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COMPLEX PAIN
MANAGEMENT IN
ONCOLOGY
Jeannine M. Brant, PhD, APRN, AOCN, FAAN
Oncology CNS and Nurse Scientist
Billings Clinic in Billings, MT
[email protected]
Disclosures
• Consulting fee: Insys
• Speaker fees: Insys, Genentech
Objectives
• Demonstrate a comprehensive pain
assessment in a patient with cancer
including physical assessment and
differential diagnoses
• List pharmacologic strategies to manage
pain according to the pain syndrome
1
Problem of Cancer Pain
Pain affects the majority of patients
sometime during the disease
• ~53% of patients receiving treatment have
pain
• ~59-64% of patients in advanced stages
have pain
• ~33% of patients post curative treatment
IASP,
IASP,
2010,
2010,
WHO,
WHO,
2010;
2010;
van
van
den
den
Beuken-van
Beuken-van
Everdingen,
Everdingen,
M.M.
H.,H.,
J. J.
M.M.
dede
Rijke,
Rijke,
et et
al.al.
(2007).
(2007).
"Prevalence
"Prevalence
of of
pain
pain
in in
patients
patients
with
with
cancer:
cancer:
a systematic
a systematic
review
review
of of
thethe
past
past
4040
years."
years."
Ann
Ann
Oncol
Oncol
18(9):
18(9):
1437-1449.
1437-1449.
Who Reports the Most Pain?
•
•
•
•
•
•
•
70% with head and neck cancer
60% with gynecologic malignancies
59% with gastrointestinal cancer
55% with lung cancer
54% with breast cancer
52% with urogenital cancer
Over 1/3 who have pain rated it as moderate to
severe
IASP, 2010, WHO, 2010; van den Beuken-van Everdingen, M. H., J. M. de Rijke, et al. (2007). "Prevalence of pain in patients with
cancer: a systematic review of the past 40 years." Ann Oncol 18(9): 1437-1449.
Pain Assessment
Interview
Physical Examination
Radiographic Examination
2
The Faces of Pain
Who’s in Pain?
Pain Interview
• Conversation
• Therapeutic Interview
Skills
• Substance Use
Disorder?
– Verbal/Nonverbal
– Focus on the patient
– Explore fears, treatment
expectations, goals
– Clarify understanding
– Encourage to talk
– Communicate a
therapeutic alliance
– Withhold judgement
– ACE
– Family and social
support
– History of depression,
anxiety, psychiatric
disorders
– SUD history
– Screen for risk
– Access PDMP
– Urine drug screening
Brant, 2016
Location
• Body Diagrams
• Point
• May involve more than one
location of pain
3
Intensity
Quality
Stretching
Sharp
Cramping
Dull
Radiating
Episodic
Deep
Constant
Pressure
Pins and Needles
Sore
Intermittent
Aching
Temporal Factors
• Constant versus episodic
• How pain changes over time
– Increase with movement/activity
– Increase at night
• What makes pain better?
• What makes pain worse?
• Breakthrough Pain
–
–
–
–
Incident
Idiopathic
End of dose failure
Nonbreakthrough
Include temporal factors in the plan of care
Holen et al., 2006
4
Brief Pain Inventory (BPI)
• Pain Severity
– Average
– Least
– Worst
• Impact on Daily Functioning
• Percent relief
• Reliability: Cronbach alpha reliability
ranges from 0.77 to 0.91s
Cleeland, 1989
Chronic Pain Goals – 4 A’s
• Analgesia - Decrease pain
– Treat underlying cause where possible
– Minimize medication use
• Activities of Daily Living - Restore function
– Physical, emotional, social
– Correct secondary consequences of pain
• Postural deficits, weakness, overuse
• Maladaptive behavior, poor coping
• Adverse Events – Minimize side effects
– Manage untoward side effects
• Aberrant Behaviors – Prevent abuse and diversion
– Monitor at each visit
Differential Diagnosis
• Somatic
• Visceral
• Neuropathic
5
Somatic Pain
• Pain Syndromes
–
–
–
–
• Characteristics
Bone metastases
Arthritis
Muscular pain
Post-operative
arthroplasty
– Culturally sensitive
– Sharp or dull, deep,
aching
– Well-localized
– Triggered with
movement or activity
Strategies
NSAIDS
Bone Modifying
Opioids
Ferrell et al., 2008
Visceral Pain
• Pain Syndromes
–
–
–
–
–
• Characteristics
Pancreatic cancer
Liver cancer
Cirrhosis
Lymphedema
Post-operative pain
– Aching, gnawing,
cramping
– Poorly localized
– Can be referred
Strategies
NSAIDS
Corticosteroids
Anticholinergics – spasm
Octreotide
Opioids
Ferrell et al., 2008
Neuropathic Pain
• Pain Syndromes
– Brachial plexopathy
– Lumbosacral
plexopathy
– Radiculopathy
– Chemotherapyinduced neuropathy
