education in palliative and end-of-life care - oncology

The EPEC-O Curriculum is produced by the EPECTM Project with major funding provided by NCI, with supplemental funding provided by the Lance Armstrong Foundation.

Education in Palliative and End-of-life Care - Oncology

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Module 2Module 2

Cancer Pain Cancer Pain ManagementManagement

Module 2Module 2Cancer Pain Cancer Pain ManagementManagement

EPEC - Oncology Education in Palliative and End-of-life Care - Oncology

EPEC - Oncology Education in Palliative and End-of-life Care - Oncology

Overall messageOverall message

Pain management is an Pain management is an essential component of essential component of

comprehensive cancer care.comprehensive cancer care.


comprehensive cancer care.comprehensive cancer care.

Objectives . . .Objectives . . .

Compare, contrast nociceptive, Compare, contrast nociceptive, neuropathic painneuropathic pain

Know steps of analgesic Know steps of analgesic managementmanagement

Demonstrate ability to convert Demonstrate ability to convert between opioids while maintaining between opioids while maintaining analgesiaanalgesia

Compare, contrast nociceptive, Compare, contrast nociceptive, neuropathic painneuropathic pain

Know steps of analgesic Know steps of analgesic managementmanagement

Demonstrate ability to convert Demonstrate ability to convert between opioids while maintaining between opioids while maintaining analgesiaanalgesia

. . . Objectives. . . Objectives

Know use of adjuvant analgesic Know use of adjuvant analgesic agentsagents

Know adverse effects of analgesics, Know adverse effects of analgesics, their managementtheir management

List barriers to pain managementList barriers to pain management

Know use of adjuvant analgesic Know use of adjuvant analgesic agentsagents

Know adverse effects of analgesics, Know adverse effects of analgesics, their managementtheir management

List barriers to pain managementList barriers to pain management

VideoVideo

General principles . . .General principles . . .

AssessmentAssessment

ManagementManagement

PharmacologicalPharmacological

Non-pharmacologicalNon-pharmacological

AssessmentAssessment


PharmacologicalPharmacological

Non-pharmacologicalNon-pharmacological

. . . General principles. . . General principles

Education – patient, family, all Education – patient, family, all caregiverscaregivers

Ongoing assessment of outcomes, Ongoing assessment of outcomes, regular review of plan of careregular review of plan of care

Interdisciplinary care, consultative Interdisciplinary care, consultative expertiseexpertise

Education – patient, family, all Education – patient, family, all caregiverscaregivers

Ongoing assessment of outcomes, Ongoing assessment of outcomes, regular review of plan of careregular review of plan of care

Interdisciplinary care, consultative Interdisciplinary care, consultative expertiseexpertise

Pain pathophysiologyPain pathophysiology Acute painAcute pain

Identified event, resolves days–weeksIdentified event, resolves days–weeks

Usually nociceptiveUsually nociceptive

Chronic painChronic pain

Cause often not easily identified, Cause often not easily identified, multifactorialmultifactorial

Indeterminate durationIndeterminate duration

Nociceptive and / or neuropathicNociceptive and / or neuropathic

Acute painAcute pain

Identified event, resolves days–weeksIdentified event, resolves days–weeks

Usually nociceptiveUsually nociceptive

Chronic painChronic pain

Cause often not easily identified, Cause often not easily identified, multifactorialmultifactorial

Indeterminate durationIndeterminate duration

Nociceptive and / or neuropathicNociceptive and / or neuropathic

Wolf CJ. Ann Intern Med. 2004.

Nociceptive pain . . .Nociceptive pain . . . Direct stimulation of intact Direct stimulation of intact

nociceptorsnociceptors

Transmission along normal nervesTransmission along normal nerves

SomaticSomatic

Easy to describe, localizeEasy to describe, localize

VisceralVisceral

Difficult to describe, localizeDifficult to describe, localize

Direct stimulation of intact Direct stimulation of intact nociceptorsnociceptors

Transmission along normal nervesTransmission along normal nerves

SomaticSomatic

Easy to describe, localizeEasy to describe, localize

VisceralVisceral

Difficult to describe, localizeDifficult to describe, localize


. . . Nociceptive pain. . . Nociceptive pain

Tissue injury apparentTissue injury apparent


OpioidsOpioids

Adjuvant / coanalgesicsAdjuvant / coanalgesics

Tissue injury apparentTissue injury apparent


OpioidsOpioids

Adjuvant / coanalgesicsAdjuvant / coanalgesics

Neuropathic pain . . .Neuropathic pain . . . Disordered peripheral or central Disordered peripheral or central

nervesnerves

Compression, transection, Compression, transection, infiltration, ischemia, metabolic infiltration, ischemia, metabolic injuryinjury

Varied typesVaried types

Peripheral, deafferentation, complex Peripheral, deafferentation, complex regional syndromesregional syndromes

Disordered peripheral or central Disordered peripheral or central nervesnerves

Compression, transection, Compression, transection, infiltration, ischemia, metabolic infiltration, ischemia, metabolic injuryinjury

Varied typesVaried types

Peripheral, deafferentation, complex Peripheral, deafferentation, complex regional syndromesregional syndromes


. . . Neuropathic pain. . . Neuropathic pain

Pain may exceed observable injury Pain may exceed observable injury

Described as burning, tingling, Described as burning, tingling, shooting, stabbing, electrical shooting, stabbing, electrical


OpioidsOpioids

Adjuvant / coanalgesics often requiredAdjuvant / coanalgesics often required

Pain may exceed observable injury Pain may exceed observable injury

Described as burning, tingling, Described as burning, tingling, shooting, stabbing, electrical shooting, stabbing, electrical


OpioidsOpioids

Adjuvant / coanalgesics often requiredAdjuvant / coanalgesics often required

Pain managementPain management

Don’t delay for investigations or Don’t delay for investigations or disease treatmentdisease treatment

Unmanaged pain => nervous system Unmanaged pain => nervous system changeschanges

Permanent damagePermanent damage

amplify painamplify pain

Treat underlying cause (eg, radiation Treat underlying cause (eg, radiation for a neoplasm)for a neoplasm)

