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Cancer Pain Management
Suzana Makowski, MD MMM FACP FAAHPM
• 50 to 90 percent of oncology inpatients report
  breakthrough pain
• 35 percent of community based oncology practices
  patients report breakthrough pain
• 1 in 3 patients with active cancer report pain
• 3 out of 4 of patients with advanced cancer report pain




Prevalence of Cancer Pain
•   Bone metastases
•   Visceral metastases
•   Immobility
•   Neuropathic pain
•   Soft tissue
•   Constipation
•   Esophagitis
•   Lymphedema
•   Muscle cramps
•   Chronic postoperative scar

•   Adapted from Twycross R, Harcourt J, Bergl S: A survey of pain in patients with advanced cancer.
    J Pain Symptom Manage 1996;12:273-282.




Common Causes
Physical                                          Emotional Existential
• Increased catabolic demands:                    Depression    Suffering –
   poor wound healing, weakness, muscle           Anxiety       “why me?”
   breakdown                                      Decreased
• Decreased limb movement:                        intimacy
                                                  Suicidality
    increased risk of DVT/PE
• Respiratory effects:
   shallow breathing, tachypnea, cough
   suppression increasing risk of pneumonia and
   atelectasis
• Sodium and water retention Decreased
  gastrointestinal mobility
• Tachycardia and elevated blood pressure
• Decreased functional status
• Increased chronic pain




      Effects of under treated pain
Effects of under treated pain
• System barriers to treating pain
  • Clinical,
  • Patient-related
  • System-related
• Racial and ethnic barriers exist
  • Language
  • Perceptions
• Concern about addiction
  •   Differences between addiction,
  •   dependence,
  •   tolerance &
  •   pseudoaddiction



Barriers to Pain Control
Intensity • Location • Quality • Timeline •
Alleviating factors • Meds tried


Pain Assessment
What about for patients who cannot self-report?




Intensity
Category          Cause                      Symptom                    Examples

Physiologic       Brief exposure to a        Rapid yet brief pain       Touching a pin or hot
                  noxious stimulus           perception                 object


                  Somatic or visceral tissue Moderate to severe pain,   Surgical pain,
Nociceptive/infla
                  injury with mediators      described as crushing or   traumatic pain, sickle
mmatory
                  having an impact on        stabbing                   cell crisis
                  intact nervous tissue


                  Damage or dysfunction      Severe lancinating,
                                                                        Neuropathy, CRPS.
Neuropathic       of peripheral nerves or    burning or electrical
                                                                        Postherpetic Neuralgia
                  CNS                        shock like pain


                                             Combinations of            Low back pain, back
                  Combined somatic and
Mixed                                        symptoms; soft tissue plus surgery pain
                  nervous tissue injury
                                             radicular pain


Pain Quality
Timeline
• What worked?
                  • What doses?
                  • What side
                    effects?




Prior medications & other tx
Common                      Rare
•   Constipation            • Respiratory suppression
•   Nausea                  • Neurotoxicity
•   Sleepiness/somnolence   • Seizures
•   Pruritus
•   Myoclonus




Side effects
Opioid Pharmacology
Short-acting                            Long-acting
•   Hydrocodone/APAP
                                 •   Transdermal fentanyl
•   Oxycodone +/- APAP
                                 •   methadone
•   Morphine
                                 •   morphine ER
•   Hydromorphone
                                 •   oxycodone ER
•   Oral transmucosal fentanyl


• Cmax ~ 45 min
                                     Cmax and T1/2 vary based on
• T1/2 ~ 4 hours
                                       formulation and drug
• Except fentanyl



       Opioid Pharmacology
• Conjugated by liver
• 90-95% excreted in urine
• Dehydration, renal failure, severe hepatic failure
  • Decrease interval/dosing size
  • If oliguria/anuria
     • STOP routine dosing (basal rate) of morphine
• Use ONLY PRN




Opioid pharmacology
What is the half life (range) for opioids?
• 2-4 hours

How many half lives to get to steady state?
• 4-5

What do you base your scheduled dosing on: Cmax or T1/2?
• T1/2

What do you base your breakthrough dosing on: Cmax or T1/2?
• Cmax


Opioid Pharmacology
Equianalgesic dosing
What is the challenge
with Step 2 of the
ladder?




        WHO Step-Ladder
Hector G - 65 yo man with colon cancer and bone metastases
Your colleague first started Mr. G on hydrocodone 5 mg +
acetaminophen 325 mg one tablet by mouth every 4 hours prn for
his hip and rib pain. He also ordered senna + docusate 2 tabs po
qday to prevent opioid‐induced constipation.
Today, he tells you he is taking the Vicodin 1 tablet every 4 hours
around the clock (including at night). His pain is generally
constant, aching and he rates it as 5/10, but worsens to 8/10 with
certain positions and movements.

• How will you titrate his opioid pain medication?


