82 Fentanyl from the transdermal system is absorbed through several

layers of the skin and deposited in the subcutaneous fat, from which it is absorbed

into the systemic circulation. It is generally observed that transdermal fentanyl is not

effective in very thin, cachectic patients. In those cases, the conversion would be

made without including the fentanyl. The patch would be removed at initiation of the

first methadone dose and supplemented with medication for breakthrough pain if

needed. In patients using multiple patches, one patch can be removed every 3 days.

Despite weight loss, G.G. (62 inches and 153 pounds) is not cachectic, and the

fentanyl should be included when calculating the conversion of her current opioid

dose to a comparable methadone dose. In this patient, her sustained-release morphine

formulation (50 mg three times daily) is equivalent to 150 mg/day of oral morphine.

Her fentanyl transdermal system 75 mcg/hour is equivalent to about 150 mg/day of

oral morphine. Her total morphine equivalents per day are 150 mg plus 150 mg, or

300 mg. Using a 1:5 to 1:10 ratio (10%–20%) for conversion of morphine

equivalents to methadone, the calculated dose of oral methadone for this patient

should be 30 to 60 mg/day.

Table 6-4

Conversion of Oral Morphine Dose to Oral Methadone Requirement

78,79

Total Daily Baseline Oral Morphine Dose (i.e.,

Dose of Morphine Equivalents) (mg)

Estimated Daily Oral Methadone Requirement

(as % of Total Daily Morphine Dose)(%)

<100 20–30

100–300 10–20

300–600 8–12

600–1,000 5–10

>1,000 <5

p. 90

p. 91

Although G.G. is relatively young, has been using opioids for some time, and has

severe pain (quantified at 8 of 10), a methadone dose of 20 mg every 8 hours (i.e., 60

mg/day) might be excessive. She should be treated with 15 mg of methadone every 8

hours (45 mg/day), and the dose increased, if needed, based on her clinical response.

This smaller initial dose would accommodate for some incomplete cross-tolerance

from the morphine and fentanyl and for any fentanyl that remains in her system for the

next several days. Patients who have been on much higher doses of opioids,

alternatively, can be converted during a period of several days (e.g., converting onethird of the previous daily dose of opioid every 3 days). This is an especially useful

method for converting opioid doses for thin, cachectic patients who have been on

multiple transdermal patches. A clinician should be in touch with G.G. frequently

during the first several days after her conversion to methadone. A telephone call

should be made 2 to 4 hours after the first dose to assess for efficacy and toxicity

(primarily somnolence, confusion, or nausea) and then every 3 to 5 days. If pain

relief with the first dose does not last for the entire dosing interval, it can be

adjusted, or G.G. can be instructed to take a one-time extra dose of methadone.

An added benefit in changing to methadone for G.G. is a financial one for the

hospice. Outpatient prescription prices for long-acting opioids are very steep and

significantly add to hospice costs. The prudent use of methadone can improve overall

pain management and keep costs in check. When methadone is not appropriate,

generic extended-release morphine is a good second choice. Transdermal fentanyl

should be reserved for patients who cannot take oral medication or for when there

are significant compliance issues. Extended-release oxycodone should be used only

when patients cannot tolerate morphine, have significant renal impairment, or have

other contraindications to its use. By converting to methadone, G.G.’s daily cost for

the opioid alone will decrease substantially, while still providing appropriate and

effective pain management.

G.G. will also need a supplemental analgesic for breakthrough pain. Some

practitioners use small doses of methadone, 2.5 mg or 5 mg, as often as every 3

hours. This is a good choice in a well-supervised (i.e., inpatient) setting with nurses

familiar with the use of methadone. However, if caregivers treat methadone as if it

were morphine, which is much more commonly used for breakthrough pain, the risk

of overmedicating the patient is very real. This can have disastrous consequences,

especially in frail, elderly patients. Because G.G. is not in an inpatient setting and

has tolerated morphine well in the past, 30 mg or 1.5 mL of morphine 20 mg/mL can

be prescribed to be taken every 2 hours as needed for breakthrough pain.

