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Palliative Care Symptom Guide Table of Contents

General Principles of Pain Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Pain Scale for patients who cannot communicate (Abbey Pain Scale) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Select Opiate Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Equianalgesic dosing (Opioid conversion) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Patient Controlled Analgesia (PCA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Transdermal Fentanyl Conversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6Guidelines for Naloxone Administration and Patient Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7Nausea and Vomiting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-9Constipation and Bowel Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10-11Delirium: Diagnosis and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12-14Dementia: Course and Prognostication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15-16Depression: Screening tools and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17-19End Stage Liver Disease: Prognostication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20-21End of life care: Symptom Management Common Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Oral Secretions at the End of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Palliative Care and Pain Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

July 2011

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Pain Scale

No Pain Worst Pain ImaginableNone = 0; Mild = 2 .5; Moderate = 5; Severe = 7 .5; Excruciating = 10

General Principles of Pain Management1. Assess pain using a standardized pain scale. Pain is a subjective feeling: ask the patient using the above 0-10 scale. If the patient is cognitively impaired, use the Abbey

pain scale. (See page 2.) Frequency of assessment: at the time of the initial interview, every eight hours, and PRN (at least every two hours when pain is severe).2. In opiate naive patients, start with short-acting opioids (morphine, hydromor-

phone, and oxycodone) to control acute, moderate to severe pain. Never use long-acting opioids to control acute pain.

3. When titrating or changing opiate dose, start by calculating the previous day’s Oral Morphine Equivalent (OME).a. Since all potent opioids produce analgesia by the same mechanism, they

will produce the same degree of analgesia if provided in equianalgesic doses (see equanalgesic table).

b. Rectal=oralc. SQ=IM=IV

4. Determine if the dose is adequate for the pain and dose adjust. a. Titrate at least every 24 hours when the pain is moderate and as often as every

four hours when using IV opioids and the pain is severe. b. Increase dose 25-50% for moderate pain and 50-100% for severe pain.5. Determine the opiate that will be used and dose adjust for incomplete

cross tolerance. a. The only reason to change from one opiate to another is side effects or

renal failure. b. When rotating opiate, decrease the dose 25-50% to correct for incomplete cross

tolerance.

6. Determine the route the opiate will be given. a. IM should never be given.7. Determine the dosing schedule. a. For non-opiate naive patients, use long-acting pain medicine for ongoing pain, not

prn; for opiate naive patients use only prn until you have a sense of how much medicine the patient needs.

b. Give 66-75% of patient’s stable daily OME as long acting. c. Consider a pca if the pain requirements are rapidly increasing or unknown.8. Determine break through dose (for acute pain in patient with otherwise

controlled pain). a. Use the same opiate for short- and long-acting pain when possible. b. 5-15% of total daily long acting opiate dose every 3 hr prn.9. Manage opiate side effects. Constipation must be treated prophylactically

(see page 6).10. Determine whether co-analgesics would help.

1 2 3 4 5 6 7 8 9 100

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Abbey Pain ScaleAbbey Pain Scale for the assessment of pain in patients who cannot communicate .

Rating ScaleAbsent = 0 Mild = 1 Moderate = 2 Severe = 3

Domain Scale

Vocalization0-3

Facial expressions 0-3

Change in body language 0-3

Behavioral change (confusion, refuse to eat, alteration in usual patterns)

0-3

Physiological changes 0-3

Physical changes (skin tear, pressure area contractions, etc .)

0-3

Total Score No Pain = 0-2 Mild = 3-7 Moderate = 8-13 Severe = 14+Reference: Abbey J., Piller N., DeBalis A., Esterman D. The Abbey pain scale: a 1-minute numerical indicator for people with end-stage dementia. International Journal of Palliative Nursing, 2004, Vol. 10, No 1, 6-13.

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PHARMACISTS WILL NOT MAKE SUBSTITUTIONS OR CORRECTIONS FOR OPIATES. IF SCRIPTS ARE NOT WRITTEN EXACTLY (e.g., CORRECT DRUG, DOSE, AND SCHEDULE), THEY WILL NOT BE FILLED.SELECT NON-INJECTABLE OPIOID PRODUCTS

Drug Formulation/Strength (mg/mg) (8)Anexsia (hydrocodone/acetaminophen) (4,6) Tabs 5/325 (scored), 5/500 (scored), 7 .5/325, 7 .5/650 (scored), 10/660 (scored)Empirin with Codeine (codeine/aspirin) (4,6) Tabs 30/325 (#3), 60/325 (#4)Lorcet (hydrocodone/acetaminophen) (3,4) Tabs 7 .5/650 (scored), 10/650 (scored) Caps 5/500Lortab (hydrocodone/acetaminophen) (3,4) Tabs 2 .5/500, 5/500 (scored), 7 .5/500 (scored), 10/500 Elixir 7 .5/500 per 15 mLNorco (Hydrocodone/acetaminophen) (3,4) Tabs 5/325, 7 .5/325, 10/325Percocet (oxycodone/acetaminophen) (3,4) Tabs 2 .5/325, 5/325, 7 .5/325, 7 .5/500, 10/325, 10/650 Percodan (oxycodone/aspirin) (4) Tabs 5/325 Roxicet (oxycodone/acetaminophen) (4) Tabs 5/325 Caps 5/500 Oral Solution 5/325 per 5 mLTylenol with Codeine (codeine/acetaminophen) (3) Tabs 15/300 (#2), 30/300 (#3), 60/300 (#4) Oral Solution 12/120 per 5 mLVicodin (hydrocodone/acetaminophen) (3,4) Tabs 5/500, 7 .5/750 (ES), 10/660 (HP)Vicoprofen (hydrocodone/ibuprofen) (6) Tabs 7 .5/200Zydone (hydrocodone/acetaminophen) (4,6) Tabs 5/400, 10/400

