Transcript Slide 1

METHADONE
MELLAR DAVIS, WAEL LASHEEN, DECLAN WALSH
METHADONE
 SYNTHETIC PSEUDOPIPERDINE DEVELOPED
OVER 50 YEARS AGO
 DISTINCTLY DIFFERENT FROM ALKALOID OPIOIDS
(MORPHINE) (CODEINE) AND SYNTHETIC
THEBAINE DERIVATIVES (OXYCODONE)
2
METHADONE
R (L) AND S (D) ENANTIOMER
 R ENANTIOMER BINDS WITH SIMILAR AFFINITY TO
MU RECEPTORS AS MORPHINE (KM 3.5NM AND
1.4NM RESPECTIVELY)
 BOTH R AND S ENANTIOMERS BIND TO NMETHYL-D-ASPARTATE RECEPTORS
 TWICE THE INTRINSIC EFFICACY OF MORPHINE
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METHADONE
 DELTA OPIOID RECEPTOR AGONIST (R AND S)
 SEROTONIN AND NOREPINEPHRINE REUPTAKE
INHIBITOR (R AND S)
 HIGH DOSES BLOCK POTASSIUM CHANNELS
4
ABSORPTION
 ABSORPTION RAPID AND COMPLETE (47 - 91%)
 DRUG LEVELS CAN BE MEASURED 30 MINUTES
AFTER ORAL DOSING, PEAK CONCENTRATIONS
OCCUR AT 2.5 HOURS
 INTESTINAL CYP3A4 AND P-GLYCOPROTEIN MAY
REDUCE ABSORPTION
 NOT A MAJOR FACTOR IN THE LARGE INTERINDIVIDUAL DIFFERENCES IN KINETICS
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ABSORPTION
 PKA IS 9.2 (BETTER ABSORBED IN AN ALKALINE
ENVIRONMENT)
 REDUCED ACIDITY (OMEPRAZOLE) INCREASES
ABSORPTION
 NON-SATURABLE KINETICS
 PRESYSTEMIC CLEARANCE (ABSORPTION AND
BIOAVAILABILITY) IS 21%
 UNALTERED BY DIET
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RECTAL METHADONE
 SIMILAR ABSORPTION AND BIOAVAILABILITY AS
ORAL METHADONE
 MICROENEMAS > HYDROGENATED OIL BASE
SUPPOSITORIES
7
SUBLINGUAL METHADONE
 ABSORPTION IS 34% (51% FENTANYL AND 18%
MORPHINE)
 BUFFERING THE PH TO 8.5 DOUBLES
ABSORPTION (75%)
8
METABOLISM
 BIEXPONENTIAL KINETICS
 EXTRACTION RATIO 0.08 - 0.16
 DEMETHYLATED TO AN INACTIVE METABOLITE
(EDDP) BY CYP3A4
 INDUCTION OF CYP3A4 BY METHADONE WITH
CHRONIC DOSING
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CYTOCHROME ENZYMES
 CYP3A4 > CYP2D6, CYP1A2, CYP2C9, CYP2C19
 ULTRARAPID METABOLIZERS HAVE HALF THE
METHADONE DRUG LEVELS AS POOR
METABOLIZERS (HOMOZYGOTE CYP2D6
MUTATIONS)
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METHADONE CLEARANCE
 METHADONE CLEARANCE CAN VARY BETWEEN
INDIVIDUALS 100-FOLD (0.023 - 2.1 LITERS PER
MINUTE) WITH A MEAN OF 0.095 LITERS PER
MINUTE
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CAUSES OF INTERINDIVIDUAL
DIFFERENCES IN METHADONE
 MU OPIOID RECEPTOR GENETICS
 P-GLYCOPROTEIN ACTIVITY
 CYP3A4 BASAL AND INDUCTION ACTIVITY
 CYP2D6, CYP1A2, CYP2C9, CYP2C19
 GENOTYPE OF ALPHA1 ACID GLYCOPROTEIN
 CO-MEDICATIONS
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ROUTES
 ORAL
 SUBLINGUAL (1:1)
 RECTAL (1:1)
 SUBCUTANEOUS (2:1)
 INTRAVENOUS (2:1)
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SAFE COMBINATIONS
 RIFAMBUTIN (FOR RIFAMPICIN)
 FAMOTIDINE (FOR CIMETIDINE)
 MIRTAZAPINE (FOR SSRI)
 HALOPERIDOL OR OLANZAPINE (FOR
RESPERIDONE)
 VALPROIC ACID, GABAPENTIN (FOR
PHENOBARBITOL, PHENYTOIN, CARBAMAZEPINE)
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METHADONE TOXICITY
 SIMILAR TO OTHER OPIOIDS
 REDUCED CONSTIPATION COMPARED TO
MORPHINE
 TORSADES DE POINTES AND PROLONGED QTC
WITH INCREASED RISK PARTICULAR WITH
PARENTERAL
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DEATH FROM METHADONE
 MORE COMMON WITH INITIAL THERAPY
 DEATHS AT STEADY STATE ARE RELATED TO:
 INTERFERING CO-MEDICATION
 ILLICIT DRUG TAKING (DIAZEPAM, ALCOHOL, COCAINE,
CANNABIS, OTHER OPIOIDS)
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METHADONE AND CANCER PAIN
 THE ORIGINAL MANUFACTURER’S
RECOMMENDATION OF 2.5 - 10MG EVERY 3 - 4
HOURS IS EXCESSIVE.
 EQUIANALGESIA TABLES THAT PUT
EQUIVALENTS NEAR UNITY WITH MORPHINE ARE
DANGEROUS.
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METHADONE AND CANCER PAIN
 METHODS OF OPIOID ROTATION INVOLVE A
“STOP-START” STRATEGY
 A Q 3-HOUR AS NEEDED SCHEDULE
 LINEAR RATIO BASED UPON MORPHINE EQUIVALENTS