G.G. should also start a bowel regimen; the use of a stool softener alone is

inadequate.

42 The nurse should perform a rectal examination to determine if stool is

present in the rectal vault. An enema or suppository can be given if needed and then

senna or PEG can be taken on a routine basis.

Aggressive Symptom Management and Palliative

Sedation

D.V.’s drug regimen is unnecessarily complicated for a patient at home. It may be

possible to simplify it by looking at each problem anew. His pain is poorly managed

as evidenced by his complaint of pain intensity at 7 of 10 (on a scale of 0–10), the

use of multiple opioids, and the use of excessive PCA boluses. Once an infusion with

PCA dosing is started, there is no need to continue other long-acting opioids (i.e.,

transdermal fentanyl) or oral agents for breakthrough pain. The PCA doses are

serving as the rescue doses for breakthrough pain, and pain relief should be titrated

using this method alone. Once pain is well controlled, an oral long-acting agent can

be considered if the patient is able to swallow. To do otherwise creates a chaotic

approach. Patients reporting allergic reactions to opioids should be carefully asked

to describe the precise nature of the purported allergic reaction. True allergies to

opioids are rare; patients often refer to an adverse reaction as an allergy or have

experienced an effect from the histamine release that is associated with opioids.

Hydromorphone, especially injectable hydromorphone, is much more expensive and

no more effective than morphine and is best reserved for use in patients who have a

genuine allergy or intolerance to morphine.

CASE 6-3

QUESTION 1: D.V., a 35-year-old man with gastric cancer metastasized to the esophagus with periaortic

involvement, is hospitalized. He was diagnosed 10 months ago, and his disease has progressed despite multiple

courses of chemotherapy (most recently, irinotecan and cetuximab). A double-lumen, peripherally inserted

central catheter line has been inserted. He has lost 65 pounds since diagnosis, weighs 150 pounds at 6 feet tall,

and presents with abdominal pain, severe nausea, vomiting, obstipation (intractable constipation), and general

malaise. D.V. describes his pain as a 7 of 10 in intensity and as “burning like a knife through my stomach.” He

uses 50 to 75 patient-controlled analgesia (PCA) bolus doses every 24 hours. He has no other medical

problems. D.V. is referred to hospice care because he and his wife have agreed to stop chemotherapy and do

not want to go back to the hospital. He states a history of allergic reactions to morphine, ondansetron, and

diphenhydramine, although these reactions are not noted. He is presently receiving hydromorphone 2 mg/hour in

an IV infusion with 1 mg PCA bolus dose every 5 minutes, hydromorphone 4 mg orally every 4 hours as needed

for pain, fentanyl transdermal 275 mcg/hour every 3 days, ketamine 20 mg orally every 3 hours, senna two

tablets twice daily, docusate sodium 250 mg twice, PEG 3350 17 g daily, lactulose 15 mL as needed for

constipation, lorazepam 2 mg orally every 4 hours as needed for nausea or vomiting, metoclopramide 10 mg

orally every 6 hours as needed for nausea or vomiting, promethazine 25 mg IV every 4 hours as needed for

nausea or vomiting, baclofen 10 mg every 8 hours as needed for hiccups, and pantoprazole 40 mg once daily.

What is your assessment of his medication regimen?

Although D.V. had been prescribed ketamine every 3 hours in the hospital, it is

unrealistic to expect that this can be continued in the home setting. D.V. and his wife

would probably be glad to discontinue it and replace it with an alternative because of

his need to be dosed so often.

D.V.’s constipation is currently treated with multiple medications within the same

therapeutic class. It would be more prudent to maximize the use of a single agent

within a category, rather than using two products at less than the maximally

recommended doses. D.V. can use a higher dose of senna (up to four tablets twice

daily), and then, if necessary, continue to use the PEG 3350.

