Pain+management+in+dementia april 2012


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Pain+management+in+dementia april 2012

  1. 1. Pain Management in Dementia: what’s new in opioids? Romayne Gallagher MD, CCFP Division of Palliative Care Providence Health Care
  2. 2. Objectives Basics of pain in dementia NOUG – is it useful for pain in dementia? New opioids New opioid formulations
  3. 3. Prevalence of pain in older adults Prevalence of any kind of pain is stable with increasing age Scudds & Ostbye 2001, Thomas et al 2004 Prevalence of persistent disabling pain increases with age Brattberg et al 1996, Mobily et al 1994
  4. 4. Pain Homeostenosis Diminshed ability to effectively respond to the stress of persistent pain        Decreased cognitive reserves Decreased opioid receptors, neurotransmitors Altered pharmacokinetics/pharmacodynamics Polypharmacy Medical comorbidity Social isolation, depression, loneliness Impairments in ADL  Karp et al. Brit. J. of Anesthesia 2008
  5. 5. Cognitive Impairment (CI) & Pain Management: Nursing Homes Pain is documented less frequently for CI residents, even with similar numbers of painful diagnoses as less impaired residents (Sengstaken & King, 1993) Less analgesic is prescribed/administered for CI residents, despite similar numbers of painful diagnoses (Horgas & Tsai, 1998) Only ¼ of demented residents who are identified as having pain receive any analgesic therapy (Scherder et al, 1999; Bernabei et al, 1998; Won et al, 1999) 5
  6. 6. Ability to self-report pain Pain Self-Report and Cognitive Impairment in Dementia Patients Nonverbal Cognitive impairment 6
  7. 7. Undertreatment of Pain in Patients With Advanced Dementia Prospective cohort study of 59 cognitively intact elderly patients with hip fracture and 38 patients with hip fracture and advanced dementia Daily rating of pain by cognitively intact patients Comparison of analgesic prescribing practices Morrison & Siu, JPSM, 2000 7
  8. 8. Analgesic Prescribing in Hip Fracture Patients with Advanced Dementia Pre-op Mg MSO4/Day 76% of cog. intact patients rated their average preoperative pain as moderate-severe 68% of cog. intact patients rated their average postoperative pain as moderate to severe Post-op 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 Cog Intact Dementia Morrison & Siu, JPSM, 2000 8
  9. 9. Analgesic Prescribing For Dementia Patients Following Hip Fracture Repair As Needed Standing 24% 76% Morrison & Siu, JPSM, 2000 9
  10. 10. Assessment of Pain in Dementia: Medical Problems - Previous and Current Concurrent medical problems (esp. hepatic, renal) Allergies Past painful conditions Past medical history    Hospitalizations Surgery Serious illness 10
  11. 11. Hierarchy of Data Sources Most reliable Resident report (if possible) Prior pain history Painful diagnoses Behavioral indicators Observer assessment Response to empirical therapy Least reliable 11
  12. 12. Empirical Trials Try pain medicine Behaviours suggest it could be pain Behaviours decrease It’s probably pain! 12
  13. 13. What do I need to know to be a better prescriber in older adults?
  14. 14. Maintaining drug levels in the body drug delivery Maximum safe concentration Minimum effective concentration
  15. 15. General factors affecting absorption, distribution & elimination - Age Absorption: Changes in drug absorption tend to be clinically inconsequential. Distribution: Lean mass to fat ratio can change with age resulting in higher concentrations of fat-soluble drugs Serum albumin decreases so in a patient with malnutrition, this may enhance drug effects because serum concentrations of unbound drug are increased.
  16. 16. General factors affecting absorption, distribution & elimination - Age Hepatic metabolism: mass and blood flow decreases which can affect hepatic drug elimination. The hepatic metabolism is reduced and clearance can fall by 30 to 40%. However, the rate of drug metabolism can vary greatly from person to person. The possibility of hepatotoxicity is generally enhanced in the elderly.
  17. 17. General factors affecting absorption, distribution & elimination - Age Reduction in hepatic metabolism Presystemic (first-pass) metabolism of some drugs given orally (eg, labetalol, propranolol, verapamil) is decreased, increasing their serum concentration and bioavailability. Many drugs produce active metabolites in clinically relevant concentrations. Examples are some benzodiazepines, amitriptyline and opioid analgesics such as morphine. The accumulation of active metabolites can cause toxicity in the elderly due to age-related decreases in renal clearance. Toxicity is likely to be severe in those with renal disease.