EVERY 8 HOURS ATC
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EQUIVALENTS AND DOSING
 MORPHINE:METHADONE
 4:1 < 90MG MORPHINE DAILY
 8:1 90 - 300MG MORPHINE DAILY
 12:1 300 - 1000MG MORPHINE DAILY
 20:1 > 1000MG MORPHINE DAILY
 DIVIDE DOSE INTO 3 AND GIVE EVERY 8 HOURS
 OPIOID NAÏVE; 3 - 5MG EVERY 8 HOURS OR 7.5MG
EVERY 12 HOURS
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EQUIVALENTS AND DOSING
 STOP-START
 USE 10% OF TOTAL MORPHINE (OR MORPHINE
EQUIVALENTS) UP TO A SINGLE MAXIMUM DOSE OF 30MG
METHADONE
 DOSE EVERY 3 HOURS AS NEEDED
 STEADY STATE OCCURS AT DAY 4 AND 5
 TOTAL DOSES ON DAY 4 AND 5, DIVIDE BY 4 AND GIVE
EVERY 12 HOURS
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METHADONE DOSING
 SHOULD BE DONE BY SOMEONE WITH
EXPERIENCE
 DO NOT ADD BENZODIAZEPINES DURING
TITRATION, AVOID ALCOHOL
 USE ACETOMINOPHEN IF PAIN RECURS BEFORE
THREE HOURS
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EQUIVALENTS WITH OTHER OPIOIDS
 HYDROMORPHONE
 PARENTERAL HYDROMORPHONE TO ORAL METHADONE
1.07 + 0.9
 FENTANYL
 FENTANYL 25µG TO 0.1MG PARENTERAL METHADONE
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NEUROPATHIC PAIN
 DOSE RATIOS BETWEEN MORPHINE AND
METHADONE ARE NOT DEPENDENT UPON THE
TYPE OF PAIN
GROND S. PAIN 1999
GAGNON B. JPSM 1999
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CANDIDATES FOR METHADONE
 REFRACTORY PAIN
 PATIENTS ON HIGH DOSE OPIOIDS WITH
BURDENSOME COSTS
 PATIENTS WITH LIMITED FINANCES
 HOSPICES
 NEUROPATHIC PAIN
 CHEAP SUSTAINED RELEASE OPIOID
Ripamonte C. Pain 1997
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METHADONE
PROS
CONS
1) LACK OF ACTIVE
METABOLITES
1) UNPREDICTABLE AND
LONG HALF-LIFE
2) SAFETY IN ORGAN
FAILURE
2) INTERINDIVIDUAL
VARIABILITY
3) HIGH LIPID SOLUBILITY
3) CHANGING
EQUIANALGESIC
POTENCY WITH DOSE
4) HIGH BIOAVAILABILITY
5) VERSATILITY
6) LOW COST
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SUMMARY
 METHADONE IS UNIQUE PHARMACOLOGICALLY
 MULITPLE RECEPTOR AGONIST, NMDA
ANTAGONISTS AND MONOAMINE REUPTAKE
INHIBITORS
 RELATIVELY SAFE IN ORGAN FAILURE
 DOSING SCHEMES ARE DIFFERENT THAN WITH
OTHER OPIOIDS
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27
METHADONE AND CARDIAC
TOXICITY
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INTRODUCTION
 METHADONE HAS BEEN ASSOCIATED WITH
PROLONGED QTC AND TORSADES DE POINTES
(TDP)
 UNIQUE BLOCK OF IONIC CURRENT THROUGH
SPECIFIC TYPE CARDIAC K+ CHANNELS
 CARDIAC K+ CHANNELS ARE DERIVED FROM
HUMAN ETHER-A-GO-GO-RELATED GENE (HERG)
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INTRODUCTION
 DELAYED REPOLARIZATION LEADS TO
PROLONGED QTC INTERVALS (>500 MSEC) AND
VENTRICULAR TACHYCARDIA (TDP)
 ALSO INTERLEAD VARIATION BETWEEN QTC
INTERVALS ON SURFACE LEADS
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SUMMARY OF ORAL METHADONE
AND QTc
 METHADONE INCREASES QTC IN 30%
 QTC > 500 MSEC RANGE 0 – 16% (5%)
 POOR CORRELATION WITH DOSE
 MAY BE ASSOCIATION WITH HYPOKALEMIA,
STRUCTURAL HEART DISEASE, LIVER DISEASE
AND DRUGS THAT INHIBIT CYTOCHROMES OR
PROLONG QTC
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RECOMMENDATIONS
 NO MONITORING FOR LOW RISK INDIVIDUALS
 AT RISK INDIVIDUALS, BASELINE ECG REPEAT IF:
 BASELINE QTC > 430 M SEC
 HIGH DOSE SYMPTOMS (SYNCOPE, PALPITATION, DYSPNEA)
 CO-MEDICATIONS THAT PROLONG QTC
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MANAGEMENT OF PROLONGED
QTc METHADONE
 DOSE REDUCE, ADD ADJUVANT
 DELETE MEDICATIONS WHICH PROLONG QTC OR
BLOCK CYTOCHROMES
 ROTATE TO MORPHINE OR BUPRENORPHINE OR
FENTANYL
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IV METHADONE AND QTc
 TOXICITY CAN OCCUR AT LOW DOSES (0.4 MG/H)
 BASELINE ECG AND REPEAT 24 – 72 HOURS
 MONITOR K+
 AVOID DRUGS THAT PROLONG QTC
 OPTIONS IF QTC >500 MSEC




