Author: Danielle Cassidy, PharmD, BCPS Audience: continuing education for hospice nurses Background: describes common developmentally appropriate tools for assessing pain in children, general principles of pediatric pharmacology, common pharmacological interventions, side effects commonly associated with opioid medications & side effect management strategies.

1. Providing Quality Pediatric Pain
Management During End of Life Care
Danielle Cassidy, Pharm.D.
May 2012

2. Learning Objectives
 Describe common developmentally appropriate tools
for assessing pain in children.
 List some general principles of pediatric
pharmacology.
 List common pharmacological interventions for
treatment of pediatric pain.
 List side effects commonly associated with opioid
medications & management strategies.

3. Background

4. Background
 Pediatric pain is a commonly undertreated symptom &
many children experience pain at end of life.
 One study reported more than 60% of parents felt their
child received inadequate pain relief at the end of life13.
 An inpatient hospital study noted that 53% of children
dying from cancer reported well controlled pain after
initiating a pediatric palliative care program2.
 Estimated 50,000 infants, children, & adolescents die
each year in the United States.
 ~16,000 are attributable to complex chronic conditions.
 ~5,000 receive hospice or palliative care services.
 Overall progress of pediatric palliative/hospice care has
lagged significantly behind the strides made in
hospice/palliative care services for adults with terminal
illness.

5. Background: Common Misconceptions
 The American Academy of Pediatrics (AAP) & The
American Pain Society (APS) recommend pediatric
pain be recognized & treated more aggressively.
 Myths/Barriers
 Infants & children do not feel pain, or suffer less from it
than adults.
 Misunderstanding of how to quantify a subjective
experience.
 Lack of routine pain assessment.
 Lack of knowledge regarding analgesic dosing strategies.
 Fears of analgesic adverse effects, including respiratory
depression & addiction.
 Belief that preventing pain takes too much time & effort.

6. Background: Medical Conditions
Appropriate for Pediatric Palliative Care
 Conditions for which curative treatment is possible,
but may fail (e.g. advanced cancer, complex
congenital heart disease or airway anomalies).
 Conditions requiring intensive long-term treatment
aimed at maintaining the quality of life (e.g. HIV,
cystic fibrosis, epidermolysis bullosa, severe GI
disorders) .
 Progressive conditions where treatment is purely
palliative after diagnosis (severe metabolic
disorders, certain chromosomal abnormalities).
 Conditions involving severe, nonprogressive
disability, causing extreme vulnerability to health
complications (severe cerebral palsy, extreme
prematurity).
Himelstein BP, Hilden JM, et al. Pediatric Palliative Care. N Engl J Med 2004;350:1752-1762

7. Background: Overview of Pediatric Pain
 Pain can be nociceptive or neuropathic.
 Nervous system is fully developed to process
nociception by 26 weeks of gestation.
 Infants & young children experience a greater
neuronal response following noxious stimuli than
adults due to:
 More robust inflammatory response.
 Immature inhibitory pathways.
 Painful experiences can lead to long-term effects
such as lowered pain tolerance for months after the
event & behavioral issues.

8. Pediatric Pain Assessment

9. Pain Assessment
 Pediatric pain scales
 Observational (neonates & infants)
 Allows assessment of those unable to verbalize their pain.
 Simple self-report (preschool & school age children)
 Uses facial expressions or small objects to describe pain
intensity.
 Adult numerical pain scale, visual analog scale, verbal report
reserved for children 7 years & older.
 Caregiver input should be included in overall
assessment.
 Gold standard is self-report for any child able to verbalize
their pain.
 Children with chronic pain rapidly adapt & may not exhibit
some of the features used in these tools.

10. Acute Pain Assessment: Neonates
Scale Scale Indicators
Degree of Crying, Required oxygen, Increased vital
CRIES signs (heart rate &/or blood pressure), Expression (e.g.
grimace), & Sleeplessness.
Premature Infant Pain Gestational age (greater than or less than 36 weeks
Profile (PIPP) gestational age), behavioral state before painful
stimulus, change in heart, change in oxygen saturation,
brow bulge, eye squeeze, nasolabial furrow.
Neonatal Infant Pain Facial expression, breathing patterns, extremity muscle
Scale (NIPS) tone , & state of arousal.
Neonatal Pain, Scores can be adjusted for gestational age.
Agitation & Sedation Crying/Irritability, Behavior state (e.g. arousal,
Scale (N-PASS) movement), facial expression, muscle tone of
extremities, & vital signs.