Drug Short Acting (mg) Long Acting (mg)Morphine Tabs (15, 30 mg) Caps (15, 30 mg) MS Contin Tabs (q12hr) (15, 30, 60, 100, 200 mg) MSIR Oral Solution (10 mg/5 mL, 20 mg/5 mL) Oramorph SR Tabs (q12hr) (15, 30, 60, 100 mg) MSIR, Roxanol Oral Concentrate (100 mg/5mL) (1) Kadian Caps (q12hr or q24hr) (10, 20, 30, 50, 60, 80, 100, 200mg) (2, 6, 7) Supp (5, 10, 20, 30 mg) Avinza Caps (q24hr) (30, 60, 90, 120 mg) (2, 5)Oxycodone Roxicodone Tabs (5, 15, 30 mg) OxyIR Caps (5 mg) OxyContin Tabs (q12hr) (10, 15, 20, 30, 40, 60, 80 mg) Roxicodone Oral Solution (5 mg/5 mL) OxyFAST, Oxydose, Roxicodone Intensol Oral Concentrate (20 mg/mL) (1,6) Hydromorphone Dilaudid Tabs (2, 4, 8 mg) (8 mg brand-name scored) (Dilaudid) Dilaudid Oral Solution (5 mg/5 mL) Supp (3 mg) Codeine Tabs (15, 30, 60 mg) Solution or Elixir (15 mg/5 mL) Fentanyl Actiq Lozenge (200, 400, 600, 800, 1200, 1600 mcg) (5) Duragesic Transdermal Patch (12 .5, 25, 50, 75, 100 mcg/hr)Oxymorphone Opana (5, 10 mg) Opana ER (5, 7 .5, 10, 15, 20, 30, 40 mg)

SELECT COMBINATION OPIOID PRODUCTS

(1) Orders for concentrated oral opioid solutions must include drug name and strength (e.g. 100 mg/5mL) to avoid confusion with other oral solutions. (2) Data supporting safe use with enteral feeding tubes (must use size 16 French or larger) . See Kadian prescribing information and UPMC PUH SHY online formulary (Avinza) for product-specific instructions . (3) Maximum daily dose of acetaminophen is 4 grams in patients with normal liver function. (4) Many other brand name products contain similar combinations of opioids. (5) Formulary restricted. (6) Non-formulary. (7) Please note 200 mg not to be confused with 20 mg. (8) As of Fall 2008, all combination opiates with more than 325 mg of acetaminophen will be non-formulary.

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Oral and Parenteral Opioid Analgesic Equivalencies and Relative Potency of Opioids as Compared with Morphine*When converting from one opioid to another, you should use 50–75% of the equivalent dose . Allow for incomplete cross-tolerance between dif-ferent opioids (may need to titrate up rapidly and use PRN dose to ensure effective analgesia for the first 24 hours) . Avoid IM injections because of inconsistent absorption and patient discomfort .

*These are rough approximations; individual patients may vary . ** Equivalency for a one time dose of IV Fentanyl only . For Fentanyl patch conversion, see page 6 .1) Meperidine is not a first-line opioid . Avoid in patients with renal dysfunction . Contraindicated with MAOIs . Please see UPMC Meperidine

Guidelines before prescribing .2) Parenteral opioid: onset of action, 5 minutes; peak, 15 min .3) Oral opioid: onset of action, 15–30 minutes; peak, 45–60 min .4) Equivalency if acute; when long-term, potency is 100 mcg=4 mg IV morphine .Please refer to APS Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain (2003); American Pain Society (APS) Guideline for the Management of Cancer Pain in Adults and Children (2005).

Opioid Agonists Parenteral mg (2) Oral mg (3) Duration of Effect Morphine 10 30 3–4 hours Oxycodone 20–30 3–4 hours Hydromorphone 1 .5 7 .5 3–4 hours Meperidine (1) (not recommended) 75 300 3 hours Fentanyl (4) 0 .1** 1–2 hours Codeine 130 200 3–4 hours Hydrocodone 25–30 Oxymorphone 1 10 3–6 hours

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Patient Controlled Analgesia (PCA)The following are suggestions for the PCA order for adults . Like all opioid orders, doses must be individualized .

Use the preprinted PCA order form for all new PCA orders and dose changes. EDUCATE FAMILIES NOT TO PRESS THE PCA BUTTON!

*Opioid tolerant and chronic/cancer pain patients may require higher doses and continuous infusions.

1.PCA alone is a maintenance technique. Patients should receive loading doses (delivered through the infuser) that are titrated to achieve an adequate level of analgesia (pain score less than or equal to 4/10).

2.Quantity delivered when button is pressed. Reduce doses by 30-50% in elderly and patients with liver disease. Do not increase dose based on increased body weight; this is especially important in patients with Obstructive Sleep Apnea. Dosing depends on the patient—young vs. elderly/opioid naive vs. tolerant.

3.How frequently demand dose can be activated. Patient must be able to

press the button and be able to comprehend instructions on when to press the button. In the elderly, consider a longer lockout interval.

4.The hour limit should not be less than the available total hourly patient administered dose. Bolus doses and the continuous infusion are included in the one-hour dose limit count.

5.Not recommended for patients who are opioid naive, the elderly, patients with altered mentation, or with Obstructive Sleep Apnea, COPD, or asthma.

6.Morphine is generally the opioid of choice. Hydromorphone is preferred in patients with impaired renal function.

If pain unrelieved following administration of loading dose(s), increase loading dose by 50% and titrate to pain score less than or equal to 4/10.

