Clinical Review

ABC of palliative care: The last 48 hours

BMJ 1997; 315 doi: (Published 13 December 1997) Cite this as: BMJ 1997;315:1600
  1. Jim Adam


    During the final 48 hours of life, patients experience increasing weakness and immobility, loss of interest in food and drink, difficulty swallowing, and drowsiness. With an incurable and progressive illness, this phase can usually be anticipated, but sometimes a deterioration can be sudden and distressing. Control of symptoms and family support take priority, and the nature of the primary illness becomes less important. This is a time when levels of anxiety, stress, and emotion can be high for patients, families, and other carers. It is important that the healthcare team adopts a sensitive yet structured approach.


    Principles of managing the last 48 hours

    • Problem solving approach to symptom control

    • Avoid unnecessary interventions

    • Review all drugs and symptoms regularly

    • Maintain effective communication

    • Ensure support for family and carers

    An analytical approach to symptom control continues but usually relies on clinical findings rather than investigation. This approach spans all causes of terminal illness and applies to care at home, hospital, or hospice.

    Drugs are reviewed with regard to need and route of administration. Previously “essential” drugs such as antihypertensives, corticosteroids, antidepressants, and hypoglycaemics are often no longer needed and analgesic, antiemetic, sedative, and anticonvulsant drugs form the new “essential” list to work from. The route of administration depends on the clinical situation and characteristics of the drugs used. Some patients manage to take oral drugs until near to death, but many require an alternative route. Any change in medication relies on information from patient, family, and carers (both lay and professional) and regular medical review to monitor the level of symptom control and side effects.

    This review should include an assessment of how the family and carers are coping; effective communication with all involved should be maintained and lines of communication made clear and open. The knowledge that help is available is often a reassurance and can influence the place of death.

    Symptom control


    Pain control is achievable in 80% of patients by following the World Health Organisation's guidelines for use of analgesic drugs, as outlined in the first chapter of this series. A patient's history and examination are used to assess all likely causes of pain, both benign and malignant. Treatment (usually with an opioid) is individually tailored, the effect reviewed, and dose titrated accordingly. Acute episodes of pain are dealt with urgently in the same analytical fashion but require more frequent review and provision of appropriate “breakthrough” analgesia. If a patient is already receiving analgesia then this is continued through the final stages; pain may disturb an unconscious patient since the original cause of the pain still exists.

    If oral administration is no longer possible the subcutaneous route provides a simple and effective alternative. Diamorphine is the strong opioid of choice because of its solubility and is delivered through a syringe driver device to avoid repeated injections every four hours. It can be mixed with other “essential” drugs in the syringe driver. Rectal administration is another alternative, but the need for suppositories every four hours in the case of morphine limits its usefulness. Oxycodone suppositories (repeated 8 hourly) may be more practicable.

    Routes of administration of drugs for last 48 hours

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    Longer acting opioid preparations (transdermal fentanyl and sustained release morphine) should not be started in a patient close to death; there is a variable delay in reaching effective levels, and, since speedy dose titration is difficult, they are unsuitable for situations where a rapid effect is required, such as uncontrolled pain. If a patient is already prescribed fentanyl patches these should be continued as baseline analgesia; if pain escalates additional quick acting analgesia (immediate release morphine or diamorphine) should be titrated against the pain.

    Opioid treatment for pain control

    Starting dose—Immediate release morphine 5 mg every 4 hours by mouth

    Increments—A third of current dose (but varies according to “breakthrough analgesia” required in previous 24 hours). For example, immediate release morphine 15 mg every 4 hours by mouth is increased to 20 mg/4 hours

    Breakthrough analgesia—A sixth of 24 hour dose. For example, with diamorphine 60 mg delivered subcutaneously by syringe driver over 24 hours, give diamorphine 10 mg subcutaneously as needed for breakthrough pain

    Conversion ratio—Morphine by mouth (or rectum) to subcutaneous diamorphine is 3:1. For example, sustained release morphine 30 mg every 12 hours by mouth plus three doses of immediate release morphine 10 mg by mouth gives total dose of oral morphine 90 mg every 24 hours; convert to diamorphine 30 mg/24 hours delivered subcutaneously

    Not all pains are best dealt with by opioids. For example, bone pain may be helped by a non-steroidal anti-inflammatory drug, while muscle spasm may be eased by diazepam. Non-drug measures still apply: for example, pain from a dry mouth requires mouth care; a pressure sore requires a change of position, a comfort dressing, local anaesthetic gel, and an appropriate mattress; and a distended bladder and loaded rectum require catheterisation and rectal evacuation respectively. It is also important to remember all the non-cancer pains, new and old, that may be present.


