• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Chronic Pain After Surgery Molecules
 

Chronic Pain After Surgery Molecules

on

  • 6,161 views

Chronic pain after surgery. More than just a nuisance?

Chronic pain after surgery. More than just a nuisance?

Statistics

Views

Total Views
6,161
Views on SlideShare
6,065
Embed Views
96

Actions

Likes
3
Downloads
206
Comments
1

8 Embeds 96

http://wspain.blogspot.com 40
http://gsmsoc.blogspot.com 21
http://wspain.blogspot.co.uk 16
http://gsmsoc.blogspot.co.uk 13
http://www.slideshare.net 3
http://www.wspain.blogspot.com 1
http://wspain.blogspot.de 1
http://wspain.blogspot.it 1
More...

Accessibility

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel

11 of 1 previous next

  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
  • Fioricet is often prescribed for tension headaches caused by contractions of the muscles in the neck and shoulder area. Buy now from http://www.fioricetsupply.com and make a deal for you.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

Chronic Pain After Surgery Molecules Chronic Pain After Surgery Molecules Presentation Transcript

  • Mick Serpell Senior Lecturer Post-op Pain & Molecules
    • Drug developments
      • algorithm
      • combinations
      • prevention?
      • new drugs
  • Combination Pain
    • post-operative
    • PHN, PDN trauma O/A, Rh/A
    • neuropathic  ---------------------------  nociceptive
        • (mixed)‏
  • Drug Developments
      • optimal drug strategy
      • drug combinations
      • drug prophylaxis
      • new drugs
  • WHO ladder - Nociceptive Pain
    • Step 1
      • Paracetamol
      • NSAIDs or COX II?
    • Step 2
      • codeine, dihydrocodeine, dextropropoxyphene, meptazinol
      • often as co-analgesics ie: co-codamol
    • Step 2  3 Tramadol
    • Step 3
      • morphine, diamorphine, pethidine
      • methadone, fentanyl, buprenorphine
      • oxycodone, hydromorphone
  • Neuropathic analgesics
    • Adjuvants
      • tricyclic antidepressants
      • anticonvulsants
    • others
      • opioids
      • sodium channel blockers
      • NMDA antagonists
      • capsaicin
      • cannabis
  • NNT 0 2 4 6 8 10 12 Topiramate* Antidepressants, SSRI Capsaicin NMDA antagonists* Mexiletine* Antidepressants, SNRI Gabapentin/pregabalin Tramadol Opioids Carbamazepine/lamotrigine/ phenytoin Valproate Tricyclic antidepressants 397 109 83 389 120 420 1057 149 81 466 150 214 Peripheral neuropathic pain drugs: NNT Adapted from Finnerup et al. Pain 118 (2005) 289–305 Lidocaine plaster NNT to achieve pain relief >50%
  • Peripheral neuropathic pain drugs: NNH (withdrawal of Rx)‏ NNH 0 5 10 15 20 Antidepressants, SSRI Valproate Mexiletine Carbamazepine/lamotrigine/ phenytoin Gabapentin/pregabalin Opioids Antidepressants, SNRI Tricyclic antidepressants NMDA antagonists Capsaicin Tramadol Topiramate ns Finnerup et al. Pain 118 (2005) 289–305 Lidocaine plaster
  • Algorithm for neuropathic pain treatment: an evidence based proposal Lidocaine patch* TCA (SNRI)‏ Gabapentin/ Pregabalin Gabapentin/ Pregabalin Postherpetic neuralgia and focal neuropathy Peripheral neuropathic pain yes TCA (SNRI)‏ yes Tramadol, Oxycodone TCA contraindication no yes TCA contra-indication no no Finnerup et al. Pain 118 (2005) 289–305
  • 2 nd Line Rx Beyond 2 nd line Rx single RCT, variable multi RCT Dworkin. Arch Neurol 2003:60:1524-34.
    • Antidepressants
      • citalopram
      • paroxetine
      • venlafaxine