Case – part 1 - outpatient
• Convert from Vicodin to Morphine
• How to convert to a combination of long- and short-
  acting morphine (the latter for breakthrough pain)?
• What co-analgesics and other treatments might you
  choose?




Case – Part 1
• Hector comes to hospital for a procedure. He is made
  NPO. His pain has been well managed. How do you
  manage his pain?
• Home regimen: MSContin 30mg BID, Roxanol 10mg q2
  hours prn, requiring 2 – 4 doses per day.

• What if he were on Oxycodone/Oxycontin instead?




Case – Part 2 – NPO inpatient
• Mr. G presents to the ER after several days of escalating hip
  and rib pain, despite taking the maximum dose of morphine he
  was prescribed as an outpatient. “I can’t take it anymore.” You
  admit him for pain management while trying to treat his
  escalating pain.
• Home medications: MSContin PO 30mg bid, Morphine liquid
  10mg PO q2 hours prn (taking every dose)


In addition to imaging him, calling radiation oncology
for evaluation, how do you manage his pain?



Case – part 3
• This is as much of a
  crisis as a code (JAMA
  2008;299(12):1457-1467. doi:
  10.1001/jama.299.12.1457)
• http://jama.ama-
  assn.org/content/299/12/1457.full.
  pdf




Pain crisis
Non-interventional      Interventional
• Methadone (opioid +   • Nerve blocks
  NMDA)                 • Intrathecal pain pumps
• Ketamine (NMDA)
  infusion
• Lidocaine infusion




Advanced pain
techniques
• Choosing to be CMO does not automatically increase
  opioid requirement
• Caution with renal failure




Pain at End-of-Life
• Pain is common in cancer. Undertreated pain worsens
  prognosis
• On a good day, patients should not need PRNs, and on a
  bad day, should not need it more than 4 times per day.
• When converting to IV from PO – don’t forget to include
  the long-acting opioid.
• Opioid conversion is not mysterious
• Pain Crises is as serious as a code
• Methadone is a great drug – but is complicated
• Avoid morphine and hydromorphone in renal failure
• Match pain pattern with opioid pharmacology
• CMO ≠ continuous morphine only
• We’re here to help

Summary: Top 10
• https://cissecure.nci.nih.gov/ncipubs/detail.aspx?prodid=
  Q014




