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Palliative care in pharmacy

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Stephanie Lai

on 7 July 2015

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Transcript of Palliative care in pharmacy

By: Stephanie Lai
Palliative care Order Set
- to reinforce the importance of end of life care through symptom management
- to differentiate the symptoms experienced by palliative patients to determine the best treatment option
- to compare efficacy and safety of pharmacological alternatives to manage common symptoms in palliative patients
- compare and contrast Mackenzie Health's palliative
order set with other hospitals
- to re-evaluate the current physician palliative order set at Mackenzie Health Hospital according to available clinical evidence

- to provide the best quality of life for patients and their family in the remaining days of their life
- to alleviate any pain and unnecessary suffering to the patients so that they may be comfortable mentally and physically
- to respect and honour the dignity of all palliative patients
- for pharmacists, we are responsible for assessing the appropriateness of medication orders to ensure
patient's receive optimal symptom control

Importance of palliative care
Conditions to satisfy before undertaking PST:
an uncontrolled (refractory) and unbearable symptom has been identified
high quality palliative care is available but inadequate to relieve suffering despite administration of optimal therapies
prognosis and diagnosis have been clearly explained and are well understood as has been the uncertainty of outcomes of any medical intervention
provision has been made to continue palliative care for analgesia and comfort
Palliative Sedation Therapy
Cause #1. Medication
related and metabolic
Cause #2. Gastrointestinal related and biliary ducts
Cause #3. Movement, change in position, vestibular disorder
sites affected
: vestibular apparatus and labrinyth
NT involved: H1, Acetylcholine
Treatment for vestibular disorder/tumour of 8th cranial nerve:
Cause #4. Psychological stimuli
sites affected: cerebral cortex (GABA)
Treatment choice: benzodiapezines
and Vomiting
• In patients with advanced cancer, 20-30% report nausea and vomiting and increases to 70% during the last week of life
Site affected
: Chemoreceptor trigger zone (CTZ)
NT involved: D2, 5HT3, H1, Acetylcholine
Treatment for chemo/radiation:

ondansetron (5H3 antagonist)
domperidone/metoclopramide (D2, 5HT3, 5HT4)
dexamethasone (corticosteroid)
methotrimeprazine (D2,H1,Ach, 5HT2 antagonist)
Treatment for drugs, endogenous toxins:
D2 receptor antagonists
metoclopramide (D2, 5HT3, 5HT4)
haloperidol (D2 antagonist)
prochlorperazine (D2,H1 antagonist)
methotrimeprazine (for refractory N/V)
Site affected:
chemoreceptors and mechanoreceptors of GI tract
NT involved: D2, 5HT3, 5HT4

Treatment for gastric stasis
domperidone/metoclopramide (D2, 5HT3, 5HT4)
Treatment for gastric irritation:
antacids, PPI, gastroprotective agents, anti-H2
Treatment for distention of biliary ducts:
corticosteroid, prokinetic agents
Treatment of bowel obstruction:
Cause #5. Intracranial hypertension
sites affected: blood-brain-barrier
Treatment choice: corticosteroids decrease permeability of BBB, decrease GABA inhibitor of antiemetic neurons, decrease leu-enkephalin and anti-inflammatory activity
Pharmacological Alternatives
Physician Order Sets
currently has
haloperidol 0.5-1mg sc q1h prn for N/V or confusion
ondansetron 4mg po/iv q8h prn
metoclopramide 5mg po/iv q6h prn
haloperidol 0.5mg po/sc/IM q4h prn
dimenhydrinate 25mg po/pr/inj q4h prn
prochlorperazine 10mg po/pr q6h prn
dimenhydrinate 25-50mg po/pr/sc q4h prn
haldol 0.5mg-1mg po/sc q6h prn
St. Mikes
prochlorperazine 10mg po/pr/IM q6 prn
Recommend to keep haloperidol sc for nausea
and vomiting since it is a potent and pure D2 receptor
blocker which means it causes less sedation and
• Prevalence of pain in cancer patients is estimated to be as high as 100% of cases, but it is not the only end stage illness associated with significant pain and suffering
• CVD, respiratory disease, respiratory disease and HIV/AIDS are also associated with painful sequelae
• Over 40% of patients with HF experience severe pain at the end of life
• Up to 80% of AIDS patients and 77% of COPD patients experience pain

