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Part Four – Treating End-of-Life Symptoms

Part Four – Treating End-of-Life Symptoms. Chronic Pain Dyspnea Nausea, Vomiting, and Constipation Depression and Anxiety Delerium, Agitation, and Psychosis. Pain near the End-0f-Life. Chronic pain: more complex and difficult to treat than acute pain

Thomas
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Part Four – Treating End-of-Life Symptoms

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  1. Part Four – Treating End-of-Life Symptoms • Chronic Pain • Dyspnea • Nausea, Vomiting, and Constipation • Depression and Anxiety • Delerium, Agitation, and Psychosis

  2. Pain near the End-0f-Life • Chronic pain: more complex and difficult to treat than acute pain • Somatic and visceral pain: usually opioids and adjuvants are effective • Neuropathic pain: adjuvants plus NMDA-receptor blocking opioids work best

  3. Acute Pain • Pathway for acute pain perception is conventional • Duration is short • Endorphins and enkephalins are released by CNS to block pain perception • Opioids are effective for acute pain

  4. Chronic Pain • Prolonged pain impulses cause “burn-out” of the AMPA receptors involved in pain transmission in the spinal cord • Endorphins become less effective • NMDA receptors, normally quiescient, are activated, causing changes in pain transmission and behavior

  5. NMDA Effects in Chronic Pain • Windup • Neural remodeling • Activation of NK-1 receptors • Afferent becomes efferent • Neurogenic inflammation

  6. Assessing Pain • Gather info from patient,family, sitter, the entire healthcare team • Observe facial expression, body language • Remember emotional, social, spiritual pain • Re-assess the effect of Rx, and adjust prn. • Let the patient help guide his/her Rx

  7. Number of Analgesic Prescriptions: United States est. 2002(millions) Step 3 WHO Stepladder Total 13.03 Morphine 3.67 Fentanyl 4.35 Meperedine 1.78 Hydromorphone .77 Methadone 1.66 All others .08 Step 2 Total 173.32 Propoxyphene 28.94 Hydrocodone 91.83 Oxycodone 28.95 Codeine* 22.61 Dihydrocodeine 0.32 Pentazocine 0.67 Step 1 Total 135.30 COX-2 52.94 Other NSAIDs 65.98 Tramadol 16.38 *Includes Fiorinal with codeine combinations Source: IMS Health’s National Prescription Audit (NPA) Retail Phcy., LTC & M.O.

  8. WHO 3-stepLadder 3 severe Morphine Hydromorphone Methadone Levorphanol Fentanyl Oxycodone ± Adjuvants 2 moderate A/Codeine A/Hydrocodone A/Oxycodone A/Dihydrocodeine Tramadol ± Adjuvants 1 mild ASA Acetaminophen NSAIDs ± Adjuvants

  9. Prescribing Opioids for Chronic Pain- Principles • Use WHO pain ladder to select analgesic • Around-the-clock, q 3-4 hr. • Assess frequently, adjust dose • Add up total opioid taken in 24 hr. • Select long-acting opioid, q 12 hr. • Use short-acting opioid for prn breakthrough pain • Use one short- and one long-acting opioid • Re-assess to titrate dose.

  10. Strong Opioids • Morphine • Hydromorphone • Oxycodone • Fentanyl • Methadone • Levorphanol

  11. Long-acting Opioid Preparations • Morphine sustained- release (q 8-12 hr) • Oxycodone sustained- release (q 8-12 hr) • Fentanyl transdermal patch (q 72 hr ) • Methadone ( q 6-12 hr ) • Levorphanol ( q 6 hr )

  12. Short-acting Opioids for Beakthrough Pain • Morphine: oral tabs, oral concentrate sol, iv, suppos. Oral conc. most useful at end-of-life, buccally or SL. • Hydromorphone: oral tabs and liquid, iv, suppos. • Oxycodone: oral tabs, oral conc. sol. • Hydrocodone/ APAP oral tabs and liquid

  13. Equianalgesic Opioid Doses if Morphine= 10 mg. p.o. • Hydromorphone = 2 mg. • Oxycodone = 5-10 mg. • Hydrocodone = 15 mg. • Codeine = 60 mg. • Tramadol = 50 mg. • Merperidine = 50 mg. • Fentanyl see next slide • Levorphanol = 1-2 mg.