      • bupropion
    • Anticonvulsants
      • lamotrigine
      • carbamazepine
    • mexilitine
    • capsaicin
    • clonidine
  • Drug Developments
      • optimal drug strategy
      • drug combinations
      • drug prophylaxis
      • new drugs
  • Multi-modal Rx
    • Well established for acute pain
    • Analgesic league table
    • data based on single dose
    • post-op dental model
    • www.jr2.ox.ac.uk/Bandolier
  • Combining drugs Neuropathic vs. Nociceptive Drugs
    • ------------
    • ------------
    • Tramadol
    • Opioids
    • Tricyclics
    • Anticonvulsants
    • Capsaicin 0.075%
    • Lidoderm
    • Paracetamol
    • NSAIDs
    • Tramadol
    • Opioids
    • Tricyclics
    • ------------
    • Capsaicin 0.025%
    • ------------
  • Gabapentin & morphine for acute pain after mastectomy Dirks Anesthesiology 2002; 97: 560-564.
    • DB-RCT, n = 70
    • GBP 1200mg 1h pre-op
    • PCA morphine post-op
    •  morphine, p<0.0001
    • 29 (21-33) v 15 mg (10-19)
    •  VAS rest & cough
    • p<0.0001 & 0.018
  • Acute Post-op Pain
    • Meta-analysis
      • Dahl JB. Acta Anaesth Scand 2004. 48(9):1130-6.
      • 7 studies – gabapentin + standard analgesic regimen
      • Lap chol, VV’s, IH repair etc.
      • all show  analgesic requirements at 24 or 48 hr
    • Editorial
      • Rowbotham D. BJA 2006. 96: 152.
  • Additive or synergistic? Isobolographs Fletcher D. Anesthesiology 1997;87:317-326. Synergy Diclofenac & Morphine Additive Propacetamol & Morphine
  • Morphine vs GBP vs Combination for NP Gilron. NEJM 2005; 352: 1324-34.
    • Patients – PHN or DN
    • single site over 33 months
    • DB-RCT (balanced Latin-square cross over)‏
    • active PBO (lorazepam)‏
    • x 4 crossover for 5 weeks each < 60kg, > 60yr
      • Morphine SR 120mg 60 mg
      • Gabapentin 3200 mg 2400 mg
      • M + G 60, 2400
      • Lorazepam 1.6 mg
  • Morphine vs GBP vs both for NeuP Gilron. NEJM 2005; 352: 1324-34.
    • Group MG M G PBO
    • Pain VAS 3.06 3.7 4.15 4.49
    • p value = 0.04 < 0.001 < 0.001
    • Single dose Combination dose
    • M 45 mg (4) 34 mg (3) p <0.05
    • G 2210 mg (90) 1705 mg (83) p <0.05
    • Side effects
    • MG > G for constipation p<0.05
    • MG > M for dry mouth p<0.05
  • GBP+Oxycontin vs GBP+PBO for NP Hanna M. Poster EFIC 2006.
    • Patients – PDN > 3/12, VAS > 5
    • 70 sites across Europe & Australia
    • DB-RCT
    • x 2 groups for 12 weeks each
      • Gabapentin max tolerated dose for 1 month
      • Oxycontin 5, 10, 20, 40 mg BD
      • PBO BD
    • RESULTS
    •  paracetamol tabs/day
    •  sleep disturbance
    • but = sleep quality
    • MPQ & BPI improved & = EQ 5D
    (33%)‏ ↓ VAS 2.1 vs PBO 1.5
  • GBP+Oxycontin vs GBP+PBO for NP Hanna M. Poster EFIC 2006.
    • S/E - mostly mild/mod
      • 88% vs 71%
    • SAE
      • 11% vs 11%
    • W/D
      • 26% vs 22%
  • Drug Developments
      • optimal drug strategy
      • drug combinations
      • drug prophylaxis ?
      • new drugs
  • Pre-emptive analgesia?? Patrick Wall
  • Pre-emptive preoperative analgesia P Wall. Pain 1988; 33:289-90.
    • afferent nociceptive barrage can trigger prolonged spinal cord hyperexcitability
    • “ consider the possibility that pre-emptive preoperative analgesia has prolonged effects which long outlast the presence of drugs”
      • brief incisional phase (1 o )‏
    longer inflammatory phase (2 o )‏ Pre-emptive analgesia
    • Reasons for weak
    • clinical effect in man