Don’t delay for investigations or Don’t delay for investigations or disease treatmentdisease treatment

Unmanaged pain => nervous system Unmanaged pain => nervous system changeschanges

Permanent damagePermanent damage

amplify painamplify pain

Treat underlying cause (eg, radiation Treat underlying cause (eg, radiation for a neoplasm)for a neoplasm)

PlacebosPlacebos

No role for placebos to assess or No role for placebos to assess or treat paintreat pain

No role for placebos to assess or No role for placebos to assess or treat paintreat pain

WHO 3-stepLadderWHO 3-stepLadder

1 mild1 mild

2 moderate2 moderate

3 severe3 severe

Morphine

Hydromorphone

Methadone

Levorphanol

Fentanyl

Oxycodone

± Adjuvants

Morphine

Hydromorphone

Methadone

Levorphanol

Fentanyl

Oxycodone

± Adjuvants

A/Codeine

A/Hydrocodone

A/Oxycodone

A/Dihydrocodeine

Tramadol

± Adjuvants

A/Codeine

A/Hydrocodone

A/Oxycodone

A/Dihydrocodeine

Tramadol

± Adjuvants

ASA

Acetaminophen

NSAIDs

± Adjuvants

ASA

Acetaminophen

NSAIDs

± Adjuvants WHO Geneva, 1996.

AcetaminophenAcetaminophen Step 1 analgesic, CoanalgesicStep 1 analgesic, Coanalgesic

Site, mechanism of action unknownSite, mechanism of action unknown

Minimally anti-inflammatory effectMinimally anti-inflammatory effect

Hepatic toxicity if > 4 grams / 24 Hepatic toxicity if > 4 grams / 24 hourshours

Increased riskIncreased risk

Hepatic disease, heavy alcohol Hepatic disease, heavy alcohol useuse

Step 1 analgesic, CoanalgesicStep 1 analgesic, Coanalgesic

Site, mechanism of action unknownSite, mechanism of action unknown

Minimally anti-inflammatory effectMinimally anti-inflammatory effect

Hepatic toxicity if > 4 grams / 24 Hepatic toxicity if > 4 grams / 24 hourshours

Increased riskIncreased risk

Hepatic disease, heavy alcohol Hepatic disease, heavy alcohol useuse

Mitchell JR, Potter WZ. Med Clin North Am. 1975.

NSAIDs . . .NSAIDs . . .

Step 1 analgesic, coanalgesicStep 1 analgesic, coanalgesic

Inhibit cyclooxygenase (COX)Inhibit cyclooxygenase (COX)

Vary in COX-2 selectivityVary in COX-2 selectivity

All have analgesic ceiling effectsAll have analgesic ceiling effects

Effective for bone, inflammatory painEffective for bone, inflammatory pain

Individual variation, serial trialsIndividual variation, serial trials

Step 1 analgesic, coanalgesicStep 1 analgesic, coanalgesic

Inhibit cyclooxygenase (COX)Inhibit cyclooxygenase (COX)

Vary in COX-2 selectivityVary in COX-2 selectivity

All have analgesic ceiling effectsAll have analgesic ceiling effects

Effective for bone, inflammatory painEffective for bone, inflammatory pain

Individual variation, serial trialsIndividual variation, serial trials

Carson LJ, Willett LR. Drugs,1993.

. . . NSAIDs. . . NSAIDs Highest incidence of adverse eventsHighest incidence of adverse events

GastropathyGastropathy

Gastric cytoprotectionGastric cytoprotection

COX-2 selective inhibitorsCOX-2 selective inhibitors

Renal insufficiencyRenal insufficiency

Maintain adequate hydrationMaintain adequate hydration


Inhibition of platelet aggregationInhibition of platelet aggregation

Assess for coagulopathyAssess for coagulopathy

Highest incidence of adverse eventsHighest incidence of adverse events

GastropathyGastropathy

Gastric cytoprotectionGastric cytoprotection


Renal insufficiencyRenal insufficiency

Maintain adequate hydrationMaintain adequate hydration


Inhibition of platelet aggregationInhibition of platelet aggregation

Assess for coagulopathyAssess for coagulopathy

Peura DA. Cleve Clin J Med, 2002.

Opioid pharmacology . . .Opioid pharmacology . . .

Conjugated in liverConjugated in liver

Excreted via kidney (90–95%)Excreted via kidney (90–95%)

First-order kineticsFirst-order kinetics

Conjugated in liverConjugated in liver

Excreted via kidney (90–95%)Excreted via kidney (90–95%)

First-order kineticsFirst-order kinetics

Collins SL, et al. J Pain Symptom Manage. 1998.

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0000 Half-life (tHalf-life (t1/21/2))Half-life (tHalf-life (t1/21/2)) TimeTimeTimeTime

IVIVIVIV

PO / prPO / prPO / prPO / pr

SC / IMSC / IMSC / IMSC / IM

CCmaxmaxCCmaxmax

. . . Opioid pharmacology . . .. . . Opioid pharmacology . . .

CCmax max afterafter

PO PO 1 hr 1 hr

SC, IM SC, IM 30 min 30 min

IV IV 6 min 6 min

Half-life at steady-state Half-life at steady-state

PO / PR / SC / IM / IV PO / PR / SC / IM / IV 3-4 hrs 3-4 hrs

CCmax max afterafter

PO PO 1 hr 1 hr

SC, IM SC, IM 30 min 30 min

IV IV 6 min 6 min

Half-life at steady-state Half-life at steady-state

PO / PR / SC / IM / IV PO / PR / SC / IM / IV 3-4 hrs 3-4 hrs

. . . Opioid pharmacology. . . Opioid pharmacology

Steady state after 4–5 half-livesSteady state after 4–5 half-lives

Steady state after one day (24 hours)Steady state after one day (24 hours)

Duration of effect of ‘immediate-Duration of effect of ‘immediate-release’ formulations (except release’ formulations (except methadone)methadone)

