Transcript Medication Use at End of Life

Medication Use at End of Life
John Swegle, PharmD, BCPS
Associate Professor (Clinical)
University of Iowa College of Pharmacy
Mercy Family Medicine Residency
“Keep them Comfortable”
• What does this mean?
– Generally
• Calm/relaxed/comfortable
• Free of pain
• At peace
– Don’t forget about the family/caregivers
• Hope is for a “good death”
General Goals
• Reduce suffering
– Many involved with this
• Patient, family, healthcare provider
• Medications not always the answer
– Spiritual issues
• Utilize spiritual care services
– Social issues
• Utilize social workers
General Goals
• Focus on symptoms that are bothersome to
the patient
– Through conversations/observations
• Family wishes/perceptions
– Make sure the patient is the focus of the
conversation
– Must have realistic goals
• All parties need to hear the same message
General Goals
• Avoid perception of giving up
– Withdrawal of unnecessary medications/turning
off devices is reasonable
• Focus is a transition of care away from a
curative approach
General Goals
• Location of patient often dictates approach
to care
– Selection of medications
– Route of administration
– Aggressiveness of titration
• Need for reassessment
– Access to healthcare professional
Communication
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Patients, families, caregivers
What to expect
What the medications are designed to do
What is the plan from here going forward
Education is involved in all these steps
Be prepared to take time
Common Symptoms Encountered
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Pain
Dyspnea
Anxiety
Nausea/vomiting
Secretions
Terminal restlessness
Fatigue
Essential Drugs for
End-of-Life Care
• Medications considered essential for comfort care
in all settings (at least available for use):
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Morphine (opioids)
Lorazepam (midazolam)
Haloperidol (other)
Antimuscarinic (atropine eye drops)
• Medications to consider:
– Dexamethasone
J Palliat Med 2013;16:38-43
Various Etiologies for Pain
• Physiologic
– Approximately ¾ of patients entering the terminal
phase will have pain requiring opioids
• Other types of pain
– Emotional: Anxiety, depression, anger
– Social: Interpersonal issues (family, loneliness,
financial)
– Spiritual: Non-acceptance, abandonment, paying for
previous transgressions
General Opioid Rules
• Do not be fearful of them but treat them with
respect
• There is not one agent that is better than
another
– Everyone responds differently
– Selection takes into account other patient factors
(age, renal function, other disease states, other
medications, etc)
• Working with opioids is an art with some
science behind it
Myths about Opioids
• Once someone goes on morphine, it means
they will die
– The intent of use is for comfort care
– Provide for pain free periods
– Often titrated/used on PRN basis
• Respiratory depression is a common side
effect
Opioids
• Main uses in palliative care:
– *Pain/comfort
– *Shortness of breath
– Overall comfort
• Potential benefits
– Sedation
– Calming effect
– Improvement in quality of life
Opioid Selection
• Agents commonly
used for end-of-life
care:
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Morphine
Hydromorphone
Fentanyl
Oxycodone
• Agents which are not
ideal choices:
– Meperidine
– Any pill form
– Any partial agonist or
agonist/antagonist
Am J Kidney Dis 2003:42:217-228
Drugs Aging 2007;24:761-776
Opioids
• Dosing:
– Individualized and will need to be adjusted
• Some do poorly on 5 mg oral morphine
• Some require very high doses
– Determine pain needs: ongoing coverage vs.
