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Fatigue in Palliative Care

Fatigue in Palliative Care. Dr Anne Hounsell, Speciality Doctor (with special thanks to PT Lucy and OT Chrissie). Objectives. Definition Who gets fatigued and why Pathophysiology Assessing fatigue What can be done to help – behavioural, psychological, medication.

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Fatigue in Palliative Care

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  1. Fatigue in Palliative Care Dr Anne Hounsell, Speciality Doctor (with special thanks to PT Lucy and OT Chrissie)

  2. Objectives • Definition • Who gets fatigued and why • Pathophysiology • Assessing fatigue • What can be done to help – behavioural, psychological, medication

  3. Personal experience of fatigue What does it feel like? What do you struggle with? .

  4. Definition “A distressing persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning.”2012 National Comprehensive Cancer Network Intensity is the key between that in healthy patients and that in palliative care patients. The definition is tricky. Wording important. Weakness is thought to paraphrase the physical dimension. Tiredness thought to paraphrase the cognitive dimension.

  5. Our patients’ experiences of fatigue.1)How do they describe it?2) How does it affect them? • Small groups

  6. Definition continued • Reduced capacity to maintain performance –reduced FS and AKPS • Often co-exists with a number of other symptoms –eg anorexia, pain, SOB • Includes mental fatigue –decrease in concentration and memory, emotional lability. Reduced ability to make decisions. • Cancer related fatigue –vicious circle of decreased physical performance, inactivity, avoidance of effort, absence of regeneration, helplessness and depressed mood. Affects QOL, functional status, mood and social interactions (So you think you are tired? MS fatigue youtube)

  7. Background • Almost a universal experience in our patients: -60-90% prevalence in patients with advanced cancer. - 48-78% in palliative care setting. • Likelihood increases with recurrence/progression of disease. • One of the most distressing symptom. (3) –most prevalence in colorectal and pancreatic cancers -least prevalence in prostate cancers

  8. Causes of fatigue in our patient population?

  9. Fatigue induced by treatments Not fully understood. Directly RT/chemotherapy SEs: Anaemia, diarrhoea, anorexia, weight loss, N/V Medication SEs : Steroids and ciclosporin –myopathy Opioids -effects on RAS Others -midazolam, cyclizine, gabapentin, amitriptyline, levomepromazine, sertraline Indirectly Eg the treatment can cause pain which in turn can contribute to fatigue Eg –immunosuppression –infection –catabolic state

  10. Psychological Issues • Anxiety, low mood, distress all contribute to fatigue though nature of this relationship is unclear. Needs further research -Adjustment reaction -Low mood –cognitive slowing -Loss of control/independence -Unable to complete their planned ideal goals -Social isolation -Family/personal pressure of doing too much ….

  11. Pathophysiology of Fatigue

  12. Proposed Pathophysiology of CRF

  13. 1) Inflammation and cytokines • Cytokines eg TNF alpha, IL1/6 –from tumour and cancer treatments. • Excess inflammation • Altered metabolism. • Can contribute to cachexia, fever, anorexia. • Can affect the HPA (hypothalamic-pituitary-adrenal axis) • Also tumours secrete lipolytic and proteolytic factors

  14. 2) Altered Metabolism and endocrine systems Cytokines Serotonin –Increases in hypothalamus. -Decreases motor drive and affects HPA. Hypothalamic pituitary axis –dysfunction includes reduced CRH. - reduced cortisol ( also less cytokine inhibition). - altered stress response and circadian rhythms. Testosterone Deficiency Anorexia Cachexia Syndrome (See reference 9)

  15. Testosterone DeficiencyLoss of muscle mass, fatigue, reduced libido, anaemia Due to : • Hypothalamic –pituitary-adrenal axis dysfunction • Anorexia-Cachexia Syndrome • Treatment –hypogonadism due to : chemotherapy, RT : anti-androgens (prostate cancer)

  16. 3)Muscle abnormalities Impaired muscle function is one of the main underlying mechanism of fatigue A)The cancer and the body’s response to the cancer • Increase in cytokines, lactate • Loss of muscle (ACS, atrophy, altered protein synthesis and breakdown) • Abnormal enzyme activity and muscle metabolism • Reduced testosterone • Paraneoplastic (eg polymyositis)

