1. Pain Management 101: Basic Skills for Opioid Prescribing
Anthony J. Caprio, MD
Assistant Professor of Medicine
Division of Geriatric Medicine
Center for Aging and Health
Palliative Care Consultation Service
University of North Carolina at Chapel

2. Objectives Examine the concept and assessment of pain
Illustrate the differences between physical dependence, tolerance, addiction, and pseudo- addiction.
Practice prescribing opioids for chronic and acute pain, titrate for adequate pain relief, and incorporate special dosing considerations
Convert between different opioids and between different routes of administration
Anticipate and treat side effects of opioids

3. “Illness is the doctor to whom we pay most heed; to kindness, to knowledge, we make promise only; pain we obey.”
-Marcel Proust

4. Case: “Please Help Me!” Mrs. D. has breast cancer with bone metastases
Received radiation to femur and ribs
Pain previously controlled using
Morphine Extended Release 30mg po q12h
Morphine Immediate Release 5mg q4h prn pain
Now has “excruciating” back and leg pain
“Please help me! I just want to die!”
What do you do?

5. Pain Assessment and Management
Types of Pain
Nociceptive Pain
Somatic: Caused by activation of pain receptors (nociceptors) in the cutaneous or deep tissues (musculoskeletal)
Visceral Pain: Poorly localized pain sensation from internal organs and structures (chest, abdomen, pelvis)
Neuropathic Pain:
Results from injury to nervous system (burning or tingling)
T. Caprio University of Rochester 2009

6. Pain and Suffering
Suffering is more than the physical experience of pain
Physical, Emotional, Social, Existential contributions to the experience of suffering
Duty of physicians to alleviate suffering
Suffering can never be completely relieved by opioids

7. Tolerance Reduced effectiveness over time
Tolerance to side effects is favorable
Tolerance to analgesia is rarely significant
When increasing doses required, suspect worsening disease rather than tolerance

8. Physical Dependence
Withdrawal Symptoms produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug and/or administration of an antagonist
Inevitable physiologic change from use of opioids
NOT evidence of addiction

9. Addiction Psychological dependence
Genetic, psychosocial, and environmental factors
Characterized by one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.
Non-adherence to a therapeutic regimen
Differentiate from under-treatment of pain, criminal drug diversion, and family dysfunction

10. Pseudo-addiction
Mimics addictive behavior, but is due to the under treatment of pain
hoarding medication
seeking prescriptions from multiple providers
repeatedly requesting more medication
Behavior disappears with proper treatment

11. Assessing Severity of Pain
Numerical Rating
Do you have pain?
How bad is your pain?
1 (mild) – 10 (severe)
Another way to think about pain severity:
Mild (1-3)
Moderate (4-7)
Severe (8-10)

12. Pain is Personal Pain ratings are relative to an individual
One person’s “4/10” may be acceptable (allowing them to function reasonably well), while another person’s “4/10” may be debilitating.
You need to understand and negotiate the level of pain control which will allow the patient to tolerate the pain and function reasonably well.

13. WHO 3-Step Analgesic Ladder
WHO: World Health Organization (see

14. Starting Opioids Pick one drug and stick with it
Avoid using multiple opioids simultaneously
You won’t know which one is working or which one is causing adverse effects
Very confusing (and expensive) for patients
If effective, titrate drug for optimal effect
If not effective (after appropriate dose escalation) or if limited by side-effects, switch to a different opioid
Acute pain and chronic pain will have different dosing considerations

15. Opioid-Induced Constipation
Never become tolerant and not necessarily dose- dependent
ALL opioid prescriptions should be linked to a bowel regimen (make it routine)
Stimulant laxative is often needed
Stool softener may be helpful, but avoid “All Mush and No Push”
Schedule senekot (Senna) and titrate as needed
Give a specific plan: “If no BM in x days then take y; if still no BM, then take z”
Methylnaltrexone is a peripherally-acting mu-opioid receptor antagonist
Methylnaltrexone is SubQ, expensive; needs palliative care approval for use at UNC

16. Acute Pain Crisis
“An event in which the patient reports pain that is severe, uncontrolled, and causing distress for the patient, family members, or both.”
Requires a “rapid response”
Reassess quickly and repeatedly
frequency is determined by time to peak concentration of the opioid
JAMA. 2008;299(12):

17. Many Opioids Demonstrate First Order Kinetics
Peak Plasma Concentrations (Cmax)
Oral: 60 to 90 min
SC or IM: 30 min
IV: 6 minutes
Half-Life (t1/2)
Often depends on renal function
Generally 3-4 hrs
Many have active metabolites
When dosed repeatedly, their plasma concentrations approach a steady state after 4 to 5 half-lives.
Source: Emanuel LL, von Gunten CF, Ferris FD. EPEC curriculum, 1999.

