Paul Daeninck
CancerCare Mani toba
WRHA Pal l ia t ive Care Program
Univers i ty o f Mani toba
Effective Pain Management in Palliative Care
Patients
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
Objectives
BRIAN
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
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
…Introduction
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 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
Pain Prevalence
PainFatigue/Asthenia
Constipation
Dyspnea
Nausea
Vomiting
Delirium
Depression/suffering
Symptom Prevalence
80 – 90+%75 - 90%
70%
60%
50 - 60%
30%
30 - 90%
40 - 60%
“We can give you enough medication to alleviate the pain, but not enough to make it
fun.”
Acute or chronic
Nociceptive or neuropathic
in cancer, inflammatory mechanisms for nociceptive pain more established
Pain Classification
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
Nociceptive 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)
…Neuropathic 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
Cancer Pain
“A Friend’s Story” by Robert Pope, © Robert Pope Foundation
Physical Source
Emotional State
Personality
Family
Patient / Family
Context
Health Care ProfessionalsHistory /
Exposure
Total Pain
Total Pain = Suffering
BRIAN
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
History
Physical exam
Imaging
Blood testing
Pain Assessment
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 featuresDaily frequencyLocation/RadiationSeverity/QualityAggravating and
alleviating factorsPrevious history (chronic pain, family)Meaning
Pain History
Medication(s) taken
Dose
Route
Frequency
Duration
Effect
Side effects
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 Tools
History
Physical exam
Imaging
X ray, CT scan (MRI, bone scan)
Blood testing
Liver/renal function, WBC
Pain Assessment
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
Cultural Issues
May express pain differently
Studies have established high prevalence of pain in the elderly, yet widespread under-treatment of pain in this group
Increasing age brings more difficulty in using assessment tools
Pain in the Elderly
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
Pain and Cognitive Impairment
BRIAN
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
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
Addiction and Tolerance
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 effect-iveness of a given dose of medication over time
…Definitions…
“What a coincidence, Mrs. Marble. You’ve become addicted to the same drugs as I’m
addicted to!”
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
Addictions
Pain: Treatment Spectrum
PHYSICAL PSYCHOSOCIAL PHARMACOLOGIC SURGICAL
Normal activities
Aqua-fitnessPhysio• Passive• Active
Stretching
Conditioning
Weight training
TENS
TCNS
Massage
Chiropractic
Acupuncture
HypnosisStress ManagementCognitiveBehaviouralFamily therapyPsychotherapy
OTC medication
Alternative therapy
Topical medications
NSAIDs
Tricyclics
Anticonvulsants OPIOIDSLocal anesthetics• Blocks• Oral congeners
Muscle relaxants
Sympathetic agents
NMDA blockers
OrthopedicNeurotomyNeurectomyImplantable stimulatorsImplantable pain pump
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
Physical Modalities
Hypnosis /distraction
Stress management
Dignity therapy
Cognitive /behavioural therapy
Family therapy
Psychotherapy
Psychosocial
Pain: Treatment Spectrum
PHYSICAL PSYCHOSOCIAL PHARMACOLOGIC SURGICAL
Normal activities
Aqua-fitnessPhysio• Passive• Active
Stretching
Conditioning
Weight training
TENS
TCNS
Massage
Chiropractic
Acupuncture
HypnosisStress ManagementCognitiveBehaviouralFamily therapyPsychotherapy
OTC medication
Alternative therapy
Topical medications
NSAIDs
Tricyclics
Anticonvulsants OPIOIDSLocal anesthetics• Blocks• Oral congeners
Muscle relaxants
Sympathetic agents
NMDA blockers
OrthopedicNeurotomyNeurectomyImplantable stimulatorsImplantable pain pump
Mild pain (0-3)
Moderate (4-6)
Severe (7-10)
By the mouthBy the clockBy the ladder
Acetaminophen & NSAIDs
Codeine + Step 1
Morphine + Step 2
WHO Analgesic Ladder
Targeted Rx may be added at any step
Acetaminophen1 g three times daily, extra dosesLonger acting preparations
NSAIDS / COX-2 inhibitorsEffective in inflammatory conditionsGI, kidney side effectsCancer prevention?Gastric protection recommended
Non-opioid Analgesics
Opioid Choice in Canada
PO IV PR LA TD TMMorphine X X X X XOxycodone X X X XHydromorphone X X X X X
Methadone X X X XFentanyl X X XSufentanil X X
----------------------------------------
PO: oral, IV: intravenous/subcutaneous, PR: rectalLA: long acting, TD: transdermal, TM: sublingual
Opioid Choice in Canada
PO IV PR LA TD TMCodeine X X X Tramadol/tapentadol X X Buprenorphine X X
PO: oral, IV: intravenous/subcutaneous, PR: rectalLA: long acting, TD: transdermal, TM: sublingual
OpioidCodeineTramadol/tapentadolMorphineOxycodone
Hydromorphone
Methadone
Fentanyl
Sufentanil
Analgesia Equivalence
PO IV/SC100 mg 50 mg75 - 150 mg? 10 mg 5 mg 5 mg
2 mg 1 mg
1 mg
50 mcg
5 mcg
-----------------------------------------------------------------------------
Morphine (po)45-69 mg
60-134 mg135-180 mg135-224 mg225-314 mg315-404 mg
Fentanyl patch (TD)
12 µg/h25 µg/h37 µg/h50 µg/h75 µg/h
100 µg/h
Morphine to Fentanyl Equivalency
Duragesic® insert, Janssen-Ortho, Inc.
