What to do when opioids fail Romayne Gallagher MD CCFP Eldercare and Palliative Care Programs Providence Health Care
Definition <ul><li>Opioid success is achieving good pain relief with manageable side effects </li></ul><ul><li>Opioid fail...
Opioid Failure  Differential Diagnosis <ul><li>Pseudo-failure –  not really failure </li></ul><ul><li>Semi-failure –  cann...
Pseudo-failure <ul><li>Inadequate dosing </li></ul><ul><ul><li>If pain uncontrolled must increase dose by 15-25% each titr...
Pseudo-failure <ul><li>Intolerable side effects before adequate pain control </li></ul><ul><ul><li>e.g. 80 year old with e...
 
Opioid Metabolites *After Smith MT. Clinical and Experimental Pharmacology and Physiology 2000
Opioid Induced Neurotoxicity <ul><li>Predisposing Factors: </li></ul><ul><ul><li>High opioid doses </li></ul></ul><ul><ul>...
Management of OIN <ul><li>Rehydration </li></ul><ul><li>Treat concurrent causes of delirium e.g. UTI, pneumonia </li></ul>...
Pseudo-failure <ul><li>Interindividual variation  </li></ul><ul><ul><li>genetic variation in opioid receptors and metaboli...
All animals received same mg/kg dose
Individualize analgesic therapy <ul><li>Opioid actions and interactions are dependent upon the genetic background of the p...
 
Pseudo-failure <ul><li>Cognitive impairment </li></ul><ul><ul><li>dementia, head injury </li></ul></ul><ul><li>Depression ...
Prevalence <ul><li>Depression in Primary Care 5-10% </li></ul><ul><li>Depression in chronic pain  24-37% </li></ul><ul><li...
Neuroconnections  <ul><li>Pain modulation system functions on serotonin and norepinephrine </li></ul><ul><li>?reduced pain...
Pain Physical   symptoms Psychological Social Cultural Spiritual Suffering Woodruff, 1999
Opioid addiction in pain patients <ul><li>Deserve to have pain adequately controlled </li></ul><ul><li>Need more: </li></u...
Semi-failure  <ul><li>Neuropathic pain </li></ul><ul><ul><li>Trigeminal neuralgia </li></ul></ul><ul><ul><li>Complex Regio...
Evidence for the Pharmacotherapy  of Neuropathic Pain <ul><li>Tricyclics   NNT 1.5-3.0 </li></ul><ul><li>Anti-convulsant d...
Canadian Pain Society:   consensus statement on management of Neuropathic Pain 2007 <ul><li>First line </li></ul><ul><ul><...
Moderate-Severe  Neuropathic Pain Treatment <ul><li>Response to monotherapy usually limited; shift to multiple drug therap...
Topical Treatments <ul><li>Capsaïcin cream (Zostrix ® ) </li></ul><ul><li>Lidoderm ®   5% patch (Lidoderm U.S. only) </li>...
Other Topical Treatment Options <ul><li>4-10% ketamine </li></ul><ul><li>2-5% amitriptyline </li></ul><ul><li>0.01mg cloni...
Incident pain <ul><li>A type of breakthrough pain that is evoked by certain activities </li></ul><ul><li>Intensity can be ...
Time Pain Having a steady level of enough opioid to treat the peaks of incident pain... … will often result in excessive d...
Sublingual sufentanil <ul><li>10mcg-25mcg s.l. </li></ul><ul><li>Onset 5 minutes, offset 30 minutes </li></ul><ul><li>For ...
Pressure ulcers <ul><li>Systemic opioids often result in intolerable side effects with poor analgesia </li></ul>
Topical Opioids <ul><li>Ischemic ulcers, pressure ulcers </li></ul><ul><li>Tumors </li></ul><ul><li>Exposed tissue has opi...
 
 
Semi-failure <ul><li>Visceral pain </li></ul><ul><ul><li>Smooth muscle spasm </li></ul></ul><ul><ul><li>e.g. bladder spasm...
Outright failure <ul><li>No analgesia at all to a trial of every available opioid </li></ul><ul><li>Extremely rare individ...
In other words…… <ul><li>Vast majority of pain can be treated either partially or completely with opioids </li></ul><ul><l...
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What To Do When Opioids Fail

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  • What To Do When Opioids Fail

