New Concepts New Concepts in Painin Pain

ManagementManagement

Melanie Christina, M.D.Melanie Christina, M.D.

Presbyterian Hospital DallasPresbyterian Hospital Dallas

Medical Director, Heartland Medical Director, Heartland HospiceHospice

INTERNATIONAL ASSOCIATION FOR THE STUDY OF PAIN

DefinitionDefinition: Pain: Pain An unpleasant sensory and An unpleasant sensory and

emotional experience associated emotional experience associated with actual or potential tissue with actual or potential tissue damage, or described in terms of damage, or described in terms of such damagesuch damage

Pain is subjective. There is no Pain is subjective. There is no neurophysiological or chemical test neurophysiological or chemical test that can measure pain.that can measure pain.

Prevalence of PainPrevalence of Pain Over 30 million Americans suffer Over 30 million Americans suffer

from chronic nonmalignant painfrom chronic nonmalignant pain 20-30% of the American public 20-30% of the American public

suffer from acute or chronic painsuffer from acute or chronic pain Over 70% of patients with Over 70% of patients with

advanced cancer report having advanced cancer report having moderate to severe painmoderate to severe pain

Barriers in the treatment Barriers in the treatment of Painof Pain

Inadequate assessmentInadequate assessment Specific populations more likely Specific populations more likely notnot to be to be

treatedtreated Patient’s reluctance to report painPatient’s reluctance to report pain Patient’s reluctance to take opioidsPatient’s reluctance to take opioids Doctor’s reluctance to prescribe opioidsDoctor’s reluctance to prescribe opioids

– Fear of regulatory scrutinyFear of regulatory scrutiny– Fear of causing addictionFear of causing addiction– Lack of knowledge regarding dosing and side effects Lack of knowledge regarding dosing and side effects

Important concepts to Important concepts to UnderstandUnderstand AddictionAddiction

– Psychological dependence on substances for their psychic effects and is Psychological dependence on substances for their psychic effects and is characterized by compulsive use despite harm.characterized by compulsive use despite harm.

Analgesic ToleranceAnalgesic Tolerance– The need to increase the dose of opioid to achieve the same level of The need to increase the dose of opioid to achieve the same level of

analgesia.analgesia.

Physical DependencePhysical Dependence– A physiologic state of neuroadaptation which is characterized by the A physiologic state of neuroadaptation which is characterized by the

emergence of a withdrawal syndrome if drug use is stopped or decreased emergence of a withdrawal syndrome if drug use is stopped or decreased abruptly, or if an antagonist is administered.abruptly, or if an antagonist is administered.

PseudoaddictionPseudoaddiction– Pattern of drug-seeking behavior of pain patients who are receiving Pattern of drug-seeking behavior of pain patients who are receiving

inadequate pain medication. Behavior is mistaken for addiction.inadequate pain medication. Behavior is mistaken for addiction.

Guidelines for the Guidelines for the management and treatment management and treatment

of Painof Pain WHO - global initiative on pain WHO - global initiative on pain

management (1986)management (1986) Texas State Board of Medical Examiners Texas State Board of Medical Examiners

(1993)(1993) Federation of State Boards (1998)Federation of State Boards (1998) JCAHO (1999)JCAHO (1999) Governmental guidelines (AHCPR)Governmental guidelines (AHCPR) American Pain SocietyAmerican Pain Society

and many more!!!!!!and many more!!!!!!

Texas State Board of Texas State Board of Medical Examiners’ Medical Examiners’

PositionPosition ““Quality medical practice dictates that those Quality medical practice dictates that those

citizens of TX who suffer pain and other citizens of TX who suffer pain and other distressing symptoms should be adequately distressing symptoms should be adequately relieved so that their quality of life is as relieved so that their quality of life is as optimum as can be.”optimum as can be.”