Loading Starting Patient Lockout One-hour Dose Continuous infusion dose(s) (1) Administered Dose* (2) Interval (3) Limit (optional) (4) rate in mg/hr (5) Morphine (6) Opioid naive: 1 mg 8 –20 min . 7–10 mg 2-4 mg q 15 min Elderly (>70 yrs .) 0 .5 mg 8 –20 min . 4– 6 mg 2mg q 20 min . titrated to pain relief Hydromorphone Opioid naive: 0 .2 mg 8 –20 min . 0 .7–1 .4 mg (Dilaudid) 0 .2–0 .3 mg q 15 min Elderly (>70 yrs .) Elderly: 0 .1 mg 8 –20 min . 0 .4–0 .6 mg 0 .2mg q 20 min titrated to pain relief

When indicated, calculate based on

intermittent PCA use or previous opioid

requirement .

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TO CONvERT TO TRANSDERMAL FENTANYL—NOT USED FOR ACUTE PAIN OR INITIAL OPIOID THERAPY. USE FOR PATIENTS WHO ARE UNABLE TO TAKE PO OR HAvE CHRONIC CANCER PAIN. Determine the 24-hr parenteral morphine equivalent . Dose patch at 50–75% of the previous 24-hr opioid use . Prescribe a short-acting opioid for breakthrough pain

(5-15% of total daily long acting opiate dose every 3 hr prn) . Patch duration = 72hrs . Increase the patch dose based on the average amount of additional short-acting opioid required in the previous 72 hrs . Allow patch at least 48hrs before adjusting the dose . For dosages of transdermal fentanyl over 100 mcg/hr multiple patches can be used .

Parenteral Morphine Transdermal Fentanyl Equivalent (mg/24 hours) Equivalent (mcg/hr) 8 to 22 25 23–37 50 38–52 75 53–67 100 68–82 125 83–97 150

TWENTY-FOUR HOUR ORAL MORPHINE EQUIvALENT DIvIDED BY 2 IS EQUAL TO FENTANYL PATCH DOSE IN MCG/HR.

Iv FENTANYL DOSE/HR=TRANSDERMAL FENTANYL DOSE

NOTE: PATCH TAKES 12–24 HRS TO ACHIEvE FULL EFFECT. WHEN REMOvING A PATCH, REMEMBER THE ANALGESIC EFFECT CAN STILL LAST 24 HRS.

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Guidelines for Naloxone Administration and Patient Monitoring1. Nurses may administer naloxone without a physician’s order

when patients who have received an opioid meet the following criteria: (a) Sedation Scale = 3 (Somnolent; Difficult to arouse), (b) RR < 8 OR Oxygen Saturation < 92% and RR < 12

2. If the criteria listed above are met, stop the administration of the opioid (including fentanyl patches) and benzodiazepines .

3. Provide oxygen via face mask STAT.

4. Method for naloxone administration: Naloxone 0.04 mg IV q 1 minute until a change in alertness is observed. Dilute 0 .4mg naloxone (one ampule) with NSS to a total volume of 10ml (1 ml = 0 .04 mg) in a 10 ml syringe .

5. Notify the primary physician and/or house staff of the need to immediately evaluate the patient. If the house staff does not arrive within five minutes or if the nurse assesses the need, a “Condition C” should be called .

6 Titrate the prescribed naloxone until the patient is responsive. The half-life of naloxone (ONE HOUR) is shorter than the half-life of opioid agonists . Naloxone administration should not cause pain to return or precipitate opioid withdrawal. If a response is not obtained after one ampule of naloxone (10 cc of diluted solu-tion) is administered, examine the patient for alternate causes of sedation and respiratory depression. For assistance with further naloxone dosing, please contact the Toxicology Treatment Program (412-647-7000) .

7. Re-evaluate the events leading to the need for naloxone administration. In cases where the prescribed opioid dosing was too high, reassess the therapeutic plan for pain management . Consider decreasing the opioid dose by 50%. Resume opioid administration when the patient is easily aroused, is beginning to experience pain, and after the RR increases to > 9 .

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Nausea and Vomiting: TreatmentMechanism-based therapy involves the following steps:1. A complete history and physical including oropha-

ryngeal, abdominal, rectal and neurological exams2. Consider labs: BUN/Cr, Na, LFT’s, amylase/lipase,

Ca, drug levels3. Consider imaging: flat plate of the abdomen to

assess for constipation, Abdominal CT to evaluate for obstruction, Head CT/MRI

4. Determine which receptors are mediating the symptoms (see below)

5. Choose an antiemetic to block the implicated recep-tors (see next page)

Pathophysiology of nausea and vomiting Nausea and vomiting are triggered by activation of one of four main pathways:1 . Chemoreceptor Trigger Zone (CTZ): Main receptors:

D2, 5HT3, NK12. Cortex: Main receptors are in the vomiting center.3. Vestibular apparatus: Main receptors: Ach, H14. Peripheral pathways: Mediates nausea from trigger-

ing of GI/visceral chemoreceptors (local toxins) and mechanoreceptors (stretch). Enterochromaffin cells release 5HT3 when damaged (ie by chemotherapy or radiation) which activates local 5HT3 receptors.

