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End of Life Care:
Pain and terminal agitation
Dr Neil Jackson Consultant in Palliative Medicine
Clinical Director Specialist Medicine
Belfast Health and Social Care Trust
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Back to basics - the three ’R’s
• Recognition
– Missing or misinterpreting
• Reversibility
– Could / Should / Would (ethics / context)
• Rx (tReatment)
– Not just the physical, all the other stuff
• Respect
– Person, life, beliefs,
^ four
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For the purposes of this guidance people are ‘approaching the end of life’ when they are likely to die within the next 12 months. This includes people whose death is imminent (expected within a few hours or days) and those with: • advanced, progressive, incurable conditions • general frailty and co-existing conditions that mean they are
expected to die within 12 months • existing conditions if they are at risk of dying from a sudden
acute crisis in their condition • life-threatening acute conditions caused by sudden
catastrophic events.
For some people the appropriate start for end of life care might be at the time of diagnosis of a condition which usually carries a poor prognosis, for example motor neurone disease or advanced liver disease. Adapted from Treatment and care towards the end of life: good practice in decision making, the General Medical Council 2010
En
d o
f Life
Ca
re - G
MC
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^
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Which of the following would be most important to you regarding how you spend your final days?
sueryder.org
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Measure it
Visual Analog Scale (VAS) 100mm long
Simple Descriptive Pain Intensity Scale
Numeric Rating Scale (NRS)
No
Pain
No Pain
No Pain
Mild
Pain
Moderate
Pain
Severe
Pain
Worst Possible Pain
0 1 2 3 4 5 6 7 8 9 10
Worst Possible Pain
Behavioural scales for rating pain in those that can’t report it
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sensory-discriminative somatosensory cortex (S1), emotional …for example, anterior cingulate cortex (ACC), amygdala (CeA) and insular cortex (IC), and cognitive…for example, pre-frontal cortex (PFC) aspects of pain
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Cicely Saunders concept of ‘Total Pain’
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Cancer pain is often a combination of all three nociceptive, inflammatory and neuropathic pains
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Performing physical &
neurological
examination
Dermatomes
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Referred pain
• Pain from internal organs felt at a site distant from the tissue damage
e.g. pancreatic cancer pain is experienced as back pain
e.g. liver capsule pain with pressure on the diaphragm can be experienced as shoulder pain
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WHO cancer pain relief programme
analgesic ladder
• By the cause of the pain(s)
• By the clock (…regularly as opposed to prn)
• By the ladder (…WHO ladder)
• By the mouth (…preferentially PO, not IM, IV, SC)
• For breakthrough pain (…1/6 of 24 hr dose)
• For the individual
• Adjuvant therapies as needed
• Prevent side effects (…assess and monitor
• Start low, go slow
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Oral Opioid Formulations
Short-acting
(4 hrly)
Oramorph (Morphine) liquid
Sevredol (Morphine) tablets
Oxynorm / Shortec
(Oxycodone)
Liquid or tablets
• Opioid-naïve patients
• Pain crises
• Breakthrough cancer pain
Long-acting
(12 hrly)
MST (Morphine)
LongTec /Oxycontin
(Oxycodone)
• Start low
• Reserve for stable situations
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Breakthrough Pain in Cancer
Around-the-clock
Medication
Time
Breakthrough
Pain
Theoretical Model
Pa
in I
nte
nsit
y
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Morphine is
‘$tandard
currency’
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approx. Dosage Conversion
• codeine ÷ 10 = oral morphine – Co-codamol 30/500 ii qid = 24mg morphine
• oral morphine ÷ 2 = sub-cut morphine – MST 30mg bd = 30 mg morphine S/C per 24 hrs
• oral morphine ÷ 3 = sub-cut diamorphine – MST 30mg bd = 20 mg diamorphine S/C per 24 hrs
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• oral morphine ÷ 2 = oral oxycodone – MST 30mg bd = 15mg bd oral oxycodone
• oral oxycodone ÷ 2 = sub-cut oxycodone – Longtec 15mg bd = 15mg S/C per 24 hr oxycodone
• Any opioid 24 hr dose ÷ 6 = breakthrough dose
– E.g. example above, dose is 2.5mg S/C oxycodone
approx. Dosage Conversion
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Opioid Side Effects
• Constipation
– Co-prescribe laxatives e.g. Senna/Lactulose
– (s/c Methylnaltrexone- see EAPC 2010)
• Nausea & vomiting (30%) – Prophylactic anti-emetics e.g..
