June 3, 2009 Palliative Care Team Drs. St. Godard, Loiselle, Hohl and Pilkey
Mar 27, 2015
June 3, 2009Palliative Care Team
Drs. St. Godard, Loiselle, Hohl and Pilkey
ObjectivesBy the end of the hour the learner will be
able to:Define neuropathic painList at least 2 types of Pain receptorsList at least 4 different types of adjuvant pain
medicationsList the mechanisms of action, benefits, and
side-effects of these 4 medicationsList 2 new/different adjuvant pain medications
Talk OutlineCase Study – Dr. Ted St. Godard & Dr. Joel Loiselle
Pathophysiology of Neuropathic Pain – Dr. Jana Pilkey
Adjuvant Medications – Dr. Chris Hohl
What’s new/different in Neuropathic Pain – Dr. Jana Pilkey
HistoryMs. G. D. 55 y.o with breast cancerMets to bonePain to left arm
History2 week hx of worsening painMid back – dull ache, PressureBurning to L hand and arm
Since 1997brachial plexus neuropathy
“Pins and needles”“Like dipped in acid”Morphine for 4 weeks not helping
Cancer HistoryBreast cancer dx 1997Lumpectomy, tamoxifen x 2 yrsMastectomy 1999 and LN dissectionOophorectomy 1999Multiple courses of chemo2008- mets to c-spine, ribs, sternum.Sept 2008 – Rx to spinePhx: PUD
Physical Exam & InvestigationsTemp 37.2Hr 100Rr 18Sao2 – 90% on RABP 150/88Lab work normal throughout
Course in HospitalAdmission orders:
Methadone 5mg bidDex 10mg bidPariet 20mg po odDilaudid 8 mg subcut q4h and q1prnFentanyl 50 per IPP
Course in HospitalDec 30
Myoclonus noticed – hydratedRotated to fentanyl patchMethadone increased
Jan 14CT head – mets to R cerebellum and R frontal
lobePain better- on methadone 40 bid, dex 8 bidStarts 12 rdtx to whole brain
Course in HospitalJan 27 Pain Crisis
Severe excruciating burning painFrom neck to top of R shoulderCrying, screamingBT HM ineffectiveSlept with 5mg versedMethadone increasedKetamine added 2.5 mg subcut tidPregabalin added 50mg bidLidocaine 2% gel to shoulder qid prn
Potentially useful Peripheral Nerve Block in this Case
Interscalene block-Performed at root level -“Single shot” -only lasts 12 h.-Catheter techniques difficult to maintain (displacement).-Disease extent limits anesthetic flow.-Risk of bleeding /epidural hematoma is prohibitive in this case.
Neuraxial (Intraspinal) blocksEpidural:comparable to bilateral
peripheral nerve block catheter outside dura would be placed at C7/T1
Intrathecal = Spinal catheter enters CSF in
lumbar cisterncan be guided to high
thoracic level as required for upper limb pain
Contraindications to Neuraxial Analgesia in this Case- Extent of Disease involving C-spine:
- Risk of epidural hematoma if needle at C7-T1.- Poor CSF flow impedes spread of analgesics
- Brain Metastasis:- Posterior Fossa- increased risk of “coning”- Relative contraindication
Remember coagulopathy (Plt <100; INR >1.3) and need for ongoing anticoagulation are contraindications.
Course in HospitalConsult to Dr J. Loiselle
Nerve-block or epidural too risky given fragility of spine and cerebellar mets
Jan 28Pain continuesOn Methadone 60mg bidStarts fentanyl 50mcg/hr IVHM stopped – twitchingKetamine 5 mg subcut tid
Course in HospitalJan 28
Family concerned about sedation on fentanylJan 29
RR 7 - fentanyl stopped, Pain again severeFentanyl IV not restarted at family requestAtivan started
Jan 30 – Mini Case conferenceKetamine IV @ 2.5mg/hrGabapentin being lowered
Course in HospitalJan 31-Feb 5 – good pain controlFeb 6 – weepy and tired, pain with movementFeb 9 – increase in ketamine IV 3.52mg/hrFeb 13 – increase in ketamine IV 6mg/hrFeb 17 – decrease po intake – deteriorating –
ketamine 7.5mg/hr
Course in HospitalFeb 19 – pt wishes she could sleep until
death – tired of trying to “hold the pain in”
Feb 23 – unresponsiveFeb 26 – prognosis hrs to days/ discussed
sedationFeb 28 – difficulty maintaining sedationMar 4 – died sedated and comfortable
What is Neuropathic Pain?Pain initiated or caused by a primary lesion
or dysfunction in the nervous system
Characterized by :Burning, Tingling, Electric ,Shooting Pain
Pain ReceptorsA delta
Mechanical sensation eg. Cut, prick
C fibresDiffuse, respond to many stimuliBurning sensation
Sleeping receptorsActive in injured tissue onlyAcquire mechanical sensitivity
(Almeida 2004)
NociceptorsDamaged tissue releases:
Serotonin, Substance P, Bradykinin, Prostaglandin
Involved in acute & chronic pain
Influenced by endorphins
SensitizationCan be a tissue level (primary) orAt CNS level (secondary)
Results in: threshold of activation after injury intensity of a response to a noxious stimulus emergence of spontaneous activity
(Aguggia 2003)
SensitizationPrimary sensitization
Sympathetic activity and Inflammatory Mediators (Chong 2003)
