Dexamethasone Therapy in Patients With Brain Tumors - A Focus on Tapering

Ann E. Nahaczewski; Susan B. Fowler; S. Hariharan

Disclosures

J Neurosci Nurs. 2004;36(6):340-343. 

In This Article

Dexamethasone Tapering

Corticosteroid therapy must be tapered because of its interactions with the hypothalamic-pituitary-adrenocortical (HPA) axis. The hypothalamus secretes corticotropin releasing factor, which acts on the anterior pituitary, where it stimulates the secretion of adrenocorticotropin (ACTH). The adrenal glands are stimulated by ACTH to release approximately 20 mg of cortisol per day, with peak levels occurring in the morning. Through a negative feedback mechanism, an increase in circulating cortisol results in the inhibition of this cycle and suppression of its activity. Suppression of the HPA axis affects a patient's ability to respond to an acute stressful event and chronically causes the axis to atrophy.

Typical doses of dexamethasone used in the brain tumor patient are pharmacologic (i.e., supraphysiologic) in nature and have the potential to suppress the HPA axis if given over a prolonged period of time (e.g., more than 2 weeks), or are abruptly tapered or withdrawn. Dexamethasone provided 4 mg at every 6 hours, the usual initial dose—equivalent to 400 mg of cortisol per day—is about 20 times the normal rate of endogenous production. In patients who have received less than 14 days of dexamethasone therapy, treatment may be abruptly discontinued without adverse events, because the HPA axis is not suppressed (Kountz & Clark, 1997; Szabo & Winkler, 1995). However, some rebound edema may occur and symptoms may recur abruptly.

In clinical practice, dexamethasone tapering schedules are often prescribed for short-term therapy, and usually consists of an empiric reduction in dose of 2-4 mg every 1-3 days, by either reducing the dose and/or the interval. Other tapering schedules have been reported in this patient population and include a "slow taper" of lowering the dose by 4 mg every week. In reality, the dose of dexamethasone and tapering schedule should be adjusted to the patient's tolerance.

Dexamethasone is often used during radiation therapy (RT). Higher doses are used at the onset of and during RT with lower doses at the end of RT (Hempen, Weiss, & Hess, 2002). Research has shown that twice daily dosing of dexamethasone can provide a good clinical response with minimal morbidity (Weissman, et al., 1991). Dosages should be adapted to each individual patient's needs, because some patients can experience radiation side effects or neurological symptoms without dexamethasone (Hempen, Weiss, & Hess).

Often corticosteroid therapy continues beyond 14-21 days to control symptoms of brain tumors, and gradual reductions in dosing must occur. The concept of a tapering schedule for chronic corticosteroid therapy evolved to prevent adrenal insufficiency syndrome and recurrence or exacerbation of signs and symptom. Patients are more likely to adhere to medication schedules if signs and symptoms are controlled and tolerated.

Although algorithms have been developed and utilized to assist clinicians in safely withdrawing patients from chronic corticosteroid therapy (Kountz & Clark, 1997), tapering schedules remain, at best, empiric and dependent on patient specific responses. A gradual decrease in dose and/or dosing interval of dexaxamethasone every 3-7 days, in an attempt to reach a physiologic dose equivalent to 20 mg of cortisol per day (i.e., approximately 0.75 mg of dexamethasone per day), should be attempted (Szabo & Winkler, 1995).

Cortisol levels peak in the morning, so a once per day or every other day morning dose of corticosteroid is optimal to minimize suppression of the HPA axis. It is suggested that after the patient is tapered to a dose of 0.75 mg of dexamethasone per day, a morning cortisol level should be drawn to determine the steroid's effect on adrenal function. If the cortisol level is greater than 10 mcg/dl, the steroid therapy can be stopped. If the morning cortisol level is less than 10 mcg/dl, the adrenal glands are still suppressed and the steroid taper should continue over 4 more weeks (Szabo & Winkler, 1995).

If further steroid tapering is required, the patient should then be switched to a more intermediate acting steroid, such as prednisone, because long-acting corticosteroids like dexamethasone do not provide a steroid free period for recovery from adrenal suppression, and prednisone also allows for more flexible dosage adjustments (Spruill & Wade, 1988). After 4 weeks, another cortisol level should be drawn. After the level is greater than 10 mcg/dl, steroid therapy may be discontinued.

To verify HPA axis recovery, the rapid ACTH stimulation test may also be utilized. A synthetic analog of ACTH, cosyntropin 0.25 mg is administered by the IV or intramuscular route. Cortisol levels are drawn before the dose is administered and again 30 min. after administration. If the increase in cortisol is less than 6 mcg/dl, the HPA axis is still suppressed and the patient still requires supplementation for another 4 weeks. If the increase is greater than 6 mcg/dl, the patient no longer requires steroid therapy, because adrenal function has returned to normal (Szabo & Winkler, 1995).

Patients receiving chronic glucocorticoid therapy may require up to 12 months for all components of the HPA axis to recover full function and are recommended to wear a Medic-alert bracelet, in the event that they are exposed to a stressful event and may not be able to mount an effective adrenal response (Kountz & Clark, 1997). Evidence of an effective adrenal response include lack of cortisol deficiency without weakness and fatigue, anorexia, nausea and vomiting, hypotension, hypoglycemia, hyponatremia, and increased susceptibility to infection (Greenspan & Stewler, 1997).

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