Using Opioids in the Hospitalized Patient Nicole Artz, MD Assistant Professor of Medicine University of Chicago No financial relationships to disclose

Outline  Rapid titration for rapid pain relief  Dosing the PCA  Converting between drug and route  Special Populations Renal/Liver Disease Opioid Tolerant/Dependent  Handling Side Effects  What’s New

Mr. P  45 y/o man (100 kg) presenting to the ED with acute rib fracture after falling off a ladder.  Pain 9/10  Takes HCTZ for HTN; no other meds.  You are evaluating him in the ED

Mr. P  What pain medication will you offer?  What dose will you order?

Equianalgesic Opioid Table OpioidOralIV/SC/IM Morphine30 mg10 mg Hydromorphone7.5 mg1.5 mg Meperidine300 mg100 mg FentanylN/A100 mcg *For severe pain start with dose in chart. For moderate pain, start with 50% of dose and start with 25% of dose for mild pain. Start even lower in patients who are elderly, have renal or hepatic disease or weigh < 50 kg American Pain Society;

Mr. P  You order 5 mg IV Morphine  15 minutes later Mr. P is still in 8/10 pain  Can you redose yet?  How much should you give?

Sedation Scale Action Required SSleeping, easily arousedNone 1Awake and AlertNone 2Occasionally drowsy, easy to arouse None 3Frequently drowsy, arousable, drifts off to sleep during conversation Physically stimulate. Decrease or discontinue the opioid. 4Somnolent, minimal or no response to stimuli Discontinue opioid and consider naloxone; measure O2 saturation *McCaffery, M. and Pasero, CL. Pain: Clinical Manual, 2 nd ed.

General Principles for Rapid Titration  Redose with 50% of loading dose until adequate relief is achieved (usually <5/10)* American Pain Society. Fifth edition National Comprehensive Cancer Network, v *Variation exists among different guidelines.

Mr. P  You redose with 2.5 mg of Morphine and reassess 15 minutes later.  Mr. P reports his pain is now 6/10  You redose with an additional 2.5 mg  15 minutes later Mr. P is comfortable with a pain score of 3-4/10.

Mr. P (Scenario 1)  What should his standing dose of Morphine be and at what interval?  10 mg Morphine IV Q3 hrs ATC  You reassess later that day and he reports adequate pain control immediately after the 10 mg dose but states the dose wears off after the first 90 minutes.

Options?  Consider changing to PCA Avoids peaks and valleys in pain control from bolus dosing Increases patient self-efficacy Less burdensome for nurses Safe way to achieve excellent pain control Joshi and White, 1998; Ballantyne, 1993; Kerr, et al. 1988

Mr. P (Scenario 1)  How will you dose the PCA?

General Principles  Avoid using a basal rate in an opioid naive patient until opioid requirements are known  To calculate an initial demand dose- use 30-50% of the effective bolus dose. *Goal is only 1-2 demands/hour needed to keep pain under control.  Titrate the demand dose to achieve good pain control  May add a basal once opioid requirements determined.

Mr. P (Scenario 1 Cont..)  Morphine PCA 3 mg demand dose  15 minute lockout  No basal rate

Mr. P Scenario 1 cont…  Day 2- pain is well controlled with Morphine PCA 3 mg demand with 15 minute lockout.  Reports trouble sleeping due to pain  Solution? Add a basal infusion on the PCA

Mr. P (Scenario 1 cont…)  24 hour use = 120 mg IV Morphine  If still in severe pain could give full amount as basal  If pain improved but trouble sleeping, consider starting 30-50% 24 hr total as basal

Mr. P (Scenario 1 Cont…)  New PCA orders  60 mg/24 hrs = 2.5 mg/hr continuous infusion  Demand dose? % of basal  2.5 mg demand with 15 minute lockout

Mr. P (Scenario 1)  Converting to orals for discharge Take 24 hr PCA requirements Give % as equianalgesic dose of oral long-acting opioid Rescue with short-acting that is 10-15% of 24 hr dose.

Mr. P (Scenario 1)  Pt used 90 mg IV Morphine past 24 hrs and currently has excellent pain control.  90 mg IV Morphine = 10 IV Morphine X mg po Morphine 30 mg po Morphine X = 270 mg po Morphine/day

Mr. P (Scenario 1)  Start 50% as long-acting 270÷2 = 135 mg long-acting Morphine 135÷3 = 45 mg MS ER po Q 8 hrs  Calculate a breakthrough dose 10-15% of total daily dose Morphine Sulfate IR 15 mg po Q 2-4 hrs prn breakthrough pain

Mr. P (Scenario 1)  How will you wean the morphine? Need to wean if >=5 days exposure 10-20% per day- more slowly if increased pain or signs of withdrawal

Mr. P (Scenario 2)  Pt just admitted from the ED  You reassess later that day and he reports worsening pain with relief only to 7/10 after each 10 mg IV morphine.  A PCA is not available.  While evaluating causes for increased pain, how will you titrate the dose to achieve better control?

