neuroandgastro.txt

Central nervous system Dementia ………………………………………………………………………………………….. Dementia is an insidious, global deterioration of cognition without impairment of consciousness. More than 100 causes are recognised, though most of these are exceedingly rare: • a terminal disease (albeit slow) with a median survi...

Central nervous system Dementia ………………………………………………………………………………………….. Dementia is an insidious, global deterioration of cognition without impairment of consciousness. More than 100 causes are recognised, though most of these are exceedingly rare: • a terminal disease (albeit slow) with a median survival of 7 to 10 years post-diagnosis • prevalence of 10% in over 65-year-olds, 20% in over 80-year-olds, 40% in 90-year-olds, and for indigenous Australians the prevalence is 3 to 5 times that of non-indigenous Australians • About 1% of all dementia is considered early-onset (age < 65). In indigenous Australians, early-onset disease is defined by an age of onset <50 years Types • Alzheimer’s is the most common (70% of all dementias) - predominant early deficits are episodic memory and orientation to time. • vascular (30% of all dementias) - accompanies a history of cardiovascular events (CVA/TIA) - islets of retained functioning - language is preserved - dysexecutive syndrome - gait disturbance - subcortical signs • frontotemporal (FTD - 10% of all dementias; commonest cause of early-onset disease) - can occur in those with Motor Neurone Disease (10 to 15%) - disinhibition, apathy and loss of empathy - hyperorality, lability, poor insight and compulsive, perseverative behaviours • Lewy body dementia (LBD) - Parkinsonism - visual hallucinations and cognitive fluctuations - cognitive fluctuations typically marked - REM-Sleep behaviour disorder - vulnerability to delirium - extreme sensitivity to antipsychotics - quetiapine is the agent of choice. • treatable causes - depressive pseudodementia - subdural and hypothyroidism - B /folate deficiency - syphilis THE PALLIATIVE CARE HANDBOOK | 9 • others - Parkinson’s disease (essentially very similar to Lewy body dementia), Huntington’s, alcoholic, post traumatic brain injury, paraneoplastic, post encephalitic Note that mixed types of dementia become increasingly common with age, and that end-stage dementia (regardless of cause) tends to assume a common phenotype. With the exception of Lewy body dementia, determining the exact type of dementia in a palliative/end-stage setting is much less important than recognition and appropriate treatment of a behavioural syndrome. Assessment • Take an extensive history (in end-stage dementia this will invariably need to be from a family member or close caregiver). • Formally assess mental state, including the use of cognitive screening tools e.g. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) - where the patient retains verbal skills. (see ‘Useful resources’ p. 162) • In many cases a formal cognitive evaluation will not be possible in advanced dementia, but the broader mental status examination remains invaluable, particularly in relation to: - General appearance and behaviour. Is the patient agitated, distressed, vocalising? Are there any signs of drug side effects (Parkinsonian facies, resting tremor, dyskinetic movements - oro-lingual dyskinesias are particularly common), dystonic reactions, motor tics or perseveration? - Affect - does the patient’s expression reflect sadness, anxiety, anger? Are they guarded and suspicious? Lability may reflect frontal involvement, and should be differentiated from depression. - Perception. Does the person appear to be responding to external stimuli? Behavioural and Psychological Symptoms of Dementia (BPSD) • delirium - a careful history is vital. The biggest single risk factor for delirium is the presence of pre-existing cognitive impairment, so those with dementia are at vastly increased risk. Reduced cognitive reserve lowers delirium threshold. - A history of acute deterioration (cognitive, functional, behavioural) in the setting of previously stable impairments should always suggest delirium, and should be treated as such. • depression (treat early initially with a SSRI or mirtazapine) - this is a difficult diagnosis to make in the presence of advanced dementia, where the patient’s ability to report symptoms accurately is compromised - clinicians are advised to fall back on the presence of ‘hard-core’ biological symptoms of depression in this setting (recent change in sleep or appetite patterns, complete anhedonia, self-harm behaviour) - if there is any doubt, erring on the side of a trial of treatment is often advisable. Depression should be on the list of differential diagnoses for most behavioural disturbances in dementia, and modern antidepressants are much less toxic than the antipsychotic drugs that might otherwise be prescribed 10 | THE PALLIATIVE CARE HANDBOOK - Mirtazapine is a useful drug in this patient group. It has beneficial effects on sleep, appetite and anxiety that occur early in the course of treatment and which are independent of its antidepressant effects - The minimum antidepressant dose of mirtazapine is 30mg. If treating depression there is generally no advantage to commencing at a lower dose (often justified on the basis of minimising sedation…mirtazapine is an inverse agonist at the histamine receptor, however, and thus is more sedating at lower doses) • agitation/aggression (consider low dose short term antipsychotics, benzodiazepines) - identify precipitants (can be difficult) - avoid confrontation - if the issue is agitation alone, antipsychotics hold no advantage over benzodiazepines, and are considerably more toxic - an intermediate half-life benzodiazepine with no active metabolites (e.g. oxazepam 7.5-15mg, temazepam 10mg) is the safest choice - there is evidence for the use of low-dose risperidone in the management of aggression, but the effect size is small (~0.2) • anxiety - peaks in early/mid stages • delusions (treat with antipsychotic) - particularly paranoid - beware ‘delusions of theft’ and ‘misidentification delusions.’ These may well be beliefs that have arisen as the artefact of cognitive impairment and/or to reflect neurological impairment (e.g. prosopagnosia) and are not likely to be antipsychotic responsive • hallucinations - visual (up to 50% in LBD, although 20% of Alzheimer’s patients will hallucinate at some stage during the course of the disease) • sleep/wake cycle reversal/sundowning • loss of insight/judgement • wandering (60% of patients) - pacing and lapping (exclude akathisia) - (dangerous) eloping i.e. getting lost, accidents • rejection of care - of food, hydration (consider artificial hydration) and hygiene Complications • eating and swallowing difficulties, cachexia • infections - pneumonia, urinary tract - in pneumonias, the mortality is sevenfold that of a non-dementia patient - treat if symptomatic, antibiotics have limited efficacy • falls - due to impulsivity, frailty, benzodiazepines and other sedatives • pain - common in very elderly (50%) - may present behaviourally (non-verbally, crying, irritability) THE PALLIATIVE CARE HANDBOOK | 11 - roughly 70% of patients with significant BPSD are likely to have under-treated or unrecognised