(CIPN)
– Diabetic neuropathy
– Sciatic nerve pain
• Characteristics
– Central: Shooting,
burning, lancinating,
electric-shock like,
burning, aching
– May radiate down an
extremity
Strategies
Antidepressants
Anticonvulsants
Antispastics
Local Anesthetics
Corticosteroids
Opioids
Ferrell et al., 2008
6
Case Study #1
• 28 year old male, married, 2 year old son,
employed in computer technology
• ED visit with abdominal pain
– CT reveals ascites
– 2.7 cm dominant omental lesion
– Carcinomatosis
• Sigmoid colon biopsy
– Poorly differentiated adenocarcinoma
• Chest CT insignificant
• Colonoscopy
– Nearly obstructing sigmoid mass
Admitted to Hospital
• Intractable pain and nausea on admission
– Pain 9/10
– Managed with hydromorphone 2 mg IV every
2 hours as needed
– Ondansetron, prochlorperazine for nausea
Opioid Analgesics
Mu (µ) Agonists
• Codeine
• Fentanyl
• Hydrocodone
• Hydromorphone
• Methadone
• Morphine
• Oxycodone
• Oxymorphone
• Tramadol
• Tapentadol
Partial agonist
• Buprenophrine
Mixed agonist-antagonists
Kappa (K) opioids
• Butorphanol
• Nalbuphine
• Pentazocine
Colson, J., D. Koyyalagunta, et al. (2011). "A systematic review of observational studies on the effectiveness of opioid therapy for
cancer pain." Pain Physician 14(2): E85-102.
7
Morphine
• Standard for comparison
– Oral CR and IR available, liquid
– SC, IV, PR, epidural, intrathecal
• Metabolites
– Morphine-3-glucuronide (M3G)
• antagonizes analgesic effect of morphine and M6G
• paradoxical neuroexcitatory effects
– Morphine-6-glucuronide (M6G)
• more potent analgesic activity than morphine
• contributes to overall analgesic effect
American Pain Society (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (Sixth ed.). Glenview,
IL, APSJPress.
Pergolizzi
et al. 2008; Morita et al., 2002. Morita T et al. J Pain Symptom Manage. 2002;23(2):107-113.
Oxycodone
• Availability: CR, IR, solution, combination with
acetaminophen
• Caution when combined with acetaminophen
– Should not exceed > 4 gms/day
• Active metabolite: oxymorphone but active drug primarily
responsible for pain relief
– No cumulative effects known
– Mediated by CYP450 but implications unclear
• Recommendations
– Consider if untoward side effects with other opioid
– Consider in patients with renal compromise over morphine
• Greater potential for addiction?
American Pain Society (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (Sixth ed.). Glenview,
IL, APSJPress.
Pergolizzi
et al. 2008
Fentanyl’s Variability
• Lipophilic – global tissue distribution
• Metabolized by CYP450 3A4 but implications unclear
• Transdermal patch
– Onset 12 hours, peak 24-48 hours, duration 72 hours
– Adhesive reaction: Triamcinolone inhaler, spray to skin
before applying patch
– Do not apply heat to patch
• Transmucosal/Intranasal (sucker, buccal tablet, sublingual, film,
nasal)
– Fast onset (5-10 minutes)
– Duration of action up to 60 minutes
• Intravenous
– Onset within minutes
– Duration 15-30 minutes
• Intrathecal/Epidural
American Pain Society (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (Sixth ed.). Glenview,
IL, APS Press.
8
TD Fentanyl Considerations
• Variability Considerations
– Consider delayed onset and delayed
elimination (accumulation)
– Differences in body weight
• Obese – delayed onset
• <BMI – may not achieve full benefit or decreased
duration of action
• Cachexia – Do Not Use!
American Pain Society (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (Sixth ed.). Glenview,
IL, APS Press.
Hydromorphone
• Availability: CR, IR, SC, IV, epidural, intrathecal
– High solubility eases use in SC/IV administration
– New extended release available
• Available in 8 mg, 12 mg, 16 mg tablets
• Dosage is every 24 hours
• Active metabolites
– Hydromorphone-3-glucuronide (H3G),
hydromorphone-6-glucuronide (H6G)
– Little data on the impact of these metabolites
• Recommendations
– Safe drug to use in hepatic and renal compromise
although NCCN guidelines state to use with caution in
renal compromise
American Pain Society (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (Sixth ed.). Glenview,
IL, APS Press; NCCN (2014). Palliative care guidelines. www.nccn.org.
