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The pharmacological approach to management of pain in palliative care

Oliver Jones takes you through a logical approach

Pain is a common feature of terminal disease. As a preregistration house officer, managing this pain can be bewildering. This article presents some principles of management. It is important to remember that pain control is only one aspect of terminal care. Empathy and attentiveness are no less important than appropriate pharmacological intervention.

First line treatment

The nature of incurable disease results in pain being almost invariably chronic and often progressive. Analgesia should be prescribed as a regular medication to prevent the onset of pain. This is best achieved through a system that avoids the patient depending on a nurse or relative for regular drug administration. This is most easily achieved with oral treatments (or infusion pumps, as described later). If simple analgesics such as paracetamol or non-steroidal anti-inflammatory drugs (NSAIDS) are not effective then oral morphine regimens are the next line of treatment.

Oral aqueous morphine

Oral aqueous morphine is a powerful analgesic that allows patients to self administer their analgesia while avoiding the need for repeated injections. Pharmacists will make up aqueous solutions of varying strength, which usually requires the patient to take a volume of 5 or 10mls a dose, normally starting with a dose of 5-10mg of morphine every four hours. However, if the patient has previously been taking weak analgesics and is experiencing severe pain it is appropriate to start at a higher dose--for example, 20mg every four hours. The dose can be increased gradually if pain persists and occasionally doses of up to several hundred milligrams every four hours are required.

Oral morphine tablets

Some patients prefer to take oral tablets rather than aqueous solutions. Slow release tablets also allow doses to be spaced at 12 hourly intervals. A reasonable starting dose of slow release morphine is around 10-30mg every 12 hours. This dose may be increased gradually to 60mg, though the interval should remain at 12 hours. Oral aqueous and oral tablet doses of morphine are equivalent over 24 hours, so10mg of oral aqueous morphine every four hours is equivalent to 30mg of slow release morphine tablets every 12 hours.

Combined regimens

These commonly combine slow release morphine tablets with a second analgesic, such as oral aqueous morphine or a NSAID, for breakthrough pain. This minimises sedation, effectively prevents pain but still preserves patient independence. An example of such a regimen would be oral morphine tablets (slow release) 20mg every 12 hours, with 10mg/5ml of oral aqueous morphine solution for breakthrough pain.

Problems with oral morphine preparations

Constipation

Dietary measures should be the first line of treatment, and early recognition of the problem may prevent the need for hazardous interventions, such as manual disimpactions. If dietary manipulations alone fail, rectal examination should be undertaken to assess faecal loading. If the rectum is full then a couple of glycerine suppositories are appropriate. For those with an empty rectum and appropriate food intake, a stimulant laxative or faecal softener or both may be appropriate. Co-danthramer is commonly employed for this purpose.

Sleep disturbance

Reliance on oral aqueous doses every four hours may result in the patient waking in the night in pain. Some of this may be overcome simply through the use of slow release tablet preparations. If the patient prefers to take only oral aqueous morphine you should give a larger dose at night, up to twice the normal amount, and this often results in the patient being able to miss one dose in the middle of the night. The higher night time dose has useful sedative properties in itself, though a hypnotic, such as 10-20mg from the period of onset of the short acting benzodiazepine, temazepam, may be added if sleep disturbance persists.

Vomiting and nausea

This may as a consequence of opioid use, but could also result from the disease process itself. It can usually be controlled with 10mg oral metoclopramide or 5mg prochlorperazine. More resistant cases may benefit from 8mg oral ondansetron. In patients in whom nausea and vomiting interferes with their ability to take oral medications, the parenteral (intravenous) route can be used for analgesia (see below).

Sedation, confusion, and dependence

These unwanted symptoms are often only transient and may be reduced by using the minimum dose required to achieve analgesia. An explanation of these symptoms should allay fears of patients and their relatives. A degree of dependence is common but not normally troublesome in the context of palliation of terminal disease.

Alternatives to oral morphine

These may be considered when the oral route becomes impractical as a consequence of dysphagia, bowel obstruction, coma, or confusion.