  14. Fentanyl: converting to and from Morphine • 25 mcg/hr Transderm.patch = 50 mg Morphine per 24 hr. 50 mcg/hr Transderm.patch = 100 mg Morphine per 24 hr. 75 mcg/hr Transderm.patch = 150 mg Morphine per 24 hr. 100 mcg/hr Transderm.patch = 200mg Morphine per 24 hr.

  15. NMDA Receptor-Blocker Drugs NMDA-Receptor Opioids: Methadone Levorphanol Non-opioids: Dextromethorphan Ketamine Amantadine Memantine

  16. Adjuvants for Neuropathic Pain • Anticonvulsants: Gabapentin Valproic Acid Tricyclic antidepressants: Amytryptiline Nortryptiline Imipramine Desipramine

  17. Adjuvants for Nociceptive Pain • Tricyclic Antidepressants (previous slide) • NSAIDS • Corticosteroids ( dexamethasone preferred) • Metachlorpropamide (for visceral pain)

  18. “Emergency Bag” Morphine solution 20mg/ml (15ml) Chlorpromazine supp 25mg (2) Diazepam supp 1 Omg (2) Hyoscyamine [1-atropine] tab 125mcg (4) Lorazepam Oral Conc, 2mg/ml (bucally) Haloperidol tabs 2mg (6) Keep in refrigerator!

  19. Dyspnea • Causes: Anxiety Airway Obstruction Bronchospasm Hypoxemia Pleural Effusion Pneumonia Pulm. Edema Pulm. Embolism Thick Secretions Anemia Metabolic Psychosocial-Spiritual

  20. Management of Dyspnea • Treat the Underlying Cause( if possible) • Symptomatic Management: Oxygen Opioids Anxiolytics Nonpharmacologic interventions

  21. Drugs often used for End-of-Life Dyspnea • Morphine Oral Conc. 20mg/ml (Roxanol) 0.25- 0.50 ml. q. 2-4 hr. prn buccally or SL • Lorazepam Oral Conc. 2mg/ml. 0.25-0.50 ml. q. 2-4 hr. prn buccally or SL • Scopolamine transdermal patch q. 72 hr. to decrease noisy bronchial secretions, or • Sublingual Hyoscyamine (LevsinSL)

  22. Nausea and Vomiting • Sites where nausea and vomiting originates: • Gastrointestinal tract • Chemoreceptor trigger zone (floor of 4th ventricle (CTZ) • Vestibular apparatus • Cerebral cortex

  23. Nausea and Vomiting • Neurotransmitters: • Serotonin: GI ; CTZ • Acetylcholine,Histamine: Vestib., CTZ, GI • Dopamine: CTZ; GI

  24. Managing Nausea and Vomiting • Dopamine antagonists: • Haloperidol, 0.5-2.0 mg. po,iv,sc q 6 hr, then titrate • Prochlorperazine, 10-20 mg. po q 6 hr; 25 mg pr q 12 hr, or 5-10 iv q 6 hr • Promethazine, 12.5-25 mg. iv; 25 mg po/pr q 4-6 hr • Metoclopramide, 10- 20mg. po q 6 hr

  25. Managing Nausea and Vomiting • Histamine antagonists (antihistamines) • Diphenhydramine, 25-50mg. po q 6 hr • Meclizine, 25-50mg. po q 6 hr • Hydroxyzine, 25-50mg po q 6 hr • Acetylcholine antagonists • Scopolamine, 1-3 transdermal patches q 72 hr, or 0.1- 0.4 mg iv or sc • Hyocyamine (Levsin sublingual tab.)

  26. Managing Nausea and Vomiting • Serotonin antagonists • Ondansetron, 8 mg po tid • Granisetron, 1 mg po q day or bid • Prokinetic agents Other agents • Metoclopramide Lorazepam 0.5-2mg po q 4-6hr Dexamethasone 6-20 mg q day

  27. Constipation from Opioids • Every patient on opioids should be on a bowel-program • Stimulant/softeners are useful: senna or casanthranol plus docusate sodium • Osmotic laxatives( lactulose, sorbitol,milk of mag., magnesium citrate) • Lubricants: Glycerin supp., mineral oil • Enemas

