Transcript Pain in Cancer patient

Pain in
Cancer Patient
Prof. Dr. Khaled Abouelkhair, PhD
Medical Oncology SCE, Royal College, UK
Ass. Professor of Clinical Oncology
Mansoura University, Egypt
Purpose
• Review basic principles of pain
management and analgesic therapy
• Case study illustrating common pain
problems and suggested
management.
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Pain in Cancer Patients
Incidence • 30-40% of patients at time of
diagnosis or during disease modifying treatment
• 70- 90% in those with
advanced disease
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Pain in Cancer Patients
Etiology
• Direct tumour involvement: 62-78%
• As a result of diagnostic or therapeutic
interventions 19-25%
– Post- radiation ( enteritis; nerve injury; osteonecrosis);
Post-chemotherapy ( eg mucositis; peripheral
neuropathy); Post- operative pain- acute and chronic
• Cancer induced syndromes <10%
– Constipation, pressure sores, shingles
• Pain unrelated to malignancy or treatment 3-10%
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Types of Pain
• Acute:
–E.g procedural pain; pathological
fracture; bowel/ureteric obstruction
• Chronic
• Acute on Chronic (Breakthrough
pain)
• Malignant; Non-Malignant
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Types of Pain
• Nociceptive: Direct response to
tissue injury
–Includes musculoskeletal (somatic)
and visceral pain
• Neuropathic: Pain associated with
damage to the nervous system
• Mixed pain syndromes
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Goals of Pain Management
•In cancer:
> 80% will achieve good control
15% will have fair control
< 5% will have poor or no
control
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Untreated Pain
Impact on
• Function
• Sleep
• Impaired
cognitive
function
• Quality of life
Outcomes
• Depression
• Decreased
socialization
• Increased health
care utilization
• Increased costs
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“Pain is a more
terrible lord of mankind
than even death itself ”
Albert Schweitzer
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George
• 83 year old widower: Lives alone
• Ca Prostate with Bony metastases;
Hx OA/ IHD/ Depression
• Brought in by daughter: Won’t leave
the house
• Increased pain in his shoulder and
lower back for 2 weeks
• Constipated
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Pain Assessment
• Listen carefully: What are the words used?
– May deny pain but will admit to having
“discomfort”, “aching” or “soreness”
–Do you hurt anywhere?
–Are you uncomfortable?
–How does it affect you?
• Believe the patient “pain is what the patient
says hurts….the best judge of a patient’s
pain is the patient” Bonica.
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Pain Assessment Tools
OLD CARTS
O: Onset – acute vs gradual
L: Location (+ radiation)
D: Duration (recent/chronic)
C: Characteristics (quality of pain)
A: Aggravating factors
R: Relieving factors
T: Treatments – previously tried - response
- dose/duration
- why discontinued?
S: Severity: Pain Scales: 0- 10; VAS
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Please rate your pain by circling the one number that best describes your pain
_____________________________________________________________
0
1
2
3
4
5
6
7
8
9
10
What is your Pain at it’s
Best / Worst/ Present/ Average
No Pain
Pain as bad as you can imagine
In the past 24 hours, how much RELIEF have pain treatments or medications
provided? Please circle the one percentage that most shows how much.
_____________________________________________________________
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
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OPQRSTUV
O NSET: When did it start?
P ATTERN: How often; When; How long?
Q UALITY: Describe it: sharp, dull...
R ELIEVING/AGGRAVATING FACTORS
S EVERITY: Scale of 1- 10
T REATMENTS: What helps; For how long
U NDERSTANDING: What do you think is
causing it?. How does it affect you?
V ALUES: Goals Of Care; expectations
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Pain History: George
• O(nset): Several months/  2 weeks
• P(attern): R shoulder/lower back pain.
Constant. Increased with movement.
• Q(uality): Steady aching pain
• R(elief): Medication helps for about 2-3 hrs
• S(everity): 6/10. 10/10 with movement
• T(reatments): T#3 helps for about 2-3
hours.Takes about 12-15 T#3 a day
• U(nderstanding): Not going on any Morphine.
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I’m not dead yet.
Examination
• No evidence of fractures but
clearly limited ROM in the shoulder
due to pain
• No vertebral tenderness and no
neurological signs
• Bowel and bladder function normal
• Xrays show bony mets in shoulder
and lumber spine
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Pain Assessment
• Once assessment complete:
•Type of pain
•Severity of Pain
•Probable cause of pain
•Options for pain relief
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George – approach to
treatment
Develop a problem list to resolve
• somatic /bone pain
• acetaminophen dosing too high (~4
gms)
• constipation contributing to pain
intensity
• compliance issues
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How would you better manage
George’s pain?
