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Pain+management+in+dementia april 2012
1. Pain Management in
Dementia: what’s new in
opioids?
Romayne Gallagher MD, CCFP
Division of Palliative Care
Providence Health Care
2. Objectives
Basics of pain in dementia
NOUG – is it useful for pain in dementia?
New opioids
New opioid formulations
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. 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. 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. Ability to self-report pain
Pain Self-Report and Cognitive
Impairment in Dementia Patients
Nonverbal
Cognitive impairment
6
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. 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. Analgesic Prescribing For Dementia Patients
Following Hip Fracture Repair
As Needed
Standing
24%
76%
Morrison & Siu, JPSM, 2000
9
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. 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. Empirical Trials
Try pain medicine
Behaviours suggest it
could be pain
Behaviours decrease
It’s probably pain!
12
13. What do I need to know to
be a better prescriber in
older adults?
14. Maintaining drug levels in the
body
drug delivery
Maximum safe
concentration
Minimum effective
concentration
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. 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. 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. 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. 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. 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. 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. What is new in opioids?
National Opioid Use Guidelines
New opioids available
tapentadol, tramadol
buprenorphine
New formulations of oxycodone & fentanyl
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. Opioid Guidelines
Generally very useful and worth following
http://nationalpaincentre.mcmaster.ca/opioid/
The bias is towards the prevention of
opioid abuse and diversion – appropriate
for about 10% of chronic pain population
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. 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. Opioids of choice
in frail elderly and renal failure
Hydromorphone
Oxycodone
Fentanyl
Methadone
27
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. 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. 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. 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. 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. 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. 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. 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. 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
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
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. Topical Opioids
Ischemic ulcers, pressure ulcers,
fungating tumors
Morphine 1% concentration in intra-site
gel
Methadone 1% concentration in inert
wound powder
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. 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. 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. 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. 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. 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. 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. 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. 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. 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