These four pathways send signals to the vomiting center

(main receptors: H1, Ach, 5HT2) which triggers nausea and vomiting when thresholds are reached.If nausea is persistent, severe or refractory:• Schedule antiemetics around the clock, not PRN• Choosesecondandthirdantiemeticswhichworkon

different receptors.• ConsiderPalliativeCareconsultforsecondandthird

line therapiesIN ADDITION TO USING ANTIEMETICS, ALWAYS TREAT ANY REVERSIBLE CAUSES (medications, anxiety, constipation, hypercalcemia, thrush, increased ICP, GERD, pain)ALWAYS EVALUATE FOR CONSTIPATION AND PERFORM A RECTAL EXAMAvoid use of promethazine because of adverse effects including sedation and respiratory depressionAvoid benzodiazepines unless the nausea is from anxiety because they can sedate the patient and increase risk of aspirationFor nausea associated with vomiting, give antiemetics via the IV route until symptoms are controlledEvaluate for clinical signs of bowel obstruction (persis-tent nausea briefly relieved by vomiting, abdominal pain, distended abdomen, obstipation)If bowel obstruction, consider surgery and/or GI consults for possible surgical repair or venting PEG tube

Consider palliative care consult for medical management of bowel obstruction.References:Wood GJ, Shega JW, Lynch B, Von Roenn JH. Management of intractable nausea and vomiting in patients at the end of life “I was feeling nauseous all of the time…nothing was working.” JAMA. 2007;298(10): 1196-1207.

Receptors:D2: Dopamine type 2 receptor, 5HT3: 5-hydroxytrypta-mine type 3 receptor, 5HT2: 5-hydroxytryptamine type 2 receptor, Achm: muscarinic acetylcholine receptor, H1: histamine type 1 receptor, NK1: Neurokinin type 1 receptor

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Drug (Generic Name)

Receptoractivity

Common ClinicalIndications Dosage/Route Cost Comments/

Side Effects

Haloperidol D2 Opioid Induced N/V 0.5-4 mg PO or SQ or IV Q6h $ IV has less EPS compared to PO

Metoclopramide Peripheral D2 Impaired GI motility Opioid Induced N/V

5-20 mg PO or SQ or IV AC and HS $ EPS, esophageal spasm,and colic inGI tract obstruction

Prochlorperazine D2 Opioid Induced N/V N/V of unknown etiology

5-10 mg PO or IV every 6 h or 25mg PR Q6h

$ EPS and sedation

Scopolamine Ach, H1 Motion induced N/V 1.5 mg Transdermal patch every 3 d $ Dry mouth, blurred vision, ileus, urinary retention, and confusion

Ondansetron 5HT 3 Chemotherapy or radiation induced N/V

4-8 mg PO as a pill or dissolvable tablet or IV every 4-8 h

$$ Headache, fatigue, and constipation

Dexamethasone Decrease ICP N/V related to Increased ICP

4-8mg QAM or BID, PO (as pill or liquid) and IV

$ Agitation, Insomnia, Hyperglycemia

N/V: Nausea/Vomiting

Nausea and Vomiting: Treatment

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Medication Onset of action Usual starting dosage Site and Mechanism of ActionOsmotic laxatives

Lactulose 24-48h 15-30ml q12-24h Colon; osmotic effect

Polyethylene Glycol 48-96h 17g (1tbsp) powder in 8oz water q24h GI tract; osmotic effect

Sorbitol 24-48h 15-30ml q12-24h, max 150ml/d Colon; delivers osmotically active molecules to the colon

Saline Laxatives*

Magnesium citrate 30min-3h 120-240ml x1; 10oz q24h Small and large bowel; attracts and retains water in the bowel lumen

Magnesium hydroxide (MOM) 30min-3h 30ml q12-24h Colon; osmotic effect & increased peristalsis

Stimulant laxatives

Bisacodyl 6-10h 5-15mg x1 Colon; stimulates peristalsis

Bisacodyl (PR) 15min-1h 10mg x1 Colon; stimulates peristalsis

Senna 6-10h 2 tabs qhs Colon; stimulate myenteric plexus, alters water and electrolyte secretion

Surface laxatives

Docusate 24-72h 100mg q12-24h Small and large bowel; detergent activity; softens feces

Constipation and Bowel Protocol

Bulk laxatives alone are not useful in the treatment of opiate induced constipation*Avoid use of MOM and related products (including sodium phosphate enema products) in patients with renal dysfunction because of risk of hyperphosphatemiaReference: Reuben DB, Herr KA, Pacala JT, et al. Geriatrics at Your Fingertips 2009, 11th edition. New York: The American Geriatrics Society; 2009 BOWEL REGIMEN: With few exceptions, all patients on opioid therapy need an individualized bowel regimen. When and effective regimen is found it must be continued for the duration of the opioid therapy. If a patient has not been on a bowel regimen, the step 1 regimen should be started. If there is no response in 24 hours, move to the next step. At any given time, if there has been no bowel movement in four or more days, a sodium phosphate or mineral oil enema should be administered. If this is not effec-tive, a high colonic tap water enema should be administered. Be aware of the possibility of bowel obstruction or fecal impaction. A digital rectal exam should be performed prior to starting a bowel regimen and if no BM for 4 days.

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Constipation and Bowel Protocol

Step 1—Begin with a laxative . The following are some suggestions: a . MOM 30cc po qd b . Senna 1 tab po qdStep 2—Senna 2 tabs bidStep 3—Senna 3 tabs bidStep 4—Senna 4 tabs bid + Lactulose 15cc po bidStep 5—Senna 4 tabs bid+ Lactulose 30 cc po bidStep 6—Senna 4 tabs bid + Lactulose 30 cc po qid

Other drugs that can exacerbate constipation: anticholinergics (tricyclic antidepressants, scopolamine, oxybutinin, promethazine, diphenhydr-amine), lithium, verapamil, bismuth, iron, aluminium, calcium saltsOpiod Antagonists to treat refractory constipation: Methylnaltrexone (MNTX) is a quaternary amine which does not cross the blood brain barrier to cause reversal of opioid analgesia or withdrawal. Use of oral naloxone for constipation has been associated with these effects. MNTX is approved for use in patients who have been on a steady opioid regimen for 2 weeks and laxative regimen for 3 days. Greater than 50% of patients will have a bowel movement within 4 hours of being given the dose by subcutaneous injection. In general, it is recommended that oral and rectal laxative regimens should have been tried, prior to utilizing MNTX. Pts with fecal ostomy bags and PD catheters were excluded from the studies. There is a dosing order set in the EMR.