““The TSBME recognizes that opioids and other The TSBME recognizes that opioids and other Scheduled Controlled substances, are Scheduled Controlled substances, are indispensable for the treatment of pain…”indispensable for the treatment of pain…”

““It is the position of the board that these drugs It is the position of the board that these drugs be prescribed for the treatment of these be prescribed for the treatment of these symptoms in appropriate and adequate doses…” symptoms in appropriate and adequate doses…”

Texas State Board of Texas State Board of Medical Examiners’ Medical Examiners’

PositionPosition

““The Board recognizes that pain, and many The Board recognizes that pain, and many other symptoms are other symptoms are subjective complaintssubjective complaints and appropriateness and adequacy of drug and appropriateness and adequacy of drug and dose will vary from individual to and dose will vary from individual to individual.”individual.”

““The standard will be determined largely by The standard will be determined largely by treatment outcome…”treatment outcome…”

Physicians should be diligent in preventing Physicians should be diligent in preventing (controlled substances) from being diverted (controlled substances) from being diverted from legitimate to illegitimate use.from legitimate to illegitimate use.

Standards used by Board when Standards used by Board when evaluating use of Controlled evaluating use of Controlled

substances:substances: DOCUMENTATIONDOCUMENTATION--Medical records should include:Medical records should include:

– medical history and physicalmedical history and physical– diagnostic, therapeutic and laboratory resultsdiagnostic, therapeutic and laboratory results– evaluations and consultationsevaluations and consultations– treatment objectivestreatment objectives– discussion of risks and benefitsdiscussion of risks and benefits– treatmentstreatments– medication (date, type, dosage, quantity)medication (date, type, dosage, quantity)– instructions and agreementsinstructions and agreements– periodic reviewperiodic review

Joint Commission Joint Commission Standards on Pain Standards on Pain

ManagementManagement

Patient’s have a right to appropriate Patient’s have a right to appropriate assessment and management of painassessment and management of pain

Pain needs to be assessed, documented and Pain needs to be assessed, documented and followed for appropriate interventionsfollowed for appropriate interventions

Policies and procedures should support the Policies and procedures should support the appropriate use of pain medicationsappropriate use of pain medications

Patients and their families should be Patients and their families should be educated on pain managementeducated on pain management

Discharge planning should include symptom Discharge planning should include symptom managementmanagement

Governmental GuidelinesGovernmental Guidelineswww.guidelines.govwww.guidelines.gov

1995 - “Clinical practice guidelines for chronic non-1995 - “Clinical practice guidelines for chronic non-malignant pain syndrome”malignant pain syndrome”

1998 - “The management of persistent pain in 1998 - “The management of persistent pain in older persons”older persons”

1999 - “Procedure guideline for bone treatment 1999 - “Procedure guideline for bone treatment pain”pain”

2000 - “Control of pain in patients with cancer. A 2000 - “Control of pain in patients with cancer. A national clinical guideline”national clinical guideline”

2002 - “Clinical practice guideline for the diagnosis, 2002 - “Clinical practice guideline for the diagnosis, treatment and management of reflex sympathetic treatment and management of reflex sympathetic dystrophy/complex regional pain syndrome”dystrophy/complex regional pain syndrome”

Current Legal Climate -Current Legal Climate -Undertreatment of PainUndertreatment of Pain

Landmark case in California with a Landmark case in California with a family suing the doctor for family suing the doctor for

inadequate pain control in their inadequate pain control in their dying, 85 year old father during dying, 85 year old father during the last week of his life. Jury trial the last week of his life. Jury trial

awarded family 1.5 million awarded family 1.5 million claiming the physicians lack of claiming the physicians lack of attention to pain was “reckless attention to pain was “reckless

negligence” and constituted elder negligence” and constituted elder abuse.abuse.

