Pain in Cancer Patients: Management
Management of cancer pain by means of pharmaceutical agents and non-drug methods are discussed. Myths about use of morphine have to be corrected. Proper selection and prescribing of different opioids is mentioned with emphasis put on proper use of morphine. Side effects should be anticipated and prevented. Different approaches are adopted to control different types of pain. Analgesics, adjuvants and non-drug methods are equally important in controlling pain. Discussion is made on the management of a number of special problems.
To achieve optimum pain management, it is essential to reach a working diagnosis by assessment. Then try to correct any reversible pathology such as those shown in table 1. Choice of management option depends on the specific condition of the patient.
Table 1: Non-analgesic management of some causes of pain
Causes |
Management |
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· pathological fracture |
· radiotherapy or operation |
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· bowel obstruction |
· operation or conservatively with anticholinergic and steroid |
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· infection |
· antibiotics |
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· muscle spasm |
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° smooth muscle |
· anticholinergics |
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° skeletal muscle |
· physiotherapy, muscle relaxant |
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· raised intracranial pressure |
· steroid |
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· liver capsule distension |
· steroid |
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· bone metastasis |
· radiotherapy |
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· spinal cord compression |
· radiotherapy, steroid, laminectomy |
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· haematological malignancy, seminoma or small cell lung cancer |
· chemotherapy |
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· metastatic prostate cancer |
· anti-androgen, radiotherapy |
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· hypercalcaemia |
· bisphosphonates |
For optimal pain control, the right analgesic has to be given of right dose by the right route at the right time.
The approach to chronic pain management is different from that for acute pain. The analgesics have to be administered regularly according to the half life of the analgesic, by mouth if possible and the dose be titrated upward according to the analgesic effect. Even after good pain control, every pain should be reviewed regularly. Side-effects have to be anticipated and prevented. Multiple drugs use for management of multiple symptoms is common in cancer patients, so beware of drug interaction.
Figure 1 shows the stepwise approach of analgesic use in pain of different severity.
Figure 1: WHO analgesic ladder
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Strong-opioids+ non-opioids± adjuvants |
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Weak-opioid+ non-opioid± adjuvants |
Morphine Oxycodone Buprenorphine Dextromoramide |
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Non-opioid± adjuvants |
Codeine Tramadol |
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Aspirin Paracetamol |
Dextropropoxyphene |
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Table 2 shows the dosage of the different types of analgesics.
Table 2: Types and dosage of analgesics (given orally unless specified otherwise)
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Types of Analgesics |
Dosage |
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Non-opioid Analgesics |
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Paracetamol |
0.5-1g q4h |
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Aspirin |
300-900mg q4h |
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Weak Opioids |
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Codeine |
15-60mg q4h |
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Dextropropoxyphene |
100mg q4h |
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Tramadol |
50-100mg q6-8h, q4-6hrs slow ivi or imi |
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Weak opioids + non-opioid analgesics combinations |
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Codeine/Paracetamol |
1-2 q4h |
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Codeine/Aspirin |
1-2 q4h |
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Dextropropoxyphene/Paracetamol |
1-2 bd-qid |
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Strong opioids |
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Morphine |
2mg-many gms q4h (no maximum dose) |
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Solution or tablet Slow Release Morphines · MS-Contin (tablet or granules for suspension) · Kapanol (granules in capsule) |
Half daily dose given q12h, Total daily dose given once daily or half daily dose given q12h. |
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Oxycodone |
Dosage same as morphine |
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· tablet · suppository · slow release tablet - OxyContin |
· can be given q6-8h · can be given q6-8h · given q12h |
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Fentanyl |
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· transdermal patches |
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· Fentanyl inj |
50-100mg im or slow ivi |
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Methadone |
Read below |
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Aspirin has the same analgesic potency as paracetamol, but has more anti-inflammatory effect. It’s antiplatelet effect is significant in cancer patients who have a bleeding cancer, low platelet count caused by chemotherapy or marrow secondaries and patients who are on steroids.
NSAIDs can also cause gastric erosion, ulcer and haemorrhage. They impair kidney function, cause salt and water retention, antagonise diuretics and aggravate lymphoedema. Suppositories can be used if the patient cannot tolerate oral preparations. However, these can still cause GI bleeding.
