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On Pain: Taking the pain out of pain management
Suzana Makowski, MD MMM FACP
Palliative Care
UMassMemorial/UMassMedicalSchool
Overview

• Pain assessment review


• Opioid pharmacology: what I wish I had known...


• Pain syndromes
•   Intensity
                     Assessing pain:             •   Location
                                                 •   Quality: Nociceptive/Neuropathic
The easiest pain to tolerate is someone else’s   •   Timeline
                                                 •   Alleviating/Exacerbating factors
Pain Intensity

• Visual analogue scale: No pain-------------------------Worst pain


• Numeric scale: 0 - 1 - 2 - 3 - 4 - 5 - 6 - 7 - 8 - 9 - 10


• Categorial scale: mild (1-3) - moderate (4-6) - severe (7-10)


• FACES scale:




• PAID-AD scale:
PAINAD Scale: for non-verbal patients with
dementia
Pain Assessment: Timeline
Intensity




                Time
Challenges to pain assessment

• Acute vs. chronic pain         • Dependence

• Concerns about addiction and   • Tolerance
  abuse/misuse

                                 • Addiction
• What else?

                                 • Pseudoaddiction
Barriers to Pain Management

Physician-Related

• Limited knowledge of pain pathophysiology and assessment skills
• Biases against opioid therapy and overestimation of risks
• Fear of regulatory scrutiny/action

Patient-Related

• Exaggerated fear of addiction, tolerance, side effects
• Reluctance to report pain: stoicism, desire to “please” physician
• Concerns about “meaning” of pain (associate increased pain with worsening disease)

System-Related

• Low priority given to pain and symptom control
• Limits on number of Rxs filled per month & number of refills allowed
• Reimbursement policies
(American Pain Society, 2001; Glajchen, 2001; Lister, 1996; Portenoy RK, 1996; Weinstein et al, 2000)
Racial & Ethnic Barriers

• Language or cultural differences make pain assessment more difficult

• Physiciansʼ perceptions and misconceptions:
   ✴minority-group patients have fewer financial resources to pay for
     prescriptions
   ✴higher drug-abuse potential among minority groups

• Patients’ lack of assertiveness in seeking treatment

• Lack of treatment expertise at many sites at which minority-group patients
    are treated

• Relative unavailability of opioids in some communities
 (Bonham, 2001; Glajchen, 2001)
Untreated pain can lead to worsening chronic pain

• In chronic pain, the nervous system remodels continuously in
  response to repeated pain signals
  • nerves become hypersensitive to pain
  • nerves become resistant to antinociceptive system
• If untreated, pain signals will continue even after injury resolves

• Chronic pain signals become embedded in the central nervous system
Chronic Pain Syndromes: Cancer, Chronic Low Back Pain, Osteoarthritis,
Fibromyalgia
Cancer pain

Highly prevalent:
• 30-50% in active treatment
• 75-90% in advanced illness


Principles of Assessment
Pain History
  • chronicity
  • intensity and severity
  • pathophysiology and mechanism
  • tumor type and stage of disease
  • pattern of pain and syndrome
  Physical and Neurologic Examination
  Radiographic Findings
Cancer Pain Treatment considerations

   Identify the cause of the pain
• Primary treatment if indicated
• WHO ladder combined with etiology-specific therapies for syndromes
   ✴pharmacologic and nonpharmacologic interventions
   ✴long-acting + short-acting opioids
   ✴adjuvant medications for neuropathic pain
   ✴NSAIDs and steroids can be helpful when there is an inflammatory
     component to pain
WHO guidelines

• Step 3: Opioid for moderate
  to severe pain
  +/- adjunctive treatment
  +/- non-opioid
                                                                      Pain Persists
• Step 2: Opioids for mild to
  moderate pain
  +/- adjunctive treatment
  +/- non-opioid
                                                                      Pain Persists
• Step 1: Non-opioid
  +/- adjunctive treatment



                                (Adapted from Portenoy et al, 1997)
Chronic Low Back Pain

• 60-85% lifetime prevalence
Clinical Characteristics
• Preoccupation with pain
• Consistently disabled from
  pain
• Depression and anxiety are
  common
• High incidence of psychiatric
  diagnoses
• Drug misuse is common, but
  addiction relatively rare
Low-Back Pain Treatment Considerations

• Analgesic Medications

• Adjuvant Analgesics

• Physical Therapy Approaches

• Neural Stimulation

• Psychologic Management

• Multidisciplinary Pain Centers
Osteoarthritis

• Affects over 80% of people over 55

• 23% have limitation of activity

Diagnosis
• History: age, functionality, degree of pain, stiffness, time of occurrence
  (e.g., morning, at rest, during activity)
• Physical examination: range of motion, tenderness, bony enlargement
  of joint
• Laboratory findings: radiograph, CBC, synovial fluid analysis
Osteoarthritis Treatment Considerations

