Pain Management and Palliative Care

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Pain Management and Palliative Care

• Andrew Tyler Putnam, MD
• Palliative Care Program
• Lombardi Cancer Center

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Objectives

• Brief Overview of Palliative Care
• Overview of Pain
• Pain Management
• Main Focus on Opioids
• The Other End

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Palliative Care
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Palliative Care

• Palliative Care is comprehensive,
  interdisciplinary care for patients whose disease
  is chronic and progressive, or unresponsive to
  curative treatment. It includes pain and symptom
  management as well as psychological, emotional
  and spiritual care. The goal of palliative care
  is to achieve the best quality of life for
  patients and their families, regardless of life
  expectancy
• Center for Health Workforce Studies
• School of Public Health, University of
  Albany
• September 2002

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Palliative Care...

• Affirms life, sees death as a personal and
  natural process
• Many diagnoses
• Appropriate early in course of illness
• Combined with disease-modifying therapies or may
  be the focus of goals of care

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Palliative Care

• Interdisciplinary care of the patient and family
• Psychological, social, spiritual support
• Focuses on relieving suffering, improving quality
  of life
• Pain and symptom management
• Bereavement support

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Curative vs. Palliative Model of Care
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The Continuum of Palliative Care
DISEASE
DISCOMFORT
DISTRESS
DYSFUNCTION
Disease Specific Rx
Bereavement Support(Palliative Care)
Comfort, Supportive Rx(Palliative Care)
Person
Family
Caregivers and Service providers

ILLNESS TRAJECTORY
BEREAVEMENT
DYING
DEATH
SYMPTOMS
DX
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PAIN
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A little pain never hurt anyoneWhat doesnt
kill you makes you strong

• Effects of pain on quality of life
• Physical Sleep disturbance decreased strength
  and endurance nausea and diminished appetite
• Psychosocial Depression anxiety irritability
  difficulty concentrating diminished social
  relationships

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Pain

• Sensory input is modified by individual memory
  and emotions.
• Anxiety
• Depression
• There are no objective biological markers for
  pain
• The most accurate assessment of pain is based on
  the patients self-report

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Pain is what the Patient Says it is!
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Classification of Pain

• Pathophysiology

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Nociceptive Pain results from the activation of
nociceptors and transmitted along normal nerves

• Somatic fractures, bone metastases,
  arthritis, cellulitis
• Typically well-localized
• Visceral pancreatitis, peptic ulcer disease,
  myocardial infarction
• Poorly localized results from compression,
  distension, stretching of viscera.
• Often described as deep, squeezing, aching,
  pressure.
• May be associated with nausea and diaphoresis.
• It is often referred to remote cutaneous
  sites--which may be tender

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Neuropathic Pain results from injury to the
peripheral and central nervous system

• Examples post-thoracotomy pain, phantom limb
  pain, H. zoster diabetic neuropathy
• sharp, lancinating pain may be due to spontaneous
  action potential propagation. Trial of
  anticonvulsant medications which inhibit these
  nervous system discharges.
• Pain described as burning (e.g., diabetic
  neuropathy) may respond better to the tricyclic
  antidepressants.

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Assessment of Pain
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Pain Assessment Characterize the nature of the
pain

• Location
• superficial vs. deep, worst site, patterns of
  radiation?
• Quality
• dull, sharp, burning, tingling, shooting,
  stabbing, electrical?
• Temporal profile
• onset, duration, diurnal variation, relation to
  movement?
• Severity
• on a 0-10 numerical or other rating scale?
• Exacerbating, relieving factors
• EPEC Project, AMA, 1999

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Pain Assessment

• Establish time course
• Constant
• Intermittent
• Both
• Type of intermittent pain
• Breakthrough
• Incident
• End of dose failure

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Intermittent pain

• Breakthrough-usual pain which increases
  episodically and unpredictably
• Incident-predictably caused by specific actions,
  either voluntary or involuntary
• End of dose failure-pain that worsens or
  reoccurs regularly before the next scheduled
  dosing interval

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Incident pain

• Often very difficult to control
• Often requires significantly more than the
  breakthrough/sustained release dose
• May require PCA for higher doses and quicker
  onset
• Often needs an intervention
• Disease specific therapy-XRT, chemo
• Vertebroplasty
• Surgical stabilization