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Pain Management
Educate patient and family:
– Myth: “Save it for when it gets worse”
• FACT: Treating early prevents pain
• FACT: No ceiling effect of strong opioids
• FACT: Tolerance is rare in Palliative Patients/PO
route
– Myth: “I’ll become addicted”
• FACT: Addiction is rare. Boston study- 0.03%
Myth: Treatment worse than pain
FACT: Side effects can be managed/treated
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Education
Constant pain requires regular dosing
• avoid peaks of pain as with prn/bolus
dosing
• uninterrupted sleep
• smoother blood levels can provide more
consistent pain control
• more convenient
• less analgesia over time
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Pharmacology of Pain
Management
• Acetaminophen
• NSAIDS
• Opioids
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Adjuvants/ Co analgesics
• Bisphosphonates/Calcitonin
• Antidepressants
• Anti-convulsants
• Disease specific therapies:
Radiation/Chemotherapy/Surgery
• Steroids
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Principles of Opioid Use
• Opioids help relieve moderate to
severe pain ( and dyspnea)
• Episodic pain - Prescribe as needed
rather than around-the-clock
• Constant pain = Regular dosing
PLUS a “breakthrough” PRN dose
• Right drug at the Right dose
– Monitor number of PRN’s used or
persistent pain; Adjust as needed
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Analgesics
• Step 1: Mild pain:
– Acetaminophen: Max 4 gm/day
• Can be very effective for mild-moderate
pain if given regularly
– NSAIDs: Issues re GI and renal toxicity
• Concerns in the elderly
• Non-specific: Use with GI protection
• COX 2 agents safer re GI morbidity and
antiplatelet effects
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Opioid Analgesics: Step 2 + 3
Step 2:
• Tramadol…PO, IV …variable
responses…Constipation and mode changes
• Codeine
 About 10% of population lack enzyme to convert
to Morphine
 Ceiling effect:> 600 mg/day
 Very constipating
 Combination product or alone
 1:10 ( Morphine:Codeine)
 Sustained release preparation :
Codeine Contin 50,100,150, 200 mg
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Oxycodone:
Moderate ->Strong Opioid
• Active at the mu and kappa receptors
• Safe with decreased renal function
• Potency Oxycodone 1.5 - 2 :1 Morphine
• Less constipating than Codeine
• Lasts ~ 4-5 hours
• No ceiling effect
• Alone or with ASA/Acetaminophen
• OxyContin 10, 20, 40, 80 mg
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Strong Opioids
• Morphine still gold standard
– Concerns re: metabolites in renal
failure; elderly….Liver impairment
• Hydromorphone:
– More soluble.
– Few metabolites
– 5x more potent than Morphine.
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Opioid Pharmacology
• Cmax = 60 mins (after PO dose)
45 mins (after SC dose)
30 mins (after IM dose)
6 mins (after IV dose)
• t1/2 = 3-4 hours
• Duration = 20-24 hrs (immediate-release)
48-72 hrs (sustained-release)
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Strong Opioids
• Fentanyl: Not at mu receptor. More
lipophilic
–
–
–
–
100x more potent than Morphine.
Less constipation and nausea.
Less histamine release
Useful in true opioid allergy
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Fentanyl
• Transdermal Patch: 4 strengths in mcg/hour:
– 25 ~ 100 mg Morphine/day (45 -134)
– 50 ~ 200 mg (135-224), 75 (225-314),
– 100 ~ 400 mg (315-404 mg M/day)
– Takes ~17 hours to reach steady state
– Patch lasts 72 hours in 90% of patients
• Sublingual, intranasal, subcutaneous, IV
routes
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Opioid equi-analgesic doses
• 10 mg PO morphine
=5 mg SQ/IV morphine (half the oral
dose)
= 100 mg PO codeine (1/10)
= 2 mg PO Hydromorphone (1mg SQ)
(5x more potent)
= 5 - 7.5 mg PO Oxycodone ( 1.5x)
= 0.5- 1 mg PO/pr methadone ( not Q4H)
( ~~10 x more potent)
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George
Proposed management strategy?
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George
• 12-15 T#3 =
– 3900- 4875 mg acetaminophen plus
– 360- 450 mg codeine
~ 36- 45 mg PO morphine TDD (total daily dose)
~ 7- 9 mg PO hydromorphone
~ 25- 30 mg PO oxycodone
~Patch?
• Concerns re Acetaminophen dose/
Approaching ceiling Codeine
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George
• Rotation to strong opioid:
• Which one?
