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Effective Pain
Management in
Palliative Care
Patients
Paul
Daeninck
CancerCare
Manitoba
W R H A P a l l i a t i ve
Care Program
U n i ve r s i t y o f
M a n i t oba
Objectives
Describe the prevalence of pain in patients
near the end of life
Discuss the concept of total pain
Demonstrate pain assessment
Manage pain using a variety of modalities
Brian
59 yo, married, truck driver
35 pack yr hx of smoking,
chronic cough
Diagnosed with NSCLC lung
(SCC)
Home visit: tells nurse he has
pain
BRIAN
Introduction…
Pain is a frequent problem that is due to
patients’ presenting illness or secondary to
other factors
A physical symptom that patients and families
may fear most
Although clinicians now have effective
treatments at their disposal, pain remains one
of the most poorly assessed and treated
physical symptoms
…Introduction
Lack of knowledge and inexperienced health
care providers as well as patient / family
myths about pain, opioids and addiction
continue to be significant barriers to good
pain management
Effective Care of the Dying
Involves:
1. Adequate knowledge base
2. Attitude / Behaviour / Philosophy
Active, aggressive management of suffering
Team approach
Recognizing death as a natural closure
Broadening your concept of “successful”
care
Dr. Mike Harlos, Personal Communication
Pain Prevalence
Pain is a common symptom for pts with
advanced progressive illnesses, especially
cancer
Most prevalent in advanced cancer patients,
reaching 70–90% prevalence in latter stages
of illness
Symptom Prevalence
Pain
80 – 90+%
Fatigue/Asthenia
Constipation
Dyspnea
Nausea
Vomiting
Delirium
Depression/suffering
75 70%
60%
50 30%
30 40 -
90%
60%
90%
60%
“We can give you enough medication to alleviate
the pain, but not enough to make it fun.”
Pain Classification
Acute or chronic
Nociceptive or neuropathic
in cancer, inflammatory mechanisms for
nociceptive pain more established
Nociceptive Pain
Involves direct stimulation of intact thermal,
mechanical or chemical sensors (nociceptors) ,
specialized sensory neurons and conversion
of stimulus into electrical impulses
transmission of electrical impulse along normally
functioning nerves to spinal cord and brain
Nociceptive Pain
Somatic pain (e.g., skin, soft tissue, muscle, bone)
well-localized, sharp, aching or throbbing
Visceral pain (e.g., cardiac, lung, GI, GU)
stimulation of pain receptors associated
with autonomic nervous system
difficult to describe or localize
Neuropathic Pain…
Disordered function of peripheral or central
nervous system due to a number of causes
Described as burning, tingling, shooting,
stabbing, numbness, or electric-like feelings
…Neuropathic Pain
Characteristic features include radiation of
pain along nerve or dermatomal regions and
lancinating pain (sharp, brief ‘electric shock-like’
pains at rest)
Changes in sensation include hyperalgesia
and allodynia (non-painful stimulation such as
light touch is perceived as painful)
Cancer Pain
Previously, cancer pain was thought to be the
result of tissue injury from tumour invasion
Recent evidence suggests cancer pain more
complex: neurobiological and molecular
mechanisms
These include nociceptors,
inflammatory/chemical factors, mechanical
factors
“A Friend’s Story” by Robert Pope, © Robert Pope Foundation
Total Pain
Family
Patient /
Family
Context
Emotional
State
Physical Source
Health Care
Professionals
History /
Exposure
Personality
Total Pain = Suffering
Brian
59 yo, married, truck driver
35 pack yr hx of smoking,
chronic cough
Diagnosed with NSCLC lung
(SCC)
Home visit: tells nurse he has
pain
BRIAN
Pain Assessment
History
Physical exam
Imaging
Blood testing
Pain History
Most important aspect of pain assessment
inter-professional team activity
collects information from pt/family/cg
complete picture of pt experience
One component of comprehensive
assessment of palliative care patient
Pain History
Temporal features
Daily frequency
Location/Radiation
Severity/Quality
Aggravating and
alleviating
factors
Previous history
(chronic pain, family)
Meaning
Medication(s) taken
Dose
Route
Frequency
Duration
Effect
Side effects
Pain Assessment Tools
No objective measures of pain
Intrinsic difficulties in measuring a
symptom that is entirely subjective and so
multidimensional
Variety of tools have been developed used to
assess pain
Not all measure all aspects of pain
Pain Assessment