3–5 hours PO / PR3–5 hours PO / PR

Shorter with parenteral bolusShorter with parenteral bolus

Steady state after 4–5 half-livesSteady state after 4–5 half-lives

Steady state after one day (24 hours)Steady state after one day (24 hours)

Duration of effect of ‘immediate-Duration of effect of ‘immediate-release’ formulations (except release’ formulations (except methadone)methadone)

3–5 hours PO / PR3–5 hours PO / PR

Shorter with parenteral bolusShorter with parenteral bolus

Routine oral dosingImmediate-release preparationsRoutine oral dosingImmediate-release preparations

Codeine, hydrocodone, morphine, Codeine, hydrocodone, morphine, hydromorphone, oxycodonehydromorphone, oxycodone

Dose q 4 hDose q 4 h

Adjust dose dailyAdjust dose daily

Mild / moderate pain Mild / moderate pain 25–50%25–50%

Severe / uncontrolled pain Severe / uncontrolled pain 50–100%50–100%

Adjust more quickly for severe Adjust more quickly for severe uncontrolled painuncontrolled pain

Codeine, hydrocodone, morphine, Codeine, hydrocodone, morphine, hydromorphone, oxycodonehydromorphone, oxycodone

Dose q 4 hDose q 4 h

Adjust dose dailyAdjust dose daily

Mild / moderate pain Mild / moderate pain 25–50%25–50%

Severe / uncontrolled pain Severe / uncontrolled pain 50–100%50–100%

Adjust more quickly for severe Adjust more quickly for severe uncontrolled painuncontrolled pain

. . . Routine oral dosingExtended-release preparations. . . Routine oral dosingExtended-release preparations

Improve compliance, adherenceImprove compliance, adherence

Dose q 8, 12 or 24 h (product Dose q 8, 12 or 24 h (product specific)specific)

Don’t crush or chew tabletsDon’t crush or chew tablets

May flush time-release granules down May flush time-release granules down feeding tubesfeeding tubes

Adjust dose q 2–4 days (once steady Adjust dose q 2–4 days (once steady state reached)state reached)

Improve compliance, adherenceImprove compliance, adherence

Dose q 8, 12 or 24 h (product Dose q 8, 12 or 24 h (product specific)specific)

Don’t crush or chew tabletsDon’t crush or chew tablets

May flush time-release granules down May flush time-release granules down feeding tubesfeeding tubes

Adjust dose q 2–4 days (once steady Adjust dose q 2–4 days (once steady state reached)state reached)

Routine oral dosingLong half-life opioidsRoutine oral dosingLong half-life opioids

Dose interval for methadone is Dose interval for methadone is variable (q 6 h or q 8 h usually variable (q 6 h or q 8 h usually adequate)adequate)

Adjust methadone dose q 4–7 daysAdjust methadone dose q 4–7 days

Dose interval for methadone is Dose interval for methadone is variable (q 6 h or q 8 h usually variable (q 6 h or q 8 h usually adequate)adequate)

Adjust methadone dose q 4–7 daysAdjust methadone dose q 4–7 days

Breakthrough dosingBreakthrough dosing

Use immediate-release opioidsUse immediate-release opioids

5–15% of 24 hr dose5–15% of 24 hr dose

offer after Coffer after Cmaxmax reached reached

PO / PR PO / PR q 1 h q 1 h

SC, IM SC, IM q 30min q 30min

IV IV q 10– q 10–15min15min

Do NOT use extended-release Do NOT use extended-release opioidsopioids

Use immediate-release opioidsUse immediate-release opioids

5–15% of 24 hr dose5–15% of 24 hr dose

offer after Coffer after Cmaxmax reached reached

PO / PR PO / PR q 1 h q 1 h

SC, IM SC, IM q 30min q 30min

IV IV q 10– q 10–15min15min

Do NOT use extended-release Do NOT use extended-release opioidsopioids

Clearance concernsClearance concerns Conjugated by liverConjugated by liver

90–95% excreted in urine90–95% excreted in urine

Dehydration, renal failure, severe Dehydration, renal failure, severe hepatic failurehepatic failure

dosing interval, dosing interval, dosage size dosage size

If oliguria or anuriaIf oliguria or anuria

STOP routine dosing of STOP routine dosing of morphinemorphine

use ONLY PRNuse ONLY PRN

Conjugated by liverConjugated by liver

90–95% excreted in urine90–95% excreted in urine

Dehydration, renal failure, severe Dehydration, renal failure, severe hepatic failurehepatic failure

dosing interval, dosing interval, dosage size dosage size

If oliguria or anuriaIf oliguria or anuria

STOP routine dosing of STOP routine dosing of morphinemorphine

use ONLY PRNuse ONLY PRN

Mercadante S, Arcuri E. J Pain. 2004.

Not recommended . . .Not recommended . . .

MeperidineMeperidine

Poor oral absorptionPoor oral absorption

Normeperidine is a toxic metaboliteNormeperidine is a toxic metabolite

Longer half-life (6 hrs), no Longer half-life (6 hrs), no analgesiaanalgesia

Psychotomimetic adverse Psychotomimetic adverse effects, myoclonus, seizureseffects, myoclonus, seizures

If dosing q 3 h for analgesia, If dosing q 3 h for analgesia, normeperidine builds upnormeperidine builds up

Accumulates with renal failureAccumulates with renal failure

MeperidineMeperidine

Poor oral absorptionPoor oral absorption

Normeperidine is a toxic metaboliteNormeperidine is a toxic metabolite

Longer half-life (6 hrs), no Longer half-life (6 hrs), no analgesiaanalgesia

Psychotomimetic adverse Psychotomimetic adverse effects, myoclonus, seizureseffects, myoclonus, seizures

If dosing q 3 h for analgesia, If dosing q 3 h for analgesia, normeperidine builds upnormeperidine builds up

Accumulates with renal failureAccumulates with renal failure

. . . Not recommended . . .. . . Not recommended . . .

