Key Facts

Terminal agitation is one of the most distressing symptoms for families witnessing the dying process. Prompt identification of reversible causes and compassionate use of sedation are essential.

Epidemiology

• Affects 25-85% of dying patients (depending on definition and setting)
• More common in younger patients, those with brain metastases, and those on high-dose opioids
• May be the most distressing symptom for families

Aetiology

Reversible causes (check first):

• Urinary retention (catheterise)
• Faecal impaction (rectal examination)
• Pain (uncontrolled; adjust analgesia)
• Opioid toxicity (myoclonus, confusion; reduce/rotate opioid)
• Medication side effects (anticholinergics, steroids)
• Hypercalcaemia
• Hypoxia
• Anxiety, fear, spiritual distress

Irreversible causes:

• Multi-organ failure
• Cerebral hypoxia
• Metabolic encephalopathy
• Brain metastases

Pathophysiology

• Terminal delirium: multifactorial neurotransmitter imbalance in the context of dying
• Hepatic/renal failure → accumulation of metabolites and toxins
• Cerebral hypoperfusion → cortical dysfunction
• Drug metabolite accumulation (morphine-6-glucuronide, etc.)
• May represent existential/spiritual distress in some patients

Features

• Restlessness, fidgeting, picking at bedclothes
• Agitation, moaning, calling out
• Confusion, disorientation
• Hallucinations (visual or auditory)
• Attempting to get out of bed
• Facial grimacing (may indicate pain)
• Fluctuating consciousness
• Myoclonus (may indicate opioid toxicity)

Assessment

• Is the patient in pain? (facial grimacing, groaning on movement)
• Is there urinary retention? (palpate bladder or bladder scan)
• Is there faecal impaction? (DRE if appropriate)
• Review medication chart (opioid toxicity? recently stopped medications?)
• Is this expected dying process or acute deterioration with treatable cause?

Red Flags

• Myoclonus with agitation (opioid toxicity — reduce/rotate)
• Palpable bladder (urinary retention — catheterise)
• Seizures (consider midazolam, review anticonvulsants)
• Severe uncontrolled distress despite medication (consider palliative sedation)

Bedside

• Reversible cause check: urinary retention (bladder scan), faecal impaction (DRE), pain assessment, medication review
• Clinical assessment of dying
• Family discussion about what is happening

Bloods

• Generally not appropriate in last days of life unless result would change management
• May check calcium if hypercalcaemia treatable and appropriate

Imaging

• Generally not appropriate in terminal phase

Special Tests

• None required in most cases; clinical assessment guides management

Non-pharmacological

• Check and treat reversible causes (retention, impaction, pain, medication toxicity)
• Calm, quiet environment
• Familiar people present
• Gentle reassurance (even if patient appears unconscious; hearing may be preserved)
• Minimise unnecessary interventions
• Communicate with family: explain agitation is common in dying; reassure medications are for comfort

Pharmacological

• First-line: midazolam 2.5-5mg SC PRN (up to hourly)
  • If frequent doses needed: CSCI midazolam 10-30mg/24h
• If agitation with delirium features (hallucinations, paranoia):
  • Haloperidol 0.5-2mg SC PRN 2-hourly (max 10mg/24h)
  • Avoid in Parkinson's/Lewy body → use midazolam or levomepromazine
• If midazolam insufficient:
  • Levomepromazine 12.5-25mg SC PRN (or CSCI 25-100mg/24h)
  • Very sedating; broad-spectrum (D2, H1, mACh, 5HT2 blockade)
• Opioid toxicity (myoclonus, confusion):
  • Reduce opioid by 30-50%
  • Consider opioid rotation
  • Add midazolam for myoclonus
• Seizures: midazolam 5-10mg SC/buccal; CSCI midazolam 20-40mg/24h
• Palliative sedation (for intractable refractory agitation):
  • Continuous deep sedation: midazolam CSCI 30-60mg/24h ± levomepromazine
  • Ethical: principle of double effect; proportionate to suffering; intention is symptom relief
  • Requires senior decision, team consensus, family discussion, documentation

Surgical/Interventional

• Urinary catheterisation (for retention)
• Rectal interventions (for impaction)

Referral Criteria

• Refractory terminal agitation: specialist palliative care (urgent)
• Ethical concerns about palliative sedation: senior clinical and ethical discussion
• Family unable to cope: additional support, bereavement counselling

• Terminal agitation is a marker of the dying process; median survival once present is typically hours to 2-3 days
• Most cases can be managed effectively with midazolam ± levomepromazine
• Uncontrolled terminal agitation is distressing for families and staff; prompt management is essential
• Palliative sedation is appropriate and ethical for intractable suffering

Terminal Agitation Management Algorithm

Principle of Double Effect