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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. Pain near the End-0f-Life. Chronic pain: more complex and difficult to treat than acute pain

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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
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
acute pain
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
chronic pain
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
nmda effects in chronic pain
NMDA Effects in Chronic Pain
  • Windup
  • Neural remodeling
  • Activation of NK-1 receptors
  • Afferent becomes efferent
  • Neurogenic inflammation
assessing pain
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

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.

who 3 step ladder
WHO 3-stepLadder

3 severe







± Adjuvants

2 moderate






± Adjuvants

1 mild




± Adjuvants

prescribing opioids for chronic pain principles
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.
strong opioids
Strong Opioids
  • Morphine
  • Hydromorphone
  • Oxycodone
  • Fentanyl
  • Methadone
  • Levorphanol
long acting opioid preparations
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 )
short acting opioids for beakthrough pain
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
equianalgesic opioid doses if morphine 10 mg p o
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.
fentanyl converting to and from morphine
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.

nmda receptor blocker drugs
NMDA Receptor-Blocker Drugs

NMDA-Receptor Opioids: Methadone


Non-opioids: Dextromethorphan




adjuvants for neuropathic pain
Adjuvants for Neuropathic Pain
  • Anticonvulsants: Gabapentin

Valproic Acid

Tricyclic antidepressants:





adjuvants for nociceptive pain
Adjuvants for Nociceptive Pain
  • Tricyclic Antidepressants (previous slide)
  • Corticosteroids ( dexamethasone preferred)
  • Metachlorpropamide (for visceral pain)
emergency bag
“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!

  • Causes: Anxiety Airway Obstruction

Bronchospasm Hypoxemia

Pleural Effusion Pneumonia

Pulm. Edema Pulm. Embolism

Thick Secretions Anemia

Metabolic Psychosocial-Spiritual

management of dyspnea
Management of Dyspnea
  • Treat the Underlying Cause( if possible)
  • Symptomatic Management:




Nonpharmacologic interventions

drugs often used for end of life dyspnea
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)
nausea and vomiting
Nausea and Vomiting
  • Sites where nausea and vomiting originates:
  • Gastrointestinal tract
  • Chemoreceptor trigger zone (floor of 4th ventricle (CTZ)
  • Vestibular apparatus
  • Cerebral cortex
nausea and vomiting23
Nausea and Vomiting
  • Neurotransmitters:
  • Serotonin: GI ; CTZ
  • Acetylcholine,Histamine: Vestib., CTZ, GI
  • Dopamine: CTZ; GI
managing nausea and vomiting
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
managing nausea and vomiting25
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.)
managing nausea and vomiting26
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

constipation from opioids
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
barriers to excellent psychiatric care at the end of life
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
barriers to excellent psychiatric care at the end of life29
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
  • Acute global change in cognition, awareness
  • Disorientation, fluctuating level of consciousness, impaired cognition usually distinguishes from dementia, depression, and anxiety
delirium and suffering in the dying patient
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?
delirium in terminal illness
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
evaluation of delirium in terminal illness
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.
clinical trials in fatigue
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.
  • Rapid effect: Methylphenidate


Usual time-frame: SSRI, Buproprion,


Trazadone, Mirtazapine

Very common sx: look for it, expect it

team approach helps



  • 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
when to use standard antidepressants
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.)
using sris in the medically ill
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
using trazodone in the medically ill
Using Trazodone in the Medically Ill
  • Advantages:* Good sedative, anxiolytic properties* Inexpensive
  • Disadvantages:* Orthostasis* Risk of priapism* Reports of increased ventricular irritability
anxiety and agitation
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)
panic attacks
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

antidepressants for anxiety
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.
delirium and heavy sedation
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?
delerium treatment summary
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

  • 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)
palliative sedation
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

before palliative sedation
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
double effect
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.

Are Requests for

Assisted Dying Issues of

Liberty and Autonomy or

Markers for Suffering and Despair?

factors associated with requests for assisted dying by terminally ill patients
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
  • 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
  • It’s up to us