PropoxyphenePropoxyphene

No better than placeboNo better than placebo

Low efficacy at commercially Low efficacy at commercially available dosesavailable doses

Toxic metabolite at high dosesToxic metabolite at high doses

PropoxyphenePropoxyphene

No better than placeboNo better than placebo

Low efficacy at commercially Low efficacy at commercially available dosesavailable doses

Toxic metabolite at high dosesToxic metabolite at high doses

. . . Not recommended. . . Not recommended

Mixed agonist-antagonistsMixed agonist-antagonists

Pentazocine, butorphanol, nalbuphine, Pentazocine, butorphanol, nalbuphine, dezocinedezocine

Compete with agonists Compete with agonists withdrawalwithdrawal

Analgesic ceiling effectAnalgesic ceiling effect

High risk of psychotomimetic High risk of psychotomimetic adverse effects with adverse effects with pentazocine, butorphanolpentazocine, butorphanol

Mixed agonist-antagonistsMixed agonist-antagonists

Pentazocine, butorphanol, nalbuphine, Pentazocine, butorphanol, nalbuphine, dezocinedezocine

Compete with agonists Compete with agonists withdrawalwithdrawal

Analgesic ceiling effectAnalgesic ceiling effect

High risk of psychotomimetic High risk of psychotomimetic adverse effects with adverse effects with pentazocine, butorphanolpentazocine, butorphanol

Addiction . . .Addiction . . .

Psychological dependencePsychological dependence

Compulsive useCompulsive use

Loss of control over drugsLoss of control over drugs

Loss of interest in pleasurable Loss of interest in pleasurable activitiesactivities

Psychological dependencePsychological dependence

Compulsive useCompulsive use

Loss of control over drugsLoss of control over drugs

Loss of interest in pleasurable Loss of interest in pleasurable activitiesactivities

. . . Addiction. . . Addiction

Continued use of drugs in spite of Continued use of drugs in spite of harmharm

A rare outcome of pain management A rare outcome of pain management

Particularly, if no history of substance Particularly, if no history of substance abuseabuse

Continued use of drugs in spite of Continued use of drugs in spite of harmharm

A rare outcome of pain management A rare outcome of pain management

Particularly, if no history of substance Particularly, if no history of substance abuseabuse

. . . Addiction. . . Addiction

ConsiderConsider

Substance use (true addiction)Substance use (true addiction)

Pseudo-addiction (under-treatment of Pseudo-addiction (under-treatment of pain)pain)

Behavioral/family/psychological Behavioral/family/psychological disorderdisorder

Drug diversionDrug diversion

ConsiderConsider

Substance use (true addiction)Substance use (true addiction)

Pseudo-addiction (under-treatment of Pseudo-addiction (under-treatment of pain)pain)

Behavioral/family/psychological Behavioral/family/psychological disorderdisorder

Drug diversionDrug diversion

ToleranceTolerance

Reduced effectiveness to a given Reduced effectiveness to a given dose over timedose over time

Not clinically significant with chronic Not clinically significant with chronic dosingdosing

If dose is increasing, suspect If dose is increasing, suspect disease progressiondisease progression

Reduced effectiveness to a given Reduced effectiveness to a given dose over timedose over time

Not clinically significant with chronic Not clinically significant with chronic dosingdosing

If dose is increasing, suspect If dose is increasing, suspect disease progressiondisease progression

Physical dependencePhysical dependence

A process of neuro adaptationA process of neuro adaptation

Abrupt withdrawal may Abrupt withdrawal may abstinence abstinence syndromesyndrome

If dose reduction required, reduce by If dose reduction required, reduce by 50% q 2–3 days50% q 2–3 days

Avoid antagonistsAvoid antagonists

A process of neuro adaptationA process of neuro adaptation

Abrupt withdrawal may Abrupt withdrawal may abstinence abstinence syndromesyndrome

If dose reduction required, reduce by If dose reduction required, reduce by 50% q 2–3 days50% q 2–3 days

Avoid antagonistsAvoid antagonists

Substance usersSubstance users

Can have pain tooCan have pain too

Treat with compassion Treat with compassion

Protocols, contractingProtocols, contracting

Consultation with pain or addiction Consultation with pain or addiction specialistsspecialists

Can have pain tooCan have pain too

Treat with compassion Treat with compassion

Protocols, contractingProtocols, contracting

Consultation with pain or addiction Consultation with pain or addiction specialistsspecialists

Pain poorly-responsiveto opioidsPain poorly-responsiveto opioids If dose escalation If dose escalation adverse effects adverse effects

More sophisticated therapy to More sophisticated therapy to counteract adverse effectcounteract adverse effect

AlternativeAlternative

Route of administrationRoute of administration

Opioid (‘opioid rotation’)Opioid (‘opioid rotation’)

CoanalgesicCoanalgesic

Use a non-pharmacological approachUse a non-pharmacological approach

If dose escalation If dose escalation adverse effects adverse effects

More sophisticated therapy to More sophisticated therapy to counteract adverse effectcounteract adverse effect

AlternativeAlternative

Route of administrationRoute of administration

Opioid (‘opioid rotation’)Opioid (‘opioid rotation’)

CoanalgesicCoanalgesic

Use a non-pharmacological approachUse a non-pharmacological approach

Ongoing assessmentOngoing assessment

Increase analgesics until pain Increase analgesics until pain relieved or adverse effects relieved or adverse effects unacceptableunacceptable

Be prepared for sudden changes in Be prepared for sudden changes in painpain

Driving is safe ifDriving is safe if

Pain controlled, dose stable, no adverse Pain controlled, dose stable, no adverse effectseffects

Increase analgesics until pain Increase analgesics until pain relieved or adverse effects relieved or adverse effects unacceptableunacceptable

Be prepared for sudden changes in Be prepared for sudden changes in painpain

Driving is safe ifDriving is safe if

Pain controlled, dose stable, no adverse Pain controlled, dose stable, no adverse effectseffects

Alternative routesof administrationAlternative routesof administration Enteral feeding tubesEnteral feeding tubes

TransmucosalTransmucosal

RectalRectal

Transdermal Transdermal

ParenteralParenteral

IntraspinalIntraspinal

Enteral feeding tubesEnteral feeding tubes

TransmucosalTransmucosal

RectalRectal

Transdermal Transdermal



Transdermal patchTransdermal patch

FentanylFentanyl

Peak effect after application Peak effect after application 24 hrs 24 hrs

Patch lasts 48–72 hrsPatch lasts 48–72 hrs

Ensure adherence to skinEnsure adherence to skin

FentanylFentanyl

Peak effect after application Peak effect after application 24 hrs 24 hrs

Patch lasts 48–72 hrsPatch lasts 48–72 hrs

Ensure adherence to skinEnsure adherence to skin

Gourlay GK, et al. Pain. 1989.