Anxiety
• Nurses report that the patient is highly
anxious
• Pain is felt to be related to his anxiety
9
Nonpharmacologic
• Interventions that affect perception
– Distraction
– Relaxation
– Hypnosis
– Anything that diverts the mind from the pain
• Psychological intervention
• Spiritual intervention
Antidepressants: Tricyclics
• Options: amitriptyline, nortriptylline
• Start at 10 mg hs and titrate upward
• Side effects:
–
–
–
–
Anticholinergic—increased sensitivity in elderly
Orthostatic hypotension
AV heart block
CNS effects
• Amitriptyline not recommended in the elderly
• Side effects of all TCAs may outweigh benefits
Saarto, T. and P. J. Wiffen (2010). "Antidepressants for neuropathic pain." Cochrane Database of Systematic Reviews(11).
Antidepressants: Serotonin Norepinephrine
Reuptake Inhibitors
• Duloxetine—first antidepressant approved for
neuropathic pain
• Dosing: 60 mg/day usual effective dose
• Side effects
– Anticholinergic
– Decrease seizure threshold
– Somnolence
– Glaucoma
– Hepatotoxicity – lower dose or avoid with liver
compromise
– Venlafaxine another SNRI (150-225 mg/day)
Saarto,
T. and P. J. Wiffen (2010). "Antidepressants for neuropathic pain." Cochrane Database of Systematic Reviews(11).
APS, 2006
10
Increased Pain - Ascites
• Paracentesis – 4500 mL removed 2/12
– Reported that pain decreased significantly
– Rapid re-accumulation
– Peritoneal catheter placed 2/19
Titration Protocol
•
Titrate Up (increase dose)
–
Criteria (patient must meet ALL of the following
criteria):
1. Pain rated 4-10 or CNPI greater than or equal to 3, AND
2. Respiratory rate greater than or equal to 12 bpm (unless
patient is actively dying), AND
3. Sedation score of 3 or greater (unless patient is actively
dying)
–
–
Document patients pain score, sedation score, and
respiratory rate at the time of titration
Downward titration also included
© Jeannine Brant, Billings Clinic
Opioid Rotation
• When to rotate
– Titration without analgesic improvement
– Intolerable side effects
– Pain crisis
• Use an equianalgesic conversion chart as a guide
• Consider dose reduction for incomplete cross
tolerance
– 50-75% with good pain control
– 0-25% with poor pain control
Mercadante, S. and A. Caraceni (2011). "Conversion ratios for opioid switching in the treatment of cancer pain: a systematic review."
Palliat Med 25(5): 504-515; American Pain Society (2008). Principles of analgesic use in the treatment of acute pain and cancer pain
(Sixth ed.). Glenview, IL, APS Press.
11
Equianalgesic Chart
Opioid
Parenteral Route
Morphine
10
Oral Route
30
Oxycodone
-
20
Hydromorphone
1.5
7.5
Fentanyl
25 mcg TD is approximately 75 mg oral morphine
Case Study #2
• Jenna is a 36 year-old patient with Stage IVA
cervical cancer
– History of substance use disorder (SUD) – heroin abuse
– Hepatitis C
– Enrolled at the local methadone clinic (20 mg/day) but has
to drive 40 miles daily to receive her dose
– Found a NA program but cannot attend because she is on
opioids for pain
– Hydronephrosis, vesicovaginal fistula
– Comes to the clinic with RLQ abdominal pain, increasing
right hip pain that radiates down her leg, and anxiety
Methadone
• Stigma – used to treat opioid addiction
• Lipophilic
– Significant tissue distribution
• Protein bound - alpha-1-acid glycoprotein (AGP)
– Drug-drug interactions through competitive binding
• Metabolized by cytochrome p450
– Drug-drug interactions
• No known active metabolites
• NMDA activity—may decrease tolerance and inhibit neuropathic
pain
• High oral bioavailability—parenteral form may not be an advantage
• Cost effective
Nicholson, A. B. (2009). "Methadone for cancer pain." Cochrane Database Syst Rev(4): CD003971.05al. 2005
12
Methadone
• Long half-life may lead to drug accumulation
– 15-60 hours average; up to 120 hours
• Recommendations for administration
–
–
–
–
Should only be used by experienced clinicians
Should be used with caution in all patients
Start low and go slow
Consider delayed onset and delayed elimination (accumulation)
• 4-5 half-lives to reach steady state
– May want to avoid with polypharmacy issues
– Recommend a pretreatment EKG before starting methadone due to
potential QT prolongation and cardiac arrhythmias; follow EKG up one
at 30 days and then annually, and if the dose exceeds 100 mg/day
American Pain Society (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (Sixth ed.). Glenview, IL,
APS Press.