Tips for Physicians to protect Tips for Physicians to protect themselves from charges of themselves from charges of

Undertreatment of pain:Undertreatment of pain: Review your practice against JCAHO Review your practice against JCAHO

standardsstandards Improve knowledge in pain assessment and Improve knowledge in pain assessment and

treatmenttreatment Utilize local consultation resourcesUtilize local consultation resources Improve knowledge and skills in assessing Improve knowledge and skills in assessing

substance abuse; utilize local resources for substance abuse; utilize local resources for substance abuse referrals and treatmentsubstance abuse referrals and treatment

TYPES OF PAINTYPES OF PAINPathophysiologic categorizationPathophysiologic categorization

NOCICEPTIVENOCICEPTIVE– SOMATICSOMATIC

Stimulation of the somatic Stimulation of the somatic nervous systemnervous system

skin, soft tissue, muscle, skin, soft tissue, muscle, bonebone

easily localizedeasily localized

– VISCERALVISCERAL stimulation of the stimulation of the

autonomic nervous systemautonomic nervous system GI and GU tracts, cardiac, GI and GU tracts, cardiac,

lunglung difficult to describe and difficult to describe and

localizelocalize

NEUROPATHICNEUROPATHIC– PERIPHERAL PERIPHERAL

PROCESSES PROCESSES (neuroma)(neuroma)

– CNS PROCESSES CNS PROCESSES (phantom pain)(phantom pain)

– COMPLEX COMPLEX REGIONAL PAINREGIONAL PAIN

Classification of Classification of PainPain

Based on clinical courseBased on clinical course

Acute painAcute painChronic pain (non-Chronic pain (non-cancer)cancer)

Cancer painCancer painPost-surgical painPost-surgical pain

AHCPR 1994

Assessment of PainAssessment of Pain“ABCDE” Mnemonic“ABCDE” Mnemonic

AAsk about pain regularly; sk about pain regularly; AAssess pain ssess pain systematicallysystematically

BBelieve the patient and family in their reports elieve the patient and family in their reports of pain and what relieves itof pain and what relieves it

CChoose pain control options appropriate for hoose pain control options appropriate for the patient, family and settingthe patient, family and setting

DDeliver interventions in a timely, logical and eliver interventions in a timely, logical and coordinated fashioncoordinated fashion

EEmpower patients and their families; mpower patients and their families; EEnable nable them to control their course to the greatest them to control their course to the greatest extent possibleextent possible

Describing Pain:Describing Pain:“PQRST” Mnemonic“PQRST” Mnemonic

PProvoking or rovoking or PPalliative alliative factorsfactors

QQuality of painuality of pain RRadiationadiation SSeverityeverity TTemporalemporal

Goals in the treatment Goals in the treatment of painof pain

Improve quality of lifeImprove quality of life Encourage mobilityEncourage mobility Reduce hospitalizations and ER Reduce hospitalizations and ER

admissionsadmissions Improve job performanceImprove job performance Impact function in a family unitImpact function in a family unit Prevent depression/suicidePrevent depression/suicide

AspirinAcetaminophen

Nonsteroidal anti-inflammatory drugs+ Adjuvants

MorphineHydromorphone

MethadoneFentanyl

Oxycodone+ Nonopioid analgesics

+ Adjuvants

Step 1, Mild Pain

Step 2, Moderate Pain

Combination opioidsTramadol+ Adjuvants

Step 3, Severe Pain

WHO 3-STEP LADDER

Utilization of Opioids:Utilization of Opioids:Chronic PainChronic Pain

Dose around the clock - achieve blood Dose around the clock - achieve blood levels in the therapeutic range and avoid levels in the therapeutic range and avoid blood levels falling below pain thresholdblood levels falling below pain threshold

Rescue dosing - 10% of total 24 hour Rescue dosing - 10% of total 24 hour dosedose

Dose titration: Dose titration: – mild pain: increase dose by 10%mild pain: increase dose by 10%– moderate pain: increase dose by 25-50%moderate pain: increase dose by 25-50%– severe pain: increase dose by 100%severe pain: increase dose by 100%

Routes of Routes of AdministrationAdministration

Oral - preferredOral - preferred Buccal/sublingualBuccal/sublingual RectalRectal TransdermalTransdermal SubcutaneousSubcutaneous IntravenousIntravenous Intramuscular - CONTRAINDICATEDIntramuscular - CONTRAINDICATED IntrathecalIntrathecal

Equianalgesic Conversion Equianalgesic Conversion TableTable

ANALGESIC ORAL DOSE PARENTERALDOSE

DURATIONOF ACTION(HOURS)

HALF-LIFE(HOURS)