SWITCH TO ORAL METHADONE
DELETE CO-MEDICATIONS THAT PROLONG QTC
DOSE REDUCE/ADD AN ADJUVANT
ROTATE TO MORPHINE, BUPRENORPHINE
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FDA BLACK BOX WARNING

DEATHS: UNINTENTIONAL OVERDOSE, DRUG
INTERACTIONS, AND CARDIAC TOXICITY (QT
PROLONGATION AND TDP)
 PHYSICIAN’S NEED TO UNDERSTAND TOXICITY
AND UNIQUE METHADONE PROPERTIES
 DOSES SHOULD BE CAREFULLY CHOSEN AND
SLOWLY TITRATED
 CAREFULLY MONITOR WHEN SWITCHING TO
METHADONE AND CHANGING DOSE
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SUMMARY
 LOW RISK WITH ORAL METHADONE
 AT RISK INDIVIDUALS REQUIRE MONITORING
 RISK GREATER WITH PARENTERAL METHADONE
DUE TO CHLOROBUTANOL
 PARENTERAL METHADONE REQUIRES ROUTINE
ECG MONITORING
 RISK AND BENEFITS OF METHADONE MUST BE
WEIGHED IF NO OTHER TREATMENT OPTIONS
ARE AVAILABLE IN TERMINAL PATIENTS
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PATIENT CONTROLLED
ANALGESIA (PCA)
MELLAR DAVIS, WAEL LASHEEN, DECLAN WALSH
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BACKGROUND
 CONCEPT
 INTER-INDIVIDUAL VARIABILITY
 OPTIMIZE OPIOID ADMINISTRATION
 IMMEDIATE ACCESS
 ON DEMAND > CONVENTIONAL DOSING
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PCA MODALITIES
 FIRST PCA PUMP 1976
 MODALITIES
 DEMAND ONLY
 CONTINUOUS INFUSION + DEMAND
 INFUSION RATE BASED ON DEMAND
 VARIABLE RATE
 VARIABLE RATE FEEDBACK
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PCA SETUP: DRUG CHOICE
 OPIOIDS
 ALL OPIOIDS
 SHORT ACTING ARE SAFER THAN LONG ACTING
 NON-OPIOIDS
 MOST COMPATIBLE WITH OPIOIDS
• ATROPINE, DEXAMETH, DIAZEPAM,
LORAZEPAM, KETEROLAC, HALDOL,
LEVOPROME, METOCHLOPRAMIDE
 PHYENYTOIN IS NOT COMPATIBLE WITH OPIOIDS
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PCA ROUTES OF DELIVERY
 INTRAVENOUS
 SUBCUTANEOUS
 INTRAMUSCULAR
 ORAL,NASAL,SUBLINGUAL
 SPINAL, VENTRICULAR
 OTHERS...
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PCA STRATEGY
• LOADING DOSE
•
•
•
•
DEMAND DOSE
LOCKOUT INTERVAL
CONTINUOUS INFUSION
DOSE LIMITS
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PCA ADVANTAGES
 PATIENT
 REMOVES DELAY DEMAND / DELIVERY
 PATIENT CONTROL / SECURITY
 DETERMINE PAIN THRESHOLDS
 DOSING
 ASSESS ANALGESIC REQUIREMENTS
 INFLUENCES TRADITIONAL DOSING PROTOCOLS
 ADAPTABLE
 INTERINDIVIDUAL REQUIREMENTS
 TEMPORAL PAIN PATTERN
44
