1. WHO Analgesic Ladder
Disclaimer: This presentation contains information on the general principles of pain management. This presentation cannot account for individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician, or health care provider, to determine the best course of treatment for the patient. Treat the Pain and its partners assume no responsibility for any injury or damage to persons or property arising out of or related to any use of these materials, or for any errors or omissions.

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

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

4. WHO Analgesic Ladder: adults
Step 3
Strong opioid
Step 2
Weak opioid
Step up if pain persists or increases
Severe pain
Step up if pain persists or increases
Step 1 Non-opioid
Moderate pain
+/- non-opioid +/- adjuvant
Mild pain
+/- non-opioid +/- adjuvant
+/- adjuvant
Consider prophylactic laxatives to avoid constipation
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 4
Adapted by Treat the Pain from World Health Organization (accessed 7 November 2013)

5. Using the WHO ladder for adults
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
Beating Pain, 2nd Ed. APCA (2012)

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
Patients with liver impairment should use lower amounts or avoid use altogether
Paracetamol can be combined with an NSAID
Beating Pain, 2nd Ed. APCA (2012)

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
Beating Pain, 2nd Ed. APCA (2012)

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)

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 impairment
Beating Pain, 2nd Ed. APCA (2012)

10. Step 2 – moderate pain: weak opioids
Tramadol
Adult dose: mg 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)

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)

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)

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)

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)

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)

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).

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).

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)

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

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)

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)

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)

23. Take home message
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
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] Available from:
African Palliative Care Association. Using opioids to manage pain: a pocket guide for health professionals in Africa [Internet] Available from:
Amery J, editor. Children’s Palliative Care in Africa [Internet] Available from: Africa-Full-Text.pdf
Kopf A, Patel N, editors. Guide to Pain Management in Low-Resource Settings [Internet] Available from: 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