NSAIDs are useful in pain due to bony metastasis and visceral pain such as pleuritic pain, liver and renal distension. They have peripheral analgesic action and paracetamol has central action. Their combination has additive analgesic effect. However, avoid concurrent use of steroid with NSAIDs because of high risk of GI bleeding.
Because of greater side effect, better use co-analgesic adequately before starting opioids. Because of different sites of action, paracetamol and opioids have additive effect. Visceral pain responds extremely well to opioids. Somatic pain does exhibit reasonable opioid sensitivity but opioids alone may not totally control somatic pain. Some pains respond only partially to opioids such as neuropathic pain and incidental pain. Pain of muscle spasm and psychosocial pain do not respond to opioids. Increasing opioid intake in cancer patients is not due to pharmacological tolerance but is usually due to pain increase from progression of disease.1 Table 3 shows some opioids and combinations which are not recommended for long term pain control.
Table 3: Opioids and combinations which are not recommended for long term pain control.
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Drugs |
Reasons |
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· Pethidine |
· short acting, 2-3 hrs analgesic effects · in large dose, accumulation of toxic metabolites |
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· Paracetamol/Dextropropoxyphene |
· different half-life of the components. |
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· Buprenorphine, Pentazocine |
· opioid partial antagonist, displace morphine from reception, reduce effect of morphine. |
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· Dextromoramide |
· Short acting, good for short procedures only · tolerance rapidly developed. |
There are a lot of myths relating to opioid use held by both the medical professional and lay people. Correction of these can result in better narcotics use with better pain control. Table 4 shows some current accepted facts for correcting misconceptions
Table 4: Current accepted facts to refute misconception in cancer pain control.
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· Use of opioid does not mean death is imminent. · Early use of morphine will not reduce its effect when it is really needed as the disease advances. · There is no ceiling for the dose of morphine. · In real pain control, morphine does not cause respiratory depression or addiction. However, sudden removal of severe pain, e.g. after nerve block, can precipitate respiratory depression. · Pain is easier to prevent than to treat. · If used properly, morphine will not cause damage to health. · Driving is allowable once the initial and transient (4-8 weeks) cognitive and psychomotor performance are no longer impaired. |
Eight mg of codeine in some preparations is sub-therapeutic. Better use preparations which contains 30mg codeine. The analgesic effect of both codeine and morphine lasts for 3-5 hours. They should be given by the clock four hourly and never as necessary, except for break-through dosages. It takes 7 half-lives to reach the steady state of effect. Immediate release preparations reach this state earlier than the slow release preparations after adjustment of dosage.
Start with morphine hydrochloride solution and the dose depends on the dosage of weak-opioid currently being used. Codeine 60mg is equivalent to morphine 5mg orally. If pain cannot be controlled with preparation containing 60mg of codeine, start morphine at 8-10mg four hourly Although nausea is a transient side effect on starting morphine, severe vomiting may be due to the side effect of the preservative added in the solution. Try asking the pharmacist to prepare a solution without preservative but it should be kept in the refrigerator.
The dosage can be increased every 24 hours until good control in steps: 5, 10, 15, 20, 30, 40, 60, 90, 120, 150, 180mg. The right dose of morphine is the dose that gives adequate relief of pain for 4 hours without intolerable side effects. A double dose at bedtime gives the patient a pain-free sleep through the night.
Lower dose of morphine should be started in the elderly. Serum creatinine can be unreliable because of muscle wasting in cancer patients. The dosage need not be reduced in patients with cirrhosis despite reduced first pass metabolism except in patients with severe end stage liver disease.2
Change to slow release morphine after pain is controlled by liquid morphine. Half of the daily dose needed is given twelve hourly as MS-Contin or Kapanol. In a minority of cases, some patients may need eight hourly doses. Total daily dose can be given once daily with Kapanol. MS-Contin must not be crushed. It also presents as long acting suspension in 30mg sachets. Kapanol granules can be sprinkled over food or in fluid for tube feeding.
