Part Four Treating EndofLife Symptoms

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Part Four Treating End-of-Life Symptoms

• Chronic Pain
• Dyspnea
• Nausea, Vomiting, and Constipation
• Depression and Anxiety
• Delerium, Agitation, and Psychosis

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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

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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

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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

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NMDA Effects in Chronic Pain

• Windup
• Neural remodeling
• Activation of NK-1 receptors
• Afferent becomes efferent
• Neurogenic inflammation

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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

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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 Healths National
Prescription Audit (NPA) Retail Phcy., LTC M.O.
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WHO 3-stepLadder
3 severe
Morphine Hydromorphone Methadone Levorphanol Fenta
nyl Oxycodone Adjuvants
2 moderate
A/Codeine A/Hydrocodone A/Oxycodone A/Dihydrocodei
ne Tramadol Adjuvants
1 mild
ASA Acetaminophen NSAIDs Adjuvants
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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.

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Strong Opioids

• Morphine
• Hydromorphone
• Oxycodone
• Fentanyl
• Methadone
• Levorphanol

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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 )

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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

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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.

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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.

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NMDA Receptor-Blocker Drugs

• NMDA-Receptor Opioids Methadone
• Levorphanol
• Non-opioids Dextromethorphan
• Ketamine
• Amantadine
• Memantine

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Adjuvants for Neuropathic Pain

• Anticonvulsants Gabapentin
• Valproic Acid
• Tricyclic antidepressants
• Amytryptiline
• Nortryptiline
• Imipramine
• Desipramine

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Adjuvants for Nociceptive Pain

• Tricyclic Antidepressants (previous slide)
• NSAIDS
• Corticosteroids ( dexamethasone preferred)
• Metachlorpropamide (for visceral pain)

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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!

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Dyspnea

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

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Management of Dyspnea

• Treat the Underlying Cause( if possible)
• Symptomatic Management
• Oxygen
• Opioids
• Anxiolytics
• Nonpharmacologic interventions

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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)

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Nausea and Vomiting

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

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Nausea and Vomiting

• Neurotransmitters
• Serotonin GI CTZ
• Acetylcholine,Histamine Vestib.,
  CTZ, GI
• Dopamine CTZ GI

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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

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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.)

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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

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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

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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

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Barriers to Excellent PsychiatricCare at the End
of Life

• Underestimation of the effectiveness of available
  treatments.- Therapeutic nihilism
• Stigma attached to psychiatric illnessPsychiatri
  c evaluations also stigmatized

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Delerium

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

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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-Pathologi
  c?-Supernatural?

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Delirium in Terminal Illness

• Treatment Overview
• Primary Goals-Maximizing Patient
  Comfort-Minimizing Patient (Family) Distress
• Tx Underlying Cause (When Possible)
• Usually involves Medication-Benzodiazepines-Neu
  roleptics
• May Require Heavy Sedation

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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.

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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.

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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

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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

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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.)

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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

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Using Trazodone in the Medically Ill

• Advantages Good sedative, anxiolytic
  properties Inexpensive
• Disadvantages Orthostasis Risk of priapism
  Reports of increased ventricular irritability

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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)

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Panic Attacks

• Discrete (5-20 minute) period of intense fear or
  discomfort, with (gt)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
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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 dont use
  probably will worsen anxiety.

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Delirium and Heavy Sedation

• Approximately 25 of cases of end-of life
  delirium are manageable only with heavy sedation.
• Especially in the last few days/hours of life
  (terminal restlessness)
• Is heavy sedation assisted death?

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Delerium- Treatment Summary

• Suspect medications as cause, first
• Reduce stimulation
• If neuroleptics are needed Haloperidol(less
  sedating)-dose can vary from 1-20mg/day
• Chlorpromazine is sedating,especially in
  terminal situation,along with benzodiazepine
• Consider the atypical neuroleptics also
• Risperidone, Olanzepine, Quetiapine

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Psychosis

• End-stage psychosis is often managed successfully
  in the home by a hospice or palliative care
  physician
• Neuroleptics (haloperidol, chlorpromazine are
  available po, iv,sc, rectal suppos.)
• Atypical neuroleptics can be titrated orally
  (risperidone, olanzepine, quetiapine)

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Palliative Sedation

• Sedation for intractable distress in the dying
• Criteria A terminal disease must be present
• The patient suffers from a
  
  refractory symptom despite all treatment
  
• Death must be imminent (days)
• A DNR order must be in effect

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Before Palliative Sedation

• Get consultation with expert in symptom
  management
• Discuss with patient, family, staff, and get
  informed consent
• Sedation and monitoring by consultant
• Document the criteria, rationale, and process
  thoroughly in the record

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Double Effect

• A single act having two possible foreseen
  effects, one good and one harmful, is not always
  morally prohibited if the harmful effect is not
  intended.

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• Are Requests for
• Assisted Dying Issues of
• Liberty and Autonomy or
• Markers for Suffering and Despair?

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Factors Associated with Requests for Assisted
Dying by Terminally Ill Patients

• Fear (of Abandonment, Sxs, Dying)
• Concerns about Loss of Dignity
• Concerns about Loss of Autonomy
• Loss of Meaning
• Pain
• Poor Social Support
• Loss of Control/Helplessness

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Summary

• If we do a good job- relieving pain and anxiety,
  supporting the patient and family until the end
• Then there will be no need for physician-assisted
  suicide or euthanasia
• Its up to us