Chapter 27: End-of-Life Care

A 75-year-old man is admitted to the hospital for a heart failure exacerbation. This is his second admission for heart failure within the last 6 months. His nurse asks if he is an appropriate candidate for hospice care.

Question 27.1.1 Which of the following would qualify your patient for the Medicare hospice benefit?

A) His cardiac ejection fraction is 20%, and he is dyspneic with moderate exertion (NYHA class II heart failure).

B) He agrees to a do not resuscitate (DNR) status in the event of cardiorespiratory failure.

C) He needs assistance with ambulation.

D) His implanted cardiac defibrillator (ICD) has fired once in the past year.

E) He has had escalating cardiac hospitalizations despite optimal medical management.

Answer 27.1.1 The correct answer is "E." If your patient has a terminal disease with declining function, worsening symptoms, worsening laboratory tests, or escalating hospitalizations, he or she probably qualifies for hospice. "A," a low cardiac ejection fraction (typically <20%), is a recommended criterion for heart disease but must be accompanied by dyspnea at rest (class IV heart failure). "B" is incorrect. Despite popular belief, a hospice patient need not agree to a DNR status; however, hospice agencies are permitted to have different admission criteria and some require a DNR status for admission. Check with your local hospice agencies. Regardless, you should have a frank discussion with the patient about the role of aggressive resuscitation and the goals of hospice care. "C" is also incorrect. While a decline in functional status is a strong indication of worsening prognosis, it is not automatically a criterion. Most patients with heart failure need assistance with at least four activities of daily living (ADLs) before having a prognosis of death within 6 months. "D" is incorrect. Patients with ICDs are eligible for hospice, and whether or not it has fired does not impact enrollment decisions. It is important to talk about the ICD, ideally before a patient approaches the final weeks/days of life. Many patients choose to have it disabled once they enroll in hospice. If an ICD is not disabled, it is important that the hospice staff be aware of it and know what to do as it will fire when the patient dies, which can be distressing for both the patient and the family.

Your heart failure patient is currently on maximal medical management with an ACE inhibitor, beta-blocker, loop diuretic, aldosterone antagonist, long acting nitrate, hydralazine, and a dual chamber ICD. He wants to discuss the management of his cardiac therapies in relation to hospice.

Question 27.1.2 Which statement is true about cardiac therapies for patients with heart failure in hospice?

A) Hospice will not enroll patients on intravenous inotropic support (such as dobutamine or milrinone infusions).

B) Oral cardiac medications like beta-blockers and diuretics should be stopped because they are unlikely to provide any benefit to quality of life.

C) A fluid restriction is no longer relevant once a patient enrolls in hospice.

D) Hospice will not enroll patients who have not deactivated their ICD.

E) None of the above

Answer 27.1.2 The correct answer is "E" none of the above. Many of the therapies for patients with advanced heart failure provide symptomatic relief and improve quality of life. Just as you would do with any other advanced illness, a thorough evaluation of each medication and intervention should occur with the goal of determining if that intervention will contribute to your patent's overall goals. Physicians need to negotiate the balance between benefit and burden of each individual therapy. Although often a surprise to physicians, "A" is incorrect. A patient can have continuous inotropic infusion and still be enrolled in hospice. Some heart failure patients are dependent on inotropes and require them to maintain a certain level of quality of life, and they are willing to accept the trade-offs of having a continuous infusion to maintain that quality of life. Be aware that inotrope infusions do not prolong survival (in fact they shorten survival compared to no inotropes). The burden of inotrope infusions include: cost, risk of line infections, and increased risk for arrhythmia.

Hospice agencies are required to provide treatment to manage symptoms related to the terminal condition and many hospice agencies utilize formularies in order to control cost. Some hospice agencies have formularies that will allow the use of inotropes for management of dyspnea, fatigue, etc., while others will specify that the symptoms be controlled with other agents such as opiates.

"B" is incorrect. There is so much more to palliative care than giving morphine for shortness of breath in heart failure! Continuing cardiac therapies may allow a patient to maintain their cardiac functional status and prevent pulmonary congestion and should never be discontinued just because a patient enrolls in hospice. With that being said, there are times when the patient's goals support the discontinuation of these medications. "C" is incorrect because as noted above, every decision comes with both a benefit and a burden, which need to be weighed. Some level of fluid restriction may help with breathing and pulmonary congestion and should be balanced against the discomfort of restricting intake. "D" is incorrect because it is not a requirement for an ICD to be deactivated. However, the incidence of arrhythmia can be high in this population and ICD shocks near the time of death can be very distressing to the patient and the family and should be discussed.