Slow release forms produce a peak serum level at 4-5 hours. The first dose of long acting morphine has to be given with the last dose of morphine solution. Morphine solution for breakthrough pain should also be prescribed simultaneously. The patient can be taught to take it if pain occurs before the scheduled time of the slow release morphine. This should not be brought forward to treat the breakthrough pains. The dosage of morphine solution for breakthrough pain equals half to one four-hourly dose. The patient should be asked to record the time and amount of morphine solution taken. Once every few days, the total 24 hour morphine consumption can then be given as slow release morphine of higher dosage.
Abolition of pain can make the patient particularly sensitive to the side-effects of morphine. The current dose has to be reduced to one third or one half after nerve block or radiotherapy to avoid respiratory depression or sedation.
If oral route is impossible because of vomiting, loss of consciousness or intestinal obstruction, subcutaneous morphine suphate injection can be given 4-hourly by the family or 24 hourly by continuous infusion via a syringe driver. Always anticipate sudden need of parenteral route and have morphine sulphate ampoules or prescription ready at patient’s home. The dosage by the subcutaneous route equals ½ to 1/3 of oral dose.
MS-Contin can be given rectally, but the absorption rate is variable.3 The dose is similar to oral dose. It can be given in emergency by the family before subcutaneous route can be set up by the professionals.
Drowsiness occurs on starting or on increasing the dose of opioid, but is usually transient. Nausea and vomiting are common initially but improve in a few days. They can be controlled with haloperidol 1.5-5mg nocte orally or prochloperazine suppository 25mg nocte. Constipation nearly always occurs, so concurrent use of laxative is essential. Start with docusate with senna 2 tablets nocte or twice daily depending on the dose of opioid. It is preferable to give a higher dose of laxative and then adjust downward appropriately because a little diarrhoea is more comfortable than constipation. Tolerance, psychological and physical dependence are not a problem in patients who really have pain.
In chronic renal failure patients, active metabolites accumulate4 and can cause overdose. The dose can be reduced or normal dose can be given six hourly instead of four hourly. Oxycodone, methadone or fentanyl can be given if the patient cannot tolerate morphine. Methadone does not have accumulative active metabolite.
Loss of consciousness can occur in the terminal phase of dying. It can be confused with the sedation of opioid overdose. The latter presents with dry mouth, myoclonus jerks, reduced respiration (rate, tidal volume and minute volume) and pin-pointed pupils. In mild respiratory depression, skip one dose and start again in reduced dosage. In more severe overdose, give naloxone diluted 1:10 in normal saline intravenously. It must be given slowly to prevent precipitation of severe withdrawal symptoms or severe pain.
Confusion is less likely if doses are titrated up slowly. If severe or hallucination is experienced, change to methadone or fentanyl because these cannot usually be managed with any medicine.
Other rarer side effects include asthma and urticaria, dysphoria, urinary retention, bradycardia and hypotension.
On switching to another opioid, the new opioid has to be started with half of the equivalent analgesic dose and adjust upwards because some tolerance may have developed to the old opioid and cross tolerance may not be complete among different opioids.
Tramadol is a centrally acting weak opioid agonist which has non-opioid spinal and CNS effects. The efficacy lies between codeine and morphine. It is indicated for moderate to severe pain. It has less sedation, respiratory depression, tolerance and constipation than with oral codeine and morphine. Transient dizziness and nausea and vomiting may occur. It can be given with or without food six to eight hourly, or twelve hourly in patients with renal or liver impairment.5
Oxycodone has a potency ratio of 0.7:1 when compared with morphine. Oral tablet or suppository can be given every 6-8 hours and slow release tablet (OxyContin) every 12 hours. Because its metabolites are different from that of morphine, it is indicated for patients who cannot tolerate morphine. Side effects are similar to those for morphine except that it is less likely to cause delirium.6
Dextropropoxyphene has a long half-life of 15 hours. Prolonged use can lead to accumulation of its long acting active metabolite causing confusion and hallucination.6
Methadone can be used in patients who cannot tolerate morphine. It is excreted via the liver so it can be used in patients with renal failure. The effect of 5mg is equivalent to 7.5mg of morphine. Its use is limited by its long and unpredictable half life which varies from 8 to 80 hours, longer with chronic administration and in the elderly with potential delayed toxicity.
