A Practical Approach to Cancer 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: Outcome Measure: Tools: 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: Emergent: 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: 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: Step 2: Step 3: Step 4: 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)

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

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

IV/SC Narcotics Use: Relative Strength: Role of PCA Schedule: Rescue: 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 Report Assessment Comply Titration Communication Requirements: Beliefs Knowledge Resources Requirements: Time Knowledge

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 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