Managing delirium and psychological symptoms in the last days of life

The cause of delirium in the last days of life is usually multifactorial, involving multiple organ failure and other factors that are now largely irreversible, e.g. hypoxia, metabolic abnormalities.^*4–6 However, some causes or exacerbating factors of delirium can be managed in the final days, such as pain, urinary retention, certain medicines (e.g. opioids, benzodiazepines, anticholinergics) or substances (e.g. nicotine withdrawal) and infection (see: “Managing symptoms of delirium”).^7–9 People with pre-existing cognitive impairment are at the greatest risk of delirium.⁷ Other risk factors include increasing age, immobility and vision or hearing impairment.^4, 10

Delirium can cause significant distress to the patient and to those supporting them in their last days of life, particularly as this is a time when the patient's cognition, awareness and ability to communicate is highly valued.^{4, 5, 11} Provide information and support to the family/whānau, including the likely causes of delirium, potential symptoms and address any questions or concerns they may have.^{4, 12} Reassure patients and their family/whānau that this is a normal part of the dying process.

^*Delirium that occurs during palliative care prior to the last days of life can often be reversed if this is in line with the person's goals of care, e.g. by correcting metabolic abnormalities, such as hypercalcaemia, hyper/hypoglycaemia and dehydration

Assessment of delirium

A clinical diagnosis of delirium can be made based on symptom history, pattern recognition and any other relevant information from the family/whānau or carers.^{1, 4} Validated tools are available to help assess patients for delirium, e.g. Confusion Assessment Method (CAM), 4AT.^{1, 4} However, these are often not practical or possible to apply in the last days of life, particularly for those with limited communication or fluctuating levels of consciousness.^{1, 4, 13}

As a general approach, ask the patient (if possible) or their family/whānau about features of delirium, including any:^{1, 4}

• Acute change in mental status and whether this fluctuates throughout the day
• Increase in distractions, disorientation, disorganised thinking or other cognitive changes, e.g. hallucinations, aggression
• Changes in consciousness or activity, e.g. lethargy, stupor, hypervigilance, difficulty sleeping

Repetitive plucking of bed sheets or clothing, groaning and facial grimacing can be signs of delirium in the last days of life.^{4, 5, 14} Some patients may also experience auditory or visual hallucinations, which can be distressing for them and their family/whānau.^{2, 14, 15} However, these should be distinguished from the positive spiritual visions and experiences that can occur at end of life which are generally comforting and reassuring to patients, and do not require medical intervention.

Managing symptoms of delirium

When deciding on an appropriate treatment plan, consider the patient’s emotional, spiritual, social and physical needs.

First consider any reversible causes or exacerbators of delirium, which can be treated.^{8, 9, 13} These may include:

• Pain – ensure adequate pain relief.^{9, 13} For further information, see: “Managing pain in the last days of life”.
• Constipation/faecal impaction or urinary retention – consider use of laxatives/an enema (if possible) or urinary catheterisation if not already in place^{14, 16}
• Medicines, e.g. corticosteroids, anticholinergics, opioids, benzodiazepines – consider discontinuation or if the medicine is required, lower doses or switching to an alternative medicine^{11, 13}
• Other substances. If the patient's symptoms are likely caused by nicotine withdrawal, consider use of nicotine replacement patches.⁶ A benzodiazepine is often useful for patients with alcohol withdrawal.¹⁷
• Infection (e.g. urinary or respiratory tract infection) – antibiotics may improve the symptoms of delirium if treatment is considered appropriate^{4, 10}
• Psychological causes, e.g. fear, anxiety or spiritual distress – use non-pharmacological management strategies, considering what interventions (if any) have helped them to overcome this in the past.^{7, 13} Antidepressants should not be introduced as there is insufficient time for them to have an effect.¹⁸ For further information on the management of psychological symptoms, see: “Support the patient’s mental health and wellbeing needs”.

Prioritise non-pharmacological interventions

Evidence suggests that non-pharmacological interventions are preferable to pharmacological treatments in patients experiencing mild symptoms of delirium.^{19, 20} Ideally, non-pharmacological management strategies will have been discussed with the patient and their family/whānau prior to the last days of life so that a plan is already in place (i.e. advance care planning, see: www.hqsc.govt.nz/our-work/advance-care-planning/).

Examples of non-pharmacological interventions for delirium:^{4, 6, 7, 15}

• Implement safety measures, e.g. lower the bed, use a floor sensor mat, remove nearby potentially hazardous objects
• Regularly reposition the patient
• Gentle mouth care, if tolerated
• Close observation (e.g. by a volunteer “sitter” or family/whānau). Having someone always present can help with re-orientation and reduce the patient’s fear/anxiety and feeling of isolation.³
• Set an ambient room temperature and consider the patient's proximity to heaters or cold draughts
• Ensure adequate lighting, avoid glare from artificial light or sunlight. Use of a night light may be helpful.
• Maintain a low level of noise in the room and reduce negative distraction, e.g. loud television volume
• Place re-orientation cues, e.g. a clock, newspaper, daily schedules, familiar belongings such as photographs or other personal items
• Access to glasses or hearing aids (if required)
• Suggest relaxation or distraction techniques, e.g. gentle touch or massage, aromatherapy, music or radio
• Spiritual or religious guidance or support (if relevant)

Support the use of other complementary techniques or methods that the patient or their family/whānau want to try if they are unlikely to cause harm, e.g. traditional techniques such as Rongoā Māori, Ayurvedic or Chinese herbal medicines.