SC, IV, IMSC, IV, IM

Bolus dosing q 3–4 hBolus dosing q 3–4 h

Continuous infusionContinuous infusion

Easier to administerEasier to administer

More even pain controlMore even pain control

SC, IV, IMSC, IV, IM

Bolus dosing q 3–4 hBolus dosing q 3–4 h

Continuous infusionContinuous infusion

Easier to administerEasier to administer

More even pain controlMore even pain control


EpiduralEpidural

IntrathecalIntrathecal

Morphine, hydromorphone, fentanylMorphine, hydromorphone, fentanyl

ConsultationConsultation

EpiduralEpidural

IntrathecalIntrathecal

Morphine, hydromorphone, fentanylMorphine, hydromorphone, fentanyl


Bolus effectBolus effect

Swings in plasma concentrationSwings in plasma concentration

Drowsiness ½ –1 hr post ingestionDrowsiness ½ –1 hr post ingestion

Pain before next dose duePain before next dose due

Must move to Must move to

Extended-release preparationExtended-release preparation

Continuous SC, IV infusionContinuous SC, IV infusion

Swings in plasma concentrationSwings in plasma concentration

Drowsiness ½ –1 hr post ingestionDrowsiness ½ –1 hr post ingestion

Pain before next dose duePain before next dose due

Must move to Must move to

Extended-release preparationExtended-release preparation

Continuous SC, IV infusionContinuous SC, IV infusion

Changing routesof administrationChanging routesof administration Equianalgesic tableEquianalgesic table

Guide to initial dose selectionGuide to initial dose selection

Significant first-pass metabolism of Significant first-pass metabolism of PO / PR dosesPO / PR doses

Codeine, hydromorphone, morphineCodeine, hydromorphone, morphine

PO / PRPO / PRtoto SC, IV, IMSC, IV, IM

2–32–3 11

Equianalgesic tableEquianalgesic table

Guide to initial dose selectionGuide to initial dose selection

Significant first-pass metabolism of Significant first-pass metabolism of PO / PR dosesPO / PR doses

Codeine, hydromorphone, morphineCodeine, hydromorphone, morphine

PO / PRPO / PRtoto SC, IV, IMSC, IV, IM

2–32–3 11

Equianalgesic dosesof opioid analgesicsEquianalgesic dosesof opioid analgesics

PO / PR PO / PR (mg)(mg) AnalgesicAnalgesic SC / IV / IM SC / IV / IM (mg)(mg)

100100 CodeineCodeine 6060

1515 HydrocodoneHydrocodone --

44 HydromorphoneHydromorphone 1.51.5

1515 MorphineMorphine 55

1010 OxycodoneOxycodone --

PO / PR PO / PR (mg)(mg) AnalgesicAnalgesic SC / IV / IM SC / IV / IM (mg)(mg)

100100 CodeineCodeine 6060

1515 HydrocodoneHydrocodone --

44 HydromorphoneHydromorphone 1.51.5

1515 MorphineMorphine 55

1010 OxycodoneOxycodone --

Changing opioids . . .Changing opioids . . .


Transdermal fentanylTransdermal fentanyl

25 25 g patch g patch 45–135 (likely 50–60) mg 45–135 (likely 50–60) mg morphine / 24 hrs morphine / 24 hrs


Transdermal fentanylTransdermal fentanyl

25 25 g patch g patch 45–135 (likely 50–60) mg 45–135 (likely 50–60) mg morphine / 24 hrs morphine / 24 hrs

. . . Changing opioids. . . Changing opioids

Cross-toleranceCross-tolerance

Start with 50–75% of published Start with 50–75% of published equianalgesic doseequianalgesic dose

More if pain, less if adverse More if pain, less if adverse effectseffects

MethadoneMethadone


Cross-toleranceCross-tolerance


More if pain, less if adverse More if pain, less if adverse effectseffects

MethadoneMethadone


Ripamonti C, Zecca E, Bruera E. Pain. 1997.

Adjuvant analgesics Adjuvant analgesics

Medications that supplement primary Medications that supplement primary analgesicsanalgesics

May themselves be primary analgesicsMay themselves be primary analgesics

Use at any step of WHO ladderUse at any step of WHO ladder

Medications that supplement primary Medications that supplement primary analgesicsanalgesics

May themselves be primary analgesicsMay themselves be primary analgesics

Use at any step of WHO ladderUse at any step of WHO ladder

Gabapentin Gabapentin

AnticonvulsantAnticonvulsant

100 mg PO daily to tid, titrate100 mg PO daily to tid, titrate

Increase dose q 1–3 dIncrease dose q 1–3 d

Usual effective dose 900–1800 mg / day; Usual effective dose 900–1800 mg / day; max may be > 3600 mg / daymax may be > 3600 mg / day

Minimal adverse effectsMinimal adverse effects

Drowsiness, tolerance develops Drowsiness, tolerance develops within dayswithin days

AnticonvulsantAnticonvulsant

100 mg PO daily to tid, titrate100 mg PO daily to tid, titrate

Increase dose q 1–3 dIncrease dose q 1–3 d

Usual effective dose 900–1800 mg / day; Usual effective dose 900–1800 mg / day; max may be > 3600 mg / daymax may be > 3600 mg / day

Minimal adverse effectsMinimal adverse effects

Drowsiness, tolerance develops Drowsiness, tolerance develops within dayswithin days

Backonja, et al. JAMA. 1998.

