pediatric pain management

1. Pediatric Pain Management Liza Li, PharmD Pediatric Pharmacy Resident Department of Pharmacy Children�s Hospital Boston

3. � Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.� International Association for the Study of Pain �Pain is an inherently subjective multi-factoral experience and should be assessed and treated as such.� American Academy of Pediatrics and American Pain Society

4. Misconceptions That Can Lead to Under Treatment of Pain in Children Children, especially infants do not: Feel pain the way adults do Remember pain Lack of assessment for presence of pain Lack knowledge in pediatric analgesics Use Dosing Adverse effects Preventing pain takes too much time

5. Consequences of Inadequate Analgesia During Painful ProceduresWeisman, SJ et al. Arch Pediatr Adolesc Med 1998; 152: 147-149 Background/Method 21 patients documenting the efficacy of oral transmucosal fentanyl citrate (OTFC) for painful procedures rated the pain associated with subsequent procedures performed with open labeled OTFC Results Children <8 yo, mean pain ratings ? for those who had received placebo in the original study compared to those who received OTFC

6. Components of Pain Nociception Sensation of pain Perception of pain Triggered by a noxious stimulus Suffering Negative response induced by pain, fear, anxiety, stress and other psychological states Pain behaviors Results from pain and suffering and are things a person does or does not do that can be ascribed to the presence of tissue damage

7. Types of Pain Acute Elicited by substantial injury of body tissue Activation of nociceptive transducers at the site of local tissue damage Chronic Commonly triggered by an injury or disease, but may be perpetuated by factors other than the cause of the pain

8. Types of Pain Transient Elicited by the activation of nociceptive transducers in skin or other tissues of the body in the absence of any tissue damage Neuropathic Pain sustained by abnormal processing of sensory input by the peripheral or central nervous system

9. �I have a boo boo �� < 6 months Do not express anticipatory fear 6 to 18 months Begin to develop fear of painful experiences and withdraw when pain is anticipated 18 to 24 months Express pain with words such as �hurt� or boo boo� 3 years � Children Begin to localize pain and identify external causes 5 to 7 years Improve understanding of pain, ability to localize and cooperate Adolescence Able to qualify/quantify pain and develop cognitive coping strategies that may help diminish pain

10. Measurement of Pain in Children Self-reported Gold standard Behavioral Crying, facial expressions, general body movements Physiological HR, BP, RR, O2 saturation

11. Pain Assessment Tools PAINS Place Amount Intensity Nullifiers Side Effects PQRST FLACC Face Legs Activity Cry Consolability N-PASS

12. Pain Scales

13. Treatment Goals Minimize physical pain and discomfort Alleviate anxiety Prevent potentially deleterious physiologic responses due to pain

14. Non-Pharmacologic Pain Treatment Communication Psychological treatment Physical therapy Distraction Biofeedback Transcutaneous electrical nerve stimulation (TENS) Acupuncture

15. Pharmacologic Pain Treatment Non-Opioids Opioids Adjuvant analgesics Topical anesthetics Routes of administration Epidural Intravenous Intramuscular Intrathecal Oral Nasal Suppository Topical

17. Ideal Analgesic Therapy Continuous analgesia No/minimal adverse effects Non-invasive mode of administration No cumbersome equipment

18. Non-Opioid Analgesics

19. Acetaminophen MOA: Inhibits the synthesis of prostaglandins in the CNS Peripherally blocks pain impulse generation Produces antipyresis from inhibition of hypothalamic heat-regulating center NOT an anti-inflammatory Adverse reactions Blood dyscrasias Hepatic necrosis w/ overdose Renal injury w/ chronic use

20. Acetaminophen Dosage Forms

21. Non-Steroidal Anti-inflammatory Drugs NSAIDs are analgesic, anti-inflammatory, anti-platelet, and antipyretic Side effects Renal Hematological Gastric mucosal damage Examples Aspirin Choline magnesium trisalicylate Diclofenac Ibuprofen Indomethacin Ketorolac Naproxen Sulindac

22. NSAIDs MOA

23. Ibuprofen Special Notes May cause allergic reactions in susceptible individuals Junior Strength Motrin caplets contain tartrazine Motrin IB gelcaps contain benzyl alcohol Some products contain sodium benzoate (metabolite of benzyl alcohol) Large amounts of benzyl alcohol (>99 mg/kg/day) have been associated with �gasping syndrome�

