Objectives. Patient Controlled Analgesia (PCA) Management in the Seriously Ill. Discuss principles for opioid dosing and titration for acute pain
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1 Patient Controlled Analgesia (PCA) Management in the Seriously Ill Jeanie Youngwerth, MD University of Colorado School of Medicine Associate Professor of Medicine, Hospitalist Associate Director, Colorado Palliative Medicine Fellowship Director, Palliative Care Program I have no financial relationships to disclose Objectives Discuss principles for opioid dosing and titration for acute pain Apply equianalgesic opioid conversions Describe adjustments for opioids in the setting of renal/liver failure and the elderly
2 Methadone Does not follow regular opioid principles! Recommend consulting Palliative Care or Pain Service for patients in acute pain crisis who are on Methadone Bruera: JPM Which of the following has not been shown to improve pain? 1. Laughter 2. Music 3. Maternal kisses for childhood boo-boos 4. Profanity Dunbar: Proc R Soc 2012; Pulvers: Addict Beh 2012; Mitchell: Europ J Pian 2006; SMACK: J of Eval Clin Pract 2015; Stephens: NeuroReport 2009; Stephens: Journal of Pain Which of the following has not been shown to improve pain? 1. Laughter 2. Music 3. Maternal kisses for childhood boo-boos 4. Profanity Dunbar: Proc R Soc 2012; Pulvers: Addict Beh 2012; Mitchell: Europ J Pian 2006; SMACK: J of Eval Clin Pract 2015; Stephens: NeuroReport 2009; Stephens: Journal of Pain 2011.
3 Tolerance Which patient is considered to be opioid tolerant? Oxycodone SR 20 mg po BID for 1 week Morphine IR 15 mg po TID for 2 weeks Fentanyl patch 12 mcg/hr TD q72 hours for 3 weeks All of the above Which patient is considered to be opioid tolerant? Oxycodone SR 20 mg po BID for 1 week
4 Opioid Tolerance Morphine 60 mg po daily Oxycodone 30 mg po daily Hydromorphone 8 mg po daily Fentanyl 25 mcg/hr TD Oxymorphone 25 mg po daily v1.0. Pain Case Study 47 y/o M with metastatic neuroendocrine tumor Oxycodone SR 80 mg po BID Hydromorphone IR 4 mg po q 4 hrs prn pain 6 tablets a day (past 10 days) Acute pain crisis from tumor burden Cr 0.7; LFTs WNL Put on PCA overnight by moonlighter PCA Errors #1 improper dose/quantity US Pharmacopeia 2004; Hicks: Am J Health Syst Pharm 2008.
5 Opioid Conversions Equianalgesic Dosing 1 Calculate total 24 hour total opioid dose 2 Convert to 24 hour new opioid equivalent 3 Adjust by 50-75% for incomplete cross tolerance 4 Triple check calculations 5 Constipation prophylaxis! EPEC Module ; v1.0; NCCN: Adult Cancer Pain v Incomplete Cross Tolerance v1.0. Incomplete Cross Tolerance When switching from one opioid to another Start the new opioid at 50-75% of the equianalgesic dose 60% good generalization Pasternak: Trends in Pharm Sciences 2001; Ballantyne: NEJM 2003; Mehta: Anaesth 2006; v1.0; NCCN: Adult Cancer Pain v
6 * Pain Pearl * Adjust for incomplete cross tolerance 60% calculated dose Opioid Conversions Equianalgesic Dosing Current Opioid = Total 24 hour Current Opioid New Opioid Total 24 hour New Opioid (X) Choice of Opioid What is considered the gold standard opioid? Grass: Anesth Analg 2005; Ripamonte: Annals of Onc 2012.
