12.1 () Fatigue Flashcards
List 3 key features of fatigue
Easy tiring - physical
Generalized weakness - emotional
Mental fatigue - cognitive
FS: TWM
- What is the prevalence of fatigue in cancer patients?
- List 3 domains of QOL that may be impacted by fatigue
- Most frequent and debilitating symptom in ADVANCED stage cancer (60-90%)
- physical
functional - social, work
psychological - mood
AND
decision making capabilities, may lead to refusal of potentially curative Rx
FS:
Physical, emotional, functional, social
Define “generalized weakness”
The anticipatory sensation of DIFFICULTY in initiating a certain activity.
Define “mental fatigue”
Defined as the presence of impaired mental concentration, loss of memory, and emotional lability.
Memory
Emotional lability
Concentration
Define cancer-related fatigue
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
List 4 conditions that fatigue should be distinguished from
Depression
Delirium (fluctuating LOC)
Drowsiness
Weakness (lack of physical/muscle/motor strength)
List 2 ways in which tumours can directly cause fatigue
- Lipolytic factors*
- Proteolytic factors*
- Pro inflammatory Cytokines* (!)
- Tumour degredation products
- Invasion of brain or pituitary gland (!)
* = tumour produced by products
List 3 pro-inflammatory cytokines implicated in cancer-related fatigue.
- TNF-alpha
- IL-1
- IL-6
How can cancer-related treatments like radiation/chemo induce fatigue?
dysregulation of proinflammatory cytokines implicated in fatigue (TNF-a, IL-1, IL-6)
What body systems do pro-inflammatory cytokines act on to induce fatigue? (4)
- Brain (HPA axis, sleep, psych, dopamine changes)
- Muscles (decrease mass/strength)
- Metabolism
- Immune system (cellular & humoral)
What 3 host factors regulate pro-inflammatory cytokines implicated in fatigue?*
- Genetic factors
- Immune factors
- HPA axis alterations
What could be one of the main underlying mechanisms of fatigue?
Impaired muscle function
Unclear if fatigue related to muscle loss/altered muscle contraction VS. a central mechanism
Contributors to Fatigue (14)
- Cachexia (E)
- Mood disorders (P)
- Inflammation (I)
- Neuroendocrine alterations (E)
- Poly pharmacy (Iatrogenic)
- Cancer-related symptoms (N)
- Anemia (V)
- Tumour by-products (N)
- Infections (I)
- Dehydration (D)
- Anti cancer treatments (Iatrogenic)
- Comorbidities (renal, hepatic, heart disease). (D)
- Autonomic dysfunction (V)
- Deconditioning (D)
- Genetics (SNPs of proinflammatory cytokine genes)
List 2 causes of muscle abnormalities due to cancer or it’s treatment.
- Abnormalities in cytokine (pro-inflammatory) production*
- Cachexia*
- Increased lactate in muscle tissues
- Atrophy* if type II muscle fibres
- Myopathies* from anti cancer treatments
- Loss of muscle mass* from corticosteroids
- What is the mechanism by which deconditioning leads to fatigue?
- What is one treatment for this?
- Prolonged bed rest + immobility = loss of muscle mass and reduced cardiac output
Deconditioning results in reduced endurance for exercise/ADLs
(may be compounded by muscle abnormalities)
- Endurance exercise training can reduce fatigue and improve physical performance in cancer pts undergoing treatment/survivors
List 4 proposed mechanisms by which fatigue is perceived/induced in the CNS*
- Primary or secondary CNS tumours
-invasion of pituitary gland –> endocrine abnormalities - Cognitive dysfunction (from brain tumour/ n.t. &hormones from other primaries/cancer treatments) can be caused by or contribute to fatigue
- Dysregulation of serotonin/its receptors in the brain due to cancer/treatments
- circadian rhythm disruptions
- dysregulation of HPA
n.t. = neurotransmitters
- When can fatigue occur with infections
- What is the underlying mechanism
- As a prodrome or may outlast infection by weeks/even months esp with recurrent or protracted infections
- Thought to share the same mediators for fatigue as cancer
6 causes of anemia in cancer pts
- Myelosuppression by chemotherapeutic agents
- Iron deficiency
- Bleeding
- Haemolysis
- Nutritional deficiencies
- Anemia of chronic disease
Microcytic: TAILS
Normocytic - high retic: bleeding or hemolysis
Normocytic - low retic: bone marrow suppression, renal disease, anemia of chronic disease
Macrocytic: liver disease, ETOH, B12/folate deficiency
List 7 physical effects of autonomic dysfunction.
