1. SYMPTOM MANAGEMENT AT THE END-OF-Life
Laura Mantine M.D.

2. Objectives Review General Principles of Symptom Management
Discuss the assessment and treatment of:
Anxiety
Delirium
Depression
Nausea & Vomiting
Pain
Anorexia
Dyspnea

3. General Principles of Symptom Management
Look for reversible causes
Most symptoms should be controlled within hours
Stringent review of medications
How much medication are you using?
Is the medication effective?
Consider ATC dosing is >3 prn doses a day
Kill two birds with one stone
Do not “prn” an ATC symptom

4. Anxiety
Culmination of physical and psychological symptoms mixed with the reality of the situation
May present in many ways
Possible Causes:
Poor pain control
Metabolic issues – hypoxia, hyper/hypocalcemia, infection, urinary retention, constipation
Drug related – steroids, benzodiazepines (paradoxical), bronchodilators, withdrawal (nicotine, ETOH, opiates, antidepressants)
Clinical Wisdom:
Asses for depression in all patients
Antidepressants (SSRI/SNRI) are preferred agents for chronic anxiety
Avoid short acting benzodiazepines if possible
Benzodiazepines are associated with falls

5. Anxiety General medications used: Benzodiazepines Antipsychotics
Lorazepam
Clonazepam
Antipsychotics
Haldol
Quetiapine
Antidepressants

6. Delirium Pneumonic – FATC Fluctuating with acute onset
Attention poor, difficulty focusing, easily distracted
Thinking disorganized, rambling, illogical
Consciousness altered (hypo or hyper or mixed)
General approach:
Look for underlying cause
Remove or treat cause if possible
Use of antipsychotics/benzodiazepines
Create a safe environment for patient/caregiver

7. Depression Two item screening tool: Non-pharmacological
Are you depressed?
Have you experienced loss of interest in things or activities that your would normally enjoy?
If the answer to both questions is yes, patient is depressed.
Non-pharmacological
Pharmacological:
SSRI – not effective for pain
SNRI – Cymbalta effective for neuropathic pain
Psychostimulants
TCA –use rarely
Atypical:
Bupropion – lowers the seizure threshold
Trazodone – helps with sleep
Mirtazapine – helps with sleep and appetite stimulation

8. Nausea & Vomiting Common Causes Clinical Picture
Principle Site of Action
Chemical • Drugs (opioids, digoxin, steroids, antibiotics, anticonvulsants, cytotoxics) • Biochemical (hypercalcemia, uremia, organ failure) • Toxins (tumor factors, infection, drug metabolites, radiation, ischemic bowel, food poisoning)
Symptoms of drug toxicity or underlying disease plus nausea as the prominent symptom. Nausea usually not relieved by vomiting.
Chemo trigger Zone (CTZ), Dopamine (D2), Serotonin receptor antagonist (5-HT3)
Gastrointestinal Tract–Vagal • Gastric irritation (ASA, NSAIDs, steroids, antibiotics, blood, ETOH, stress, radiotherapy) • Obstruction (partial or complete) • Constipation • Gastric stasis • Mass effect (GI, GU, hepatic distention, carcinomatosis) • Anatomic / Structural
Epigastric pain, fullness, acid reflux, early satiety, flatulence, hiccup, intermittent nausea relieved with vomiting. Altered bowel habit, pain may occur with oral intake. Vomitus may be large volume and fecal smelling.
Vagal & sympathetic afferent nerve pathways. Dopamine (D2), Serotonin receptor antagonist (5-HT3) and 5HT4 receptors H2 receptors Acetylcholine
CNS • Increased Intracranial Pressure (brain metastases, infectious meningitis, cerebral edema, bleeding) • Psychological (fear, anxiety, pain
Headache +/- cranial nerve signs, (diurnal). Vomiting often without nausea. Anticipatory nausea / vomiting to sights, smells, etc.
Histamine (H1) receptors
Vestibular • Motion sickness • Cerebellar tumor
Nausea +/- vomiting with movement.
Acetylcholine

9. Nausea & Vomiting
Treatment recommendations – select antiemetic according to etiology, if the nausea is not controlled:
Titrate up antiemetics to their full dose before adding another drug
If nausea not controlled with a specific antiemetic, add another drug from another group but do not stop initial agent
Use regular dosing of antiemetics if experiencing constant nausea and vomiting
Antiemetics should be prescribed as a regularly scheduled dose with a breakthrough dose
Give antiemetics prophylactically to prevent nausea with high dose opioids and chemotherapeutic agents
Assess hydration and consider IVF if necessary

10. Nausea & Vomiting Drug Doses/Routes Major Side Effect
Serotonin Antagonists
Zofran
8-24 mg IV/PO qd
Constipation
Dopamine Antagonists
Compazine
Reglan
Haldol
10 mg PO/PR q 4-6 h
10-40 mg PO/IV TID-QID
0.5-2 mg IV/PO q 4-8 h
EPS
Corticosteroids
Decadron
4-20 mg PO/IV qd-BID
Delirium, anxiety, insomnia
Antihistamines
Benadryl
Antivert/Vistaril
Phenergan
25-50 mg IV/PO q 4-6 h
25-50 mg PO q 6 h
PO/PR/IV/IM q 4 h
Sedation, confusion
Anticholinergics
Scopolamine
1.5-3 mg TD q 72 h
Dry mouth, blurred vision
Cannabinoids
Marinol
2.5 – 10 mg BID-TID
Confusion, ataxia
Anxiolytics
Ativan
0.5 – 2 mg PO/IV q 4-6 h
Confusion, sedation
Atypical Antipsychotics
Zyprexa
2.5 – 5 mg qd
Sedation