pain as a contributing factor • adverse reactions to drugs - antipsychotics - sensitivity (Lewy body disease), parkinsonism, akathisia, acute dystonic reactions, sedation, peripheral oedema, chest infections, accelerated cognitive decline, stroke risk (3 fold that of non-dementia patients, 1.5 fold mortality), hypotension - benzodiazepines - sedation, falls Treatment As curative treatment does not exist, ensure that end-of-life discussions/advance directives/appointment of enduring power of attorney all happen early before loss of capacity. The environment of care is important - it should be simple, safe, involve attentive and patient staff, include support and education for family and carers, person-centred, proactive, include distractions, activities, routine, memory cues and benign paternalism. • Mild - cholinesterase inhibitors may have temporary cognitive benefit • Moderate - focus on quality of life and maintenance of function • Severe - maximise comfort, avoid aggressive, burdensome or futile treatments, avoid enteral tube nutrition, consider a secure facility, allow a natural death (AND) Depression ……………………………………………………………………………………….. In end-of-life care it is important to distinguish between clinical depression and profound sadness. • depression is a pervasive sense of misery • sadness is a normal response to loss which waxes and wanes but enjoyment and future planning are retained • most terminally ill patients do not become clinically depressed • prevalence is about 15% (compared with 5 to 10% in the general population), most commonly in the early cancer stages • reaching a diagnosis of depression in terminal patients is difficult as the usual physical symptoms of depression in the otherwise well such as anorexia, weight loss, sleep disturbance are often already present in patients with malignant disease whether they are depressed or not • the psychological symptoms are more discriminative • asking ‘Are you depressed?’ provides a bed-side assessment of mood • suicide is rare, however, fleeting suicidal thoughts and fluctuating ‘will to live’ in cancer patients are common and not necessarily pathological • requests for euthanasia and/or physician assisted suicide are more common although, as for suicide, this is not limited to depressed patients • clinical depression is under-recognised and under-treated yet it is generally very responsive to treatment • the cause of depression is unknown but imbalances in neurotransmitters, especially serotonin, in the brain may play a part 12 | THE PALLIATIVE CARE HANDBOOK Psychological symptoms of major depression may include • hopelessness • anhedonia (loss of pleasure) • morbid guilt and shame • worthlessness and low self esteem • request for physician assisted euthanasia • persisting suicidal ideation • lowered pain threshold • decreased attention and concentration • cognitive slowing • impaired memory • indecisiveness • early morning wakening • ruminative negative thoughts • nihilistic and depressive delusions • feeling of unreality Depression in older people and people with dementia It is worth noting that the ‘textbook’ symptoms of major depression as they appear in references such as DSM-V have not been validated in older persons. Many older people with depression will not use the word ‘depression’ to describe their feeling state, but will instead use terms such as ‘anxiety,’ or ‘I’m just worried, doctor.’ Taking these terms at face value may lead to the inappropriate prescription of anxiolytics. Older persons also tend to express their depression more frequently in terms of somatic symptoms than younger persons do, which can clearly present diagnostic difficulties in a setting where palliative care is being provided. Similarly, the diagnosis of depression in the setting of dementia is fraught. In cognitively intact populations, the diagnosis is made on the basis of symptom self-report. In advanced dementia, however, most patients will be unable to reliably verbalise their symptoms. The psychological distress that depression causes may instead be expressed in terms of externalising behaviours, which may include agitation, aggression, pacing and calling out, themselves common behavioural and psychological symptoms of dementia (BPSD). Two of the more reliable ‘biological’ symptoms of depression in the setting of dementia are recent worsening in sleep or appetite. SSRI antidepressants are considered first-line pharmacological management for symptoms of BPSD. One of the likely reasons for their apparent success in controlling BPSD is that many cases labelled as BPSD are, in fact, cases of depression manifesting as disturbed behaviour. In a similar vein, while drug treatment trials of depression in the setting of dementia have been disappointing/contradictory, part of the problem inherent in such trials is a lack of certainty around diagnosis. In other words, these trials may well have included persons with undifferentiated BPSD, rather than depression. THE PALLIATIVE CARE HANDBOOK | 13 A number of screening tools for depression in dementia exist. Perhaps the most commonly used tool is the Cornell Scale for Depression in Dementia. Clinicians should be wary of placing too much faith in the Cornell, however, as it has not been validated in patients with an MMSE of 10 or less, nor in patients with significant BPSD. The role of antidepressants in treating depression in advanced dementia is controversial, and is likely to remain so, given the methodological problems in ‘true case’ ascertainment. When in doubt, however, clinicians are advised to err on the side of a trial of treatment. Risk factors • inadequate symptom control - unrelieved pain, nausea • poor quality of life • lack of social support • past and/or family history of depression • older age • substance abuse • misinformed prognosis • polypharmacy • specific drugs - steroids, cytotoxics, antibiotics, anti-hypertensives, neuroleptics, sedatives, beta-blockers, opioids • immobility • advanced malignant disease Differential diagnosis • adjustment/grief reaction (sadness) • ‘vital (physiological) exhaustion’ • demoralisation (a state of existential despair, meaninglessness and hopelessness but not of anhedonia and joylessness) • delirium/sedation • detachment (the terminal shedding of attachments) • ‘giving up’ (affect neutral, rational, decisive) Management • mild to moderate depression - support, empathy, clarification of stressors or precipitators, explanation, cognitive therapy, symptomatic relief • severe depression - supportive psychotherapy plus drug therapy - drug therapy - antidepressants are effective in 50 to 70% of cases > a therapeutic trial is usually appropriate > if in doubt, refer to a specialist psychiatrist > SSRI e.g. escitalopram, sertraline, fluoxetine 14 | THE PALLIATIVE CARE HANDBOOK > although full response to antidepressant therapy may not be evident for 4-6 weeks, the lack of any response in the first 10-14 days should prompt consideration of a dosage increase or change of agent. > alternative agents include mirtazapine, duloxetine and venlafaxine > mirtazapine - can be useful due to its beneficial early effects on appetite, sleep and anxiety, which can be expected to occur well in advance of its