11. Example of CRIES Scale
Krechel, SW and Bildner, J. CRIES: a new neonatal postoperative pain measurement score– initial testing of validity and
reliability. Paediatric Anaesthesia 1995;5 53-61.

12. Acute Pain Assessment: Observational
Scales for Nonverbal Young Children
Scale Measurement
FLACC For ages 2 months to 7 years. Measures physiologic
changes of the Face (degree of grimace), Legs (degree of
restlessness/tension), Activity (degree of agitation), Cry
(degree of crying); & Consolability (amount of physical
consoling needed to comfort child).
Cognitively R-FLACC, The Non-Communicating Children’s Pain
Impaired Checklist-Revised (NCCPC-R), & The Paediatric Pain Profile
(PPP).

13. Acute Pain Assessment: Simple Self Report
Scales for Verbal Young Children
Scale Measurement
FACES Ages 3 years & up. Uses 6 faces starting with a happy face &
progressing to a crying face. Explain to the child the 1st face has
no pain, the 2nd face has a little pain, the 3rd face has a little more
pain, the 4th has more pain still, the 5th face has a lot of pain, &
the 6th face is the worst pain ever, but the child does not need to
be crying to experience the worst pain ever. Then the child is
asked which face best describes how they feel.
Oucher Ages 3 years & up. Similar to FACES, but uses a picture scale
for young children & a numeric scale for older children. Available
in different ethnic & gender versions. (www.oucher.org)
Hester’s Ages 5 years & up. Given 4 chips & told that one chip represents
Poker Chip a small amount of pain, 2 chips mean more pain, 3 chips mean
Scale even more pain, & 4 chips mean the worst pain ever. The
children are then asked to put the number of chips in the
interviewer’s hand & that best describes their pain.

14. Examples of the OUCHER Scale
Accessed February 24, 2012 at http://www.oucher.org/order.html

15. Chronic Pain Assessment
Scale Measurement
The Varni-Thompson Pediatric Pain Ages 4-16 years. Provides a
Questionnaire comprehensive assessment of the
pain experience in children with
chronic pain.
Douleur Enfant Gustav-Roussy For ages 2 to 6 years. Measures
chronic pain by incorporating several
items that deal with pain, anxiety, &
psychomotor behaviors.

16. Developmental Pharmacology:
An Overview

17. Pharmacology: Body Compartments
 Age: neonates
 Trend: decreased fat, decreased muscle, &
increased water.
 Clinical implications: Some water soluble drugs have
 Increased drug distribution in extracellular fluids.
 Increased duration of action.
 Increased dosing interval.
 How does body composition differ in aging adults?
 Increasing fat & decreasing water.
 Result- increased drug distribution & accumulation of lipid
soluble drugs.

18. Pharmacology: Plasma
 Age: Neonates
 Trend: Decreased concentrations of drug binding
proteins (albumin & α-1 glycoprotein)
 Clinical Implications:
 Higher concentrations of active (unbound) drug for highly
protein-bound medications.
 Increased potential for overdose or toxicity.
 How does plasma differ in aging adults?
 Decreasing/unchanged albumin & increasing α-1
glycoprotein.
 Result- decreased distribution of water soluble drugs.

19. Pharmacology: Hepatic
 Age: neonates, infants, & children 2-6 years.
 Trend:
 Neonates & infants: enzymes involved in drug metabolism
mature at varying rates over 1-6 months of life.
 Children 2-6 years: increased hepatic mass.
 Clinical Implications:
 Neonates & infants: decreased metabolic clearance; decreased
infusion rates or increased dosing intervals.
 Children 2-6 years: increased metabolic clearance; increased
infusion rates or decreased dosing intervals.
 How does hepatic function differ in aging adults?
 Decreased liver mass, decreased liver blood flow, &
decreased/unchanged function of enzymes.
 Decreased metabolism & increased duration of action.