    1. 1. What to do when opioids fail Romayne Gallagher MD CCFP Eldercare and Palliative Care Programs Providence Health Care
    2. 2. Definition <ul><li>Opioid success is achieving good pain relief with manageable side effects </li></ul><ul><li>Opioid failure is little or no analgesia and/or intolerable side effects </li></ul>
    3. 3. Opioid Failure Differential Diagnosis <ul><li>Pseudo-failure – not really failure </li></ul><ul><li>Semi-failure – cannot relieve pain without adjuvant medication </li></ul><ul><li>Outright failure – no pain relief </li></ul>
    4. 4. Pseudo-failure <ul><li>Inadequate dosing </li></ul><ul><ul><li>If pain uncontrolled must increase dose by 15-25% each titration </li></ul></ul><ul><li>Poor absorption </li></ul><ul><ul><li>Short GI tract not suitable for long-acting opioids </li></ul></ul><ul><ul><li>Elders who are emaciated will not absorb fentanyl patch well </li></ul></ul>
    5. 5. Pseudo-failure <ul><li>Intolerable side effects before adequate pain control </li></ul><ul><ul><li>e.g. 80 year old with extensive compression fractures resulting in chronic pain </li></ul></ul><ul><ul><li>morphine, oxycodone, methadone all resulted in intolerable drowsiness with inadequate pain control </li></ul></ul>
    6. 7. Opioid Metabolites *After Smith MT. Clinical and Experimental Pharmacology and Physiology 2000
    7. 8. Opioid Induced Neurotoxicity <ul><li>Predisposing Factors: </li></ul><ul><ul><li>High opioid doses </li></ul></ul><ul><ul><li>Prolonged opioid use </li></ul></ul><ul><ul><li>Recent rapid dose escalation </li></ul></ul><ul><ul><li>Dehydration </li></ul></ul><ul><ul><li>Renal failure </li></ul></ul><ul><ul><li>Advanced age </li></ul></ul><ul><ul><li>Other psychoactive drugs </li></ul></ul><ul><ul><li> *Daeninck PJ, Bruera E. Acta Anaesthesiol Scand. 1999 </li></ul></ul>
    8. 9. Management of OIN <ul><li>Rehydration </li></ul><ul><li>Treat concurrent causes of delirium e.g. UTI, pneumonia </li></ul><ul><li>Reduce dose if pain controlled </li></ul><ul><li>Switch to a different opioid </li></ul><ul><li>Intrathecal administration of opioids </li></ul>
    9. 10. Pseudo-failure <ul><li>Interindividual variation </li></ul><ul><ul><li>genetic variation in opioid receptors and metabolism </li></ul></ul>
    10. 11. All animals received same mg/kg dose
    11. 12. Individualize analgesic therapy <ul><li>Opioid actions and interactions are dependent upon the genetic background of the patient. </li></ul><ul><li>This may involve intrinsic analgesic mechanisms and/or pharmacokinetics/metabolism </li></ul><ul><li>The choice of drug is empiric. At this time, it is not possible to predict which patients will be sensitive to which specific drugs. </li></ul><ul><li>Patients may differ with regards to the necessary dose of specific drug and whether or not that drug, at a reasonable dose, is capable of relieving their pain </li></ul>G. Pasternak MD, PhD Head, Molecular Neuropharmacology Memorial Sloan-Kettering Cancer Centre
    12. 14. Pseudo-failure <ul><li>Cognitive impairment </li></ul><ul><ul><li>dementia, head injury </li></ul></ul><ul><li>Depression presenting as pain </li></ul><ul><li>Total pain </li></ul><ul><li>Opioid addiction in a patient with pain </li></ul>
    13. 15. Prevalence <ul><li>Depression in Primary Care 5-10% </li></ul><ul><li>Depression in chronic pain 24-37% </li></ul><ul><li>Pain symptoms in depressed pts. 65% </li></ul><ul><li>Depressive symptoms in pain pts. 38% (5-85%) </li></ul>
    14. 16. Neuroconnections <ul><li>Pain modulation system functions on serotonin and norepinephrine </li></ul><ul><li>?reduced pain modulation in depression </li></ul><ul><li>Serotonin and norepinephrine given intrathecally block peripheral pain signals as do opioids </li></ul><ul><li>Neuroanatomical connections between brain emotion-generating areas and pain modulation areas </li></ul>
    15. 17. Pain Physical symptoms Psychological Social Cultural Spiritual Suffering Woodruff, 1999
    16. 18. Opioid addiction in pain patients <ul><li>Deserve to have pain adequately controlled </li></ul><ul><li>Need more: </li></ul><ul><ul><li>Assessment: addiction consult </li></ul></ul><ul><ul><li>Structure: contract, shorter dispensing intervals, no prn meds, one pharmacist… </li></ul></ul><ul><ul><li>Monitoring: frequent follow up, random urine screen, function diary, collateral info.. </li></ul></ul>
    17. 19. Semi-failure <ul><li>Neuropathic pain </li></ul><ul><ul><li>Trigeminal neuralgia </li></ul></ul><ul><ul><li>Complex Regional Pain Syndrome </li></ul></ul><ul><ul><li>Central post stroke pain </li></ul></ul>