GI:
Malnutrition
Anorexia
Delayed gastric emptying
Chronic nausea
General:
Poor performance status
Fatigue
Vascular:
Orthostatic hypotension
feeling hot or cold in some parts of or all over your body, due to issues that cause the blood vessels to narrow or widen;
Skin:
excessive or decreased sweating, salivating, or eye-tearing;
bladder:
such as being unable to empty one’s bladder fully;
sexual problems:
such as vaginal dryness and difficulty maintaining an erection;
FS:
Vascular, GI, bladder, sexual
General
Skin
List 3 psychological issues that can cause fatigue.
Depression
Anxiety
Adjustment reaction
List 3 endocrine disorders that could be a cause of fatigue
- Diabetes mellitus
- Addison’s disease
- Hypothyroidism
- Testosterone/androgen insufficiency/hypogonadism
- HPA axis abnormalities of corticotropin releasing factor
- List 4 signs/symptoms of testosterone deficiency
- List 4 causes of testoterone deficieny in cancer patients
- In cancer treatment-related testosterone deficiency, list 1 possible intervention and 4 of its benefits
- loss of muscle mass
fatigue
reduced libido
anemia - anorexia/cachexia sydrome
chemotherapy
radiation
hormone ablative therapy - Androgenic anabolic steroids (i.e. testosterone + its derivatives)
benefits: increase muscle mass/energy/libido/Hb
List 4 electrolyte abnormalities that can cause fatigue.
Hyponatremia
Hypokalemia
Hypomagnesemia
Hypercalcemia
List 6 cancer-related symptoms that can cause fatigue.
Pain
Psychological symptoms
Dyspnea
Sleep disturbances
Anorexia
Constipation
List 9 paraneoplastic neurological syndromes associated with fatigue*
Progressive multifocal leucoencephalopathy
Paraneoplastic encephalomyelitis
Amyotrophic lateral sclerosis
Subacute motor neuropathy
Peripheral paraneoplastic neurological syndrome
Ascending acute polyneuropathy
Dermatomyositis polymyositis (neuromuscular)
Eaton-lambert syndrome (neuromuscular)
Myasthenia Gravis (neuromuscular)
PML - usually with leukemia & lymphoma
Paraneoplastic encephalomyelitis - 70% cases in lung cancer
List 4 anti cancer therapies that commonly contribute to fatigue.
Cytotoxic therapeutic agents
Radiotherapy
Biological response modifiers (i.e interferon)
Targeted therapy (I.e tyrosine kinase inhibitor)
(but rule out endocrinopathies from immunotherapy PD-1 inhibitors)
List 11 medication classes commonly used in palliative care that can cause fatigue.
Opioids
Anxiolytics
Anticholinergics
Antiepileptics
Neuroleptics
Alpha-adrenergic blocking agents
Diuretics
SSRIs
TCAs
Benzos
compounded by polypharmacy!
6 components to assessment of fatigue
Severity
Duration
Onset
Level of interference with ever day life
Associated psychological or social problems
Possible underlying causes
FS: OPQRSTUV - DIMS
Name 3 clinical assessment tools for fatigue.
Visual analogue scale* !
Numerical rating scales* !
Functional assessment of cancer therapy-fatigue*
Brief Fatigue Inventory* !
Piper Fatigue Scale*
Fatigue Questionnaire**
Multidimensional Fatigue Inventory**
Pearson and Byars Fatigue Feeling Checklist
- = subjective tools
** = multidimensional tools
List 3 specific assessments for fatigue in the clinical setting.
Subjective assessment tools (VAS, NRS, FACT-F, Piper, BFI)
Performance status
Functional capacity (assess task: walking, driving, cycling)
Task-related fatigue (VAS, NRS, Pearson&Byars)
VAS= visual analogue scale
NRS = numerical rating scale
List 3 “dimensions” of fatigue that can be assessed
- Physical
- Cognitive
- Emotional
List 3 tools to assess performance status
Karnofsky performance status
European Cooperative Oncology Group score (ECOG)
Edmonton functional assessment test
3 questions to consider in the assessment of fatigue*
- Is fatigue a symptom of primary concern to the patient?
- What are the major, probable causes?
- Are there therapeutic measures available that have reasonable cost/benefit ratio?
List 5 non-pharm measures to manage fatigue.
PT
OT
Acupuncture
Exercise if deconditioning (early cancer and cancer survivors… not so much late stage)… best evidence.
CBT
Education about fatigue + instruction in self-care, coping techniques, activity management
List 3 classes of medications that can help manage fatigue.
- Corticosteroids (dex)
- Progestational agents (megastrol acetate)/ other anti-cachexia agents
- Psychostimulants (methylphenidate)
(Lack of compelling data to support any of these other than very short term corticosteroids)
List 10 specific measures to address in the evaluation and management of fatigue.*
Psychological issues
Cachexia
Anemia
Infection
Autonomic failure
Metabolic and endocrine disorders
Opioid induced sedation
Hypoxia
Dehydration
Deconditioning
List 3 ways corticosteroids are thought to help combat fatigue.