Free CME from NCI

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Cancer pain

  • 1. Cancer Pain Management Suzana Makowski, MD MMM FACP FAAHPM
  • 2. • 50 to 90 percent of oncology inpatients report breakthrough pain • 35 percent of community based oncology practices patients report breakthrough pain • 1 in 3 patients with active cancer report pain • 3 out of 4 of patients with advanced cancer report pain Prevalence of Cancer Pain
  • 3. Bone metastases • Visceral metastases • Immobility • Neuropathic pain • Soft tissue • Constipation • Esophagitis • Lymphedema • Muscle cramps • Chronic postoperative scar • Adapted from Twycross R, Harcourt J, Bergl S: A survey of pain in patients with advanced cancer. J Pain Symptom Manage 1996;12:273-282. Common Causes
  • 4. Physical Emotional Existential • Increased catabolic demands: Depression Suffering – poor wound healing, weakness, muscle Anxiety “why me?” breakdown Decreased • Decreased limb movement: intimacy Suicidality increased risk of DVT/PE • Respiratory effects: shallow breathing, tachypnea, cough suppression increasing risk of pneumonia and atelectasis • Sodium and water retention Decreased gastrointestinal mobility • Tachycardia and elevated blood pressure • Decreased functional status • Increased chronic pain Effects of under treated pain
  • 5. Effects of under treated pain
  • 6. • System barriers to treating pain • Clinical, • Patient-related • System-related • Racial and ethnic barriers exist • Language • Perceptions • Concern about addiction • Differences between addiction, • dependence, • tolerance & • pseudoaddiction Barriers to Pain Control
  • 7. Intensity • Location • Quality • Timeline • Alleviating factors • Meds tried Pain Assessment
  • 8. What about for patients who cannot self-report? Intensity
  • 9. Category Cause Symptom Examples Physiologic Brief exposure to a Rapid yet brief pain Touching a pin or hot noxious stimulus perception object Somatic or visceral tissue Moderate to severe pain, Surgical pain, Nociceptive/infla injury with mediators described as crushing or traumatic pain, sickle mmatory having an impact on stabbing cell crisis intact nervous tissue Damage or dysfunction Severe lancinating, Neuropathy, CRPS. Neuropathic of peripheral nerves or burning or electrical Postherpetic Neuralgia CNS shock like pain Combinations of Low back pain, back Combined somatic and Mixed symptoms; soft tissue plus surgery pain nervous tissue injury radicular pain Pain Quality
  • 11. • What worked? • What doses? • What side effects? Prior medications & other tx
  • 12. Common Rare • Constipation • Respiratory suppression • Nausea • Neurotoxicity • Sleepiness/somnolence • Seizures • Pruritus • Myoclonus Side effects
  • 14. Short-acting Long-acting • Hydrocodone/APAP • Transdermal fentanyl • Oxycodone +/- APAP • methadone • Morphine • morphine ER • Hydromorphone • oxycodone ER • Oral transmucosal fentanyl • Cmax ~ 45 min Cmax and T1/2 vary based on • T1/2 ~ 4 hours formulation and drug • Except fentanyl Opioid Pharmacology
  • 15. • Conjugated by liver • 90-95% excreted in urine • Dehydration, renal failure, severe hepatic failure • Decrease interval/dosing size • If oliguria/anuria • STOP routine dosing (basal rate) of morphine • Use ONLY PRN Opioid pharmacology
  • 16. What is the half life (range) for opioids? • 2-4 hours How many half lives to get to steady state? • 4-5 What do you base your scheduled dosing on: Cmax or T1/2? • T1/2 What do you base your breakthrough dosing on: Cmax or T1/2? • Cmax Opioid Pharmacology
  • 18. What is the challenge with Step 2 of the ladder? WHO Step-Ladder
  • 19. Hector G - 65 yo man with colon cancer and bone metastases Your colleague first started Mr. G on hydrocodone 5 mg + acetaminophen 325 mg one tablet by mouth every 4 hours prn for his hip and rib pain. He also ordered senna + docusate 2 tabs po qday to prevent opioid‐induced constipation. Today, he tells you he is taking the Vicodin 1 tablet every 4 hours around the clock (including at night). His pain is generally constant, aching and he rates it as 5/10, but worsens to 8/10 with certain positions and movements. • How will you titrate his opioid pain medication? Case – part 1 - outpatient
  • 20. • Convert from Vicodin to Morphine • How to convert to a combination of long- and short- acting morphine (the latter for breakthrough pain)? • What co-analgesics and other treatments might you choose? Case – Part 1
  • 21. • Hector comes to hospital for a procedure. He is made NPO. His pain has been well managed. How do you manage his pain? • Home regimen: MSContin 30mg BID, Roxanol 10mg q2 hours prn, requiring 2 – 4 doses per day. • What if he were on Oxycodone/Oxycontin instead? Case – Part 2 – NPO inpatient
  • 22. • Mr. G presents to the ER after several days of escalating hip and rib pain, despite taking the maximum dose of morphine he was prescribed as an outpatient. “I can’t take it anymore.” You admit him for pain management while trying to treat his escalating pain. • Home medications: MSContin PO 30mg bid, Morphine liquid 10mg PO q2 hours prn (taking every dose) In addition to imaging him, calling radiation oncology for evaluation, how do you manage his pain? Case – part 3
  • 23. • This is as much of a crisis as a code (JAMA 2008;299(12):1457-1467. doi: 10.1001/jama.299.12.1457) • http://jama.ama- assn.org/content/299/12/1457.full. pdf Pain crisis
  • 24. Non-interventional Interventional • Methadone (opioid + • Nerve blocks NMDA) • Intrathecal pain pumps • Ketamine (NMDA) infusion • Lidocaine infusion Advanced pain techniques
  • 25. • Choosing to be CMO does not automatically increase opioid requirement • Caution with renal failure Pain at End-of-Life
  • 26. • Pain is common in cancer. Undertreated pain worsens prognosis • On a good day, patients should not need PRNs, and on a bad day, should not need it more than 4 times per day. • When converting to IV from PO – don’t forget to include the long-acting opioid. • Opioid conversion is not mysterious • Pain Crises is as serious as a code • Methadone is a great drug – but is complicated • Avoid morphine and hydromorphone in renal failure • Match pain pattern with opioid pharmacology • CMO ≠ continuous morphine only • We’re here to help Summary: Top 10

Editor's Notes

  1. Cognition and memory play a large role in the experience of pain.10 Fear and depression reduce pain thresholds and produce anatomic changes that accentuate pain. Long-term neuroanatomic changes have been discovered in amygdala and hippocampus, sites that affect pain memory. These changes involve calcium-calmodulin–dependent protein kinases.17
  2. Increased catabolic demands: poor wound healing, weakness, muscle breakdownDecreased limb movement: increased risk of DVT/PERespiratory effects: shallow breathing, tachypnea, cough suppression increasing risk of pneumonia and atelectasisIncreased sodium and water retention (renal)Decreased gastrointestinal mobilityTachycardia and elevated blood pressureDecreased functional statusDepression/anxietyIsolation – decreased intimacyExistential suffering
  3. Increased catabolic demands: poor wound healing, weakness, muscle breakdownDecreased limb movement: increased risk of DVT/PERespiratory effects: shallow breathing, tachypnea, cough suppression increasing risk of pneumonia and atelectasisIncreased sodium and water retention (renal)Decreased gastrointestinal mobilityTachycardia and elevated blood pressureDecreased functional statusDepression/anxietyIsolation – decreased intimacyExistential suffering