D.V. also takes multiple medications for his nausea and vomiting. Promethazine

primarily blocks the histamine receptor and can be continued if there is a vertigo

component to his nausea and vomiting. The injectable promethazine can be converted

to suppositories for use at home. Ondansetron ODT can be a good option when

patients or caregivers refuse to use suppositories. He had also been directed to take

lorazepam for his nausea and vomiting; however, benzodiazepines are not effective

antiemetics. They are given to manage the anxiety associated with nausea and

vomiting and are particularly useful in managing the anticipatory

p. 91

p. 92

nausea and vomiting that is commonly encountered during chemotherapy

administration. Metoclopramide can be useful for D.V.’s nausea and vomiting if his

physical examination reveals hypoactive bowel sounds. It is also useful for treating

hiccups, and the need for baclofen can be reassessed.

In patients who are terminally ill, suffering may continue despite maximal

palliative efforts. As a result, practitioners continually encounter patients’ requests

for the ending of their lives because of overwhelming suffering. Clinicians may be

averse to this practice both ethically and legally.

83–92 Although substantial numbers of

clinicians can imagine situations in which assisted suicide would be acceptable, few

are willing to actively participate in the ending of a patient’s life.

93,94

CASE 6-3, QUESTION 2: A few days after arriving home, D.V. asks his hospice nurse, “Can’t you just give

me something to end it all?” He has not been sleeping well, is tired of taking so many medications, and wants to

alleviate the burden he feels he is imposing on his wife.

In a small number of patients, it may be desirable to reduce suffering by the

thoughtful use of medications to induce sedation.

95–102

It is not appropriate to increase

opioid doses to achieve the desired sedated state. Medications used successfully to

induce sedation for these patients include benzodiazepines, barbiturates, and

propofol, generally given in combination. Opioids are continued to manage pain and

prevent withdrawal.

A trial of palliative sedation with intravenous midazolam could be initiated and

managed by the hospice nurse at a rate of 1 mg/hour and gradually increased if

needed to the desired effect.

88 For use in the home, compounded phenobarbital

suppositories could be added if the desired effect is not attained with midazolam

alone. Although palliative sedation has a small potential to shorten life, the need to

relieve terminal agitation or other symptoms could justify this risk. Palliative

sedation should only be initiated as a last resort in severe cases not responsive to

other palliative measures, and only after thorough discussion of the important clinical

and ethical issues with the patient, family, and other clinical team members.

Before considering palliative sedation, patients should be thoroughly assessed for

insomnia, depression, pain, and other symptoms. Underlying reasons for insomnia

should be explored and treated. Poor pain management is often the cause for

considering palliative sedation. As many as 10% to 20% of patients with cancer may

have pain that does not respond to standard systemic analgesics.

103

Interventional

techniques, including the administration of spinal opioids and/or local anesthetics

may be useful, but may not be practical to initiate for the actively dying patient at

home.

104,105

In D.V., lidocaine 0.5 to 1 mg/kg/hour administered IV or subcutaneously

might be useful to assist in the management of his severe neuropathic pain.

106–110

Lidocaine purportedly interrupts pain transmission by blocking sodium channels (see

Chapter 55, Pain and Its Management).

CASE 6-3, QUESTION 3: Repeated increases in the hydromorphone infusion basal rate (he is now at 25

mg/hour) had little effect on managing D.V.’s pain, and his consistent use of up to 120 PCA attempts in 24

hours reflects his continued pain. He describes the intensity of his pain as 8 of 10. Before considering palliative

sedation, what other therapeutic interventions can be implemented for D.V.?

D.V. was started on lidocaine 1 mg/kg/hour IV. A bolus dose was not given

because of the short half-life of lidocaine. Overnight, his use of hydromorphone

boluses dropped to one. He now reports his pain as 1 of 10 and that he slept through

the night for the first time in months. During the next 2 days, the hydromorphone basal

rate was tapered to 5 mg/hour. He did not experience any lidocaine toxicity, such as

perioral numbness, metallic taste, or somnolence. D.V. continued on lidocaine, using

no hydromorphone boluses for the next 2 weeks, until he died at home surrounded by

his family.

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

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(30)

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