Inhibition of tumour induced substances
Central euphoriant effects
Improvement of physical symptoms
*probably not through appetite stimulation as steroids not shown to impr
List 8 potentially reversible causes of fatigue in palliative care patients.*
Infection
Anemia
Autonomic factors
Psychological factors
Sleep disturbances (daytime sleepiness and/or insomnia)
Metabolic disorders
Drug induced
Nutritional deficiency
Dehydration
Hypoxia
optimize underlying cardio-resp conditions
List 5 ways to manage fatigue caused by autonomic dysfunction.
(Name 2 drug names)
Midodrine (alpha-1 sympathomimetic agent)
Consider mineralocortocoid if indicated (fludrocortisone)
Adjust doses of meds contributing to fatigue
Decrease poly pharmacy
Encourage exercise
Increase salt intake
Avoid triggers of autonomic insufficiency.
List 4 triggers of autonomic insufficiency
Heat
Motionless standing
Large morning meals
Etoh
What is one common nutritional deficiency in patients with advanced cancer?
Carnitine
(but in RCT, supplementation did not improve fatigue)
List 2 nutritional supplements that may help combat cancer-related fatigue.
L-carnitine
Ginseng
Co-Enzyme Q-10
Guarana
*more studies needed re: efficacy & safety
What are common changes associated with cancer related fatigue? (6)
Decreased cognitive function
Decreased muscle endurance
Decreased sleep quality
Decreased control over body processes
Increased social withdrawal
Increased emotional reactivity
What is the pathophysiology of cancer related fatigue?
Proposed mechanisms include energy imbalance caused by a variety of mechanisms including:
Pro-inflammatory cytokines
HPA axis dysregulation
Circadian rhythms desynchronization
Persistent immune system activation
Establishment of a chronic inflammatory state.
Describe the brief fatigue inventory?
0-10 numeric scale rating fatigue over designated time period.
0-3 mild
4-7 moderate
8-10 severe
List 4 psychosocial interventions to manage cancer related fatigue.
CBT
Behavioural therapy
Psychotherapy
Support groups
Changing coping strategies
Relaxation
Energy conservation
Stress management
What are 4 considerations when prescribing/recommending exercise to patients?
Frequency
Intensity
Time
Type
(FITT)
What advice would you give a patient to manage fatigue in advanced cancer? (6)
- Plan activities during times in the day when pt is least tired.
- Integrate regular, gentle activities into the day (stretching, sitting at table for meals).
- Avoid stress and include relaxation/meditation techniques throughout the day.
- Suggest multiple short naps throughout the day.
- Limit visiting hrs for family and friends.
- Look into home meal delivery options.
FS
Physical fatigue
- Physical activity (pacing)
- Nutrition
Mental fatigue
- Relaxation
- Meditation
Emotional fatigue
- Social
- Avoid stress
What are the five elements of the definition of fatigue according to the NCCN?*
Distressing
Persistent
Physical tiredness
Emotional tiredness
Cognitive tiredness
List 4 CNS abnormalities that may contribute to fatigue
Primary and secondary tumours*
Anti neoplastic tx
Drugs used to treat complications of cancer (ie opioids)
Dis regulation of seretonin and or its receptors in the brain due to cancer tx.*
Circadian rhythm disruption*
Dysregulation of the HPA axis*
What is the relationship between fatigue and cachexia?
Fatigue can be caused by muscle weakness and malnutrition which are characteristic of cachexia. But profound fatigue can exist in the absence of cachexia.
On a numerical rating scale what value has been shown to suggest clinically relevant fatigue?
> 5
3 benefits of exercising to manage fatigue.
Maintain muscle mass
Improved self-reported physical functioning
Improved sense of wellbeing
Improved self esteem
Improved outcomes (ie maintaining independence)
List 4 lifestyle modifications that can be undertaken for management if fatigue and which can be explored in counseling.
Adapting activities
Spending more time in bed or exercise if deconditioned.
Rearranging schedules with respect to fatigue patterns.
Change causative medications
Treatment for what level of anemia is associated with improved fatigue in palliative care?
<80
List 4 disadvantages of epo for treatment of fatigue.
- Increased thrombotic events*
- It may decrease survival time
- 4-8 weeks before hgb increases*
- Tumour growth (via angiogenesis)*
- High cost*
What is the typical dose of corticosteroids for fatigue?
Prednisone 40mg daily (about Dex 6 mg)
*corticosteroid effects usually only last 2-4 weeks
* long term risk of osteoporosis, myopathies, infections
You have a patient with major depression and cancer-related fatigue.
List 1 pharmacological treatment option for both issues
Major depression could be treated with anti-depressant but this has not been found to be effective for cancer-related fatigue
Consider psychostimulant for rapid anti-depressant effect + helpful with fatigue, opioid-induced sedation
