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Because M.P. is to be enrolled into a hospice program, her care should not be

focused on curative treatments, but rather on the management of discomforting

symptoms and on improving her quality of life in the time remaining. M.P.’s

medications should be analyzed with the goal of simplification. Unnecessary

medications should be discontinued and alternatives added to manage two or more

symptoms concurrently. The following changes should be considered:

Acetaminophen. This analgesic is often helpful in relieving mild pain,

particularly in immobile elderly patients. A trial of around-the-clock acetaminophen

could be helpful.

Albuterol/ipratropium combination. The hospice program is required to pay for

medications related to M.P.’s aspiration pneumonia and COPD because the hospice

medical director determined that these conditions are related to her terminal

prognosis. This combination inhalation formulation should be continued if she is able

to participate in her nebulizer treatments and it improves her breathing. (See Chapter

19, Chronic Obstructive Pulmonary Disease.)

Alendronate. This bisphosphonate drug can be discontinued because the treatment

of osteoporosis is not an important consideration at this terminal stage of her life nor

is it in the hospice POC. Thus, hospice would not cover it. Furthermore, M.P. is bedbound; alendronate should be ingested in the upright position, and patients should

remain upright after taking the medication to decrease the risk of alendronate-induced

esophageal irritation (see Chapter 110, Osteoporosis). Pain that she may experience

from osteoporosis can be treated with analgesics.

p. 86

p. 87

Table 6-2

Palliative Performance Score (PPS) Version 2

PPS

Level

(%) Ambulation

Activity and Evidence of

Disease Self-Care Intake

Conscious

Level

100 Full Normal activity and work

No evidence of disease

Full Normal Full

90 Full Normal activity and work

Some evidence of disease

Full Normal Full

80 Full Normal activity with effort

Some evidence of disease

Full Normal or

reduced

Full

70 Reduced Unable to do normal job/work

Significant disease

Full Normal or

reduced

Full

60 Reduced Unable to do hobby/housework

Significant disease

Occasional

assistance

necessary

Normal or

reduced

Full or

confusion

50 Mainly sit/lie Unable to do any work

Extensive disease

Considerable

assistance

required

Normal or

reduced

Full or

confusion

40 Mainly in bed Unable to do most activity

Extensive disease

Mainly

assistance

Normal or

reduced

Full or drowsy

± confusion

30 Totally bedbound

Unable to do any activity

Extensive disease

Total care Normal or

reduced

Full or drowsy

± confusion

20 Totally bedbound

Unable to do any activity

Extensive disease

Total care Minimal to sips Full or drowsy

± confusion

10 Totally bedbound

Unable to do any activity

Extensive disease

Total care Mouth care

only

Drowsy or

coma ±

confusion

0 Death

Instructions: PPS level is determined by reading left to right to find a “best horizontal fit.” Begin at left column

reading downwards until current ambulation is determined, then, read across to next and downwards until each

column is determined. Thus, “leftward” columns take precedence over “rightward” columns.

Reprinted with permission from Victoria Hospice Society. Palliative Performance Scale (PPSv2), version 2.

Medical Care of the Dying. 4th ed. Victoria, British Columbia, Canada: Victoria Hospice Society; 2006:120.

http://www.victoriahospice.org/health-professionals/clinical-tools. Accessed April 13, 2016. Copyright ©

2001 Victoria Hospice Society. The Palliative Performance Scale version 2 (PPSv2) tool is copyright to Victoria

Hospice Society and replaces the first PPS published in 1996 [J Pall Care 9(4):26–32]. Victoria Hospice Society,

1952 Bay Street, Victoria, BC, V8R 1J8, Canada www.victoriahospice.org edu.hospice@viha.ca

Aspirin. The low-dose aspirin is intended to decrease the risk of cardiovascular

clotting. The aspirin will not increase M.P.’s comfort or quality of life. Although the

aspirin would not be covered by her Medicare Hospice Benefit, it can be continued

unless her primary-care provider prefers its discontinuation.