ORAL:PARENTERALRATIO

POMORPHINE:ANALGESICRATIO

Morphine 30mg 10mg 4-6hr 2-4hr 3:1 1:1Oxycodone 20mg 3-5hr 4-5hr 1.5:1Hydro-morphone 7.5mg 1.5mg 3-4hr 2-3hr 5:1 4:1Methadone 20mg 10mg 4-6hr 15-50h 2:1 3:1Codeine 200mg 130mg 4-6hr 3hr 1.5:1 1:7Hydro-codone 30mg 3-6 hr 3-4hr 1:1Meperidine 300mg 75mg 2-4hr 2-3hr 4:1 1:10

Variables in ConsideringVariables in ConsideringEquianalgesic DosesEquianalgesic Doses

Pain intensityPain intensity Prior opioid exposurePrior opioid exposure Incomplete cross toleranceIncomplete cross tolerance Age of PatientAge of Patient Route of administrationRoute of administration Level of ConsciousnessLevel of Consciousness Preexisting conditionsPreexisting conditions

Common Side Effects and Common Side Effects and treatmentstreatments

Constipation - All patients on opioids Constipation - All patients on opioids need a regular bowel program.need a regular bowel program.

Nausea - quickly develop tolerance to thisNausea - quickly develop tolerance to this Pruritus - may need to switch opioidsPruritus - may need to switch opioids Sedation - if tolerance doesn’t occur can Sedation - if tolerance doesn’t occur can

use stimulantsuse stimulants Respiratory depression - most feared yet Respiratory depression - most feared yet

rare side effect if proper dosing followedrare side effect if proper dosing followed

Fear of Respiratory Fear of Respiratory Depression from Opioid Depression from Opioid

UseUse

Patients develop tolerance to the respiratory Patients develop tolerance to the respiratory depressant effects early in course of therapydepressant effects early in course of therapy

Patients with COPD have been shown to Patients with COPD have been shown to experience improvement in exercise experience improvement in exercise tolerance and decreased SOB tolerance and decreased SOB

Terminally ill patients required 1.5-2.5 times Terminally ill patients required 1.5-2.5 times their regular dose of analgesia to control their regular dose of analgesia to control breathlessness; without effect on O2 breathlessness; without effect on O2 saturation or respiratory rate saturation or respiratory rate Annals Internal Medicine 119: 906, 1993Annals Internal Medicine 119: 906, 1993

Fentanyl Transdermal Fentanyl Transdermal SystemSystem

Medication is absorbed into the subcutaneous tissue; Medication is absorbed into the subcutaneous tissue; then absorbed into systemic circulation via capillariesthen absorbed into systemic circulation via capillaries

May take 18-24 hours before effect of medication May take 18-24 hours before effect of medication therefore therefore not idea for acute pain managementnot idea for acute pain management

Continue previous medicine for 18-24hr after placing Continue previous medicine for 18-24hr after placing the patchthe patch

Use short-acting opioid for rescue dosingUse short-acting opioid for rescue dosing Adjust dose no sooner than every 6 daysAdjust dose no sooner than every 6 days Once removing patch the effect may persist for up to Once removing patch the effect may persist for up to

24 hours24 hours

GOOD RULE OF THUMB: 2 X DURAGESIC DOSE = 24 HOUR MORPHINE DOSE

Duragesic: Oral Morphine Duragesic: Oral Morphine Equianalgesic TableEquianalgesic Table

Morphine dose in24hr

Duragesic PatchStrenth

90mg (range 45-134mg) 25ug/hr

180 (range 135-224mg) 50ug/hr

270 (range 225-314mg) 75ug/hr

360 (range 315-404mg) 100ug/hr

For each additional 90mg(range 45-134mg)

Add 25ug/hr

Steps in Changing Steps in Changing OpioidsOpioids

Calculate 24 hour dose of current opioidsCalculate 24 hour dose of current opioids Use equianalgesic table - convert dose of Use equianalgesic table - convert dose of

current drugs to equivalent new drugcurrent drugs to equivalent new drug Adjust the dose of new drug to accommodate Adjust the dose of new drug to accommodate

patient variability and incomplete cross patient variability and incomplete cross tolerancetolerance

Determine dosing intervals according to Determine dosing intervals according to duration of action of new opioidduration of action of new opioid

Calculate rescue doseCalculate rescue dose

Example:Example: Mr. Kaye is receiving 8mg Dilaudid Mr. Kaye is receiving 8mg Dilaudid po q 3h, and his physician would like to po q 3h, and his physician would like to change the patient to a sustained release change the patient to a sustained release morphine product for patient convenience.morphine product for patient convenience.

