Morphine is the strong opioid of choice.
pains (visceral and soft tissue) respond well to morphine and
some (bone, nerve and colic) do not.
morphine should usually be started in a dose of 5mg to 10mg
every 4 hours when moderate analgesics are no longer
effective. Never prescribe PRN. A laxative and an anti-emetic
must be started at the same time.
doses morphine is an analgesic and does not cause euphoria.
Mild drowsiness may occur for the first 2 to 3 days of
treatment. The principle is to increase the dose in steps
until the patient is pain-free but still alert.
patient who is pain-free becomes drowsy, the dose
should be reduced. When morphine is used carefully by
finding the correct dose for a particular patient’s pain,
there are no dangers of needing escalating doses, or of
causing respiratory depression.
myths of tolerance, addiction, and respiratory depression
have contributed to the poor management of cancer pain. These
myths are based on single dose studies in animals and humans
without pain. Chronic pain prevents these side effects.
(morphine sulfate controlled release) is a very useful
drug in terminal care (particularly for home care) when
properly administered on a 12-hourly schedule. It is
ordinary morphine in a slow release form. Its bioavailability
is excellent. (Absorption of MS-Contin may be delayed by a
usually safe to start MS-Contin 30mg every 12 hours for pain,
unless the patient is debilitated or elderly. A starting dose
of MS-Contin 15mg every 12 hours is recommended for elderly or
debilitated patients. (Start MS-Contin 10mg every 12 hours for
these patients in countries where 10mg tablets are available.)
Start haloperidol 1.5 mg at bedtime simultaneously to prevent
nausea. Start a laxative (Peri-Colace or Senokot-S)
usually best to titrate the dose using 4-hourly oral morphine.
Once the patient is pain-controlled on a regular 4-hourly
dose, then change to the equivalent dose of MS-Contin
given every 12 hours. The total dose of MS-Contin over 24
hours is the same as the total dose of 4-hourly morphine.
(4-hourly dose of morphine x 3=12-hourly dose of MS-Contin.)
of oral morphine
prescribe MS-Contin on a 12-hourly regime. Increase the dose
if pain occurs. A 6-hourly or 8-hourly regime should be
avoided, as it can cause episodes of drowsiness due to peaks
of absorption. When increasing the dose, it is safe to use the
MS-Contin increments shown above. If the patient is pain-free
and drowsy, reduce the dose.
In a study
of 38 patients switched from oral MS-Contin to the same dose
rectally, pain control was maintained in all the patients. The
dose range (using 30mg tablets) was between 2 and 10 tablets
every 12 hours. The duration of use ranged from 1 to 30 days
(mean 11.5 days). None of the patients experienced any local
rectal side-effects such as irritation of burning. (Rectal
administration of MS-Contin is not approved by the FDA.)
patients on MS-Contin who have their pain controlled by other
means, such as nerve block. The sudden reduction in pain can
mean that the patient is getting too much morphine, and this
has caused severe respiratory depression. Change to an
equivalent dose of 4-hourly morphine before such
procedures, and observe the patient carefully afterwards.
it wrong to use morphine? It is wrong to use morphine
without proper assessment of the pain. Intermittent pains
(bone pain, nerve pain, colic) respond poorly or not at all to
morphine. Many pains (15%) are not related to the cancer
(heartburn, peptic ulcer, anal fissure, etc.) and will not
respond to morphine.
morphine be started too early? No. A common fear of
doctors is this: “If morphine is started now the patient’s
body will develop tolerance. Higher and higher doses will be
needed. When pain worsens later, it will no longer be
effective.” This does not occur. Used properly in chronic
pain, morphine is an analgesic with no properties of
tolerance. If the pain is constant the correct dose (the
one that controls the pain without causing drowsiness) can
remain constant – for weeks, for months, or even for years in
some cases. If the pain is reduced, the dose of morphine will
need to be reduced. If the pain increases, the dose will need
to be increased.
the correct dose? The correct dose of morphine is the dose
that relieves the pain without causing drowsiness. To find the
correct dose, the principle is to titrate – start with a low
dose and then promptly increase it until the pain is relieved.