Beclomethasone. This patient is not functioning well cognitively (i.e., not

oriented to time, person, or place) and would be unable to effectively time the

inhalation of a breath to the actuation of her metered-dose inhaler. A systemic

corticosteroid (e.g., prednisone) might improve her COPD symptoms and also

improve her appetite and sense of well-being. The potential for adverse effects is

modest with short-term corticosteroid use.

Bisacodyl, milk of magnesia. Constipation in patients with terminal illnesses is

common, occurring in as many as 94% because of decreased gastrointestinal motility

with advanced age, metabolic disturbances, decreased physical activity, lack of

adequate fiber and fluid intake, and use of constipating medications (e.g., opioids,

anticholinergics, psychotropic agents).

40–43 The milk of magnesia, with an occasional

bisacodyl suppository, has been an adequate laxative regimen for this patient. If an

opioid is later prescribed for M.P., a mild stimulant laxative (e.g., senna) can be

added. Osmotic agents such as polyethylene glycol (PEG), oral sorbitol, or lactulose

can be prescribed if needed. Mineral oil 30 mL daily is an option if the stool is hard;

however, mineral oil should not be considered for M.P. because of her risk of

aspiration. Bulk-forming laxatives should also be avoided in this population as they

may not ingest adequate water to prevent a fecal impaction. In cases of refractory

constipation, the use of methylnaltrexone bromide, an injectable opioid antagonist,

can reverse opioid-induced constipation by antagonizing opioid effects within the

gastrointestinal tract without affecting systemic analgesia.

44–46 This quaternary

derivative of naltrexone does not cross the blood–brain barrier. Dosing is weight

based; it is given subcutaneously as either 8 mg for patients weighing 38 to 62 kg

(84–136 pounds) or 12 mg for patients weighing 62 to 114 kg (136–251 pounds)

once a day. The most common adverse events are abdominal pain, flatulence, nausea,

and dizziness.

43

Esomeprazole. This proton-pump inhibitor would probably be unnecessary

because alendronate-induced esophageal or gastrointestinal irritation would not be

an issue subsequent to its discontinuation. However, if a proton-pump inhibitor is

needed, nonprescription generic omeprazole or lansoprazole is preferred because

they are more cost-effective.

47

If a patient such as M.P. cannot swallow intact tablets,

a capsule formulation can be opened with the contents mixed with soft food and

swallowed intact.

p. 87

p. 88

Levothyroxine. This thyroid medication should be continued until M.P. is no

longer able to swallow. This medication, however, would not be covered under her

Medicare Hospice Benefit, which is based on her Alzheimer disease, and was

deemed not related to the terminal prognosis.

Lovastatin. Cholesterol-lowering agents are not necessary during the last 6

months of life and should be discontinued. Lovastatin would not improve the quality

of life of M.P. at this stage of her terminal illness and would not be covered by her

Medicare Hospice Benefit.

Megestrol. The progesterone derivative, megestrol, in doses of 400 to 800 mg

daily, can substantially stimulate appetite.

48,49

If an undernourished hospice patient

desires to eat more, the hospice may choose to provide an appetite stimulant. It is

unclear whether stimulation of appetite in a cognitively impaired patient will result

in weight gain or improved nutritional status. Because the benefits in this situation

are unclear, the potential of adverse effects (e.g., venous thrombosis) of megestrol

needs to be considered, especially in M.P., who is not ambulatory and had been

taking low-dose aspirin for prevention of cardiovascular clotting.

50

Memantine. Because the N-methyl-D-aspartate antagonist, memantine, has been

modestly effective in improving performance in patients with moderate to severe

Alzheimer disease,

51,52 but with decreasing effectiveness over time,

53

it is probably of

limited utility for M.P. (See Chapter 108, Geriatric Neurocognitive Disorders.) It

would be reasonable to discontinue M.P.’s memantine subsequent to discussion with

appropriate hospice team members and M.P.’s family.

Multivitamins. Multivitamins and other nutritional supplements are unlikely to

improve M.P.’s comfort or quality of life. The discontinuation of these drugs would

simplify medication administration, decrease the potential for medication errors, and

decrease costs.