    • incomplete analgesia
    • inadequate duration
    • hyperalgesia not addressed
  • Incisional (post-op) Pain Brennan TJ. Anesthesiology 2002, 97: 535-537
    • typically regarded as nociceptive
    • tissue injury converts pain system from
      • a 'physiological' to a 'pathological' mode
    • gabapentin is active in animal models of 'pathological' pain
  • Gabapentin & morphine for acute pain after mastectomy Dirks Anesthesiology 2002; 97: 560-564.
    • DB-RCT, n = 70
    • GBP 1200mg 1h pre-op
    • PCA morphine post-op
    •  morphine, p<0.0001
    • 29 (21-33) v 15 mg (10-19)
    •  VAS rest & cough
    • p<0.0001 & 0.018
  • Prophylaxis of PHN Bowsher. J Pain Symp Manage 1997;13:327-31 .
    • DB-RCT, n = 72 (> 60 yrs) acute onset herpes zoster
    • amitriptyline 25 mg for 90 days
    • PHN prevalence reduced by 50% at 6/12
      • Control 50%
      • vs.
      • Amitriptyline 25%
  • ? Prophylaxis of PHN Berry JD. Neurology 2005;65:444-7.
    • DB-RCT x over, n = 26 acute zoster pain
    • single dose - gabapentin 900 mg vs. PBO
    • Pain VAS improved during 1.5-6 hrs
      • 66% vs. 33%
    • Allodynia area reduced Allodynia intensity reduced
      • 44% vs. 11% - 54% vs. 38%
  • Post-op Pain … what outcomes? Wu C. Anesthesiology 2002; 97: 533-534.
    •  pain VAS - dynamic
    •  analgesic dose
    •  side effects - N/V, HR, RR, M & M
    •  recovery profile
      • PO, PU, PR, mobility, discharge
      • hyperalgesia (alteration in CNS processing) -> QST
    • HRQoL - “soft” outcome
      • global function, patient preferences, cost
      • chronic pain
  • Drug Developments
      • optimal drug strategy
      • drug combinations
      • drug prophylaxis?
      • new drugs
  • Cannabinoids
    • fat soluble “vitamin M”
    • 21 carbon alkaloids -60 members
    • CB1 R (CNS)
    • CB2 R (immune cells)
    • delta-9-tetrahydrocannabinol (THC) mimics anandamide
      • GW Pharma S/L Sativex spray
      • THC:CBD 27:25 mcg/ml
  • Sativex in NeuP + Allodynia: a 5/52 RCT DB Trial Nurmikko, Serpell et al. Pain (in press)‏
    • parallel, 63 Sativex & 62 PBO
    • remained on usual analgesic Rx
    • titrated sprays up to max 24/day
    • 1 ° outcome – VAS pain
    • 2 ° outcomes
      • - NPS, sleep, PDI, PGIC
      • allodynia – punctate & dynamic
  • 7.5 7.0 6.5 6.0 5.5 5.0 4.5 0 Baseline Wk 2 Wk 3 Wk4 Wk 5 Pain Baseline Titration Wk 1 Wk 2 Wk 3 Wk 4 Sleep disturbance * P<0.05 4 3 2 1 0 ## P<0.001 CBM Placebo Wk 1 ** # P<0.01 ## ## ## ## # ** P<0.01 ** ** * Sativex in NeuP + Allodynia: a 5/52 RCT DB Trial Nurmikko, Serpell et al. Pain (in press)‏ -0.52 -1.48
    • All 2° outcomes +ve
    • - NPS, sleep, PDI, PGIC
    • allodynia: punctate & dynamic
    • W/D due to S/E 18% vs. 3%
  • Short term adverse effects
    • Usually transient & resolve during titration
    • Depression of CNS
      • Dizziness
      • Dry mouth
      • Sedation
      • myalgia or muscle weakness
      • palpitations
      • mood changes
  • Canada & Cannabis
  • Canada & Cannabis www.torontohemp.com
  • Lidocaine Plaster: A new treatment option
    • • Soft, stretchy, adhesive plaster
    • • Hydrogel-plaster
    • • 14 x 10 cm
    • • 5% lidocaine (total 700 mg)‏
    • • applied 12 hrs ON, 12 hrs OFF
    • Indication:
    • • Topical treatment of PHN
  • Post-op Pain & Molecules
    • Drug developments
      • algorithm
      • combinations
      • prevention?
      • new drugs
    [email_address]
  • The Patient