antidepressant effects. > tricyclic antidepressants should be avoided, as the doses required for adequate response are likely to produce significant anticholinergic side effects, and may thus precipitate delirium, particularly in those with dementia. - psychostimulants e.g. methylphenidate > not as effective as SSRIs - may help retarded/withdrawn, frail patients for a few weeks only > a response may be achieved from small doses (5 to 30 mg each morning) within days either alone or in combination with an SSRI - watch for additive serotonergic effects. Modafinil may be a useful alternative to methylphenidate Delirium …………………………………………………………………………………………….. Toxic confusional states, like delirium, are common in people who are dying. • if irreversible, may be an indication of impending death • can be most distressing for patients, family and staff Diagnosis • abrupt onset, typically, but may be subacute in those with dementia. • impairment of consciousness - the primary symptom which results in: - disorientation (to time) - fear and dysphoria - memory impairment (short term memory) - reduced attention span to external stimuli - hyperactive (frenzy) or hypoactive (retardation, torpor) but usually mixed hyperactive and hypoactive motor activity - reversal of sleep-wake cycle - perceptual disturbance (illusions, hallucinations) - disorganised thinking (paranoia, rambling) - dysgraphia (difficulties with writing) • fluctuating symptoms (‘sundowner effect’) Causes There are often multiple organic causes but in up to 50% of cases, specific causes are not found, despite investigations. Diagnosis is dependent on the presence of an appropriate history, rather than the results of a ‘delirium screen’. Causes may include: • infection • organ failure (liver, kidney) and underlying medical conditions THE PALLIATIVE CARE HANDBOOK | 15 • drugs - sedatives - anticholinergics - opioids - benzodiazepine or alcohol withdrawal - steroids • metabolic disturbances - dehydration - hypercalcaemia - hyponatraemia - hyper/hypoglycaemia • hypoxia • anaemia (severe) • vitamin deficiency • cerebral metastases • cerebral haemorrhage • epilepsy - post-ictal Predisposing/precipitating/aggravating factors • dementia and CNS immaturity • any other cause of pre-existing cognitive impairment (e.g. intellectual disability, ABI) • pain • fatigue • urinary retention • constipation • unfamiliar excessive stimuli • change of environment • sensory deprivation • sleep deprivation Management • treat the underlying organic causes if identifiable and treatable • treat fever, hypoxia, anaemia, dehydration, constipation, fear and anxiety and pain if possible • ensure there is a safe and secure environment - have adequate staffing, remove potentially dangerous objects, have the mattress on the floor • prevent sensory over-stimulation - have a single room, minimise noise and staff changes and maintain a warm and comfortable environment • psychological interventions - reassurance - orienting aids (clock, personal belongings, presence of a supportive family member) 16 | THE PALLIATIVE CARE HANDBOOK - cognitive strategies (clarification, reality testing, validation and repetition during lucid periods) - emotional support (touch, empathy) • drugs - use if symptoms are severe (in combination with above management) - antipsychotics (goal is to calm or pacify rather than sedate) > haloperidol is traditionally the drug of choice BUT not in AIDS delirium (HIV makes the CNS more sensitive to dopamine antagonists), hepatic encephalopathy or alcohol withdrawal where benzodiazepines only should be used (see haloperidol in drug section) ~ Haloperidol regimen in acute delirium: ~ Oral (tablets, liquid) if compliant, subcut if not ~ initial dosage - 0.5 to 1.5 mg orally ~ repeat and titrate every 30 to 40 minutes until controlled. In general, daily doses in excess of 3mg should be avoided due to high risks of extrapyramidal side effects (EPSE) in older patients. Only in physically robust, younger patients in whom significant aggression is present should doses in the order of 5-10mg daily be used. ~ maintenance - 50% of daily dose required to achieve control usually 1 to 3 mg/day (oral) ~ only add anticholinergic agent e.g. benztropine 1-2 mg if acute dystonia occurs. Routine use of anticholinergic agents will worsen delirium ~ extrapyramidal side effects are less pronounced with the parenteral route. Thus, if IV access is present, parenteral administration is preferable > risperidone (tablets, liquid, wafers) - dosage regimen as per haloperidol > olanzapine (tablets, wafers) - doses of up to 2.5mg TDS can be considered. Doses in excess of this tend to have significant anticholinergic activity, and may make things worse > Quetiapine - doses of 12.5-25mg are useful for acute sedation for short periods. Tolerance rapidly develops over several days to the sedative effects of this agent, leading to a tendency towards ‘dose-creep’ over time. If rapid control of distressing psychotic symptoms is required, however, this agent is not recommended, as it must be titrated up over several days in order to avoid both oversedation and postural hypotension. - sedatives (should not be used alone in most cases of delirium as they may aggravate symptoms, particularly if inadequate doses are used, so use with an antipsychotic) > benzodiazepines e.g. midazolam, clonazepam > barbiturates e.g. phenobarbitone > melatonin may be useful - anaesthetics e.g. propofol (rarely indicated) - drug-induced delirium > opioid-induced - decrease dose or change opioid > anticholinergic-induced - e.g. physostigmine may reverse this. THE PALLIATIVE CARE HANDBOOK | 17 Even if the aetiology is irreversible, the symptoms of delirium may be palliated. Only 10 to 20% of patients with terminal delirium should require ongoing sedation to achieve control. Disorders of sleep and wakefulness …………………………………………….. Sleep disturbance in people who are dying is a frequent occurrence and it requires careful assessment and management. • sleep patterns change with age and with illness e.g. cancer - reduction of depth and continuity of sleep and an increasing propensity for day-time naps occurs - many cancer patients have difficulty falling and staying asleep - cytokines are implicated in these changes Insomnia This is common and distressing. It undermines coping strategies through tiredness. Causes • poor symptom control of - anxiety, depression, pain, urinary frequency, faecal incontinence, nausea, vomiting, delirium, cough, delirium • environmental changes - admission to hospital or hospice - disturbance by staff or family • fear of going to sleep and never waking up • drugs - stimulants e.g. methylphenidate - steroids (particularly if given after noon) - bronchodilators - alcohol, caffeine • withdrawal of benzodiazepines, alcohol or tobacco Management • symptom control of above • establish good sleep hygiene - regular bedtimes - minimise daytime napping - reduce evening stimulants e.g. caffeine, alcohol - comfortable bedding - comfortable temperature • relaxation techniques • drugs - hypnotics > short acting benzodiazepines e.g. temazepam > longer acting benzodiazepines e.g. oxazepam 18 | THE PALLIATIVE CARE HANDBOOK > melatonin 2 to 4 mg at night - sedative