  17. 3)Muscle abnormalities continued B) Due to medications • Steroids • Cyclopsorin –mitochondrial myopathies C) Due to deconditioning Prolonged best rest and inactivity –reduced muscle mass and reduced cardiac output –causes reduction in endurance D) Due to over-exertion Esp in younger pts with aggressive treatment trying to maintain job/social life etc E) Non malignant neurological conditions Eg MS, MND

  18. 4) Central Nervous System Abnormalities Perception or induction of fatigue by the CNS –important but not well understood. General • Experience of fatigue controlled by the reticular activating system? • Disturbed cognitive functioning can contribute to fatigue • Paraneoplastic Cancer specific • Brain tumours/metastases. Esp if invades pituitary gland

  19. 5)Anorexia Cachexia Syndrome Involuntary weight loss + 3 of the following: -reduced muscle strength -reduced muscle mass -fatigue -anorexia -biochemical abnormalities (eg raised CPR, lowered Hb/albumin) Increase in cytokines Occurs in other long term conditions not just cancer –eg HF/lung disease A catabolic state Malnutrition can worsen. NB however often no obvious link between weight loss/fatigue/malnutrition …..

  20. 6) Anaemia Anaemia is common in cancer patients : • Bone marrow infiltration /failure (myeloma, bone metastases, leukaemia) chemotherapy) • Bleeding (eg GI cancer) • Haemolysis Anaemia occurs in our non cancer patients also eg: • Renal failure –lack of erythropoetin • Anaemia of chronic disease • Malabsorption –eg Fe, B 12 or folate deficiency • Bleeding (eg peptic ulcer)

  21. Assessing Fatigue?

  22. Assessing fatigue • Firstly a comprehensive general assessment (often multiple causes). • Severity, onset, duration, level of interference with life, associated cognitive psychological or social problems. • No gold standard tools for formally assessing fatigue. Complex as multidimensional and subjective. Functional capacity eg treadmill, driving Performance Status AKPS, ECOG, Edmonton functional assessment tool Subjective Assessment tools Unidimensional - NRS/VRS, Mulidimensional –MANY!! Chalder, Fatigue Severity Scale, FACTIT, Brief Fatigue Inventory , Piper Fatigue Scale.

  23. Subjective Assessment Tools

  24. Visual Analogue Scale

  25. Managing Fatigue?

  26. 1)Energy ConservationPrinciples:-Plan-Prioritise-Pace-Eliminate unnecessary activities-Ask for/accept help

  27. Energy Conservation continuedPacing • Encourage patients to remain active – balancing rest and activity • Focus on enjoyable important activity • Break into manageable chunks • Set achievable goals. Completion psychologically important • Activity /fatigue diary might be helpful Even phone calls can be tiring Emotional energy used up eg with staff talking too long. Discussions with relatives present so they understand also

  28. 2) Exercise

  29. Rest vs Exercise • Increased rest may exacerbate the problem. • Leading to loss of muscle strength and lower energy levels. Alongside energy conservation, exercise is important: (the balance depending on the patients situation) • Reduces tiredness, boosts mood, stimulates appetite, aids sleep and improves self esteem. • It can also help build muscle strength, improve heart and bone health, and help with managing constipation.

  30. Other Practical Tips to Help Fatigue Sleep • Use relaxation techniques to settle busy minds • Routine hours, limit the naps • Sleep in a cool room • Short term course of sleeping tablets –reset cycle? Diet • Digestion uses up a lot of energy (postprandial nap) • Eat little and often • Depends a little on prognosis (balanced diet/forget the rules) • Drink plenty of fluids

  31. Other Practical Tips to Help Fatigue Memory/cognition • Keep a diary/lists/pin boards/notes • Take someone with you to appointments Emotions/Stress • Focus on the positives and what can be done. • Realistic goals • Distraction ( eg craft supplies), relaxation techniques, mindfulness • Talking therapies • Complementary therapies –Acupuncture, Aromatherapy, Reflexology, Massage etc

  32. Living Well Centre groups Living Better, Living Well. • 8 weekly sessions (though can drop in and out of) • Run by OT and PT • Information on fatigue, stress, anxiety, relaxation, sleep, pain management Well Being Exercise Group • Pace according to the individual. Referral from PT needed Chair Based Exercise Group Referral from PT needed Living with Breathlessness Includes information on fatigue.