History
Physical exam
Imaging
X ray, CT scan (MRI, bone scan)
Blood testing
Liver/renal function, WBC
Cultural Issues
Culture has an impact on pain expression
Care providers need to be culturally
competent with pts to fully understand how
that person may express pain
Pain in the Elderly
May express pain differently
Studies have established high prevalence of
pain in the elderly, yet widespread undertreatment of pain in this group
Increasing age brings more difficulty in using
assessment tools
Pain and Cognitive Impairment
Cognitive impairment due to underlying primary
brain disorders, secondary brain dysfunction
(meds such as opioids and sedatives), or
delirium secondary to infections and metabolic
causes
Pain and Cognitive Impairment
Although the pt may appear impaired, ask if
he/she is experiencing pain
Many pts can provide consistent, useful
information about their pain
Pain assessment tools for cognitively impaired
pts exist, but few subjected to extensive
reliability, validity tests
Presented with difficulty
swallowing x 3 mo
CXR: 3 cm nodule in RUL
CT=LN mass around esophagus
Full staging includes sclerosis of
L4/L5 vertebral body
Had chest RT for symptoms
Refused chemotherapy
BRIAN
He has aching back pain, 7/10,
especially with movement
Also has mild pain on
swallowing
Tylenol #3s help, but makes him
nauseated
Says his friend Jack helps out a
lot…
Jack Daniels
BRIAN
Addiction and Tolerance
Perception that opioids used for pain
management frequently causes addiction is
prevalent
Part of this arises from confusion about
differences between addiction and physical
dependence
Definitions…
Drug addiction: impaired control over drug
use, compulsive use and craving, and
continued use despite harm
Pseudo-addiction: situations where a
patient’s behavior appears drug-seeking but is
a need for more medication to achieve pain
control
…Definitions…
Drug (physical) dependence: physiologic
changes in the presence of opioids, whereas
drug addiction is behavioral
Pharmacologic tolerance: reduced effectiveness of a given dose of medication over
time
“What a coincidence, Mrs. Marble. You’ve
become addicted to the same drugs as I’m
addicted to!”
Addictions
Pain in addicted patients
Assessment includes careful disease
assessment, thorough addiction history,
specific validated scales and tools, urine
drug testing, careful monitoring of
prescription medication use
Develop clinical judgement as to
appropriateness and reasonable dosing for
pain syndrome
Pain: Treatment Spectrum
PHYSICAL
Normal activities
Aqua-fitness
Physio
• Passive
• Active
Stretching
PSYCHOSOCIAL
PHARMACOLOGIC SURGICAL
Hypnosis
Stress
Management
Cognitive
Behavioural
Family therapy
Psychotherapy
OTC medication
Alternative therapy
Topical medications
NSAIDs
Tricyclics
TCNS
Anticonvulsants
OPIOIDS
Local anesthetics
• Blocks
• Oral congeners
Massage
Muscle relaxants
Chiropractic
Sympathetic agents
Acupuncture
NMDA blockers
Conditioning
Weight training
TENS
Orthopedic
Neurotomy
Neurectomy
Implantable
stimulators
Implantable
pain pump
Physical Modalities
Dependent upon functional state
Active:
Normal activities
Physio
Passive / Active / Stretching
Aqua-fitness
Conditioning exercises / weight training
Massage
Physical Modalities
Low activity level:
Physio
Passive / Stretching
TENS / TCNS
Massage
Acupuncture
Psychosocial
Hypnosis /distraction
Stress management
Dignity therapy
Cognitive
/behavioural therapy
Family therapy
Psychotherapy
Pain: Treatment Spectrum
PHYSICAL
Normal activities
Aqua-fitness
Physio
• Passive
• Active
Stretching
PSYCHOSOCIAL
PHARMACOLOGIC SURGICAL
Hypnosis
Stress
Management
Cognitive
Behavioural
Family therapy
Psychotherapy
OTC medication
Alternative therapy
Topical medications
NSAIDs
Tricyclics
TCNS
Anticonvulsants
OPIOIDS
Local anesthetics
• Blocks
• Oral congeners
Massage
Muscle relaxants
Chiropractic
Sympathetic agents
Acupuncture
NMDA blockers
Conditioning
Weight training
TENS
Orthopedic
Neurotomy
Neurectomy
Implantable
stimulators
Implantable
pain pump
WHO
Analgesic
Ladder
Acetaminophen
& NSAIDs
Mild pain
(0-3)
Targeted Rx may be
added at any step
Morphine
+ Step 2
Codeine
+ Step 1
Severe
(7-10)
Moderate
(4-6)
By the mouth
By the clock
By the ladder
Non-opioid Analgesics
Acetaminophen
1 g three times daily, extra doses
Longer acting preparations
NSAIDS / COX-2 inhibitors
Effective in inflammatory conditions
GI, kidney side effects
Cancer prevention?