antidepressants e.g. mirtazapine 7.5-15mg nocte - sedating antipsychotics e.g. quetiapine 25 to 50 mg at night may be considered if insomnia is resistant to above. Note that tolerance to sedation from quetiapine can occur rapidly (within several days). Drowsiness/hypersomnia These are common symptoms, particularly as the end-of-life approaches. Causes • organ failure e.g. renal, hepatic, cardiac, respiratory • delirium (hypoactive) • metabolic disturbances e.g. hyperglycaemia, hypercalcaemia • fatigue or ‘vital exhaustion’ • infection • raised intracranial pressure • drugs - adverse effects e.g. opioids, anticholinergics, benzodiazepines, cyclizine, levomepromazine (methotrimeprazine) Management • accurate assessment • treat/remove causes where possible • it may be unresolvable and be a natural part of the dying process Sleep phase (circadian) disorder (Delayed Sleep Phase Syndrome or Sleep-Wake Reversal) • a dysregulation of the sleep-wake cycle - profound initial insomnia and - the inability to arise at desirable hours • particularly associated with cerebral tumours • presents a major burden for carers Management • shifting the circadian rhythm with behavioural strategies and bright light therapy is impractical in the terminally ill • relief care for the family and a night nurse may be necessary as this tends to be an intractable symptom • drugs are of limited benefit - sedatives e.g. benzodiazepines - psychostimulants e.g. methylphenidate can promote daytime alertness - sedating antipsychotics e.g. quetiapine 25 to 200 mg at night - pericyazine 20 to 30 mg at night - melatonin 2 to 6 mg at night THE PALLIATIVE CARE HANDBOOK | 19 Terminal agitation ……………………………………………………………………………. Perhaps best conceptualised as a prolonged delirium, this may indicate physical, psychological and/or spiritual discomfort. It is usually a ‘pre-death’ event. A significant proportion of new-onset BPSD-type behaviours in fact represent terminal agitation. Early recognition of the syndrome enables appropriate palliative measures to be instituted early. In the residential care setting, predictors of terminal agitation can include chest infections, unexplained fevers, poor oral intake, significant recent weight loss, the presence of bed sores, and increases in verbal and motor behaviours. Terminal agitation is poorly recognised, and is often interpreted by care staff as a worsening of behavioural and psychological symptoms of dementia (BPSD). Early data from the Australian national Severe Behaviour Response Teams (SBRT) found that up to 10% of referrals to this service were ultimately revealed to have been on a terminal trajectory. Causes • physical discomfort - unrelieved pain - distended bladder or rectum - physical restraint - insomnia - uncomfortable bed or environment • delirium (see delirium section) • psychological discomfort - anger - fear - guilt - unfinished business • spiritual discomfort/distress - helplessness - hopelessness • drugs - akathisia induced by dopamine antagonists e.g. metoclopramide, haloperidol (and occasionally via sedating antihistamines such as promethazine) Management • assess and treat/remove possible causes • explain what’s happening to the family, patient (if appropriate) or main carers • have the family present to reassure and support • discuss psychological discomfort e.g. anger, fear, guilt • drugs - see delirium section and anxiety and fear section 20 | THE PALLIATIVE CARE HANDBOOK - e.g. midazolam in inadequate doses can aggravate (by disinhibition) rather than relieve restlessness in some patients - if levomepromazine (methotrimeprazine) with a benzodiazepine are ineffective consider phenobarbitone or dexmedetomidine Palliative sedation …………………………………………………………………………… This is considered when all other symptom-relieving measures have failed and the patient is clearly distressed. Reasons for palliative sedation • terminal restlessness (see terminal agitation) • uncontrolled delirium (see delirium) • severe breathlessness (see dyspnoea) • massive haemorrhage (see haemorrhage) • neurogenic or cardiogenic pulmonary oedema • intractable distress How palliative sedation is achieved • the level of sedation should be titrated to removal of distress • drugs - benzodiazepines e.g. midazolam, clonazepam - sedating antipsychotics e.g. levomepromazine (methotrimeprazine) (subcut 12.5 to 200 mg/24hours) - barbiturates e.g. phenobarbitone (subcut 600 to 1,200 mg/24 hours) - dexmedetomidine - experience in palliative care is limited - opioids > BUT increasing doses may not result in increased sedation (opioids tend only to be sedating in the opioid naive) and may instead induce respiratory depression or seizures Sedation of this type may be subject to the principle of ‘double effect’ which has the dual effects of intentional relief of suffering and increased risk of hastening death. Palliative sedation itself has not been shown to hasten death. Fear and anxiety………………………………………………………………………………. Fear A brief, reflexive, rational and unpleasant emotional response (being afraid) caused by anticipation or awareness of danger. A present-focused, reality-based reaction initiating avoidant behaviours. Associated with physiological and psychological arousal. May be adaptive and enhance safety, or non-adaptive. • innate fear (pain, bleeding, being alone, odours, confined spaces, novel places) • learned fear (dying, death, being buried alive, needles, chemotherapy) THE PALLIATIVE CARE HANDBOOK | 21 Anxiety Sustained and excessive uneasiness. Future-focused, irrational, grossly exaggerated response to perceived threat to the ‘self’, to one’s existence. An intrapsychic conflict. Encourages (unsuccessful) attempts to resolve threat. • may be a normal alerting response • may be a symptom of a medical condition (e.g. delirium, depression, hormone-secreting tumour), or a symptom of an impending medical catastrophe • may be the result of an adverse reaction to a drug e.g. bronchodilators, steroids, methylphenidate • may be a symptom of Generalised Anxiety, Panic or Depressive disorders Common anxieties and fears centre on • being ill • separation from loved ones, homes or jobs • becoming dependent on others (being a ‘nuisance’ or ‘burden’) • losing control of physical faculties • failing to complete life goals or obligations • uncontrolled pain or other symptoms • abandonment • not knowing how death will occur • ‘death anxiety’ (the fear of non-being) • spirituality Management of fear • avoid threat if possible • forewarning and preparations • emotional first aid • behaviour desensitisation for phobias (a syndrome of pathological fear) • psychotropic medications of limited effectiveness Management of anxiety • careful listening and attention to detail • support to maintain independence and autonomy • honest and open discussion about the future with the patient and family at a pace that they can accommodate • support realistic hope for the future • provide distractions to avoid boredom and excessive self-reflection • attend to social and financial problems • provide focussed spiritual care if appropriate • psychotropic drugs - may be a useful adjunct - benzodiazepines e.g. lorazepam can be very effective in the short term (days to weeks) but this may fade and