• After comprehensive assessment of function and pain



        Mild to moderate pain               Acetaminophen



       Moderate to severe pain             COX-2 and NSAIDs


  Severe arthritic pain (unresponsive
  to non-opioid, or for elderly at risk        Opioids
        for renal insufficiency)

      Drug therapy ineffective or
                                               Surgery
       debilitating pain/function
Pain treatment

• Pharmacotherapy
• Rehabilitative Approaches
• Psychologic Interventions
• Anesthesia/Interventional Pain Approaches
• Neurostimulatory Techniques
• Radiotherapy
• Surgery
• Complementary/Alternative Approaches
• Lifestyle Changes
Opioids

• Pure (Full) Agonists: Preferred for Chronic Pain
   • Bind to opioid receptor(s)
   • No antagonist activity
   • No ceiling effect
• Agonist-Antagonists
   • Ceiling effect for analgesia
   • Can reverse effects of pure agonists
      ✴ mixed agonist-antagonists (butorphanol,
      ✴ nalbuphine, pentazocine, dezocine)
      ✴ partial agonists (buprenorphine)
• Antagonists
   • Reverse or block agonist effects of pure opioids
   • Naloxone has been used to treat opioid overdose, addiction
Oral Opioids

        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 in liver


• First pass metabolism


• Excreted by kidney (90-95%)


• First order kinetics
First order kinetics of opioids




       6-7 min   15-20 min   45-60 min
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
Delivery of opioids

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
Scheduling oral short-acting opioids

• Scheduled dosing based on t1/2
  • Q4 hours
• PRN dosing based on time to Cmax
  • Can be as frequent as Q1 hour PRN
• Adjust scheduled dose daily based on prn use
Scheduling long-acting opioids
(except methadone)

• Reason for use:
  • Improve compliance, adherence
• Dose q8, q12, q24 hours (depending on product)
  • Don’t crush or chew
  • May use time-release granules (Kadian)
• Adjust dose every 2-4 days (once steady state is reached.)
Side effects of opioids


            Common                     Uncommon

                                 Bad dreams/hallucinations
        Constipation*                     Delirium
         Dry mouth                      Myoclonus
       Nausea/Vomiting                   Seizures
          Sedation                   Pruritus, urticaria
           Sweats                 Respiratory suppression
                                     Urinary retention

  *No development of tolerance
Opioid side effects: Constipation

• Stimulant laxative:
   • Senna, bisacodyl, glycerine, etc.
• Stool softener
   • Docusate
• Prokinetic agent
   • Metoclopramide
• Osmotic laxative (from above or below)
• Specific to peripheral opioid receptors
   • methylnatrexone
Opioid side effects: Nausea/Vomiting

• Onset with start of opioids, tolerance may develop
• Mechanism: dopamine receptors and decreased motility
• Prevent or treat with dopamine-blocking anti-emetics (avoid with
    long-QT):
  • Haloperidol 0.5-1mg every 6 hours
  • Droperidol 0.625 mg (PACU order set)
  • Metoclopramide 10mg every 6 hours
• Alternative opioid if refractory
Opioid side-effects: Sedation

• Onset with start of opioids
  • Distinguish from exhaustion due to pain*
  • Tolerance develops within days
• Complex assessment in advanced disease
• If persistent, may consider alternative opioid or route of
     administration
• Psychostimulants may play a role as well
  • Methylphenidate 5mg qAM and 1 noon
Opioid side-effects: Neuroexcitability

• Presentation
  • Cognitive changes: CAM assessment             Reason to avoid “titrate
                                                 to comfort” order at end-
     • acute onset or fluctuating course,                 of-life
     • inattention,
     • disorganized thinking/altered level of consciousness
  • Restlessness, agitation
  • Can cause hyperalgesia
  • Myoclonic jerks, seizures (may be repressed if on benzodiazepines)
  • More common in renal failure
• Mechanism:
  • Morphine/hydromorphone 6-glucoronide build-up
• Management:
  • Benzodiazepines, fluids, and perhaps dialysis - antipsychotics
    exacerbate symptoms
Opioid side-effects: respiratory depression

• Opioid effects differ among patients
  • Change in LOC occurs before respiratory suppression
  • Pharmacologic tolerance develops rapidly
  • Most studies of respiratory depression in opioids looked at patients
     with drug overdose
• Management:
  • Identify and treat contributing causes
     • Reduce opioid dose and observe
  • If unstable vital signs:
     • Naloxone 0.1-0.2 mg IV q 1-2 min
Summary

• Treat pain as though it were your own:
   ✴remember under/untreated acute pain can lead to severe chronic pain