BOWEL REGIMEN: With few exceptions, all patients on opioid therapy need an individualized bowel regimen. Start with the step 1 regimen . When an effective regimen is found it must be continued for the duration of the opioid therapy .

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Delirium: Diagnosis DSM-IV criteria for delirium include four components: A . Acute onset, over hours to days .B . Behavioral disturbance, marked by a reduced clarity in the patient’s

awareness of the environment, with impaired ability to focus, sustain, or shift attention . The patient may be agitated, irritable, and emotionally labile, OR drowsy, quiet, and withdrawn .

C . Consciousness level fluctuates over the course of the day . D . Different from dementia, delirium cannot be accounted for by a patient’s

preexisting, established, or evolving dementia . Delirium is conceptualized as a reversible illness, except in the last 24–48 hours of life .

1 . Delirium occurs in at least 25–50% of hospitalized cancer patients, and in a higher percentage of patients who are terminally ill . Delirium increases the risk of in-hospital and six-month mortality .

2 . Differential diagnosis: D: Drugs (opioids, anticholinergics, sedatives, benzodiazepines, steroids, chemo- and immunotherapies, some antibiot-ics); E: Eyes and Ears (poor vision and hearing, isolation); L: Low flow states (hypoxia, MI, CHF, COPD, shock); I: Infections; R: Retention (urine/stool), Restraints; I: Intracranial (CNS metastases, seizures, subdural, CVA, hypertensive encephalopathy); U: Under-hydration, Under-nutrition, Under-sleep; M: Metabolic disorders (sodium, glucose, thyroid, hepatic, deficiencies of vitamin B12, folate, niacin, and thiamine) and Toxic (lead, manganese, mercury, alcohol) .

3 . Routinely screen for delirium, and monitor delirious patients frequently .

AssessmentAsk family or friends of patient

Patient is easily distracted . Abnormal Digit Span: Inability to repeat a series of five digits (start with reading aloud a string of two random digits, then increase) and vigilance A: At least two errors (read aloud in neutral normal tone a list of 10 letters with four A’s . Patient taps when A is read) . Rambling or irrelevant conversation, unclear or illogical flow of ideas, or topic switching, or ask patient’s family . Ask: 1) Can a rock float? 2) Are there fish in the sea? 3) Is one pound more than two pounds? 4) Do you use a hammer to pound a nail? 5) Command say to patient, “Hold up this many fingers .” (Examiner holds two fingers in front of patient .) Next, do the same thing with the other hand (not repeating holding up the number of fingers) .

Hyper-alert, drowsy, stuporous, or unarousable

Feature1 . Acute onset and fluctuating course

AND 2 . Inattention

PLUS3 . Disorganized thinking >2 errors

OR4 . Altered level of consciousness

Confusion Assessment Method (CAM) ICU for the Diagnosis of DeliriumDiagnosis positive with 1 and 2, plus 3 or 4

See www.icudelirium.org for more information and http://elderlife.med.yale.edu for more information on the CAM and delirium in the hospital.

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Delirium: Treatment Rule out other medical causes of delirium . Review medications, and discontinue or decrease anticholinergic and/or benzodiazepine doses . Check for drug-drug interactions . Rotate opioids, reduce doses by 25% if possible, and avoid meperidine .

Benzodiazepines are NOT effective in treating delirium, may worsen delirium, and should be used cautiously only as adjunct therapy with neuroleptics when relief of agitation is required .

Neuroleptics are used for treatment of delirium . Haloperidol is the standard neuroleptic for treatment of delirium . Risperidone, olanzapine, and quetiapine are atypical neuroleptics, generally with fewer side effects . All neuroleptics can cause QT prolongation .

Supportive care to prevent and reduce delirium includes frequent orientation (well-lit rooms, caregivers, calendars, clocks, communication), therapeutic activities (patient mobilization 3x/day when possible), non-pharmacologic sleep aids (see page 12), treatment of hearing and vision problems, treatment of incontinence, and volume repletion . Confusion increases the risk of falls . Pay attention to patient safety . Constant supervision (sitter) may be more beneficial than restraints or sedation .

Table 2: Drugs used for treatment of delirium in the hospital setting

Generic name(Common brandname)

Starting dose

Dosing interval

Max q24hdose

Formulations EPS Anti-cholinergic

Sedation Comments**

Haloperidol(Haldol®)

0 .5-1mg(2mg in ICU*)

0 .5-1hour forurgentsymptoms .Otherwise Q6Hor Q8H

20mg 0 .5, 1, 2, 5, 10 mgtablets . Available asoral solution and asan injectableproduct .

+++ + ++ IV has less EPScompared to PO .***

(continued)

14

Abbreviations: EPS: extrapyramidal symptoms; IM: intramuscular; IV: intravenous; ODT: oral disintegrating tablet; SQ: subcutaneous .Definition: †Sundowning: Onset of confusion in the elderly that typically begins in the evening*Refer to the UPMC Presbyterian Shadyside “Acute Agitation Management” order set .** The FDA has determined that the use of antipsychotic medications in the treatment of behavioral disorders in elderly patients with dementia is associated with increased mortality . This risk appears to be highest during the first two weeks of use .*** Use IV haloperidol with caution in patients with prolonged QT interval . Increased risk of arrhythmia and sudden death exists with high IV doses .