24. Ketorolac Only IV NSAID for pain management Contraindicated Coagulopathy Gastropathy Hypovolemia Max duration=5 days

25. COX-2 Inhibitors Reduce risk of gastric irritation and bleeding Inhibits prostaglandin synthesis Indications Signs/symptoms of osteoarthritis Management of acute pain in adults Treatment of menstrual cramps Rheumatoid arthritis in adults and children Examples Celocoxib (Celebrex�) Valdecoxib (Bextra�) Rofecoxib (Vioxx�) Voluntarily withdrawn from market:? risk CVD Clinical evidence VIGOR- VOIXX GI Outcomes Research APPROVe- Adenomatous Polyp Prevention on VOIXX

26. PK/PD Properties of Non-Opioid Analgesics

27. Relative Side Effects of Non-Opioid Analgesics

28. Opioid Analgesics

29. Opioid Analgesics Morphine-Like Opioids Morphine Hydromorphone Codeine Oxycodone Hydrocodone Meperidine-Like Opioids Meperidine Fentanyl Methadone-Like Agonists Methadone Propoxyphene

30. Opioid Analgesics Binds to opiate receptors in the CNS Inhibits ascending pain pathways, altering the perception of and response to pain Produces generalized CNS depression

31. Pharmacokinetics of Opioid Analgesics

32. Opioid Analgesic Route of Administration

33. Combination Analgesics Consider content of combination products DO NOT exceed acetaminophen or aspirin maximum daily doses! Examples: Codeine/Acetaminophen (Tylenol � #2,3,4) Hydrocodone/Acetaminophen (Vicodin �, Narco�) Oxycodone/Acetaminophen (Percocet �) Oxycodone/Aspirin (Pecodan �) Propoxyphene/Acetaminophen (Darvocet �)

34. Conversions Between Opioids Calculate total milligrams of opioid administered for the past 24 hr. Convert 24 hr dose to chosen equivalent dose. Divide 24 hr daily dose into appropriate dose per time interval. When switching from one opioid to another, dose reductions should be considered if the patient has stable, controlled pain. Effective pain management may be achieved at 50-70% of the calculated equianalgesic dose because there is incomplete cross-tolerance among these drugs. Most patients benefit from availability for a short-acting opioid for breakthrough pain.

35. Opioid Analgesics: Equianalgesic Dose Conversion

36. Case 1 KG is a 5 yo girl w/ sickle cell disease who�s pain is controlled on 10mg of morphine solution po q3h. Her team is preparing for her discharge and would like to simplify her therapy to allow for fewer daily doses. As her primary nurse, the team looks to you for guidance in dosing MS Contin� (long acting morphine) which is available in 15mg and 30mg tablets.

37. Answer to Case 1 Total daily dose: 10mg of Morphine po q3h = 80mg/day of morphine Sustained release morphine: MS Contin� is available in 15mg, 30mg tabs Possible recommendations: Aggressive management MS Contin� 30mg po q12H + Morphine 10mg po q4h prn for breakthrough Conservative management MS Contin� 45mg po q12H + Morphine 15mg po q4h prn for breakthrough

38. Case 2 DB is a 9 yo boy s/p spinal fusion. His fentanyl PCA requirement has ?ed significantly. He is only requiring on average 60 mcg/12 hr. The physician would like to convert DB to oxycodone po and has asked you for assistance in the calculations.

39. Answer to Case 2 Total daily dose: 60mcg/12hr ? 120 mcg/24hr Conversion to equivalent dose: Fentanyl = 100mcg = 120mcg Oxycodone 20mg xmg Fentanyl = 0.1mg = 0.120mg Oxycodone 20mg xmg x= 24mg/day of Oxycodone

40. Answer to Case 2 Remember incomplete CROSS-TOLERANCE and effective pain management at 50-75% of calculated equianalgesic dose! Possible Recommendations: Aggressive management (50% of calculated dose) Oxycodone 3mg po q6h prn Conservative management (75% of calculated dose) Oxycodone 4.5mg po q6h prn

41. Case 3 SO is a 17 yo male s/p ACL repair on OxyContin� (long acting oxycodone) 20mg po q12h and Percocet� (oxycodone 5mg/325mg acetaminophen) 1 tab po q3-4h PRN. The patient�s pain has been well controlled on this regimen (only requiring 1 Percocet� tab daily). Oral administration has become a contraindication in this patient and therefore you have been asked to convert the patient to a continuous infusion of morphine.