• Schedule routine opioids based on half-life


• Consider offering prns based on Cmax:
   ✴IV=6-12 min;
   ✴SQ=20-30min;
   ✴PO=45-1hour


• When ordering opioids, always order bowel regimen to avoid constipation


• Watch for neurotoxicity in renal insufficiency - especially at end-of-life

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On pain

  • 1. On Pain: Taking the pain out of pain management Suzana Makowski, MD MMM FACP Palliative Care UMassMemorial/UMassMedicalSchool
  • 2. Overview • Pain assessment review • Opioid pharmacology: what I wish I had known... • Pain syndromes
  • 3. Intensity Assessing pain: • Location • Quality: Nociceptive/Neuropathic The easiest pain to tolerate is someone else’s • Timeline • Alleviating/Exacerbating factors
  • 4. Pain Intensity • Visual analogue scale: No pain-------------------------Worst pain • Numeric scale: 0 - 1 - 2 - 3 - 4 - 5 - 6 - 7 - 8 - 9 - 10 • Categorial scale: mild (1-3) - moderate (4-6) - severe (7-10) • FACES scale: • PAID-AD scale:
  • 5. PAINAD Scale: for non-verbal patients with dementia
  • 7. Challenges to pain assessment • Acute vs. chronic pain • Dependence • Concerns about addiction and • Tolerance abuse/misuse • Addiction • What else? • Pseudoaddiction
  • 8. Barriers to Pain Management Physician-Related • Limited knowledge of pain pathophysiology and assessment skills • Biases against opioid therapy and overestimation of risks • Fear of regulatory scrutiny/action Patient-Related • Exaggerated fear of addiction, tolerance, side effects • Reluctance to report pain: stoicism, desire to “please” physician • Concerns about “meaning” of pain (associate increased pain with worsening disease) System-Related • Low priority given to pain and symptom control • Limits on number of Rxs filled per month & number of refills allowed • Reimbursement policies (American Pain Society, 2001; Glajchen, 2001; Lister, 1996; Portenoy RK, 1996; Weinstein et al, 2000)
  • 9. Racial & Ethnic Barriers • Language or cultural differences make pain assessment more difficult • Physiciansʼ perceptions and misconceptions: ✴minority-group patients have fewer financial resources to pay for prescriptions ✴higher drug-abuse potential among minority groups • Patients’ lack of assertiveness in seeking treatment • Lack of treatment expertise at many sites at which minority-group patients are treated • Relative unavailability of opioids in some communities (Bonham, 2001; Glajchen, 2001)
  • 10. Untreated pain can lead to worsening chronic pain • In chronic pain, the nervous system remodels continuously in response to repeated pain signals • nerves become hypersensitive to pain • nerves become resistant to antinociceptive system • If untreated, pain signals will continue even after injury resolves • Chronic pain signals become embedded in the central nervous system
  • 11. Chronic Pain Syndromes: Cancer, Chronic Low Back Pain, Osteoarthritis, Fibromyalgia
  • 12. Cancer pain Highly prevalent: • 30-50% in active treatment • 75-90% in advanced illness Principles of Assessment Pain History • chronicity • intensity and severity • pathophysiology and mechanism • tumor type and stage of disease • pattern of pain and syndrome Physical and Neurologic Examination Radiographic Findings
  • 13. Cancer Pain Treatment considerations Identify the cause of the pain • Primary treatment if indicated • WHO ladder combined with etiology-specific therapies for syndromes ✴pharmacologic and nonpharmacologic interventions ✴long-acting + short-acting opioids ✴adjuvant medications for neuropathic pain ✴NSAIDs and steroids can be helpful when there is an inflammatory component to pain
  • 14. WHO guidelines • Step 3: Opioid for moderate to severe pain +/- adjunctive treatment +/- non-opioid Pain Persists • Step 2: Opioids for mild to moderate pain +/- adjunctive treatment +/- non-opioid Pain Persists • Step 1: Non-opioid +/- adjunctive treatment (Adapted from Portenoy et al, 1997)
  • 15. Chronic Low Back Pain • 60-85% lifetime prevalence Clinical Characteristics • Preoccupation with pain • Consistently disabled from pain • Depression and anxiety are common • High incidence of psychiatric diagnoses • Drug misuse is common, but addiction relatively rare
  • 16. Low-Back Pain Treatment Considerations • Analgesic Medications • Adjuvant Analgesics • Physical Therapy Approaches • Neural Stimulation • Psychologic Management • Multidisciplinary Pain Centers
  • 17. Osteoarthritis • Affects over 80% of people over 55 • 23% have limitation of activity Diagnosis • History: age, functionality, degree of pain, stiffness, time of occurrence (e.g., morning, at rest, during activity) • Physical examination: range of motion, tenderness, bony enlargement of joint • Laboratory findings: radiograph, CBC, synovial fluid analysis
