1. Treatment in children 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. Last updated on January 12, 2015

2. Objectives Review methods of assessing pain in children Discuss treatment options and dosing for children based on the age of the child and their level of pain 2

3. Three ways to assess pain in children Ask the child: FACES scale Ask the parent or caregiver – Ask about previous exposure to pain, verbal pain indicators, usual behavior or temperament Observe the child: FLACC scale The child is the best person to report their pain Children’s Palliative Care in Africa, 20093

4. Wong-Baker FACES scale Use in children who can talk (usually 3 years and older) Explain to the child that each face is for a person who feels happy because he has no pain, or a little sad because he has a little pain, or very sad because he has a lot of pain Ask the child to pick one face that best describes his or her current pain intensity Record the number of the pain level that the child reports to make treatment decisions, follow-up, and compare between examinations Palliative Care for HIV/AIDS and Cancer Patients in Vietnam, Basic Training Curriculum: Harvard Medical School, Centre for Palliative Care (2007)4

5. FLACC scale ICPCN (2009): Adapted from Merkel et al5 Use in children less than 3 years of age or older children who can’t talk Use it like an APGAR (Appearance, Pulse, Grimace, Activity, Respiration) score, arriving at a score out of 10

6. Practice using FLACC scale Samuel is 18 months old. You observe that he is withdrawn, kicking his legs, and squirming. He is constantly crying or screaming, but is calmed down by breastfeeding. 6 CategoryScore Face Legs Activity Cry Consolability Total Score 1 1 2 1 2 1 1 2 1 2 1 2 1 2 1 1 2 1 2 1 7

7. Practice using FLACC scale Samuel is 18 months old. You observe that he is withdrawn, kicking his legs, and squirming. He is constantly crying or screaming, but is calmed down by breastfeeding. 7 CategoryScore Face Legs Activity Cry Consolability Total Score 1 1 2 1 2 1 1 2 1 2 1 2 1 2 1 1 2 1 2 1 7

8. 8 Mild pain Moderate or Severe pain Step 1 Non-opioid Step 2 Strong opioid +/- adjuvant +/- non-opioid +/- adjuvant Consider prophylactic laxatives to avoid constipation Step up if pain persists or increases Non-opioids Age>3 mos: ibuprofen or paracetamol (acetaminophen); Age<3 mos: paracetamol Strong opioids morphine (medicine of choice) or 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 Ref: Adapted by Treat the Pain from World Health Organization http://www.who.int/cancer/palliative/painladder/en/ (accessed 7 November 2013) WHO Analgesic Ladder: Pediatric 8

9. WHO ladder: pediatric Recently updated guidelines from the World Health Organization (WHO) recommend using a 2-step ladder which does not include the rung for weak opioids Weak opioids are not recommended for use in children – Codeine Safety and efficacy problems related to genetic variability that affects metabolism Low analgesic effect in infants and young children – Tramadol Data are lacking on safety and efficacy in children WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)9

10. Step 1: mild pain Paracetamol and ibuprofen are the only medicines in this step – No other NSAIDs are recommended Infants <3 months old – Only paracetamol is recommended Children >3 months old – Paracetamol or ibuprofen can be used WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)10

11. Dosing of Step 1 analgesics WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)11 Medicine<1 month1-3 months3 months-12 years Maximum daily dose Paracetamol5-10mg/kg every 6-8 hours 10mg/kg every 4- 6 hours 10-15mg/kg every 4-6 hours (max 1g at a time) 4 doses per day IbuprofenNot recommended5-10mg/kg every 6-8 hours 40mg/kg/day * Children with poor nutritional state may be more susceptible to toxicity at standard doses

12. Step 2: moderate or severe pain “There is no other class of medicines than strong opioids that is effective in the treatment of moderate and severe pain. Therefore, strong opioids are an essential element in pain management.” World Health Organization WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)12

13. Step 2: moderate or severe pain Morphine is the “medicine of choice” – Alternatives can be used if a child experiences intolerable side-effects As with adults, there is no maximum dose for opioids – Titrate upward to find the dose that relieves pain with tolerable side-effects Constipation is a common side effect, and all children taking opioids should also take a stimulant laxative and a stool softener WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)13

14. Starting dose for opioid-naïve neonates WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)14 MedicineRouteStarting dose MorphineIV/Sc injection25-50mcg/kg every 6 hours IV infusionInitial IV dose 25-50mcg/kg, then 5-10mcg/kg/hour 100mcg/kg every 4 or 6 hours FentanylIV injection1-2mcg/kg every 2 to 4 hours IV infusionInitial IV dose 1-2mcg/kg, then 0.5-1mcg/kg/hour *Administer IV morphine slowly over at least 5 minutes *IV doses are based on acute pain management and sedation. Lower doses are required for non-ventilated neonates *Administer IV fentanyl slowly over 3-5 minutes