20. Pharmacology: Renal Filtration
 Age: neonates & infants.
 Trend:
 Decreased glomerular filtration rate.
 Sufficiently mature to clear medications by 2 weeks of age &
normalizes by 8-12 months.
 Clinical Implications:
 Accumulation of renally excreted drugs or their active
metabolites.
 Decreased infusion rates or increased dosing intervals.
 How does renal function differ in aging adults?
 Decreased filtration, decreased renal mass, & decreased renal
blood flow.
 Decreased elimination & increased duration of action.

21. Aging & Renal Function: Example
Infants to 19 years of age:
>120 mL/min
20 to 49 years of age:
99-116 mL/min
50+ years of age:
<99 mL/min

22. Pharmacology: Respiratory
 Age: neonates.
 Trend: diminished ventilatory responses to
hypoxemia & hypercarbia.
 Clinical Implications
 Respiratory pauses or apnea lead more rapidly to
hypoxemia.
 Further impairment can be seen with central nervous
system depressant drugs such as opioids &
benzodiazepines (these medications are still appropriate
for symptomatic relief & comfort when needed).

23. Pain Management

24. Pain Management: Nonpharmacologic
Therapies
 World Health Organization (WHO) recommends
considering to augment pain & anxiety.
 Examples include:
 Improved sleep hygiene.
 Cognitive behavior techniques, such as hypnosis, guided
imagery, biofeedback, & mindfulness based stress
reduction.
 Child life specialists to help distract the child with games,
toys, & play therapy.
 Yoga.
 Massage.
 Acupuncture or Accupressure
 Art or music therapy.
 Transcutaneous electrical nerve stimulation.
 Aromatherapy

25. Pain Management: General Treatment
Principles
 Dosing is based on mg/kg.
 Infants younger than 6 months or less than 10 kg,
opioid doses are usually reduced by 25-30% of the
nominal starting dose.
 Adolescents heavier than 50 kg can be dosed using
typical adult dosing.
 As in adults, renal & liver function must also be
considered & adjusted for according to the degree of
organ dysfunction.

26. Pain Management: WHO Analgesic
Treatment Principles
 By the ladder: analgesics should be started &
escalated in a stepwise approach based on the
severity of symptoms.
 By the clock:
 Analgesics should be given on a scheduled basis to
provide stable blood levels of the medication.
 Rescue doses should be available for breakthrough pain.
 By the mouth: analgesics should be given by the
simplest, most effective, & least painful route
available that allows for effective pain control.
 By the child: analgesics dose/frequency should be
based on the individual child’s circumstances & their
response to therapy.

27. Pain Management: WHO Analgesic Ladder
Step 1: Mild pain (pain scores 1-4 out 10)
Acetaminophen, non-steroidal anti-
Non-Opioid Analgesics
inflammatory drugs
Step 2: Moderate pain (pain scores 5-7)
Weak Opioids Codeine, hydrocodone, tramadol
Step 3: Severe pain (pain scores 8-10)
Morphine, oxycodone,
Strong Opioids
hydromorphone, fentanyl, methadone

28. Pain Management: Routes of Administration
Pros & Cons
Zernikow B, Michel E, et al. Pediatric Palliative Care: Use of Opioids for the Management of Pain. Pediatr Drugs
2009;11(2):129-151.

29. Pain Management: Oral Drug
Considerations
 Many children less than 6 years cannot swallow
pills/capsules.
 Alternative opioid formulations
 Liquid: methadone, morphine immediate release,
hydrocodone/APAP, oxycodone, codeine.
 Transmucosal: fentanyl lollipop (Actiq®)
 Transdermal: fentanyl patch
 Crushable pills are an alternative when the drug is
not available in liquid formulation.
 Masking aversive-tasting medications: stir into small
quantities (~5 mL) of chocolate/strawberry syrup,
pudding, ice cream, applesauce, or 100% fruit juice
(not recommended for less than 6 months of age) .