Generic name(Common brandname)

Starting dose

Dosing interval

Max q24hdose

Formulations EPS Anti-cholinergic

Sedation Comments**

Risperidone(Risperdal®)

0 .25-1mg BID or up to Q6HPRN

6mg 0 .25, 0 .5, 1, 2, 3,4mg tablets .Available as ODT (not for 0 .25)

++ + + Caution withrenal failure .

Olanzapine(Zyprexa®)

2 .5-10mg

Debilitatedor elderly:2 .5 mg .

DAILY

IM: Q2H

20mg 2 .5, 5, 7 .5, 10, 15,20 mg tablets .Available as ODT (5, 10,15 & 20 mg)and IM injection

+ +++ ++ Patients with hypoactivedelirium, >70yearsCNS malignancymay not respond well .

Quetiapine(Seroquel®)

12 .5- 50mg

BID 800mg 25, 50, 100, 200,300, 400 mg tablets

+ ++ +++ Start DAILY at 4pm forsundowning† and then time subsequent, additional dosesbased on symptoms .

Aripiprazole(Abilify®)

5-15mg Q AM 30mg 2, 5, 10 . 15, 20,30mg . Available asIM and oral solution . Available as ODT (10 & 15 mg)

++ + ++ Useful for hypoactivedelirium . Can cause insomnia if given at night

Delirium: Treatment

15

Estimated frequencies of Causes of DementiaAlzheimers Disease (AD): 60-70%Other progressive disorders: 15-30% (eg, vascular, Lewy body, frontotemporal)Completely reversible dementia (eg, drug toxicity, metabolic changes, thyroid diseases, subdural hematoma, normal pressure hydrocephalus: 2-5%

Dementia: Course

Progression of AD Common clinical features Usual MMSE; CDR* scores

Mild Cognitive impairment(preclinical)

Report by patient or caregiver of memory lossNo functional impairmentObjective signs of memory impairment6-15% annual conversion rate to dementia syndrome

26-30; 0.5

Early, mild impairmentYr 1-3 from onset of symptoms

Disoriented to date; naming difficulties; recent recall problemsDecreased insight; social withdrawal; irritability, mood changes

21-25; 1

Middle, moderate impairmentYr 2-8 from onset of symptoms

Disoriented to date, place; comprehension difficulties; impaired new learning; getting lost in familiar areasDelusions, agitation, aggression; restless, anxious, depressionNot cooking, shopping, bankingProblems with dressing, grooming

11-20; 2

Late, severe impairmentYr 6-12 from onset of symptoms

Nearly unintelligible verbal output; remote memory goneNo longer grooming or dressing; incontinentMotor or verbal agitation

0-10; 3

* MMSE: Mini Mental Status Exam, CDR: Clinical Dementia Rating ScaleReference: Reuben DB, Herr KA, Pacala JT, et al. Geriatrics at Your Fingertips 2009, 11th edition. New York: The American Geriatrics Society; 2009

16

Dementia: PrognosticationFunctional Assessment Staging (FAST) Mortality Risk Index Score (Mitchell)

Stages Points Risk Factor

1 . No difficulties2 . Subjective forgetfulness3 . Decreased job functioning and organizational capacity4 . Difficulty with complex tasks, instrumental ADLs5 . Requires supervision with ADLs6 . Impaired ADLs, with incontinence7 . A . Ability to speak limited to six words B . Ability to speak limited to single word C . Loss of ambulation D . Inability to sit E . Inability to smile F . Inability to hold head up

1 .9 Complete dependence with ADLs1 .9 Male gender1 .7 Cancer1 .6 Congestive heart failure1 .6 O2 therapy needed w/in 14 days1 .5 Shortness of breath1 .5 <25% of food eaten at most meals1 .5 Unstable medical condition1 .5 Bowel incontinence1 .5 Bedfast1 .4 Age > 83 y1 .4 Not awake most of the day

National Hospice and Palliative Care Organization- FAST Stage 7A- hospice appropriate7C or worse, median survival- 3.2 months

Risk estimate of death within 6 months Score Risk %

Compared to FAST Stage 7C, the MRI had greater predictive value of six-month prognosis .

Mortality Risk Index has been validated only in newly admitted nursing home residents .

0 8 .9 1-2 10 .8 3-5 23 .26-8 40 .49-11 57 .0≥12 70 .0

Tsai S, Arnold RA. Fast Fact and Concept #150. Prognostication in Dementia. February 2006. End-of-Life/Palliative Education Resource Center (www.eperc.mcw.edu).

17

Depression: Screening Tools and TreatmentA shorter screening test for depression is to ask:

1 . Are you feeling either depressed or hopeless most of the time over the last 2 weeks?

2 . Have you found little brings you pleasure or joy over the last 2 weeks?

From: R Arnold . Fast Fact and Concept #146: Screening for Depression in Palliative Care . End-of-Life/Palliative Education Resource Center (www .eperc .mcw .edu) . 2005

Spiritual Distress Screen—A Quick Screen

1 . Ask “Are you at peace”?

2 . If the answer is no, ask the patient if he/she would like to see a chaplain .

Source: Archives of Internal Med 2006:166:101-5 .