• Dose: ? Equianalgesic
– ? Increase dose
– BT (Break Through)
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Opioid Adverse Effects
• Constipation: “ The hand that
writes the opioid prescription
should start the laxative”
٠ Stimulant (+/- softener) (+/- osmotic)
٠ Nausea:
٠Approximately 50% will have some nausea
in first week; 30% after that
٠In those prone to nausea consider antiemetic (metoclopramide)
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Opioid Adverse Effects
• Neurologic:
٠ gait disturbances
٠ dizziness
٠ falls
• Cognitive-behavioural effects:
٠ sedation
٠ impaired concentration
• Respiratory depression: RARE
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George: 2 days later
Morphine SR 30 mg BID = 60 mg
PLUS 6 BT of 5 mg
= 30mg
90mg
• Increase to morphine SR 45 mg BID
• BT: 10% of TDD or 1/2 of Q4H dose
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Bone Pain
What role would the following play?
– Radiotherapy
– NSAIDs
– steroids
– bisphosphonates
– calcitonin
• What else might you do?
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Bone Pain
• Bone metastases are associated with
bone destruction and new bone
formation
• Also compression or pathologic fractures
• High density of pain fibres in the
periosteum
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Bone Pain
• Prostaglandins:
– Produce both osteolytic and osteoclastic
bone changes
– Sensitize nociceptors and can produce
hyperalgesia
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Management
• Opioids effective BUT often need
adjuvants/co-analgesics
– NSAIDS
– Radiotherapy
– Bisphosphonates
– Calcitonin
– Systemic treatment
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NSAIDS
• Both peripheral and central effects
• Inhibit cyclo-oxygenase (COX) enzyme -
>  Decreased prostaglandin production
• Specific COX 2 inhibitors: Celecoxib,
rofecoxib. Less GI effects
• Less effect on platelet function
– “Selective” COX 2 inhibitors: Diclofenac
– Nonacetylated salicylates: Diflunisal
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Management of Bone Pain
• Radiotherapy: Cochrane review
– Complete pain relief in 25% at one month
– Reduction in pain in further 41%
– Median duration of relief: 12 weeks
– In “long bones” may be just one dose
• Chemotherapy
• Orthopedic: Pre-emptive pinning of an
incipient bone fracture; bracing;
vertebroplasty
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Incident Pain
Pain occurring as a direct
and immediate
consequence of a
movement or activity
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Breakthrough Pain
• End of dose pain:
– Usually requires dose increase regular
medication
• Paroxysmal/Idiopathic:
– Titrate to only 1-3 BT’s /day
– BTD should be 10% of TDD/1/2 of Q4H
• Incident Pain
– Precipitant. Peaks early. Short duration
– 65% last 30 minutes or less
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Incident Pain
• Bone metastases
• Neuropathic pain
• Intra-abdominal disease aggravated by
respiration
• Skin ulcer with dressing changes,
debridement
• Disimpaction
• Catheterization
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Approach to Incident Pain
• Treat underlying problem
• Radiotherapy, chemotherapy
• Bisphosphonates
• Orthopedic intervention
• Nerve blocks
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Ideal Analgesic
• Easily administered
•
•
•
•
Rapid onset
Short-duration of action
In patient’s control
Before the event
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George: 3 months later
• Confused , drowsy
• Not eating
• Pain on any weight bearing despite
recent RXT radiating into his L leg
• Some myoclonus
• LAB: Normal Calcium, Creatinine 200
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George
• Current medication:
٠ morphine SR 100 mg PO BID
٠ Also taking about 5 BT of 20 mg/day.
٠ 200 mg plus 100 mg = 300 mg
morphine TDD
What do you recommend re his
pain management?
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George
?Bone Pain with Incident Pain
?Opioid toxicity
?Neuropathic Pain
? New mets to brain or liver
? Constipation
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Opioid Toxicity
• Hyperalgesia
• Allodynia
• Agitated delirium
• Myoclonus
• Respiratory depression
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OpioidToxicity
Several strategies
• Reduction in opioid dose by 25- 50%
• Symptomatic treatment:
– Hydration
– +/- haloperidol/nozinan; lorazepam/
midazolam; phenobarb
• Opioid rotation
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Opioid rotation
Better balance between analgesia and
unmanageable side effects
• different receptors
• accumulation of morphine metabolites
• tolerance to a specific opioid
• variability in analgesia due to incomplete
cross-tolerance
OR need for alternate route/more potent opioid57
Opioid rotation
For dose-limiting toxicity/unacceptable
side effects and good pain control:
• May be due to incomplete crosstolerance
• Give approximately 50- 75% of
equianalgesic dose
For pain that is not well controlled:
• Switch at equianalgesic dose
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Opioid rotation
• Prospective studies:
– Maddocks: Opioid rotation (morphine to
oxycodone) relieved delirium in 61%;
Gagnon 34%; Ashby 72%
• Many retrospective studies and case
studies
• Now considered standard therapy
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Opioid Rotation
• Clinically important tool in achieving
good pain management
• Need good monitoring
• Understanding and utilization of
equianalgesic tables
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Opiate conversion:
Knowing he was taking Morphine 300
mg /day
What dosage would you initiate the
following with:
– Hydromorphone?