PATIENT RISK FACTORS
 AGE
 HEAD INJURY
 SLEEP APNEA
 OBESITY
 RESPIRATORY FAILURE
 BENZODIAZEPINES
 HYPONATREMIA
 RENAL FAILURE
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COMPLICATIONS
 OPERATOR ERRORS
 PROGRAMMING ERRORS
 ACCIDENTAL BOLUS
 INAPPROPRIATE
DOSE
LOCKOUT
DRUG SELECTION
 SURROGATE ACTIVATION
 PUMP MALFUNCTION
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PATIENT SELECTION
 AGE = > 5 YRS
 COGNITIVE ABILITY
 UNDERSTAND THE RELATIONSHIPS BETWEEN PAIN,
ACTIVATING THE PUMP, AND GOALS OF PAIN RELIEF
 INTACT MEMORY
 PHYSICAL ABILITY TO ACTIVATE THE BUTTON
 PSYCHOLOGICAL: NEED TO MAINTAIN CONTROL
 EXTREME FEAR OF SIDE EFFECTS
 PRESENCE OF A RELIABLE SURROGATE
47
PCA IN CANCER MAYBE USED IN:
 INCIDENT PAIN
 KIDNEY FAILURE (DEMAND ONLY)
 EXCESSIVE SIDE EFFECTS (N&V, SEDATION)
 INTESTINAL OBSTRUCTION
 IMPAIRED ORAL INTAKE
 CIRCARDIAN VARIATION IN PAIN INTENSITY
 INITIAL TITRATION
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PCA DOSING (INTRODUCTION)
 LOADING DOSE
 DEMAND DOSING & CONTINUOUS INFUSION(CI)
 A DOSE SHOULD RESULT IN PERCEPTIBLE ANALGESIA
 TITRATION
 LOCKOUT INTERVAL
 PHARMACOKINETICS / DYNAMICS, CNS DWELL TIME
 LONG ENOUGH FOR THE PATIENT TO EXPERIENCE BENEFIT
 LONGER IF CONCOMITTENT CONTINUOUS INFUSION
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PCA DOSING IN CANCER
 OPIOID NAIVE: 0.5MG/H CI , DEMAND 1MG Q2H
 OPOID TOLERANT: THE HOURLY MORPHINE DOSE
Q2HRS, RARELY Q1HR
 RATIONALE LONG CNS DWELL TIME
 DEMAND DOSE IS TITRATED TO BREAKTHROUGH
PAIN SEVERITY AND DURATION
50
POST-OP DOSING (ON OPIOID)
 MORPHINE LOADING TO EFFECTIVE ANALGESIA:
 2-5MG Q 10 MINUTES
 DEMAND DOSE
 USE 50 -75% OF LOADING DOSE
 CONTINUOUS INFUSION:
 PRE-OPERATIVE DOSE
 >50% PRE-OP DOSE TO AVOID WITHDRAWAL
 HOURLY OPIOID REQUIREMENT:
 75% BY CI
 25% BY DEMAND
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POST-OP DOSING (OPIOID NAIVE)
PCA OPIOID
DEMAND LOCKOUT
CI
MORPHINE
1-2MG
6-10
0-2MG/H
HYDROMOR
0.2-0.4MG
6-10
0-0.4MG/H
FENTANYL
20-40MCG
5-10
0-60MCG/H
SUFENTANIL
4-6MCG
5-10
0-8MCG/H
TRAMADOL
10-20MG
6-10
0-20MG/H
52
CONCLUSION: PCA IN CANCER
 RARELY STUDIED
 PCA SEEMS USEFUL AND SAFE
 COMPLICATION RATES UNKNOWN
 OPTIMAL DOSING AND LOCKOUT UNKNOWN
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PERIOPERATIVE
MANAGEMENT OF
CHRONIC PAIN PATIENTS
54
INTRODUCTION

