Opioid Analgesia for children

1. Pre-reading about Opioid
Analgesia for Children
Royal Children’s Hospital
Melbourne Australia

2. The use of opium
• Opium was first discovered in pre-
biblical times; derived from the opium
poppy
• Opium was widely used from the middle
ages in a medicine known as “tincture of
opium” or Laudanum
Children's Pain Management Service,
RCH, Melbourne

3. What are opioids?
• All drugs with morphine-like actions are
described as opioids
• Opioids were originally derived from the
opium poppy (papaver somniferum)
which has 25 alkaloids
• Only two of these alkaloids have any
analgesic action: morphine and codeine
Children's Pain Management Service,
RCH, Melbourne

4. GlaxoSmithKline supplies ~25% of the world's
medicinal opiate needs from opium poppies
grown by farmers in Tasmania
Children's Pain Management Service,
RCH, Melbourne

5. Opioid or Narcotic?
Opioid:
natural, semi-synthetic and synthetic drugs that
relieve pain by binding to opioid receptors in the
nervous system
Narcotic:
obsolete term for opioid, because governments
and media use the term loosely to refer to a
variety of substances of potential abuse including
opioids, cocaine and other substances
Children's Pain Management Service,
RCH, Melbourne

6. Opiate or Opioid?
Opiate:
term used to refer to drugs derived from
the opium poppy, for example, morphine
(thus excluding synthetic opioids such
as fentanyl)
Opioid:
refers to any substance with morphine-
like activity including natural, semi-
synthetic and synthetic opioids
Children's Pain Management Service,
RCH, Melbourne

7. How morphine was named
• In 1805, a German pharmacist
(Serturner) isolated an opium alkaloid
• He named it morphine (after Morpheus,
the Greek god of sleep)
Children's Pain Management Service,
RCH, Melbourne

8. How do opioids work?
• All opioids bind to opioid receptors
• Opioid receptors are located in the:
• peripheral nervous system
• spinal cord
• brain
• When opioids bind to these receptors
they affect the transmission of pain
signals to the brain
Children's Pain Management Service,
RCH, Melbourne

9. Opioid receptors
There are three main types of opioid
receptors:
• mu ()
• delta ()
• kappa ()
These receptors have multiple actions
Children's Pain Management Service,
RCH, Melbourne

10. Mu() opioid receptors
• The mu receptors are associated with:
• analgesia
• side effects
• Mu receptors are subtyped: mu-1 & mu-
2
Children's Pain Management Service,
RCH, Melbourne

11. Action at the mu() receptor
• Mu-1 receptor is responsible for
analgesia
• Mu-2 receptor is responsible for the
opioid side-effects:
• respiratory depression
• cardiovascular depression
• decreased gastrointestinal motility
• sedation
• euphoria
• urinary retention
Children's Pain Management Service,
RCH, Melbourne

12. Mu-1 specific opioids do not exist
• The opioid action of all known natural
and synthetic opioids at mu receptors is
non-specific
• No opioid has yet been found or
developed that acts only on the mu-1
receptor
Children's Pain Management Service,
RCH, Melbourne

13. Opioid receptor antagonist
• Naloxone (NarcanTM) is a pure opioid
receptor antagonist
• Naloxone displaces opioids bound to
opioid receptors
• The duration of action of naloxone is 30-
60 minutes
• Thus naloxone may wear off before a
longer acting opioid and symptoms of
opioid toxicity may reappear
Children's Pain Management Service,
RCH, Melbourne

14. Indications for opioids
• Pain
• Intractable diarrhoea
• Cough
• Air hunger (end-stage respiratory
failure)
Children's Pain Management Service,
RCH, Melbourne

15. Contraindications to opioids
The following are not absolute
contraindications,
as opioids may be used in small titrated
doses:
• depressed conscious state (relative)
• head injury (relative)
• respiratory insufficiency (relative)
Children's Pain Management Service,
RCH, Melbourne

16. Precautions
Neonates:
• lower doses may be required
• decreased clearance of opioids and
opioid metabolites
Children's Pain Management Service,
RCH, Melbourne

17. Side effects of opioids
• Opioid side effects occur regardless of
which opioid is used
• Side effects are usually dose-related
Children's Pain Management Service,
RCH, Melbourne

18. Side effects of opioids
• respiratory
depression
• sedation
• euphoria
• pinpoint pupils
• itch
• muscle rigidity
• bradycardia
(with high doses)
• vasodilation
• hypotension
• urinary retention
• nausea & vomiting
• delayed gastric emptying
• constipation
Children's Pain Management Service,
RCH, Melbourne

19. Respiratory depression
• Respiratory depression from opioids is
due to the combination of sedation,
decreased tidal volume, reduced
respiratory rate and a drop in oxygen
saturation
• This results in hypoxia and raised
carbon dioxide levels, which leads to
further sedation and further respiratory
depression
Children's Pain Management Service,
RCH, Melbourne

20. Different opioid drugs
Morphine:
• pure opioid
• powerful mu agonist
• varied formulations (oral, IV/IM/SC)
• oral immediate release eg Morphine mixture/tabs,
KapanolTM
• oral sustained release eg MS ContinTM
• the metabolites are M3G and M6G
• morphine 3 glucuronide & morphine 6 glucuronide
Children's Pain Management Service,
RCH, Melbourne