PRN use
• Often dictated by setting
• PRN use is preferred at end-of-life however realize
who will be administering the drugs
Initial Opioid Dosing
• IV/SQ
– If using PCA, must determine if capable of pushing the
button
– Initial dosing
• Standard morphine PCA dose is 1-2 mg every 10-15 minutes
PRN
– If on basal/bolus – bolus dose is typically 50-100% of hourly
basal rate
• Example:
– Morphine 2 mg hourly infusion with 1 or 2 mg bolus every 15
minutes PRN
Initial Opioid Dosing
• PO/SL
– Standard morphine dosing
• 2.5-5 mg MSIR every 1-2 hours PRN
– Liquid morphine often used (Roxanol 20 mg/ml SL
administration)
• If on basal/bolus – bolus dose is 10-15% of 24-hour
dose
• Example:
– Morphine sulfate 15-15-30 over 24 hours
– Bolus is typically 5 mg every hour PRN
Opioid Comparison Dosing
Medication
Equianalgesic dose
(parenteral)
Equianalgesic dose
(oral)
100mcg (single dose)
200 mcg (continuous dosing)
25 mcg/hr  SR morphine
65-90 mg per day
Hydrocodone
N/A
30
Hydromorphone
1.5
7.5
Methadone
Varies
Varies
Morphine
10
30
Oxycodone
N/A
20-30
Oxymorphone
N/A
10
Fentanyl
Opioid Adverse Effects
• Constipation
– Address and prevent
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CNS: sedation, confusion
Nausea/vomiting
Urinary retention
Pruritis
Respiratory depression
Hyperalgesia
Drugs Aging 2009;26(suppl 1):63-73
Canadian Family Physician 2007;53:426-427
Dyspnea
• Definition of dyspnea
– Bad or difficult breathing
• Subjective symptom (similar to pain)
– Many people are unable to relate to dyspnea
– Unable to always correlate dyspnea with
objective findings
• As with pain, focus more on what the patient tells
you rather than what you or the family may observe
Dyspnea at End-Of-Life
• Focus on the symptom and not the sign
• Discuss treatment options with patient/family
• Most treatable causes of dyspnea have already
been dealt with at this stage
• Routine use of oxygen near death is not supported
by evidence (though some will use it)
• Attempt to reduce dyspnea by non-pharmacologic
means (i.e. – fan at the bedside)
Dyspnea at End-Of-Life
• Common causes
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Lung mets
Anxiety/panic
Secondary infection
Pulmonary edema
Metabolic acidosis secondary to multi-system
failure
– Newly developed pleural effusion
– Anemia
Common Respiratory
Medications
• Bronchodilators
– Utilized in those with underlying pulmonary disorders
• Not always able to see objective improvement but the patient
may claim to feel better
– Oral/nebulized/IV all are available depending on which
agent is selected
• Corticosteroids
– Target inflammation
– Dose appropriately and be aware of objective
improvement versus “steroid effect”
Semin Oncol 2011;38:450-459
Respiratory Depressants –
Bezodiazepines
• Main agents to use:
– Diazepam
– Lorazepam
• Mechanism of action
– Depression of hypoxic or hypercapnic ventilatory
response
– Alter the emotional response to dyspnea
• Avoid widespread use unless there is underlying
anxiety
J Palliat Med 2012;15:106-114
Respiratory Depressants –
Opioids
• Morphine
– Most frequently used opioid for treating dyspnea
– Dosing/frequency similar to pain
• Order often written PRN pain/dyspnea
– Not always useful for treating dyspnea
• Similar to the idea that not all pain should be treated with
morphine
• Do not rely completely on opioids that the overall picture is
ignored
Respiratory Depressants –
Opioids
• Morphine:
– Mechanism of action (multiple theories)
• Shifting of central PCO2 perception
– Resetting of the homeostatic control of PCO2
– Will allow the body to tolerate higher levels of CO2
without feeling respiratory fatigue
• Preload reduction
• Relaxation effect?
• Miscellaneous mechanisms
Am J Respir Crit Care Med 2011;184:867-869
Anxiety
• Culmination of physical and psychological
symptoms mixed in with the reality of the
situation
– Psychological factors (i.e. – fears of isolation,
factors associated with death) may impact the
physical findings
• Presents in many ways
– Restlessness, insomnia, hyperactivity,
jitteriness, apprehension, worry
Management of Anxiety
• Attempt to identify the etiology
– Example: anxiety secondary to dyspnea, delirium
– Drug-induced or drug withdrawal
– The relative from California
• Consider non-pharmacologic solutions
– Other disciplines: social worker, spiritual care
– Family support
– Psychological support
Curr Opin Support Palliat Care 2007;1:50-56
Management of Anxiety
• General medications used:
– Benzodiazepines
• Lorazepam 0.5-1 mg hourly PRN
• Clonazepam (similar dosing)
– Antipsychotics
• Haloperidol 0.5-2 mg hourly PRN
• Quetiapine 12.5-25 mg every 2 hours PRN
– Antidepressants
Curr Opin Support Palliat Care 2007;1:50-56
Nausea
• Entirely subjective experience
– Sensation which typically precedes vomiting
• Epidemiology is uncertain due to
methodological challenges
– Heterogeneity of patient populations, various
study settings, etc.