Calculate the 24 hour dose of DilaudidCalculate the 24 hour dose of Dilaudid– 8mg x 8 = 64mg Dilaudid8mg x 8 = 64mg Dilaudid

Using the morphine:Dilaudid ratio figure the 24 Using the morphine:Dilaudid ratio figure the 24 hour equianalgesic dose morphinehour equianalgesic dose morphine– Morphine: Dilaudid (4:1)Morphine: Dilaudid (4:1)– Multiply 64 by 4 = 256mg morphine equivalentMultiply 64 by 4 = 256mg morphine equivalent

Divide the 24 hour dose by 12 for the long-acting Divide the 24 hour dose by 12 for the long-acting morphine dosemorphine dose– 256 divided by 2 = 128 or rounded up to MS 256 divided by 2 = 128 or rounded up to MS

Contin 130mg q 12hourContin 130mg q 12hour

On the same patient, figure what the On the same patient, figure what the rescue dose of short-acting rescue dose of short-acting morphine would be?morphine would be?

Figure the total 24 hour dose of routine Figure the total 24 hour dose of routine medication being givenmedication being given– 260mg morphine per day260mg morphine per day

10% of that can be given every 1-2 10% of that can be given every 1-2 hours as needed for breakthrough painhours as needed for breakthrough pain– 10% of 260 = 26mg10% of 260 = 26mg– can give morphine immediate release can give morphine immediate release

tablets (30mg) q 1-2 h or morphine liquid tablets (30mg) q 1-2 h or morphine liquid (20mg/ml) 1.25 ml q 1-2 hour(20mg/ml) 1.25 ml q 1-2 hour

On the same patient, if he were On the same patient, if he were to stop swallowing what could to stop swallowing what could be done?be done? Switch to IV therapySwitch to IV therapy

– Figure the total dose of morphine given (260mg)Figure the total dose of morphine given (260mg)– Use the equianalgesic chart to figure oral:parenteral Use the equianalgesic chart to figure oral:parenteral

ratio (3:1)ratio (3:1)– Divide 260mg by 3 = 87mg IV morphine/dayDivide 260mg by 3 = 87mg IV morphine/day– Decide the route (subcutaneous or IV) Decide the route (subcutaneous or IV) – Divide 87mg/24hour = 3.6mg/hourDivide 87mg/24hour = 3.6mg/hour– Have boluses of 25-50% total hourly dose available q Have boluses of 25-50% total hourly dose available q

15-30mins (1-2mg)15-30mins (1-2mg) Use MS Contin rectallyUse MS Contin rectally at the same dose and give the at the same dose and give the

rescue dose as a sublingual medicationrescue dose as a sublingual medication Use sublingual medication on a q 4 hour scheduleUse sublingual medication on a q 4 hour schedule

On the same patient, if Mr. Kaye On the same patient, if Mr. Kaye stopped swallowing tablets but had stopped swallowing tablets but had an extended prognosis?an extended prognosis?

Consider switching to Duragesic PatchConsider switching to Duragesic Patch– Total Morphine dose 260mgTotal Morphine dose 260mg– Duragesic patch dose (per table) is Duragesic patch dose (per table) is

75ug/h75ug/h– Via 2x rule: 260/2=130 or 125ug/h Via 2x rule: 260/2=130 or 125ug/h – Same breakthrough medication is Same breakthrough medication is

appropriateappropriate Stop the previous routine medication Stop the previous routine medication

18-24 hours 18-24 hours afterafter the patch is placed the patch is placed

Bone Pain from Bone Pain from MetastasisMetastasis

NSAIDNSAID SteroidsSteroids BisphosphonatesBisphosphonates RadiopharmaceuticalsRadiopharmaceuticals Radiation TherapyRadiation Therapy

Neuropathic painNeuropathic pain Definition: Arising directly from Definition: Arising directly from

central and peripheral damage by central and peripheral damage by injury, disease or medical injury, disease or medical treatment. A pathological pain that treatment. A pathological pain that serves no adaptive purpose. serves no adaptive purpose.

