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DOSING STRATEGIES

MELLAR DAVIS, WAEL LASHEEN, DECLAN WALSH

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GUIDELINES

BARRIERS

HEALTHCARE PROFESSIONAL

PATIENTS

PAIN

OPIOIDS

BACKGROUND

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GUIDELINES

STEP 1

STEP 3

STEP 2

PA

IN S

EV

ER

ITYNON-OPIOID ANALGESICS

± ADJUVANT

WEAK OPIOID ANALGESICS

± NON-OPIOID ANALGESICS

± ADJUVANT

POTENT OPIOID ANALGESICS

± NON-OPIOID ANALGESICS

± ADJUVANT

WALSH ET AL SUPP. CANC. THER. 2004

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INADEQUATE ASSESSMENTS

FAILURE TO PRESCRIBE

INAPPROPRIATE OPIOID USE

HEALTHCARE PROFESSIONAL

PATIENTS UNDER-REPORT

COMPLIANCE

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LOCATION

TEMPORAL PATTERN (CP / IP)

INTENSITY

QUALITY

AGGREVAT / ALLEVIATING FACTORS

MEDICATION

IMPACT

ASSOCIATED FACTORS (ANXIETY / DEPRESSION)

PAIN HISTORY

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TEMPORAL PAIN PATTERN

Incident

Non-Incident

Mixed

Incident

Non-Incident

Mixed

EODF

Intermittent with Continuous Pain

(BP)

Continuous Pain Alone(CP)

Continuous Pain

Intermittent PainAlone(NBP)

Intermittent Pain(IP)

Cancer Pain

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PAIN PATHOPHYSIOLOGY

VISCERALSOMATIC NEUROPATHIC

CANCER PAIN

MIXED

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MORPHINE (MU AGONIST)

FENTANYL (MU AGONIST)

HYDROMORPHONE (MU AGONIST)

OXYCODONE (MU AND KAPPA AGONIST)

METHADONE (MU AND DELTA AGONIST)

OPIOID CHOICES

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ADJUVANTS AND INTERVENTIONS

ADJUVANTS INTERVENTIONS

ACETAMINOPHEN

BISPHOSPHONATES

CORTICOSTEROIDS

GABAPENTIN

NERVE BLOCK

KYPHOPLASTY

IRRIDIATION

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GUIDELINES (WHO LADDER)

BARRIERS

PAIN HISTORY

OPIOIDS

SUMMARY

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PAIN EMERGENCY

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OPIOID LOADING (OPIOID NAÏVE / EXPER.)

FREQUENT

SMALL DOSES

SHORT ACTING OPIOID

GOALS

PAIN CONTROL

TOXICITY

OPIOID LOADING

IV OPIOID LOADING

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DOSE

√ 1 MG MORPHINE

√ 0.2 MG HYDROMORPHONE

√ 20 MICGR FENTANYL

FREQUENCY

√ EVERY MINUTE X 10; RESPITE 5 MIN; REPEAT

IV OPIOID LOADING

SC AND ORAL OPIOID LOADING

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2

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IV

SC

ORAL

1MG/ 1 MIN

5MG/ 30 MIN

2 MG/ 5 MIN

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IV ROUTE IS PREFERRED

FIXED DOSE INTERVAL STRATEGY

√ 2-4 MG IV MORPHINE

√ EVERY 2 HOURS UNTIL PAIN IMPROVES

CARDIO-PULMONARY INSTABILITY

WALSH ET AL SUPP. CANC. THER. 2004

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ALTERNATIVE LOADING STRATEGY: ORAL

DOUBLE ORAL RESCUE DOSE (RD)

GIVE EVERY 30 MINS UNTIL PAIN CONTROL

PATIENT ON CHRONIC OPIOID

2 X 5MG = 10 MG

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TOTAL IV (SC) OPIOID PAST 24 HOURS

√ ATC

√ RD (FOR NON-INCIDENT PAIN)

CALCULATE THE HOURLY DOSE

LOADING

√ DOSE: 1ST 2 X HOURLY THEN HOURLY DOSE

√ FREQUENCY: EVERY 15 MINS PAIN CONTROL

ALTERNATIVE STRATEGY: IV (SC)

24 MG/ 24HRS = 1 MG

24 MG

2 MG THEN 1 MG

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ACUTE ONSET OF EXCRUCIATING PAIN OPIOID