Tramacet Ralivia Zytram / Nucynta
Active at the µ-opioid receptorWeak inhibitor of epinephrine, serotonin
uptake (TCA-like)Metabolism by CYP2D6, 3A4Caution: SSRIs, SNRIs increase levelsFavourable S/E profile (less constipation ?less
nausea)
Tramadol/Tapentadol
Methadone Morphine (po) Morphine: Methadone
For methadone equianalgesic ratio varies by morphine dose
30–90 mg 4:1
90–300 mg 8:1
300–500 12:1
> 500 15–20:1
Methadone
Oral
Transmucosal
Enteral via g-tube
ParenteralSC, IV, IM
Rectal
Transdermal
Neuraxial
Routes of Administration
Opioid Metabolism & Excretion
MetabolismExcretion
Codeine Hepatic (2D6/3A4)
RenalTramadol Hepatic (2D6)
RenalMorphine Hepatic (2D6)
RenalOxycodone Hepatic (2D6)
RenalHydromorphone Hepatic (?)RenalMethadone Hepatic
Intestinal
(2D6/1A2/3A4)
Fentanyl Hepatic (3A4)
TissuesSufentanil Hepatic (3A4)
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
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
Opioid Adverse Effects
Reduce opioid dose
Symptomatic management of adverse effect
Opioid rotation (or switching)
Switching route of administration
Treatment of Adverse Effects
ASCO Consensus statement, JCO 2001
Onset of confusion
Bad dreams, hallucinations
Restlessness, agitation
Significantly depressed LOC
Myoclonic jerks or seizures
Opioid Toxicity
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
Adverse Cognitive Effects
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
Respiratory Depression
Brian benefits from the addition of laxatives, and enjoys a few weeks at the cottage. At follow-up, 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 PSYCHOSOCIAL PHARMACOLOGIC SURGICAL
Normal activities
Aqua-fitnessPhysio• Passive• Active
Stretching
Conditioning
Weight training
TENS
TCNS
Massage
Chiropractic
Acupuncture
HypnosisStress ManagementCognitiveBehaviouralFamily therapyPsychotherapy
OTC medication
Alternative therapy
Topical medications
NSAIDs
Tricyclics
Anticonvulsants OPIOIDSLocal anesthetics• Blocks• Oral congeners
Muscle relaxants
Sympathetic agents
NMDA blockers
OrthopedicNeurotomyNeurectomyImplantable stimulatorsImplantable pain pump
Opioids
Tramadol
Morphine
Oxycodone
Hydromorphone
Fentanyl
Methadone
Receptor Specific
TCAs
Anti-convulsants
SNRIs
NMDA antagonists
Cannabinoids
Corticosteroids
α-adrenergic agonists
(clonidine)
Targeted Therapies
NMDA
Presynaptic Neuron
V-G N
a+
Relea
se
V-G N
a+
Cytoplasm
Postsynapti
c Neuron
AMPA
AMPA AMPA
AMPA
DEPOLARIZATION
NMDANMDA NMDA
NMDA
α2
α2
V-G
Ca2
+
V-G
Ca2
+
μ μ
Ca2+
Ca2+
Mg2+
Ca2+
Ca2+
Glu
Glu
Na+Na+
Glu
Glu
μ μ
5HT
NE
Na+
NMDA
Presynaptic Neuron
V-G N
a+
Relea
se
V-G N
a+
Cytoplasm
Postsynapti
c Neuron
AMPA
AMPA AMPA
AMPA
DEPOLARIZATION
NMDANMDA NMDA
NMDA
α2
α2
V-G
Ca2
+
V-G
Ca2
+
μ μ
Ca2+
Ca2+
Mg2+
Ca2+
Ca2+
Glu
Glu
Na+Na+
Glu
Glu
μ μ
5HT
NE
Na+
Lidocaine
Clo
nid
ine
TCA
Gab
ap
en
tin
Ketamine
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
AnticonvulsantsPregabalin (Lyrica )
Gabapentin (Neurontin )
Carbamazepine (Tegretol )
Topiramate (Topamax )