there is a risk of tolerance and dependency - beta-blockers e.g. propranolol may block the peripheral symptoms and thus ease the unease 22 | THE PALLIATIVE CARE HANDBOOK - antidepressants e.g. escitalopram, fluoxetine may be more effective longer term than benzodiazepines Raised intracranial pressure …………………………………………………………. Raised intracranial pressure is a life-threatening event that needs to be carefully assessed and managed to optimise quality of life and minimise symptoms. Symptoms • severe headache which is worse when lying down or straining • vomiting • convulsions • mental - drowsiness, delirium • diplopia • restlessness Causes/risk factors • cerebral metastases (more common with some primaries, e.g. lung, breast, melanoma than with others, e.g. prostate) • primary brain tumour • abscess • cerebro-vascular event • sagittal sinus thrombosis • secondary hydrocephalus following surgery Management If raised intracranial pressure is suspected look for papilloedema and signs of cerebral irritation. Computerised tomography or MRI may be appropriate. • raise the head of the bed • consider cranial radiotherapy or neurosurgery for malignancy if prognosis/status warrants it • drugs - dexamethasone up to 16 mg per day. Avoid doses after noon as may add to insomnia. Gradually reduce dose to minimum effective. Withdraw after 7 days if ineffective (note - some anticonvulsants can reduce effectiveness - see dexamethasone page) - codeine (sometimes eases head pain) - consider anticonvulsants particularly if seizures are present - consider acetazolamide 250 to 500 mg once daily to bd THE PALLIATIVE CARE HANDBOOK | 23 Convulsions ……………………………………………………………………………………… Convulsions can be distressing not only for the patient but also for the family and other carers. They should be managed effectively to reduce distress and anxiety wherever possible. It is important to have a clear history of the convulsion in order to diagnose the type (grand mal, focal, absence or status epilepticus). At times a convulsion can be mistakenly diagnosed when the true cause of loss of consciousness or absence is a syncopal attack, cardiac arrhythmia, or a transient ischaemic attack. Causes • previously diagnosed epilepsy, brain trauma/surgery, brain tumour/mets • drugs - some lower seizure threshold e.g. phenothiazines, tricyclics - interactions - antiepileptics have many variable and unpredictable interactions (see individual drug pages) - withdrawal e.g. of steroids, alcohol • metabolic disturbance, e.g. hypoxia, hyponatraemia, hypoglycaemia Management Prophylaxis • drugs - consider dexamethasone if related to raised intracranial pressure (primary brain tumour/metastases) - sodium valproate initially 500 mg bd to tds increasing every 3 days to 1 to 2 g per day - levetiracetam 500 mg bd initially - carbamazepine initially 100 to 200 mg once daily to bd increasing by 100 to 200 mg every 2 weeks to 800 to 1,200 mg per day - consider therapeutic drug monitoring of plasma concentrations - phenytoin 200 to 300 mg nocte - consider therapeutic drug monitoring of plasma concentrations - if oral route is not available consider > clonazepam 1 to 4 mg/24 hours by subcut infusion > midazolam 10 to 60 mg/24 hours by subcut infusion > consider the use of phenobarbitone if convulsions are not effectively managed by other agents Grand mal convulsions or status epilepticus management • make the patient safe, explain what is happening and reassure • drugs - rectal diazepam 10 to 20 mg - buccal midazolam 5 to 10 mg - between the cheek and gum - subcut boluses of clonazepam or midazolam - if these measures are not effective consider the use of phenobarbitone 24 | THE PALLIATIVE CARE HANDBOOK Pain The assessment and management of pain and other symptoms are the cornerstones of effective palliative care. There are different types of pain and many patients have more than one. Comprehensive assessment …………………………………………………………. • listen to the patient’s story and the language used • ask about the site(s) of pain • measure intensity with a validated tool to assess changes: - a visual analogue scale (some patients find this hard to use) - a numerical rating scale - perhaps the most common method used - patients rate their pain on a scale of 0 (no pain) to 10 (the worst pain they can imagine) - colour charts - facial expression charts • ask about timing and duration of pain e.g. constant or episodic • ask about the nature (e.g. stabbing, aching) and duration of the pain - this will determine management - identifies the type and source of pain > somatic nociceptive is usually constant and localised > visceral is usually described as deep or aching (capsular stretch pain) or intermittent and griping (colicky pain) > bone pain is usually deep or boring > neuropathic pain is usually burning, shooting or stabbing • ask about what relieves the pain (body position, heat, cold) and what exacerbates the pain (movement, position, heat) • ask about the significance of the pain - ask how much of a nuisance it is - discuss its significance - explain the likely causes - often helpful in allaying fears or anxieties and can significantly contribute to the relief of pain • examine the part(s) that are painful - look, touch and move • consider further investigation such as X-ray, CT or MRI but only if the result is going to influence management • document all findings to compare and communicate • review regularly - essential after any therapeutic intervention THE PALLIATIVE CARE HANDBOOK | 25 Other assessment factors ……………………………………………………………… In a bio-medical model of practice it is tempting to assume that pain has a predominant physical component. Often, physical pain is only part of the symptom complex (through direct or indirect tumour effects or non-malignant processes). Psychological, spiritual and sociological elements will also be identifiable in many people with pain. Fear, anxiety, sadness, anger, frustration and isolation are but a few of the feelings that can contribute to the total perception of pain. All of these elements help to build a realistic picture of the overall impact of pain on the individual’s quality of life. Assessment in the setting of dementia People living with dementia who require palliative care may not, by virtue of cognitive impairment, be able to validly report either the presence of pain, or the level of pain they are experiencing. There is good evidence that those with dementia are likely to be prescribed up to 50% less analgesia in acute hospital settings than those with comparable needs who lack a dementia diagnosis. There are a number of validated pain assessment scales that can inform pain assessment in the presence of dementia. They include the Abbey Pain Scale, the PAIN-AD and the electronic ePAT (electronic Pain Assessment Tool), which uses facial coding to determine the presence of pain. These are screening tools only, and are no substitute for a comprehensive clinical assessment. The emergence of new behavioural symptoms (such as withdrawal, agitation, anger, aggression and resistiveness to care) in a person with previously stable dementia symptoms should always be an indicator that pain may be an issue. It should be noted that the pain assessment tools mentioned above have