7 S S Pain Case Study 1. Calculate total 24 hour opioid dose Oxycodone SR 160 mg / day + Hydromorphone IR 24 mg / day TDD = Morphine X mg IV / day Avoid Mixing Opioids é risk for confusion and mistakes by patients and providers SIMPLIFY Morphine SR + Morphine IR prn NCCN: Adult Cancer Pain v
8 Pain Case Study 2. Convert to 24 hour new opioid equivalent Current Opioid New Opioid = Total 24 hour Current Total 24 hour New (X) Oxycodone 20 mg po Morphine 10 mg IV = Oxycodone 160 mg/day po Morphine IV X X = Morphine 80 mg IV/day Pain Case Study 2. Convert to 24 hour new opioid equivalent Current Opioid New Opioid = Total 24 hour Current Total 24 hour New (X) Hydrom 7.5 mg po Morphine 10 mg IV = Hydrom 24 mg/day po Morphine IV X X = Morphine 32 mg IV/day Pain Case Study 3. Adjust by 60% for incomplete x- tolerance Morphine = 112 mg IV / day X 0.6 = Morphine 67 mg IV / day
9 4. Triple check calculations 5. Constipation prophylaxis! -Senna 2 tabs po BID Pain Case Study Hawley: JPSM 2008; Librach: JPSM 2010; Tarumi: JPSM Pain Case Study Morphine 67 mg IV / day PCA settings? PCA Parameters Basal Demand Lockout PCA Initiation FIRST ask yourself Opioid tolerant or not???
10 PCA Basal Rate Tolerant Convert 24 hour total opioid requirement to hourly rate (by equianalgesic dosing) Naive No basal rate é respiratory depression No ê pain scores Grass: Anesth Analg PCA Demand Dose Tolerant 50% of the basal rate (50-100%) Naive? Sidebotham: JPSM 1997; Krenn: Euro J Pain 2001; Macintrye: Br J Anaesth 2001; Didem: Can J Anesth 2003; Lehmann: JPSM 2005; Grass: Anesth Analg 2005; Herr: Iowa City Guideline Summary NGC PCA Demand Dose- Opioid Naive
11 Morphine Demand Dose 2 mg Opioid Naive 0.5 mg 1 mg Owen: Anaesth 1989; Sidebotham: JPSM Morphine Demand Dose Outcome Opioid Naive 1 mg Optimal balance Owen: Anaesth 1989; Sidebotham: JPSM PCA Demand Dose Tolerant Naive 50% of the basal rate (50-100%) Morphine 1 mg IV equivalent Sidebotham: JPSM 1997; Krenn: Euro J Pain 2001; Macintrye: Br J Anaesth 2001; Didem: Can J Anesth 2003; Lehmann: JPSM 2005; Grass: Anesth Analg 2005; Herr: Iowa City Guideline Summary NGC
12 PCA Lockout Time Based on time to peak effect IV: 8-10 min Plasma Concentration Cmax SC / IM: min PO / PR: min Time Half-life (t1/2) PCA Lockout Time Morphine 7 vs 11 minutes Fentanyl 5 vs 8 minutes No difference in pain, anxiety or side effects Ginsberg: Pain 1995.
13 PCA Lockout Time 10 minutes is a standard interval Ginsberg: Pain 1995; Macintrye: Br J Anaesth 2001; Walder: Acta Anaesthesiol Scand 2001; Grass: Anesth Analg 2005; Craft: Proc Bayl Univ Med Cent PCA Nurse Initiated Bolus Up to twice the demand dose Grass: Anesth Analg 2005; Craft: Proc Bayl Univ Med Cent Morphine 67 mg IV / day 24 hrs = 2.8 mg/hr Pain Case Study Basal 3 mg/hr Demand dose 1.5 mg Lockout time 10 min Nurse-bolus 3 mg
14 Summary: Opioid Naïve PCA Dosing (initial) Drug Basal Demand Lockout Nurse- Bolus Morphine X 1 mg 10 min 2 mg Hydromorphone X 0.2 mg 10 min 0.4 mg Fentanyl X 10 mcg 10 min 20 mcg SD Patient Safety Taskforce: Tool Kit: PCA Guidelines of Care Summary: Opioid Tolerant PCA Dosing Drug Basal Demand Lockout Nurse Bolus Morphine Convert 24 hr Hydromorphone total opioid Fentanyl requirement to hourly rate 50% (100%) basal rate 10 min 2x demand dose Nurse calls 3 hours later for patient with severe pain. What is the best next step when titrating the PCA for acute pain control? 3/1.5/10 1. Increase basal rate to 4 mg/hr 2. Increase demand dose to 3 mg 3. Decrease lockout time to 6 minutes 4. Opioid rotation to PCA IV Fentanyl 5. Add Oxycodone/Acetaminophen 5/ tablet oral q4 hours prn