30. Pain Management: Nonopioid Drugs
Drug Dose <50kg (max dose) Dose ≥50kg (max dose)
Acetaminophen PO/IV: 10-15 mg/kg every 4-6 PO/IV: 650-1000 mg every 4-6
hours (90 mg/kg/day or 4g/day) hours (4g/day)
Rectal: One time 40mg/kg Rectal: 1000mg every 4-6
loading dose followed by, hours (4g/day)
20mg/kg rectally every 4-6
hours (120 mg/kg/day or
4g/day)
Ibuprofen 5-10 mg/kg PO every 6-8 hours 400-600 mg PO every 6-8
(40mg/kg or 2.4 g/day) hours (2.4 g/day)
Naproxen 5 mg/kg PO every 8-12 hours 250-375 mg every 8-12 hours
(24mg/kg or 1 g/day)× (1 g/day)
Ketrolac 0.25-0.5 mg/kg IV every 6 15-30 mg IV every 6 hours
hours (2 mg/kg or 120mg/day) x (120mg/day) x 5 days
5 days
× Higher doses can be used for children with rheumatologic disease.
Berde CB & Sethna NF. Analgesics for the Treatment of Pain in Children. N Engl J Med 2002;347(14)1094-1103.

31. Pain Management: Initial Opioid Dosing In
Opioid Naïve Children
Berde CB & Sethna NF. Analgesics for the Treatment of Pain in Children. N Engl J Med 2002;347(14)1094-1103.

32. Pain Management: Methadone
 Only long acting opioid available as an oral liquid.
 No published studies evaluating its use in pediatric
palliative/hospice care.
 Advantages:
 May still exhibit analgesia even if morphine, fentanyl, or
hydromorphone have failed.
 May be beneficial for patients with neuropathic pain.
 Disadvantages:
 Extremely long half-life (children: 4-62 hrs, adults: 9-87 hrs)
 Biphasic elimination- can result in slow accumulation &
toxicity 2-5 days after initiation or dose changes (monitor for
side effects).

33. Pain Management: WHO Recommendation
for Methadone
 Use only after failing morphine & hydromorphone.
 Oral route is preferred.
 To prevent toxicity:
 Initiation: Administer on as needed basis for the first 2-3
days. When frequency requirements are well established,
round the clock dosing can be initiated.
 Maintenance: increase dose as needed every 2-5 days as
needed to achieve pain control.
 Avoid in kids with rapidly changing clinical conditions or
metabolic conditions that could interfere with drug
clearance.

34. Case Study: Initial IV morphine titration
 A 2 year old (weight= 12 kg) has severe pain & is
unable to hold down any oral liquids at this time.
 Initial IV morphine titration:
 Starting dose of morphine 0.1 mg/kg x 12 kg = 1.2 mg.
 Reassess the child in 30 minutes
 If still in pain & not sedated provide a repeat dose of 1.2 mg.
 If still in pain, but somewhat sedated provide a repeat dose at
25-50% of the starting dose (0.3-0.6 mg).
 The child is now comfortable.
Adapted from: WHO. Cancer pain relief & palliative care in children. Geneva: World Health Organization, 1998.

35. Case Study: Initial IV morphine titration
continued…
 Continuous infusion of morphine:
 Starting infusion rate 0.03 mg/kg/hour x 12 kg =
0.36 mg/hour.
 Provide hourly rescue doses for PRN breakthrough pain
at 50-200% of the hourly infusion rate (0.18-0.72 mg).
 Assess the child in one hour. Child is still comfortable.
 Reassess the child in 4 hours. Child has moderate pain,
is withdrawn, & cries when not held.

36. Case Study: Initial IV morphine titration
continued…
 Titration:
 Administer a rescue bolus dose 0.1 mg/kg x 12 kg=
1.2mg.
 If repeated breakthrough pain occurs increase the
infusion rate by 25% (0.25 x 0.36 mg/hour) + 0.36
mg/hour = 0.45 mg/hour. Continue to provide rescue
doses PRN .
 Alternatively, continue rescue doses for 24 hours then
increase the infusion rate by the amount of rescue doses
administered over that 24 hour period.
 For example if six rescue doses of 0.5 mg were given then
increase the infusion rate by [(0.5mg x 6 doses) ÷ 24 hours] +
0.36mg/hour = 0.48mg/hour.

