METHADONE

MELLAR DAVIS, WAEL LASHEEN, DECLAN WALSH

2

SYNTHETIC PSEUDOPIPERDINE DEVELOPED

OVER 50 YEARS AGO

DISTINCTLY DIFFERENT FROM ALKALOID OPIOIDS

(MORPHINE) (CODEINE) AND SYNTHETIC

THEBAINE DERIVATIVES (OXYCODONE)

METHADONE

3

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 N-

METHYL-D-ASPARTATE RECEPTORS

TWICE THE INTRINSIC EFFICACY OF MORPHINE

METHADONE

4

DELTA OPIOID RECEPTOR AGONIST (R AND S)

SEROTONIN AND NOREPINEPHRINE REUPTAKE

INHIBITOR (R AND S)

HIGH DOSES BLOCK POTASSIUM CHANNELS

METHADONE

5

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 INTER-

INDIVIDUAL DIFFERENCES IN KINETICS

ABSORPTION

6

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

ABSORPTION

7

SIMILAR ABSORPTION AND BIOAVAILABILITY AS

ORAL METHADONE

MICROENEMAS > HYDROGENATED OIL BASE

SUPPOSITORIES

RECTAL METHADONE

8

ABSORPTION IS 34% (51% FENTANYL AND 18%

MORPHINE)

BUFFERING THE PH TO 8.5 DOUBLES

ABSORPTION (75%)

SUBLINGUAL METHADONE

9

BIEXPONENTIAL KINETICS

EXTRACTION RATIO 0.08 - 0.16

DEMETHYLATED TO AN INACTIVE METABOLITE

(EDDP) BY CYP3A4

INDUCTION OF CYP3A4 BY METHADONE WITH

CHRONIC DOSING

METABOLISM

10

CYP3A4 > CYP2D6, CYP1A2, CYP2C9, CYP2C19

ULTRARAPID METABOLIZERS HAVE HALF THE

METHADONE DRUG LEVELS AS POOR

METABOLIZERS (HOMOZYGOTE CYP2D6

MUTATIONS)

CYTOCHROME ENZYMES

11

METHADONE CLEARANCE CAN VARY BETWEEN

INDIVIDUALS 100-FOLD (0.023 - 2.1 LITERS PER

MINUTE) WITH A MEAN OF 0.095 LITERS PER

MINUTE

METHADONE CLEARANCE

12

MU OPIOID RECEPTOR GENETICS

P-GLYCOPROTEIN ACTIVITY

CYP3A4 BASAL AND INDUCTION ACTIVITY

CYP2D6, CYP1A2, CYP2C9, CYP2C19

GENOTYPE OF ALPHA1 ACID GLYCOPROTEIN

CO-MEDICATIONS

CAUSES OF INTERINDIVIDUAL DIFFERENCES IN METHADONE

13

ORAL

SUBLINGUAL (1:1)

RECTAL (1:1)

SUBCUTANEOUS (2:1)

INTRAVENOUS (2:1)

ROUTES

14

RIFAMBUTIN (FOR RIFAMPICIN)

FAMOTIDINE (FOR CIMETIDINE)

MIRTAZAPINE (FOR SSRI)

HALOPERIDOL OR OLANZAPINE (FOR

RESPERIDONE)

VALPROIC ACID, GABAPENTIN (FOR

PHENOBARBITOL, PHENYTOIN, CARBAMAZEPINE)

SAFE COMBINATIONS

15

SIMILAR TO OTHER OPIOIDS

REDUCED CONSTIPATION COMPARED TO

MORPHINE

TORSADES DE POINTES AND PROLONGED QTC

WITH INCREASED RISK PARTICULAR WITH

PARENTERAL

METHADONE TOXICITY

16

MORE COMMON WITH INITIAL THERAPY

DEATHS AT STEADY STATE ARE RELATED TO:

INTERFERING CO-MEDICATION

ILLICIT DRUG TAKING (DIAZEPAM, ALCOHOL, COCAINE,

CANNABIS, OTHER OPIOIDS)

DEATH FROM METHADONE

17

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.

