Worsening pain in palliative care

A 78-year-old man with advanced lung cancer is receiving palliative care. Previously, regular codeine had controlled abdominal pain in the right upper quadrant, relating to liver metastases. However, over the past week this has progressively worsened and today he is distressed by moderate to severe pain, which is constant.

His current medication includes:

• Codeine tablets 60mg qds
• Paracetamol tablets 1g qds
• Co-danthramer capsules 25/200 ii on
• Cyclizine tablets 50mg every six to eight hours when required

His liver function is normal, but he has mild renal impairment. 

The codeine is to be switched to morphine. What regular dose of oral morphine should he receive initially? According to “Prescribing in palliative care” (BNF November 2013), during the titration phase the initial dose is based on previous medication, pain severity and other factors, such as the presence of renal impairment and increasing age or frailty. Recommended starting doses vary but, generally, a starting dose of 40-60mg of morphine daily is reasonable for patients being switched from a regular weak opioid, such as codeine. The table on “Equivalent doses of opioid analgesics” in the BNF shows that 100mg of codeine by mouth is approximately equivalent to 10mg of morphine by mouth.

This patient has been receiving 240mg codeine by mouth per day, which is equivalent to 24mg of morphine by mouth per day; he has moderate to severe pain despite this so a higher equivalent starting dose would be appropriate (ie, traditionally an increase by one-third to one-half of the total daily dose). Taking his age and mild renal impairment into account, rounding down the daily dose to 30mg would be reasonable. The morphine could be given either as an immediate-release preparation every four hours or as a modified-release preparation every 12 hours.

The patient is to be started on Oramorph oral solution, 5mg every four hours as regular pain relief. What dose of Oramorph should be prescribed for breakthrough pain? “Prescribing in palliative care” advises that an additional dose of immediate-release morphine should be given if pain occurs between regular doses of morphine. The standard dose of a strong opioid for breakthrough pain is usually one-10th to one-sixth of the regular 24-hour dose, repeated every two to four hours as required.

This patient should be prescribed Oramorph oral solution 5mg every two to four hours when required for breakthrough pain. Sometimes a dose range is prescribed to allow for situations where the lower dose is found to be ineffective. The aim is to ensure the patient has access to an effective and tolerated prn dose. Each administration should be recorded so that appropriate dose increases may be prescribed if needed.

How should this patient’s pain management be reviewed? Patients with unrelieved pain should be reviewed regularly to ensure progressive pain relief is being achieved using a dose of morphine that does not cause unacceptable undesirable effects (seek specialist help if this occurs). The regular and prn doses of Oramorph should be recalculated every 24–48h. Titration should be continued until the pain is adequately controlled (usually indicated by the use of two or fewer prn doses per day).

According to “Prescribing in palliative care”, nausea and vomiting may occur with opioid therapy, particularly in the initial stages, and a regular antiemetic may be required for the first four to five days. The patient is already being prescribed cyclizine for occasional nausea. Is this an appropriate choice of antiemetic? Because this patient has previously received codeine, his risk of nausea and vomiting with morphine is probably reduced. Thus, ensuring that he has access to an antiemetic on a prn basis would be reasonable.

Although cyclizine can be used, antiemetics that act on the chemoreceptor trigger zone (eg, metoclopramide, haloperidol) are more usually prescribed for drug-related nausea and vomiting. These avoid the sedative and antimuscarinic effects of cyclizine. (See the article on p240 for more learning on treating nausea and vomiting in palliative care.)

Over the next 48 hours the patient reports that his pain is more manageable. Nonetheless, he has required three doses of Oramorph 5mg oral solution for breakthrough pain each day, which were effective. What adjustments should be made to the dose of oral morphine? When adjusting the dose of morphine, the number of rescue doses required and the response to them should be taken into account. Generally, increments of morphine should not exceed one-third to one-half of the total daily dose every 24 hours. The patient has used a total of 45mg of oral morphine in the past 24 hours (30mg + 15mg), and his total daily dose should be increased to reflect this.

In practice this could be administered as 7.5mg of Oramorph oral solution every four hours. In addition, he should be prescribed 7.5mg of Oramorph oral solution every four hours when required for breakthrough pain.

Four days later the patient reports that the pain is much better. He is now receiving Oramorph oral solution 20mg every four hours and he has not required any rescue analgesia in the past 24 hours. How should this patient be transferred to a modified-release preparation of morphine? Once the pain is controlled, patients started on four-hourly immediate-release morphine can be transferred to the same total 24-hour dose of morphine given as the modified-release preparation for 12-hourly or 24-hourly administration.

In this instance, the patient is transferred to MST Continus tablets 60mg every 12 hours and continues with Oramorph oral solution 15-20mg every two to four hours when required. The first dose of the modified-release preparation should be given with the last dose of the immediate-release preparation. Increments should be made to the dose of the modified-release preparation and not the frequency of administration.

Further reading

• A further article on the questions to ask when supplying morphine is available online. bit.ly/1b9CDrM