37. Managing Opioid Side Effects

38. Opioid Side Effects: Constipation
 Constipation is an anticipated chronic side effect that
is uncomfortable & sometimes painful.
 ~50% of terminally ill children experience prolonged
constipation & should be treated preventively when
on opioid therapy.
 Prophylactic treatment:
 Combination therapy is generally indicated with a
stimulant laxative (senna) plus either a stool softener
(docusate) or osmotic agent (magnesium, lactulose,
polyethylene glycol).
 Adding more fiber to the diet may be helpful only if liquids
are also increased.

39. Opioid Side Effects: Nausea & Vomiting
 Quickly develop tolerance to the emetic effect of
opioids & usually resolves within one week of
initiation.
 Potential treatments therapies:
 Ondansetron (preferred), granisetron
metoclopramide, prochlorperazine (PO/PR),
chlorpromazine.
 Alternatives: lorazepam, low-dose olanzapine,
droperidol, haloperidol.
 Severe nausea/vomiting: consider rotating to
different opioid or initiate low-dose naloxone
infusion.

40. Opioid Side Effects: Pruritus
 Common side effect (~25%).
 Usually resolves after several days.
 Treatment:
 If the pain situation is stable attempt a opioid dose
reduction, or initiate scheduled antihistamine
(diphenhydramine, hydroxyzine) therapy, or initiate low-
dose naloxone infusion.
 If pain is unstable or above measures are unsuccessful,
opioid rotation is indicated.

41. Opioid Side Effects: Somnolence
 Often improves within a few days after initiation or
titration of the opioid.
 Management:
 If persistent or intolerable, the most effective therapy is
rotating the opioid.
 Alternately may try a trial of psychostimulant (e.g.
methylphenidate).

42. Opioid Side Effects: Delirium & Myoclonus
 Delirium (rare)
 Commonly occurs when receiving multiple medications or
patient is critically ill.
 Management: if clearly opioid related initiate a trial of
haloperidol or rotate to a different opioid.
 Myoclonus
 May be provoked in patients on high dose opioids (i.e.
morphine or hydromorphone).
 Management:
 Considered benign if occurs during sleep.
 If present during waking hours or severe a benzodiazepine can
be scheduled or the opioid rotated.

43. Opioid Side Effects: Respiratory depression
 True respiratory depression is rare when opioids are
dosed appropriately.
 Usually seen during rapid IV opioid administration for
painful procedures or when co-administered with a
centrally active medication such as benzodiazepines.
 Management (determined by treatment goals of the child
& family):
 Mild to moderate: stimulating the child, holding opioid dose,
opioid dose reduction by 50%.
 Severe: Respiratory support & if necessary naloxone
(should be administered with extreme caution, as sudden
opioid antagonism can lead to life-threatening withdrawal).

44. Conclusions
 Common tools to assess pain in children include
observational scales (FLACC, CRIES) & simple-self
report scales (OCHER, FACES).
 Neonates, infants, & young children often have
pharmacological differences such as altered renal or
hepatic function as compared to adults.
 The type of pharmacological intervention is
dependent upon the level of pain observed and/or
reported by the child.
 Common opioid side effects include constipation,
nausea/vomiting, pruritus, & somnolence.

45. Aging & Renal Function: Example
Infants to 19 years of age:
>120 mL/min
20 to 49 years of age:
99-116 mL/min
50+ years of age:
<99 mL/min

46. References
1) American Medical Association Pediatric Pain Management (module 6).
AMA release September 2007.
2) Moody K, Siegel L, et al. Pediatric Palliative Care. Prim Care Clin Office
Pract 2001;38:327-361.
3) Berde CB & Sethna NF. Analgesics for the Treatment of Pain in Children.
N Engl J Med 2002;347(14):1094-1103.
4) Himelstein BP, Hilden JM, et al. Pediatric Palliative Care. N Engl J Med
2004;350:1752-1762.
5) Committee on Psychosocial Aspects of Child & Family Health, American
Academy of Pediatrics; Task Force on Pain in Infants, Children, &
Adolescents, American Pain Society. The assessment & management of
acute pain in infants, children, & adolescents. Pediatrics 2001;108(3):793-
797.
6) Mathews TJ, et al. Annual summary of vital statistics: 2008. Pediatrics
2011:127(1):146-157.
7) Klick JC & Hauer J. Pediatric Palliative Care. Curr Probl Pediatr Adolesc
Health Care 2010;40:120-151.
8) Lawrence J, Alcock D, McGrath P, et al. The development of a tool to
assess neonatal pain. Neonatal Netw 1993;12(6):59–66.