– Oxycodone?
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Opiate conversion:
• Morphine 300 ( MEDD)
=
mg Hydromorphone
=
mg Oxycodone
=
mcg Patch
* Don’t forget to increase your
breakthrough
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Neuropathic Pain
Pain that arises from injury,
disease or dysfunction
in the peripheral or
central nervous system.
Incidence in Cancer : 30-50%
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Neuropathic pain in cancer
Causes:
• Tumour infiltration or compression of nerve,
plexus, or roots
• Remote effects of malignant and nonmalignant disease processes (eg diabetes)
• As a result of
– viral infection
– treatment with surgery, radiotherapy, or
chemotherapy
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Neuropathic Pain Syndromes
• Deafferentation pains: Central pain,
phantom pain and post-herpetic
neuralgia
• Peripheral mono-neuropathies and
polyneuropathies
• Complex regional pain syndromes
– Can develop months or years post
treatment
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Treatment of Neuropathic Pain
• Treat early as central mechanisms
can cause persistence of pain
• Adjuvant medications are essential
• Titrate one medication at a time
• Push dose until pain relief or
intolerable side effects seen
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Opioids in Neuropathic Pain
• Should always be tried
• Individual variation
• Methadone may be the most useful
opioid in neuropathic pain
• Some evidence for oxycodone also
being more useful
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Antidepressants in Neuropathic
Pain
• Tamoxifen
• Tricyclic antidepressants still the best
– Effective in 50-65% of cases
• Nortriptyline = amitriptyline as first line
• Desipramine for those who don’t tolerate
• Starting dose 10 –25 mg
• Usual therapeutic dose is 50 –150mg
• Analgesic effect seen 4-7 days after
reaching therapeutic dose
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Antidepressants in Neuropathic
Pain
• SSRI generally don’t work very well
• New SSRI citalopram seems to have
analgesic properties. Also fluoxetine.
• SNRI venlafaxine has analgesic
properties and is helpful in some
• Use these agents when TCA not
tolerated
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Anticonvulsants in Neuropathic
Pain
• Try gabapentin first
• Gabapentin has good evidence for
efficacy
• Most respond to 2100 – 3600mg/day
• Push dose to 6000mg/day 80%of
patient can tolerate
• Others: Carbamazepine; Clonazepam;
Phenytoin
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Miscellaneous Medications
• Corticosteroids useful with associated
swelling and inflammation
• Baclofen if associated with muscle spasm
• Calcitonin 100-200 units/day helpful with
phantom limb pain and sympathetically
maintained pain
• ketamine
• Clonidine
• Mexiletine, flecanide, lidocaine
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Topical Therapy in Neuropathic
Pain
• Capsaicin cream helpful in peripheral
nerve pain. Need to use it consistently
• ? Destruction of nerve endings
• If burns on application reduce
concentration for first week or add
lidocaine ointment
• Lidocaine 5% patch effective in some
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Non-Pharmacological Options
• physical activity program
• patient education program
• cognitive-behavioural therapies
• other:
e.g. heat/cold, massage, liniments,
TENS, chiropractic, acupuncture, XRT,
etc.
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Summary
•
•
•
•
•
•
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Comprehensive assessment is paramount
Avoid unnecessary delay in treating pain
Educate patient, family & caregivers
Use interdisciplinary approach
Choose medications based on stepped approach,
as well as well as side effect profile
Tailor medication regimens to meet individual
needs and life styles
Consider non-pharmacological options
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Palliative Care
• Combination of active and compassionate
therapies designed to comfort and
support those living with a life
threatening illness
• Addresses physical, psychological, social,
and spiritual expectations and needs
• Best delivered by an interdisciplinary
team which includes the patient, family,
caregivers and health providers
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References
• Bruera E, Sweeney C. Methadone use in cancer patients
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with pain: a review. J of PM 5(1): 127-138, 2002
Bruera et al. A prospective open study of oral methadone in
treatment of cancer pain. 9th World Congress on Pain, 2000
Lawlor PG, Turner KS, Hanson J, Bruera E. Dose ratio
between morphine and methadone in patient with cancer
pain - a retrospective study. Cancer 82(6): 1167-73, 1998
Ripamonti C. J Clinical Oncology, 1998
C Gannon. The Use of Methadone in the Care of the Dying,
EJPC, 1997
R Fainsinger, T Schoeller, E Bruera. Methadone in the
Management of Cancer Pain: A Review. Pain 52: 137-147,
1993
Bruera et al. Opioid Rotation in Patients with Cancer Pain.
Cancer78(4): 852-857,1996
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