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)
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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
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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
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SUBLINGUAL METHADONE
ABSORPTION IS 34% (51% FENTANYL AND 18%
MORPHINE)
BUFFERING THE PH TO 8.5 DOUBLES
ABSORPTION (75%)
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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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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
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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
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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
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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
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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
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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
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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
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.
CAUSES OF INCREASED
POSTOPERATIVE PAIN AND OPIOID
REQUIREMENTS IN OPIOIDTOLERANT
.
PROGRESSIVE CANCER
TOLERANCE
OPIOID-INDUCED HYPERALGESIA
INCREASED PAIN SENSITIVITY
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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
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PLAN PERIOPERATIVE
MANAGEMENT
EPIDURALS
REGIONAL BLOCKS
DISCONTINUE NSAIDS 48 HRS BEFORE EPIDURAL
OPIOID DOSE MAINTAINED ON DAY OF SURGERY
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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
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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)
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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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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
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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
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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
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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
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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
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MANAGEMENT BUPRENORPHINE
MAINTENANCE
CONVERT TO 20-40MG METHADONE DAILY
AND USE SHORT ACTING OPIOIDS FOR PAIN
CONVERT BACK TO BUPRENORPHINE AT
DISCHARGE
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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.
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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
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CASE 1
• ECG QTC 450MSEC
• LABORATORY:CREATININE 1.8, NORMAL
BILIRUBIN
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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
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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.
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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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