15 Nurse calls 3 hours later for patient with severe pain. What is the best next step when titrating the PCA for acute pain control? 3/1.5/10 1. Increase basal rate to 4 mg/hr 2. Increase demand dose to 3 mg 3. Decrease lockout time to 6 minutes 4. Opioid rotation to PCA IV Fentanyl 5. Add Oxycodone/Acetaminophen 5/ tablet oral q4 hours prn Acute control Opioid Titration IR / prn Demand dose Chronic control SR / scheduled Basal rate Hanks: British J Cancer 2001; Grass: Anesth Analg 2005; NCCN Adult Cancer Pain V * Pain Pearl * Titrate the demand dose for acute pain
16 PCA Demand Dose Titration Practically reevaluate in 1 hour Can change every minutes if needed Opioid Titration Pain Severity Increase Dose Up To Mild 25% Moderate 50% Severe 100% EPEC Module ; NCCN Adult Cancer Pain V
17 PCA Basal Rate Titration Every 24 hours reasonable 8-24 hours to achieve steady state Avoid changing more frequently than q 8 hrs EPEC Module ; APS PCA Basal Rate Titration Dose based on Patient pain rating Your assessment Daily trend of 24 hr requirements Summary: PCA Titration Basal Rate Consider change daily based on 24 hour use Demand Dose (acute pain control) é 25% mild pain é 50% moderate é 100% severe Lockout 10 minutes
18 PCA to Oral Opioids Once stable opioid requirements for ~2 days TDD from PCA to calculate equianalgesic oral dose of new opioid Patient using TDD Morphine 130 mg IV / day Pain Case Study PCA to Oral Opioid Current Opioid New Opioid = Total 24 hour Current Total 24 hour New (X) Morphine 10 mg IV Morphine 30 mg po = Morphine 130 mg/day IV Morphine po X X = Morphine 390 mg po/day (no x-tolerance needed) Pain Case Study PCA to Oral Opioid X = Morphine 390 mg po/day Morphine ER 200 mg po BID Breakthrough pain (BTP)? 1. Oxycodone / Acetaminophen 5/ tab po q4 hrs prn 2. Oxycodone IR 10 mg po q 2 hrs prn 3. Morphine IR 45 mg po q 1 hrs prn 4. Hydromorphone IR 4 mg po q 4 hrs prn
19 Pain Case Study PCA to Oral Opioid X = Morphine 390 mg po/day Morphine ER 200 mg po BID Breakthrough pain (BTP)? 1. Oxycodone / Acetaminophen 5/ tab po q4 hrs prn 2. Oxycodone IR 10 mg po q 2 hrs prn 3. Morphine IR 45 mg po q 1 hrs prn 4. Hydromorphone IR 4 mg po q 4 hrs prn * Pain Pearl * BTP IR Dose: 10-15% of 24 hour total opioid dose Interval: time to peak effect NCCN: Adult Cancer Pain v Pain Case Study PCA to Oral Opioid X = Morphine 390 mg po/day Morphine ER 100 mg 2 tabs po BID BTP: Morphine IR 45 mg (30 mg x 1.5 tab) po q1 hr prn pain Or Morphine elixir 20 mg/ml 40 mg po q1 hr prn pain Poop Prophylaxis: Senna 4 tab po BID
20 Poop Protocol Poop Protocol When to Keep SR Opioids with PCA SR opioids (act as the basal) PCA demand only (for BTP) Periprocedural Consider for sickle cell crisis
21 When to Avoid Morphine Renal Failure Majority of opioids renally cleared Active metabolites Limited studies; no RCTs No consensus on GFR (<30 ml/min) Dean: J Pain Symptom Manage 2004; King: Palliat Med 2011; Ripamonte: Annals of Onc 2012: Lee: JPM Morphine Codeine Renal Failure Hydromorphone Oxycodone Tramadol Fentanyl AVOID Cautious Dosing Safer No dose adjustment short term Potent, active metabolites cleared renally Increased risk for oversedation & neurotoxicity Poorly studied No known active renal metabolites Limited studies Dean: J Pain Symptom Manage 2004; King: Palliat Med 2011; Lee: JPM 2016.