Initiate pharmacological treatment as indicated

If non-pharmacological interventions have been inadequate or if the patient is experiencing severe or distressing symptoms, e.g. hallucinations, significant agitation, pharmacological treatment can be initiated.^{1, 19}

An antipsychotic (haloperidol) or benzodiazepine (midazolam) administered subcutaneously is recommended first-line for patients requiring pharmacological treatment for delirium, agitation or restlessness, with the initial choice dependent on consciousness level (Figure 1).^{6, 15} Benzodiazepines are particularly useful for patients with agitation and anxiety due to their sedating effects, but they can exacerbate symptoms of delirium at high doses.^{9, 10, 16} They are also useful for patients whose symptoms of delirium are caused by alcohol withdrawal.¹⁷ Haloperidol is particularly useful for patients who are also experiencing nausea and vomiting as it is the first-line treatment for this in the last days of life; combining indications means fewer medicines are required.

N.B. Some patients, e.g. those with behavioural and psychological symptoms of dementia, will already be taking oral antipsychotics and require conversion to a subcutaneous formulation.¹⁵

Practice Point: Anticipatory prescribing of “as needed” subcutaneous doses of haloperidol and/or midazolam is also recommended in patients without symptoms of delirium or who do not yet require pharmacological treatment; if symptoms occur/worsen, the “as needed” dose can be administered and then regular dosing initiated (see regimens below).¹⁵

Haloperidol is recommended first-line for patients who are conscious

If the patient is conscious or semi-conscious, 0.5 mg of subcutaneous haloperidol^* should be prescribed and administered stat (subcutaneous injection; unapproved route),²¹ with additional doses prescribed on an “as needed” basis, e.g. 0.5 – 1 mg every one to two hours, as needed (to a maximum dose of 5 mg within 24 hours).¹⁵ Ideally, the patient should be reassessed within six hours of initiation to review treatment response.¹⁵

N.B. Antipsychotics can be associated with restlessness; consider haloperidol as a potential cause if a patient experiences worsening symptoms after treatment initiation.^{10, 18} Midazolam can be added early to reduce this effect (or used instead – see below), but do not persist with haloperidol if the patients’ distress is worsening.

If there has been inadequate response to treatment with haloperidol after six hours:¹⁵

• Switch to midazolam 2.5 mg, administered subcutaneously (stat), and prescribe additional “as needed” doses, e.g. 2.5 – 5 mg, every 30 minutes, as needed; and/or
• Add levomepromazine^† 6.25 mg, administered subcutaneously, every four to six hours, as needed. Levomepromazine is a second-line option to haloperidol (with or without midazolam) and is highly sedative. If levomepromazine is used on an “as needed” basis with effect, discontinue haloperidol and convert the daily dose of levomepromazine to a 24-hour dose for continuous subcutaneous infusion, and prescribe additional “as needed” doses.

^*Contraindicated in patients with Parkinson’s disease and should be avoided in patients with Lewy body dementia²¹

^†Previously known as methotrimeprazine

Midazolam is recommended first-line for patients who are unconscious

If the patient is unconscious, 2.5 mg of subcutaneous midazolam (unapproved indication) should be prescribed and administered stat, with additional doses prescribed on an “as needed” basis, e.g. 2.5 – 5 mg, every 30 minutes, as needed (to a maximum dose of 20 mg within 24 hours).¹⁵ Ideally, the patient should be reassessed within six hours of initiation to review treatment response.¹⁵

If treatment is ineffective after six hours, add levomepromazine 6.25 mg administered subcutaneously (stat), and prescribe additional “as needed” doses, e.g. 6.25 mg, every four to six hours, as needed.¹⁵

Practice Point: Patients already established on high dose anxiolytics may require higher doses of midazolam.¹⁵

Consider conversion to a continuous subcutaneous infusion

If multiple “as needed” doses of haloperidol, midazolam or levomepromazine have been required, consider converting to a 24-hour dose for continuous subcutaneous infusion, i.e. total (regular + “as needed”) subcutaneous doses required in previous 24 hours (Figure 1).¹⁵ Each of these medicines can be used alone for continuous subcutaneous infusion or combination treatment may also be trialled.¹⁵ Continue subcutaneous “breakthrough” doses as needed.¹⁵

Contact the local hospice or palliative care team for advice if the patient's symptoms do not respond to appropriate treatment, or if there is unwanted sedation.⁸

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Figure 1. Anticipatory prescribing flowchart for delirium, agitation and restlessness. Adapted from South Island Palliative Care Workstream, 2020.¹⁵