Secondary sensitizationCNS changes in spinal cord and brainNMDA receptors activated“Wind-up” = increased amplitude and frequency
summation in neurons after prolonged stimulation (Chong 2003)
Blocked by NMDA antagonists, anti-inflammatories (McHugh 2000)
The Dorsal Root Ganglion
Tricyclic Antidepressants (TCAs)40-60% efficacy for partial relief (NNT~2.5-3)Start 10-25 mg/d and 10-25mg each week
Best effects: 50-150 mg/dayMechanism:
NE & 5HT reuptake blockade +/- NMDA antagonism, +/- Na channel blockade
Anticholinergic effectsSecondary amine better tolerated
Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
DuloxetineNNT ~4-5 (~7 for SSRI)Start & efficacious @
60mg/dayAntidepressant &
anxiolyticFavorable side effect
profileLimited long term data
VenlafaxineStart 37.5 mg/day Increase by 37.5 mg
weeklyEffective @ 150-225 mg/dLower doses – results
inconsistentShort vs XR preps
ά2-δ Ligands (Gabapentinoids)
GabapentinFew drug interactionsDizziness & sleepinessExacerbate cognitive
impairment Start 100-300mg TIDTitrate to 1800-3600 mg/dPeak effect in >2 weeks
PregabalinNo drug interactionsSimilar side effects to gabaStart 50-150mg divided Q8-
12HTitrate 50-150mg/day
weeklyGoal 300-600 mg/d in 1-2
weeksPeak effect in 2 weeks
Bind to ά2-δ subunit of voltage gated Ca channels glutamate, NE, substance P releaseNNT ~3.5-4.5
Opioids20-30% pain reduction, NNT
~2.5Provides rapid reliefRapid titration No ceiling effectMultiple forms & delivery
methodsMore side effects than 1st line
treatments Risk of misuse and abuse (5%)
Methadoneμ-receptor agonist + NMDA antagonist
Very long half-life, variable in individuals
Slow titration: start 2.5mg TID
Increase 50-100% every 48-72 hours
~5:1 to ~30:1 morphine equivalency (depending on
dose)
Little literature support, ++ practical support
NMDA AntagonistsKetamineStart 2.5-5mg PO TID Titrate by 50-100% dose to 1-2 mg/kg/dayStart IV infusion @ 0.05-0.1mg/kg/hr IV bolus @ 0.1-0.2 mg/kg/dose over 20 minutesNo NNT data
Poor performance in studies, good efficacy in practice
Topical or gargle preparations possible*opioid sparing effects
Other/New Things to TryIV Lidocaine And po Mexilitine
Cochrane Review 2005
Good quality evidence in neuropathic painBoth decrease VAS by 11 on 1-100 scale47% of people in trials had a 30% decrease in pain
(22% in placebo)35% had Side –effects
Numbness, dizziness, fatigue, metallic tasteAuthors conclude similar efficacy to other
adjuvants and good safety profile
Other/New Things to TryCapsaicin – High dose patch in PHN (640mcg/cm2)
1 – 60 min applicationLasts up to 12 weeksMean decrease in pain score of 29.6%Side-effects – Pain and erythema at site
(Backonja – Lancet Neurology, 2008)
Cannabis – Sativex - Neuropathic pain with AllodyniaImprovements of 1.43 on 10 point VASGood safety profile – SE include GI upset & drowsiness
(Nurmikko – Pain 2007)
Other/New Things to TryIntrathecal Ziconotide
N-type Ca Channel blocker (NCCB)Median dose 6.48mcg/dayImproved VASPI scores in 53.1%Decreased opioid usage in 9%Very expensiveSide Effects:
Memory loss, dizziness, nystagmus, somnolence, gait, CK rise
(Pommer - J Pain Symptom – 2009)
A Comparison of AdjuvantsDrug NNT Titratio
nNotes Side Effects
TCA 2.5-3 2-15 wks Antidepressant, cheap Anticholinergic
Duloxetine 4-5 none Anxiolytic, antidepressant
few
Venlafaxine 4-5 3-5 wks Antidepressant few
Gabapentin 3.5-4.5
1.5-6 mo Min drug interactions Dizzy/sleepy
Pregabalin 3.5-4.5
1-2 wks Min drug interactions Dizzy/sleepy
Methadone ? variable Opioid, cheap Opioid, drug interactions
Ketamine ? 1-4 wks Opioid sparing Hallucinations
Tramadol 3.8 4-8 wks For Diabetes, PHN Anticholinergic
Carbamezapine 1.7 1-4 wks For Trigeminal neuralgia
Drug interactions
Lidocaine/Mexilitine
4 none IV trial then po Cardiac, neurologic
Capsaicin ? none/days Topical Burning, redness
Cannabinoids ? none/days For MS, allodynia GI, drowsiness
Clonidine ? none/days Effective IT, topical Hypotension
Summary/ObjectivesBy the end of the hour the learner will be
able to:Define neuropathic painList at least 2 types of Pain receptorsList at least 4 different types of adjuvant pain
medicationsList the mechanisms of action, benefits, and
side-effects of these 4 medicationsList 2 new/different adjuvant pain medications
Recommended References1. Cruccum, G. Treatment of painful neuropathy.
Current Opions in Neurology. 2007; 20; 531-535.2. Dworkin, R. et al. Pharmacologic management of
neuropathic pain: evidence-based recommendations. Pain. 2007; 132; 237-251.
3. Gilron, I. et al. Neuropathic pain: a practical guide for the clinician. CMAJ. 2006; 175(3); 265-275.