Methadone in acute pain: the W5

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Methadone in acute pain the W5

• Saifee Rashiq MB MSc FRCPC
• Associate Professor
• Director, Division of Pain Medicine
• Department of Anesthesiology and Pain Medicine
• University of Alberta
• Edmonton AB
• srashiq_at_ualberta.ca

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Objectives

• WHAT do I need to know about methadone ?
• WHY use methadone for acute pain ?
• WHO are the best patients to use it in ?
• WHEN do I need to be concerned ?
• HOW do I get through the paperwork ?

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Arthur A

• 51 years old
• Major cancer resection flap
• 24h post-op
• Heavy smoker/drinker
• Was on lots of opioids pre-op
• G-tube. NPO
• Pain out of control

4
Brittany B

• 5 yrs old
• Propane explosion
• Amputation of leg
• 1 week in ICU
• Cant wean morphine drip

5
Chuck C

• Bowel leak following colectomy
• ARDS, ATN
• In ICU for 42 days
• Repeat washouts
• Outgrowing PCA
• Line sepsis / access problems

6
Derek D

• Frostbite injury
• Amputation / debridements
• Severe pain
• Neuropathic component

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What is methadone ?

• Synthetic opioid 60 yrs
• Best known in addiction context
• Potent opioid analgesic (µ and d receptors)
• NMDA antagonist
• Neuropathic pain, tolerance
• Monoamine uptake inhibitor
• Incomplete cross-tolerance with other opioids
• Mostly enteral elimination
• Metabolites are inactive
• Cheap
• Significant individual variation in
  Pharmacokinetics

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Methadone indications on APS

• LA opioid needed in NPO patient
• LA opioid needed in small child
• To spare an i.v. line in ICU
• Neuropathic pain
• Opioid tolerance
• Renal impairment
• True morphine allergy

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Pharmacokinetics

• Highly bioavailable - 85 (morphine 30)
• Highly protein bound
• Highly Lipophilic
• Easily crosses BBB, placenta, and into breast
  milk
• Detectable in plasma 30 mins, peak 4h
• Acute (?)distribution half life is 14.3 ? 6
  h
• Chronic (?) elimination half life is 54.8 ?
  26.8 h
  
• Steady state 2-9 days
• Chronic receptor occupancy half life is 22.5 ?
  6.8 h
• Analgesic dose interval is 8-12h

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CONC
?
?
TIME
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STEADY STATE
Plasma Conc
TIME
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Drug interactions P450 metabolism

• Decreased effect (Increased metabolism)
• Rifampicin
• Respiridone
• Phenytoin
• Spironolactone
• Carbamazepine
• HIV drugs

• Increased Me effect (Decreased metabolism)
• Fluconazole
• Fluvoxamine
• Ciprofloxacin
• ? Amitriptyline

Plus Lots of easily imagined pharmacodynamic
interactions
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Dosage Forms

• Generic powder 1mg/ml oral solution
• Proprietary powder
• Proprietary tablets 1, 5, 10, 25 mg

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Cross-conversion to M.

• Complex literature
• Depends on the situation

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Arthur A

• 12 percocet/ day pre-op
• MS 15 mg s.c. x 8 in past 18 h
• Miserable and angry
• Other issues excluded
• 120 mg i.m. morphine 360 p.o.
• 360/8 mg 45 mg/ day methadone
• Plus rescue morphine

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Brittany B

• 20 Kg
• 70 mcg/kg/hr morphine i.v. 33.6 mg/day iv
• 100 mg/day p.o. morphine
• 100/12 8 mg/day of methadone

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How to switch

• The whole-in-one approach
• Convert, divide into 3 doses and away you go
• The correct approach
• Convert one third at a time over three or more
  days
• Always provide a rescue dose of something

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Malignant arrhythmia with Methadone

• Several reports in high dose methadone
• Usually other explanation exists
• Often asymptomatic ?QTc
• Do ECG etc if gt200mg/d
• www.torsades.org

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Chuck C

• Methadone 25 mg po q8h
• Methadone 7.5 mg po q1h prn
• Or
• Morphine 75 mg po q1h prn
• Morphine 25 mg sq q 1 h prn
• Use PO methadone even when NPO
• 1 or 2 missed doses not a big deal

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Derek D

• Severe pain with neuropathic component
• Poor sleep
• Frequent dressing changes
• Amitriptyline, gabapentin, oxycodone and
  zoplicone
• Methadone, with morphine injected prior to
  dressing changes is a potentially simpler solution

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Regulatory

• You apply to Ottawa for exemption from Section 56
  of the Controlled Drugs and Substances Act.
• Pain, Addiction or both
• General or patient specific
• They obtain a recommendation from your provincial
  college
• Exemption lasts 3 years
• Emergency provisions available to any physician
  in our institution

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Reading

• Lynch ME. A review of the use of methadone for
  the treatment of non-cancer pain Pain Res Manage
  200510(3)133-145
• Handout
• www.uofapain.ca