Olanzapine. An antipsychotic (e.g., olanzapine, haloperidol, chlorpromazine) is

often prescribed off-label to manage the agitation and confusion encountered by

patients with dementia. Behavioral modifications can be tried (see Chapter 108,

Geriatric Neurocognitive Disorders), but paranoid or delusional behavior may

require drug therapy. At the time of admission to hospice, patients may be receiving

atypical agents (e.g., olanzapine). Small doses of the first-generation antipsychotics,

such as haloperidol and chlorpromazine, may offer a dual effect and be very useful in

treating opioid-induced nausea and vomiting, although randomized clinical trials

demonstrating efficacy are lacking.

54 They would be covered by M.P.’s Medicare

Hospice Benefit. Chlorpromazine would be preferable when more sedation is

desired.

SYMPTOM MANAGEMENT

The American College of Physicians has developed clinical guidelines, based on a

systematic review of evidence and on a report by the Agency for Healthcare

Research and Quality, to improve palliative care at the end of life. These guidelines

provide strong recommendations for the regular assessment of patients at the end of

life for symptoms of pain, dyspnea, and depression, and for therapies of proven

effectiveness for these symptoms. For patients with cancer, these include the use of

opioids, nonsteroidal anti-inflammatory drugs, and bisphosphonates for pain;

tricyclic antidepressants, selective serotonin reuptake inhibitors, and psychosocial

interventions for depression; and opioids for unrelieved dyspnea and oxygen for

short-term relief of hypoxemia. The guidelines do not address other variables of

palliative care at the end of life or the management of other matters (e.g., nutritional

support) because the quality of evidence is limited rather than because other issues or

symptoms are unimportant.

55 The National Consensus Project for Quality Palliative

Care recommends the measurement and documentation of pain and other symptoms

using available scales with timely assessment and symptom management acceptable

to both the patients and their families as a preferred practice.

4

CASE 6-1, QUESTION 3: As soon as the hospice admission and assessment is completed, the nurse in

consultation with the IDG develops a plan for symptom management and orders a comfort kit for M.P. What

are the components of this kit, and why is it useful?

Some hospices use a general comfort kit that contains specific medications to

manage symptoms commonly encountered by most hospice patients, or they order

medications to treat anticipated symptoms for a specific patient. These medications

are placed in the home or facility where the patient resides. This facilitates the

availability of medications to patients who encounter anticipated symptoms and is

convenient when caregivers are instructed by the patient’s primary-care provider to

provide the medication to the patient. Patients living with cancer can encounter as

many as 27 symptoms (median, 11), many of which occur together.

56

In one study,

patients (n = 176) experienced an average of 6.6 to 6.8 distressing symptoms during

the last week of life.

57

In general, the prevalence of each symptom is difficult to

measure and demonstrates a high degree of variability. Pain (34%–96%), fatigue

(32%–90%), and breathlessness (10%–95%) appear to be the most common in

patients with a variety of terminal conditions, with the prevalence of pain in cancer

patients reported as 35% to 96%.

58 Patients with terminal illnesses, including

dementia as in M.P., also experience depression (3%–82%), anxiety (8%–79%),

confusion (6%–93%), insomnia (9%–74%), nausea (6%–68%), constipation (23%–

70%), diarrhea (3%–90%), and anorexia (21%–92%).

58 The disparity in symptom

prevalence may be attributed to a host of variables (e.g., study design, patient

population, underlying disease, inconsistent definitions, and where care was

provided). The occurrence of symptoms, however, can vary significantly, even

within the last week of life, and the need for frequent assessment of patients cannot

be overemphasized. Morphine, lorazepam, haloperidol, prochlorperazine

suppositories, and an anticholinergic agent are commonly ordered for hospice

patients. Drugs that can palliate more than one symptom, such as morphine for pain or

dyspnea, or haloperidol for agitation or nausea, are particularly suited to inclusion in

a comfort kit.