• Fair to say that the symptom is very
disturbing
Clin Interv Aging 2011;6:243-259
Nausea
• Similar to many symptoms, it’s best to try and
identify the etiology
– Or at least identify the receptors you wish to target
– Not always possible (multiple causes may be involved)
• Areas of involvement
– Chemoreceptor trigger zone
– Labyrinths
– Peripheral afferents
• Do not forget the bowels
Antihistaminic Agents for Nausea
Selected Medications
Comments
Diphenhydramine (Benadryl)
Useful agent but sedating
Dimenhydrinate (Dramamine)
Often used for “motion sickness”
Meclizine (Bovine, Antivert)
Often prescribed for “dizziness”
Promethazine (Phenergan)
Predominately an antihistamine but
has small amount of dopamine
blocking properties
Medications for Nausea
• Dopamine receptor antagonists
– Work by blocking dopamine 2 (D2) receptors
– Useful group of medications for nausea
• Often used as first-line for generalized nausea
– Adverse effects may be limiting factor
• Dystonic reactions, akathesia, sedation
Dopamine Receptor Antagonists
Selected Medications
Comments
Prochlorperazine
(Compazine)
Generic dopamine blocker and
preferred agent to use in many acute
situations; Less sedating than
promethazine
Haloperidol (Haldol)
Baggage associated with use; newer
antipsychotics also used but tend to
be more expensive
0.5-1 mg PO/0.5 mg SQ/IV
every 6-8 hours (may be more
frequent administration)
Metoclopramide (Reglan)
Dual mechanism: blockade of
dopamine receptors and prokinetic
agent on GI tract
Medications for Nausea
• Serotonin antagonists (i.e. – ondansetron)
– Block serotonin (5-HT3) receptors through
blockade of local receptors in the GI tract
(primary) and will block serotonin receptors
centrally (secondary)
– Key concept….. These agents are very useful
for emetogenc causes which are associated with
release of serotonin
Secretions
• Often distressing to caregivers/family
• Precise mechanism unclear
– Generally referred to as inability to clear
secretions
– Air flowing over secretions with respiration
creates the noise
• The “death rattle”
– Associated with death being near
Secretions – Management
• Education of family
• Non-pharmacologic
– Repositioning
– Suctioning
• Often short-lived benefit and may be more
distressing to family
Am J Health Syst Pharm 2009;66:458-464
Secretions – Management
• Medications:
– Atropine
• 1% eye drops; 1-2 drops po hourly PRN
• 0.4 mg SQ/IV q4-6 hours PRN
– Glycopyrrolate
• 1-2 mg po BID-TID
• 0.1-0.2 mg SQ/IV every 4-8 hours PRN
– Scopolamine
– Octreotide
CNS - Fatigue
• Numerous causes
– Pain, medications, deconditioning, anemia,
cytokine release, metabolic abnormalities,
depression, infection, dehydration
– Increased sleep is an expected outcome as end
of life gets closer
• Is there a need to treat?
– Is it a primary concern to the patient?
– Are there reasonable options that minimize
risks?
Terminal Restlessness
• This is a one hour talk
• Generally defined as unsettling behaviors in the
last few days of life
• General approach:
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Look for underlying cause
Remove or treat cause if possible (i.e. – drugs)
Create safe environment for all parties
Maintain patient dignity
Terminal Restlessness
• Non-pharmacologic
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Comfortable environment (i.e. – music)
Familiar home objects
Involve family members
Limit room/staff change
Limit interruptions (i.e. – blood draws)
Reorienting by family or staff
Terminal Restlessness
• Pharmacologic
– Haloperidol usual agent of choice
• 0.5-1 mg every 1-2 hours PRN
– Lorazepam typically second line
• 0.5-2 mg hourly PRN
– Often will see combinations of these two agents
used
Other Symptoms Encountered
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Depression
Behavioral problems
Anorexia
Insomnia
Family crisis situations
Discontinuing Medications
• If actively dying, stop everything but
comfort meds
• And stop the monitoring…..
Concluding Remarks
• Be realistic in your expectations from drugs
– Not everyone responds the same way
• Include the patient in the discussion
• More expensive medications are not always
better
• Don’t wait to treat the symptoms
Questions?