Mr. P (Scenario 2 Cont…)  Severe Pain (7-10)- Increase by 100%  Moderate Pain (4-6)- Increase by 50%  Mild Pain (0-3)- Increase by 25%

Mr. P (Scenario 2)  New Morphine dose = 15 mg IV Q 3hrs OR 20 mg IV Q 3hrs  Avoid writing a range for dose or interval  Consider dosing ATC patient may refuse instead of prn

Renal/Liver Insufficiency  Start with Lower Dose, Longer Interval  Avoid Meperidine (even for pts w/o renal insuff)  Avoid scheduled doses of Morphine in renal insufficiency  Preferred opioids in renal insufficiency: Fentanyl, Hydromorphone, Methadone

The Opioid Tolerant Patient  What is tolerance?  What is physical dependence?  Difference between physical dependence and psychological dependence/(addiction)?

Mrs. G  60 y/o woman with metastatic breast cancer admitted with intractable pain  Home regimen: Two 100 mcg Fentanyl patches Hydromorphone 12 mg po Q 3 hrs prn breakthrough pain Reports severe nausea with morphine

Mrs. G  Calculate a basal rate for a Hydromorphone PCA Convert Fentanyl to Morphine using 1:2 ratio 200 mcg Fentanyl patch equiv to 400 mg po Morphine/day 400 mg po Morphine/day = 30 X mg IV Hydromorphone/day 1.5 X = 20 mg IV Hydromorphone/day  Consider reducing dose by 25%-50% due to incomplete cross-tolerance

Mrs. G Add in breakthrough pain medication  Hydromorphone 12 mg Q 3 hrs = 96 mg/day po Hydromorphone  96 mg po hydromorphone/day = 7.5 X mg IV hydromorphone/day 1.5 X = 19 mg IV Hydromorphone/day 20 mg + 19 mg = 39 mg IV Hydromorphone/24 hrs

Mrs. G cont..  Given intractable pain, would give total amount as basal and add demand dose 39mg/24hrs = 1.6 mg/hr basal infusion Demand dose?  % of basal 1.5 mg demand available every 10 minutes * In addition to this, you add ketoralac and Dexamethasone

Mrs. G  Later that day, the patient is more comfortable, with pain 5/10 and decreased to 3/10 after using the demand dose on PCA.  Reports no bowel movement for 2 weeks at home and increased abd bloating;  Abd series reveals constipation but no obstruction

Opioid Side Effects  Nausea Metoclopramide, haloperidol, prochlorperazine  Constipation Prophylactic bowel regimen with stimulants (Senokot, Bisacodyl)  Pruritis Diphenhydramine,  Sedation Decrease opioid dose, caffeine, methylphenidate  Dysphoria,Visual/tactile hallucinations, Delirium Adjust dose or change opioid; haloperidol  Myoclonus Adjust dose or change opioid  Allodynia/Hyperalgesia Wean opioid, change opioids

What’s new… Methylnaltrexone Peripheral opioid receptor antagonist Does not cross the blood-brain barrier Effective for treatment of opioid induced constipation and nausea Subcutaneously administered Recently approved by the FDA for treatment of opioid-induced constipation in palliative care pts with inadequate response to laxatives.

Take Home Points  Rapid Titration:  reassess every 15 minutes and redose with 50% of loading dose until adequate relief achieved.  Add up total mg required to achieve relief during rapid titration- this is your scheduled bolus dose.  Titrate opioids by 25%, 50%, or 100% for mild, moderate, or severe pain  When transitioning to po make sure to calculate an equianalgesic dose using the opioid conversion tables.

Take Home Points  Use PCA’s when available In opioid naive- set demand at 30-50% of loading or bolus dose In opioid tolerant- convert current opioids to equianalgesic basal rate on pca; set starting demand dose the same as the basal rate

References  Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, American Pain Society, Fifth edition,  Education for Physicians on End-of-Life Care (EPEC), Pain Management Module, RWJF,  National Comprehensive Cancer Network: Practice Guidelines in Oncology- v

Resources  Hopkins Opioid Program  Fast Facts, National Residency End- of-Life Curriculum Project Download at