A Practical Approach toCancer Pain Management

The Problem:

• One out of three people in the U.S. will develop cancer

• One out to two people who develop cancer, will die of their disease

• Three out of four patients who die of cancer, will have significant pain during their illness

Impact of Uncontrolled Pain:

• Physical:– symptom complex (fatigue, depression, NC)– decreased function (work, AIDLs, ADLs)

• Emotional– total mood disorder– spiritual distress

• Social– family interactions– alters support structures

Pain Assessment:

• Intensity• Etiology• Type

Measurement:• Scales:

– Numeric rating scales– Visual analogue – Descriptive

• Outcome Measure: – Pain intensity– Distress– Relief– Interference– Breakthrough dosing

• Tools:– Brief Pain Index– Memorial Pain Assessment Card

Clinically Important Questions:

• Current pain level• Average pain level• Worst pain level• Pain relief with medications

Etiology:

• Treatable Causes:– pathologic fracture– bone met– chest wall recurrence

• Emergent:– cord compression– brain met

Nociceptive Pain

• Mechanism: Pain receptor activation• Subtypes:

– Somatic• most common type in cancer patients• bone mets most common cause• characterized by aching, throbbing, gnawing

– Visceral• deep, squeezing, crampy

Neuropathic Pain:

• Mechanism: Damage to receptor or nerve• Frequently unrecognized• Types of Syndromes:

– Peripheral• Drug induced (Cisplatin, Taxol)

– Central• Cord compression

Neuropathic Pain Syndromes:

• Post-amputation Limb Pain• Post-thoracotomy Pain• Post-mastectomy Pain• Brachial Plexopathy• LS Plexopathy• Celiac Infiltration

Assessment of the Patient:

• Medical Problems• Psychological Function• Physical Function• Cognitive Function• Support Services• Financial Services• Educational Status

Ready to Prescribe:

Rx

Skill Sets Required for Adequate Pain Control:

• Develop a framework for writing prescriptions

• Write a fixed dose regimen• Calculate an appropriate breakthrough dose• Convert from one opioid to another• Dose titrate• Understand the issues of substance abuse

WHO Step Ladder of Pain Management:

• Step 1– NSAID – Acetaminophen– Non-pharmacological techniques

• Step 2– Mixed opioid + non-opioid– Low dose pure opioid (oxycodone)– Alternative pharmacological agents (i.e. Ultram)

• Step 3 – Pure opioids– Adjunctive medications– Invasive procedures

Step 3: Basic Rules for Opioid Administration

• Goal: Controlled Pain (4 or fewer rescues)• Dose Escalation: Quickly until controlled pain • Maximum Dose: Does not exist• Side Effects:

– Accommodation in 7-10 days– Treat aggressively– Bowel Regimen

Basic Rules for Opioid Administration:

• Use oral or transdermal formulations if possible• Start with immediate release formulations in

patients with significant pain• Use medications around-the-clock for constant

pain (fixed dosing)• Fixed dose interval should be based on T1/2 of the

agent• Rescue dose interval should be based on time to

peak effect

Meperidine:

• By product - normeperidine• T1/2 of normeperidine is longer than

meperidine• Normeperidine has a neuroexcitatory effect• Toxicity is seen when administered over a

prolonged period or in patients with renal insufficiency

Fixed Dose Administration:

• Goal: to maintain opioid levels within the therapeutic window

• Fixed dosing allows a steady state to be achieved

• Once steady state is achieved, dose modifications can be made in a calculated way

Dosing on a Fixed Interval:

PRN Dosing:

• Patients take pain medication as needed, thus they are in pain when they take a dose.

• Patients are in pain more frequently• They are more likely to have side effects

Dosing on A PRN Basis:

Fixed Dosing:Medication Half Life

• Immediate Release:– Morphine: 3-4 hours– Dilaudid: 2-4 hours– Oxycodone: 3-4 hours– Hydrocodone: 3-4 hours

• Sustained release:– Morphine

• MS Contin: 8 to 12 hours• Avenza, Cadian: 24 hours

– Oxycodone• Oxycontin: 8 to 12 hours

– Fentanyl• Duragesic Patch 18 hours

Write a Fixed Dose Prescription for the Following:

• Morphine Sulfate IR 30 mg tabs• MS Contin 30 mg tabs• Dilaudid 4 mg IR tabs• Duragesic 25 ug patch• Oxycontin 20 mg tabs

Write a Fixed Dose Prescription for the Following:

• Morphine Sulfate IR 30 mg po q 4 hours ATC

• MS Contin 30 mg po q 12 hours• Dilaudid IR 4 mg po q 3-4 hours ATC• Duragesic 25 ug patch to skin q 72 hours• Oxycontin 20 mg po q 12 hours

Breakthrough Dosing:

• Breakthrough medications should be fast acting

• Dose interval based on Time to Peak Effect• Dose should be 10-15% of the 24 hour

opioid fixed dose total

Example Breakthrough Dosing:

• MS IR 60 mg po q 4 hours– 24 hour fixed total = 360 mg– MS IR 30 mg po q 1-2 hours

• Dilaudid 16 ug po q 4 hours– 24 hour fixed total = 64 ug– Dilaudid 6 ug po q 1-2 hours

• Duragesic 100 ug patch q 72– 24 hour morphine equivalent 200-300– MS IR 20-30 mg po q 1-2 hours

Acute Management:Moderate to Severe Pain

• Previously on Mixed Agents:– Start with MSIR 30 mg po q 4 hours– With MS IR 15 mg po q 1-2 hours prn

• Opioid Naive or Frail/Elderly– Start with MSIR 15 mg po q 4 hours– With 1/2 of a 15 mg tab po q 1-2 hours prn

Equi-analgesics:• Need to be able to convert from one agent

to another• Most tables compare to a specified dose of

morphine• Equi-analgesics charts are rough estimates• Considerable inter-patient variability exists• General rule: when converting form one

agent to another, find the equi-analgesic dose and decrease by 25% due to non-cross resistance

Key Equi-analgesics Ratios

• Morphine to Dilaudid: 5 to 1• Morphine to Hydrocodone: 1 to 1• Morphine to Oxycodone: 1 to 1• Morphine to Duragesic: 2-3 to 1

Method:• Step 1:

– Calculate the 24 hour fixed dose total• Step 2:

– If necessary, convert to morphine equivalents• Step 3:

– Using the appropriate ratio, calculate the 24 hour fixed dose equivalents of the new agent

• Step 4: – Divide the 24 hour fixed dose total by the number of

doses per day

Conversion Examples:

• Convert MS IR 30 mg po q 4 hours to Dilaudid

• Convert MS IR 30 mg po q 4 hours to Duragesic

• Convert Dilaudid 8 mg po q 3 hours to Duragesic

Conversion Example 1:

• Step 1: (calculate the 24 hour fixed dose total) – Morphine 30 mg po q 4 hours = 30 x 6 =180 mg

• Step 2: (convert to morphine equivalents) – Not needed

• Step 3: (apply appropriate ratio)– 180 x 1/5 = 36 mg of Dilaudid

• Step 4: (divide by number of doses per day)– 36 / 6 = 6 mg every 4 hours

Conversion Example 2:

• Step 1: (calculate the 24 hour fixed dose total) – Morphine 30 mg po q 4 hours = 30 x 6 =180 mg

• Step 2: (convert to morphine equivalents) – Not needed

• Step 3: (apply appropriate ratio)– 180 / 2-3 = 60-90 ug of Duragesic

• Step 4: (divide by number of doses per day)– Not needed

Conversion Example 3:

• Step 1: (calculate the 24 hour fixed dose total) – Dilaudid 8 mg po q 4 hours = 8 x 6 = 48 mg

• Step 2: (convert to morphine equivalents) – 48 x 5 = 240 mg

• Step 3: (apply appropriate ratio)– 240 / 2-3 = 80 - 120 mg of Duragisic

• Step 4: (divide by number of doses per day)– Not needed

Titration Schema:

Initial Fixed and Rescue Dose

Controlled Pain Moderate Pain

Severe Pain

No Change 25% Increase 50% Increase

Example 1:• 65 yo with bone pain due to metastatic prostate cancer • Current regimen:

– MSIR 30 mg po q 4h ATC– MSIR 15 mg po q 1-2h prn

• Reports pain 1/10 with 10 rescue doses/24h• Calculations:

– 24h narcotic total = (30mg x 6)+(15mg x 10) = 330mg– New Fixed dose = 330 / 6 = approx 60 mg

• New Regimen:– MSIR 60 mg po q 4h ATC– MSIR 30 mg po q 1-2h prn

Example 2:• 65 yo with bone pain due to metastatic prostate cancer • Current regimen:

– MSIR 60 mg po q 4h ATC– MSIR 30 mg po q 1-2h prn

• Reports pain 5/10 with 8 rescue doses/24h• Calculations:

– 24h narcotic total = (60mg x 6)+(30mg x 8) = 600mg– New 24h narcotic total = 600 + 150 = 750 mg– New Fixed dose = 750 / 6 = 120 mg

• New Regimen:– MSIR 120 mg po q 4h ATC– MSIR 75 mg po q 1-2h prn

Example 4:• 65 yo with bone pain due to metastatic prostate cancer • Current regimen:

– MSIR 60 mg po q 4h ATC– MSIR 30 mg po q 1-2h prn

• Reports pain 9/10 with 8 rescue doses/24h• Calculations:

– 24h narcotic total = (60mg x 6)+(30mg x 8) = 600mg– New 24h narcotic total = 600 + 300 = 900 mg– New Fixed dose = 900 / 6 = 150 mg

• New Regimen:– MSIR 150 mg po q 4h ATC– MSIR 90 mg po q 1-2h prn

Long Acting Formulations:

• Should be used in controlled pain only• Determine the amount of narcotic needed to

control pain with short opioids then convert to long acting formulations

• If pain becomes uncontrolled, switch to short acting agents, titrate rapidly, then convert back to long acting agent

Sustained Release Formulations:

• Morphine• Oxycodone• Fentanyl• Dilaudid

Example 5:• 65 yo with bone pain due to metastatic prostate cancer • Current regimen:

– MSIR 60 mg po q 4h ATC– MSIR 30 mg po q 1-2h prn

• Reports pain 1/10 with 1-2 rescue doses/24h• Calculations for MSSR with half-life of 8-12 hrs:

– 24h narcotic total = (60mg x 6) =360– New Fixed dose = 360 / 2 = 180 mg

• New Regimen:– MSSR 180 mg po q 12h ATC– MSIR 30 mg po q 1-2h prn

Transdermal Fentanyl

• Patch Size: 25, 50, 75 and 100 micrograms• Duration of Action: 72 hours• Advantages:

• Easy, convenient use• No need to remember to take meds

• Disadvantages:• Difficult when using high dose of narcotics• Thin patients with little subcutaneous tissue

Consider Patch in the Following Patient Populations:

• Non-compliant patients• Patients unable to take oral medications• Question of drug abuse• Question of cognition

Conversion Factor:

100 mg Morphine

50 micrograms Fentanyl

Example 6:• 65 yo with bone pain due to metastatic prostate cancer • Current regimen:

– MSIR 60 mg po q 4h ATC– MSIR 30 mg po q 1-2h prn

• Reports pain 1/10 with 1-2 rescue doses/24h• Calculations for Fentanyl (Duragesic®) Patch:

– 24h narcotic total = (60mg x 6) =360– New Fixed dose = 360 / 2 = 150 g

• New Regimen:– Duragesic 150 g to skin q 72h ATC– MSIR 30 mg po q 1-2h prn

IV/SC Narcotics

• Use:– Pain Emergency– Unable to take po– High narcotic needs– Toxicity from po

• Relative Strength: – IV 3 times more potent

than po • Role of PCA

• Schedule:– Continuous Infusion

with bolus for rescue• Rescue:

– Rapid Peak– Fast Clearance– q 10 minutes– Hourly dose equal

hourly rescue

IV Example 1:• Pt admitted for elective surgery• Controlled pain on:

– MSIR 60 mg po q 4h ATC– MSIR 30 mg po q 1-2h prn

• 24 hour narcotic total = 360 mg• IV equivalent = 360 / 3 = 120mg/24h• Hourly rate = 120 / 24 = 5 mg h• Order:

– MS 5 mg/hr CIV– MS 1 mg q 10 minute IVB prn

Pain Emergency:

• Step 1: Narcotic Load – Narcotic Load using IV boluses until pain level

reduced by 50-75%• Step 2: Calculate Maintenance Dose

– MD = Load/2 x half-life• Step 3: New Order

– MD in mg/hr– rescue - bolus q 10 minutes

Pain Emergency

• High Dose Decadron• Anesthesiology Consult• Neurosurgery Consult

Barrier Reduction:• Patient education:

– Endpoint to be assessed: • Beliefs• Communication skills • Knowledge pain control

– Outcome of interventions: • Improve beliefs and adherence • Results variable for improved pain control

• Physician and staff education:– Endpoints to be assessed:

• Knowledge • Attitudes• Practice patterns• Pain control

Ongoing Education: Testing Two Intervention Strategies

• Patient population:– Patients with cancer related pain requiring

narcotics• Design:

– Group 1: baseline education only– Group 2: “hot line” for questions or emergencies– Group 3: Provider initiated weekly follow-up

• Results:– Improvement in beliefs with baseline education– No improvement in outcome with ongoing

interventions

Narcotic Titration Order Schema:A Pilot Trial

• Endpoint:– severe adverse events

• Patient Selection:– pain with a level of 3 or greater– requiring narcotics

• Methods:– nurse managed order schema with “physician contact”

parameters– tools:

• Patients: MMSE, pain dairy, BPI, CES-D, STAI• Family: F-COPES, FIRM, CSI

Narcotic Titration Order Schema:A Pilot Trial

• Results:– No severe adverse events– Feasible in the clinic setting

• Future Directions:– Phase III Trial through VICCAN

• Issues for further exploration:– Non-compliance– Effect if pain on family functioning

Randomized Phase III Trial of Standard Care Vs Opioid Titration Order Schema

AssessmentTitration

Communication

Report

Comply

Requirements:1. Time2. Knowledge

Requirements:1. Beliefs2. Knowledge3. Resources

Cancer Pain Management:Requirements for Success

• Setting the Right Priorities• Dedicated Team• Willing to Take Time• Systematic Approach• Understanding of the Basic Principles

of Symptom Control

Instructors can impart only a fraction of the teaching. It is through your own devoted

practice that the mysteries are brought to life.

Morihei Ueshiba