Other anticonvulsantsOther anticonvulsants CarbamazepineCarbamazepine

100 mg PO bid, titrate100 mg PO bid, titrate

Valproic acidValproic acid

250 mg PO q hs, titrate250 mg PO q hs, titrate

Monitor plasma levels for risk of toxicityMonitor plasma levels for risk of toxicity

ClonazepamClonazepam

LamotrigineLamotrigine

CarbamazepineCarbamazepine

100 mg PO bid, titrate100 mg PO bid, titrate

Valproic acidValproic acid

250 mg PO q hs, titrate250 mg PO q hs, titrate

Monitor plasma levels for risk of toxicityMonitor plasma levels for risk of toxicity

ClonazepamClonazepam

LamotrigineLamotrigine

McQuay, et al. BMJ. 1995.Eisenberg E, et al. Neurology. 2001.

Tricyclic antidepressantsTricyclic antidepressants

AmitriptylineAmitriptyline

Most extensively studiedMost extensively studied

10–25 mg PO nightly, titrate 10–25 mg PO nightly, titrate (escalate q 4–7 d)(escalate q 4–7 d)

Analgesia in days to weeksAnalgesia in days to weeks


Most extensively studiedMost extensively studied

10–25 mg PO nightly, titrate 10–25 mg PO nightly, titrate (escalate q 4–7 d)(escalate q 4–7 d)

Analgesia in days to weeksAnalgesia in days to weeks

Max, et al .N Engl J Med. 1992.

. . . Tricyclic antidepressants . . .. . . Tricyclic antidepressants . . .


Monitor plasma drug levels Monitor plasma drug levels > 100 mg / 24h for risk of toxicity> 100 mg / 24h for risk of toxicity

Anticholinergic adverse effects Anticholinergic adverse effects prominent, cardiac toxicityprominent, cardiac toxicity

Sedating limited usefulness in frail, Sedating limited usefulness in frail, elderlyelderly


Monitor plasma drug levels Monitor plasma drug levels > 100 mg / 24h for risk of toxicity> 100 mg / 24h for risk of toxicity

Anticholinergic adverse effects Anticholinergic adverse effects prominent, cardiac toxicityprominent, cardiac toxicity

Sedating limited usefulness in frail, Sedating limited usefulness in frail, elderlyelderly

. . . Tricyclic antidepressants. . . Tricyclic antidepressants

DesipramineDesipramine

Minimal anticholinergic or sedating Minimal anticholinergic or sedating adverse effectsadverse effects

10–25 mg PO q hs, titrate10–25 mg PO q hs, titrate

Tricyclic of choice in seriously illTricyclic of choice in seriously ill

Nortriptyline is an alternativeNortriptyline is an alternative

DesipramineDesipramine

Minimal anticholinergic or sedating Minimal anticholinergic or sedating adverse effectsadverse effects

10–25 mg PO q hs, titrate10–25 mg PO q hs, titrate

Tricyclic of choice in seriously illTricyclic of choice in seriously ill

Nortriptyline is an alternativeNortriptyline is an alternative

Corticosteroids . . .Corticosteroids . . .

Many usesMany uses

DexamethasoneDexamethasone

Long half-life (>36 hrs), dose once / dayLong half-life (>36 hrs), dose once / day

Minimal mineralocorticoid effectMinimal mineralocorticoid effect

Doses of 2–20 + mg / dayDoses of 2–20 + mg / day

Many usesMany uses

DexamethasoneDexamethasone

Long half-life (>36 hrs), dose once / dayLong half-life (>36 hrs), dose once / day

Minimal mineralocorticoid effectMinimal mineralocorticoid effect

Doses of 2–20 + mg / dayDoses of 2–20 + mg / day

. . . Corticosteroids. . . Corticosteroids

Adverse effectsAdverse effects

Steroid psychosisSteroid psychosis

Proximal myopathyProximal myopathy

Other long-term adverse effectsOther long-term adverse effects


Steroid psychosisSteroid psychosis

Proximal myopathyProximal myopathy

Other long-term adverse effectsOther long-term adverse effects

Bone pain . . .Bone pain . . .

Constant, worse with movementConstant, worse with movement

Metastases, compression or Metastases, compression or pathological fracturespathological fractures

Prostaglandins from inflammation, Prostaglandins from inflammation, metastasesmetastases

Rule out cord compressionRule out cord compression

Constant, worse with movementConstant, worse with movement

Metastases, compression or Metastases, compression or pathological fracturespathological fractures

Prostaglandins from inflammation, Prostaglandins from inflammation, metastasesmetastases

Rule out cord compressionRule out cord compression

Blum, et al. Oncology. 2003.

. . . Bone pain . . .. . . Bone pain . . .


OpioidsOpioids

NSAIDsNSAIDs

CorticosteroidsCorticosteroids

BisphosphonatesBisphosphonates

CalcitoninCalcitonin


OpioidsOpioids

NSAIDsNSAIDs


BisphosphonatesBisphosphonates

CalcitoninCalcitonin

. . . Bone pain. . . Bone pain


RadiopharmaceuticalsRadiopharmaceuticals

External beam radiationExternal beam radiation

Orthopedic interventionOrthopedic intervention

External bracingExternal bracing



RadiopharmaceuticalsRadiopharmaceuticals

External beam radiationExternal beam radiation

Orthopedic interventionOrthopedic intervention

External bracingExternal bracing


Pain from bowel obstruction . . .Pain from bowel obstruction . . . ConstipationConstipation

External compressionExternal compression

Bowel wall stretch, inflammationBowel wall stretch, inflammation

Associated symptomsAssociated symptoms

Definitive interventionDefinitive intervention

Relief of constipationRelief of constipation

Surgical removal or bypassSurgical removal or bypass

ConstipationConstipation

External compressionExternal compression

Bowel wall stretch, inflammationBowel wall stretch, inflammation

Associated symptomsAssociated symptoms

Definitive interventionDefinitive intervention

Relief of constipationRelief of constipation

Surgical removal or bypassSurgical removal or bypass

. . . Pain from bowel obstruction. . . Pain from bowel obstruction ManagementManagement

OpioidsOpioids


NSAIDsNSAIDs

Anticholinergic medications Anticholinergic medications eg, scopolamineeg, scopolamine

OctreotideOctreotide


OpioidsOpioids


NSAIDsNSAIDs

Anticholinergic medications Anticholinergic medications eg, scopolamineeg, scopolamine

OctreotideOctreotide

Muir JC, von Gunten CF. Clin Geriatr Med. 2000.