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Treating Pain with Opioids
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Some Principles of Pharmacologic Treatment

• Assess pain thoroughly
• Use simplest schedule and least invasive route
• Prevent persistent pain with around the clock
  analgesia
• Breakthrough pain is common and will usually
  require treatment
• Driving is generally safe if
• pain controlled, dose stable, no adverse effects

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Problems with Managing Pain

• No test to demonstrate pain
• Physician can neither prove nor disprove it
• Patient also can not prove it
• Opioids are drugs of abuse and carry baggage
  for patients, clinicians and even pharmacies.

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Whats so Great about Opioids?

• They relieve pain
• No analgesic ceiling
• No risk of damage to liver, kidneys, gastric
  mucosa.
• No increased risk of bleeding.

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Opioid Effectiveness

• Most common reason an opioid is ineffective is
  reluctance to titrate up till pain is relieved.
• Fear of the numbers
• Increase dose until
• pain is relieved or
• there are dose limiting side effects.
• No upper limit to amounts of opioid

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WHO 3-step Analgesic Ladder
3 Severe
Morphine Hydromorphone Methadone Fentanyl Oxycodon
e Adjuvants
2 Moderate
A/Codeine A/Hydrocodone A/Oxycodone Tramadol
Adjuvants
1 Mild
ASA Acetaminophen NSAIDs Adjuvants

• Adapted from the EPEC Project

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IV
SC / IM
Cmax
po / pr
Plasma Concentration
0
Time
Half-life (t1/2)
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Six Opioids for Chronic Pain

• Morphine
• Oxycodone
• Hydromorphone
• Fentanyl
• Methadone
• Oxymorphone

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Morphine

• May be delivered by multitude of routes oral,
  SL IV, SQ rectal nebulizer epidural,
  intrathecal.
• Available in wide variety of preparations
• Concentrate 20mg/ml SL/PO
• and many other liquid concentrations
• MSO4 tablets and capsules 15 30 mg
• Controlled release (12 hours) 15, 30, 60, 100 mg
• Extended release (24 hours) 20, 30, 50, 60 etc.
• Anecdotally best for dyspnea

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Hydromorphone

• Oral, IV, SC or PR formulations
• Short-acting pills 1,2, 3, 4, 8 mgs
• No long-acting oral formulation
• Rectal suppositories 3 mgs
• Liquid 5mg/ 5cc. Hard to find
• No problematic active metabolites
• Used in renal failure

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Hydromorphone

• Same mechanism of action as morphine
• Parenteral hydromorphone is 7 times more potent
  than parenteral morphine
• Parenteral hydromorphone is 5 times more potent
  than oral Dilaudid
• Dilaudid 2 mg. po/iv q2 hours prn ?????

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Fentanyl

• Available as IV, patch, lollipop (Actiq) and
  new dissolving tablet forms (Fentora)
• Very lipophilic, Need to saturate fat stores.
• Not good for isolated IV prns
• Least affect on blood pressure
• Anecdotally less constipation
• 100x stronger than morphine 10 mcg 1 mg MSO4

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Fentanyl Patch

• Fentanyl patch is useful for chronic, stable
  pain
• Difficult to titrate for rapidly escalating pain
• Peak effect after application is about 24 hours
• Fentanyl patch 25 mcg to skin on call to Rad Onc.
  ????
• D/C when return to floor
• Half-life of 18 hours even after removal of patch
• Listed q 72h but many require change q 48h
• A 25 mcg/h patch changed q3 days is equivalent to
  approximately 60 mg of oral morphine or 20 mg of
  IV morphine a day.
• Do not cut the patch and ensure adherence to skin

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Oxycodone

• Oral preparations only
• Short acting forms 5, 15, 30 mg
• Controlled release (12 hours) 10, 20, 40, 80 mg
• OxyContin 30 mg tabs 2 tabs po bid 120
  ????????
• Approximately equianalgesic with morphine
• Often in combination with acetaminophen or aspirin