Caused by

bone infiltration, nerve infiltration, or compression, invasion of the viscera, blood vessels, mucosa, soft tissue
Related to

post-operative syndrome, postchemotherapy neuropathy, phantom pain, candidiasis, mucositis, osteonecrosis)
Related to
constipation, lymphedema, neuralgia, thrombosis, etc
Unrelated to cancer

gastropathy, arthritis, diabetes)
Types of Pain
Physician Order Sets
MCK order set
acetaminophen 325-650mg per rectum or po q4h prn for fever or pain
hydromorphone 0.2-0.4mg sc q3h or q4h for pain and/or dyspnea if no opiod on admission order set
LHSC order set:

acetaminophen 650mg po q4h prn fever or pain
hydromorphone 1-2mg sc/po for pain or dyspnea
hydromorphone 3mg CR cap q12 h
fentanyl 12.5mcg sc q30 min prn pain or dyspnea
fentanyl 25mcg/hr patch q72 h
morphine 5mg sc q1h prn pain or dyspnea
morphine 10mg po q1h prn pain
TEGH order set:
tylenol 325-650mg po/pr q4h, tylenol No 2 1-2 tab po q4h prn, tylenol No 3 1-2 tab po q4h prn pain
percocet 1-2 tab po q4h
morphine 5mg q4h or 10mg q6h , morphine 5mg sc/iv q4h
dilaudid 2mg po q4h or prn, 1mg inj q4h or q1h prn
acetaminophen 325-500mg q4-6h for pain
“ unpleasant sensory and emotional experience associated with actual or potential tissue damage “
Step 1: Non- opiods
for mild pain (Scale 1-3)
acetaminophen 650-1000mg q6h or ibuprofen 200-800mg po q6h
NSAIDs including COX2 inhibitors should be avoided in elderly
Step 2: weak opiods
for mild to moderate pain (Scale 4-6)
acetaminophen/codeine/caffeine (Tylenol #1, 2, 3)
oxycodone/acetaminophen (Percocet)
Step 3: strong opiods
for moderate to severe pain (Scale 7-10)

Recommend to keep hydromorphone 0.2-0.4mg sc
for pain and/or dyspnea
Incoherent speech
problems with short term memory
disorientation in time or space
agitation or slowing down to the point of extreme lethargy
fear, irritability, aggression, anger, euphoria, or apathy
perceptual problems, hallucinations, nightmares or morbid fears, disturbed sleep
Hyperactive delirium
: agitation, disorientation, delusions, hallucinations
Hypoactive delirium
: repression, disorientation, apathy, silent retreat

Typically develops with cerebral dysfunction and has been described as a transient organic syndrome of acute onset with “
global cerebral dysfunction"

disturbed level of consciousness, attention, thinking, memory, psychomotor behavior, emotion and sleep-wake cycle”

(opiods, anticholinergics, steroids, benzos, antidepressants, sedatives)
drug withdrawal
(alcohol, sedatives, antidepressants, nicotine)
dehydration, constipation, urinary retention, uncontrolled pain
liver or real impairment, electrolyte disturbance (Na+, Ca+2, glucose), infection, hypoxia
cerebral tumour, cerebral disease (stroke and dementia)

1st line choice
traditional neuroleptics
generally effective for both hypoactive and hyperactive delirium
for mild delirium
12.5-50mg q4-8h po,sc,iv/
12.5-50mg q2-12h po,iv for severe delirium
preferable for patients with hallucinations or aggression
may be limited by adverse effects: extrapyramidal reaction, lowering of seizure threshold, possible paradoxical agitation

2nd line choice: atypical antipsychotics (risperidone 0.25-1mg daily or BID, olanzapine 2.5-20mg/day po, quetiapine 25-100mg bid po)
alternatives to haloperidol for patients with mild delirium
useful for calming agitation because they produce sedation and carry less risk of extrapyramidal reactions and better tolerated
newer atypicals may cause orthostatic hypotension (risperidone) and have more Ach side effects (olanzapine)
do not act as quickly as traditional agents

do not improve cognition and may induce distrust because of the amnesia they cause which can exacerbate delirium
can be used with alcohol withdrawal, antidepressant withdrawal and are preferred in PD

Other treatment options
initial 2.5-5mg po daily
effective for hypoactive delirium with no specific cause
can be used alone or with antipsychotic
should not be used if patient has hallucinations or illusions
AE : tachycardia, headache, hyperhidrosis, decreased appetite, xerostomia
2.5-10mg po daily
effective for CNS toxicity due to opiods (indicated by sedation/disturbed sleep) or for delirium due to anticholinergics
AE: fatigue, diarrhea, N/V, muscle cramps, fecal incontinence, bloating, epigasric discomfort
Physician Order Set
haloperidol 0.5mg-1mg sc q1h prn for nausea,vomiting, confusion
methotrimeprazine 12.5mg po q2h prn for delirium and terminal restlessness or 6.25mg sc q2h prn
St. Michaels:


Recommend to add methotrimeprazine 12.5mg po or 6.25mg sc q2h prn for delirium or terminal restlessness
Confusion and Delirium
“non-observable phenomenon of an unpleasant sensation experienced in the back of the throat and the epigastrium that may or may not culminate in vomiting”
• delirium occurs in 28-83%
of patients near end of life
Palliative Sedation


disfigurement, disability, dying in isolation
fear of painful death is formost on the minds of terminally ill patients and their families

• symptoms include:
restlessness, worry, foreboding, apprehension
panic symptoms
: palpitations, tachycardia, sweating, breathlessness, GI distress and nausea, feelings of impending doom, difficulty falling asleep or awakening in the middle of the night and irritability
• prevalence of anxiety was 28% in patients with metastatic melanoma
• in the Canadian national palliative care survey, the median prevalence of at least one depressive or anxiety disorder was 24.4%
• the prevalence of anxiety in advanced illness has not been well studied but researchers report a prevalence rate for anxiety as a symptom in palliative care patients 23-43%

poor pain control, hypoxia, delirium, sepsis, bleeding, pulmonary embolus, hypocalcemia, nutritional failure
drug induced:
corticosteroids, antiemetics, bronchodilators and substance abuse or withdrawal (e.g. alcohol, opiods, benzos)
adjustment disorder, panic disorder, generalized anxiety disorder, phobia, agitated depression, PTSD, organic anxiety, delirium, hypoxia, dyspnea, infection, uncontrolled pain

1st line: benzodiazepine
treatment of choice for insomnia and anxiety
MOA: stimulates GABA receptor which reduces excitatory NT
benzos with short duration of action such as lorazepam, oxazepam should be favored to reduce the risk of toxic effects
side effects: sedation, drowsiness, psychomotor impairment and ataxia
Midazolam has a very short duration of action and is usually administered parenterally, it is useful where continuous sedation is needed to obtain rapid anxiolytic, sedative and amnesic effect

2nd line: antipsychotics
useful in treatment of anxiety when the suspected cause is organic or the anxiety is accompanied by psychiatric symptoms such as delusions or hallucinations
use when benzos are CI or only partially effective
recommended for treatment of concomitant anxiety, psychotic symptoms and nausea
methotrimeprazine , chlorpromazine, haloperidol are more often used
extrapyramidal side effects are troublesome symptoms
atypical neuroleptics such as olanzapine could be a good choice because of its action on multiple receptors including histamine, serotonin, and dopamine which yield antinausea, antidepressant and antipsychotic

Physician Order Set
MCK order set
: midazolam for restlessness and agitation, nothing indicated for anxiety
LHSC order set
lorazepam 1mg sl tab q4h prn for agitation, sedation, myoclonus
midazolam 2mg sc q2h prn for anxiety and 1mg for moderate anxiety
TEGH order set
oxazepam 15-30mg po qhs prn for sedation/anxiety
imovane 3.75mg po qhs prn for sedation/anxiety
lorazepam 0.5-1mg tab sl/sc q4h prn for anxiety
St. Michaels
: lorazepam 0.5-2mg po/sl q4h for anxiety/sedation

Recommend to add lorazepam 0.5-1mg po/sl for agitation, anxiety or insomnia
agitation presents in the form of anxiety, nervousness or distress
crying out
repetitive actions
general excessive behaviour
physiologic factors:
urinary retention, constipation, hypoxia
heart failure, metabolic disturbances and sometimes infection
opiods, steroids, anticholinergics, phenothiazines, benzodiazepines
pain, distended bladder, alcohol/or nicotine withdrawal, sleeplessness
nonspecific agitation
can be a result of psychoses, fear, anger, irritation or interpersonal conflict

medications used to either reduce dopaminergic and adrenergic or increase serotonergic and GABAergic activity will support effective management of both agitation and anxiety

• 1st line: antipsychotics (haloperidol 0.5-2mg q1h po/sc)
most commonly used and is often initiated at low doses and adjusted
AE: lowers seizure threshold
• OR
atypical antipsychotics
quetiapine, and risperidone have been shown to be equally effective but may be cost prohibitive
• 2nd line: benzos
such as lorazepam 0.5-2mg q4-8h po/sl and diazepam 5-10mg q12h po/pr
Midazolam 1.5mg q1h or 2.5mg q2-4h sc,po is effective for agitation and restlessness as onset is rapid and has short half life without significant metabolites
AE: paradoxical agitation, respiratory depression, tolerance, N/V
• 3rd line: methotrimeprazine 12.5-50mg q24h po/6.25mg sc inj
recommended if midazolam is ineffective
rapid onset, antispychotic effect and some analgesic effect
AE: orthostatic hypotension, paradoxical agitation, extrapyramidal symptoms, Ach effects