not been validated in the presence of significant behavioural disturbance, as they do not reliably distinguish between pain and distress. In the absence of valid pain self-reporting in the setting of severe dementia, considering the views of a family caregiver who knows the patient and their usual behaviours well may be useful as part of the assessment process. Unrecognised or undertreated pain can lead to the inappropriate prescription of psychotropic medication instead of adequate pain management. Management…………………………………………………………………………………….. It is important to encourage patients to develop self-management strategies -recognising that this may not be possible in people with dementia - and to utilise non-pharmacological strategies such as rest, positioning, pacing etc. There are also a number of enabling strategies like goal setting, pain management plans, scripts and diaries that many will find useful. Analgeics • some pains may not respond completely to opioids • co-analgesics are useful when response to opioids is poor • switching route can sometimes help e.g. from oral to subcutaneous 26 | THE PALLIATIVE CARE HANDBOOK • in prescribing analgesics use a step-wise approach: • regular paracetamol may be useful in opioid induced hyperalgesia although use should be continued only if effective as up to 8 tablets per day adds significantly to the tablet burden • there is some debate over the second step in this ladder - most palliative care practitioners go to step 3 either after step 1 or initially depending on the severity of the pain - pain relief from codeine may be from the active metabolite, morphine - the place of tramadol in palliative care remains unclear - it can be extremely emetogenic Initiating morphine in opioid naive patients • start with small regular oral (if possible) immediate release doses • titration with slow release morphine is less common than with immediate release • if using immediate release prescribe morphine elixir (immediate release) (2.5 to 5 mg) every four hours regularly and titrate • prescribe ‘when required’ doses of 1/5th to 1/6th of the regular 24 hour dose for ‘breakthrough’, ‘episodic’ or ‘incident’ pain • document the amount of morphine taken • once a stable dosing regimen is achieved (2 to 3 days) convert to a long-acting preparation - calculate the total 24 hour dose of immediate release morphine required from ‘breakthrough’ and regular dosing, divide by 2 and give twice daily - ‘when required’ doses of 1/5th to 1/6th of the regular 24 hour dose should be prescribed as immediate release once again for pain between doses • if the patient can no longer swallow - give 1/2 the total 24 hour oral dose by continuous subcutaneous infusion - ‘when required’ doses of 1/5th to 1/6th of the regular 24 hour dose should be prescribed once again for pain between doses Drugs that are either not available or not funded in New Zealand THE PALLIATIVE CARE HANDBOOK | 27 • consider reducing dose if another mode of pain relief is used (e.g. radiotherapy, ketamine) Initiating oxycodone in opioid naive patients • start with small regular oral (if possible) doses • prescribe oxycodone immediate release capsules or liquid every 4 to 6 hours and titrate • prescribe ‘when required’ doses of 1/10th to 1/12th initially (although many practitioners use 1/5th to 1/6th) of the regular 24 hour dose for ‘breakthrough’, ‘episodic’ or ‘incident’ pain • document the amount of oxycodone taken • once a stable dosing regimen is achieved (2 to 3 days) convert to a long-acting preparation calculate the total daily dose of oxycodone required from ‘breakthrough’ and regular dosing, divide by 2 and give twice daily ‘when required’ doses of 1/10th to 1/12th initially (although many practitioners use 1/5th to 1/6th ) of the regular 24 hour dose should be prescribed as immediate release for pain between doses • consider reducing dose if another mode of pain relief is used (e.g. radiotherapy, ketamine) • the long acting preparation has a layer of immediate acting drug round it • if the patient can no longer swallow give 1/2 the total 24 hour oral dose by continuous subcutaneous infusion ‘when required’ doses of 1/10th to 1/12th initially (although many practitioners use 1/5th to 1/6th ) of the regular 24 hour dose should be prescribed once again for pain between doses • consider reducing dose if another mode of pain relief is used (e.g. radiotherapy, ketamine) Initiating hydromorphone* in opioid naive patients • as with oxycodone start with small regular oral (if possible) doses • titrate upwards in small increments as with morphine and oxycodone • otherwise the same principles apply Initiating fentanyl patches in opioid naive patients • don’t - fentanyl patches should only be used in patients who have already been exposed to opioids Initiating methadone in opioid naive patients • as methadone has a long and variable half life it should be commenced at low dosage e.g. 1 mg to 2.5 mg bd and consideration should be given to dose reduction once at steady state (minimum 5 days) • should be used under advice of a specialist palliative care physician only Adverse effects of opioids Drugs that are either not available or not funded in New Zealand 28 | THE PALLIATIVE CARE HANDBOOK • all opioids are associated with the following adverse effects but the incidence (incidences below are for morphine) and severity vary from opioid to opioid (e.g. fentanyl is less constipating than morphine) • tolerance to some of these adverse effects can develop e.g. nausea/vomiting but not to others e.g. constipation constipation - 95% of patients (less with fentanyl [50%] and the naloxone/ oxycodone combination product) - prescribe a laxative prophylactically - nausea/vomiting - 30-50% of patients - usually in the first 10 days until tolerance develops drowsiness - 20% of patients - usually in the first 3 to 5 days until tolerance develops confusion - 2% of patients - either reduce the dose, change to a different opioid or consider adding haloperidol. Rates of worsening confusion are greatly elevated in those with a pre-existing cognitive impairment, due to diminished cognitive reserve. Frank delirium can be precipitated. hallucinations/nightmares - 1% of patients - give haloperidol or change to a different opioid hyperalgesia - usually to touch as a result of too high a dose of opioid which may improve on dose reduction hyperkatafeia - emotional lability induced by long-term opioid use Opioid rotation • opioid rotation (or changing from one opioid to another) is often used when tolerance to the analgesic effects of opioids (stimulation of NMDA receptors) or severe adverse effects occur • works because of the difference in the mix of opioid receptors stimulated by each individual opioid in each patient • most often from morphine to oxycodone, fentanyl or methadone • rotation should only occur under supervision and by a specialist as conversion doses are difficult to predict and are often much smaller doses than those listed below - see oxycodone, hydromorphone*, fentanyl and methadone in the second section Opioid equivalents • the following are ‘single dose’ equivalences i.e. ONLY equivalents in healthy volunteers given a single dose • equivalence in sick patients who