Morphine. Every hospice patient should have a short-acting opioid available for

the palliation of unrelieved dyspnea and pain. Although morphine can cause

respiratory depression, small doses are very effective in controlling dyspnea by

multiple mechanisms: vasodilation, reduced peripheral vascular resistance,

inhibition of baroreceptor responses, reduction of brainstem responsiveness to

carbon dioxide (the primary mechanism of opioid-induced respiratory depression),

and lessened reflex vasoconstriction caused by increased blood PCO2

levels. Opioids

can also reduce the anxiety associated with dyspnea and might also act directly on

opioid receptors present in the airways (Table 6-3).

59–64

Hospice patients generally do not have IV access (i.e., an IV catheter) into which

medications can be easily administered. As a result, medications are primarily

administered orally and, occasionally, by sublingual, buccal, transdermal, rectal, or

subcutaneous (if an infusion is warranted) routes of administration. When patients

lose the ability to swallow near the end of life (or have a condition that precludes

swallowing), the sublingual or buccal routes of administration are the most useful,

especially if drugs are lipophilic. The use of orally disintegrating tablets (ODTs)

may also be useful at this time. Morphine is hydrophilic, and although some of it

might be absorbed across the mucous membranes, the primary clinical effect

probably results from gastrointestinal absorption after the drug has trickled down the

back of the throat.

p. 88

p. 89

Table 6-3

Treatment of Dyspnea at End of Life

59,64

Nonpharmacologic methods

Pursed-lip breathing

Upright position

Relaxation

Meditation

Use of a fan or open window to circulate air over the face

Pharmacologic therapy

Systemic opioids (short-acting) in small doses given orally, sublingually, or via injection can be given every 1–

2 hours as needed

Long-acting agents can be added to supplement the routine use of short-acting opioids

Inhaled opioids deliver medication via nebulization directly into the airway, avoiding first-pass metabolism,

allowing use of smaller doses, theoretically minimizing side effects such as drowsiness. May cause local

histamine release, leading to bronchospasm. Use nonpreserved sterile injectable products. More cumbersome

and expensive owing to use of nebulizer and nonpreserved parenteral products; evidence does not show that

nebulized opioids provide greater benefit than nebulized saline

Agents: morphine 2.5–10 mg in 2 mL of 0.9% saline; hydromorphone 0.25–1 mg in 2 mL of 0.9% saline;

fentanyl 25 mcg in 2 mL of 0.9% saline

Generally given every 2–4 hours as needed for breathlessness

Benzodiazepines are useful for the anxiety associated with breathlessness

Oral morphine sulfate, in a concentration of 20 mg/mL, is commonly packaged in a

30-mL bottle at the beginning of hospice care. This bottle of morphine can provide

sixty 10-mg doses, and at this concentration, only 0.5 mL of morphine needs to be

administered. Oxycodone or hydromorphone, in comparable adjusted doses, can be

substituted for morphine when needed. There is no evidence demonstrating the

superiority of any of these over the others in severe cancer pain.

65

Lorazepam. A short-acting benzodiazepine (e.g., lorazepam 0.5 mg every 4 hours

as needed) is useful for the treatment of anxiety. Patients, especially those with

respiratory symptoms, can experience episodes of extreme anxiety near the end of

life. Caution should be used to not overuse these drugs in the elderly because they

can increase the risk of falling or cause paradoxical reactions and worsen delirium

or restlessness.

Haloperidol. Small doses of haloperidol (e.g., 0.5–1 mg) are useful for the

treatment of restlessness, delirium, or nausea and vomiting.

Prochlorperazine. When patients cannot take oral medications to manage nausea

and vomiting, rectal suppositories of prochlorperazine are often effective. Although it

is necessary to consider the etiology of the nausea and vomiting, prochlorperazine is

generally a good initial agent.

Anticholinergic agent. As death approaches, patients can have difficulty in

clearing pharyngeal secretions and, as a result, generate a sound commonly known as

a death rattle.