LOADING

√ IV

√ SC

√ ORAL

SEVERELY ILL

ALTERNATE STRATEGY

SUMMARY

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OPIOID (OVERDOSE)

EMERGENCY

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INDICATIONS FOR NALOXONE:

√ PATIENT UN-RESPONSIVE

√ RR < 10 / MIN WITH EVIDENCE OF

INADEQUATE VENTILATION (LOW OXYGEN

SATURATION)

TREATMENT OF OPIOID OVERDOSE

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STOP OPIOID ADMINISTRATION

PREPARE NALOXONE:

NP

VIAL OF NALOXONE (0.4MG/ML) + 9 ML SALINE

= 40 MICG / ML NALOXONE

FLOW-CHART

PROTOCOL

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Opioids

Evaluate every 3 minutes: Responsive And RR > 10/min

Observation for at least 4 hours

1 ml NP

(40MICG)

YES

NO

START OPIOIDS AT LOWER DOSE WITH ONSET OF PAIN

Naloxone Infusion: Sum of Doses Given /

hour

Observation for at least 24 hours

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STARTING

ATC AND RD THERAPY

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OPIOID NAÏVE

IV ORAL

ATC 1 MG / 1 H 15 MG M / 12 H

RD 1 MG / 2 H 5 MG M / 4 H

RD = 5% - 15% OF 24 HR ATC DOSE

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FRAIL / ORGAN DYSFUNCTION

IV ORAL

ATC 0.5 MG / 1 H 15 MG M / 12 H

RD 0.5 MG / 2 H 5 MG M / 4 H

RD = 5% - 15% OF 24 HR ATC DOSE

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OPIOID TITRATION

FOR

CONTIUOUS PAIN (NO S/E)

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RD RDRDRDRDRD

ATC

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ASSESSMENT EVERY 24 HOURS

√ PAIN SEVERITY / RELIEF

√ DURATION OF RELIEF

√ INTERFERENCE WITH SLEEP AND ACTIVITY

√ SIDE EFFECTS

TITRATION FOR PAIN CONTROL

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NEW ATC DOSE / 24 HRS =

PAST 24 HR OPIOID DOSE + (30% TO 50%)

√ ATC PAST 24 HOURS

√ RD (FOR NON-INCIDENT PAIN) PAST 24H

ATC DOSE TITRATION

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PAST 24 HOURS

√ ATC M = 40MG

√ RD M = 5 MG (5MG X 6 = 30 MG)

√ TOTAL = ATC + RD = 40 + 30 = 70 MG

EXAMPLE

NEW ATC DOSE

(30% TO 50%) = (21 TO 35) 30 MG

NEW ATC / 24HRS = 70 + 30 = 100MG / 24

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OPIOID TITRATION

INCIDENT AND

NON-INCIDENT PAIN

(NO S/E)

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MILD SEDATION

NAUSEA

VOMITING

CONSTIPATION / DRY MOUTH / URINE RETENTION

VISUAL / TACTILE HALLUCINATIONS

MANIFESTATIONS

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RD RD

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NEW RD

√ IF OLD RD < 50% RELIEF

INCR. RD BY 100%

√ IF OLD RD = 50% - 75%

INCR. RD BY 50%

√ IF 100% RELIEF BUT PAIN RETURN (0.5 HRS)

INCR. RD BY 100%

TITRATING RD

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GOAL

√ < 4

√ > 4 ADD THE RD TO THE ATC DOSE

NON-INCIDENT PAIN

NEVER ADD RD TO ATC

PRE-EMPTIVE DOSING

INCIDENT PAIN

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DEFINITION

STRATEGIES:

√ INCREASE ATC DOSE

√ INCREASE ATC FREQUENCY

√ INCREASE RD (50%)

END OF DOSE FAILURE

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SIDE EFFECTS

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TOLERANCE

PROPHYLAXIS

CHECK MEDICATION / HYDRATION

ATC VS. RD

S/E SHOULD BE TREATED

DOSE LIMITING S/E (GI , CNS)

SIDE EFFECTS

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ATC = ↓ DOSE ( 30%) + SAME RD

RD = ↓ DOSE ( 50%) + ADJUVANT + SAME ATC

CONTROLLED PAIN

OPIOID ROTATION

SYMPTOMATIC TREATMENT OF S/E

ADJUVANT + ↓ DOSE (30-50%)

