Effective use of morphine

The keystone to using morphine for moderate to severe pain is in proper prescribing, patient reassessment, patient information, and prevention of side-effects.

Ideally start with a quick-acting morphine preparation. This has onset of analgesia in 20-30 minutes, which peaks at 60 minutes, and, when the required dose for the individual's pain is reached, will last four hours. This information should be given to the patient.

Morphine may relieve pain completely, partially, or not at all. It was previously thought that some pains, especially neuropathic pain, were unresponsive to opioids. Clinical practice and evidence from clinical trials tells us that opioid responsiveness is a continuum and no pain can be predicted as opioid-unresponsive. It is true that neuropathic pain often requires larger doses of opioids and titration is limited because at higher doses unacceptable side-effects, especially sedation, are problematic.

It is obvious that if side-effects of opioids are not prevented or minimized, especially sedation, then titration of opioids and subsequently pain control is not achieved. Review and rationalization of all drugs, especially drugs with sedative side-effects, is mandatory for successful titration of opioids. Monitoring of symptoms of opioid toxicity as part of regular patient review will prevent much distress and also save on resources such as unnecessary hospital admissions with confusion, cerebral imaging, and blood analysis. Opioid toxicity is a spectrum, which includes vivid dreams, shadows at the periphery of visual fields, nightmares, hallucinations, agitation and confusion. These features can be associated with myoclonic jerks or even generalized seizures.

The management of opioid toxicity is to reduce the dose of the opioid and reassess the pain syndrome, psychological factors, and

Table 14.2 Preventing opioid toxicity




Regular codanthramer or codanthrusate

Dry mouth

Frequent sips of cool water and regular mouth washes


Haloperidol 1.5-3 mg nocte or metoclopramide 10 mg



Explanation very important. Expect to settle in about

2-3 days. Avoid other sedating medication where


Table 14.3 Management of difficult pain

Bone pain

Palliative radiotherapy; NSAIDs with opioids

titrated to control pain; consider


Neuropathic (nerve) pain

Titrate through analgesic ladder,

remembering adjuvants (amitriptyline,

carbamazepine, or steroids);consider nerve


Rectal/vaginal/bladder pain

Use standard analgesic ladder approach

(+ nifedipine amitriptyline, steroids);consider

nerve block, local anaesthetic gel, steroid


Bed sores


biochemistry as appropriate. Haloperidol (1.5-3 mg po/sc, repeated as necessary) may be required to manage the altered sensorium in the acute situation. Rehydrate as appropriate—patients who are opioid-toxic are usually dry-mouthed.

Often pain is still controlled on the reduced dose of opioid. Sometimes an adjuvant drug may be needed. If the patient was using the opioid as an anxiolytic, another approach to anxiety is needed.

Occasionally opioid toxicity heralds renal dysfunction. In renal failure, a reduction in opioid dose may need to be accompanied by a reduction in dosing frequency. Liver dysfunction usually has to be severe before opioids accumulate. Methadone is safer than morphine in severe liver dysfunction.

NMDA antagonists

N-methyl-D-aspartate (NMDA) antagonists have a role in some pains, especially neuropathic pain and difficult inflammatory pains. Unfortunately, a convenient preparation is missing. However, SC or IV ketamine may be considered after seeking advice from a palliative care or pain team.

Alternative opioids

There are second-line opioids for moderate to severe cancer pain. The potential benefit in a switch from one opioid to another is a better balance between analgesia and unwanted effects. There are no controlled trial data at present to indicate definite benefits of one opioid over another. However, the following is suggested: ♦ TTS-Fentanyl—may cause less constipation than morphine. Suitable for stable pain. Time to peak blood levels is 12 hrs (up to 48 hrs in some patients) and terminal half-life after patch removal is up to 24 hrs. It is usually unsuitable in uncontrolled pain. The manufacturer's conversion chart is about right.

♦ Hydromorphone—useful if patient has cognitive impairment or hallucinations on morphine. May be useful in renal dysfunction because no known accumulation of active metabolites. Available as quick-acting and controlled-release capsules. Hydromorphone is about seven times as potent as morphine.

Oxycodone—similar benefits to hydromorphone. It is about equipotent with morphine (2:3). Available as quick-acting and controlled-release preparations.

♦ Phenazocine—useful if dysphoria with morphine. Size of tablets limits use (5 mg tablet is equivalent to 20 mg morphine).

♦ Methadone—alternative to morphine. However, for the non-specialist, difficult to titrate. Equianalgesic dose is variable; methadone can be up to 10 times as potent as morphine.

When switching from one opioid to another, the equi-analgesic doses are not always easily predictable because the relative potencies of the two drugs are the result of the complex variables. Equi-analgesic doses are just for guidance and careful reassessment is required after an opioid switch.

Incident pain

Bone pain is, in fact, responsive to opioid analgesia. However, bone pain on movement can be difficult to control with opioids alone. Pain is a physiological antagonist to the side-effects of opioids, and intermittent pain allows less titration of opioids since the patient is unacceptably sedated at rest. NSAIDs and radiotherapy are usually essential adjuncts where possible. It is appropriate to try a breakthrough dose of quick-acting oral morphine 20-30 minutes before movement. However, surgical intervention (e.g. for spinal stabilization or anaesthetic block techniques) should be considered sooner rather than later.


Bisphosphonates should be considered in bone pain secondary to breast carcinoma an to multiple myeloma; intravenous pamidronate, in doses ranging from 60-90 mg, 2-4 times weekly, is used. Work to assess the role of bisphosphonates in other cancers, such as prostatic carcinoma, is underway. Whilst intravenous pamidronate is successful in some acute-pain situations, there is no way at present of predicting for whom it will be effective.

Anaesthetic techniques

In a minority of patients, carefully managed drug treatment, with or without palliative radiation or chemotherapy or hormonal therapy, fails to provide acceptable pain relief or does so only at the cost of intolerable side-effects. In these cases anaesthetic techniques should be considered. Anaesthetic techniques should also be considered in acute situations e.g. pathological fracture awaiting internal fixation. Consider the early use of anaesthetic techniques if:

♦ Failure of pharmacological management due to side-effects in the presence of opioid-responsive pain; this may benefit from spinal opioids

♦ Pancreatic pain—coeliac plexus block

♦ Nerve infiltration—brachial plexus block or epidural local anaesthetic/steroids if lumbosacral nerve pain

♦ Unfixed/unfixable fractures or unstable bones

Non-drug methods

These should be used in conjunction with drug treatment and include:

♦ Occupational therapy

♦ Physiotherapy

Relaxation therapies

♦ Transcutaneous electrical nerve stimulation (TENS)


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