Gastric protection recommended
Opioid Choice in Canada
Morphine
Oxycodone
Hydromorphone
PO IV PR LA TD TM
X X X X
X
X
X X
X
X X X X
X
---------------------------------------Methadone
Fentanyl
Sufentanil
X
X
X
X
X
X
PO: oral, IV: intravenous/subcutaneous, PR: rectal
LA: long acting, TD: transdermal, TM: sublingual
X
X
X
Opioid Choice in Canada
Codeine
Tramadol/tapentadol
Buprenorphine
PO IV PR LA TD TM
X
X X
X
X
X
X
PO: oral, IV: intravenous/subcutaneous, PR: rectal
LA: long acting, TD: transdermal, TM: sublingual
Analgesia Equivalence
Opioid
PO
IV/SC
Codeine
100 mg
50 mg
Tramadol/tapentadol
75 - 150 mg?
Morphine
10 mg
5 mg
Oxycodone
5 mg
Hydromorphone
2 mg
1 mg
----------------------------------------------------------------------------Methadone
1 mg
Fentanyl
50 mcg
Sufentanil
5 mcg
Morphine to Fentanyl
Equivalency
Morphine (po)
45-69 mg
60-134 mg
135-180 mg
135-224 mg
225-314 mg
315-404 mg
Fentanyl patch (TD)
12 µg/h
25 µg/h
37 µg/h
50 µg/h
75 µg/h
100 µg/h
Duragesic® insert, Janssen-Ortho, Inc.
Tramadol/Tapentadol
Tramacet  Ralivia  Zytram  / Nucynta 
Active at the µ-opioid receptor
Weak inhibitor of epinephrine, serotonin
uptake (TCA-like)
Metabolism by CYP2D6, 3A4
Caution: SSRIs, SNRIs increase levels
Favourable S/E profile (less constipation ?less
nausea)
Methadone
Methadone
Morphine (po)
For methadone
equianalgesic
ratio varies by
morphine dose
30–90 mg
Morphine:
Methadone
4:1
90–300 mg
8:1
300–500
12:1
> 500
15–20:1
Routes of Administration
Oral
Transmucosal
Enteral via g-tube
Parenteral
SC, IV, IM
Rectal
Transdermal
Neuraxial
Opioid Metabolism & Excretion
Metabolism
Excretion
Codeine
Hepatic (2D6/3A4) Renal
Tramadol
Hepatic (2D6)
Renal
Morphine
Hepatic (2D6)
Renal
Oxycodone
Hepatic (2D6)
Renal
Hydromorphone
Hepatic (?)
Renal
----------------------------------------------------------------------------Methadone
Hepatic
Intestinal
(2D6/1A2/3A4)
Fentanyl
Sufentanil
Hepatic (3A4)
Hepatic (3A4)
Tissues
Tissues
Brian is prescribed Tylenol ES
and hydromorphone LA twice
daily. 3 wks later at follow-up, he
states his pain is better, but he
is constipated, and feel
nauseated at times.
BRIAN
Opioid Adverse Effects
Risk increases with age (10-25% if >60 y)
Ass’d with females, small size, poor liver/renal
function, # Rx, prior A/E
Changes in drug distribution, metabolism,
elimination
Same dose of opioid may give higher plasma
concentrations and  A/E
Opioid Adverse Effects
GI
Constipation, nausea, vomiting,
GE reflux (rare)
Autonomic
Dry mouth, urinary retention,
postural hypotension
CNS
Drowsiness, delirium, resp
depression (rare)
Cutaneous
Itch, sweating
Treatment of Adverse Effects
Reduce opioid dose
Symptomatic management of adverse effect
Opioid rotation (or switching)
Switching route of administration
ASCO Consensus statement, JCO 2001
Opioid Toxicity
Onset of confusion
Bad dreams, hallucinations
Restlessness, agitation
Significantly depressed LOC
Myoclonic jerks or seizures
Adverse Cognitive Effects
Bad dreams / nightmares may occur
Many patients on opioids report some degree
of short-term memory loss, variable degrees
of loss of ability to concentrate
All of this is influenced by illness progression
Respiratory Depression
Many clinicians have exaggerated view of risk
of respiratory depression when using
opioids to relieve pain
Pain is a potent stimulus to breathe, and
tolerance to resp depression develops
quickly
Opioid naïve pts ≠ opioid tolerant pts
As doses increase, depression is not sudden
Adequate assessment, appropriate titration
Brian benefits from the addition
of laxatives, and enjoys a few
weeks at the cottage. At followup, he states his pain has
changed and now is a constant
burning radiating down his L leg.