Parenteral opioids (see case study)

Morphine may be given intramuscularly or subcutaneously. The total parenteral dose over 24 hours is one half the total oral (aqueous and tablet) 24 hour dose. This total parenteral dose should then be divided by six and given every four hours. Diamorphine is probably more suitable for parenteral administration because it is more soluble than morphine and can be given in smaller volumes. The total 24 hour diamorphine dose is one third the total oral 24 hour dose. This figure should also be divided by six and this amount is given every four hours.

Infusion pumps can also be useful, and these may be portable so as not to restrict patient mobility. With appropriate support, they may also be employed for use with patients at home. If given as an infusion the diamorphine should be dissolved in water, and a solution made up that requires infusion rates of 0.1-0.3ml an hour. A subcutaneously placed butterfly needle is an effective means of delivery, and these needles should be changed every 24 hours. In many hospitals, these subcutaneous needles will be inserted and changed by the nursing staff. If nausea is a problem, haloperidol 2.5-10mg every 24 hours may be added.

Transdermal fentanyl

These are patches applied to the skin and changed every 72 hours. They provide a sustained release of the opioid fentanyl. They come in four "strengths": 25, 50, 75, and 100. These numbers refer to the number of micrograms of fentanyl released per hour for 72 hours, by the patch. Conversion from oral morphine is made by calculating the total 24 hour oral morphine dose. A dose of 90mg of oral morphine in 24 hours is equivalent to 25µg/hour from a fentanyl patch. The clinical effect of fentanyl patches is not seen until 24 hours after starting treatment. If symptoms permit, pre-existing analgesics should be phased out gradually during this period.

Specific pain syndromes

Neuropathic pain may respond dramatically to tricyclic antidepressants, such as amytriptyline, starting at a dose of around 25mg at night (10mg in the elderly or frail). These cause sedation and may aid sleep. An alternative to this is an anticonvulsant such as carbamezepine or sodium valproate.

Gastrointestinal colic may benefit from loperamide, but this may exacerbate constipation, which is frequently experienced in those on morphine. Hyoscine hydrobromide 300 µg every eight hours sublingually may also be effective. This has a further effective role in terminal care in drying secretions in those with upper respiratory rattle. The side effect of dry mouth may limit usefulness of this drug.

Summary

Effective palliation of pain in terminal care is a small, but important part of management of the terminally ill patient. Following the guidelines outlined above should provide effective pain relief in the majority of cases. Further help is available in every hospital. Apart from advice from more senior members of your team, many hospitals have a pain team and others have physicians with an interest in terminal care management.

Case study

Mr A has terminal oesophageal cancer and worsening dysphagia. Reviewing his drug chart, you note that he has been taking MST (slow release morphine tablets) 60mg twice daily and has oramorph (aqueous oral morphine) 20mg/5ml for breakthrough pain. He has been taking 20mg of his oramorph approximately three times daily for the past few days. He reports that this combined regimen has been controlling his pain well, but that he has been having difficulty swallowing his medication.

His current average total 24 hour oral morphine dose is: (60x2) + (20x3) = 180mg per 24 hours.

If you wish to switch him to parenteral (subcutaneous or intramuscular) morphine you must halve this 24 hour dose--that is, 90mg (see text). Parenteral morphine should be given every four hours, which is the equivalent of 15mg of morphine every four hours.

If you wish to switch him to parenteral diamorphine you must use one third of the 24 hour oral morphine dose--that is, 60mg (see text). This is again given every four hours, which is the equivalent of 10mg of diamorphine every four hours.

If you wish to give him a diamorphine pump this must deliver 60mg per 24 hours, which is the equivalent of 2.5mg an hour. The total volume infused per hour should be 0.1-0.3ml. The syringe could be made up using 100mg of diamorphine, enough to ensure that it did not need to be changed for 24 hours. If you wish to run the pump at 0.2ml per hour and deliver 2.5mg of diamorphine per hour, then the 100mg of diamorphine should be dissolved in: (100/2.5) x 0.2ml = 8ml of water.

The prescription should read: "100mg of diamorphine in 8mls of water, to run at a rate of 0.2ml/hour through a subcutaneous butterfly needle." This is equivalent to Mr A's initial oral dose. If he has breakthrough pain the infusion rate may be increased, or a second analgesic, such as oral aqueous morphine, added as required.


Oliver Jones research fellow, department of pharmacology, University of Oxford
oliver.jones@pharm.ox.ac.uk