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Providing quality pediatric pain management during end of life care

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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.

Published in: Health & Medicine
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Providing quality pediatric pain management during end of life care

  1. 1. Providing Quality Pediatric PainManagement During End of Life Care Danielle Cassidy, Pharm.D. May 2012
  2. 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. 3. Background
  4. 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. 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. 6. Background: Medical ConditionsAppropriate 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. 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. 8. Pediatric Pain Assessment
  9. 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. 10. Acute Pain Assessment: NeonatesScale Scale Indicators Degree of Crying, Required oxygen, Increased vitalCRIES signs (heart rate &/or blood pressure), Expression (e.g. grimace), & Sleeplessness.Premature Infant Pain Gestational age (greater than or less than 36 weeksProfile (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 muscleScale (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. 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. 12. Acute Pain Assessment: ObservationalScales for Nonverbal Young ChildrenScale MeasurementFLACC 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 PainImpaired Checklist-Revised (NCCPC-R), & The Paediatric Pain Profile (PPP).
  13. 13. Acute Pain Assessment: Simple Self ReportScales for Verbal Young ChildrenScale MeasurementFACES 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 representsPoker Chip a small amount of pain, 2 chips mean more pain, 3 chips meanScale 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. 14. Examples of the OUCHER Scale Accessed February 24, 2012 at http://www.oucher.org/order.html
  15. 15. Chronic Pain AssessmentScale MeasurementThe Varni-Thompson Pediatric Pain Ages 4-16 years. Provides aQuestionnaire 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. 16. Developmental Pharmacology: An Overview
  17. 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. 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. 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. 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. 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. 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. 23. Pain Management
  24. 24. Pain Management: NonpharmacologicTherapies 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. 25. Pain Management: General TreatmentPrinciples 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. 26. Pain Management: WHO AnalgesicTreatment 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. 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. 28. Pain Management: Routes of AdministrationPros & ConsZernikow B, Michel E, et al. Pediatric Palliative Care: Use of Opioids for the Management of Pain. Pediatr Drugs2009;11(2):129-151.
  29. 29. Pain Management: Oral DrugConsiderations Many children less than 6 years cannot swallowpills/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. 30. Pain Management: Nonopioid DrugsDrug 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. 31. Pain Management: Initial Opioid Dosing InOpioid Naïve ChildrenBerde CB & Sethna NF. Analgesics for the Treatment of Pain in Children. N Engl J Med 2002;347(14)1094-1103.
  32. 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. 33. Pain Management: WHO Recommendationfor 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. 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. 35. Case Study: Initial IV morphine titrationcontinued… 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. 36. Case Study: Initial IV morphine titrationcontinued… 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. 37. Managing Opioid Side Effects
  38. 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. 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. 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. 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. 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. 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. 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. 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. 46. References1) 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. 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. 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. 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. 50. Pain Management: WHO Recommendationfor 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. 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. 52. Pain Management: NonpharmacologicTherapies 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

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