Frequently becomes chronic and Frequently becomes chronic and may escalate over timemay escalate over time

Challenging to diagnose and treatChallenging to diagnose and treat

NOCICEPTORS react to noxiousstimuli (heat, chemical, mechanical)

A-delta fibersC fibers

Nociceptors terminate in the DORSAL HORN and

synapse in the Rexed Laminae

SPINOTHALAMIC TRACTSsend transmission rostrally after

decussating in spinal cord

Nociceptive signals ascend in the ANTEROLATERAL

WHITE MATTER

Termination in THALAMUSwith afferent fibers

projecting rostrally to the somatosensory

CORTEX and LIMBICSYSTEM

Afferent PainPathways

Mechanism and Mediators Mechanism and Mediators of Painof Pain

Painful stimuli causes depolarization of A-DELTA (thinly Painful stimuli causes depolarization of A-DELTA (thinly myelinated) and C-FIBER (unmyelinated)myelinated) and C-FIBER (unmyelinated)

Inflammation from chemical messengers released from Inflammation from chemical messengers released from damaged tissue (AMP, Protein), mast cells damaged tissue (AMP, Protein), mast cells (Prostaglandin), macrophages (cytokines)(Prostaglandin), macrophages (cytokines)

This leads to This leads to lowering of activation threshold and ectopic lowering of activation threshold and ectopic dischargesdischarges = = Peripheral sensitizationPeripheral sensitization

Neuron itself releases substance P which turns on Neuron itself releases substance P which turns on messengers of immune cellsmessengers of immune cells

Positive feedback loopPositive feedback loop Increase input into Dorsal HornIncrease input into Dorsal Horn

Peripheral Peripheral SensitizationSensitization

Lowering of the nociceptor Lowering of the nociceptor depolarization threshold and depolarization threshold and increase in ectopic dischargesincrease in ectopic discharges

Due to altered expression and Due to altered expression and distribution of sodium channels at distribution of sodium channels at the level of injured nociceptor and the level of injured nociceptor and Dorsal Root GanglionDorsal Root Ganglion

Mechanisms of Pain Mechanisms of Pain in the Dorsal Hornin the Dorsal Horn

Depolarized Nociceptors release Glutamate at Depolarized Nociceptors release Glutamate at the terminal endthe terminal end

Glutamate normally binds to AMPA receptor Glutamate normally binds to AMPA receptor causing depolarization of DH cellscausing depolarization of DH cells

With peripheral sensitization and increase input, With peripheral sensitization and increase input, the NMDA receptor becomes exposed and the NMDA receptor becomes exposed and Glutamate binds NMDA and AMPA. (wind-up)Glutamate binds NMDA and AMPA. (wind-up)

This sensitizes central nervous system such that This sensitizes central nervous system such that subthreshold input depolarize neuronssubthreshold input depolarize neurons

Central Central SensitizationSensitization

Lowering of the threshold of spinal horn Lowering of the threshold of spinal horn neurons, with an increase magnitude and neurons, with an increase magnitude and duration of response to stimulationduration of response to stimulation

Expansion in size of receptive fieldExpansion in size of receptive field Release of tachykinins (substance P and Release of tachykinins (substance P and

neurokinin A)neurokinin A)– These bind to neurokinin receptor and increase These bind to neurokinin receptor and increase

intracellular calcium intracellular calcium – Increases NMDA receptor up regulationIncreases NMDA receptor up regulation– Increase in Nitrous oxide synthetaseIncrease in Nitrous oxide synthetase

ImportanceImportance of NMDA of NMDA ReceptorReceptor

The NMDA Receptor is involved in the The NMDA Receptor is involved in the propagation of neuropathic pain propagation of neuropathic pain

