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DOSING STRATEGIES
MELLAR DAVIS, WAEL LASHEEN, DECLAN WALSH
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BACKGROUND
 GUIDELINES
 BARRIERS
 HEALTHCARE PROFESSIONAL
 PATIENTS
 PAIN
 OPIOIDS
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GUIDELINES
STEP 3
POTENT OPIOID ANALGESICS
STEP 2
± ADJUVANT
WEAK OPIOID ANALGESICS
± NON-OPIOID ANALGESICS
± ADJUVANT
STEP 1
NON-OPIOID ANALGESICS
± ADJUVANT
PAIN SEVERITY
± NON-OPIOID ANALGESICS
WALSH ET AL SUPP. CANC. THER. 2004
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HEALTHCARE PROFESSIONAL
 INADEQUATE ASSESSMENTS
 FAILURE TO PRESCRIBE
 INAPPROPRIATE OPIOID USE
PATIENTS
 UNDER-REPORT
 COMPLIANCE
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PAIN HISTORY
 LOCATION
 TEMPORAL PATTERN (CP / IP)
 INTENSITY
 QUALITY
 AGGREVAT / ALLEVIATING FACTORS
 MEDICATION
 IMPACT
 ASSOCIATED FACTORS (ANXIETY / DEPRESSION)
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TEMPORAL PAIN PATTERN
Cancer Pain
Continuous Pain
Continuous Pain
Alone
(CP)
Intermittent Pain
(IP)
Intermittent with
Continuous Pain
(BP)
Intermittent Pain
Alone
(NBP)
Incident
Incident
Non-Incident
Non-Incident
Mixed
Mixed
EODF
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PAIN PATHOPHYSIOLOGY
CANCER PAIN
SOMATIC
VISCERAL
NEUROPATHIC
MIXED
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OPIOID CHOICES
 MORPHINE (MU AGONIST)
 FENTANYL (MU AGONIST)
 HYDROMORPHONE (MU AGONIST)
 OXYCODONE (MU AND KAPPA AGONIST)
 METHADONE (MU AND DELTA AGONIST)
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ADJUVANTS AND INTERVENTIONS
ADJUVANTS
INTERVENTIONS
 ACETAMINOPHEN
 NERVE BLOCK
 BISPHOSPHONATES
 KYPHOPLASTY
 CORTICOSTEROIDS
 IRRIDIATION
 GABAPENTIN
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SUMMARY
 GUIDELINES (WHO LADDER)
 BARRIERS
 PAIN HISTORY
 OPIOIDS
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PAIN EMERGENCY
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OPIOID LOADING
 OPIOID LOADING (OPIOID NAÏVE / EXPER.)
 FREQUENT
 SMALL DOSES
 SHORT ACTING OPIOID
 GOALS
 PAIN CONTROL
 TOXICITY
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IV OPIOID LOADING
11
10
9
8
7
6
5
4
3
2
1
0
-1
IV OPIOID LOADING
 DOSE
√ 1 MG MORPHINE
√ 0.2 MG HYDROMORPHONE
√ 20 MICGR FENTANYL
 FREQUENCY
√ EVERY MINUTE X 10; RESPITE 5 MIN; REPEAT
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SC AND ORAL OPIOID
LOADING
11
10
9
8
7
IV
1MG/ 1 MIN
6
5
SC
2 MG/ 5 MIN
4
3
2
1
0
-1
ORAL
5MG/ 30 MIN
CARDIO-PULMONARY INSTABILITY
 IV ROUTE IS PREFERRED
 FIXED DOSE INTERVAL STRATEGY
√ 2-4 MG IV MORPHINE
√ EVERY 2 HOURS UNTIL PAIN IMPROVES
WALSH ET AL SUPP. CANC. THER. 2004
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PATIENT ON CHRONIC OPIOID
 ALTERNATIVE LOADING STRATEGY: ORAL
 DOUBLE ORAL RESCUE DOSE (RD)
2 X 5MG = 10 MG
 GIVE EVERY 30 MINS UNTIL PAIN CONTROL
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ALTERNATIVE STRATEGY: IV (SC)
 TOTAL IV (SC) OPIOID PAST 24 HOURS
√ ATC
24 MG
√ RD (FOR NON-INCIDENT PAIN)
 CALCULATE THE HOURLY DOSE 24 MG/ 24HRS = 1 MG
 LOADING
2 MG THEN 1 MG
√ DOSE: 1ST 2 X HOURLY THEN HOURLY DOSE
√ FREQUENCY: EVERY 15 MINS PAIN CONTROL
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SUMMARY
 ACUTE ONSET OF EXCRUCIATING PAIN OPIOID
LOADING
√ IV
√ SC
√ ORAL
 SEVERELY ILL
 ALTERNATE STRATEGY
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OPIOID (OVERDOSE)
EMERGENCY
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TREATMENT OF OPIOID OVERDOSE
 INDICATIONS FOR NALOXONE:
√ PATIENT UN-RESPONSIVE
√ RR < 10 / MIN WITH EVIDENCE OF
INADEQUATE VENTILATION (LOW OXYGEN
SATURATION)
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PROTOCOL
 STOP OPIOID ADMINISTRATION
 PREPARE NALOXONE:
NP
VIAL OF NALOXONE (0.4MG/ML) + 9 ML SALINE
= 40 MICG / ML NALOXONE
 FLOW-CHART