    The scope for correcting “reversible” causes of breathlessness becomes limited. A notable exception is cardiac failure, for which diuresis may be effective. In most cases the priority is to address the symptom of breathlessness and the fear and anxiety that may accompany it.

    Management of breathlessness

    • Reverse what is reversible

    • General supportive measures—Explanation, position, breathing exercises, fan or cool airflow, relaxation techniques

    • Oxygen therapy

    • Opioid

    • Benzodiazepine

    • Hyoscine

    • Nebulised saline (if no bronchospasm and patient able to expectorate)

    General supportive measures should be considered in all cases. Face masks may be uncomfortable or intrusive at this time, but oxygen therapy may help some patients (even in the absence of hypoxia). Nebulised 0.9% saline is useful if a patient has a dry cough or sticky secretions but should be avoided if bronchospasm is present.


    Non-drug measures which can help a breathless patient

    Opioids and benzodiazepines can be helpful and should be initiated at low doses. Immediate release morphine can be titrated to effect in the same way as for pain. If a patient is using morphine for pain control then a dose slightly higher than the appropriate breakthrough dose (oral or parenteral) is usually required for treating acute breathlessness. The choice of anxiolytic is often determined by what is the most suitable route of administration, but the speed and duration of action are important.

    Noisy respiration may be helped by repositioning the patient and, if substantial secretions are present, hyoscine hydrobromide (0.4-0.6 mg subcutaneous bolus or up to 2.4 mg/24 hours via syringe driver). Occasionally, gentle suction may be required. End stage stridor is managed with opioids and anxiolytics, when it is usually too late for corticosteroids.

    Restlessness and confusion

    These may be distinct entities or they may overlap. A problem solving approach is essential. The threshold for discomfort and disorientation is often lowered in cachectic or anxious patients. Attention to a patient's surroundings is therefore important—a stable, comfortable, and safe environment should be fostered; soft light, quiet, and familiar faces are reassuring.

    Causes of restlessness and confusion

    • Drugs—Such as opioids, corticosteroids, neuroleptics, alcohol (intoxication and withdrawal)

    • Physical—Unrelieved pain, distended bladder or bowel, immobility or exhaustion, cerebral lesions, infection, haematological, major organ failure

    • Metabolic upset—Urea, calcium, sodium, glucose, hypoxia

    • Anxiety and distress

    The key to treatment lies in calming the acute state while addressing the cause, if apparent and appropriate. A notable example is the mental clouding, hallucinations, confusion, and restlessness associated with opioid toxicity, which can be eased with haloperidol while the opioid dose is reviewed. In general, choice of drug treatment depends on the likely cause. Doses are titrated up or down to achieve the desired effect, and the situation should be reviewed regularly and often until the acute episode settles. Highly agitated patients may need a large dose, and continuous infusion may be needed. Rectally administered drugs are possible alternatives. Explanation and support for the relatives and carers are paramount at this time.

    If a patient is experiencing distressing twitching or jerks then metabolic disorders, opioid toxicity, or drugs that lower seizure threshold should be considered. A review of medication and treatment with a benzodiazepine or anticonvulsant (such as clonazepam orally, diazepam rectally, or midazolam subcutaneously) is indicated. Anxiety or distress not responding to general supportive measures may be helped by diazepam or midazolam, but it should always be remembered that a patient may be suffering from an emotional or spiritual anguish that cannot be relieved by drugs.

    Management of restlessness and confusion

    • Treat the acute state and address cause

    • General supportive measures—Light, reassurance, company

    • Choice of drug treatment relates to likely cause


    • Haloperidol

    Indications—Drug toxicity, altered sensorium, metabolic upset

    Dose—Oral drug 1.5-3 mg, repeat after 1 hour and review; subcutaneous bolus 2.5-10 mg; subcutaneous infusion 5–30 mg over 24 hours

    • Midazolam

    Indications—Anxiety and distress, risk of seizure

    Dose—Subcutaneous bolus 2.5-10 mg; subcutaneous infusion 5–100 mg over 24 hours

    • Methotrimeprazine

    Indications—Need for alternative or additional sedation

    Dose—Subcutaneous bolus 25 mg; subcutaneous infusion up to 250 mg over 24 hours (lowers seizure threshold, use with care)