Mr. J.P. has carcinoma of the larynx with metastases in the
right cervical nodes. He enjoys going to the pub for a drink
in the evenings, but finds that his neck and right shoulder
ache. Codeine 60mg every 4 hours has previously relieved the
pain, but the ache is getting worse. Mr. J.P. is frightened
of starting morphine, saying “It’s only an ache, if it turns
into pain I’ll let you know.” Before long, even wearing his
heavy tweed jacket makes his shoulder ache, and an alert
home care nurse observes that he has stopped going to the
pub. He is persuaded to try oral morphine, 10mg every 4
hours. His ache is better, and he is able to go out again in
the evenings. In fact, although he is much better, the ache
returns about 3½ hours after each dose, and he has about ½
hour of increasing pain before each dose. The dose of
morphine is therefore increased to 20mg every 4 hours, and
he is completely free of the ache. He is changed to MS-Contin
60mg every 12 hours for the sake of convenience. Mr. J.P. is
delighted, and so is the owner of the pub he frequents!
the patient gets drowsy? In any patient on morphine the
rule is this: if pain-free and drowsy, reduce the dose. Be
sure to exclude other causes of drowsiness (hypercalcemia, for
some pains respond poorly to morphine. Neuralgias, bone
pains, incidental pains like tension headaches, anal fissures,
abscesses, colics (gut, renal and biliary), and distention
pains like gastric distention and tenesmus are among those.
Increasing the dose of morphine for those pains will make the
patient drowsy without relieving the pain.
a maximum safe dose of morphine? No. The principle is
this: if 4-hourly morphine relieved the pain a bit, increase
the dose in steps until the pain is relieved, using the
increments of 5mg, 10mg, 20mg, 30mg, 45mg, 60mg, etc. The dose
should be increased every four hours if there is still pain.
90% of patients with morphine-responsive pains will have
relief within that 5mg to 60mg range, but occasionally, as the
case history below shows, the dose may need to be 500mg or
Mr. N.C. is 27, a computer programmer, with a hepatoma. A
previous embolization for liver pain had little effect, and
his family doctor prescribed oral morphine 10mg every 4
hours. He found that taking a double dose every 2 hours was
helping but not abolishing the pain. He was seen at the
hospice outpatient clinic, and the dose was increased to
60mg every 4 hours. This abolished the pain, and he returned
to work. A week later he was still pain-free, and was
changed to MS-Contin 180mg every 12 hours – to make it
easier to take as a twice-a-day regime. Three weeks later he
again had severe right-sided pain, and was admitted to the
hospice. Morphine was re-started at a dose of 90mg every 4
hours and was increased after one dose to 150mg every 4
hours. He was then pain-free, and after 36 hours returned
home and went back to work. A week later in the clinic he
was complaining of breakthrough pain between doses. The dose
of morphine was increased to 300mg every 4 hours, with a
double dose (600mg) at bedtime to allow him 8 hours of
sleep. On this regime he remained pain-free for 8 weeks,
working full time, driving his car, and not feeling drowsy.
higher doses of morphine the incremental increases have to be
bigger. (For example, increase straight from 150mg to
300mg 4-hourly. The dose has been doubled, as when increasing
from 5mg to 10mg, or from 10mg to 20mg.)
dose of morphine should you use for the patient with severe
pain, when you are unsure of the analgesic history? The
principle is to start with a low dose and observe frequently.
Mr. A. U. is 67, is known to have advanced carcinoma of the
bronchus, and presents with severe continuous lateral chest
pain. He is unable to give a detailed history. His wife says
he has been taking a lot of analgesics of various kinds
recently, but has never had morphine. We start with a low
dose – morphine 5mg IM – and observe. (In severe pain the IM
route is initially better than oral medication as it works
faster.) After 20 minutes Mr. A.U. still complains of severe
pain – give morphine 10mg IM and observe. After another 20
minutes, the pain is easing but still troublesome – another
10mg morphine IM. Mr. A. U. is now pain-free and drowsy. (He
may be drowsy at this stage because of previous lack of
sleep and exhaustion.) We re-assess the patient 4 hours
after the first injection and he is pain-free. He has had
25mg morphine IM, so we prescribe morphine 25mg IM every 4
hours. (if he remains pain-free but drowsy, we reduce the
dose.) Mr. A.U. is able to swallow and is not feeling sick
(nausea causes gastric stasis and prevents absorption) so we
promptly change to oral medication – 50mg morphine orally
every 4 hours (twice the IM dose!) and observe.
the best route for morphine? Morphine is effective by all
routes: oral, rectal, sublingual, subcutaneous, intramuscular,
intravenous. The sublingual dose is equivalent to the oral or
rectal dose. When changing from the oral or rectal route to
one of the other systemic routes (subcutaneous, IM or IV), cut
the dose in half.
infusions of morphine are often used if a patient has a
permanent indwelling intravenous catheter. This route can be
effective (although it may well not be ideal from the
patient’s point of view and is rarely used for analgesia in
Britain). It has one major disadvantage: tolerance
sometimes develops to morphine administered by the IV route
(either infusion or bolus). The patient needs higher and
higher doses every 1 to 2 hours, and pain can escape control.
Transferring such patients to oral morphine, or to morphine by
continuous subcutaneous infusion, gives better pain
control with lower doses. The reason why tolerance can develop
rapidly to IV morphine, but not by other routes,
What about tolerance?
commonly fear that tolerance will occur. (“I didn’t take the
pain medication in case it doesn’t work later when I’ll need
it more.”) This misconception needs to be explained.
