoporosis.

Enhancing Healthcare Team Outcomes

Dexamethasone is a widely prescribed drug by many healthcare professionals, including the nurse practitioner. However, it is essential to know that this potent steroid has many adverse effects, and patient monitoring is critical. In general, clinicians should avoid long-term prescriptions, and the drug tapered quickly if the patient is improving. If chronic use is warranted, then the patient must be educated about the potential side effects of the steroid. Healthcare workers must monitor the patient for mood changes, development of osteoporosis, weight gain, hyperglycemia, electrolyte changes, and depression.


References

[1] Corssmit EPM,Dekkers OM, Screening in adrenal tumors. Current opinion in oncology. 2019 Mar 5;     [PubMed PMID: 30844886]
[2] Bano G,Mir F,Beharry N,Wilson P,Hodgson S,Schey S, A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With Neurofibromatosis Type 1. International journal of endocrinology and metabolism. 2013 Winter;     [PubMed PMID: 23853621]
[3] Monreal JA,Duval F,Mokrani MC,Fattah S,Palao D, Differences in multihormonal responses to the dopamine agonist apomorphine between unipolar and bipolar depressed patients. Journal of psychiatric research. 2019 Feb 19;     [PubMed PMID: 30836201]
[4] Teachey DT,Pui CH, Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. The Lancet. Oncology. 2019 Mar;     [PubMed PMID: 30842058]
[5] Brinks J,van Dijk EHC,Habeeb M,Nikolaou A,Tsonaka R,Peters HAB,Sips HCM,van de Merbel AF,de Jong EK,Notenboom RGE,Kielbasa SM,van der Maarel SM,Quax PHA,Meijer OC,Boon CJF, The Effect of Corticosteroids on Human Choroidal Endothelial Cells: A Model to Study Central Serous Chorioretinopathy. Investigative ophthalmology     [PubMed PMID: 30489628]
[6] Eckhard L,Jones T,Collins JE,Shrestha S,Fitz W, Increased postoperative dexamethasone and gabapentin reduces opioid consumption after total knee arthroplasty. Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2019 Mar 2;     [PubMed PMID: 30826856]
[7] Matheson EC,Thomas H,Case M,Blair H,Jackson RK,Masic D,Veal G,Halsey C,Newell DR,Vormoor J,Irving JAE, Glucocorticoids and selumetinib are highly synergistic in RAS pathway mutated childhood acute lymphoblastic leukemia through upregulation of BIM. Haematologica. 2019 Jan 17;     [PubMed PMID: 30655370]
[8] Orton S,Censani M, Iatrogenic Cushing's Syndrome Due to Intranasal Usage of Ophthalmic Dexamethasone: A Case Report. Pediatrics. 2016 May;     [PubMed PMID: 27244810]
[9] Polderman JAW,Farhang-Razi V,van Dieren S,Kranke P,DeVries JH,Hollmann MW,Preckel B,Hermanides J, Adverse side-effects of dexamethasone in surgical patients - an abridged Cochrane systematic review. Anaesthesia. 2019 Mar 1;     [PubMed PMID: 30821852]
[10] Kolias AG,Edlmann E,Thelin EP,Bulters D,Holton P,Suttner N,Owusu-Agyemang K,Al-Tamimi YZ,Gatt D,Thomson S,Anderson IA,Richards O,Whitfield P,Gherle M,Caldwell K,Davis-Wilkie C,Tarantino S,Barton G,Marcus HJ,Chari A,Brennan P,Belli A,Bond S,Turner C,Whitehead L,Wilkinson I,Hutchinson PJ, Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial. Trials. 2018 Dec 4;     [PubMed PMID: 30514400]
[11] Sun W,Wang D,Yu C,Huang X,Li X,Sun S, Strong synergism of dexamethasone in combination with fluconazole against resistant Candida albicans mediated by inhibiting drug efflux and reducing virulence. International journal of antimicrobial agents. 2017 Sep;     [PubMed PMID: 28673609]