He is drowsy at times, but
sleeps poorly, mostly because of
the pain.
BRIAN
Pain: Treatment Spectrum
PHYSICAL
Normal activities
Aqua-fitness
Physio
• Passive
• Active
Stretching
PSYCHOSOCIAL
PHARMACOLOGIC SURGICAL
Hypnosis
Stress
Management
Cognitive
Behavioural
Family therapy
Psychotherapy
OTC medication
Alternative therapy
Topical medications
NSAIDs
Tricyclics
TCNS
Anticonvulsants
OPIOIDS
Local anesthetics
• Blocks
• Oral congeners
Massage
Muscle relaxants
Chiropractic
Sympathetic agents
Acupuncture
NMDA blockers
Conditioning
Weight training
TENS
Orthopedic
Neurotomy
Neurectomy
Implantable
stimulators
Implantable
pain pump
Targeted Therapies
Opioids
Tramadol
Morphine
Oxycodone
Hydromorphone
Fentanyl
Methadone
Receptor Specific
TCAs
Anti-convulsants
SNRIs
NMDA antagonists
Cannabinoids
Corticosteroids
α-adrenergic agonists
(clonidine)
Presynaptic Neuron
Ca2+
Ca2+
Glu
Glu
5HT
Na+
Ca2+
Glu
NE
Glu
Ca2+
Na+
Na+
Mg2+
NMDA
Cytoplasm
Presynaptic Neuron
Ca2+
Ca2+
Glu
Glu
5HT
Na+
Ca2+
Glu
NE
Glu
Ca2+
Na+
Na+
Mg2+
NMDA
Cytoplasm
Neuropathic Pain Therapy
TCA
Gabapentin or Pregabalin
SNRI
Topical Lidocaine
Tramadol
Opioid Analgesics
Fourth-line Agents
Moulin et al Pain Res Manage 2007;12:13-21
Targeted Therapy
Anticonvulsants
Pregabalin (Lyrica  )
Gabapentin (Neurontin  )
Carbamazepine (Tegretol  )
Topiramate (Topamax  )
Lamotrigine (Lamictal  )
Targeted Therapy
Antidepressants
TCAs
(amitriptyline, nortriptyline, desipramine)
SNRIs
(venlafaxine, duloxetine)
SNRI Use
Original Contribution | April 03, 2013
Effect of Duloxetine on Pain, Function, and
Quality of Life Among Patients With
Chemotherapy-Induced Painful Peripheral
Neuropathy A Randomized Clinical Trial
Ellen M. Lavoie Smith et al
JAMA. 2013;309(13):1359-1367.
doi:10.1001/jama.2013.2813.
SNRI Use
SNRI Use
Targeted Therapy
Steroids
 inflammation / edema
 spontaneous nerve depolarization
Dexamethasone 4-12 mg daily
Multipurpose
nausea, appetite, energy
Long term use = adverse effects
General Issues
Titrate these meds every 3–7 days depending
on adverse effects
May take up to 4 wks to see significant effect
If no benefit, move on to other meds
Targeted Therapy
Fourth-line agents:
Methadone, ketamine
Cannabinoids
Lidocaine infusion
Clonidine
Moulin et al Pain Res Manage 2007;12:13-21
When to Use Methadone?