4th line:

100-200mg then 90-1600mg/day po/sc
sedative drug of last resort, recommended if midazolam is ineffective
AE: paradoxical excitation in high doses or in the elderly, respiratory depression, skin irritation, hepatotoxiciy, hypotension, N/V

Physician order set
midazolam 1.25-2.5mg sc q1h prn for restlessness and agitation
lorazepam 1mg sl tab, oral, q4h prn for agitation, sedation or myoclonus
methotrimeprazine 12.5mg po q2h prn or 6.25mg sc q2h prn for delirium and terminal restlessness
haloperidol 0.5-1mg po/sc q6h prn for restlessness
methotrimeprazine po/sc prn for restlessness (MD to specify dose)
St. Michaels hospital:
haloperidol 1-5mg po/sc q4h prn for restlessness and/or nausea
lorazepam 0.5-2mg po/sl q4h prn for anxiety/sedation
oxazepam 15-30mg po qhs prn for sedation
may arise at any moment in he final stages of life and is experienced by about 40% of patients in the terminal phase of a disease
At the end of life or in the days preceding death, between 25-85% of patients exhibit signs and symptoms of "terminal agitation"
• occurs in 50-70% of all patients with terminal cancer, with a higher incidence in the last 6 weeks of life
• more common in patients with lung cancer and those with a poor prognosis , occurring in over 90% of lung cancer patients
• regional study of care for the dying reported dyspnea in 54% of patinets dying from cancer and 61% of patients dying from HD

• subjective discomfort or difficulty related to breathing
• increase in respiratory rate and leads to decrease in activity
• often occurs with advanced disease of various types (cancer, chronic obstructive pulmonary disease)
• major treatment is to alleviate the feeling of suffocation and to calm the associated anxiety

• tumours of the otorhinolargynoglogical sphere
• pulmonary tumours or metaseses
• increased ganglia volume
• infection (pneumonia)
• lymphangitic carcinomatosis
• pulmonary embolism
• COPD, asthma, emphysema
• Tracheoesophageal fistula
• Aspiration
• Secretions
• MI, heart failure, pericardial effusion, superior venca compression
• Bone tumour, tumour of the diaphgram, impairment of the phrenic nerve

- very effective for relieving dyspnea associated with
various terminal disease (cancer, COPD, HF, renal failure)
• Act on the respiratory centre, reducing pathological respiratory effort
• They have a central sedative effect, attenuating the ventilator response
• Lower sensitivity to hypercapnia and hypoxemia, reduce oxygen consumption and diminish the perception of dyspnea and of anxiety

2. Benzodiazepines/Anxiolytic
• Benzos break the viscious circle of anxiety-dyspnea through anxiolytic and sedative properties and possibly through muscle relaxation
Lorazepam can be administered 0.5mg sl as required esp for episodic anxiety, panic attacks or alternatively diazepam 5mg qhs if patient is experiencing more anxiety
• Neuroleptics for serious dyspnea such as methotrimeprazine (2.5-10mg PO or SC q6-8 hrs prn)
• Chlorpromazine (7.5-25mg po or iv) is used less frequently

3. Bronchodilators
• Most effective in bronchospasm
• beta agonists, anticholinergics
• useful in known situations of airway obstruction (e.g. tumour, asthma, COPD)

Treatment con't
4. Anticholinergic
• Glycopyrrolate is useful if sedation is not required
• Scopolamine is useful if sedation and amnesia are required but in higher doses is excitatory and may cause agitation and confusion, often accompanied by delirium

5. Corticosteroid
• Relieves dyspnea through mainly through anti-inflammatory effect
• Useful mainly for asthma, COPD, superior vena cava compression syndrome
• Lymphangitic carcinomatosis
• Dexamethasone 4-16mg/day po, sc or IV bid to qid
• Prednisone 20-60mg/day po once daily or BID
• Inhaled steroid for treating dyspnea secondary to asthma or COPD with bronchospasm
passing harder and or less frequent stools than normal, fecal impaction may present with overflow, rectal exam: empty or impacted
Associated with other symptoms such as flatulence, bloating and abdominal pain or discomfort