UNCONTROLLED PAIN

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CHRONIC DOSING

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PARENTERAL ATC PAST 24 HOURS

MULTIPLY BY 3 (FOR MORPHINE)

ORAL ATC 24 HOUR DOSE

DIVIDED ACCORDING TO DOSING FREQUENCY

FOLLOW UP 48 HOURS

ORAL CONVERSION & CHRONIC DOSING

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PAST 24 HR ATC IV MORPHINE DOSE = 30MG

ORAL ATC = 30 X 3 = 90 MG / 24 HRS

IF SRM ( / 12 HRS) = 90 / 2 = 45 MG / 12 HRS

IF SRM ( / 8 HRS) = 90 / 3 = 30 MG / 8 HRS

IF IRM ( / 4 HRS ) = 90 / 6 = 15 MG / 4 HOURS

EXAMPLE

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PAIN EMERGENCY

OPIOID OVERDOSE

START OPIOID THERAPY

TITRATE OPIOIDS (ATC & RD)

STARTING LONG TERM REGIMEN

SUMMARY

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SPECIAL SITUATIONS

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ASSESS CAREFULLY / CONSULT CAREGIVER

ENSURE CONTINUOUS ANALGESIA EVEN IF

PATIENT UNABLE TO COMMUNICATE

ALTERNATE ROUTES

GIVE SPECIFIC ORDERS NOT TO WITH HOLD

OPIOIDS EVEN IN FALLING BP OR CHANGING

BREATHING RATES

PAIN CONTROL IN THE ACTIVELY DYING

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REQUIRED DOSAGE USUALLY HIGHER

MONITORING COMPLIANCE AND SUPERVISION

ONE PHYSICIAN / SHORT Rx / METHADONE

DRUG TESTING

SUBSTANCE ABUSE HISTORY

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ATC PAIN WELL CONTROLLED DURING THE

NIGHT BUT POORLY CONTROLLED BY DAY

√ INCREASE DAY TIME DOSE ONLY

RD FOR INCIDENT PAIN CONTROLLED BY DAY

WAKE THE PATIENT BY NIGHT

√ A SINGLE LONG ACTING DOSE AT BED TIME

√ DOUBLE RD

DIURNAL PAIN PATTERN

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EXTEND DOSING INTERVAL

REDUCE DOSAGE

FRAIL / ELDERLY / ORGAN IMPAIRMENT

DO NOT STOP OPIOID ABRUPTLY

↓ DOSAGE BY 30-50 % EVERY DAY

MAINTAIN RD

OPIOID DOSE REDUCTION

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QUESTIONS

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CASE 1

• 52 YEAR OLD MALE WITH PANCREATIC CANCER AND SEVERE ABDOMINAL PAIN (10 NRS ) ON SR MORPHINE 30 MG TWICE DAILY

• PHYSICAL EXAMINATION:EPIGASTRIC MASS, NO REBOUND TENDERNESS, NO ASCITES, NO JAUNDICE.HE IS DOUBLED OVER IN A FETAL POSITION WHICH RELIEVES HIS PAIN SLIGHTLY