Tolerance (needing higher and higher doses with diminishing
analgesic effect) does not occur when oral, rectal,
sublingual, subcutaneous or intramuscular morphine is used to
control visceral or soft tissue cancer pain. (As explained
above, it may occur in IV use.) The fear of tolerance is based
on the clinical mis-use of morphine in pains poorly responsive
to morphine, such as nerve pain, bone pain or colicky pain.
(Morphine is ineffective for these pains, and the tendency is
to give higher and higher doses, which are also ineffective.)
In fact, 90% of patients never need more than 60mg of oral
morphine every 4 hours, irrespective of duration of use.
The dose of
morphine may increase for the first few weeks as the dosage is
titrated (starting with a low dose, then increasing). Dose
increase is usually of the order of 30% over two weeks.
Once a pain is controlled by morphine, the patient can stay on
the same dose for weeks or months. The longer a patient is
on morphine, the more likely he is to have a decrease
Mr. J.M., age 55, with hepatic liposarcoma and liver pain,
was well controlled on oral morphine 150mg every 4 hours. On
this dose he was pain-free and mentally alert (demonstrated
by his ability to complete The Times crossword puzzle each
day). After some weeks he noticed some drowsiness, and he
had one hallucination (he thought he saw someone sitting on
his bed). The dose of oral morphine was decreased to 120mg
every 4 hours, and after a few days (because he still felt a
bit drowsy) to 90mg every 4 hours. He remained pain-free on
this dose until he died 2 months later.
What about addiction?
Patients often fear addiction. Patients with chronic pain do
not and cannot get addicted to morphine. This is proved
clinically by seeing patients whose pain is abolished (with a
nerve block, for example) when even high doses of morphine
used for several months can be stopped immediately with no
withdrawal effects. Patients who are terminally ill still
often fear that they may become addicted to morphine. They and
their families can be reassured. This cannot happen when
morphine is correctly used to control their pain.
Mr. N.C., who was well controlled on 300mg morphine every 4
hours (see case history earlier), had increasingly severe
pain. For three weeks he was pain-free on 600mg morphine
every 4 hours, but he then needed a further dose increase to
1000mg morphine every 4 hours. At this point a celiac plexus
nerve block was performed for pain control and this
abolished his pain. He stopped all morphine the same day and
he suffered no withdrawal effects (proving he was not
addicted despite the high doses).
A month later he suffered a different pain, this time due to
an ileofemoral thrombosis in his left leg. Morphine was
started while he was in the hospital for monitoring of anti-coagulant therapy, and the dose was gradually increased to
60mg every 4 hours. This dose controlled the pain for 2 to 3
hours, and he was told (wrongly) that higher doses could not
be given. On returning to hospice care his morphine dose was
increased to 150mg every 4 hours, and his pain was
controlled. After a week his pain decreased as the
thrombosis resolved and he became drowsy. Morphine was
decreased to 100mg every 4 hours. He remained pain-free and
alert until his death 10 days later. Mr. N. C. had not
developed tolerance to morphine. A different pain required a
about narcotic addicts? Known narcotic addicts with cancer
pain respond normally to morphine. The dose is titrated, and
the pain is controlled. The regular use of oral morphine to
control pain does not have any euphoric effects (which usually
occur only after an IV bolus of a relatively high dose).
should never be withheld from a patient with proven cancer “in
case the patient is a narcotic addict”. If the patient is
pretending to have pain in order to get morphine for his
addiction, then oral doses every 4 hours will bring no
satisfaction, which will be clinically obvious.
What about respiratory depression?
Respiratory depression does not occur when morphine is
correctly used to control pain.
study of 20 cancer patients (12 with COPD) taking at least
100mg of morphine per day for at least 7 days, only one had an
elevated pC02 level. As long as morphine is titrated, and the
dose is reduced if drowsiness occurs, there is no danger of
respiratory depression. Following pain relieving procedures
(such as a nerve block), morphine should be stopped. If
pain persists morphine should be promptly restarted in low
dosage and titrated.
about drug interactions? Morphine can be safely prescribed
with all other drugs except monoamine oxidase (MAO)
inhibitors, which are occasionally used as
anti-depressants. Hypertensive crisis or mental excitation can
about morphine and alcohol? It is safe to have an
alcoholic drink. Many patients taking morphine enjoy their
accustomed cocktail each evening. In fact, most British in-patient hospices have a small bar or a drinks trolley for just
The author and publisher have taken
precautions to ensure that the information in this book is
error-free. However, readers must be guided by their own
personal and professional standards of good practice in
evaluating and applying recommendations made herein. The
contents of this book represent the views and experience of
the author, and not necessarily those of the publisher.