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