Some select antidepressants are listed in the table next page:

18

Category Generic(Common Brand Name)

Starting PO dose(depression)*

Dosinginterval

Therapeuticdose/day range*

Generic(Y/N)

Formulations (mg)

SSRIs Citalopram(Celexa®)

10-20mg DAILY 10-60mg Y 10, 20, 40 (tablets)10mg/5mL (solution)

Escitalopram(Lexapro®)

5-10mg DAILY 10-20mg N 5,10, 20 (tablets)5mg/5mL (solution)

Sertraline(Zoloft®)

25-50mg DAILY 50-200mg Y 25, 50, 100 (tablets)100mg/5mL (solution)

SNRIs Venlafaxine(Effexor®)

75mg/day divided BID-TID 150-375mg Y 25, 37 .5, 50, 75, 100 (tablets)

Venlafaxine XR(Effexor XR®)

37 .5-75mg DAILY 75-225mg N 37 .5, 75, 150 (capsules)

Duloxetine(Cymbalta®)

20mg BID 30-60mg N 20, 30, 60 (delayed-released capsules)

Stimulants Methylphenidate(Ritalin®)

2 .5-5mg BID 8a,12p 5-40mg (fordepression)

Y 5, 10, 20(tablets)

Commonly used antidepressants: dosing, formulations

Abbreviations: CR, SR, XL, XR: sustained-release products SSRIs: Serotonic Specific Reuptake Inhibitors, SNRIs: Serotonin Norepinephrine Reuptake InhibitorsOthers: Use the following w/caution in renally impaired patients: all SNRIs, all formulations of buproprion and mirtazapineUse the following w/caution in hepatically impaired patients: All SSRIs, methylphenidate, all SNRIs and bupropion*The therapeutic dose/day range varies from the minimum efficacious dose up to the maximum tolerated or daily recommended amounts . Maximum daily doses are dependent upon indication for use and should only be used as a guide . Initial doses should be low in elderly patients and increased gradually . Doses of up to 300 mg of venlafaxine XR have been used in practice, but are not FDA-approved . The doses for methylphenidate can be higher than 20mg but are generally not recommended .

19

Drug (Commonbrand name)

Cost perday*

Anticholinergic Insomnia GI Distress Comments**

Citalopram(Celexa®)

<$ + + ++ Mild to moderately activating, few drug interactions .

Escitalopram(Lexapro®)

$ + +++ ++ t1/2 similar to Sertraline and Citalopram

Sertraline(Zoloft®)

$ -- + +++ Moderately activating .

Venlafaxine(Effexor®)

$ $ + +++ +++ Dual serotonin/norepinephrine action at doses of 150-225mg which is effective in neuropathic pain and is mildly activating . On switching from thevenlafaxine XR to venlafaxine, the shorter half life of venlafaxine requires frequent dosing to reach the same dose of venlafaxine XR .Use with caution in patients with hypertension .

Venlafaxine XR(Effexor® XR)

$ $ $ $ + +++ ++

Duloxetine(Cymbalta®)

$ $ $ $ ++ ++ ++ FDA-approved for diabetic neuropathy and off-label use for urinary incontinence . Do not use in patients with liver dysfunction . Use caution in patients with seizure disorder .

Methylphenidate(Ritalin®)***

<$ -- +++ + Energizing, may increase appetite .

Commonly used antidepressants: costs, side effects, comments

Abbreviations: ODT: oral disintegrating tablet; t1/2: half-life .*Cost per day of a typical daily dose was calculated based on generic products when available . Cost data was extrapolated from www .drugstore .com .**Activating antidepressants tend to cause insomnia .***Not FDA-approved for treatment of depression . Differences in arrythmogenicity are not clinically relevant among these groups .

20

End-Stage Liver DiseaseDefine as cirrhosis + 2 of (alb<3, bili>3, ascites require Tx; encaph with Glasgow <10; cachexia or UGIB require > 2 units)

Child C- roughly 90% die if admit to ICU; if Cr >1.3 and ventilator closer to 95+%

Child 1 2 3

Ascites none slight moderate

Bilirubin (mg/dL) <2 2-3 >3

Albumin (mg/L) >3 .5 28 .-3 .5 <2 .8

PT < 1 .7 1 .8-2 .3 >2 .3

Encephalopathy none Gr I-II Gr II-III

Child Score 1-year mortality 2-year

A 5-6 <5% 15%

B 7-9 20% 40%

C >10 55% 65%

21

End-Stage Liver Disease (continued)SUPPORT data for prognosis in cirrhosis:

MELD=.957 x logc(cr in mg/dl)+ .378 xlogc(bili) +1.120 logc(INR)

Cr 1-2 1 pt Age >65 1 pt

Cr > 2 2 pt PT>16 1 pt

Glasgow 10-14 1 pt Vent or pO2<60 1 pt

Glasgow<10 2 pt

Total 1-month 6-month mortality

0-1 12% 25%

2-3 40% 50%

>4 75% 90%

Total popl 30% 50%

Score 3-month mortality

0-9 0-5%

10-19 13-29%

20-29 50%

30-39 60-80%

40+ 95+%

Calculator- http://www .mayoclinic .org/meld/mayomodel6 .html

22

Opioids in Actively Dying Patients 1 . The following guidelines are for “comfort measures” patients

ONLY . See Print On Demand and/0r CPOE CMO order sets .

• “Titratetocomfort”medicationordersarenotacceptable.Parameters for drug dosing and titration must be included on all written and electronic care sets .

2 . Opioid naive patient (all doses are for morphine):

• Loadingdose:2–5mgIVpush.

• Ifdistressnotrelievedin15minutesafterinitialloadingdose,give bolus equal the loading dose increased by 50 percent . If severe distress persists repeat the dose every 15 minutes until comfortable .

• Forincreasedpain/distressgiveextrabolusdose/sequaltothelast given bolus dose every 30 min . as needed .

• Ifusingmorethan2bolusdosesover6-hourperiod,considerstarting a continuous infusion . To calculate the continuous infusion rate divide the total dose over last 6 hours by 6 .