  18. 18. General factors affecting absorption, distribution & elimination - Age Reduction in renal clearance with age The renal mass and renal blood flow decreases significantly Renal physiological changes decrease renal drug elimination. Because renal function continues to decline, the dose of drugs given long-term needs to be reviewed periodically. Elderly people may also have a reduced rate of compliance Disease - Liver and renal disease reduces rate of elimination
  19. 19. Opioid Induced Neurotoxicity Definition  Neuroexcitability manifested by agitation, confusion, myoclonus, hallucinations and rarely seizures Predisposing Factors:        High opioid doses Prolonged opioid use Recent rapid dose escalation Dehydration Renal failure Advanced age – lack of cognitive reserve, pharmacokinetics changes Other psychoactive drugs *Daeninck PJ, Bruera E. Acta Anaesthesiol Scand. 1999
  20. 20. Opioids and Older Adults Opioids have been associated with a higher risk of fracture (so has chronic pain) Opioids have been associated with delirium - but so have many other medications Most of the studies do not differentiate between opioids or involve pain as a risk factor
  21. 21. Delirium in Hip Fracture Patients 541 patients, no delirium at entry to study 16% of patients became delirious Subjects able to self-report pain  Severe pain prior to delirium OR 9.0 p=0.01  Low doses of opioids (<10 mg of parenteral milligrams of mso4/day) OR 4.4 p=0.03   Received meperidine (NS) Increase in opioid dose after pain detected (NS) Subjects unable to self-report pain  Low doses of opioids (<10 mg of parenteral milligrams of mso4/day) OR 4.0 p=0.004  Received meperidine OR 3.4 p=.001 21 Morrison et al, J Gerontol Med Sci, 2003
  22. 22. What is new in opioids? National Opioid Use Guidelines New opioids available   tapentadol, tramadol buprenorphine New formulations of oxycodone & fentanyl
  23. 23. National Opioid Use Guidelines National opioid use group: mostly regulators Literature review by researchers who derived recommendations National Advisory Panel – Delphi Process Responses from NAP not made public
  24. 24. Opioid Guidelines Generally very useful and worth following The bias is towards the prevention of opioid abuse and diversion – appropriate for about 10% of chronic pain population
  25. 25. Opioid Guidelines Opioid suggestions for frail older adults do not make pharmacokinetic sense  Codeine and tramadol Short-acting opioids Both must be metabolized to be active Codeine metabolized to morphine and active metabolites accumulate in renal failure q4hr opioids in residential care is nursing nightmare
  26. 26. Opioid classes Are all opioids the same?      Opioids bind to three opioid receptors with differing effects There are at least two distinct classes of opioids based on structure Methadone also targets NMDA receptors There are two pathways of metabolism for opioids Two opioids are lipophilic and the rest are more hydrophillic
  27. 27. Opioids of choice in frail elderly and renal failure Hydromorphone Oxycodone Fentanyl Methadone 27
  28. 28. Equianalgesic conversion Morphine Tylenol #3 Codeine Hydromorphone Oxycodone Methadone variable ratio 10mg 2 tablets 60mg 2mg 5-7.5mg 1mg (not q4hr)
  29. 29. Equianalgesic conversion Fentanyl is highly lipophilic A 25mcg fentanyl patch = 100mg morphine/day = 20 Tylenol #3 per day
  30. 30. Notes about the Fentanyl patch Takes 12 hours for onset of analgesia Need adequate subcutaneous tissue for absorption Takes 24 hours to reach maximum effect Change patch every 72 hours Dosage change after six days on patch Suitable for stable pain only
  31. 31. OxyNeo replaces OxyContin Oxycodone in a new formulation Turns to gel on contact with water   not injectable can’t delay swallowing Extremely crush resistant Special authority needed
  32. 32. Targin Oxycodone with core of naloxone Lower incidence of constipation Naloxone not absorbed from the gut – no effect on analgesia Comes in 10, 20, 40mg oxycodone size Naloxone core too large for 5mg SR size so will be phased out Not covered by Pharmacare
  33. 33. Tramadol Tramadol available in Europe (30 years) and US (12 yrs) Dual Action   Opioid agonist Inhibits reuptake of Serotonin and Norepinephrine Metabolism: like codeine requires metabolism to become active View as a weak opioid – ie for moderate pain Available dosage strengths (CR tramadol, q24h)    150, 200, 300 and 400 mg 150mg q24h is the usual adult starting dose for opioid naïve patients Not to exceed 400 mg total daily dose
  34. 34. Tapentadol Very similar to tramadol but new Dual action – mu receptor agonist and norepinephrine reuptake inhibitor Short acting formulation only May be more potent than tramadol Not covered by Pharmacare Needs a duplicate prescription pad
  35. 35. Buprenorphine Semi-synthetic derivative of morphine alkaloid thebaine Highly lipid-soluble High affinity for the μ-opioid receptor   Potent partial agonist action Thought to dissociate slowly from the receptor
  36. 36. Buprenorphine Partial agonist of mu receptor Requires metabolism to become analgesic Ceiling effect – consider as a weak opioid Slow onset, highly bound to receptor Highly lipophilic
  37. 37. The BuTrans® Patch Transdermal delivery eliminates first-pass metabolism Patch delivers very small amounts of buprenorphine  Low plasma concentrations: levels measured in picograms (one trillionth of a gram or 10-12 g) per milliliter Buprenorphine binds and dissociates from the mu-receptor slowly  May account for the prolonged duration of analgesia and, in part, for its limited physical dependence potential Patch provides steady delivery of buprenorphine for up to 7 days  Steady state concentrations achieved during the first application after day 3 Clinical significance has not been fully established. Purdue Pharma Canada. BuTrans® Product Monograph, February 2010.