are chronically dosed is difficult to quantify - use care when converting from one opioid to another Drugs that are either not available or not funded in New Zealand THE PALLIATIVE CARE HANDBOOK | 29 • pethidine is NOT recommended in palliative care codeine 60 mg oral = 6 mg oral morphine tramadol 100 mg oral = 10 mg oral morphine oxycodone 5 mg oral = 10 mg oral morphine 5 mg subcut = 5 mg subcut morphine hydromorphone* 6 mg oral = 30 mg oral morphine 2 mg subcut = 10 mg subcut morphine methadonesee methadone page in the ‘Drug information’ section fentanyl see fentanyl page in the ‘Drug information’ section buprenorphine see buprenorphine page in the ‘Drug information’ section Co-analgesics • drugs usually used for a different indication with analgesic properties (sometimes such use is outside the product license) • can be used in combination with other analgesics or alone • choice is determined by the types of pain • the use of co-analgesics is probably most helpful in neuropathic pain • bone pain - due to tumour or metastatic involvement - NSAIDs e.g. diclofenac - inhibit prostaglandins bisphosphonates e.g. pamidronate, zoledronic acid - denosumab* • skeletal muscle spasm pain - due to tumour involvement muscle relaxants e.g. diazepam, clonazepam, baclofen • smooth (intestinal) muscle spasm pain - ‘colic’ from intestinal spasm - anticholinergic/antimuscurinic e.g. hyoscine butylbromide • tenesmus - due to tumour or metastatic involvement of the rectal muscles steroids e.g. dexamethasone, prednisone - decrease inflammation around tumour • raised intracranial pressure - due to tumour or fluid steroids e.g. dexamethasone - decrease inflammation around tumour - NSAIDs e.g. diclofenac - inhibit prostaglandins • liver capsule stretch pain - from an enlarged liver steroids e.g. dexamethasone - decrease inflammation Neuropathic pain …………………………………………………………………………….. • often the most severe and difficult to manage of all persisting pains • caused by damage to the nervous system • involves NMDA receptor stimulation to some extent • severity cannot usually be linked to the amount of damage - ‘trivial’ lesions can produce severe pain Drugs that are either not available or not funded in New Zealand 30 | THE PALLIATIVE CARE HANDBOOK Causes • peripheral nerve damage - post-surgical, post-trauma or compression • herpetic nerve invasion • amputation - phantom limb pain • Chronic Regional Pain Syndrome (CRPS) • nerve root injury - traumatic avulsion, post-spinal surgery • epidural scarring, arachnoiditis • spinal cord injury and disease • stroke • diabetes • chemotherapy e.g. vincristine, oxaliplatin, taxanes, cisplatin Characterisation • characterised by description and by cause BUT the pain is not always within the distribution of a dermatome or a peripheral nerve • includes allodynia (pain in an area of altered sensitivity) and other sensory symptoms • generally continual and of varying intensity variability in intensity is spontaneous and often has a paroxysmal component not necessarily related to stimulation • descriptive terms include burning, cutting, stabbing sharp/shooting crushing • episodic pain, which can be present on top of the continuous pain, may itself be brief but often a long-lasting aching pain remains for several hours Management • a multidisciplinary approach is useful • behavioural modification - any treatment will be of only limited value unless certain behaviours are changed so address cognitive, mood and behavioural aspects of the patient’s pain individually or in a group • drugs opioid analgesics (first line for neuropathic pain) should be trialed but doses may increase rapidly - some opioids may be more useful than others e.g. methadone which has NMDA blocking activity centrally acting agents reduce spinal hyperexcitability some drugs have an effect on nociceptor neuromodulators, neurotransmitters and cell membrane stability efficacy is highly variable between drugs so tailor the drug to the patient > gabapentin, pregabalin > anticonvulsants e.g. valproate > benzodiazepines e.g. clonazepam > tricyclic antidepressants e.g. nortriptyline SSRIs e.g. escitalopram, sertraline - limited efficacy in palliative care > SNRIs e.g. duloxetine, venlafaxine Drugs that are either not available or not funded in New Zealand THE PALLIATIVE CARE HANDBOOK | 31 > antiarrhythmics e.g. mexiletine > muscle relaxants e.g. baclofen > NMDA antagonists e.g. ketamine > alpha-adrenergic agents e.g. clonidine > calcium channel blockers e.g. nifedipine > steroids e.g. dexamethasone for nerve pressure pain > sodium channel blockers e.g. lignocaine* combining an antidepressant with an anticonvulsant or similar may be more effective than either alone e.g. nortriptyline + gabapentin, pregabalin* if the above are ineffective consider intrathecal/epidural opioids, local anaesthetics and clonidine • other analgesic modalities - nerve blocks > availability is dependent on the skills of the team > access to a specialist anaesthetist is not always possible > for pain which breaks through analgesia, or is controlled at rest but not on movement or is nonresponsive > upper abdominal pain due to pancreatic cancers may respond to coeliac plexus blocks others - often used in conjunction with analgesics > mobilisation e.g. structured stretching, progressive resistance training > radiotherapy/surgery > cytotoxic drugs > hormone therapy > spinal delivery systems > neuromodulation e.g. transcutaneous nerve stimulation (TENS) and, very occasionally, implanted devices such as peripheral nerve or spinal cord stimulation Drugs that are either not available or not funded in New Zealand 32 | THE PALLIATIVE CARE HANDBOOK Gastrointestinal system Nausea/vomiting……………………………………………………………………………… These are common symptoms in palliative care and are often difficult to control. • it is important to separate nausea from vomiting • consider how each affects the individual patient - a vomit a day with no nausea may be more acceptable than continuous low-level nausea - for some patients, nausea is more distressing than pain • nausea and/or vomiting often has more than one cause • choose a management strategy to fit the cause(s) • antiemetics work at differing sites and receptors • antiemetics that affect multiple receptors in multiple areas, such as levomepromazine (methotrimeprazine), may be useful choices regardless of cause • a combination of antiemetics is useful, particularly where there are multiple causes Causes There are two distinct areas in the central nervous system (CNS), which are predominantly involved with nausea and vomiting: • chemoreceptor trigger zone (CTZ) close to the area postrema - part of the central nervous system, the CTZ is thought to lie outside the blood/brain barrier and so can be affected by causes and treatment which are unable to penetrate the CNS • the vomiting centre in the medulla oblongata - can be directly stimulated or inhibited by certain agents The CTZ sends impulses to the vomiting centre, which then initiates nausea and/or vomiting. Higher centres involved with fear and anxiety also communicate with the vomiting centre, as do the peripheral vagal and sympathetic afferents and the vestibular nerve. The causes can be summarised as: • higher centre