Pain Management

1
Pain Management

• Matthew Fitz, MD
• July 31, 2007

2
Objectives

• Compare contrast different pain patterns
• Increase knowledge of analgesic pharmacology
• Develop an approach to administering adequate
  pain relief during common clinical scenarios

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General principles . . .

• Assessment Reassessment
• Acute versus Chronic
• Management
• pharmacologic
• nonpharmacologic

4
Pain pathophysiology

• Acute pain
• identified event, resolves daysweeks
• usually nociceptive
• Chronic pain
• cause often not easily identified, multifactorial
• indeterminate duration
• nociceptive and / or neuropathic

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Nociceptive pain . . .

• Direct stimulation of intact nociceptors
• Transmission along normal nerves
• sharp, aching, throbbing
• somatic
• easy to describe, localize
• visceral
• difficult to describe, localize
• Management
• opioids
• adjuvant / coanalgesics

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Neuropathic pain

• Pain may exceed observable injury
• Described as burning, tingling, shooting,
  stabbing, electrical
• Management
• opioids
• adjuvant / coanalgesics often required

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Burning, tingling, neuropathic pain

• Tricyclic antidepressants
• Gabapentin (anticonvulsant)
• SSRIs usually not so useful

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Tricyclic antidepressants for burning pain . . .

• Amitriptyline
• most extensively studied
• 1025 mg po q hs, titrate (escalate q 47 d)
• analgesia in days to weeks

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Tricyclic antidepressants for burning pain . . .

• Amitriptyline
• monitor plasma drug levels gt 100 mg / 24 h for
  risk of toxicity
• anticholinergic adverse effects prominent,
  cardiac toxicity
• sedating limited usefulness in frail, elderly

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. . . Tricyclic antidepressants for burning pain

• Desipramine
• minimal anticholinergic or sedating adverse
  effects
• 1025 mg po q hs, titrate
• tricyclic of choice in seriously ill
• nortriptyline is an alternative

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Gabapentin for burning pain

• Anticonvulsant
• 100 mg po q d to tid, titrate
• increase dose q 13 d
• usual effective dose 9001800 mg / d max may be
  gt 3600 mg / d
• minimal adverse effects
• drowsiness, tolerance develops within days

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Shooting, stabbing, neuropathic pain

• Anticonvulsants
• gabapentin
• 100 mg po tid, titrate
• carbamazepine
• 100 mg po bid, titrate
• valproic acid
• 250 mg po q hs, titrate
• monitor plasma levels for risk of toxicity

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Adjuvants for Neuropathic PainPearls

• ..titrate to effect
• ..stop if no effect after 2 weeks.

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Special cases

• Bone Pain
• Pain from bowel obstruction

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Opioid pharmacology . . .

• Cmax after
• po ? 1 h
• SC, IM ? 30 min
• IV ? 6 min
• half-life at steady state
• po / pr / SC / IM / IV ? 3-4 h

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. . . Opioid pharmacology

• Steady state after 45 half-lives
• steady state after 1 day (24 hours)
• Duration of effect of immediate-release
  formulations (except methadone)
• 35 hours po / pr
• shorter with parenteral bolus

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Routine oral dosingimmediate-release preparations

• Codeine, hydrocodone, morphine, hydromorphone,
  oxycodone
• dose q 3h
• adjust dose daily
• mild / moderate pain ? 2550
• severe / uncontrolled pain ? 50100
• adjust more quickly for severe uncontrolled pain

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Routine oral dosingextended-release preparations

• Improve compliance, adherence
• Dose q 8, 12, or 24 h (product specific)
• dont crush or chew tablets
• may flush time-release granules down feeding
  tubes
• Adjust dose q 24 days (once steady state reached)

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Breakthrough dosing

• Use immediate-release opioids
• 515 of 24-h dose
• offer after Cmax reached
• po / pr ? q 1 h
• SC, IM ? q 30 min
• IV ? q 1015 min
• Do NOT use extended-release opioids

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Clearance concerns

• Conjugated by liver
• 9095 excreted in urine
• Dehydration, renal failure, severe hepatic
  failure
• ? dosing interval, ? dosage size
• if oliguria or anuria
• STOP routine dosing of morphine
• use ONLY prn

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WHO 3-Step Ladder
Step 3 - Severe
Step 2 - Moderate
Morphine Hydromorphone Methadone Levorphanol Fenta
nyl
Codeine Hydrocodone Oxycodone Tramadol
Step 1 - Mild
Aspirin Acetaminophen NSAIDs
Always consider adding an adjuvant Rx
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Level I Medications

• Acetaminophen
• 12 - 15 mg/kg, Q 4hr, PO or PR
• NSAIDs
• Ibuprofen
• 10 mg/kg, max 40mg/kg/day, Q 6hr, PO
• Ketorolac (variable efficacy)
• 0.5 mg/kg IV/IM, 5-10 mg PO, Q 6hr
• Rotation of NSAIDs is a good strategy