  • 18. Osteoarthritis Treatment Considerations • After comprehensive assessment of function and pain Mild to moderate pain Acetaminophen Moderate to severe pain COX-2 and NSAIDs Severe arthritic pain (unresponsive to non-opioid, or for elderly at risk Opioids for renal insufficiency) Drug therapy ineffective or Surgery debilitating pain/function
  • 19. Pain treatment • Pharmacotherapy • Rehabilitative Approaches • Psychologic Interventions • Anesthesia/Interventional Pain Approaches • Neurostimulatory Techniques • Radiotherapy • Surgery • Complementary/Alternative Approaches • Lifestyle Changes
  • 20. Opioids • Pure (Full) Agonists: Preferred for Chronic Pain • Bind to opioid receptor(s) • No antagonist activity • No ceiling effect • Agonist-Antagonists • Ceiling effect for analgesia • Can reverse effects of pure agonists ✴ mixed agonist-antagonists (butorphanol, ✴ nalbuphine, pentazocine, dezocine) ✴ partial agonists (buprenorphine) • Antagonists • Reverse or block agonist effects of pure opioids • Naloxone has been used to treat opioid overdose, addiction
  • 21. Oral Opioids 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
  • 22. Opioid pharmacology • Conjugated in liver • First pass metabolism • Excreted by kidney (90-95%) • First order kinetics
  • 23. First order kinetics of opioids 6-7 min 15-20 min 45-60 min
  • 24. 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
  • 25. Delivery of opioids 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
  • 26. Scheduling oral short-acting opioids • Scheduled dosing based on t1/2 • Q4 hours • PRN dosing based on time to Cmax • Can be as frequent as Q1 hour PRN • Adjust scheduled dose daily based on prn use
  • 27. Scheduling long-acting opioids (except methadone) • Reason for use: • Improve compliance, adherence • Dose q8, q12, q24 hours (depending on product) • Don’t crush or chew • May use time-release granules (Kadian) • Adjust dose every 2-4 days (once steady state is reached.)
  • 28. Side effects of opioids Common Uncommon Bad dreams/hallucinations Constipation* Delirium Dry mouth Myoclonus Nausea/Vomiting Seizures Sedation Pruritus, urticaria Sweats Respiratory suppression Urinary retention *No development of tolerance
  • 29. Opioid side effects: Constipation • Stimulant laxative: • Senna, bisacodyl, glycerine, etc. • Stool softener • Docusate • Prokinetic agent • Metoclopramide • Osmotic laxative (from above or below) • Specific to peripheral opioid receptors • methylnatrexone
  • 30. Opioid side effects: Nausea/Vomiting • Onset with start of opioids, tolerance may develop • Mechanism: dopamine receptors and decreased motility • Prevent or treat with dopamine-blocking anti-emetics (avoid with long-QT): • Haloperidol 0.5-1mg every 6 hours • Droperidol 0.625 mg (PACU order set) • Metoclopramide 10mg every 6 hours • Alternative opioid if refractory
  • 31. Opioid side-effects: Sedation • Onset with start of opioids • Distinguish from exhaustion due to pain* • Tolerance develops within days • Complex assessment in advanced disease • If persistent, may consider alternative opioid or route of administration • Psychostimulants may play a role as well • Methylphenidate 5mg qAM and 1 noon
  • 32. Opioid side-effects: Neuroexcitability • Presentation • Cognitive changes: CAM assessment Reason to avoid “titrate to comfort” order at end- • acute onset or fluctuating course, of-life • inattention, • disorganized thinking/altered level of consciousness • Restlessness, agitation • Can cause hyperalgesia • Myoclonic jerks, seizures (may be repressed if on benzodiazepines) • More common in renal failure • Mechanism: • Morphine/hydromorphone 6-glucoronide build-up • Management: • Benzodiazepines, fluids, and perhaps dialysis - antipsychotics exacerbate symptoms
  • 33. Opioid side-effects: respiratory depression • Opioid effects differ among patients • Change in LOC occurs before respiratory suppression • Pharmacologic tolerance develops rapidly • Most studies of respiratory depression in opioids looked at patients with drug overdose • Management: • Identify and treat contributing causes • Reduce opioid dose and observe • If unstable vital signs: • Naloxone 0.1-0.2 mg IV q 1-2 min
  • 34. Summary • Treat pain as though it were your own: ✴remember under/untreated acute pain can lead to severe chronic pain • Schedule routine opioids based on half-life • Consider offering prns based on Cmax: ✴IV=6-12 min; ✴SQ=20-30min; ✴PO=45-1hour • When ordering opioids, always order bowel regimen to avoid constipation • Watch for neurotoxicity in renal insufficiency - especially at end-of-life

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