stimulation - fear/anxiety • direct vomiting centre stimulation - radiotherapy to the head, raised intracranial pressure • vagal and sympathetic afferent stimulation - cough, bronchial secretions, hepatomegaly, gastric stasis, constipation, intestinal obstruction • chemoreceptor trigger zone stimulation - uraemia, hypercalcaemia, drugs e.g. opioids, cytotoxics • vestibular nerve stimulation - motion Management • higher centre stimulation (emotion - fear/anxiety) - counselling/explanation/listening - a benzodiazepine THE PALLIATIVE CARE HANDBOOK | 33 • direct vomiting centre stimulation (radiotherapy to the head, raised intracranial pressure) - cyclizine - dexamethasone • vagal and sympathetic afferent stimulation (cough, bronchial secretions, hepatomegaly, gastric stasis, constipation, intestinal obstruction) - cough - see ‘Cough’ p. 45 - bronchial secretions - see ‘Excessive (retained) secretions’ p. 47 - constipation - see ‘Constipation’ p. 35 - hepatomegaly > dexamethasone > cyclizine - gastric stasis > domperidone (minimal extrapyramidal effects) > metoclopramide > erythromycin - a strong prokinetic - intestinal obstruction > cyclizine > levomepromazine (methotrimeprazine) > avoid prokinetics e.g. metoclopramide in complete obstruction although use in partial obstruction may help - see ‘Intestinal obstruction’ p. 38 • chemoreceptor trigger zone stimulation (uraemia, hypercalcaemia, drugs e.g. morphine) - haloperidol - levomepromazine (methotrimeprazine) • vestibular nerve stimulation (motion) - cyclizine - hyoscine patch (scopolamine) • other drugs which may be useful where others have failed - atypical antipsychotics e.g. olanzapine - ondansetron, palonosetron* (may cause constipation) - experience in palliative care is limited - aprepitant (a neurokinin 1 (NK1) antagonist from the class of drugs known as substance P antagonists) - used with steroids and ondansetron for delayed emesis following highly emetogenic chemotherapy. Its place in palliative care has not been established. • other therapies with little evidence include acupuncture, ginger, cannabis Drugs that are either not available or not funded in New Zealand 34 | THE PALLIATIVE CARE HANDBOOK Bowel management ………………………………………………………………………… • alteration in bowel function is common in terminally ill people • constipation is more common than diarrhoea • efficient bowel management may alleviate distress • carefully assess bowel function on a daily basis • regimens should be discussed, carried out and reported on daily Constipation • diagnose through an accurate history followed by examination • it is the difficult or painful and infrequent passage of hard stools • comparison with an individual’s normal bowel habit and usual use of laxatives may highlight changes related to disease or treatment • a record of bowel habits will help in the management • examination of the abdomen and the rectum may exclude faecal impaction or rectal pathology Causes • metabolic disturbances e.g. hypercalcaemia • dehydration from vomiting, polyuria, sweating, tachypnoea • drugs cytotoxics e.g. vinca alkaloids (via neuropathies) opioids via opioid receptors in the GI tract and perhaps in the CNS - > 95% of people taking morphine will become constipated although other opioids may be less constipating e.g. fentanyl, methadone anti-cholinergics e.g. tricyclic antidepressants - aluminium salts in antacids iron antispasmodics e.g. hyoscine butylbromide - anti-Parkinsonian drugs e.g. levodopa antipsychotics/anxiolytics ondansetron, palonosetron* • immobility e.g. weakness • low fibre diet e.g. milky/invalid foods or reduced intake • inability to obey the call to stool • concurrent medical problems e.g. haemorrhoids, anal fissure, diabetes, hypothyroidism • intestinal obstruction from tumour, faeces or adhesions (abdominal X-ray may help with diagnosis) • gastrointestinal tract nerve compression or damage or autonomic neuropathy Symptoms • anorexia • vomiting/nausea Drugs that are either not available or not funded in New Zealand THE PALLIATIVE CARE HANDBOOK | 35 • abdominal discomfort or cramping • spurious diarrhoea or overflow • confusion • anxiety • bowel obstruction • pain Management • prevention is the key • if a cause (or causes) are identified remove it (or them) if possible • exercise reduces the risk of constipation so encourage it where possible • encourage increased fibre e.g. bran, kiwi crush or soluble fibre formulations (require activity and fluids to avoid impaction) • laxatives when opioids are prescribed anticipate constipation and prescribe an oral softener with a stimulant laxative e.g. docusate with senna or bisacodyl which may prevent the need for rectal intervention later (NB if combinations cause cramps reduce the dose or use an osmotic laxative such as macrogol 3350 with electrolytes (MovicolTM, Lax-SachetsTM) low dose opioid antagonists such as naloxone (marketed in combination with oxycodone and methylnaltrexone*) are effective in opioid-induced constipation without affecting analgesia if constipation is already present give a bisacodyl 10 mg suppository and a glycerin suppository or a sodium lauryl sulphoacetate enema (MicoletteTM) - avoid stimulant laxatives in people with signs of GI obstruction if the patient has a partial obstruction use an osmotic/softener laxative e.g. docusate, and avoid stimulant laxatives if the patient has a spinal cord compression where evacuation is difficult keep the bowel motion firm (avoid softeners) and use a stimulant if a patient taking laxatives has no bowel motion for two days and this is not their normal bowel habit give extra laxatives and, if appropriate, kiwi fruit or prune juice if a patient taking laxatives has no bowel motion for three days and this is not their normal bowel habit a rectal examination should be carried out > if soft faeces are found give 2 bisacodyl 10 mg suppositories or 1 to 2 MicoletteTM enemas > if hard faeces are found give 1 or 2 glycerine suppositories or 2 bisacodyl 10 mg suppositories or consider macrogol 3350 with electrolytes (MovicolTM, Lax-SachetsTM) > if rectum is empty (or no result from first action) repeat abdominal palpation and consider an abdominal X-ray suppositories must make contact with the bowel wall to work - methylnaltrexone* Drugs that are either not available or not funded in New Zealand 36 | THE PALLIATIVE CARE HANDBOOK • faeces consist of approximately 50% water, 25% bacteria and 25% food residue so even if the patient is not eating there will be faeces in the bowel Diarrhoea ………………………………………………………………………………………….. • a relatively uncommon problem in palliative care • rotation from morphine to fentanyl may result in a sudden reduction in opioid constipating effects resulting in diarrhoea Causes • faecal impaction (overflow) - identify with a clinical examination (including rectal) • colo-rectal carcinoma (also causes discharge and tenesmus) • loss of sphincter tone and sensation e.g. from spinal cord compression • incomplete gastrointestinal obstruction - frequent or recurrent diarrhoea suggests partial obstruction so try lower bowel evacuation • malabsorption or food intolerance e.g. from lack of pancreatic enzymes • concurrent disease e.g. diabetes mellitus, hyperthyroidism, inflammatory