Haloperidol/ Cyclizine/ Domperidone/Metoclopramide
• Sedation – Reassure and monitor
– Advise re driving
• Respiratory depression
• Also pruritus, anaphylaxis, sweating, urinary retention
• Opioid Induced Neurotoxicity (OIN) – Severe sedation
– Cognitive failure
– Hallucinations/delirium
– Myoclonus/grand mal seizures
– H yperalgesia/ allodynia
• Also – Non cardiogenic pulmonary
oedema
– Immune system effects
– Endocrine function effects
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Routes of Opioid Administration
• Preferred route – oral (PO)
• When unable to swallow: SC, CSCI*, IV, TD*, PEG – *CSCI – Continual sub-cut
infusion [syringe driver]
– *TD – Transdermal [patch]
• Seldom used (only in special
situations): – Sub Lingual (breakthrough pain,
fentanyl)
– Intranasal (Fentanyl)
– Intraspinal (epidural or intrathecal)
• Do NOT use IM
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Use of Syringe Drivers
• Intractable vomiting
• Severe dysphagia
• Unable to swallow oral medication
• Decreased level of consciousness in the dying patient
• Poor alimentary absorption
• Poor patient compliance
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Adjuvants for Bone Pain
• NSAIDs – Limited use in severe pain – Renal and gastro-intestinal
side effects
• Radiotherapy
– 75% to 85% response rate (decreased pain)
– Few side effects with palliative therapy
– Response within 1 to 2 weeks (maximum response up to 4 weeks later)
– Duration of analgesia is several months
• Steroids – Useful in pain crises
• Bisphosphonates – Reduction of skeletal
events (good evidence)
– Management of more acute pain with parenteral infusion (some controversy)
• Surgery – impending or pathological
fracture
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Adjuvants for Visceral Pain
• Liver metastases or malignant bowel obstruction – Corticosteroids (Dexamethasone 2-8 mg OD or BD)
– NSAIDs e.g. Diclofenac SR 75mg bd
• Colic (intenstinal spasm) – Hyoscine Butylbromide SC (20mg)
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Drugs for Neuropathic Pain
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Pain Management Take Home Points
• Comprehensive assessment of pain is required
• Individualize pain management for the patient
• Constant pain needs regular medication
• Titrate opioids to the best analgesia with fewest
side effects
• Use adjuvant medications and treatments
when necessary
• Educate the patient and family
• Recognize the concept of total suffering and
total pain
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Terminal agitation
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Terminal agitation
• Terminal agitation, is a particularly distressing form of delirium that sometimes occurs in dying patients. It is characterized by spiritual, emotional or physical restlessness, anxiety, agitation and cognitive failure
• Terminal agitation is distressing (*to loved ones and staff) because it has a direct negative impact on the dying process.
www.verywell.com
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Terminal agitation -
personal observations
• War / Terrorism / Conflict
• Military personnel / Police
• Physical / Emotional / Sexual abuse
• PTSD / Trauma
• Beliefs conflict with reality
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Cicely Saunders concept of ‘Total Pain’
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What is Delirium?
• Neuropsychiatric syndrome
• Global cognitive dysfunction
• Acute onset
• Fluctuating course
• Physical aetiology
• called…‘Acute confusional state’, ‘post-op confusion, ‘ICU psychosis’, ‘septic encephalopathy’
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DSM 5
• A. Disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment)
• B. The disturbance develops over a short period of time (usually hours to a few days), represents an acute change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day.
• C. An additional disturbance in cognition (e.g. memory deficit, disorientation, language, visuospatial ability, or perception).
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DSM 5
• D. The disturbances in Criteria A and C are not better explained by a pre-existing, established or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal such as coma.
• E. There is evidence from the history, physical examination or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e. due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple etiologies.
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Pathophysiology of Delirium
• Deficiency of Acetylcholine (Gunther, 2008)
• Discrepancies in Melatonin availability
• Dopamine excess (Maldonado, 2009)
• Excess of norepinephrine/glutamate
• Variable alterations – serotonin, histamine, GABA
• Decreased plasma concentration Protein C, increased concentration of TNF receptor-1
• Inflammatory cytokines (de Rooj)
• Markers of CNS damage (Hall et al)
• Reduced overall cerebral blood flow (Yokota et al, 2003)
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How common is delirium?
• in specialist palliative care inpatient setting...incidence 3-45%
• Prevalence rates
• 13 - 42% at admisssion
• 26 - 62% during length of stay
• 58 – 88% weeks to hours preceding death
• In hospital - nearly 30 percent of older patients experience delirium at some time during hospitalization;
• the incidence is higher in intensive care units.
