When decisions arise concerning the treatment of dying patients, these options present complex clinical and ethical dilemmas. Many are faced with decisions about the best treatment to ease a patient’s final suffering, or perhaps even a decision will need to be made about terminating treatment altogether.
Cancer pain is a complex symptom, resulting from mixed mechanisms and which changes over time. The actual pain experience is modified by past experience, mood, cultural and social factors, as well as the meaning the patient attaches to the pain.
When this pain occurs in a situation where restoration of health is no longer a likely outcome, it would be termed terminal cancer pain.
Current treatment guideline for terminal cancer pain
Management of cancer pain has been based worldwide on the World Health Organisation’s (WHO) concept of the analgesic ladder, whereby pain medication is determined by a patient’s pain severity and the likely mechanism of the pain. (See figure of analgesic ladder). In Step 1 of the ladder, non-opioids drugs are used for mild to moderate pain. If this fails to control the pain, a weak opioid is added (Step 2). Step 3 strong opioids are used in patients with severe cancer pain and pain not controlled with Step 2 medications. When moving to Step 3, the weak opioid should be stopped and replaced with a strong opioid. Non-opioid medications can be continued in Step 3 for their opioid-sparing effect, which helps to minimise opioid side effects. At any level of the ladder, appropriate adjuvant medication is used in addition to standard analgesics.
When treating cancer pain, analgesics should be used around the clock and not only as necessary. Oral formulations are preferred wherever possible and are as effective as parenteral medication in equivalent doses.
Non-opioids include paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs). The maximum dose of paracetamol of 4 grams daily should not be exceeded and extra caution exercised in patients with significant hepatic disease. NSAIDs are effective for a diverse range of cancer related pain. Possible adverse effects include gastrointestinal toxicity and increased risk of thrombotic events.
Tramadol is the drug of choice for a step 2 opioid. Some patients experience significant nausea related to tramadol, therefore it is best to start with lower doses and titrate up. In terminal cancer pain, it is not unusual to bypass the tramadol and use low doses of a strong opioid in Step 2.
Morphine is widely used as the strong opioid of choice for reasons of availability and cost. However, available data show no important differences in efficacy and tolerability between morphine, oxycodone and hydromorphone, therefore it is recommended that any one of these can be used as a first choice step 3 opioid for moderate to severe cancer pain.
Oral formulations of strong opioids include immediate release syrup or tablets, given four hourly and sustained release tablets or capsules used 12 hourly. A usual starting dose for morphine is 5-10 mg four hourly. Strong opioids do not have a ceiling effect and the dose is up titrated (by 50% of the current dose) until a satisfactory response is achieved, or side effects become problematic. Traditionally, immediate release opioid formulations are used for titration, but sustained release preparations have also been used successfully. Immediate release preparations should be available to the patient for breakthrough pain, dosed as at least 50% of the four hourly doses.
When prescribing morphine syrup, the clinician needs to specify to the pharmacist what strength elixir should be made up (e.g. 5 or 10 mg per millilitre). Sustained release opioid preparations come in a range of strengths and are usually easy to swallow.
Transdermal fentanyl or buprenorphine are useful alternatives to oral opioids and come in the form of different strength skin patches, which release their active ingredient over several days. Transdermal fentanyl patches are replaced every three days. These formulations are especially useful in cancer patients with painful or difficult swallowing, vomiting, bowel obstruction or severe sedation. Some patients prefer the skin patches for their convenience and transdermal fentanyl has been found to cause less constipation than other strong opioids.
Strong opioid adverse effects
On initiation of opioids, side effects that occur commonly are nausea and vomiting, drowsiness and light-headedness, however these usually resolve over a few days. It may be necessary to prescribe an antiemetic (such as metoclopramide or haloperidol) and patients should be advised not to drive in the first week after being started on a strong opioid or following dose increases.
Constipation is a very significant side effect, which should be managed as soon as opioids are initiated and ongoing, because this side effect does not resolve over time. Patients will usually require a stool softener (such as lactulose), as well as a laxative (such as senna) and often need larger amounts than standard doses. Laxative suppositories may be used in addition as required.
The risk of respiratory depression is minimal in patients with pain and where doses of strong opioids are titrated. However, extra care should be exercised in patients who are frail, those on other sedative medication or co-morbid conditions such as chronic obstructive airways disease.
These are drugs designed for other conditions, but help to relieve certain types of pain. Adjuvants can be classified as:
For neuropathic pain: tricyclic antidepressants (TCA), serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants (such as gabapentin, pregabalin, valproate).
For bone pain: bisphosphonates
For bowel obstruction or colic: hyoscine butylbromide
Multi-purpose: glucocorticoids, TCA, SNRI’s
Clinical considerations when treating terminal cancer pain
- An important aspect of effective cancer pain management is a meticulous assessment of the pain, in terms of likely mechanisms of pain, severity and other factors that may influence the pain experience, since this will guide treatment modalities.
Nociceptive pain is due to soft tissue, bone or visceral infiltration, while neuropathic pain occurs as result of lesions in either the central or peripheral nervous system. Antineoplastic therapy (surgery, radiotherapy and chemotherapy) can result in both types of pain, as in mucositis or painful peripheral neuropathy. Colicky pain due to obstruction of a hollow organ is important to identify since specific antispasmodic treatment would be required.