22 Liver Failure Impaired oxidation and glucuronidation Limited studies- most extrapolated from RF High prevalence & risk of RF in cirrhosis Avoid Morphine, Codeine, Tramadol Transdermal preparations Davis: Clin Pharmacokinet 2007; Rhee: J Palliat Med 2007; Chandok: Mayo Clin Proc Avoid Morphine in renal/liver failure Consider IR preparations longer dosing intervals * Pain Pearl * Ripamonte: Annals of Onc 2012; Lee: JPM Which PCA settings would you order for 83 y/o F opioid naïve with multi-trauma s/p motor vehicle crash (nl CrCl; alert; not delirious)? Morphine basal 1 mg/hr demand 0.5 mg lockout 12 min Hydromorphone basal 0 demand 0.5 mg lockout 8 min Hydromorphone basal 0 demand 0.3 mg lockout 10 min Morphine basal 0 demand 0.5 mg lockout 10 min
23 Which PCA settings would you order for 83 y/o F opioid naïve with multi-trauma s/p motor vehicle crash (nl CrCl; alert; not delirious)? Morphine basal 0 demand 0.5 mg lockout 10 min Elderly- Opioid Reduction Require less opioid to achieve same relief Opioid sensitivity é by 50% Pain intensity ê by 10-20% each decade after age 60 Herr: Iowa City Guideline Summary NGC ; v1.0. * Pain Pearl * Initiate opioids at 25-50% lower dose than recommended for younger adults Herr: Iowa City Guideline Summary NGC Evidence Grade = B; v1.0.
24 QI: PCA Safety Checklist FOR ALL STEPS: Document exceptions to any step of the safety checklist. Address psycho-social-spiritual pain. INITIATION Patient has confirmed cognitive function physical capability Patient and family educated Document PCA indication Discontinue all other opioids CALCULATIONS GUIDELINES 40% reduction for cross tolerance when converting to another opioid For basal and demand: Is demand % of basal rate? Is RN bolus % of demand? Is demand lockout 10 minutes? Double check calculations with a palliative care team member PCA conversion verbally communicated to primary team and nurse Is patient IPC bed status? Document conversion calculations (.pccalc and.pcpca) TITRATION CALCULATIONS GUIDELINES Incremental 24 hour basal rate increase not to exceed 100% of previous basal rate For basal and demand: Is demand % of basal rate? Is RN bolus % of demand? Is demand lockout 10 minutes? Double check previous 24 hour use with a palliative care team member Double check titration calculations with a palliative care team member PCA titration verbally communicated to primary team and nurse Document titration calculations (.pcpca) TRANSITIONING Patient has confirmed GI absorption renal function appropriate for medication CALCULATIONS GUIDELINES Stable PCA use x 48 hours 40% reduction for cross tolerance when converting to another opioid Is oral PRN dose 10-15% of total daily dose? Double check calculations with a palliative care team member Patient has confirmed outpatient insurance coverage outpatient provider follow up PO conversion verbally communicated to primary team and nurse Document conversion calculations (.pccalc) PCA Safety Checklist current 24 hour dose *** = New X current ratio*** new ratio*** Total X = *** mg Total X 60% incomplete cross tolerance = *** mg Based on this calculation, patient's report of pain, and my assessment of patient, Date Basal Demand Lockout Total Use Avg per hour Recommend: **** Date Basal Demand Lockout Total Daily Avg / hour PCA table Opioid: *** Use Resources REMS NCCN Adult Cancer Pain Guidelines _guidelines.asp
25 * Pain Pearls * Adjust for incomplete cross tolerance (60%) Titrate demand dose for acute pain 25% mild pain 50% moderate pain 100% severe pain Oral BTP: 10-15% of TDD Avoid Morphine with renal / liver failure ê opioids 25-50% in elderly
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