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Agitation in palliative care

Agitation -shaking , moving , unsettled – it can be linked to emotional, physical or spiritual distress. Terminal agitation is the agitation seen in the last few days of life.

 

Delirium -Defined as an acute syndrome involving a global cerebral dysfunction of the brain with a complex neuropathogenesis and multiple causes

 

Terminal restlessness -characterized by sudden appearance of in congruent behaviours rather than anger , depression or other emotions commonly experienced during the the stages of dying.

This is also described as terminal agitation or terminal delirium , terminal anguish , confusion at the end of life

 

Palliative sedation this is the intentional administration of sedatives to reduce a dying person’s consciousness to relieve intolerable suffering from refractory symptoms
Other terms to note here ( based on health care setting ) continuous sedation until death ( CSD ) proportionate palliative sedation palliative sedation to unconsciousness ( PSU )

 

How common -Exact prevalence is not known It is quite common and Karen A Kehl writes in the Journal of Pain Palliat Care Pharmacother in 2004 that terminal restlessness is an important issue in the management of symptoms at the end of life with between 25 % and 88 % of dying patients exhibiting this condition Restlessness and agitation occurs in 42 % of patients in the last 48 hrs of life ( Twycross & Lichter , 1995 ) Hosie et al reported in 2017 based on a systematic review that the estimated prevalence of terminal agitation was at 59 % in patients that passed away and 88 % in the last 6 hours of life Lawlor , Bush in 2015 reported that up to 88 % develop delirium in the last hours or days of life It has also been reported that in palliative care settting prevalence of delirium is reported at 13 % – 42 % on admission to inpatient palliative care units increasing to 88 % at the end of the life ( weeks- hours before death )

 

We can conclude from above figures that terminal agitation is quite a common presentation in the dying patient.

 

Background -distinguishing delirium from agitation can be difficult consider using DSM criteria on delirium
 BMJ article quotes that the core clinical features that may point towards delirium in a palliative care setting include
○ rapid onset of disturbed attention
○ fluctuating levels of consciousness
○ cognitive impairment
○ psychomotor disturbance
○ disruption of the wake – sleep cycle

The article also points at some clues in behaviour which has been observed in palliative patients as
○ purposeless repetitive movements – plucking at bedsheets , removing clothes
○ moaning , facial grimacing
○ emotional changes as fear , anxiety , agitation
○ multifocal myoclonus can also be seen 2ary to opioid toxicity , renal failure or other drug relates toxicity
 Delirium is a poor prognostic indicator & often predicts death within few days to weeks
 other indications of terminal distress – reported by carers/ relatives include
○ distressed behaviour
○ confusion
○ calling out – shouting screaming
○ hallucinations
○ trying to get out of the bed or wandering
○ sleep cycle disturbance
○ unable to relax / concentrate
○ jerking or twitching – fidgety.

 

Past history -pre-existing cognitive impairment increased age cerebrovascular disease already severe illness state previous episode of delirium lower performance state presence of metastases lung cancer male sex alcohol / drug abuse or withdrawal

 

uncontrolled pain urinary retention bleeding constipation breathlessness deafness /blindness cerebral ( brain tumors ) , raised ICP , seizures sleep deprivation anxiety , fear , spiritual distress , emotional distress

 

Metabolic -infection / sepsis hypoxia uraemia liver failure cancer – paraneoplastic raised calcium hypo or hyperglycemia low or raised sodium dehydration organ failure ( liver , renal , resp )

 

Drugs -corticosteroids benzodiazepines opioids anticholinergics neuroleptics acute withdrawal of alcohol , nicotine , anti-depressants , benzodiazepines , steroids etc

 

Several assessment scales are available for e.g Confusion assessment method , The 4 As , Nursing Delirium Rating Scale -these can often be difficult to use as the communication / co-operation from the patient may be limited & these tools may lack sufficient sensitivity and specificity to be solely relied on.