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Opioids
1 ml NP
(40MICG)
Evaluate every 3 minutes:
Responsive And RR > 10/min
NO
YES
Observation for
at least 4 hours
Observation for at
least 24 hours
Naloxone Infusion:
Sum of Doses Given /
hour
START OPIOIDS AT LOWER DOSE WITH ONSET OF PAIN
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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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9
8
7
6
5
ATC
4
3
2
1
RD
RD
RD
RD
RD
RD
0
-1
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TITRATION FOR PAIN CONTROL
 ASSESSMENT EVERY 24 HOURS
√ PAIN SEVERITY / RELIEF
√ DURATION OF RELIEF
√ INTERFERENCE WITH SLEEP AND ACTIVITY
√ SIDE EFFECTS
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ATC DOSE TITRATION
 NEW ATC DOSE / 24 HRS =

PAST 24 HR OPIOID DOSE + (30% TO 50%)
√ ATC PAST 24 HOURS
√ RD (FOR NON-INCIDENT PAIN) PAST 24H
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EXAMPLE
 PAST 24 HOURS
√ ATC M = 40MG
√ RD M = 5 MG (5MG X 6 = 30 MG)
√ TOTAL = ATC + RD = 40 + 30 = 70 MG
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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9
8
7
6
MANIFESTATIONS
 MILD SEDATION
 NAUSEA
5
4
 VOMITING
3
 CONSTIPATION / DRY MOUTH / URINE RETENTION
2
1
 VISUAL / TACTILE HALLUCINATIONS
RD
RD
0
-1
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TITRATING RD
 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%
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NON-INCIDENT PAIN
 GOAL
√ <4
√ > 4 ADD THE RD TO THE ATC DOSE
INCIDENT PAIN
 NEVER ADD RD TO ATC
 PRE-EMPTIVE DOSING
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END OF DOSE FAILURE
 DEFINITION
 STRATEGIES:
√ INCREASE ATC DOSE
√ INCREASE ATC FREQUENCY
√ INCREASE RD (50%)
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SIDE EFFECTS
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SIDE EFFECTS
 TOLERANCE
 PROPHYLAXIS
 CHECK MEDICATION / HYDRATION
 ATC VS. RD
 S/E SHOULD BE TREATED
 DOSE LIMITING S/E (GI , CNS)
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CONTROLLED PAIN
 ATC = ↓ DOSE ( 30%) + SAME RD
 RD = ↓ DOSE ( 50%) + ADJUVANT + SAME ATC
UNCONTROLLED PAIN
 OPIOID ROTATION
 SYMPTOMATIC TREATMENT OF S/E
 ADJUVANT + ↓ DOSE (30-50%)
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CHRONIC DOSING
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ORAL CONVERSION & CHRONIC DOSING
 PARENTERAL ATC PAST 24 HOURS
 MULTIPLY BY 3 (FOR MORPHINE)
 ORAL ATC 24 HOUR DOSE
 DIVIDED ACCORDING TO DOSING FREQUENCY
 FOLLOW UP 48 HOURS
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EXAMPLE
 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
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SUMMARY
 PAIN EMERGENCY
 OPIOID OVERDOSE
 START OPIOID THERAPY
 TITRATE OPIOIDS (ATC & RD)
 STARTING LONG TERM REGIMEN
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SPECIAL SITUATIONS
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PAIN CONTROL IN THE ACTIVELY DYING
 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
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SUBSTANCE ABUSE HISTORY
 REQUIRED DOSAGE USUALLY HIGHER
 MONITORING COMPLIANCE AND SUPERVISION
 ONE PHYSICIAN / SHORT Rx / METHADONE
 DRUG TESTING
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DIURNAL PAIN PATTERN
 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
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FRAIL / ELDERLY / ORGAN IMPAIRMENT
 EXTEND DOSING INTERVAL
 REDUCE DOSAGE
OPIOID DOSE REDUCTION
 DO NOT STOP OPIOID ABRUPTLY
 ↓ DOSAGE BY 30-50 % EVERY DAY
 MAINTAIN RD
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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
MORPHINE 30 MG TWICE DAILY
SR
• 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
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