21. Different opioid drugs
Codeine:
• pure opioid
• mu agonist
• prodrug (converts to another form)
• converts to morphine
• 7-10% of some population groups are
unable to convert codeine to morphine, thus get no analgesia
effect while others are rapid converters and become sedated.
Children's Pain Management Service,
RCH, Melbourne

22. Different opioid drugs
Pethidine: (rarely used at RCH)
• synthetic opioid
• mu agonist
• metabolite is nor-pethidine
• pethidine infusions should be avoided
due to the concerns of nor-pethidine
toxicity
Children's Pain Management Service,
RCH, Melbourne

23. Different opioid drugs
Fentanyl:
• synthetic opioid
• mu agonist
• structurally similar to pethidine
• short acting, but a lipophilic (fat soluble)
drug which may result in accumulation
• no metabolites
Children's Pain Management Service,
RCH, Melbourne

24. Different opioid drugs
Hydromorphone (DilaudidTM):
• synthetic opioid
• related to oxycodone and hydrocodone
• varied formulations (oral, IV/IM/SC,
epidural)
• the metabolites are H3G and H6G
• hydromorphone 3 glucuronide & hydromorphone 6
glucuronide
Children's Pain Management Service,
RCH, Melbourne

25. Different opioid drugs
Oxycodone:
• synthetic opioid
• related to hydrocodone and
hydromorphone
• similar strength to oral morphine
• sustained release version available
• OxycontinTM
Children's Pain Management Service,
RCH, Melbourne

26. Different opioid drugs
Dextropropoxyphene:
• synthetic opioid
• weak mu agonist
• preparations often mixed with other
analgesics
• eg combined with paracetamol as DigesicTM
Children's Pain Management Service,
RCH, Melbourne

27. Different opioid drugs
Methadone:
• synthetic opioid
• strong mu agonist
• very long acting opioid
• useful for neuropathic pain
• no metabolites
Children's Pain Management Service,
RCH, Melbourne

28. Different opioid drugs
Tramadol:
• not a true opioid
• has opioid and non-opioid properties
• non-opioid effects are via nor-adrenaline
and serotonin pathways
• active metabolite (M1) has mu receptor
affinity
Children's Pain Management Service,
RCH, Melbourne

29. Misbeliefs about opioids and children
• ‘Children are more sensitive to opioids’
• ‘Infants and neonates do not feel pain’
• ‘Pain is character building’
• ‘Children have little requirements for
opioids’
• ‘Children can be easily overdosed’
• ‘The use of opioids leads to addiction’
Children's Pain Management Service,
RCH, Melbourne

30. Misunderstanding of definitions
• Confusion about the definitions of
addiction, tolerance, withdrawal and
the implications for patients are the
main reason that opioids are under
utilised
Children's Pain Management Service,
RCH, Melbourne

31. Definitions
• Addiction: psychological dependence
with compulsive drug use, and craving
for opioids for effects other than pain
relief
• Tolerance: when increased doses of a
drug is needed to produce the same
pharmacological effect
Children's Pain Management Service,
RCH, Melbourne

32. Definitions
• Withdrawal: a cluster of physiological
signs and symptoms, which occur after
sudden ceasing of some drugs
• Dependency: when sudden absence of
an opioid produces physical withdrawal
syndrome
Children's Pain Management Service,
RCH, Melbourne

33. Fear of addiction
• Fear of creating addiction in patients
contributes to the under use of opioid
analgesics (Ferrell BR et al, J Pain & Sympt Manage,
1992)
• The risk of addiction for patients having
opioids for medical reasons is
extremely low
• Tolerance to an opioid does not mean
the patient has an addiction
Children's Pain Management Service,
RCH, Melbourne

34. Caring for children receiving opioids
• Accurate documentation
• Correct dose of opioid
• Correct and safe delivery of opioid
• Observation of vital signs
• Minimal side effects
• Documented pain scores
• Adequate analgesia achieved
Children's Pain Management Service,
RCH, Melbourne

35. Caring for children receiving opioids
• Monitoring
 sedation score
 pain score
 respiratory effort, rate, depth
 oxygen saturation
 heart rate
Children's Pain Management Service,
RCH, Melbourne

36. Combining opioids
• It is not good practice to administer more than
one opioid at a time, as this increases the risk of
side effects
• At RCH we do not administer morphine and
codeine together
• An exception is when long-acting and short-
acting formulations of the same opioid are
administered for optimal analgesia in patients
with severe pain
eg MS Contin & morphine mixture OR Oxycontin & oxycodone
Children's Pain Management Service,
RCH, Melbourne

37. Optimising opioid analgesia
• The child needs to be comfortable
• The child needs to be able to breathe
deeply/cough without pain
• The child needs to be able to mobilise
freely without being limited by pain
Children's Pain Management Service,
RCH, Melbourne

38. Optimising opioid analgesia
• Pre-emptive pain management is
important
• Treat side effects early and adequately
• Adjunctive analgesia may be required
• Children should not be sedated
• Believe the child’s pain assessment
• Act on assessment
Children's Pain Management Service,
RCH, Melbourne

39. Children's Pain Management Service
• The Children's Pain Management
Service supervises most patients with
opioid infusions at Royal Children's
Hospital
• CPMS can be contacted at all times on
pager 5773
Children's Pain Management Service,
RCH, Melbourne

40. Finally…
Optimal pain management
is the right of all patients
and the responsibility of
all health professionals
Children's Pain Management Service,
RCH, Melbourne