Converting to Methadone
• If morphine equivalents:
– <90 mg – 1 mg methadone: 4 mg morphine
– 90-300 mg – 1:8
– >300 mg – 1:12
– >600-1000 mg – 1:20
American Pain Society (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (Sixth ed.). Glenview, IL,
APS Press.in Society, 2008
Pain Assessment
• Location: RLQ abdominal and right hip
• Intensity: 7/10 and 9/10
– Best 7, Worst 10
• Quality: RLQ (deep aching); Right hip (deep
aching, radiating down right leg)
• Temporality: Increases with movement or activity
• Supportive Care Medications:
–
–
–
–
Gabapentin 2400 mg/day
Morphine CR 60 mg every 8 hours
Morphine IR 20 mg every 4 hours as needed
Lorazepam 1 mg po tid prn
13
Anticonvulsant: Gabapentin
• First line treatment for neuropathic pain of all types
• Dosing
– Starting at 100-300 mg daily to effective dose 900-3,600 daily in
2-3 divided doses
– Renal insufficiency
• GFR 30-59 mL/min 600 mg twice daily
• GFR 15-29 mL/min 300 mg twice daily
• GFR < 15 mL/min 300 mg daily
• Titration
– Multiple steps of 50-100% every 3 days
– Slower with elderly and renal insufficiency
• Side Effects
– Somnolence dose limiting toxicity
– Dizziness, ataxia, edema, wt. gain, dyspepsia, leukopenia
American Pain Society (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (Sixth ed.). Glenview,
IL, APS Press.
Anticonvulsant: Pregabalin
• Advantages
– More efficiently absorbed through the GI tract
– More rapid onset of analgesia
– Simpler titration
• Dosing
– Starting 150 mg/daily
– Usual effective dose 150-300 mg bid
• Titration simple with 2-3 steps
• Side Effects
– Somnolence, dizziness, edema, ataxia, HA,
confusion, diarrhea
American Pain Society (2008). Principles of analgesic use in the treatment of acute pain and cancer pain (Sixth ed.). Glenview,
IL, APS Press.
Opioid Dosing and Titration
• Perform titration after reaching steady state
– Average 4-5 half-lives for IR opioids
– Average 2-3 days for CR opioids (or >)
– 3-6 days for TD fentanyl
• Titrate 24 hour dose by 25-33%
• Keep breakthrough dose at approximately 1020% - higher with severe incident pain
• Consider dose reduction for incomplete cross
tolerance
– 50-75% with good pain control
– 0-25% with poor pain control
Zeppetella, G. and M. D. C. Ribeiro (2008). "Opioids for the management of breakthrough (episodic) pain in cancer patients."
Cochrane Database of Systematic Reviews(1); American Pain Society (2008). Principles of analgesic use in the treatment of acute
pain and cancer pain (Sixth ed.). Glenview, IL, APS Press.
14
Case Study Update
•
•
•
•
•
Patient ‘s pain is stable
She is running out of lorazepam early
High anxiety
Father is concerned about SUD relapse
Challenges with NA due to current opioid
use
• Rural challenges with methadone clinic
Miscellaneous Adjuvants
• Corticosteroids
• NMDA Antagonists
– Ketamine, Dextromethorphan, Methadone
• Local Anesthetics
– Lidocaine
• Alpha-2 Adrernergic Agonists
– Clonidine
• Muscle Relaxants
• Antispasmodics
• Ziconotide
Bell, R. F., C. Eccleston, et al. (2012). "Ketamine as an adjuvant to opioids for cancer pain." Cochrane Database of Systematic
Reviews(3).; Challapalli, V., I. W. Tremont-Lukats, et al. (2005). "Systemic administration of local anesthetic agents to relieve
neuropathic pain." Cochrane Database Syst Rev(4): CD003345.
Summary
• Nurses can encounter tough pain cases while
caring for patients with cancer
• Opioids and adjuvants are usually effective in
managing pain
• Occasionally, out of the box strategies are
necessary for comprehensive management, e.g.
ketamine, lidocaine, intraspinal routes, etc.
• Patients with SUDs require an individualized
approach
• A team approach is essential to discuss
management options
15
References
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