Pain scales such as a visual analogue or numerical rating scale can be useful to measure pain severity and its response to treatment. However, in certain cases, it is more practical to enquire about pain interference with daily activities and sleep. In the situation of terminal cancer pain, cognitive impairment may hamper assessment of pain severity. In such cases, it may be necessary to observe pain-related behaviours such as facial expression, vocalisation or body movements.
A caring relationship between the clinician and the patient and family will assist in identifying emotional and other factors that may aggravate the pain experience.
- Patients vary in their response to- and tolerance of analgesic medication. This calls for individualised pain management. Adverse effects to analgesic medication should be managed well since these are likely to jeopardise treatment adherence.
- Cancer pain is prone to changing in nature or severity over time, therefore, particularly in the terminal phase; frequent review and adjustment of therapy may be required. This means that terminal cancer patients must have ready access to trained health care personnel. Most patients with life-limiting illness prefer to spend their remaining days at home, rather than in a hospital or hospice. In this situation, trained palliative care nurses offering domiciliary care to patients at home are of great benefit.
- Treatment modalities other than drugs should always be considered where appropriate. Radiotherapy is very effective for treating pain due to bone metastases and often a single dose is sufficient. This would generally not be appropriate for patients with a very short prognosis, such as a few weeks. Other non-drug methods may include heat pads, splints, slings, walking aids and relaxation therapy.
- It is not unusual for patients with terminal cancer to experience financial constraints following prolonged and costly medical management, besides several other factors. There are vast price differences between the different formulations of strong opioids. In resource limited settings and situations, excellent pain control can be achieved using morphine syrup at a fraction of the price of many of the other strong opioid formulations.
Ethical considerations when treating terminal cancer pain
The World Medical Association (WMA) Declaration on Terminal Illness in 2006 states that ‘the dying phase must be recognised and respected as an important part of a person’s life’. Therefore, clinicians should give terminally ill patients the same quality of care as all other patients.
Whilst this may appear obvious, in practice, many patients with terminal illness receive less or even minimal care from their treating doctor. There is evidence to show that more than 70% of cancer patients achieve good pain relief when using the WHO recommendations for treating cancer pain. Treating clinicians should at least ensure appropriate referrals for adequate palliative care.
When a patient’s medical condition precludes the hope of health being restored, there needs to be a shift in medical care emphasis from the unrealistic goal of cure to a reasonable goal of a more comfortable death. There needs to be an understanding between clinicians and patient and/or families concerning the goals of care. This enables the clinician to focus on good symptom control, while allowing the patient to accomplish necessary end-of-life tasks.
One of the barriers to good pain management in terminal cancer is the clinician’s fear of causing harm or creating a perception amongst patient family members or other health care workers of hastening the patient’s death. The perceived risks surrounding the use of morphine and other strong opioids result in under-prescribing and consequent under-treated cancer pain.
The 2006 World Medical Assembly (WMA) Declaration on Terminal Illness also stated ‘physicians should be able to pursue clinically appropriate aggressive pain management without undue fear of regulatory or legal repercussions’. In addition, morphine and other strong opioids have been widely used in palliative care for many years and guidelines based on evidence and expert clinical consensus, such as those from the European Association of Palliative Care; recommend strong opioids as the analgesics of choice for moderate to severe cancer.
There is no clinical evidence that opioids, when used according to guidelines, hasten death. Increasing dose requirements are mostly due to progression of disease and not tolerance to morphine. Neither do patients (without pre-existing opioid addiction) become psychologically dependent on morphine. As previously mentioned, respiratory depression does not occur when doses are titrated.
There is a small group of terminal cancer patients with pain that is very difficult to manage. These patients may require more extreme palliative measures, such as heavy sedation. Such cases may raise the question of whether palliation of pain is not similar to euthanasia. The ethical and legal opinion clearly distinguishes palliative interventions from euthanasia, in that the goal of palliation is relief of pain and medication doses used are those, which relieve pain, while the primary goal of euthanasia and methods used, are to bring about the patient’s death.
In end-of-life situations, the ethical principle of autonomy of the patient becomes particularly relevant. Patients need an opportunity to negotiate concerning medical interventions designed to prolong life, as well as the nature of palliation. It is therefore important for doctors to communicate to patients the benefits versus potential risk of all interventions, including palliative interventions. Examples of such interventions would include surgery, radiotherapy, opioid and sedative medication. Patients are under no obligation to accept recommended treatment, even if their decision is likely to accelerate dying. Clinicians should also take care not to assume what a patient might consider an acceptable quality of life.
In the terminal cancer situation, a significant number of patients may lack the capacity to make decisions concerning their care. Some patients may have written advance directives to guide clinical decisions, in other cases, close family or significant others will need to inform the health care team of the patient’s likely preferences. In addition, the clinician should always do what he/she considers to be in the best interests of the patient.
Terminal cancer can be a challenging for the patient, family and clinician. Some ways of ensuring optimal outcome include following evidence-based guidelines, good communication with patients and families, good documentation of conversations, decisions, and obtaining advice and second opinions from experienced colleagues or experts, when appropriate
Dr Sonia Hitchcock, Department of Family Medicine at the Kalafong Hospital and University of Pretoria.