66 Although patients are often unconscious at this point, this sound can

be very distressing to those nearby. An anticholinergic agent (e.g., glycopyrrolate,

hyoscyamine, scopolamine, atropine) can be administered in an attempt to prevent

these pharyngeal secretions from forming. Patient positioning and gentle suctioning

can remove secretions already present. This treatment modality is usually initiated

after the patient has become obtunded; if begun too early, patients might develop

problems with thickened bronchial or pulmonary secretions, tachycardia, delirium,

dry mouth, urinary retention, or other adverse anticholinergic effects. However,

efficacy is best if these agents are started earlier in the active dying process.

67

Glycopyrrolate, available in a tablet, injectable formulation and oral solution, is a

good choice for an anticholinergic agent because it minimally crosses the blood–

brain barrier. The 1-mg tablets could be crushed and placed under the tongue every 8

hours. Hyoscyamine is available as oral tablets, ODT, oral sustained-release tablets,

sublingual tablets, oral liquid, oral solution, and injection. Either the ODT,

sublingual tablets, or oral solution of hyoscyamine can be given in a 0.125- to 0.25-

mg dose sublingually every 4 hours as needed. Scopolamine transdermal patches

have a slow onset of action (blood levels are detected 4 hours after application)

68

and are of limited utility in this situation. The oral or sublingual administration of

atropine ophthalmic solution 1% is convenient to administer. Recent shortages and

price increases have made it less cost-effective. Assuming that 20 drops is

approximately equivalent to 1 mL, patients can be given 0.5 to 1 mg (1–2 drops) of

the atropine ophthalmic solution orally or sublingually every 4 hours as needed.

Families and caregivers must be instructed not to use this in the eye.

CASE 6-1, QUESTION 4: The hospice nurse for M.P. has difficulty finding oral morphine sulfate available

from a pharmacy and difficulty in finding a pharmacy willing to accept a faxed prescription. Why is morphine so

difficult to obtain, and how should the nurse manage this problem?

Providing relief for pain or other symptoms with opioids is often difficult owing to

numerous barriers. Patients and caregivers are often fearful of opioids, or mistakenly

believe these medications will cause addiction or hasten death.

69 Pharmacists can

create barriers by not having opioids in the pharmacy, sometimes because of the fear

of robbery, fear of investigation by drug regulatory agencies, or insufficient

appreciation of the usefulness of opioids in pain management and palliative care.

70

Pharmacists who are inexperienced in providing service to hospice patients might not

be knowledgeable about federal regulations governing the provision of controlled

substances to hospice patients. Federal statutes, as well as most state statutes, permit

prescriptions for Schedule II controlled substances for hospice patients to be faxed.

According to the Code of Federal Regulations (21 CFR 1306.11) paragraph (g): “A

prescription prepared in accordance with 1306.05 written for a Schedule II narcotic

substance for a patient enrolled in a hospice care program certified and/or paid for

by Medicare under Title XVIII or a hospice program which is licensed by the state

may be transmitted by the practitioner or the practitioner’s agent to the dispensing

pharmacy by facsimile. The practitioner or the practitioner’s agent will note on the

prescription that the patient is a hospice patient. The facsimile serves as the original

written prescription for purposes of this paragraph (g) and it shall be maintained in

accordance with 1304.04(h).”

71

p. 89

p. 90

The process of ordering controlled substances for use by hospice patients at home

can take many hours, and sometimes as much as an entire day. Hospice providers

should anticipate possible difficulties when placing orders for Schedule II controlled

substance medications. M.P.’s nurse should take the time to address any concerns

M.P.’s caregivers and family may have about these medications (i.e., how they may

affect her, any worries about addiction, side effects) and allow ample time to order

them so that symptoms can be managed as they develop.