    18. 20. Evidence for the Pharmacotherapy of Neuropathic Pain <ul><li>Tricyclics NNT 1.5-3.0 </li></ul><ul><li>Anti-convulsant drugs NNT 2-3 </li></ul><ul><li>Opioids* NNT 2-3 </li></ul><ul><li>Gabapetinoids NNT 3-5 </li></ul><ul><li>Venlafaxine NNT: 4.5-5 </li></ul><ul><li>SSRIs NNT: 6-7 </li></ul><ul><li>Mexiletine NNT:10-16 </li></ul>(NNT= # of patients treated to get 1 with a 50% pain reduction) *Opioids avg. pain reduction across studies ~ 30% (Kalso Pain, 2004)
    19. 21. Canadian Pain Society: consensus statement on management of Neuropathic Pain 2007 <ul><li>First line </li></ul><ul><ul><ul><li>TCA/ gabapentin/ pregabalin </li></ul></ul></ul><ul><li>Second line </li></ul><ul><ul><ul><li>SNRI/ 5% lidocaine cream(PHN only) </li></ul></ul></ul><ul><li>Third line </li></ul><ul><ul><ul><li>CR opioids or tramadol </li></ul></ul></ul><ul><li>Fourth line </li></ul><ul><ul><ul><li>Cannabinoids/ methadone/ lamotrigine/ topiramate </li></ul></ul></ul>
    20. 22. Moderate-Severe Neuropathic Pain Treatment <ul><li>Response to monotherapy usually limited; shift to multiple drug therapy </li></ul><ul><li>Opioids </li></ul><ul><li>Adjuvants: </li></ul><ul><ul><li>Antidepressants, selective noradrenaline and serotonin reuptake inhibitors </li></ul></ul><ul><ul><li>TCAs including pregabalin and gabapentin for diabetic neuropathy and postherpetic neuralgia </li></ul></ul>Davis MP. What is new in neuropathic pain? Support Care Cancer 2006;[Epub ahead of print]
    21. 23. Topical Treatments <ul><li>Capsaïcin cream (Zostrix ® ) </li></ul><ul><li>Lidoderm ® 5% patch (Lidoderm U.S. only) </li></ul><ul><li>Xylocaïne ® 10% Cream: </li></ul><ul><ul><li>10 g of xylocaine powder (Xenex ® ) </li></ul></ul><ul><ul><li>90 g Glaxal base </li></ul></ul><ul><ul><li>q4h prn – warn re: toxicity symptoms </li></ul></ul><ul><li>NSAIDs (Pennsaid ® , 5% diclofenac in Phlogel) </li></ul><ul><li>Usually of benefit for peripheral nerve injuries </li></ul>
    22. 24. Other Topical Treatment Options <ul><li>4-10% ketamine </li></ul><ul><li>2-5% amitriptyline </li></ul><ul><li>0.01mg clonidine (for flushing or swelling) </li></ul><ul><li>2-5% carbamazepine (for burning) </li></ul><ul><li>6-10% gabapentin </li></ul><ul><li>Use in those who do not tolerate medications orally </li></ul>In…PLO Gel
    23. 25. Incident pain <ul><li>A type of breakthrough pain that is evoked by certain activities </li></ul><ul><li>Intensity can be significantly higher than baseline pain </li></ul><ul><li>Matching the intensity of the pain with dosage of opioid </li></ul>
    24. 26. Time Pain Having a steady level of enough opioid to treat the peaks of incident pain... … will often result in excessive dosing for the periods between incidents Incident Incident Incident
    25. 27. Sublingual sufentanil <ul><li>10mcg-25mcg s.l. </li></ul><ul><li>Onset 5 minutes, offset 30 minutes </li></ul><ul><li>For use in those already on opioids </li></ul><ul><li>For opioid naïve – use fentanyl 10-50mcg s.l. as is about 1/10 th potency </li></ul>
    26. 28. Pressure ulcers <ul><li>Systemic opioids often result in intolerable side effects with poor analgesia </li></ul>
    27. 29. Topical Opioids <ul><li>Ischemic ulcers, pressure ulcers </li></ul><ul><li>Tumors </li></ul><ul><li>Exposed tissue has opioid receptors </li></ul><ul><li>Morphine 1% concentration in intra-site gel </li></ul><ul><li>Methadone 1% concentration in Stomahesive powder </li></ul>
    28. 32. Semi-failure <ul><li>Visceral pain </li></ul><ul><ul><li>Smooth muscle spasm </li></ul></ul><ul><ul><li>e.g. bladder spasm, rectal spasm </li></ul></ul><ul><ul><li>Calcium channel blockers, nitroglycerin paste </li></ul></ul><ul><ul><li>Belladonna and opium suppositories </li></ul></ul><ul><li>Skeletal muscle contracture </li></ul><ul><ul><li>Botulinum toxin </li></ul></ul>
    29. 33. Outright failure <ul><li>No analgesia at all to a trial of every available opioid </li></ul><ul><li>Extremely rare individuals </li></ul>
    30. 34. In other words…… <ul><li>Vast majority of pain can be treated either partially or completely with opioids </li></ul><ul><li>If pain is not responding….. </li></ul><ul><ul><li>Change opioid </li></ul></ul><ul><ul><li>Adjuvant medications </li></ul></ul><ul><ul><li>Depression or other psychiatric illness </li></ul></ul><ul><ul><li>Interventional pain management? </li></ul></ul><ul><ul><li>Total pain </li></ul></ul>

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