 

There is a lack of robust evidence on management. The NICE guideline on delirium is not tailored to palliative setting and does not recognise delirium as a terminal event. Several trusts have issued guidance on management , we present here the approach advocated by Christian M G Hosker et al in the BMJ – Delirium and agitation at the end of life and focus on drugs that are useful in the primary care setting

 

Safety assessment -risk assess – consider 1 : 1 nursing -is the patient at risk to him / herself others alarm systems can be used where setting permits remove hazardous objects as high beds , electrical cords , knives , cigarette lighters ensure that the delirious patient is observed all the time

 

Treating reversible causes -are investigations indicated ? consider stage of illness – goals / wishes / context review all medications and discontinue non-essential medications consider dose reduction / switching – if opioid related cause is suspected antibiotic for infections may improve symptoms address if present / possible – aspects as pain , hypoxia , retention , constipation , electrolyte imbalance , pressure mattress

 

Symptom control- reassurance presence of familial faces and use of well lit and quite room gentle , repeated reorientation where possible – use clock , calendar , schedule of daily routines ( explain where are they , who they are , who you are and your role ) try to maintain a normal sleep-wake cycle psychological and spiritual support make sure patient has access to eye glasses , hearing aids & dentures

 

Non pharmacological -reassurance presence of familial faces and use of well lit and quite room gentle , repeated reorientation where possible – use clock , calendar , schedule of daily routines ( explain where are they , who they are , who you are and your role ) try to maintain a normal sleep-wake cycle psychological and spiritual support make sure patient has access to eye glasses , hearing aids & dentures+

 

Midazolam -drug of choice for management of agitation and restlessness at the end of life- included in the list of medication ( Just-in-case ) for anticipatory prescribing in most UK palliative care guidelines sedative , anxiolytic , anti-convulsant shorter duration of action than diazepam prn dose can be from 2.5 mg to 5 mg every 1-2 hrs s/c prn 24 hrs dose via syring driver 10- 20 mg Titrate dose as required Usual total maximum dose is 60 mg in 24 hrs – it is advised to seek specialist advice if > 30 mg / 24 hrs is rerquired Higher doses may be needed if the patient has been on oral diazepam

 

Haloperidol -antipsychotic -dopamine antagonist for agitated distressed patient -consider 0.5 mg to 1.5 mg mg SC stat 5-10 mg /24 hrs SC via syringe driver 2.5 mg 4 hrly s/c prn use lower starting doses in elderly avoid in those who suffer with Parkinsonism / Lewy body dementia do not co-prescribe with metoclopramide

 

Lorazepam -if the patient is anxious / frightened but lucid consider 0.5 mg oral or S/L maximum 4 mg in 24 hrs ( elderly debilitated max dose 2 mg )

 

Levomepromazine -considered 2nd line – usually if not responding to midazolam sedative , antipsychotic and anti-emetic can be used in addition to to midazolam under specialist advice consider using lower doses in frail / elderly for e.g 2.5 mg -to 5 mg Sc prn 2 hrly higher doses for persistent distress for e.g 10 mg – 25 mg s/c PRN 2 hrly

REFERENCES

  1. Bush, Shirley Harvey et al. “Clinical Assessment and Management of Delirium in the Palliative Care Setting.” Drugs vol. 77,15 (2017): 1623-1643. doi:10.1007/s40265-017-0804-3
  2. Hosker C M GBennett M IDelirium and agitation at the end of life doi:10.1136/bmj.i3085 Delirium and agitation at the end of life | The BMJ
  3. Guideline for the management of agitation in advanced cancer Agitation.pdf (nwcscnsenate.nhs.uk)
  4. Management of terminal agitation BAWC MCN Guidelines for Management of Terminal Agitation FINAL Oct15.pdf (bradford.nhs.uk)
  5. Severe uncontrolled distress – Scottish Palliative Care Guidelines Scottish Palliative Care Guidelines – Severe Uncontrolled Distress
  6. Agitation – Sheffield Palliative Care Formulary Agitation (sth.nhs.uk)
  7. Management of delirium and agitation in the palliative care setting Dr Richard Partridge Sue Ryder Thorpe Hall Hospice Management of Agitation in the Palliative Care setting (cam.ac.uk)
  8. Lothian Palliative Care Guidelines – Confusion / Agitation in Palliative Care Microsoft Word – LGGCONFUS.doc (palliativedrugs.com)
  9. The Royal Marsden School – Management of terminal agitation and its impact on patients and healthcare professionals by Felicity Hafner and Martin Galligan Management of terminal agitation and its impact on patients and healthcare professionals | TRM School (royalmarsdenschool.ac.uk)

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