42. Answer to Case 3 Daily requirements: OxyContin� (long acting oxycodone) 20mg po q12h Percocet� (oxycodone 5mg/325mg acetaminophen) 1 tab/day Total of oxycodone 45mg/day Conversion to equivalent dose: Morphine = 10mg = xmg Oxycodone 20mg 45mg X= 22.5mg/day of morphine

43. Answer to Case 3 Remember incomplete CROSS-TOLERANCE and effective pain management at 50-75% of calculated equianalgesic dose! Possible Recommendations Aggressive management (50% of calculated dose) Morphine IV 11.24mg/day? ~ 0.5mg/hr Conservative management (75% of calculated dose) Morphine IV 16.9mg/day? 0.7mg/hr

44. Opioid Antagonists Antagonist Competes and displaces narcotics at narcotic receptor sites Example Naloxone Mixed Agonist/Antagonist Binds to opiate receptors in the CNS Cause inhibition of ascending pain pathways Alters the perception of and response to pain Produces generalized CNS depression Opiate antagonistic effect may result from competitive inhibition at the opiate mu site Example Nalbuphine

45. More Definitions � Tolerance Present when increasing amounts of drug are required to produce an equivalent level of efficacy Physical Dependence With rapid discontinuation of a drug following prolonged administration, results in withdrawal symptoms Addiction A form of psychological dependence and refers to the extreme behavior patterns that are associated with procuring and consuming drugs

46. Opioid Tolerance Opioids have no MAXIMUM dose Doses are titrated to adverse effects and control of pain Rate of development of opioid tolerance varies among patients Earliest sign is reduction in duration of analgesic effect Requirement for opioids ? as a log function of dose Switch to an alternate opioid at half of the equianalgesic dose

47. Tapering of Opioids Scheduled opioid taper is not essential unless Opioid use is prolonged Total daily requirement is in excess of 160mg of oral morphine (or its equivalent) Reduce by 10-15% each day

48. Opioid WithdrawalSigns and Symptoms Lacrimation Rhinorrhea Sweating Yawning Restlessness Pupillary dilation Nausea/Vomiting Diarrhea ? irritability Insomnia Abdominal cramping ? BP Hyperthermia Chills Flushing

49. Management of Adverse Effects Associated with Opioid Therapy Allergic Reactions Stop opioid and switch to another class Confusion Delirium or Hallucinations Dose reduction, opioid rotation within in class Haldoperidol, risperidone Myoclonic jerking Dose reduction, opioid rotation, benzodiazepines Sedation Hold dose, dose reduction, stimulant therapy

50. Management of Adverse Effects Associated with Opioid Therapy Nausea/Vomiting (Tolerance develops over time) Ondansetron Metoclopramide Prochlorperazine Promethazine Pruritis Diphenhydramine Nalbuphine Respiratory Depression Stop drug, supportive measures (oxygen) Naloxone

51. Management of Adverse Effects Associated with Opioid Therapy Bowel Regimen Stool softener Docusate Laxatives Bisacodyl Lactulose Milk of Magnesia Senna Polyethylene glycol

52. Case 4 JW is a 10 yo girl s/p a left tibia fracture. She is complaining of itching from her morphine, but shows no sign of rash. What treatment can be initiated to alleviate JW�s discomfort? What other adverse effects from morphine should be monitored? What are the 2 components of a bowel regimen that should be initiated for JW?

53. Answers to Case 4 JW is a 10 yo girl s/p a left tibia fracture. She is complaining of itching from her morphine, but shows no sign of rash. What treatment can be initiated to alleviate JW�s discomfort? Pruritis treatment w/ diphenhydramine or nalbuphine What other adverse effects from morphine should be monitored? Nausea/vomiting, sedation, respiratory depression What are the 2 components of a bowel regimen that should be initiated for JW? Stool softener and laxative

54. Misc. Opioid Clinical Pearls Morphine Active metabolite may accumulate in patients with ? renal function Meperidine Toxic metabolite can accumulate with high doses or in patients with ? renal function May precipitate tremors or seizures Fentanyl Patches Steady state levels of are not achieved until 72 hours after application of the patch Patients with elevated temperatures may have ? fentanyl absorption transdermally OxyContin� (oxycodone sustained release) Swallow tablets whole; do not crush, chew, or break Empty tablet shell may appear in stool after medication is absorbed

55. Patient Controlled Analgesia (PCA) Opioid medications are administered using a pre-programmed infusion pump Patient Nurse Parent PCA Order Components Bolus dose (optional) PCA dose Lockout interval Basal dose (optional) Four hour limit

56. Pain Management with PCA Agents: Morphine, Hydromorphone, and Fentanyl Pain assessment Inadequate pain relief Excessively pushing PCA button Adequate pain relief Utilize ordered or less than ordered PCA dose Assess pain quality and severity