11. Pain Treatment recommendations: Opiates are generally very safe
Morphine is the preferred opiate for pain
Do not mix opiates
Most patients “allergies” are actually side effects
Commons side effects:
Constipation (90%) – ALL patients need a bowel regimen
Sedation (33%) – usually resolves in 3-7 days
Nausea (33%) – usually resolves in 3-7 days

12. Pain 3 5 4 7 Equianalgesic conversions Oxycodone x 1.5 = Morphine
Example: 10 mg Oxycodone = 15 mg Morphine
Duragesic patch x 2 = 24 hour oral Morphine
Example: 25 mcg/hr Duragesic = 50 mg oral Morphine
Morphine/Diluadid
10 mg IV Morphine = 30 mg po Morphine
30 mg po Morphine = 7.5 mg po Dilaudid
7.5 mg po Dilaudid = 1.5 mg IV Dilaudid
1.5 mg IV Dilaudid = 10 mg IV Morphine 3 5 4 7
Morphine
Dilaudid
(30) PO
(7.5)
(1.5)
IV (10)

13. Pain
If pain is well-controlled: when converting from one opiate to another, use the conversions above and decrease the dose of the new opiate by 25%
If pain is moderate to severe: when converting from one opiate to another, use the conversions above and do not decrease the dose
Opioid Equianalgesic Doses
Drug
PO/PR (mg)
SQ/IV (mg)
Morphine 30 10
Oxycodone 20
N/A
Hydrocodone
Hydromorphone
7.5
1.5
Fentanyl
0.1 (=100mcg)

14. Anorexia Non-pharmacological therapy: Pharmacological therapy:
Patient and family education about pathophysiology of the anorexia and cachexia in the terminal illness, and the ineffectiveness of forced feeding and hydration
Eliminate dietary restrictions
Reduce portion size and eliminate unpleasant foods
Pharmacological therapy:
Decadron: 2-20mg PO each morning; effect may diminish after 4-6 weeks of use Megace: 200 mg PO every 4-6 hours; titrate dosage to achieve and maintain desired effect
Marinol: 2.5 mg PO BID-TID; titrate dosage to patient tolerance and to achieve and maintain desired effect

15. Dyspnea
Opioids are the drug of first choice in the palliation of dyspnea in advanced disease of any cause.
When dyspnea occurs with most/any activity or for dyspnea at rest, initiate opioids while continuing with non-pharmacological strategies.
Dose is individualized and titrated until patient states they are comfortable or until restlessness, agitation or apparent breathlessness are controlled in non-verbal/confused patients. Continued titration may be necessary as tolerance develops.
Nebulized opioids have NOT been shown to be superior to oral opioids and are therefore not recommended.
Relief occurs in the absence of significant changes in blood gases or oxygen saturation.
Respiratory depression from opioids is rare and they do not hasten death if appropriately titrated.

16. Dyspnea (continued)
Provide access to prophylactic anti-emetic and introduce palliative care bowel protocol to avoid iatrogenic symptoms when initiating opioids.
If using parenteral route remember S.C. and I.V. = ½ PO dose (for example 10 mg I.V. or S.C. = 20 mg PO).
Opioid naive protocol:
Morphine 2.5 to 5 mg PO q4h; use lower dose in the elderly
Hydromorphone 0.5 to 1 mg PO q4h; use lower dose in the elderly
Oxycodone 5mg PO q4h
Consider hydromorphone in the elderly and if there is decreased renal function.
Breakthrough ½ of q4h dose ordered q1h prn
Opioid tolerant – increase current dose by 25% to 50%.

17. CASE What do you want to do?
58 year-old white male with metastatic lung cancer to the bone admitted to AIS program. Received palliative radiation to spine. PPS 60%
PMHx: CHF (EF 45%) and Stage III CKD
Medications: Lisinopril 20mg qd; Lasix 20mg qd; Aspirin 81mg qd
NKDA
PE: Unremarkable
ROS: 7/10 dull low back pain; feeling “down”
What do you want to do?
Feeling down is not the same as depressed. Use 2 question screening. Treat pain and mood will improve.

18. CASE Continues What do you want to ask?
Treat pain and re-evaluate mood
Start Oxycodone 5-10 mg every 4-6 hours as needed for pain
What do you want to ask?
How much are you using and does it work? Assess for side effects (nausea, sedation and constipation)

19. What do you want to do next?
CASE Continues
The patient’s pain remains tolerable and prescribed bowel regimen is effective (Colace BID and Senna qhs). Approximately four weeks later, patient’s wife calls AIS for an urgent appointment. She is reporting uncontrolled pain while using Oxycodone 10mg every 4 hours around the clock (averaging mg per day) with nausea, poor appetite and inability to sleep.
PE: Cachectic male in moderate distress with activity and temporal wasting; heart rate bpm and regular and BP 160/84; bowel sounds hypoactive and abdomen distended
What do you want to do next?
Enema more aggressive bowel regimen. Long acting opoid + prn + decadron. Addition antiemetic. Remeron to sleep.

20. CASE Continues
You start OxyContin 40mg BID with oxycodone 10mg every 2 hours for breakthrough pain. Enema is given at visit and bowel regimen intensified (Colace BID, Senna 2 tabs BID). Nausea improves with bowel movement. Remeron 15mg qhs added for sleep and appetite stimulation.
Could also consider Decadron 2-4 mg BID for bony pain and nausea as well.

21. Final Thoughts…
“Our ultimate goal, after all, is not a good death but a good life to the very end.” Atul Gawande M.D.