Neuropathic pain
Very high opioid doses
Reactions/adverse effects to Rx
Severe neurotoxicity
Significant addictions history
Cost of Rx is an issue
Cannabinoids in Canada
Nabiximols (2.7mg THC + 2.5mg CBD)
Oromucosal spray
1 spray qHS; incr 1 spray q6h or more prn; ave 9 – 15 sprays per
day
Approved for MS-associated neuropathic pain & cancer pain
Nabilone (0.25 - 1.0mg)
Oral capsule
0.25 to 0.5mg qHS and slowly titrate to bid as tolerated
Approved for chemotherapy-induced nausea and vomiting
Dronabinol/THC (2.5 - 10mg)
Oral capsule
Start with 2.5mg qHS and increase up to 5mg bid
Approved for CINV and anorexia associated with HIV/AIDS
Herbal cannabis (12.5% THC)
Authorized use via Marihuana Medical Access Regulations (MMAR)
Average 2 grams per day (4 joints)
Not formally approved as prescription drug
Product monographs: Marinol, Cesamet, Sativex
“A brain tumour? Thank goodness-all this time I
thought you were on medical marijuana!”
His pain is well controlled with
the hydromorphone LA,
duloxetine and a small dose of
dexamethasone. One day, as
he is getting out bed, he slips
and lands heavily on the floor.
His pain immediately
increases, and his wife takes
him to the ER. An X-ray
reveals fracture of L5, and
involvement of L2-S1
BRIAN
Pain: Treatment Spectrum
PHYSICAL
Normal activities
Aqua-fitness
Physio
• Passive
• Active
Stretching
PSYCHOSOCIAL
PHARMACOLOGIC SURGICAL
Hypnosis
Stress
Management
Cognitive
Behavioural
Family therapy
Psychotherapy
OTC medication
Alternative therapy
Topical medications
NSAIDs
Tricyclics
TCNS
Anticonvulsants
OPIOIDS
Local anesthetics
• Blocks
• Oral congeners
Massage
Muscle relaxants
Chiropractic
Sympathetic agents
Acupuncture
NMDA blockers
Conditioning
Weight training
TENS
Orthopedic
Neurotomy
Neurectomy
Implantable
stimulators
Implantable
pain pump
Bone Pain
Pharmacologic treatment
Opioids
NSAIDs/steroids
Bisphosphonates
pamidronate (Aredia  )
zoledronic acid (Zometa  )
Calcitonin (Miacalcin  )
Denosumab? (Prolia  /Xgeva  )
“Radiation” by Robert Pope, © Robert Pope Foundation
Surgical options
Pathologic # (splint, cast, ORIF)
Intramedullary support
Spinal cord decompression
Vertebral fusion / reconstruction
Vertebroplasty
Amputation
Other Modalities
Neuraxial opioids and local anesthetics
Nerve blocks
Implantable pain pumps
Other Modalities
Complementary therapies, although evidence
is lacking for sustained effects in pain
Monitoring Patients
One of the most important aspects of pain
control is evaluation of outcomes of pain
management plan
Must be discussed with every patient, family
and health care team
Monitoring Patients
Follow up with pts who are just starting meds
or who are changing dosages within 72 hrs
phone / email / text; any team member
Monitor for adverse effects
Involve patient, family in monitoring of pain
Pain diary, assessment scales, spreadsheet
Be accessible 24/7 if problems develop
Following his verterbroplasty and
RT, Brian’s pain improves, but
he spends more time in bed due
to general weakness and fatigue.
A rotation to the fentanyl patch
goes well, and he stays at home
with the support of the palliative
care team. His wife calls one
morning to tell you that Brian
hasn’t woken up, and she thinks
he is close to death. The visiting
nurse is present when he dies,
and the family are thankful of his
peaceful demise.
BRIAN
Questions?
“Death is taking another holiday. I’m the fat lady who sings”
Breakthrough Dosing
Transitory flares of pain, called breakthrough
pain, experienced by many patients both at
rest and during movement
When such pain lasts for longer than a few
minutes, extra doses of analgesics, i.e.,
breakthrough or rescue doses, will likely
provide additional relief
Pain
Excessive
sedation
Baseline dose
Incident Incident Incident
Time
Breakthrough Dosing
To be effective and to minimize risk of adverse
effects, consider IR preparation of same
opioid
When methadone or transdermal fentanyl is
used, use alternative short-acting opioid,
e.g., morphine or hydromorphone, as rescue
dose
Sublingual immediate-acting fentanyl
available
Breakthrough Dosing
For each breakthrough dose, offer 5–15% of
the 24-hour dose
Extra breakthrough dose can be offered q 1
hour orally, or possibly less frequently for
frail patients; q 30 min SC / IM, q 10–15 min
IV
Pain
Classification
Assessment
Management
Opioid Adverse
Effects
Targeted Analgesics
Other Modalities
“The pain, Mr. Renfrew, is nature’s way of having fun”