You think that your patient may be appropriate for hospice and decide that a palliative medicine consult might be useful to address his goals of care, review symptom management, and discuss hospice.

Question 27.1.3 Which statement accurately reflects how palliative medicine is different from hospice?

A) Only palliative medicine affirms life and attempts to help patients live as fully as possible.

B) Palliative medicine offers treatments including aggressive medical treatments such as radiation therapy, intravenous (IV) fluids, or interventional radiologic procedures, while hospice does not.

C) Palliative medicine is performed by a physician only, while hospice care involves an entire team of providers.

D) Palliative care can be offered at any time during a life-limiting illness, even if a patient is still actively seeking a cure.

E) Palliative medicine consults are billed under Medicare Part B while hospice care is reimbursed through the Medicare Part H.

Answer 27.1.3 The correct answer is "D." Palliative care is specialized medical care for people with serious illnesses that is focused on providing patients with relief from the symptoms, pain, and stress of the serious illness—whatever the diagnosis. The goal is to improve quality of life for both the patient and the family. Palliative care is provided by a team of doctors, nurses, and other specialists who work with a patient's primary team to provide an extra layer of support. Palliative care is appropriate at any time in a serious illness and can be provided together with curative treatment. Hospice care is a type of palliative care, which occurs during the final months of someone's life when cure is no longer possible or no longer consistent with the patient's goals. "A" is incorrect because both hospice and palliative care strive to make life meaningful and comfortable for patients. "B" is incorrect. Since the goal of both hospice and palliative care is to prevent and relieve suffering, any of these modalities may be used if appropriate. In fact, any intervention can be considered palliative if the intention is to relieve distressing symptoms associated with the fatal disease (such as a hip-pinning for pain control after a pathologic fracture). There are no restrictions prohibiting a hospice agency from providing "aggressive" interventions designed to relieve pain and suffering. "C" is incorrect because both hospice and palliative medicine are built on the concept of a team providing care to the patient and family. Hospice care usually (but not always) is directed by the primary physician. "E" is incorrect because palliative medicine services are typically billed as inpatient consult services and are reimbursed by Medicare Part A, and there is no such thing as Medicare Part H—yet!

Question 27.1.4 Which of the following is TRUE regarding the Medicare hospice benefit?

A) The Medicare hospice benefit requires all care related to the primary admitting illness to be covered by the hospice agency, including physician fees, as long as the hospice program does not employ the physician.

B) The hospice benefit, similar to the Medicare home care benefit, requires that the patient be homebound.

C) Respite care within an acute hospital setting is provided for up to 5 days every 6 months.

D) Hospice entry requires that the patient cannot live alone (must have an on-site primary caregiver).

E) A flat per diem rate is paid to the licensed hospice program regardless of the level of services provided.

Answer 27.1.4 The correct answer is "A." The Medicare hospice benefit requires all care related to the primary admitting illness to be covered by the hospice agency. Think of it as capitated care. However, Medicare affords individual hospice agencies wide latitude in determining what modalities they use to treat the symptoms of a particular illness. For example, one agency might allow blood transfusions for the relief of dyspnea, while another agency only covers the use of medications such as morphine or lorazepam for dyspnea. If necessary for acute symptom management, Medicare also covers acute hospitalizations related to the primary illness. "B" is incorrect. A hospice patient does not need to be homebound. Respite care can be offered as frequently as needed, which makes "C" incorrect. The Medicare hospice benefit provides respite care. This can last up to five nights at a time. The respite care needs to be provided in a setting where there is a registered nurse available continuously, and the patient must come from a home setting (including assisted living). This can be used if the caregiver is unable to care for the patient for a variety of reasons. "D" is incorrect because Medicare does not require that the patient have a primary caregiver in the home to receive the hospice benefit; however, an individual hospice agency may require a primary caregiver be identified before enrolling a patient. "E" is incorrect because Medicare pays the hospice organization a stratified per diem rate depending on the level of care the patient requires.

After meeting with the palliative care team, your patient's family inquires more about hospice care. They ask what other services are covered.

Question 27.1.5 The Medicare hospice benefit includes coverage for all of the following expenses EXCEPT:

A) Medications related to symptom management.

B) Social work visits.

C) Home health aide services.

D) Room and board for a patient living in a nursing home.

E) Bereavement services.

Answer 27.1.5 The correct answer is "D." All of the other options listed are services covered under the Medicare hospice benefit. A patient living in a nursing home is eligible for hospice care, but the cost of room and board for the nursing home is not paid by the hospice benefit. In some special circumstances, nursing home care will be paid for a short duration (e.g., when a hospice patient uses the five-night respite care benefit or if the patient is admitted to a nursing home for management of a distressing symptom that cannot be controlled in the home setting).