  28. Barriers to excellent PsychiatricCare at the End of Life • Difficulty in accurate and reliable diagnosis of mental disorders in the setting of significant physical illness. • Beliefs (held by patients, families, and providers) that psychiatric symptoms are a normal part of the dying process.-Especially true for depression

  29. Barriers to Excellent PsychiatricCare at the End of Life • Underestimation of the effectiveness of available treatments.- Therapeutic nihilism • Stigma attached to psychiatric illness*Psychiatric evaluations also stigmatized

  30. Delerium • Acute global change in cognition, awareness • Disorientation, fluctuating level of consciousness, impaired cognition usually distinguishes from dementia, depression, and anxiety

  31. Delirium and Suffering in the Dying Patient • Suffering caused by delirium is hard to assess, even retrospectively. • Interferes with meaningful contact • Distressing to families • Visions and visitation on the deathbed:-Pathologic?-Supernatural?

  32. Delirium in Terminal Illness: Treatment Overview • Primary Goals:-Maximizing Patient Comfort-Minimizing Patient (Family) Distress • Tx Underlying Cause (When Possible) • Usually involves Medication:-Benzodiazepines-Neuroleptics • May Require Heavy Sedation

  33. Evaluation of Delirium in Terminal Illness • Bruera, et al, 1992- In 56% of cases, cause of delirium could not be determined.-In 33% of cases, delirium improved • Reversible delirium in terminal illness is usually due to metabolic disturbances or medication side effects.

  34. Clinical Trials in Fatigue • Methylphenidate for fatigue in advanced cancer: a prospective open-label study.Sarhill, Walsh, Nelson et al. Am J. Hosp & Pall Care: 18(3) May 2001- 11 patients; dose 10mg a day- Quick relief of fatigue and improvement of other common symptoms (pain, sedation, anorexia) with few side-effects.

  35. Depression • Rapid effect: Methylphenidate Dexamethasone Usual time-frame: SSRI, Buproprion, Venlafaxine,Tricyclics, Trazadone, Mirtazapine Very common sx: look for it, expect it team approach helps

  36. Psychostimulants Agents: • Dextroamphetamine (Dexedrine) - Starting Dose 2.5 -5.0 mg/day (am) - “High” Dose 20 mg/day • Methylphenidate (Ritalin) - Starting dose 2.5 – 5.0 mg BID (AM and Noon) - “High” Dose 40 mg/day • Pemoline (Cylert) - Starting Dose 18.75 – 37.5 mg BID (AM and Noon) - “High” Dose 160 mg/day

  37. When to use Standard Antidepressants • Unable to tolerate stimulants. • Poor response to stimulants. • History of vigorous response to standard antidepressants. • Relatively long life expectancy. • Other therapeutic benefits (e.g., analgesic for neuropathic pain.)

  38. Using SRIs in the Medically Ill • Advantages:* Reliable efficacy, emerging anecdotal track record of safety in the medically ill.* Ease of administration.* Minimal side effects (nausea, vomiting, jitteriness, sexual dysfunction)* Relatively nonsedating • Disadvantages:* Cost* May suppress appetite* Poor analegesic properties* Sex

  39. Using Trazodone in the Medically Ill • Advantages:* Good sedative, anxiolytic properties* Inexpensive • Disadvantages:* Orthostasis* Risk of priapism* Reports of increased ventricular irritability

  40. Anxiety and Agitation • Most common emotional symptom in end-of-life • When cortical function intact, use benzo- • diazopines first: lorazepam, alprazolam • hydroxyzine also useful • If agitation/anxiety in cortically-impaired, • haloperidol or chlorpromazine work • best • Look for treatable cause (urinary retention,etc)

  41. Panic Attacks Discrete (5-20 minute) period of intense fear or discomfort, with (>)or(-) 4 of the following. * Palpitations, tachycardia* Sweating* Trembling, Shaking* Choking feeling* SOB, smothering* Chest discomfort * Nausea, GI distress* Fear of dying* Dizziness, faintness* Paresthesias* Fear of losing control* Chills, hot flushes* Depersonalization derealization

  42. Antidepressants for Anxiety • Effective, particularly SSRIs. • Consider as primary agents in long-term maintenance therapy. • Cautions:* Lag time to onset of effect.* Cover with BZD* Stimulantsand bupropion: don’t use; probably will worsen anxiety.

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