18. Managing an Acute Pain Crisis
Administer double the rescue (breakthrough) dose intravenously.
Repeat same dose in 15 minutes if there is no or minimal pain relief.
If pain persists at 7 or higher on a 10-point scale without adverse effects, increase the intravenous rescue dose by 50%.
Continue to administer this dose every 15 minutes until patient experiences more than 50% pain relief or adverse effects develop.
Because the analgesic effect is a logarithmic function of the dose of the opioid, a doubling of the dose in an opioid-tolerant patient may be needed.
JAMA 2008;299:

19. Titrating Opioids for Pain Relief
For ongoing moderate to severe pain increase opioids doses by %
For ongoing mild to moderate pain increase by %
When dose escalating long-acting opioids or opioid (continuous) infusions, do not increase the long- acting drug or infusion basal rate more than 100% at any one time
Use short-acting medications for breakthrough pain, keep track of these extra doses and use this information to adjust doses
Lasix analogy
Source: Fast Fact #020

20. Breakthrough Medications
Generally 10% of the total daily dose
Divided into intervals based on the route of administration and onset to peak analgesia
(ie. q4hours for oral medications)
More frequent intervals may be necessary
Generally, if a patient is requiring more than 3-4 breakthrough doses per day, you should consider increasing the long-acting dose

21. Other Dosing Considerations
Theoretically no ceiling dose for opioids
Elderly
Lower doses of any drug may be necessary
Caution with NSAIDs (bleeding and renal effects)
Tylenol 3g/day maximum
Caution with neuropathic pain medications (start low and go slow; avoid tricyclic antidepressants)
Renal failure
Consider 25-50% dose reductions for opioids
Fentanyl and methadone are safest
Hydromorphone (Dilaudid) is a reasonable choice
Oxycodone should be used with caution (can accumulate)
Do Not Use meperidine (Demerol)

22. Changing Route of Administration
Parenteral (IV/IM) is more potent than oral (po)
Intravenous and subcutaneous dosing are usually similar
Oral : Parenteral
Morphine : 1
Hydromorphone : 1 (wide range)

23. Case: Mrs. D. Calculate 24-hour oral morphine use:
Morphine 30mg po q12h = 60mg/24h
Morphine 5mg every 4h (prn)  30mg/24h
Total: 90mg oral morphine equivalents/24h
Convert to IV morphine
90mg oral morphine = 30mg iv morphine
Calculate Breakthrough Dose
10% of 30mg = 3mg iv (give q10-15min prn)

24. Case: Mrs. D’s Pain Crisis
Pain is 10/10
Double dose of the prn
Give at least 6mg iv x 1 now
Re-evaluate in 15 minutes
Pain still rated 10/10
Give another 6mg iv x 1
Pain rated 8/10
Consider giving 9mg iv (50% increase)
Re-evaluate pain in 15 minutes
Pain rated 5/10
50% reduction of her pain with 21mg iv morphine over 45 minutes

25. Indications for Changing Opioids
Intolerable adverse effects
Poor analgesic efficacy despite dose titration
Drug-drug interactions
Preference or need for a different route of administration
Change in clinical status or clinical setting that necessitates an opioid with different properties
Financial or drug-availability considerations
J Pain Symptom Manage 2009;38:

26. Common Adverse Effects
Pain Assessment and Management
Common Adverse Effects
Constipation
Nausea
Common adverse effect, not an allergy
Try antiemtics, trying other opioid or adjusting dose
Likely will become tolerant to these effects
Consider other causes of nausea like chemo and constipation
Sedation
Tolerance usually develops in hours
Appears well before respiratory depression
Decrease dose or increase interval
Caution when starting neuropathic pain medications
(additive effects)
Consider other sources of fatigue and sedation
(disease progression, process of dying)
Nausea: mechanism: stimulates chemoreceptor trigger zone (4th ventricle), stimulate vestibular apparatus, constipation stimulates afferent cholinergic pathways
T. Caprio University of Rochester 2009

27. Other Adverse Effects Urinary retention Delirium Myoclonus
Consider rotating opioid, try lower doses
Avoid anticholinergics and sedatives
Myoclonus
observed with renal insufficiency, hepatic insufficiency, and high opioid doses
Switch opioids, correct electrolytes if possible
Benzodiazepines may be helpful

28. Equianalgesic Dosing No “one-size fits all” approach
Genetic differences may account for variance
Pain is complex and often has many components
Starting doses and equianalgesic conversions are educated guesses (at best)
Assume that you will need to adjust up or down based on clinical judgment
Codeine example: about 10% of the Caucasian population lacks sufficient levels of a key CYP450 enzyme to convert codeine to morphine and therefore derive no significant analgesia from codeine

29. Equianalgesic Table Not based on much evidence
Large variability observed
Table does not replace clinical judgment
You need to think and reassess, not just plug-in numbers and write orders!
J Pain Symptom Manage 2009;38:

30. UNC HealthCare “Pain Card”

31. Equianalgesic Dosing: More Than Just Reading the Table
Step 1:
Calculate equianalgesic dose from table
Apply “safety factor”: % automatic reduction to account for incomplete cross-tolerance and individual variation
Exceptions: methadone (reduce more), transdermal fentanyl patch (safety factor built-in to conversion tables) and transmucosal fentanyl (use lowest dose)
Step 2:
Consider severity of the pain and other medical or psychosocial factors that potentially alter potency or shift the likelihood that the initial dose of the new drug will be analgesic, relatively free of adverse effects, and unlikely to precipitate withdrawal
Determine whether to apply an additional increase or decrease of 15% - 30%
J Pain Symptom Manage 2009;38:

32. Case: Mrs. D.
Eventually titrated to morphine PCA 6mg/h iv over then next 2 days with better pain control but increased itching and “jerking” noted
Convert to oral oxycodone
Morphine iv 6mg/h x 24h = 144mg
Oral morphine equivalents = 432mg
Oxycodone (oral) : Morphine (oral) = 1 : 1.5
Set-up ratio and then X= 432/1.5 = 288mg
Oxycodone equianlagesic dose = 288mg

33. Case: Dosing Considerations
Reduce dose by 50% for incomplete cross-tolerance
Increase dose by 20% based on your clinical judgment
Normal renal and hepatic function
Severe pain coming into hospital, still not optimally controlled
No problems with sedation
Good social support and will be monitored at home
Net effect is dose reduction by 30%
30% of Oxycodone 288mg ≈ 200mg
Prescribe
Oxycodone Sustained Release 100mg po q12h
Oxycodone Immediate Release 20mg po q4h prn breakthrough pain
(10% of 200mg = 20mg)
Reduce by 25-50% for incomplete cross-tolerance
Increaser or reduce by 15-30% based on clinical judgment

34. Patient-Controlled Analgesia (PCA)
Advantages:
Quick administration
Patient “in-control”
Record of demands to help with dose titration
Disadvantages:
can’t be used by delirious patients or those with an altered LOC
reduces an important element of nursing pain assessment
patient may avoid demands
Dosing considerations
basal vs. demand
basal + demand
Need to review PCA logs and interpret the MAR

35. Patient-Controlled Analgesia (PCA) Orders
Continuous infusion Rate: mg/hr or mcg/hr
-Depends on whether patient is opioid naïve, nature of the pain, and any previous information about opioid needs
Demand Dose: mg or mcg
(‘patient initiated dose,’ ‘patient demand dose,’ or ‘bolus dose’)
-Based on patterns of breakthrough pain, consider a bolus dose of 50% % of the hourly rate
Dosing Interval (Delay Interval): minutes
-Peak analgesic effect from an IV bolus dose is 5-10 minutes
-Should be in the range of minutes
Hour Limit: mg or mcg
-Maximum amount of drug to be dispensed in a defined period of time
-Often set to deliver 3-5 times the estimated required hourly dose

36. Methadone
NMDA receptor antagonist and mu-opioid receptor agonist properties
Decreasing opioid tolerance
Attenuating neuropathic pain
No active metabolites, not removed by dialysis
Inexpensive and Long-acting
Disadvantages
Non-linear conversion
Risk for overdose (by both prescribers and patients)
Many drug interactions
QTc prolongation
ASK for help with dosing!!

37. Pitfalls Under-treated pain Long-acting vs. short-acting opioids
Avoiding opioids or not increasing the dose of an opioid
Too long of an interval between breakthrough doses
Long-acting vs. short-acting opioids
Starting long-acting opioids in a opioid-naïve patient
Using long-acting medications for breakthrough pain
Precipitating opioid-withdrawal by abruptly stopping (or dose- reducing) opioids
Treating patients with opioids but missing other sources of suffering
Methadone dosing without understanding pharmacokinetics
Potentially exceeding 4g of acetaminophen/day (3g/day in elderly)

38. Mrs. D.
PCA morphine is reduced and then discontinued after po oxycodone sustained release is started
Myoclonus and itching resolve
Pain is generally 2-3/10 with exacerbations up to 6/10, treated with immediate release oxycodone
Also started on dexamethasone and evaluated for additional radiation therapy
Discharged home with outpatient follow-up
Taking about 2-3 immediate release oxycodone daily and able to care for herself and family

39. Summary
All patients on chronic opioid therapy will develop physical dependence
Tolerance develops
Withdrawal symptoms if opioid is stopped
Few patients will become addicted to opioids with appropriate prescribing and assessments
Pseudo-addictive behavior related to the under-treatment of pain

40. Summary (cont’d)
Pain crisis may require repeated q15min iv opioid dosing until pain <7/10 or 50% reduction in pain scores
Titrate opioids based on severity of pain
Breakthrough about 10% of total daily dose given as short-acting opioid PRN; for oral opioids generally no longer than q4h dosing intervals
If >3-4 breakthrough doses per day, need to titrate long-acting opioids

41. Summary (cont’d) Try to use only one drug at a time
Parenteral is more potent than oral
Use equianalgesic tables with caution
Automatic dose reduction by 25-50%
Increase or decrease by 15-30% based on clinical judgment
Dose-reduce for advanced age and renal impairment
Ask for help with methadone dosing
Bowel regimen with every opioid prescription!!

42. Closing Thoughts
Patients are different; pain relief and side effects will vary with the same dose of the same medication
Incomplete or inconsistent literature regarding dosing, conversions, and equianalgesic tables
Clinical judgment is key; no card, lecture, or consultant can replace good judgment
Good judgment comes from thoughtfulness, careful observation/assessments, and lots of practice
Suffering is more than the physical experience of pain; suffering can never be completely relieved by opioids