Management of pain

1. WHO Analgesic Ladder
By James Kateregga

2. Objectives
• Review the World Health Organization (WHO) analgesic ladder
• Discuss treatment for treat mild, moderate, or severe pain
• Review additional treatment principles when using opioids
2

3. Background
• The WHO analgesic ladder was introduced in 1986
– 3-step ladder for adults
– Updated in 2012 to include 2-step ladder for children
• Framework for pharmacological management of pain
• 80-90% of patients are effectively treated using the WHO 3-
step approach
http://www.who.int/cancer/palliative/painladder/en/ 3

4. 4
Mild pain
Moderate pain
Severe pain
Step 1
Non-opioid
Step 2
Weak opioid
Step 3
Strong opioid
+/- adjuvant
+/- non-opioid
+/- adjuvant
+/- non-opioid
+/- adjuvant
Consider prophylactic laxatives to avoid constipation
Step up if pain
persists
or increases
Step up if pain
persists
or increases
Non-opioids ibuprofen or other NSAID, paracetamol (acetaminophen), or aspirin
Weak opioids codeine, tramadol, or low-dose morphine
Strong opioids morphine, fentanyl, oxycodone, hydromorphone, buprenorphine
Adjuvants antidepressant, anticonvulsant, antispasmodic, muscle relaxant, bisphosphonate, or
corticosteroid
Combining an opioid and non-opioid is effective, but do not combine drugs of the same class.
Time doses based on drug half-life (“dose by the clock”); do not wait for pain to recur
Adapted by Treat the Pain from World Health Organization http://www.who.int/cancer/palliative/painladder/en/ (accessed 7 November 2013)
WHO Analgesic Ladder: adults
4

5. Using the WHO ladder for adults
Beating Pain, 2nd Ed. APCA (2012) 5
• Mild pain - start with a non-opioid, for example with regular paracetamol or non-
steroidal anti-inflammatory drug (NSAID), then move up steps if pain remains
uncontrolled
• Moderate - start with a weak opioid, for example, codeine or low-dose morphine
• Severe - start with a strong opioid, for example, morphine, to control pain early
• Adjuvants can be used at any step

6. Step 1 – mild pain: non-opioids
Paracetamol
• Adult dose: 500mg-1g by mouth every 6 hours; maximum daily
dose 4g
• Note: Hepatoxicity can occur if more than the maximum dose
is given per day
• Paracetamol can be combined with an NSAID
Beating Pain, 2nd Ed. APCA (2012) 6

7. Step 1 – mild pain: non-opioids
Ibuprofen (NSAID)
• Adult dose: 400mg by mouth every 6-8 hours; maximum daily
dose 1.2g
• Give with food and avoid in asthmatic patients
• The maximum dosing limit should be lowered in patients with
liver impairment
Beating Pain, 2nd Ed. APCA (2012) 7

8. Step 1 – mild pain: non-opioids
Diclofenac (NSAID)
• Adult dose: 50mg by mouth every 8 hours; maximum daily
dose 150mg
• Give with food and avoid in asthmatic patients
Beating Pain, 2nd Ed. APCA (2012) 8

9. Cautions with NSAIDs
NSAIDs can cause serious side effects, particularly after using for
more than 7-10 days
• Gastro-intestinal (GI) bleeding or renal toxicity
– If GI symptoms occur, stop and give H2 receptor antagonist.
e.g. Ranitidine
• Not for use in patients with renal failure
Beating Pain, 2nd Ed. APCA (2012) 9

10. Step 2 – moderate pain: weak opioids
Tramadol
• Adult dose: 50-100mg by mouth every 4-6 hours
• Start with a regular dose and increase if no response (dose
limit: 400mg/day)
• Use with caution in epileptic cases, especially if patient is
taking other drugs that lower the seizure threshold
• May cause serotonin syndrome in patients on other
serotonergic medications
Beating Pain, 2nd Ed. APCA (2012) 10

11. Step 2 – moderate pain: weak opioids
Codeine
• Adult dose: 30-60mg by mouth every 4 hours; maximum daily
dose 240mg
• If pain relief is not achieved with 240mg/day, move to strong
opioid
• Can be combined with Step 1 analgesic
• Give laxative to avoid constipation unless patient has
diarrhoea
• Genetic variability can lead to variable rates of metabolism
which may make codeine ineffective or lead to excessive
side effects
Beating Pain, 2nd Ed. APCA (2012) 11

12. Step 2 – moderate pain: weak opioids
Low-dose morphine
• Some palliative care experts recommend using low-dose
morphine in step 2 because it is associated with fewer side
effects compared to other weak opioids
Beating Pain, 2nd Ed. APCA (2012) 12

13. Step 3 – severe pain: strong opioids
Morphine
• “Gold standard” against which other opioid analgesics are
measured
• When used correctly, patients don’t become dependent or
addicted, tolerance is uncommon, and respiratory depression
doesn’t usually occur
Beating Pain, 2nd Ed. APCA (2012) 13