• Among older patients who have had surgery, the risk of delirium varies from 10 to greater than 50 percent.
Hosie, Palliative Medicine 2012
UpToDate®
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Types of delirium (Lipowski 1990)
• Delirium is not a homogeneous syndrome
• Three sub-types based on psychomotor activity/alertness
1. Hyperactive - hyperalert (agitated)
2. Hypoactive – hypoalert (somnolent)
3. Mixed sub-type
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Identifying risk factors for delirium
• Age >65 • Previous diagnosis of dementia • Multiple medications • Sensory impairment • Dehydration • Chronic physical illness • Substance use • Depression • Neurological impairment • Functional disability
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Differentiating
Delirium from Dementia
Delirium Dementia
Acute onset Slow, gradual inset
Identifiable time of onset Time of onset unclear
Cause usually treatable Due to chronic disorder
Usually reversible Progressive process
Attention impaired Attention not impaired until late stages
Consciousness ranges from lethargic to hyperalert
No effect on consciousness until late stages
Effect on memory varies Loss of memory, especially for recent events
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Precipitants of Delirium
• Severe acute illness
• Acute fracture
• Malnutrition
• Infection
• Introduction of ≥3medications
• Pain
• Changes to electrolyte balance
• Immobility
• Stroke
• Changes to acid/base balance
• Use of restraints
• Head injury
• Alterations in oxygenation
• Use of urinary catheters
• Encephalitis
• Heart/renal/liver failure
• Constipation
• Space Occupying Lesion
• Hypoglycaemia
• Alcohol/BDZ withdrawal
• Burns
• Post ictal state/epilepsy
• Major trauma
• Surgery (especially cardiac/orthopaedic)/other invasive procedures
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Medications and Drugs
• Medications – Opioids - Li+ – Antipsychotics - Steroids – Anticonvulsants - L-dopa – Sedatives - Antibiotics – Digoxin - Chemotherapy – Diuretics - Antidepressants – NSAIDs - OTC medication
• Drug Intoxication – Prescribed medication - LSD – Alcohol - Amphetamines – Cannabis - Cocaine – Inhalants/solvents - Poisons
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Scottish palliative care guidelines -
delirium • Ix – FBC, biochemistry (Ca), check for infection (UTI in elderly),
review all meds, assess for sensory impairment/opioid toxicity, constipation, urinary retention, catheter problems
• Management
– Treat underlying cause
– Terminal delirium – Last Days of Life guideline
– Maintain hydration, oral nutrition and mobility
• Non-pharmacological management
• Medication
– Haloperidol 1st line (0.5 – 3.0 mg S/C daily)
– BDZs 2nd line – midazolam S/C – start at 10mg
– If increase sedation desirable, add/increase BDZ/change Haloperidol to Levopromazine SC 12.5 to 25mg OD/BD
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Management of Delirium
• Review medication
• Correct visual/auditory deficit
• Adequate analgesia
• Calming, unambiguous communication, approach patient from the front
• Attend to nutrition, fluid balance, skin care, mobilisation, remove unnecessary lines
• Well lit room
• Keep staff changes to a minimum; staff should be easily identifiable
• Orientating cues, familiar items from home, family
• Quiet/relaxing night environment
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You can help someone with delirium
feel calmer and more in control if you:
• stay calm • talk to them in short, simple sentences • check that they have understood you - repeat
things if necessary • try not to agree with any unusual or incorrect
ideas, but tactfully disagree or change the subject
• reassure them • remind them of what is happening and how
they are doing • remind them of the time and date
Royal College of Psychiatrists Delirium Advice leaflet – www.nhs.uk
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• make sure they can see a clock or a calendar
• try to make sure that someone they know well is with them. This is often
• most important during the evening, when confusion often gets worse.
• if they are in hospital, bring in some familiar objects from home
• make sure they have their glasses and hearing aid
• help them to eat and drink
• have a light on at night so that they can see where they are if they wake up.
Royal College of Psychiatrists Delirium Advice leaflet – www.nhs.uk
2. You can help someone with delirium feel calmer and more in control if you:
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Complications of Delirium
• Frightening for patients (and relatives)
• May last a few days, but can last a few weeks or longer
• Increased risk of falls, pressure sores, loss of functional status
• Increased risk of morbidity and mortality
• Increased length of stay
• Increased institutionalisation
• Increased social and health costs
• May worsen progression of dementia