• drugs especially oral opiods, antidepressants, antispasmodic, ondansetron, anticholinergics, TCA, antipychotics, antihypertensive, diuretics.
• inactivity, immobility, weakness, lack of privacy
• dehydration due to poor fluid intake, vomiting, polyuria, fever
• hypercalcemia
• concurrent disease including painful and conditions, neurological disorders

• in some cases, the simple act of distending the anus by introducing a glycerin suppository produces spontaneous elimination but if this doesn’t work then administer a glycerin suppository first and then a 10 mg bisacodyl suppository
• generally need to use combination of softener and a stimulant

stimulant laxatives
(i.e. senna, bisacodyl, sodium picosulfate) act on the myenteric nerves to evoke muscle contraction and can reduce the absorption of water from the bowel
• onset of action: 6-12 hrs and can produce marked colic if not combined with softening agent

softening laxative
may be osmotic (lactulose, magnesium sulfate, PEG), surfactant (e.g. docusate) or lubricant (e.g. liquid paraffin)

second line treatment
: rectal suppository and enema

third line treatment:
manual evacuation

avoid bulk forming agents
such as psyllium, methylcellululose, polycarbophil to preven constipation in patients taking opiods because it may worsen symptom making dry, hard, stool that is more difficult to pass

• associated with advanced disease has been most prevent in patients with advanced cancer and has been reported by up to 50% of all patients admitted to palliative care units
• state of apprehension and fear resulting from the perception of a current or future threat to oneself
Neuroleptics (methotrimeprazine, chlorpromazine, not haloperidol)
use if benzos are ineffective or in combination with benzo
first choice in cases of delirium
AE: extrapyramidal reaction, lower seizure threshold, possible paradoxical agitation
when delirium is difficult to manage with neuroleptic regimen and symptoms are severe enough to be distressing to the patient and family, consider palliative sedation using phenobarbital, sedating benzos such as midazolam or anesthetics such as propofol

Barbituates (phenobarbital/thiopental)
sedation more profound than with benzo
useful in cases of severe agitation or seizures
may be combined with benzo if benzo alone is ineffective
AE: respiratory depression, hypotension, rapid development of tolerance, skin irritation, nausea/vomiting

Anticholinergic (scopolamine)
given concomitantly with other sedatives in the presence of substantial secretions
Physician Order Set
: hydromorphone 0.2-0.4mg sc q3h or q4h prn for pain or dyspnea
fentanyl 12.5mcg sc q30prn for pain/dyspnea
hydromorphone 1mg po/sc q1h prn for pain/dyspnea
morphine 5mg sc q1h prn pain/dyspnea
: N/A
t. Michael's Hospital
: N/A
Physician Order Set
morphine, hydromorphone (sc,pr,IV), fentanyl (sc,iv)
preferred when analgesia is required or in case of dyspnea
continuous infusion possible (sc or iv)
gradual increase in dose to desired degree of sedation
AE (myoclonus, agitation, hallucinations) frequent


(diazepam, lorazepam, midazolam)
first choice in cases of anxiety, agitation
AE infrequent but include paradoxical agitation, respiratory depression, tolerance, N/V, drowsiness, lightheadedness, muscle weakness
anticonvulsant activity
amnesic effect

Updated Palliative
Order Set Recommendation
Recommend to add methotrimeprazine 12.5mg mg po q2h prn or 6.25mg sc q2h prn for delirium and terminal restlessness
Recommend to keep hydromorphone 0.2-0.4mg sc prn for dyspnea
: N/A
docusate 100 mg cap BID
senna 8.6 mg po BID prn
magnesium hydroxide 30ml sus BID prn
lactulose 30ml po TID prn
bisacodyl 10mg supp prn daily
fleet enema 133ml rectal daily prn
PEG 3350 17g pwd daily prn in 250ml of water
: bowel management module
St. Michael's hospita
docusate 100mg po BID
bisacodyl 10mg po or suppository qhs
magnesium hydroxide was cascara 15-30ml po qhs prn
glycerin supp pr daily prn
fleet q2d pr prn

Recommend to add bowel management
medications to MCK order set
Opiod Adverse Effects
add methotrimeprazine 12.5mg po or 6.25mg sc q2h prn for delirium or terminal restlessness
Recommend to add lorazepam 0.5-1mg po/sl for agitation, anxiety or insomnia
Recommend to add bowel management medications to MCK order set
docusate 100mg po bid
glycerin suppository pr daily prn
senna 1-2 tabs po BID
bisacodyl 10mg po/pr qhs
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