Tolerance is also related to this Tolerance is also related to this receptorreceptor

When the NMDA Receptor is activated, When the NMDA Receptor is activated, there is Central Sensitization there is Central Sensitization

The opioid receptor, mu receptor, is The opioid receptor, mu receptor, is less responsive to opioidsless responsive to opioids

NEUROPATHIC PAIN

Medical Management

Surgical ManagementDecompression

Nerve BlocksLocal Anesthetics

Membrane stabilizingAgents

Drugs that enhancedorsal horn inhibition

NMDA ReceptorAntagonist

STEROIDSANTIARRHYTHMICS

LidocaineMexilitine

ANTIEPILEPTICSCarbamazepineOxcarbazepine

PhenytoinValproate

KetamineDextromethoraphan

MethadoneAmantadine

GABA-BagonistsBaclofen

ANTIDEPRESSANTSAmitriptylineDesipramineImipramine

Nortriptyline

ANTIEPILEPTICSOxcarbazepine

ClonazepamGabapentin

Most commonly used Most commonly used adjunctive treatmentsadjunctive treatments

AmitryptillineAmitryptilline CarbamazepineCarbamazepine GabapentinGabapentin CorticosteroidsCorticosteroids

MethadoneMethadone A Mu agonist and noncompetitive A Mu agonist and noncompetitive

NMDA receptor antagonistNMDA receptor antagonist No neuroactive metabolitesNo neuroactive metabolites Elimination is independent of renal Elimination is independent of renal

functionfunction Less constipating Less constipating Good oral bioavailabilityGood oral bioavailability Extremely low costExtremely low cost

Conversion to Conversion to MethadoneMethadone

Daily oral morphine doseequivalents

Conversion ratio of oralmorphine to methadone

< 100mg 3:1 (ie. 3mg morphine:1mgmethadone)

101-300mg 5:1

301-600mg 10:1

601-800mg 12:1

801-1000mg 15:1

> 1000mg 20:1

Interesting Case: 65yr old Interesting Case: 65yr old Anesthesiologist with Diabetic Anesthesiologist with Diabetic

Peripheral neuropathyPeripheral neuropathy

Mr. C. has stocking-glove distribution Mr. C. has stocking-glove distribution neuropathy. He had excruciating pain neuropathy. He had excruciating pain (10/10) while on Norco (10/325mg) 6-8 (10/10) while on Norco (10/325mg) 6-8 per day.per day.

Neurontin was not well toleratedNeurontin was not well tolerated Elavil was contraindicated due to cardiac Elavil was contraindicated due to cardiac

history and conduction system disorderhistory and conduction system disorder Mr. C. was depressed and didn’t think life Mr. C. was depressed and didn’t think life

was worth living with this painwas worth living with this pain

Neuropathic pain due to Neuropathic pain due to DiabetesDiabetes

After discussion with patient and family, After discussion with patient and family, we initiated a course of Methadonewe initiated a course of Methadone

His current dose of Hydrocodone was His current dose of Hydrocodone was 60-80mg daily or the equivalent of 60-60-80mg daily or the equivalent of 60-80mg morphine80mg morphine

My conversion with Methadone at low My conversion with Methadone at low dose morphine is 5:1dose morphine is 5:1

I started Mr. C on Methadone 5 mg q 8 I started Mr. C on Methadone 5 mg q 8 ATC with 2.5mg q 3 hours prnATC with 2.5mg q 3 hours prn

Methadone for Methadone for neuropathic painneuropathic pain

Patient tolerated Methadone wellPatient tolerated Methadone well Within 24 hours his 10/10 pain was Within 24 hours his 10/10 pain was

rated at 3/10rated at 3/10 Within 1 week, his pain was gone Within 1 week, his pain was gone

(0/10); (0/10); Precaution using MethadonePrecaution using Methadone: Slow : Slow

accumulation, varied half-life, needs to accumulation, varied half-life, needs to be adjusted upward slowly (about q 7 be adjusted upward slowly (about q 7 days)days)