Fentanyl has a lower incidence of constipation, confusion and drowsiness.7 Substitution with fentanyl can sometimes relieve bowel obstruction caused by morphine. In palliative care, it is often used in the form of transdermal patches which release 25,50,75,100 mcg/hr of fentanyl. Its potency is about 100 times of morphine. (25mcg/hr patch = 135mg/day oral morphine) The peak plasma concentration is achieved after 12-24 hours. Another analgesic is needed for the first day of use. The action remains for 24 hours after the patch is removed. Fever and external heat increase the rate of drug delivery. The patch has to be change once every 72 hours on a new site. Care must be taken in disposal of the patch as significant amount of fentanyl remains in the patch after three days. It is expensive, but generally patient satisfaction is high.8
Buprenorphine is well absorbed through buccal mucosa and can be used as a booster analgesic before procedures such as changing dressings. Each tablet of 0.2mg is equivalent to 15mg morphine orally.
Table 5 shows the adjuvants for cancer pain management, their indications and dosages.
Table 5: Adjuvants for cancer pain management, their indications and dosage. (given orally unless specified otherwise)
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Tissue destruction, bone metastasis, arthritis, other inflammations |
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· NSAIDs |
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Aspirin |
300-900mg q4h |
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Ibuprofen |
200-400mg tds-qid |
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Piroxicam |
25-50mg daily |
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Diclofenac |
25-50mg bd pc |
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Naproxen |
1000mg daily, 1 supp bd-tds pr |
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Infection |
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· Oral antibiotics for deep infections |
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· Topical antiseptic for superficial infection |
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Metronidazole gel |
Local application twice daily |
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Betadine solution or ointment |
Local application 2-3 times daily |
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Pressure, distension |
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· Dexamethasone tablet or injection |
2-16mg daily |
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Muscle spasm (relaxants) |
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· Benzodiazepines |
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Diazepam |
2-10mg tds-qid |
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Alprazolam |
0.5-4mg/day |
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Clonazepam |
0.5mg nocte - 2.5mg bd , 1-5mg/day sc |
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· Dantrolene |
25-50mg qd-qid |
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· Baclofen |
10-25mg tds |
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Bone Metastases |
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· Pamidronate disodium11 |
60-90 mg iv infusion in 4-6 hrs |
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Metastatic Prostate Cancer |
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· Cyproterone |
200mg/day |
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Tenesmus |
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· Chlorpromazine |
25-50mg tds-qid |
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Table 6 shows the main causes of visceral pain and their management apart from the use of analgesics.
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Cause |
Management |
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· hollow organ spasm |
· anticholinergic - hyoscine, atropine |
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· duct obstruction - ureter, intestine, biliary duct |
· antispasmodic - mebeverine · anti-cholinergic - hyoscine, atropine |
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· distension of solid organ capsule - liver, kidney |
· steroid · radiotherapy |
In nerve injury pain, although opioids and non-opioid analgesics are relatively ineffective, morphine can be tried first. A tricyclic antidepressant or anti-convulsant can be added. It can be changed to the other kind if it is not effective after a few days. If either antidepressant or anticonvulsant is not effective, a combination of them can be tried, but beware of drug interaction. A combination of morphine and dexamethasone 4-8mg daily is used for nerve compression. If the pain is refractory to the above treatment, spinal analgesia done by anaesthetist via epidural or intrathecal routes has to be considered.
Sympathetically mediated pain such as complex regional pain syndrome can be relieved by systemic steroid, clonidine9,10 or nifedipine.11 The steroid acts by reducing spontaneous discharge of injured nerves. Clonidine can be used for phantom limb pain. Sympathetic nerve block done at the stellate ganglion or lumbar sympathetic nerve chain may also be tried.
Their analgesic effect is not due to mood elevation.12 They are indicated for continuous unpleasant dull aching, superficial burning pain and allodynia, but they may also be effective for stabbing and lacinating pain of some patients. They have synergistic effect with morphine resulting in a reduction in opioid requirement and are good for mixed vascular and tension type headache. The dose used is lower and the response is faster than for depression.
