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1
DOSING STRATEGIES
MELLAR DAVIS, WAEL LASHEEN, DECLAN WALSH
2
GUIDELINES
BARRIERS
HEALTHCARE PROFESSIONAL
PATIENTS
PAIN
OPIOIDS
BACKGROUND
3
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
4
INADEQUATE ASSESSMENTS
FAILURE TO PRESCRIBE
INAPPROPRIATE OPIOID USE
HEALTHCARE PROFESSIONAL
PATIENTS UNDER-REPORT
COMPLIANCE
5
LOCATION
TEMPORAL PATTERN (CP / IP)
INTENSITY
QUALITY
AGGREVAT / ALLEVIATING FACTORS
MEDICATION
IMPACT
ASSOCIATED FACTORS (ANXIETY / DEPRESSION)
PAIN HISTORY
6
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
7
PAIN PATHOPHYSIOLOGY
VISCERALSOMATIC NEUROPATHIC
CANCER PAIN
MIXED
8
MORPHINE (MU AGONIST)
FENTANYL (MU AGONIST)
HYDROMORPHONE (MU AGONIST)
OXYCODONE (MU AND KAPPA AGONIST)
METHADONE (MU AND DELTA AGONIST)
OPIOID CHOICES
9
ADJUVANTS AND INTERVENTIONS
ADJUVANTS INTERVENTIONS
ACETAMINOPHEN
BISPHOSPHONATES
CORTICOSTEROIDS
GABAPENTIN
NERVE BLOCK
KYPHOPLASTY
IRRIDIATION
10
GUIDELINES (WHO LADDER)
BARRIERS
PAIN HISTORY
OPIOIDS
SUMMARY
11
PAIN EMERGENCY
12
OPIOID LOADING (OPIOID NAÏVE / EXPER.)
FREQUENT
SMALL DOSES
SHORT ACTING OPIOID
GOALS
PAIN CONTROL
TOXICITY
OPIOID LOADING
IV OPIOID LOADING
-1
0
1
2
3
4
5
6
7
8
9
10
11
14
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
-1
0
1
2
3
4
5
6
7
8
9
10
11
IV
SC
ORAL
1MG/ 1 MIN
5MG/ 30 MIN
2 MG/ 5 MIN
16
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
17
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
18
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
19
ACUTE ONSET OF EXCRUCIATING PAIN OPIOID
LOADING
√ IV
√ SC
√ ORAL
SEVERELY ILL
ALTERNATE STRATEGY
SUMMARY
20
OPIOID (OVERDOSE)
EMERGENCY
21
INDICATIONS FOR NALOXONE:
√ PATIENT UN-RESPONSIVE
√ RR < 10 / MIN WITH EVIDENCE OF
INADEQUATE VENTILATION (LOW OXYGEN
SATURATION)
TREATMENT OF OPIOID OVERDOSE
22
STOP OPIOID ADMINISTRATION
PREPARE NALOXONE:
NP
VIAL OF NALOXONE (0.4MG/ML) + 9 ML SALINE
= 40 MICG / ML NALOXONE
FLOW-CHART
PROTOCOL
23
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
24
STARTING
ATC AND RD THERAPY
25
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
26
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
27
OPIOID TITRATION
FOR
CONTIUOUS PAIN (NO S/E)
28
-1
0
1
2
3
4
5
6
7
8
9
RD RDRDRDRDRD
ATC
29
ASSESSMENT EVERY 24 HOURS
√ PAIN SEVERITY / RELIEF
√ DURATION OF RELIEF
√ INTERFERENCE WITH SLEEP AND ACTIVITY
√ SIDE EFFECTS
TITRATION FOR PAIN CONTROL
30
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
31
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
32
OPIOID TITRATION
INCIDENT AND
NON-INCIDENT PAIN
(NO S/E)
33
MILD SEDATION
NAUSEA
VOMITING
CONSTIPATION / DRY MOUTH / URINE RETENTION
VISUAL / TACTILE HALLUCINATIONS
MANIFESTATIONS
-1
0
1
2
3
4
5
6
7
8
9
RD RD
34
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
35
GOAL
√ < 4
√ > 4 ADD THE RD TO THE ATC DOSE
NON-INCIDENT PAIN
NEVER ADD RD TO ATC
PRE-EMPTIVE DOSING
INCIDENT PAIN
36
DEFINITION
STRATEGIES:
√ INCREASE ATC DOSE
√ INCREASE ATC FREQUENCY
√ INCREASE RD (50%)
END OF DOSE FAILURE
37
SIDE EFFECTS
38
TOLERANCE
PROPHYLAXIS
CHECK MEDICATION / HYDRATION
ATC VS. RD
S/E SHOULD BE TREATED
DOSE LIMITING S/E (GI , CNS)
SIDE EFFECTS
39
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
40
CHRONIC DOSING
41
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
42
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
43
PAIN EMERGENCY
OPIOID OVERDOSE
START OPIOID THERAPY
TITRATE OPIOIDS (ATC & RD)
STARTING LONG TERM REGIMEN
SUMMARY
44
SPECIAL SITUATIONS
45
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
46
REQUIRED DOSAGE USUALLY HIGHER
MONITORING COMPLIANCE AND SUPERVISION
ONE PHYSICIAN / SHORT Rx / METHADONE
DRUG TESTING
SUBSTANCE ABUSE HISTORY
47
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
48
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
49
QUESTIONS
50
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
51
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
52
CASE 1
• HE HAS SIGNIFICANT PAIN RELIEF WITH 9 MG OF IV MORPHINE
53
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
54
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
55
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
56
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
57
CASE 3
• PHYSICAL EXAMINATION: NO FOCAL NEUROLOGIC DEFICITS
• LABORATORY: NORMAL CALCIUM , CREATININE AND BILIRUBIN
58
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
59
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
60
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