3 . Non-naive patients:

• Forpatientswhohavebeentakingopioidpainmedicationswithin last 24 hours calculate the equianalgesic parenteral dose of morphine for the last 24 hrs (see page 4 for opioid equivalencies) .

• Dividethetotal24hourIVmorphinedoseby24todetermineinitial hourly infusion rate (mg/hour, IV) . Start continuous infusion at this rate .

• Ifpatientinpain/distressuseloadingdose=hourly infusion rate .

• Ifdistressnotrelievedin15minafterinitialloadingdoseorthe patient in increased pain/distress, administer the loading dose increased by 50 percent and repeat every 15 minutes until comfortable .

• Ifusingmorethantwobolusdosesover6-hourperiod,deter-mine new continuous infusion rate by recalculating total dose given over last 6 hours and dividing it by 6 .

23

Oral Secretions at the End of Life As the level of consciousness decreases in the dying process, patients lose their ability to swallow and clear oral secretions . As air moves over the secretions, the resulting turbulence produces noisy ventilation with each breath, described as gurgling or rattling noises . Death rattle is a good predictor of near death; one study indicated the median time from the onset of death rattle to death was 16 hours .

Non-pharmacological treatments: Position the patient on their side or in a semi-prone position to facilitate postural drainage . Reassure family about noise; can compare to snoring .

While there are no evidence-based guidelines, the standard of care is to use muscarinic receptor blockers (anti-cholinergic drugs) .

*Use atropine ophthalmic drops .Tertiary amines which cross the blood-brain barrier (all but glycopyrrolate) cause CNS toxicity (sedation, delirium) . Source: K Bickel; R Arnold . Fast Fact and Concept #109: Death Rattle and Oral Secretions, 2nd Edition . End-of-Life/Palliative Education Resource Center (www .eperc .mcw .edu) 2003 .

Drug (Trade Name) Route Starting Dose Onset

hyoscyamine hydrochloride Scopolamine Transdermal 1 (~1 mg/3 days) 12 hrs .

hyoscyamine sulfate Levsin Drops, Tabs (oral) 0 .125 mg 30 min .

glycopyrrolate Robinul Pills (oral) 1 mg 30 min .

glycopyrrolate Robinul Injection (SC, IV) 0 .2 mg 1 min .

atropine Atropine Injection 0 .1 mg 1 min .

atropine multiple Sublingual* 1 gtt (1%) 30 min

24

UPMC Pain and Palliative Care Resources (area code 412) PUH/MUH Palliative Care Service/Cancer Pain 647-7243, pager: 8511

PUH/MUH Chronic Pain Service 647-4991

PUH/MUH Medical Ethics 647-7243, pager: 2881

PUH/MUH Acute Interventional Perioperative Pain Service (AIPPS) 647-7243, pager: 7246 (PAIN)

Shadyside Acute Interventional Perioperative Pain Service (AIPPS) 692-2333

Shadyside Dept . of Medical Ethics 263-8347, pager

Shadyside Dept . of Palliative Care 647-7243, pager: 8513

Shadyside Chronic Pain Service 665-8030, after hours call 665-8031

Magee-Womens Hospital of UPMC Palliative Care (malignant pain) 647-7243, pager: 8510

Magee-Womens Hospital of UPMC Pain Medicine (nonmalignant/outpatient) 641-7600

Magee-Womens Hospital of UPMC Pain Medicine (chronic pain / inpatient) 901-2891

Childrens Hospital of Pittsburgh Supportive Care Program 692-3234

Magee-Womens Hospital UPMC Womens Cancer Center Palliative Care Clinic (E . Weinstein) 641-4530

VA Palliative Care Program inpatient and oncology 688-6000 Ext . 816178; or pager 645-2345 Geriatric palliative care—pager 958-0215

UPMC Hillman Cancer Pain, Rehabilitation and Supportive Care (outpatient) 692-4724

UPMC Cardiopulmonary Disease Palliative Care Clinic (W . Teuteberg) 647-6000

UPMC PUH Pain Medicine (outpatient) 692-2234

Centre Commons Pain Medicine (outpatient) 665-8030

St . Margaret—Pain Medicine (outpatient) and Chronic Pain Service (outpatient) 784-5119 (outpatient) or 784-4000 (UPMC St . Margaret Operator)

Family Hospice and Palliative Care 572-8800

25

Questions or comments regarding this information, contact Robert Arnold, MD (rabob@pitt.edu), 692-4834, pager 2322. This information provided by the Palliative Care Program is merely in the form of recommendations and does not replace the service of a physician. Author: Mamta Bhatnagar, MD with feedback from Colleen Dunwoody, RN; Justin Engleka, NP; Paul Han, MD; Susan Hunt, MD; Linda King, MD; Ray Paronish, NP; Rowana Schwatz, PharmD; Susan Skledar, RPh, MPH; Peg Verrico, RPh; Elizabeth Weinstein, MD; Gordon Wood, MD and Robert Arnold, MD. This pain card was made possible with generous support of the The Center for Quality Improvement and Innovation. Produced in cooperation with the University of Pittsburgh. The University of Pittsburgh is an affirmative action, equal opportunity institution. UMC78126-0511

•Psychological or spiritual counseling for patients and their families•Discharge planning and interface with local hospices•Bereavement services in the event of death•Outpatient palliative care follow-up

Indications for Palliative Care Referral:•Pain in patients with life-limiting illness•Management of other symptoms such as nausea, vomiting, shortness of breath, delirium •Negotiating goals of treatment or end-of-life decision making•Family support for a patient with a life-limiting illness

VERSION 9 .0 PAIN CARD

Institute to Enhance Palliative Care