Pediatric Pain Management

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Pediatric Pain Management

• Liza Li, PharmD
• Pediatric Pharmacy Resident
• Department of Pharmacy
• Childrens Hospital Boston

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Objectives

• Define different types of pain
• Review general guidelines for the pharmacological
  management of pain
• Compare and contrast
• Non-opioid analgesics
• Opioid analgesics
• Topical agents
• Miscellaneous analgesics
• Calculate equianalgesic opioid doses using
  conversion guidelines
• Discuss management strategies for treating
  adverse effects associated with opioid therapy
• Recognize major drug interactions with analgesic
  agents
• Discuss medication safety issues with analgesic
  agents
• Develop patient-specific pain management plans

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• 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

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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

Pediatrics 2001 108(3) 793-797
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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 lt8 yo, mean pain ratings ? for those who
  had received placebo in the original study
  compared to those who received OTFC

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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

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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

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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

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I have a boo boo

• lt 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

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Measurement of Pain in Children

• Self-reported
• Gold standard
• Behavioral
• Crying, facial expressions, general body
  movements
• Physiological
• HR, BP, RR, O2 saturation

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Pain Assessment Tools

• FLACC
• Face
• Legs
• Activity
• Cry
• Consolability
• N-PASS

• PAINS
• Place
• Amount
• Intensity
• Nullifiers
• Side Effects
• PQRST

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Pain Scales
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Treatment Goals

• Minimize physical pain and discomfort
• Alleviate anxiety
• Prevent potentially deleterious physiologic
  responses due to pain

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Non-Pharmacologic Pain Treatment

• Communication
• Psychological treatment
• Physical therapy
• Distraction
• Biofeedback
• Transcutaneous electrical nerve stimulation
  (TENS)
• Acupuncture

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Pharmacologic Pain Treatment

• Non-Opioids
• Opioids
• Adjuvant analgesics
• Topical anesthetics

• Routes of administration
• Epidural
• Intravenous
• Intramuscular
• Intrathecal
• Oral
• Nasal
• Suppository
• Topical

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(No Transcript)
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Ideal Analgesic Therapy

• Continuous analgesia
• No/minimal adverse effects
• Non-invasive mode of administration
• No cumbersome equipment

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Non-Opioid Analgesics
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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

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Acetaminophen Dosage Forms
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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

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NSAIDs MOA
http//www.arcoxia.co.il/secure/pharmaco/pharma_me
chanism_of_action.html
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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 (gt99 mg/kg/day)
  have been associated with gasping syndrome

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Ketorolac

• Only IV NSAID for pain management
• Contraindicated
• Coagulopathy
• Gastropathy
• Hypovolemia
• Max duration5 days

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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

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PK/PD Properties of Non-Opioid Analgesics
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Relative Side Effects of Non-Opioid Analgesics
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Opioid Analgesics
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Opioid Analgesics

• Morphine-Like Opioids
• Morphine
• Hydromorphone
• Codeine
• Oxycodone
• Hydrocodone
• Meperidine-Like Opioids
• Meperidine
• Fentanyl
• Methadone-Like Agonists
• Methadone
• Propoxyphene

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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

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Pharmacokinetics of Opioid Analgesics
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Opioid Analgesic Route of Administration
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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 )

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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.

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Opioid Analgesics Equianalgesic Dose Conversion
Per Boston Medical Center Pain Guidelines
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Case 1

• KG is a 5 yo girl w/ sickle cell disease whos
  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.

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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

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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.

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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

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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

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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 patients 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.

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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

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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

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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

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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

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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

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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

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Opioid WithdrawalSigns and Symptoms

• Lacrimation
• Rhinorrhea
• Sweating
• Yawning
• Restlessness
• Pupillary dilation
• Nausea/Vomiting
• Diarrhea

• ? irritability
• Insomnia
• Abdominal cramping
• ? BP
• Hyperthermia
• Chills
• Flushing

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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

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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

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Management of Adverse Effects Associated with
Opioid Therapy

• Bowel Regimen
• Stool softener
• Docusate
• Laxatives
• Bisacodyl
• Lactulose
• Milk of Magnesia
• Senna
• Polyethylene glycol

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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 JWs
  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?

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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 JWs 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

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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

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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

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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

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Advantages and Disadvantages of PCA
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Regional Analgesia
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Regional Anesthesia

• Epidural
• Moderate-to-severe pain relief
• Caudal, lumbar, thoracic, cervical

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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 gt Hydrophilic
• Duration
• Lipophilic lt Hydrophilic
• Area
• Lipophilic lt Hydrophilic

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Epidural Solutions

• Chloroprocaine 1.5
• clonidine
• fentanyl
• Bupivacaine 0.1 or 0.125
• clonidine
• fentanyl
• hydromorphone
• Ropivacaine
• Mepivacaine

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Local Anesthetics

• MOA Blocks nociceptive transmission and
  interrupting sympathetic reflexes

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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

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Topical Agents
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Topical Analgesics

• Temporary pain relief
• Most commonly used for osteoarthritis

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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 lt3 yo
• Available without a prescription
• No covering required
• Application time 30 min

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Topical Anesthetic Preparations

• SyneraTM
• Patch
• lidocaine 70 mg and tetracaine 70 mg
• Age gt 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 gt 3 yrs
• Skin Intact or non-intact
• Onset of Action 10 seconds
• Duration of Analgesia 1 minute

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Miscellaneous Analgesics
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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
• Childrens Hospital Boston
• Sucrose 24 solution (Sweet-Ease)

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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 action2-3 days
• Patch changed every 7 days
• Tablets 0.1mg 0.2mg 0.3 mg
• Must taper dose slowly

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Neuropathic Pain
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Muscle Spasms
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Major Drug Interactions
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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

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Pain Management
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Multimodal Analgesia

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

Am J Health-Syst Pharm. 2004 61(Suppl 1)S11-4
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Interdisciplinary Pain Management Team

• Physician
• Nurse
• Pharmacist
• Physical and occupational therapist
• Psychologist

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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

Pediatrics 2001 108(3) 793-797
79
General Guidelines for the Pharmacological
Management of Pain

• Individualize each patients 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

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Questions