Lamotrigine (Lamictal )
Targeted Therapy
AntidepressantsTCAs
(amitriptyline, nortriptyline, desipramine)SNRIs
(venlafaxine, duloxetine)
Targeted Therapy
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
SNRI Use
Steroids inflammation / edema spontaneous nerve depolarizationDexamethasone 4-12 mg dailyMultipurpose
nausea, appetite, energyLong term use = adverse effects
Targeted Therapy
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
General Issues
Fourth-line agents: Methadone, ketamine
Cannabinoids
Lidocaine infusion
Clonidine
Targeted Therapy
Moulin et al Pain Res Manage 2007;12:13-21
Neuropathic pain
Very high opioid doses
Reactions/adverse effects to Rx
Severe neurotoxicity
Significant addictions history
Cost of Rx is an issue
When to Use Methadone?
Cannabinoids in Canada
Product monographs: Marinol, Cesamet, Sativex
Nabiximols (2.7mg THC + 2.5mg CBD)Oromucosal spray1 spray qHS; incr 1 spray q6h or more prn; ave 9 – 15 sprays per dayApproved for MS-associated neuropathic pain & cancer pain
Nabilone (0.25 - 1.0mg)Oral capsule0.25 to 0.5mg qHS and slowly titrate to bid as toleratedApproved for chemotherapy-induced nausea and vomiting
Dronabinol/THC (2.5 - 10mg)Oral capsuleStart with 2.5mg qHS and increase up to 5mg bidApproved 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
“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 PSYCHOSOCIAL PHARMACOLOGIC SURGICAL
Normal activities
Aqua-fitnessPhysio• Passive• Active
Stretching
Conditioning
Weight training
TENS
TCNS
Massage
Chiropractic
Acupuncture
HypnosisStress ManagementCognitiveBehaviouralFamily therapyPsychotherapy
OTC medication
Alternative therapy
Topical medications
NSAIDs
Tricyclics
Anticonvulsants OPIOIDSLocal anesthetics• Blocks• Oral congeners
Muscle relaxants
Sympathetic agents
NMDA blockers
OrthopedicNeurotomyNeurectomyImplantable stimulatorsImplantable pain pump
Pharmacologic treatment
Opioids
NSAIDs/steroids
Bisphosphonates
pamidronate (Aredia )
zoledronic acid (Zometa )
Calcitonin (Miacalcin )
Denosumab? (Prolia /Xgeva)
Bone Pain
“Radiation” by Robert Pope, © Robert Pope Foundation
Pathologic # (splint, cast, ORIF)
Intramedullary support
Spinal cord decompression
Vertebral fusion / reconstruction
Vertebroplasty
Amputation
Surgical options
Neuraxial opioids and local anesthetics
Nerve blocks
Implantable pain pumps
Other Modalities
Complementary therapies, although evidence is lacking for sustained effects in pain
Other Modalities
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
Monitoring Patients
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”
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
Breakthrough Dosing
Time
Incident Incident Incident
Pai
nExcessive sedation
Baseline dose
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
Breakthrough Dosing
Pain Classification
Assessment
Management
Opioid Adverse Effects
Targeted Analgesics
Other Modalities
“The pain, Mr. Renfrew, is nature’s way of having fun”
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