Recommended medicine: DEXAMETHASONE
Injection: 4 mg/ml in 1‐ml ampoule (as disodium phosphate salt)
Oral liquid: 2 mg/5 mL
Fatigue is defined as a subjective feeling of tiredness, weakness or lack of energy. The pathophysiology is not fully understood but in most palliative care patients will be multifactorial, including disease- and treatment-related causes. Physical fatigue is the transient inability of a muscle to maintain optimal physical performance, and is made more severe by intense physical exercise.
Mental fatigue is a transient decrease in maximal cognitive performance resulting from prolonged periods of cognitive activity. It can manifest as somnolence, lethargy, or directed attention fatigue.
Cancer-related fatigue (CRF) is defined as a common, persistent, and subjective sense of tiredness related to cancer and/or its treatments that interferes with usual functioning. This is distinguishable from normal fatigue in that symptoms in CRF are severe, distressing and persist, regardless of adequate amounts of sleep and rest.
CRF is usually multifactorial; it may be caused by tumour-related and/or treatment-related factors such as decreases in the availability of metabolic substrates, hormonal changes, increase in proinflammatory cytokines, cachexia, neurophysiological changes in skeletal muscle, muscle wasting, decreased ventilatory ability, anaemia, and altered sleep patterns.
However, fatigue is a common symptom in palliative care, not only in cancer patients, but also in patients with diseases that are not associated with cancer, but who require palliative care (e.g. cardiac, pulmonary or renal failure, amyotrophic lateral sclerosis or multiple sclerosis).
• Fatigue is a complex multidimensional symptom comprising physical, cognitive and emotional aspects.
• Fatigue at the end of life may have a protective role. Treatment of fatigue may not be appropriate if this symptom is not having a direct impact on quality of life.
• Management of fatigue comprises identification and, if appropriate, treatment of possible underlying cause(s) and the use of pharmacological and non pharmacological management of the fatigue itself.
is a potent synthetic member of the glucocorticoid class of steroid drugs.
acts as an anti-inflammatory and immunosuppressant.
• When taken orally, it is more potent than the naturally occurring hormone cortisol and than prednisone
• The plasma half life of dexamethasone
is 3.5-4.5 hours but as the effects outlast the significant plasma concentrations of steroids, the plasma half-life is of little relevance and the use of biological half life is more applicable.
• The biological half life of dexamethasone
is 36-54 hours, therefore dexamethasone is especially suitable in conditions where continuous glucocorticoid action is desirable.
• The approximate equivalent anti-inflammatory doses 750 microgram dexamethasone
~ 5 mg prednisolone
• Dexamethasone has high glucocorticoid activity but insignificant mineralocorticoid effect and is
particularly suitable for high dose therapy.
Additional supporting information for this medication:
• Dexamethasone is widely available worldwide as oral tablets (0.5mg, 2mg).
• Very few studies have been conducted to evaluate the effectiveness of corticosteroids in fatigue in adults.
• Improvements in pain and quality of life with corticosteroids had a resultant positive effect on fatigue with a reduction in severity of this symptom. However, clinical trials with corticosteroids do not use improvement in fatigue as a primary outcome.
• No trials were identified to compare effectiveness of one corticosteroid with another.
• A recent systematic review on treatment with corticosteroids and androgens for the relief of fatigue in palliative care patients found that glucocorticoids improved quality of life but results for changes of fatigue and weakness were inconsistent. Tiredness and energy were not improved.
• Considering the lack of evidence from clinical trials, the recommendation for dexamethasone
has to be based on clinical expertise. Expert opinion strongly supports the short-term use of dexamethasone in adults.
• There are a number of known potential adverse effects of corticosteroids and these must always be considered before dexamethasone
is used. This includes muscular weakness with prolonged use of corticosteroids.
• Given the toxicity associated with long term use, consideration of steroids in palliative care should be restricted to use in the terminally ill with fatigue and a specific short-term treatment goal
• There is no difference in effectiveness between oral and parenteral application. The oral route is easier and is preferred by most patients.
• Although expert opinion supports the use of corticosteroids for the management of a variety of symptoms, including fatigue in palliative care, the evidence is weak.
• Other options for treatment of fatigue include megestrol acetate
. However, evidence for these medications is weak as well, and clinical expertise disfavours their use except for selected patients.
• Non-pharmacological support includes light aerobic training as well as energy-conserving therapies.
Adapted from Radbruch L et al. Essential medicines in palliative care - An application for the 19th WHO Expert committee on the selection and use of essential medicines. Kindle Edition, 135 pages. Published June 5th 2013 by IAHPC Press. Available at https://www.amazon.com/Essential-Medicines-Palliative-Care-Application-ebook/dp/B00D7S2D0C