  38. 38. Bu-Trans patch Experience in other countries is good Useful for moderate pain Potential for use in residential care as would reduce work load of administering pills Not covered by Pharmacare
  39. 39. Incident Pain
  40. 40. Sufentanil for incident pain Well absorbed through buccal, sublingual and nasal mucosa      Onset is 5-10 minutes Cleared in 30 minutes 12.5mcg- 25mcg starting dose Up to 100mcg per dose For sublingual use must be able to follow directions
  41. 41. Intranasal application Inexpensive Reusable on same pt
  42. 42. New formulations of fentanyl Abstral – fentanyl buccal tablets Onsolis – fentanyl buccal film More effective than sl or intranasal sufentanil   pH adjusted less chance of swallowing and inactivating medication Not covered by Pharmacare
  43. 43. Topical Opioids Ischemic ulcers, pressure ulcers, fungating tumors Morphine 1% concentration in intra-site gel Methadone 1% concentration in inert wound powder
  44. 44. Methadone in older adults Well tolerated and effective Starting dose 1mg q12hr Well absorbed orally and bucally Titrate once weekly only Use other short acting opioid for breakthrough pain while titrating methadone Use methadone for breakthrough dose bid-tid once on stable dose Gallagher Pain Med. 2009
  45. 45. Methadone in older adults Many potential interactions but few are clinically significant Clinically significant:    Clarithromycin, rifampin Carbamazepine, phenytoin Fluconazole, ketoconazole QTc prolongation in doses greater than 100-200mg per day
  46. 46. Titrating opioids Increase dose by 15-20% each time if symptom not controlled Starting with long acting opioids?    In residential care inadequate staff to do q4hr opioids Oxycodone SR 10mg = 3 Tylenol #3 Hydromorphone SR 3mg = 3 Tylenol #3 Methadone 1mg q12 hrs = 2 Tylenol #3 ½ 12mcg patch = 5 Tylenol #3
  47. 47. Treating side effects Docusate not useful Senna helpful but can cause cramps Lactulose works well but horrible taste PEG 3350 (Laxaday) works well and can be mixed with drink of choice
  48. 48. Neuropathic Pain Adjuvants Anticonvulsants not well tolerated in oldest adults – ie gabapentin, pregabalin, topiramate  32% withdrawal from study of pregabalin in neuropathic pain Dworkin et al Neurology 2003
  49. 49. Neuropathic Pain Adjuvants TCAs have intolerable side effects  In a trial of TCA vs opioids for neuropathic pain both were effective but patients preferred opioids (54%) to TCAs(30%) to placebo(10%) p=0.02 Raja et al Neurology 2003 SNRIs are likely the best option for older adults with neuropathic pain  Study of >80 years old found it safe and efficacious for depression Baca et al Int J Geriatr Psychiatry 2006
  50. 50. Pain and depression Study of 524 older adults Pain hinders recovery from depression Mavandadi et al JAGS 2007 Disabling chronic low back pain and depression were independent factors that increased the prevalence of each other Meyer et al Spine 2007 Anxiety is also a predictor of pain Feeney J. Anxiety Disord 2004
  51. 51. Interventional pain management Epidural steroid injections: for spinal stenosis, facet joint, nerve compression secondary to OA Vertebroplasty for lumbar compression fractures causing uncontrollable pain/disability
  52. 52. Take Home Messages Older adults with chronic pain are not the same as younger patients with pain There is “pain homeostenosis” (less ability to respond effectively to the stress of chronic pain) Older adults are more likely to loose function with chronic pain if there is a lack of timely intervention
  53. 53. Take Home Messages Minimize polypharmacy Opioids are a safer choice in older adults Opioids with no active metabolites are a better choice in older adults If patients with dementia and pain become drowsy with opioid try reducing neuroleptics Analgesic trials while monitoring behaviour Analgesic trials need to include opioids
  54. 54. Questions? Cases?