CASE 6-2

QUESTION 1: G.G., a 40-year-old woman, is admitted to hospice with stage IV ovarian cancer, metastatic to

her pelvis, liver, and lungs. She was diagnosed after many months of nonspecific complaints of gastric distress

and bloating. On laparotomy, she was evaluated as stage III and underwent a total abdominal hysterectomy and

bilateral salpingo-oophorectomy and tumor debulking at that time. She has undergone subsequent chemotherapy

and repeated tumor debulkings. In the past 6 months, her weight has decreased from 175 pounds to 153 pounds

(she is 62 inches tall). Her primary complaints are constant nausea, constipation, and gripping abdominal pain,

which she characterizes as burning and twisting. She quantifies the pain as 8 of 10 (on a 0-to-10-point scale)

and describes the pain as one that moves into her groin and leg. Her family is unhappy about the drowsiness she

experiences from her medications; they believe she is overmedicated. She is starting to have difficulty

swallowing. She has no known allergies. Her current medications include fentanyl transdermal system 75

mcg/hour every 72 hours, extended-release morphine sulfate capsules 50 mg three times daily (usually intended

for once-daily administration), docusate sodium 250 mg daily, lansoprazole 30 mg daily, and lorazepam 0.5 mg

every 4 hours as needed for nausea and anxiety. What is the most accurate assessment of her pain

management regimen?

G.G. is currently using two long-acting opioids (i.e., fentanyl transdermal,

sustained-release morphine which is being dosed too frequently), but is still unable

to achieve relief of her pain, which is probably neuropathic pain (described as

burning and twisting). It is estimated that up to 39% of patients with cancer pain have

neuropathic pain.

72–74 This may be caused by tumor growth around nerves,

postoperative nerve damage, chemotherapy-induced neuropathy or following

radiation therapy. Opioids alone may be of limited value or may require higher than

usual dosing.

72 The addition of adjuvant analgesics such as antidepressants,

anticonvulsants, and local anesthetics play an important role in treating neuropathic

pain (see Chapter 55, Pain and Its Management).

The use of two long-acting agents is duplicative and should be replaced with one

opioid. Methadone may be a better long-acting agent for G.G. because it has activity

against neuropathic pain (see Chapter 55, Pain and Its Management) and can reduce

the amount of medication she uses. Methadone affects the reuptake of serotonin and

norepinephrine, and blocks the NMDA receptor.

75 Studies, however, do not show

methadone to be superior to other opioids.

76 Advantages for G.G. include long halflife, high bioavailability, excellent absorption across mucous membranes, lack of

active metabolites, and lower cost. Methadone liquid is long-acting which may be

useful when patients lose the ability to swallow as death approaches. Disadvantages

in using methadone are its long and variable elimination half-life, drug–drug

interactions, prolongation of the QTc interval, and the variability of dosing

equivalence with other opioids. Dosing methadone is complex and should be

undertaken by experienced clinicians.

76,77

When converting fentanyl and morphine to methadone, the following should be

considered: (a) patient adherence and ability to follow prescription directions, (b)

use of an appropriate conversion formula, (c) converting a transdermal formulation

of fentanyl to an oral opioid formulation, and (d) a supplemental opioid for

breakthrough pain.

Because of its long and variable elimination half-life, the dose of methadone

should generally be adjusted only once every 4 to 6 days, and patients must be able

and willing to precisely follow directions for its use. The methadone prescribing

information should be used for the conversion, with a general rule of thumb being that

the initial methadone dose should not exceed 30 mg (Table 6-4).

78,79

New safety guidelines recommend electrocardiographic monitoring prior to and

during methadone use

80;

the need for this is terminally ill patients should be balanced

by life expectancy and goals of care. Caution should be used in patients with

electrolyte abnormalities (hypokalemia or hypomagnesemia), impaired liver function,

heart disease, prolonged QT syndrome, or the use of other QTc-prolonging drugs

(e.g., amiodarone, azithromycin, citalopram, fluconazole, haloperidol,

ondansetron).

81

Once the conversion is made, the calculated dose is adjusted and the dosing

interval is set at every 12, 8, or 6 hours, based on patient age, previous use of

opioids, and current clinical status. Clinical judgment is vital in individualizing a

regimen for each patient based on his or her needs.

Before calculating the conversion to methadone for G.G., an important

consideration in patients using transdermal fentanyl is an assessment of its

absorption.

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