• KUB:UNREMARKABLE

• CT SCAN ABDOMEN ; LARGE UPPER ABDOMINAL AND CELIAC LYMPH NODES COMPRESSING MESENTERIC VESSELS

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CASE 1 TREATMENT

• DOUBLE SR MORPHINE TO 60 MG TWICE DAILY, PROVIDE A RESCUE OF 20 MG EVERY 4 HOURS AS NEEDED

• IMMEDIATE CELIAC BLOCK

• METHADONE SWITCH SINCE MORPHINE IS NOT EFFECTIVE,START WITH 10 MG EVERY 3 HOURS AS NEEDED

• PARENTERAL MORPHINE 1MG EVERY MINUTE FOR 10 MINUTES WITH 5 MINUTE RESPITE REPEAT UNTIL PAIN CONTROL OR 30 MG

• HYDROMORPHONE 0.4 MG EVERY 5 MG SC

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CASE 1

• HE HAS SIGNIFICANT PAIN RELIEF WITH 9 MG OF IV MORPHINE

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CASE 1:ADJUSTED OPIOID DOSE

• MORPHINE 2MG PER HOUR CONTINUOUS IV AND 2MG EVERY 2 HOURS AS NEEDED

• MORPHINE 4 MG CONTINUOUS AND 4 MG EVERY 2 HOURS AS NEEDED

• MORPHINE IMMEDIATE RELEASE 30-40MG EVERY 4 HOURS BY MOUTH AND 15-30MG EVERY 4 HOURS AS NEEDED

• METHADONE 0.4MG CONTINUOUS AND 0.4MG EVERY 2-3 HOURS AS NEEDED

• FENTANYL TRANSDERMAL 100MCG /HOUR PATCH AND ORAL MORPHINE RESCUE

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CASE 2

• 70 YEAR OLD MALE WITH ADVANCED COLON CANCER AND PAINFUL LIVER METASTASES

• LESS THAN 25% RESPONSE THE MORPHINE SR 60MG TWICE DAILY AND 20MG OF IMMEDIATE RELEASE EVERY 4 HOURS

• LABORATORY:NORMAL CREATININE AND BILIRUBIN

• CT SCAN ABDOMEN: MULTIPLE LIVER METASTASES, DISTENDED LIVER, MILD INTRAHEPATIC BILE DUCT DILATATION

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CASE 2:TREATMENT

• INCREASE THE SR MORPHINE TO 120MG EVERY 12 HOURS AND ADJUST THE RESCUE DOSE TO 40MG EVERY 4 HOURS

• IMMEDIATE CELIAC BLOCK

• INCREASE THE SR MORPHINE TO 160MG TWICE DAILY AND ADJUST THE RESCUE TO 60 MG EVERY 4 HOURS

• TRANSDERMAL FENTANYL 100MCG /H PATCH WITH 60MG MORPHINE RESCUE OR 400MCG FENTANYL RESCUE

• HEPATIC RADIATION

• HEPATIC ARTERY EMBOLIZATION

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CASE 3

• 35 YEAR OLD WITH METASTATIC BREAST CANCER TO BONE WITH PAIN LEVEL 6 (NRS) AND MILD CONFUSION ASSOCIATED WITH VIVID DREAMS

• MEDICATIONS:SR OXYCODONE 40MG TWICE DAILY AND IR OXYCODONE 15 MG EVERY 4 HOURS AS NEEDED, 3 DOSES IN LAST DAY:MIRTAZAPINE 15MG AT NIGHT,LORAZEPAM AS NEEDED,2 DOSES PER DAY ON AVERAGE, LAXATIVES

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CASE 3

• PHYSICAL EXAMINATION: NO FOCAL NEUROLOGIC DEFICITS

• LABORATORY: NORMAL CALCIUM , CREATININE AND BILIRUBIN

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CASE 3:TREATMENT

• START HALOPERIDOL 1MG EVERY 12 HOURS AND AS NEEDED EVERY 4 HOURS

• STOP MIRTAZAPINE AND REDUCE OR ELIMINATE LORAZEPAM

• START KETOROLAC 15MG SC EVERY 6-8 HOURS AND REDUCE SR OXYCODONE TO 20 MG EVERY 12 HOURS, MAINTAIN RESCUE DOSES

• SWITCH TO MORPHINE IMMEDIATE RELEASE 15 MG EVERY 4 HOURS ATC

• FENTANYL TRANSDERMAL 50MCG / HOUR WITH BUCCAL FENTANYL 200MCG EVERY 2 HOURS AS NEEDED

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CASE 3

• YOU SWITCH TO MORPHINE IR 15 MG EVERY 4 HOURS WITH IMPROVED PAIN AND COGNITION.THE VIVID DREAMS RESOLVE

• YOU THEN CONVERT TO SR MORPHINE 45MG (15MG PLUS 30MG) WITH RESCUE DOSES AND DISCHARGE HER HOME

• TWO WEEKS LATER SHE PRESENTS CONFUSED WITH MYOCLONUS AND A RESPIRATORY RATE OF 8

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CASE 3 : TREATMENT

• SWITCH BACK TO EQUIVALENT SR OXYCODONE DOSES

• MRI THE BRAIN AND PLACE HER ON DEXAMETHASONE

• CHECK SERUM CALCIUM,ET-CO2 AND CREATININE, STOP NASIDS IF SHE WAS ON THEM

• USE HALOPERIDOL 1MG EVERY 4 HOURS AS NEEDED FOR CONFUSION

• IMMEDIATELY START NALOXONE 40MCG IV EVERY 3 MINUTES UNTIL RESPIRATION >10 AND MYOCLONUS RESOLVES