57. Advantages and Disadvantages of PCA

58. Regional Analgesia

59. Regional Anesthesia Epidural Moderate-to-severe pain relief Caudal, lumbar, thoracic, cervical

60. Epidurals Administration Bolus Continuous Patient Controlled Epidural Administration (PCEA) Greater analgesia than other modes of pain therapy Agents Opioids Local Anesthetics Clonidine Use caution in patients that are anticoagulated Increase risk of hematoma Analgesic Effect Onset Lipophilic > Hydrophilic Duration Lipophilic < Hydrophilic Area Lipophilic < Hydrophilic

61. Epidural Solutions Chloroprocaine 1.5% � clonidine � fentanyl Bupivacaine 0.1% or 0.125% � clonidine � fentanyl � hydromorphone Ropivacaine Mepivacaine

62. Local Anesthetics MOA: Blocks nociceptive transmission and interrupting sympathetic reflexes

63. Infiltration of Local Anesthetics Indications Large wounds Mucous membranes involved Need for immediate anesthetic effect Route Intradermal Subcutaneous Amides Lidocaine, mepivicaine, bupivacaine Esters Procaine, chloroprocaine, tetracaine, benzocaine Rarely used Diphenhydramine May be used in patients allergic to amides

64. Topical Agents

65. Topical Analgesics Temporary pain relief Most commonly used for osteoarthritis

66. Topical Anesthetic Preparations EMLA � (lidocaine/prilocaine) Concentrated in micron-sized droplets Maybe used in infants 32 weeks gestation and older Cream is applied to the skin and then covered with an occlusive dressing Application time: 1 hour Adverse effects Methemoglobinemia L-M-X � (lidocaine) Lidocaine encapsulated in liposomes Use in children <3 yo Available without a prescription No covering required Application time: 30 min

67. Topical Anesthetic Preparations SyneraTM Patch lidocaine 70 mg and tetracaine 70 mg Age: > 3 yrs Skin: Intact only Onset of Action: as little as 20 minutes Duration of Analgesia: 2 hours Pain Ease Mist SprayTM Counterirritant/skin vaporcoolent Age: > 3 yrs Skin: Intact or non-intact Onset of Action: 10 seconds Duration of Analgesia: 1 minute

68. Miscellaneous Analgesics

69. Concentrated Sucrose Diminishes pain response MOA: unknown Most effective when administered intra-orally Need to use in conjunction with other pain relievers No apparent adverse effects Dose 0.012g-0.12g/dose Single vs. multiple dose Product Multiple Children�s Hospital Boston Sucrose 24% solution (Sweet-Ease�)

70. Clonidine MOA: a2-adrenergic agonist Sedation and analgesia Effective analgesia in burn and surgical patients Reduces post-operative vomiting, and attentuates symptoms of opioid withdrawal Dosage forms Transdermal patch (TTS-1, 2, 3) Delivers 0.1-0.3mg/24 hours Onset of action:2-3 days Patch changed every 7 days Tablets 0.1mg; 0.2mg; 0.3 mg Must taper dose slowly

71. Neuropathic Pain

72. Muscle Spasms

73. Major Drug Interactions

74. Medication Safety with Analgesics Range orders Frequency: PRN vs standing Dose Look-alike; Sound-alike Oxycodone and Oxycontin Hydromorphone and Hydrocodone Clonidine and Klonopin� Morphine sulfate (MSO4) and magnesium sulfate (MgSO4) Celebrex� and Celexa�

75. Pain Management

76. Multimodal Analgesia Several analgesic agents Different mechanism of action Different mode of administration Minimizes adverse effects Improves pain control Labor-intensive for caregiver

77. Interdisciplinary Pain Management Team Physician Nurse Pharmacist Physical and occupational therapist Psychologist

78. Recommendations from American Academy of Pediatrics and American Pain Society Expand knowledge about pediatric pain and management principles and techniques Provide a calm environment for procedures that reduce distress producing stimulation Anticipate predictable painful experiences, intervene, and monitor accordingly Use a multi-modal (pharmacologic, cognitive, behavioral, physical) to pain management and multidisciplinary approach when possible Involve families and tailor child specific interventions Advocate for the effective use of pain medications in children to ensure compassionate and complete management of their pain

79. General Guidelines for the Pharmacological Management of Pain Individualize each patient�s treatment regimen Simplify the dosage schedule and the least invasive modality should be utilized Pain prevention is always easier than relieving pain Medication for persistent acute or chronic pain should be administered Around the Clock vs. PRN Meperidine has a toxic metabolite and generally should be avoided for long-term pain management Naloxone and mixed agonists/antagonists should be used cautiously in patients on chronic opioid therapy Constipation is a preventable problem associated with the use of opioids Pain management issues should always be addressed when a patient is transferred from one setting to another

80. Questions