Opioid adverse effectsOpioid adverse effects

CommonCommon UncommonUncommon

ConstipationConstipation Bad dreams / Bad dreams / hallucinationshallucinations

Dry mouthDry mouth Dysphoria / deliriumDysphoria / delirium

Nausea / vomitingNausea / vomiting Myoclonus / seizuresMyoclonus / seizures

SedationSedation Pruritus / urticariaPruritus / urticaria

SweatsSweats Respiratory depressionRespiratory depression

Urinary retentionUrinary retention

CommonCommon UncommonUncommon

ConstipationConstipation Bad dreams / Bad dreams / hallucinationshallucinations

Dry mouthDry mouth Dysphoria / deliriumDysphoria / delirium

Nausea / vomitingNausea / vomiting Myoclonus / seizuresMyoclonus / seizures

SedationSedation Pruritus / urticariaPruritus / urticaria

SweatsSweats Respiratory depressionRespiratory depression

Urinary retentionUrinary retention

Opioid allergyOpioid allergy

Nausea / vomiting, constipation, Nausea / vomiting, constipation, drowsiness, confusiondrowsiness, confusion

Adverse effects, not allergic reactionsAdverse effects, not allergic reactions

Anaphylactic reactions are the only Anaphylactic reactions are the only true allergiestrue allergies

BronchospasmBronchospasm

Urticaria, bronchospasm can be Urticaria, bronchospasm can be allergies; need careful assessmentallergies; need careful assessment

Nausea / vomiting, constipation, Nausea / vomiting, constipation, drowsiness, confusiondrowsiness, confusion

Adverse effects, not allergic reactionsAdverse effects, not allergic reactions

Anaphylactic reactions are the only Anaphylactic reactions are the only true allergiestrue allergies

BronchospasmBronchospasm

Urticaria, bronchospasm can be Urticaria, bronchospasm can be allergies; need careful assessmentallergies; need careful assessment

Urticaria, pruritusUrticaria, pruritus

Mast cell destabilization by Mast cell destabilization by morphine, hydromorphonemorphine, hydromorphone

Treat with routine long-acting, non-Treat with routine long-acting, non-sedating antihistaminessedating antihistamines

Fexofenadine 60 mg PO bid, or higherFexofenadine 60 mg PO bid, or higher

or try diphenhydramine, loratadine or or try diphenhydramine, loratadine or doxepindoxepin

Mast cell destabilization by Mast cell destabilization by morphine, hydromorphonemorphine, hydromorphone

Treat with routine long-acting, non-Treat with routine long-acting, non-sedating antihistaminessedating antihistamines

Fexofenadine 60 mg PO bid, or higherFexofenadine 60 mg PO bid, or higher

or try diphenhydramine, loratadine or or try diphenhydramine, loratadine or doxepindoxepin

ConstipationConstipation

Common to all opioidsCommon to all opioids

Opioid effects on CNS, spinal cord, Opioid effects on CNS, spinal cord, myenteric plexus of gutmyenteric plexus of gut

Easier to prevent than treatEasier to prevent than treat

Common to all opioidsCommon to all opioids

Opioid effects on CNS, spinal cord, Opioid effects on CNS, spinal cord, myenteric plexus of gutmyenteric plexus of gut

Easier to prevent than treatEasier to prevent than treat

. . . Constipation . . .. . . Constipation . . .

Diet usually insufficientDiet usually insufficient

Bulk forming agents not Bulk forming agents not recommendedrecommended

Stimulant laxativeStimulant laxative

Senna, bisacodyl, glycerine, Senna, bisacodyl, glycerine, casanthranol, etc.casanthranol, etc.

Combine with a stool softenerCombine with a stool softener

Senna + docusate sodiumSenna + docusate sodium

Diet usually insufficientDiet usually insufficient

Bulk forming agents not Bulk forming agents not recommendedrecommended

Stimulant laxativeStimulant laxative

Senna, bisacodyl, glycerine, Senna, bisacodyl, glycerine, casanthranol, etc.casanthranol, etc.

Combine with a stool softenerCombine with a stool softener

Senna + docusate sodiumSenna + docusate sodium

. . . Constipation. . . Constipation

Prokinetic agentProkinetic agent

Metoclopramide, cisaprideMetoclopramide, cisapride

Osmotic laxativeOsmotic laxative

MOM, lactulose, sorbitolMOM, lactulose, sorbitol

Other measuresOther measures

Prokinetic agentProkinetic agent

Metoclopramide, cisaprideMetoclopramide, cisapride

Osmotic laxativeOsmotic laxative

MOM, lactulose, sorbitolMOM, lactulose, sorbitol

Other measuresOther measures

Nausea / vomiting . . .Nausea / vomiting . . .

Onset with start of opioidsOnset with start of opioids

Tolerance develops within daysTolerance develops within days

Prevent or treat with dopamine-Prevent or treat with dopamine-blocking antiemeticsblocking antiemetics

Prochlorperazine 10 mg q 6 hProchlorperazine 10 mg q 6 h

Haloperidol 1 mg 6 hHaloperidol 1 mg 6 h

Metoclopramide 10 mg q 6 hMetoclopramide 10 mg q 6 h



Prevent or treat with dopamine-Prevent or treat with dopamine-blocking antiemeticsblocking antiemetics

Prochlorperazine 10 mg q 6 hProchlorperazine 10 mg q 6 h

Haloperidol 1 mg 6 hHaloperidol 1 mg 6 h

Metoclopramide 10 mg q 6 hMetoclopramide 10 mg q 6 h

. . . Nausea / vomiting. . . Nausea / vomiting

Other antiemetics may also be Other antiemetics may also be effectiveeffective

Alternative opioid if refractoryAlternative opioid if refractory

Other antiemetics may also be Other antiemetics may also be effectiveeffective

Alternative opioid if refractoryAlternative opioid if refractory

Sedation . . .Sedation . . .