14. Step 3 – severe pain: strong opioids
Less commonly used strong opioids (covered in separate lecture)
• Fentanyl
• Oxycodone
• Hydromorphone
• Methadone
Beating Pain, 2nd Ed. APCA (2012) 14

15. Step 3 – severe pain: strong opioids
Morphine
• Adult starting dose: 2.5–20mg by mouth every 4 hours
depending on age, previous use of opiates, etc.
– Patients changing from regular administration of a Step 2
opioid: 10mg by mouth every 4 hours
– If the patient has experienced weight loss from sickness or
has not progressed onto Step 2 analgesics: 5mg by mouth
every 4 hours
– Frail or elderly patients: 2.5mg by mouth every 6 to 8
hours due to the likelihood of impaired renal function
Beating Pain, 2nd Ed. APCA (2012) 15

16. Step 3 – severe pain: strong opioids
• Morphine is available as immediate-release or sustained-
release formulations
• Immediate-release
– Dose every 4 hours
– Use to titrate starting dose and treat breakthrough pain
Beating Pain, 2nd Ed. APCA (2012). 16

17. Step 3 – severe pain: strong opioids
• Sustained-release (or slow-release)
– Dose every 8-24 hours, depending on the formulation
– After determining daily dose with immediate-release
morphine, can change to sustained-release morphine,
being careful to adjust dose as needed to maintain the
total daily dose
• Priority should be given to making immediate-release
formulations available
Beating Pain, 2nd Ed. APCA (2012). 17

18. Step 3 – severe pain: strong opioids
Morphine
• Increase dose gradually until pain is controlled
• The correct morphine dose is the one that gives pain relief
without side effects: there is no ‘ceiling’ or maximum dose
Beating Pain, 2nd Ed. APCA (2012) 18

19. Caution: pethidine
Pethidine is not suitable for patients with chronic pain
• It has a faster onset of action and a shorter duration of action
than morphine and needs more frequent dosing: every 2–3
hours
• Pethidine is metabolised to norpethidine which has side
effects inducing central nervous system excitability including
mood changes, tremors, myoclonus (sudden jerking of the
limbs) and convulsions
• Pethidine was removed from the WHO essential medicines list
in 2003 because it was judged to be inferior to morphine due
to its toxicity on the central nervous system and is generally
more expensive than morphine
Beating Pain, 2nd Ed. APCA (2012); The Selection and Use of Essential Medicines – WHO Technical Report Series, No. 920. 2003. 19

20. Treatment principles
• By the mouth: Use the oral route whenever possible
• By the clock: Administer analgesics according to regular
schedule based on duration of effectiveness rather than “as
needed”, except when titrating dose
• By the ladder: Use the WHO analgesic ladder. If after giving
the optimum dose an analgesic does not control pain, move
up the ladder; do not move sideways in the same level
• By the patient: The right dose is the one that relieves pain.
Titrate the dose upwards until pain is relieved or side effects
prevent moving up further
Beating Pain, 2nd Ed. APCA (2012) 20

21. Stopping or changing opioids
• When stopping an opioid, reduce daily dose by 25% each day
to avoid symptoms of withdrawal
• When changing from one opioid to another, be mindful of
the need to convert doses
– Check reference materials or consult an expert
Oxford Textbook of Palliative Medicine (2010) 21

22. Key treatment principle: prophylactic laxatives
• All patients on opioids are at high risk for constipation, and
laxatives should be ordered unless contraindicated
Beating Pain, 2nd Ed. APCA (2012) 22

23. Take home message
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• The WHO ladder, an important tool of managing pain, can
effectively treat 80-90% of the patients at this facility
• For non-responsive pain, please refer to a pain specialist

24. Practical Assessment
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Esther, a 28 year-old woman with cancer, reports a pain score of 5 out
of 10. Which medicines would you consider prescribing?
A. Codeine
B. Tramadol
C. Low-dose morphine
D. Any of the above
If you prescribe low-dose morphine, what is Esther’s starting dose?
2.5mg every four hours
What other prescriptions must be written at the same time?
Laxatives

25. References
• African Palliative Care Association. Beating Pain: a pocketguide for pain
management in Africa, 2nd Ed. [Internet]. 2012. Available from:
http://www.africanpalliativecare.org/images/stories/pdf/beating_pain.pdf
• African Palliative Care Association. Using opioids to manage pain: a pocket guide
for health professionals in Africa [Internet]. 2010. Available from:
http://www.africanpalliativecare.org/images/stories/pdf/using_opiods.pdf
• Amery J, editor. Children’s Palliative Care in Africa [Internet]. 2009. Available from:
http://www.icpcn.org/wp-content/uploads/2013/08/Childrens-Palliative-Care-in-
Africa-Full-Text.pdf
• Kopf A, Patel N, editors. Guide to Pain Management in Low-Resource Settings
[Internet]. 2010. Available from: http://www.iasp-
pain.org/files/Content/ContentFolders/Publications2/FreeBooks/Guide_to_Pain_
Management_in_Low-Resource_Settings.pdf
• The Palliative Care Association of Uganda and the Uganda Ministry of Health.
Introductory Palliative Care Course for Healthcare Professionals. 2013.
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