Amitriptyline can be started with 10-25mg nocte and be increased to 50-75mg nocte in a few days.12 In patients older than 65 years old, it should be started with 10mg and increased more slowly. It takes four days to be effective and can be stopped if no benefit occurs in one week.13
Mianserin which is a tetracyclic antidepressant is less effective.5 The selective serotonin reuptake inhibitors and meclobamide14 are not effective for neuropathic pain of cancer patient.
They are more suitable for shooting or lacinating neuropathic pain. The dose is lower than for epilepsy. They can be stopped if no benefit occurs when the serum level is in the therapeutic range for epilepsy. Sodium valproate is the first choice and has fewer side effects. It can be commenced with 200mg twice daily and increased once every four days to 0.4-2.4g/day in 2-3 doses. Side effects include nausea, tremor and increase in appetite.
Carbamazepine has more side effects. The white cell count should be checked periodically especially in those who have undergone chemotherapy recently. It can be commenced with 100mg twice daily and be increased to 200mg three times daily with an increment of less than 200mg per day per week.
Phenytoin is less effective than valproate and carbamazepine. It has more side effects than valproate and also need regular monitoring of serum level.
Clonazepam, a benzodiazepine and an anti-epileptic, is suitable for patients who also have anxiety, insomnia and epilepsy. It often causes drowsiness, occasionally ataxia and withdrawal symptoms with sudden withdrawal of high dose. It can be administered sublingually as drops or subcutaneously via syringe driver, so it is convenient for unconscious or vomiting patients. The dose ranges from 0.5mg nocte to 2.5mg twice daily orally or 1-5mg/day subcutaneously.
A number of new anti-epileptic drugs such as gabapentin have been shown to have analgesic effect on non-cancer related neuropathic pains with minimal side effect.15 It can be tried on patients with refractory neuropathic pain.
The three most commonly used agents are mexiletine, flecanide and lignocaine. Their use should be restricted to those who are experienced because of risk of arrhythmia.
Non-drug therapy is as important as, if not more important than, drug therapy for pain control. Explanation of the condition to the patient is paramount because anxiety and depression can lower pain threshold. The best analgesic is often the close attention to detail provided by an obviously interested and caring doctor or nurse.
Apart from using heat and massage, immobilization and passive exercise, physiotherapist, through repeated contact, can also give support and care. Prophylactic physiotherapy may help in minimising and preventing pains from muscle spasm and contracture. Occupational therapists can help in providing walking aid, wheelchair, cushion, sheepskin, mattress and hoist. They can also help in designing and modifying the home environment to facilitate living at home such as raising the toilet seat and installing railings on walls.
Pain signals can be interrupted at the nerve roots, coeliac plexus, brachial plexus and intercostal nerve for controlling regional pains. Transcutaneous Electrical Nerve Stimulators (TENS) and acupuncture which inhibit pain signal transmission are effective for neuralgia and soft tissue pains.
Table 7: Non-drug Management
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The aggravating factors must be identified and avoided. Explanation of the condition. The patient’s myth of pain must be corrected. Assure the patient our ready availability and accessibility. Convey to the patient a sense of security, confidence, optimism and encouragement. Make available what the patient wants: family member, pet, food, alcohol and hobby. Relax the environment with music, television and games. Encourage visits from friends and volunteers. Attend to his emotional and spiritual needs. Radiotherapy is effective in controlling pain of bone metastasis. Physiotherapists can help in pain caused by muscle spasm or contracture. Occupational therapist contributes in reducing handicap. Transcutaneous Electrical Nerve Stimulators (TENS) and acupuncture Music therapy, aromatherapy, Chi-kung and Tai-chi Interruption of pain pathway. |
It is relatively common and is often associated with bone and joint pains. Anxiety can exacerbate muscle spasm and can present as myofascial trigger points in the shoulder girdle and neck. Physiotherapy with massage, hot or cold compress is more effective than drug therapy. Diazepam 2-10mg three times daily is effective particularly if the spasm is associated with anxiety. Baclofen can be started at 5mg three times daily and increased by 15mg per day every third day to 25mg three times daily.16
Very high dose of dexamethasone given intravenously can produce immediate relief lasting for several hours. The dosage can be as high as 40-60mg three times daily and be maintained at 20mg three times daily. With control of pain and vomiting, it can be changed to high oral dose for maintenance.