CHRONIC PAIN
 “PAIN WITHOUT APPARENT BIOLOGIC VALUE WHICH
PERSISTS BEYOND NORMAL TISSUE HEALING TIME”
(3 MONTHS)
 PATHOLOGY DOES NOT EXPLAIN PAIN PRESENCE OR
EXTENT
 10-55% IN NORMAL POPULATION
 > 50% IN ADVANCED CANCER
Turk, DC 2001
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SIGNIFICANCE OF POST-OP PAIN
.
 MODERATE TO SEVERE PAIN IN 20-30%
 CARDIOPULMONARY COMPLICATIONS
 UNEXPECTED ADMISSIONS FROM AMB. SURGERY
 PROLONGED CONVALESCENCE
56
POST-OP PAIN IN OPIOID TOLERANT
 POORER PAIN CONTROL
 INCREASED OPIOID REQUIREMENTS

3X EPIDURAL MORPHINE THAN OPIOID-NAÏVE

4X MORPHINE BY INTERMITTENT BOLUS

POSTOPERATIVE PCA DOSES > REPLACEMENT
57
.
CAUSES OF INCREASED
POSTOPERATIVE PAIN AND OPIOID
REQUIREMENTS IN OPIOIDTOLERANT
.

PROGRESSIVE CANCER

TOLERANCE

OPIOID-INDUCED HYPERALGESIA
 INCREASED PAIN SENSITIVITY
58
DIFFERENCES IN SIDE EFFECTS
BETWEEN OPIOID-NAÏVE AND
TOLERANT INDIVIDUALS
 ↓ NAUSEA & PRURITUS IN OPIOID-TOLERANT
DELEON CASASOLA 1993
RAPP 1995
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OPTIMIZING PERIOPERATIVE
OPIOIDS USE IN OPIOID-TOLERANT
 MINIMAL EFFECTIVE OPIOID DOSE IS UNKNOWN
 POSTOPERATIVE OPIOID > ANTICIPATED
 ADEQUATE OPIOIDS TO AVOID WITHDRAWAL
 TRANSITION TO PREOPERATIVE OPIOID DOSES
CHALLENGING AND OFTEN DELAYED
60
PLAN PERIOPERATIVE
MANAGEMENT
 EPIDURALS
 REGIONAL BLOCKS
 DISCONTINUE NSAIDS 48 HRS BEFORE EPIDURAL
 OPIOID DOSE MAINTAINED ON DAY OF SURGERY
61
ACUTE POSTOPERATIVE
MANAGEMENT
.
 EXPECT OPIOID REQUIREMENTS 2-4 X NAÏVE
INDIVIDUALS
 START PCA
 ORAL ROUTE: 1.5X PREOPERATIVE ORAL OPIOID
DOSE PLUS DEMAND ONLY FOR RESCUE DOSES
62
ACUTE POSTOPERATIVE
MANAGEMENT
.
 IV ROUTE: CONTINUOUS DOSE TO MATCH
PRE-OP OPIOID REQUIREMENT + DEMAND
 REGIONAL BLOCK: PROVIDE ½ THE PRE-OP
OPIOID DOSE
 ADD ADJUNCT (ACETAMINOPHEN,
KETOROLAC, KETAMINE, GABAPENTIN)
63
MANAGEMENT POSTOPERATIVE
TRANSITION PHASE
 USE OPIOID DOSE DURING FIRST 24-48 HOURS
 DELIVER ½ AS LONG-ACTING OPIOID
 DELIVER ½ AS RESCUE EVERY 3-4 HOURS
 ADD NSAID, ACETAMINOPHEN AND TAPER OPIOID
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65
PERIOPERATIVE MANAGEMENT OF
ADDICTION: MISCONCEPTIONS
 MAINTENANCE OPIOIDS (BUPRENORPHINE ,
METHADONE) PROVIDES ADEQUATE ANALGESIA
POSTOPERATIVE