    • For altered sensorium plus anxiety, combine haloperidol and midazolam

    • Avoid “slippery slope” of inappropriate sedation in patient who needs to talk—So called terminal agitation can result from the inappropriate use of drugs

    Nausea and vomiting

    If antiemetics have been needed within the previous 24 hours then continuation is advisable. Nausea and vomiting may rarely occur as a new symptom at this time (<10% of cases), and treatment of the likely cause is preferred if this is practical in the clinical situation, otherwise an appropriate antiemetic should be selected. If the aetiology is unclear then choose a centrally acting or broad spectrum antiemetic in the first instance.

    Causes and treatment of nausea and vomiting

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    Occasionally, more than one antiemetic is required if resistant vomiting of a multifactorial cause exists. Subcutaneous administration of antiemetics is preferable, but suppositories (such as prochlorperazine, cyclizine, or domperidone) may be useful if no syringe driver is available. Antiemetic treatment that has been initiated for bowel obstruction should be continued.

    Emergency situations

    Appropriate and timely action has an important immediate effect on patients and families. It can also influence bereavement and future coping mechanisms of both lay and professional carers. Emergencies can sometimes be anticipated: thus, previous haemoptysis may predict haemorrhage, bone metastases predict pathological fracture, enlarging upper airway tumour predict stridor, and previous hypercalcaemia predict confusion.


    • Stridor

    • Seizure

    • Haemorrhage

    • Pain

    • Confusion

    Some emergencies may be preventable. For example, a patient with a brain tumour who can no longer take corticosteroids may have a seizure unless anticonvulsant treatment is maintained: subcutaneous infusion of midazolam (starting at 30 mg/24 hours) and rectally administered diazepam (10 mg) may be the strategy required.

    However, most emergencies in the last 48 hours are irreversible, and treatment should be aimed at the urgent relief of distress and concomitant symptoms. Drugs should be made available for immediate administration by nursing staff without further consultation with a doctor. Directions regarding use should be written clearly in unambiguous language. Useful drugs are injections of midazolam (5-10 mg if patient not previously exposed to benzodiazepine, otherwise titrate as appropriate) and diamorphine (5-10 mg if no prior exposure to opioid, otherwise a sixth to a third of the 24 hour dose).

    Haemorrhage is distressing and memorable for both patients and carers. Haemoptysis, haematemesis, and erosion of a major artery such as the carotid are visually traumatic. The prompt use of drugs, dark coloured towels to make the view less distressing (green surgical towels in hospital), and warmth will aid comfort. In these situations death may occur quickly. A supportive presence is helpful, and explanations to patients and their carers of what is being done will help minimise distress in a crisis.


    Patient with ulcerated neck tumour is at risk of erosion of the carotid artery and massive bleed


    Support means recognising and addressing the physical and emotional issues that may face patients, families, and carers during this time. Honesty, listening, availability, and assurance that symptom control will continue are valued by patients and carers. Fears or religious concerns should be acknowledged and addressed appropriately, and respect for cultural differences should be assured. Explain what is happening, what is likely to happen, the drugs being used, the support available, and how the family can help with care.

    Risk factors for bereavement


    Illness—Short, protracted, disfiguring, distressing

    Death—Sudden, traumatic (such as haemorrhage)

    Relationship—Ambivalent, hostile, dependent

    Main carer—Young, other dependants, physical or mental illness, concurrent crises, little or no support

    Lack of practical support is one of the commonest reasons for admission to hospital or hospice at this time, and, therefore, consideration should be given to extra help—such as Marie Curie nurses (organised through the district nursing service) to give carers rest and support. An assessment of the risk of bereavement allows care to be planned for the family after the patient's death. Professional carers may also need support, particularly if the last 48 hours have been difficult, and this requires an open line of communication.


    Jim Adam is consultant physician in palliative medicine and medical director at Hunters Hill Marie Curie Centre, Glasgow.

    The ABC of palliative care is edited by Marie Fallon, Marie Curie senior lecturer in palliative medicine, Beatson Oncology Centre, Western Infirmary, Glasgow, and Bill O'Neill, science and research adviser, British Medical Association, BMA House, London. It will be published as a book in June 1998.