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Methadone

• Oral and IV formulations
• No active metabolites
• Half-life of 36 145 hours makes it tricky to
  use
• Cheapest long-acting opioid
• Best known use is in methadone maintenance
  clinics
• Used due to long half-life
• Need to write for pain on scripts
• Arguably the most effective opioid for
  neuropathic pain due to NMDA receptor antagonism

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Oxymorphone

• Opana ER and Opana
• Long acting and short acting
• Major metabolite of oxycodone
• Oral only
• 3 times stronger than oral morphine

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Equianalgesia
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Equianalgesic Dosing

• Opioid IV, SC, IM Oral
• Morphine 10 mg 30 mg
• Oxycodone n/a 20-30 mg
• Hydromorphone 1.5 mg 7.5 mg
• Fentanyl 100 mcg 100 mcg
• Methadone (Chronic dosing) 0.75-1.5 mg
  1.5-3 mg
• Oxymorphone n/a 10 mg

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Equianalgesia

• For example, if you have a patient with
  metastatic pancreatic cancer who is comfortable
  on
• IV (or SQ) morphine at 5mg/h,
• then in the course of a day she is receiving
• 5mg/h x 24h 120mg parenteral morphine/day
• Since parenteral morphine is 3 times more potent
  than oral morphine,
• 120mg of IV morphine x 3 360mg oral
  morphine/day.

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Equianalgesia (cont)

• 120mg of IV morphine x 3 360mg oral
  morphine/day.
• Therefore, you could change this patient to
• 180 mg of slow-release morphine BID or
• 60 mg of oral morphine q4h
• 30-45 mg of morphine should be available for
  breakthrough pain

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Changing Opioids

• Cross-tolerance
• If rotating to another opioid start with 5075
  of known equianalgesic dose
• more if patient is in pain, less if adverse
  effects
• Methadone
• start with 525 of published equianalgesic dose
  

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Patient SJ

• 53 y.o. woman diagnosed with non-small cell lung
  CA 18 months ago, s/p chemo, RT, now with
  metastases to left ribs, spleen and liver.
• The patient is admitted for control of escalating
  pain. She describes diffuse pain throughout her
  body. The worst pain is in her left chest and
  left abdomen. Pain is 10/10. She feels constant
  pain with sudden cramping.

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Patient SJ (cont-2)

• SJ has been taking 12 hour morphine 400 mg BID.
• She has been taking liquid morphine concentrate
  20 mg for breakthrough pain she has taken 20 mg
  doses x 10 over the last 12 hours, without any
  relief of her pain.
• She is also taking dexamethasone 4 mg TID.

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Patient SJ (cont-3)

• 53 y.o. woman with metastatic lung CA with
  visceral and bone pain 10/10.
• No relief on oral morphine 1,000 mg day
  steroids.

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Equianalgesia

• Oral MSO4 1,000 mg/ day ?3 333 mg/
  day IV/SQ MSO4
• 14 mg/hour infusion
• (?7) IV/SQ hydromorphone
• 48 mg/ day 2 mg/hour

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Titrating Opioids

• Moderate pain increase dose by 25-50
• Severe pain increase dose by 50-100
• Note Think percent
• Clinicians find it easy to ? 100 from 2 mg/h to
  4 mg/h
• We balk at an increase of even 50 from 20 mg to
  30 mg/h

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Equianalgesia and Breakthrough Dosing

• 50 y.o. man CA pancreas discharged from hospital
  on
• 12 hour oxycodone 160mg po bid
• and
• Percocet 5/325 mg, 1-2 tabs q 4h prn
• What should he be on for breakthrough pain?

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Long-acting Opioids

• Same drug as the short-acting but in a timed
  release form
• Goal is to prevent as much pain as possible with
  a stable blood level of the opioid
• Breakthrough medication about 0 2 times a day
  is expected.