METHADONE AND CANCER PAIN

18

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

METHADONE AND CANCER PAIN

19

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

EQUIVALENTS AND DOSING

20

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

EQUIVALENTS AND DOSING

21

SHOULD BE DONE BY SOMEONE WITH

EXPERIENCE

DO NOT ADD BENZODIAZEPINES DURING

TITRATION, AVOID ALCOHOL

USE ACETOMINOPHEN IF PAIN RECURS BEFORE

THREE HOURS

METHADONE DOSING

22

HYDROMORPHONE

PARENTERAL HYDROMORPHONE TO ORAL METHADONE

1.07 + 0.9

FENTANYL

FENTANYL 25µG TO 0.1MG PARENTERAL METHADONE

EQUIVALENTS WITH OTHER OPIOIDS

23

DOSE RATIOS BETWEEN MORPHINE AND

METHADONE ARE NOT DEPENDENT UPON THE TYPE

OF PAIN

GROND S. PAIN 1999

GAGNON B. JPSM 1999

NEUROPATHIC PAIN

24

REFRACTORY PAIN

PATIENTS ON HIGH DOSE OPIOIDS WITH

BURDENSOME COSTS

PATIENTS WITH LIMITED FINANCES

HOSPICES

NEUROPATHIC PAIN

CHEAP SUSTAINED RELEASE OPIOID

CANDIDATES FOR METHADONE

Ripamonte C. Pain 1997

25

METHADONE

PROS

1) LACK OF ACTIVE METABOLITES

2) SAFETY IN ORGAN FAILURE

3) HIGH LIPID SOLUBILITY

4) HIGH BIOAVAILABILITY

5) VERSATILITY

6) LOW COST

CONS

1) UNPREDICTABLE AND LONG HALF-LIFE

2) INTERINDIVIDUAL VARIABILITY

3) CHANGING EQUIANALGESIC POTENCY WITH DOSE

26

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

SUMMARY

27

28

METHADONE AND CARDIAC

TOXICITY

29

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)

INTRODUCTION

30

DELAYED REPOLARIZATION LEADS TO

PROLONGED QTC INTERVALS (>500 MSEC) AND

VENTRICULAR TACHYCARDIA (TDP)

ALSO INTERLEAD VARIATION BETWEEN QTC

INTERVALS ON SURFACE LEADS

INTRODUCTION

31

32

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

SUMMARY OF ORAL METHADONE AND QTc

33

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

RECOMMENDATIONS

34

DOSE REDUCE, ADD ADJUVANT

DELETE MEDICATIONS WHICH PROLONG QTC OR

BLOCK CYTOCHROMES

ROTATE TO MORPHINE OR BUPRENORPHINE OR

FENTANYL

MANAGEMENT OF PROLONGED QTc METHADONE

35

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

IV METHADONE AND QTc

36

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

FDA BLACK BOX WARNING

37

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

SUMMARY

38

PATIENT CONTROLLED

ANALGESIA (PCA)

MELLAR DAVIS, WAEL LASHEEN, DECLAN WALSH

39

CONCEPT

INTER-INDIVIDUAL VARIABILITY

OPTIMIZE OPIOID ADMINISTRATION

IMMEDIATE ACCESS

ON DEMAND > CONVENTIONAL DOSING

BACKGROUND

40

FIRST PCA PUMP 1976

MODALITIES

DEMAND ONLY

CONTINUOUS INFUSION + DEMAND

INFUSION RATE BASED ON DEMAND

VARIABLE RATE

VARIABLE RATE FEEDBACK

PCA MODALITIES

41

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

42

PCA ROUTES OF DELIVERY

INTRAVENOUS

SUBCUTANEOUS

INTRAMUSCULAR

ORAL,NASAL,SUBLINGUAL

SPINAL, VENTRICULAR

OTHERS...

43

PCA STRATEGY

• LOADING DOSE

• DEMAND DOSE

• LOCKOUT INTERVAL

• CONTINUOUS INFUSION

• DOSE LIMITS

44

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

PCA ADVANTAGES

45

PATIENT RISK FACTORS

AGE

HEAD INJURY

SLEEP APNEA

OBESITY

RESPIRATORY FAILURE

BENZODIAZEPINES

HYPONATREMIA

RENAL FAILURE

46

COMPLICATIONS

OPERATOR ERRORS

PROGRAMMING ERRORS

ACCIDENTAL BOLUS

INAPPROPRIATE

DOSE

LOCKOUT

DRUG SELECTION

SURROGATE ACTIVATION

PUMP MALFUNCTION

47

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

PATIENT SELECTION

48

INCIDENT PAIN

KIDNEY FAILURE (DEMAND ONLY)

EXCESSIVE SIDE EFFECTS (N&V, SEDATION)

INTESTINAL OBSTRUCTION

IMPAIRED ORAL INTAKE

CIRCARDIAN VARIATION IN PAIN INTENSITY

INITIAL TITRATION

PCA IN CANCER MAYBE USED IN:

49

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

PCA DOSING (INTRODUCTION)

50

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

PCA DOSING IN CANCER

51

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

POST-OP DOSING (ON OPIOID)

52

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

POST-OP DOSING (OPIOID NAIVE)

53

RARELY STUDIED

PCA SEEMS USEFUL AND SAFE

COMPLICATION RATES UNKNOWN

OPTIMAL DOSING AND LOCKOUT UNKNOWN

CONCLUSION: PCA IN CANCER

54

PERIOPERATIVE

MANAGEMENT OF

CHRONIC PAIN PATIENTS

55

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

INTRODUCTION

Turk, DC 2001

56

MODERATE TO SEVERE PAIN IN 20-30%

CARDIOPULMONARY COMPLICATIONS

UNEXPECTED ADMISSIONS FROM AMB. SURGERY

PROLONGED CONVALESCENCE

SIGNIFICANCE OF POST-OP PAIN.

57

POORER PAIN CONTROL

INCREASED OPIOID REQUIREMENTS

3X EPIDURAL MORPHINE THAN OPIOID-NAÏVE

4X MORPHINE BY INTERMITTENT BOLUS

POSTOPERATIVE PCA DOSES > REPLACEMENT

POST-OP PAIN IN OPIOID TOLERANT.

58

PROGRESSIVE CANCER

TOLERANCE

OPIOID-INDUCED HYPERALGESIA

INCREASED PAIN SENSITIVITY

CAUSES OF INCREASED POSTOPERATIVE PAIN AND OPIOID REQUIREMENTS IN OPIOID-TOLERANT.

59

↓ NAUSEA & PRURITUS IN OPIOID-TOLERANT

DIFFERENCES IN SIDE EFFECTS BETWEEN OPIOID-NAÏVE AND TOLERANT INDIVIDUALS

DELEON CASASOLA 1993

RAPP 1995

60

MINIMAL EFFECTIVE OPIOID DOSE IS UNKNOWN

POSTOPERATIVE OPIOID > ANTICIPATED

ADEQUATE OPIOIDS TO AVOID WITHDRAWAL

TRANSITION TO PREOPERATIVE OPIOID DOSES

CHALLENGING AND OFTEN DELAYED

OPTIMIZING PERIOPERATIVE OPIOIDS USE IN OPIOID-TOLERANT

61

EPIDURALS

REGIONAL BLOCKS

DISCONTINUE NSAIDS 48 HRS BEFORE EPIDURAL

OPIOID DOSE MAINTAINED ON DAY OF SURGERY

PLAN PERIOPERATIVE MANAGEMENT

62

EXPECT OPIOID REQUIREMENTS 2-4 X NAÏVE

INDIVIDUALS

START PCA

ORAL ROUTE: 1.5X PREOPERATIVE ORAL OPIOID

DOSE PLUS DEMAND ONLY FOR RESCUE DOSES

ACUTE POSTOPERATIVE MANAGEMENT .

63

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)

64

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

MANAGEMENT POSTOPERATIVE TRANSITION PHASE

65

66

MAINTENANCE OPIOIDS (BUPRENORPHINE ,

METHADONE) PROVIDES ADEQUATE ANALGESIA

POSTOPERATIVE

USE OF SHORT ACTING OPIOIDS IN THE

POSTOPERATIVE PERIOD INCREASES RISK OF

ADDICTION RELAPSE

PERIOPERATIVE MANAGEMENT OF ADDICTION: MISCONCEPTIONS

67

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

68

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

ISSUES PARTICULAR TO ADDICTION

69

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

MANAGEMENT

70

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

MANAGEMENT

71

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

MANAGEMENT BUPRENORPHINE MAINTENANCE

72

MANAGEMENT BUPRENORPHINE MAINTENANCE

CONVERT TO 20-40MG METHADONE DAILY

AND USE SHORT ACTING OPIOIDS FOR PAIN

CONVERT BACK TO BUPRENORPHINE AT

DISCHARGE

73

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.

REFERENCES

74

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

75

CASE 1

• ECG QTC 450MSEC

• LABORATORY:CREATININE 1.8, NORMAL BILIRUBIN

76

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

77

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.

78

CASE 1

• REPEAT ECG QTC 460 MSEC

• IV HYDRATION IS STARTED

79

CASE 1:TREATMENT

• STOP METHADONE AND START FENTANYL OR BUPRENORPHINE

• START METHADONE IV AT 0.5MG PER HOUR WITH 0.5-1MG 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

80

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

81

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 0.8-1MG 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