 USE OF SHORT ACTING OPIOIDS IN THE
POSTOPERATIVE PERIOD INCREASES RISK OF
ADDICTION RELAPSE
66
PERIOPERATIVE MANAGEMENT OF
ADDICTION: MISCONCEPTIONS
 ADDITIVE EFFECTS OF SHORT ACTING
OPIOIDS WITH MAINTENANCE OPIOIDS
INCREASES RESPIRATORY DEPRESSION
 REPORTING PAIN MAY BE A MANIPULATION
TO OBTAIN OPIOID ANALGESICS OR DRUG
SEEKING
67
ISSUES PARTICULAR TO
ADDICTION
 PSEUDO-ADDICTION:”DRUG SEEKING” DUE TO
INADEQUATELY CONTROLLED PAIN
 THERAPEUTIC DEPENDENCE:”DRUG SEEKING”
OUT OF FEAR OF EMERGENCE OF WITHDRAWAL
 PSEUDO-OPIOID DEPENDENCE:CONTINUED
REPORTS OF PAIN TO PREVENT CURRENTLY
EFFECTIVE DOSES OF OPIOIDS FROM BEING
REDUCED
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MANAGEMENT
 REASSURANCE THAT ADDICTION DOES NOT
PREVENT PAIN CONTROL
 CONTINUE OPIOID MAINTENANCE IN THE
PERIOPERATIVE PERIOD
 CONFIRM OPIOID TIMING AND DOSE WITH
ADDICTION SPECIALIST
 DISCUSS PAIN MANAGEMENT PLANS W/ PATIENT
69
MANAGEMENT
 SHORT ACTING OPIOIDS TO TREAT PAIN
 REQUIREMENTS MAY BE 3-4 Fold > OPIOID NAÏVE
 MAY REQUIRE SCHEDULED RATHER THAN AS
NEEDED SHORT ACTING OPIOIDS
 DO NOT STOP MAINTENANCE THERAPY
 PCA MAY BE USED BUT SHOULD BE MONITORED
70
MANAGEMENT BUPRENORPHINE
MAINTENANCE
 CONTINUE BUPRENORPHINE AND ADD SHORT
ACTING OPIOIDS
 DIVIDE & GIVE BUPRENORPHINE EVERY 6-8 HRS
 DISCONTINUE BUPRENORPHINE AND USE SHORT
ACTING OPIOIDS VIA CONTINUOUS AND DEMAND
PCA
71
MANAGEMENT BUPRENORPHINE
MAINTENANCE
 CONVERT TO 20-40MG METHADONE DAILY
AND USE SHORT ACTING OPIOIDS FOR PAIN
 CONVERT BACK TO BUPRENORPHINE AT
DISCHARGE
72
REFERENCES

Buvanendran, A. and J. S. Kroin (2007). "Useful adjuvants for postoperative pain management." Best
Pract Res Clin Anaesthesiol 21(1): 31-49.

Carroll, I. R., M. S. Angst, et al. (2004). "Management of perioperative pain in patients chronically
consuming opioids." Reg Anesth Pain Med 29(6): 576-91.

De Leon-Casasola, O. A., D. P. Myers, et al. (1993). "A comparison of postoperative epidural analgesia
between patients with chronic cancer taking high doses of oral opioids versus opioid-naive patients."
Anesth Analg 76(2): 302-7.

Kopf, A., A. Banzhaf, et al. (2005). "Perioperative management of the chronic pain patient." Best Pract
Res Clin Anaesthesiol 19(1): 59-76.