  33. Possible Medications for Fatigue?

  34. Possible Medication for fatigue Dexamethasone Methylphenidate Megestrol acetate Amantadine Modafenil (Etanercept) • Studies are heterogenous, with variable definitions and outcome parameters • Limited evidence such that a particular medication for CRF cannot be recommended

  35. Dexamethasone 2-4mg OD (what is the best dose?) 2-4 week effect Mechanism of action unknown ? Inhibition of tumour induced substances Often used but minimal evidence Study (6) –dexamethasone vs placebo – -4mg BD dexamethasone for 14 days. Physical aspects of the scale improved but not the emotional or psychological aspects. Most studies have used 40mg prednisolone

  36. Methylphenidate Psychostimulant. Increase DA/A/NA in prefrontal cortex Main use in ADHD Off licence for patients with advanced cancers with fatigue/depression/opioid induced sedation start 2.5-5mg BD. Usual maximum dose 20mg BD Conflicting evidence Suggested by NCCN guidelines for those active cancer - at end of life and no other reversible factors.

  37. Progestogens Eg Megestrol acetate (MEGACE) or cyproterone acetate Modulates cytokine production and effects. MEGACE -80-800mg OD Rapid improvement in about 10 days • Efficacy in cachexia is debatable • Can help with anorexia. • Expensive, side effects • Better for long term than steroids.

  38. Amantadine Licensed for use in Parkinsons disease and some viral infections Side effects –insomnia and vivid dreams. Use in Multiple Sclerosis -Fatigue is a common and disabling feature -Mechanism unclear -?effect on the immune system, ?amphetamine like action -100mg OD PO -Generally the studies are inconclusive but promising. -NICE recommends offer amantadine (may be small benefit)

  39. Modafenil • For narcolepsy, obstructive sleep apnoea, sleepiness • ? enhances DA and orexin levels in hypothalamus -heightened arousal • Suggested for MS patients (not in NICE), but weak to inconclusive evidence (1). • Only consider if MS and narcolepsy if benefits > risks (4) • Can have significant SEs –psychiatric, cardiovascular, skin.

  40. Etanercept • Used for rheumatoid arthritis, ankylosing spondylosis, psoriatic arthritis • Tumour necrosis factor inhibitor –TNFi - a soluble inflammatory cytokine • Paper (5) : • Given for psoriasis but significant and meaningful reduction in fatigue

  41. However ….. In the final stages of life, fatigue can provide protection and shielding from suffering. Therefore treatment might be detrimental. Its important to identify when treatment is no longer indicated to alleviate distress –’giving permission’ (2)

  42. Summary -1 Definition • Fatigue -distressing, persistent, subjective sensation of physical/emotional/cognitive tiredness/exhaustion. • Interferes with usual functioning and profound effect on QOL. Who gets fatigued and why? • Common symptom in many palliative care patients –cancer, COPD, HF, MND, MS. • Related to the condition itself, medications, treatments, nutrition, sleep, psychological and other symptoms. Pathophysiology • Inflammation and cytokines. • Altered metabolism and endocrine systems (including 5HT, testosterone, HPA, ACS) • Muscle and CNS abnormalities. • Anaemia.

  43. Summary -2 Assessing fatigue • Impact on function, QOL. Ask about associated symptoms. • Multidimensional. Scales and tools eg NRS, AKPS, Fatigue severity scale. What can be done to help? • Treat reversible components if appropriate. • Education (+ family), energy conservation (plan, prioritise, pacing), exercise, psychological support. • Limited evidence for particular medications. Examples are dexamethasone, methylphenidate, progestogens, amantadine, modafenil.

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