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Enteral Narcotics

• Codeine
• 1 mg/kg, Q 2-4 hrs, PO
• Ineffective for age gt10-12 years
• Hydrocodone (Lortab)
• 0.1 mg/kg PO q 2-4 hours (very good for moderate
  pain)
• Oxycodone 5 - 10 mg/ dose PO q 2-4 hours (Tylox)
• Tramadol (Ultram)
• 0.7 - 2.0 mg/kg/dose PO Q 4-6 hours (variable
  efficacy)
• Morphine (the gold standard)
• 0.3 mg/kg PO Q 2-4hr
• Morphine SR (MS Contin)
• 0.5 mg/kg, BID, PO (Do not crush)

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Patient-Controlled Analgesia
Medication Basal Rate Bolus Dose
Lockout Max/Hr Morphine .03 mg/kg
Same 6-10 min .15 mg/kg Dilaudid
5 mcg/kg Same 6-10 min
25 mcg/kg Fentanyl 1 mcg/kg Same
6-10 min 4 mcg/kg
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Patient-Controlled Analgesia

• Medication
• Basal rate (applicable if opiate-tolerant)
• Bolus dose
• Lockout interval
• Max/hr.

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Equianalgesic dosesof opioid analgesics

• po / pr (mg) Analgesic SC / IV / IM (mg)
• 100 Codeine 60
• 15 Hydrocodone -
• 4 Hydromorphone 1.5
• 15 Morphine 5
• 10 Oxycodone -

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Objectives

• Know alternative routes for delivery of opioid
  analgesics
• Demonstrate ability to convert between opioids
  while maintaining analgesia

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Alternative routes

• Enteralincluding feeding tubes
• Transdermal
• Parenteral
• Transmucosal
• Rectal
• Intraspinal

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Transdermal patch

• Fentanyl
• peak effect after application ? 24 hours
• patch lasts 4872 hours
• ensure adherence to skin
• Increased absorption with increased body temp

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Parenteral

• SC, IV, IM
• bolus dosing q 2-4 h
• continuous infusion
• easier to administer
• more even pain control

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Bolus effect

• Swings in plasma concentration
• drowsiness ½ 1 hour after ingestion
• pain before next dose due
• Transition to
• extended-release preparation
• continuous SC, IV infusion

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Changing routesof administration

• Equianalgesic table
• guide to initial dose selection
• Significant first-pass metabolism of po / pr
  doses
• codeine, hydromorphone, morphine
• po / pr to SC, IV, IM
• 23 1

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Changing opioids . . .

• Equianalgesic table
• Transdermal fentanyl
• 25 mg patch 45135 (likely 5060) mg morphine /
  24 h
• 12.5 mg patch is available now

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. . . Changing opioids

• Cross-tolerance
• start with 5075 of published equianalgesic
  dose
• more if pain, less if adverse effects
• Methadone
• start with 1025 of published equianalgesic dose

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Opioid Side Effects
More Common Uncommon Constipation
Bad dreams /
hallucinations Dry mouth
Dysphoria / delirium Nausea / vomiting
Myoclonus / seizures Sedation
Pruritus / urticaria Sweats
Respiratory depression
Urinary retention
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Opioid allergy

• Nausea / vomiting, constipation, drowsiness,
  confusion
• adverse effects, not allergic reactions
• Anaphylactic reactions are true allergies
• bronchospasm
• Urticaria, bronchospasm can be allergies need
  careful assessment

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Urticaria, pruritus

• Mast cell destabilization by morphine,
  hydromorphone
• Treat with routine long-acting, nonsedating
  antihistamines
• fexofenadine, 60 mg po bid, or higher
• or try diphenhydramine, loratadine, or doxepin

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Constipation . . .

• Common to all opioids
• Opioid effects on CNS, spinal cord, myenteric
  plexus of gut
• Prophylaxis is critical

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Constipation . . .

• Prokinetic agent
• metoclopramide, cisapride,
• Osmotic laxative
• MOM, lactulose, sorbitol
• Other measures

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. . . Constipation

• Diet usually insufficient
• Bulk forming agents not recommended
• Stimulant laxative
• senna, bisacodyl, glycerine, casanthranol, etc
• Combine with a stool softener
• senna docusate sodium

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Nausea / vomiting . . .

• Onset with start of opioids
• tolerance develops within days
• Prevent or treat with dopamine-blocking
  antiemetics
• prochlorperazine, 10 mg q 6 h
• haloperidol, 1 mg q 6 h
• metoclopramide, 10 mg q 6 h

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. . . Nausea / vomiting

• Other antiemetics may also be effective
• Alternative opioid if refractory

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Sedation . . .

• Onset with start of opioids
• distinguish from exhaustion due to pain
• tolerance develops within days
• Complex in advanced disease

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. . . Sedation

• If persistent, alternative opioid or route of
  administration
• Psychostimulants may be useful
• methylphenidate, 5 mg q am and q noon, titrate

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Respiratory depression . . .

• Opioid effects are variable for every patient
• pain is a potent stimulus to breathe
• pharmacologic tolerance is rapid
• Loss of consciousness precedes respiratory
  depression

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. . . Respiratory depression

• Management
• identify, treat contributing causes
• reduce opioid dose
• observe
• if unstable vital signs
• naloxone, 0.1-0.2 mg IV q 1-2 min

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Pain Management

• Assess thoroughly
• Look up your doses (mg/kg)
• Dose to reduce pain by at least 50
• Know your patient
• Reassess