Rapp, S. E., L. B. Ready, et al. (1995). "Acute pain management in patients with prior opioid
consumption: a case-controlled retrospective review." Pain 61(2): 195-201.

Rapp, S. E., L. B. Ready, et al. (1995). "Acute pain management in patients with prior opioid
consumption: a case-controlled retrospective review." Pain 61(2): 195-201.

Tiippana, E. M., K. Hamunen, et al. (2007). "Do surgical patients benefit from perioperative
gabapentin/pregabalin? A systematic review of efficacy and safety." Anesth Analg 104(6): 1545-56.
73
CASE 1
• 48 YEAR OLD FEMALE WITH OVARIAN CANCER
AND TOXICITY AS WELL AS FOR RESPONSE TO
MORPHINE SR 60MG TWICE DAILY FOR
ABDOMINAL PAIN
• PHYSICAL EXAMINATION DEMONSTRATES
WASTING, ASCITES ,PERIUMBILICAL NODES
• MEDICATIONS:SERTRALINE 50MG,
METOPROLOL 25MG TWICE DAILY AND ORAL
STOOL SOFTENERS
74
CASE 1
• ECG QTC 450MSEC
• LABORATORY:CREATININE 1.8, NORMAL
BILIRUBIN
75
CASE 1:TREATMENT
• METHADONE SHOULD NOT BE STARTED DUE TO
THE QTC INTERVAL
• METHADONE SHOULD NOT BE USED DUE TO
INTERACTIONS WITH SERTRALINE
• METHADONE SHOULD NOT BE STARTED DUE TO
THE CREATININE
• “STOP-START” STRATEGY MAY BE USED WITH
STOPPING MORPHINE AND STARTING
METHADONE 10MG EVERY 3 HOURS AS NEEDED
76
CASE 1
• YOU START METHADONE EVERY 3 HOURS AS
NEEDED
• 6 DAYS LATER SHE IS TAKING 20MG PER DAY ON
AVERAGE WITH PAIN CONTROL.
• SHE IS DISCHARGED HOME ON METHADONE
10MG TWICE DAILY AND EVERY 3 HOURS AS
NEEDED
• TWO WEEKS LATER SHE IS ADMITTED WITH
NAUSEA AND VOMITING AND IS UNABLE TO
TAKE HER ORAL MEDICATIONS.
77
CASE 1
• REPEAT ECG QTC 460 MSEC
• IV HYDRATION IS STARTED
78
CASE 1:TREATMENT
• STOP METHADONE AND START FENTANYL OR
BUPRENORPHINE
• START METHADONE IV AT 0.5MG PER HOUR WITH 0.51MG EVERY 3 HOURS, REPEAT ECG IN 2-3 DAYS
• SWITCH TO RECTAL METHADONE 10MG EVERY 12
HOURS AND AS NEEDED
• START HALOPERIDOL FOR NAUSEA AND OBTAIN A
PLAIN X-RAY OF THE ABDOMEN
• START ONDANSETRON FOR NAUSEA AND OBTAIN A
PLAIN X-RAY OF THE ABDOMEN
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CASE 2
• 65 YEAR OLD FEMALE WITH BREAST CANCER
ON 40MG METHADONE TWICE DAILY FOR BONE
PAIN
• SHE SUSTAINS A PATHOLOGIC HIP FRACTURE
REQUIRING SURGERY
• MEDICATIONS: METHADONE , TEMAZEPAM 15MG
AT NIGHT, PRINIVIL 20MG DAILY AND LAXATIVES
• LABORATORY: NORMAL CREATININE AND
BILIRUBIN
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CASE 2 :TREATMENT
• DISCONTINUE METHADONE ON THE DAY OF SURGERY
AND USE AS NEEDED HYDROMORPHONE 2MG
HOURLY AS NEEDED
• USE METHADONE 7.5MG EVERY 3 HOURS AS NEEDED
FOR PAIN FOR POST- OP PAIN
• CONTINUE METHADONE 40MG TWICE DAILY IN THE
POST- OP PERIOD AND USE HYDROMORPHONE 0.81MG EVERY 1-2 HOURS AS NEEDED BY PCA
• START KETOROLAC 15MG IV Q 6 HOURS POST- OP
AND CONTINUE METHADONE 40MG TWICE DAILY
• AVOID COMBINING SHORT ACTING POTENT OPIOIDS
AND METHADONE. USE TRAMADOL100MG EVERY 6
HOURS WITH METHADONE
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