It may be caused by wrong diagnosis of type or cause of pain, poor compliance to therapy, progression of disease, inadequate dosage or inadequate absorption because of gastrointestinal problems. However, psychosocial or spiritual pain must be excluded. Chronicity of pain in delayed treatment or prolonged suboptimal control contributes to opioid resistance. Second opinions must be sought early when the pain seems to be refractory to treatment.
Epidural morphine, bupivacaine or clonidine can be administered through micropumps implanted subcutaneously. Previously it was restricted to patients with a life expectancy shorter than three months. However, because of recent advances in technology, more patients are being treated in this way earlier.
Radiotherapy is the management of choice. It takes a couple of weeks to become effective. Before that, it can be infiltrated with local anaesthetic and corticosteroid if the metastasis is palpable. Because bone secondaries have a high level of prostaglandin, NSAIDs are effective adjuvants.
1. Collin E, Poulain P, Gauvain-Piquard A, et al, Is disease progression the main factor in morphine 'tolerance' in cancer pain treatment? Pain, 1993; 55(3):319-26.
2. Hasselstrom J, Eriksson S, Persson A, Rane A, Svensson J, Sawe J. The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Br J of Clin Pham 1990; 29(3):289-97.
3. Kaiko R, Fitzmartin R, thomas G. The bioavailability of morphine in controlled-release 30mg tablets per rectum compared with immediate release 30mg rectal suppositories and controlled release 30mg oral tablets. Pharmacotherapy 1992;12:107-13.
4. Chauvin M, Sandouk P, Scherrmann J, Farinotti R, Strumaza P, Duvaldestin P. Morphine pharmacokinetics in renal failure. Anesthesiology 1987 March; 66(3):327-31.
5. McQuay H, Moore A. An evidence-based resource for pain relief. Oxford University Press: New York, 1998.
6. Maddocks I. Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone. J of Pain Symptom Management. 1996; 12(3):182-9
7. Ahmedzai South, Brooks J. Transdermal fentanyl versus sustained-release oral morphine in cancer pain: preference, efficacy, and quality of life. The TTS-Fentanyl Comparative Trial Group. J of Pain Symptom Manag 1997; 13(5):254-61.
8. Payne R, Mathias South, Pasta D, Wanka J, Williams R, Mahmoud R. Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine. J Clin Oncology 1998; 16(4):1588-93.
9. Petros AJ, Wright RMB. Epidural and oral clonidine in domiciliary control of deafferentation pain. Lancet, 1987; 1:1034.
10. Porchet H, Piletta P, Dayer P. Objective assessment of clonidine analgesia in man and influence of naloxone. Life Sciences 1990; 1990(14):991-8.
11. Prough DS. Efficacy of oral nifedipine in the treatment of reflex sympathetic dystrophy. Anesthesiology, 1985; 62:796-9.
12. McQuay H, Carroll D, Glynn C. Dose-response for analgesic effect of amitriptyline in chronic pain. Anaesthesia 1993; 48(4):281-5.
13. McQuay H, Carroll D, Glynn C. Low dose amitriptyline in the treatment of chronic pain. Anaesthesia, 1992; 47(8):646-52.
14. Menkes D, Fawcett J, Busch A, Jones D. Moclobemide in chronic neuropathic pain: preliminary case reports. Clin J of Pain 1995; 11(2):134-8.
15. Merren M. Gabapentin for treatment of pain and tremor: a large case series. Southern Med J 1998; 91(8):739-44.
16. Steado L, Leo A, Marano E. Efficacy of baclofen in trigeminal neuralgia and other painful conditions. European Neurology 1984; 23(1):51-5.
1. To achieve optimum pain management, it is essential to reach a working diagnosis by assessment, whether the pain is somatic, visceral, neuropathic or a mixture.
2. For optimal pain control, the right analgesic has to be given of right dose by the right route at the right time.
3. Morphine and codeine needs to be given 4 hourly together with paracetamol for better effect and laxatives to prevent constipation.
4. Morphine is not reserved for those who are in terminal phase. Early control of pain can prevent development of refractory pain.
5. Morphine is not the panacea of pain control. Appropriate use of adjuvants can spare the patient from high doses of opioids.
6. Non-drug management is sometime more effective than drug management.