47. References Continued…
9) Hummel P, Puchalski M, et al. Clinical reliability and validity of the N-PASS:
neonatal pain, agitation and sedation scale with prolonged pain. J Perinatol
2008;28:55-60.
10) Stevens B, Johnston C, et al. Premature Infant Pain Profile: Development & initial
validation. Clin J Pain 1996;12:13-22.
11) Gauvain-Piquard A, Rodary C, et al. Pain in children 2-6 years: A new observational
rating scale elaborated in a pediatric oncology unit – preliminary report. Pain
1987;31:177-188.
12) Varni JW, Thompson KL, et al. The Varni-Thompson pediatric pain questionnaire I.
Chronic musculoskeletal pain in juvenile rheumatoid arthritis. Pain 1987;28:29-38.
13) Zernikow B, Michel E, et al. Pediatric Palliative Care: Use of Opioids for the
Management of Pain. Pediatr Drugs 2009;11(2):129-151.
14) WHO. Cancer pain relief & palliative care in children. Geneva: World Health
Organization, 1998.
15) Krechel SW and Bildner J. CRIES: a new neonatal postoperative pain
measurement score– initial testing of validity and reliability. Paediatr Anaesth
1995;53-61.
16) National Kidney Foundation. Frequently asked questions about GFR
estimates. National Kidney Foundation, Inc., 2010.

48. Pain Management: Routes of Administration
Oral Transdermal Intravenous Intramuscular Rectal
Generally not
Rapid pain Generally not
Painless Painless preferred by
control recommended
children
Not indicated for
Wide variability in
Preferred by acute or Easiest to titrate
Painful therapeutic drug
children escalating pain & adjust rapidly
levels
management
Useful for
Used only when Wide variability in Can be used
intermittent bolus
pain has therapeutic drug when transient
& continuous
stabilized levels vomiting present
infusions
Appropriate for
PCA use

49. Initiating Opioid Therapy for Severe Pain
 By the clock:
 Initiate a strong opioid & administer the medication on a
routine schedule basis.
 Order a strong opioid for breakthrough pain.
 By the mouth:
 Determine the appropriate route of administration that is
the least invasive & most effective.
 By the child:
 If taking oral opioids re-access the child at several days to
determine if the treatment is adequate.
 If using IV opioids re-access the child every 30 minutes.

50. Pain Management: WHO Recommendation
for Methadone
 Use only after failing morphine & hydromorphone.
 Oral route is preferred.
 To prevent toxicity:
 Initiation: Administer on as needed basis for the first 2-3
days. When frequency requirements are well established,
round the clock dosing can be initiated.
 Maintenance: increase dose as needed every 2-5 days as
needed to achieve pain control.
 Avoid in kids with rapidly changing clinical conditions or
metabolic conditions that could interfere with drug
clearance.

51. Pain Management: Methadone
 Only long acting opioid available as an oral liquid.
 No published studies evaluating its use in pediatric
palliative/hospice care.
 Advantages:
 May still exhibit analgesia even if morphine, fentanyl, or
hydromorphone have failed.
 May be beneficial for patients with neuropathic pain.
 Disadvantages:
 Extremely long half-life (children: 4-62 hrs, adults: 9-87 hrs)
 Biphasic elimination- can result in slow accumulation &
toxicity 2-5 days after initiation or doses changes (monitor
for side effects).

52. Pain Management: Nonpharmacologic
Therapies
 WHO recommends considering to augment pain &
anxiety.
 Examples include:
 Improved sleep hygiene.
 Cognitive behavior techniques, such as hypnosis, guided
imagery, biofeedback, & mindfulness based stress
reduction.
 Child life specialists to help distract the child with games,
toys, and play therapy.
 Yoga.
 Massage.
 Acupuncture or Accupressure
 Art or music therapy.
 Transcutaneous electrical nerve stimulation.
 Aromatherapy