15. Starting dose for opioid-naïve infants (1 mo-1 yr) WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)15 MedicineRouteStarting dose MorphineOral (immediate release)80-200mcg/kg every 4 hours IV/Sc injection1-6 months: 100mcg/kg every 6 hours 6-12 months: 100mcg/kg every 4 hours (max 2.5mg/dose) IV infusion1-6 months: Initial IV dose: 50mcg/kg, then: 10-30mcg/kg/hour 6-12 months: Initial IV dose: 100- 200mcg/kg then: 20-30mcg/kg/hour Sc infusion1-3 months: 10mcg/kg/hour 3-12 months: 20mcg/kg/hour *Administer IV morphine slowly over at least 5 minutes

16. Starting dose for opioid-naïve infants (1 mo-1 yr) WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)16 MedicineRouteStarting dose FentanylIV injection1-2mcg/kg every 2 to 4 hours IV infusionInitial IV dose 1-2mcg/kg, then 0.5- 1mcg/kg/hour OxycodoneOral (immediate release)50-125mcg/kg every 4 hours *IV doses of fentanyl are based on acute pain management and sedation dosing information

17. Starting doses for opioid-naïve children (1-12 yrs) WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)17 MedicineRouteStarting dose MorphineOral (immediate release)1-2 years: 200-400mcg/kg every 4 hours 2-12 years: 200-500mcg/kg every 4 hours (max 5mg) Oral (prolonged release)200-800 mcg/kg every 12 hours IV/Sc injection1-2 years: 100mcg/kg every 4 hours 2-12 years: 100-200mcg/kg every 4 hours (max 2.5mg) IV infusionInitial IV dose: 100-200mcg/kg, then 20-30 mcg/kg/hour Sc infusion20mcg/kg/hour *Administer IV morphine slowly over at least 5 minutes

18. Starting doses for opioid-naïve children (1-12 yrs) WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)18 MedicineRouteStarting dose FentanylIV injection1-2mcg/kg, repeated every 30-60 minutes IV infusionInitial IV dose 1-2mcg/kg, then 1mcg/kg/hour HydromorphoneOral (immediate release)30-80mcg/kg/hour every 3 to 4 hours (max 2mg/dose) IV/Sc injection15mcg/kg every 3 to 6 hours MethadoneOral (immediate release)100-200mcg/kg every 4 hours for the first 2-3 doses, then every 6 to 12 hours (max 5mg/dose initially) IV/Sc injection OxycodoneOral (immediate release)125-200 mcg/kg every 4 hours (max 5mg/dose) Oral (slow release)5mg every 12 hours *Administer IV fentanyl slowly over 3-5 minutes *Hydromorphone is a potent opioid and significant differences exist between oral and intravenous dosing. Use extreme caution when converting from one route to another. In converting from parenteral to oral hydromorphone, doses may need to be titrated up to 5 times the IV dose. Administer IV hydromorphone slowly over 2-3 minutes *Due to the complex nature and wide inter-individual variation in pharmacokinetics, methadone should only be commenced by experienced practitioners These opioids are more complex and should be started by an experienced provider

19. General principles Dose at regular intervals – Medicines should always be given on a regular schedule and not “as needed”, except for rescue doses Use the appropriate route of administration – Medicines should be given by the simplest, most effective, and least painful route Oral is preferred IV or subcutaneous, rectal, or transdermal are alternatives when oral is not feasible IM is discouraged because it is painful Adapt treatment to the individual child – Titrate to get to the correct dose WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses, WHO (2012)19

20. Side effects of opioids Opioids are generally well-tolerated Mild sedation for first 48 hours is normal while child catches up on sleep Constipation: treat with laxatives Pruritis: treat with topical treatments (calamine or hydrocortizone) or oral antihistamines Urinary retention: treat with carbachol or bethanechol; catheterization may be required Children’s Palliative Care in Africa, Amery (2009)20

21. Co-analgesia in children The WHO does not recommend corticosteroids or biphosphonates to treat pain in children Neuropathic pain in children – Consult an expert – WHO guidance in this area is limited due to lack of evidence WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses. WHO (2012)21

22. Procedural pain management principles Avoid non-necessary procedures Prepare for the procedure Involve the child and family Encourage the parents to be helpful and supportive Carry out procedures in child-friendly area away from the bed Use non-pharmacological and pharmacological interventions to manage pain and anxiety After completing the procedure, congratulate the child and instill a sense of achievement Children’s Palliative Care in Africa, Amery (2009)22

23. Procedural pain management Drugs to use Topical anaesthetic agents (EMLA cream) Local anaesthetic: S/c lidocaine (make sure it is at body temperature and buffer with sodium bicarbonate to reduce pain of administration) If anxiety, rather than pain, is the issue: sedate with benzodiazepine, pedichloryal (50-100mg/kg by mouth) or promethizine (5mg/kg by mouth) If pain is the issue: use opioids in treatment doses Children’s Palliative Care in Africa, Amery (2009)23

24. Take home messages Pain in children can be assessed using observation and easy tools Children as young as 3 years old can indicate their severity of the pain For children, the WHO analgesic ladder is 2 steps 24

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. World Health Organization. WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses [Internet]. 2012. Available from: http://www.who.int/medicines/areas/quality_safety/guide_perspainchild/en/ 25