Distinguish from exhaustion due to painDistinguish from exhaustion due to pain


Complex in advanced diseaseComplex in advanced disease


Distinguish from exhaustion due to painDistinguish from exhaustion due to pain


Complex in advanced diseaseComplex in advanced disease

. . . Sedation. . . Sedation

If persistent, alternative opioid or If persistent, alternative opioid or route of administrationroute of administration

Psychostimulants may be usefulPsychostimulants may be useful

Methylphenidate 5 mg q am and q noon, Methylphenidate 5 mg q am and q noon, titratetitrate

If persistent, alternative opioid or If persistent, alternative opioid or route of administrationroute of administration

Psychostimulants may be usefulPsychostimulants may be useful

Methylphenidate 5 mg q am and q noon, Methylphenidate 5 mg q am and q noon, titratetitrate

Delirium . . .Delirium . . .

PresentationPresentation

Confusion, bad dreams, hallucinationsConfusion, bad dreams, hallucinations

Restlessness, agitationRestlessness, agitation

Myoclonic jerks, seizuresMyoclonic jerks, seizures

Depressed level of consciousnessDepressed level of consciousness

Respiratory depressionRespiratory depression

PresentationPresentation

Confusion, bad dreams, hallucinationsConfusion, bad dreams, hallucinations

Restlessness, agitationRestlessness, agitation

Myoclonic jerks, seizuresMyoclonic jerks, seizures

Depressed level of consciousnessDepressed level of consciousness

Respiratory depressionRespiratory depression

. . . Delirium. . . Delirium

Rare, unless multiple factors Rare, unless multiple factors contributing, if contributing, if

Opioid dosing guidelines followedOpioid dosing guidelines followed

Renal clearance normalRenal clearance normal

Rare, unless multiple factors Rare, unless multiple factors contributing, if contributing, if

Opioid dosing guidelines followedOpioid dosing guidelines followed

Renal clearance normalRenal clearance normal

Respiratory depression . . .Respiratory depression . . . Opioid effects differ for patients Opioid effects differ for patients

treated for paintreated for pain

Pain is a potent stimulus to breathePain is a potent stimulus to breathe

Loss of consciousness precedes Loss of consciousness precedes respiratory depressionrespiratory depression

Pharmacological tolerance rapidPharmacological tolerance rapid

Opioid effects differ for patients Opioid effects differ for patients treated for paintreated for pain

Pain is a potent stimulus to breathePain is a potent stimulus to breathe

Loss of consciousness precedes Loss of consciousness precedes respiratory depressionrespiratory depression

Pharmacological tolerance rapidPharmacological tolerance rapid

. . . Respiratory depression. . . Respiratory depression ManagementManagement

Identify, treat contributing causesIdentify, treat contributing causes

Reduce opioid doseReduce opioid dose

ObserveObserve

If unstable vital signsIf unstable vital signs

Naloxone 0.1-0.2 mg IV q 1-2 minNaloxone 0.1-0.2 mg IV q 1-2 min


Identify, treat contributing causesIdentify, treat contributing causes

Reduce opioid doseReduce opioid dose

ObserveObserve

If unstable vital signsIf unstable vital signs

Naloxone 0.1-0.2 mg IV q 1-2 minNaloxone 0.1-0.2 mg IV q 1-2 min

Non-pharmacological pain management . . .Non-pharmacological pain management . . . NeurostimulationNeurostimulation

TENS, acupunctureTENS, acupuncture

AnesthesiologicalAnesthesiologicalNerve blockNerve block

SurgicalSurgicalCordotomyCordotomy

Physical therapyPhysical therapyExercise, heat, coldExercise, heat, cold

NeurostimulationNeurostimulationTENS, acupunctureTENS, acupuncture

AnesthesiologicalAnesthesiologicalNerve blockNerve block

SurgicalSurgicalCordotomyCordotomy

Physical therapyPhysical therapyExercise, heat, coldExercise, heat, cold

. . . Non-pharmacological pain management. . . Non-pharmacological pain management Psychological approachesPsychological approaches

Cognitive therapiesCognitive therapies(relaxation, imagery, hypnosis)(relaxation, imagery, hypnosis)

BiofeedbackBiofeedback

Behavior therapy, psychotherapy Behavior therapy, psychotherapy

Complementary therapiesComplementary therapies

MassageMassage

Art, music, aroma therapyArt, music, aroma therapy

Psychological approachesPsychological approaches

Cognitive therapiesCognitive therapies(relaxation, imagery, hypnosis)(relaxation, imagery, hypnosis)

BiofeedbackBiofeedback

Behavior therapy, psychotherapy Behavior therapy, psychotherapy

Complementary therapiesComplementary therapies

MassageMassage

Art, music, aroma therapyArt, music, aroma therapy

Barriers . . .Barriers . . .

Not importantNot important

Poor assessmentPoor assessment

Lack of knowledgeLack of knowledge

Fear ofFear of

AddictionAddiction

ToleranceTolerance


Not importantNot important

Poor assessmentPoor assessment

Lack of knowledgeLack of knowledge

Fear ofFear of

AddictionAddiction

ToleranceTolerance


. . . Barriers. . . Barriers

Regulatory oversightRegulatory oversight

Patient’s unwilling to report painPatient’s unwilling to report pain

Patients unwilling to take medicinePatients unwilling to take medicine

Regulatory oversightRegulatory oversight

Patient’s unwilling to report painPatient’s unwilling to report pain

Patients unwilling to take medicinePatients unwilling to take medicine

EEPPEECC

OO

EEPPEECC

OO

SummarySummary


comprehensive cancer carecomprehensive cancer care


comprehensive cancer carecomprehensive cancer care

education in palliative and end-of-life care - oncology

Documents

j pain symptom

ann intern

careinterdisciplinary

life care oncologymodule

neuropathicwolf cj

localizewolf cj

cleve clin j med

med clin north