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1 Month Cost of Long Acting Opioids

• Fentanyl 25 mcg. patch q3D 201.90
• 12 hour morphine 15 mg. bid 60.60
• 12 hour oxycodone 10 mg. bid 103.30
• Kadian 20 mg. q Day 65.20
• Avinza 30 mg. q Day 109.80
• Methadone 10 mg. tid 22.60
• Fentanyl 100 mcg. patch q3D 747.05
• 12 hour morphine 200 mg. bid 921.85
• 12 hour oxycodone 90 mg. bid 702.95
• Methadone 20 mg. tid 37.15

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Opioid Adverse Effects

• Common Uncommon
• Constipation Bad dreams / hallucinations
• Dry mouth Dysphoria / delirium
• Nausea / vomiting Myoclonus / seizures
• Sedation Pruritus / urticaria
• Sweats Respiratory depression
• Urinary retention

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Opioid Allergy

• Only true allergies
• Anaphylactic reactions e. g. bronchospasm
• Urticaria
• Both need careful assessment to verify allergy
• Nausea / vomiting, constipation, drowsiness,
  confusion
• ADVERSE EFFECTS, not allergic reactions

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Respiratory Depression

• Opioid effects differ for patients treated for
  pain
• pain is a potent stimulus to breathe
• loss of consciousness precedes respiratory
  depression
• pharmacologic tolerance rapid

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. . . Respiratory Depression

• Management
• Identify, treat contributing causes
• Reduce opioid dose
• Observe
• If unstable vital signs
• naloxone, 0.1-0.2 mg IV q 1-2 min

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Tolerence, Dependence, Addiction
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Tolerance

• Reduced effectiveness of a given dose over time
• If dose is increasing in cancer patient, first
  suspect disease progression

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Physical Dependence

• A process of neuroadaptation
• Abrupt withdrawal may ? abstinence syndrome
• Also beta blockers, steroids, other meds
• If dose reduction required, reduce by 50 q 23
  days
• avoid antagonists

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Addiction . . .

• Psychological dependence
• Compulsive use in spite of harm
• Loss of control over drugs
• Loss of interest in pleasurable activities
• An uncommon outcome of pain management
• particularly, if no history of substance abuse

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Adjuvant Pain Medications
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Adjuvant Analgesics

• Medications that supplement primary analgesics
• may themselves be primary analgesics
• use at any step of WHO ladder

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Non-opioid Pain Medications

• Acetaminophen
• Non-steroidal anti-inflammatory drugs
• Corticosteroids
• Antispasmodics
• Tricyclic antidepressants
• Anticonvulsants
• NMDA antagonists (ketamine)
• Anesthetics

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Burning, Tingling, Neuropathic Pain

• Antidepressants
• Amitriptyline limited usefulness in frail,
  elderly
• Nortriptylline
• Desipramine tricyclic of choice in seriously ill
• Duloxetine (Cymbalta)
• Anticonvulsant
• Gabapentin minimal adverse effects
• drowsiness, tolerance develops within days
• SSRIs usually not so useful

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Shooting, Stabbing, Neuropathic Pain

• Anticonvulsants
• Oxcarbazepine
• Pregabalin
• Gabapentin
• carbamazepine
• valproic acid
• monitor plasma levels for risk of toxicity

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The Other End
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Constipation

• Medications
• opioids
• calcium-channel blockers
• anticholinergic
• Decreased motility
• Ileus
• Mechanical obstruction

• Metabolic abnormalities
• Spinal cord compression
• Dehydration
• Autonomic dysfunction
• Malignancy

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Constipation

• Common to all opioids
• Opioid effects on CNS, spinal cord, myenteric
  plexus of gut
• Physiologic tolerance usually does not develop
• Much easier to prevent than treat

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Constipation

• Diet usually insufficient
• OTC bulk forming agents not recommended
• Stool softeners
• Sodium docusate
• Phosphosoda enema prn
• Stimulant laxative
• senna, bisacodyl, casanthranol
• Combine with a stool softener
• senna docusate sodium
• casanthranol docusate sodium

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Constipation

• Osmotic laxative
• Lactulose or Sorbitol 15-30 ml QD to Q4h
• Bisacodyl 5-15 mg PO/PR QD-BID
• Polyethylene glycol (MiraLax, GlycoLax)
• Prokinetic agent
• Metoclopramide
• Other measures
• Mineral oil, magnesium hydroxide, magnesium
  citrate, suppositories, enemas

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Summary

• Palliative care teams can be effective in
  treating difficult symptoms at all stages of
  disease
• Pain can severely affect patients
• It is important to use opioids when appropriate
  to treat pain
• Constipation is easier to prevent than to treat

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