A few months go by and your patient has again been hospitalized. You now believe that he has fewer than 6 months to live. The local hospice medical director reviews the case and agrees. The patient is dyspneic at rest, requires 24-hour oxygen by nasal cannula, and his cardiac ejection fraction has decreased to 15%. He wishes to avoid further hospitalization and has elected to have a DNR status. His family wants to know what you can do when he becomes severely dyspneic.

Question 27.1.6 Which of the following is appropriate palliative treatment of severe dyspnea in this patient?

A) Intubation and ventilation.

B) Morphine.

C) Scopolamine.

D) Buspirone.

E) Hyperventilating into a paper bag.

Answer 27.1.6 The correct answer is "B." Morphine and other opioids analgesics are indicated for palliation of dyspnea in cardiac failure. Despite concerns about opiates worsening respiratory function in end-stage heart failure, studies have concluded that oral morphine improves dyspnea in this patient population and does not cause respiratory failure or hasten death. This is supported by recommendations from the American College of Cardiology and the American Heart Association. If morphine or other therapies for shortness of breath were to shorten life, the ethical principle of "double effect" would be applicable. The double effect principle states that as long as the intention of a therapy is to reach a good outcome (such as improve pain and alleviate suffering), then even if the unintended consequences result in a negative outcome (e.g., shortening life) the intervention is permissible. The key here is intention. If you choose "A," your patient's ghost will be back to haunt you. This patient has chosen a far less aggressive stance toward life-prolonging measures, and his wishes should be honored. "C" is incorrect. Scopolamine is used to reduce oropharyngeal secretions (resulting in sonorous respirations) but is not likely to relieve dyspnea in this patient. In addition, scopolamine is highly anticholinergic and crosses the blood–brain barrier, which can result in delirium and should be used with caution in an awake and alert patient. Glycopyrrolate is a better choice to control secretions in a patient who is alert and awake. "D" is incorrect. While anxiety and dyspnea often occur together and exacerbate each other, buspirone (BuSpar) is a weak anxiolytic and has no direct effect on dyspnea. Low-dose lorazepam would be a reasonable alternative if you felt his dyspnea was complicated by anxiety. And "E" is just plain wrong—although still not as bad a choice as "A."

Consider diuretics to relieve dyspnea in heart failure patients in hospice. Often times we are guilty of forgetting to treat the underlying illness when someone is in hospice, reaching for morphine first. Are there signs of volume overload (e.g., elevated JVD, diffuse crackles, profound edema)? Diuretic therapy may reduce pulmonary congestion and relieve dyspnea, and the benefits and burdens should be weighed. The burdens that need to be considered include: patient's bed bound status, risk for incontinence decreasing quality of life, patient's agreement with using a bladder catheter, renal function, etc.

Objectives: Did you learn to…

• Identify appropriate patients for end-of-life care, particularly for the Medicare hospice benefit?

• Describe the features of the Medicare hospice benefit?

• Treat patients with dyspnea related to end-stage cardiac disease?

A 30-year-old male patient you have known for several years was diagnosed with metastatic melanoma several months ago. He presents now with intermittent, severe headaches associated with nausea. A head CT scan performed last week showed three metastatic foci with surrounding edema. He currently takes maximum doses of acetaminophen and large doses of morphine.

What is the best initial treatment option to help relieve his headache and nausea?

A) Neurosurgical intervention.

B) Dexamethasone.

C) Sumatriptan.

D) Ibuprofen.

E) Increased morphine doses.

The correct answer is "B." Corticosteroids are the preferred therapy for headaches due to increased intracranial pressure from edema, as is presumably the case here. Whole brain or stereotactic radiation therapy, alone or in combination with corticosteroids, may also be used as palliative therapy for multiple brain metastases. "A" is incorrect because neurosurgical consultation for craniotomy should be reserved for patients who fail other interventions or who present with rapidly worsening symptoms. "C" and "D" are incorrect. Sumatriptan and ibuprofen should not be used to treat increased intracranial pressure. "E," increased morphine doses, may be required, but corticosteroids are typically used first.

A 74-year-old woman presents to your clinic with a new diagnosis of nonsmall cell lung cancer found during an evaluation for hip pain that revealed diffuse bony metastases on x-ray. She inquires about ways to improve her quality of life in addition to the care recommended by her oncologist. You recall reading the landmark study (a study that every primary care and palliative care physician should know—and if you don't know you should read it cover to cover several times) by Temel et al., regarding the introduction of early palliative care in patients with metastatic nonsmall-cell lung cancer.

Which of the following is NOT true about the outcomes for the patients that received the novel intervention of early palliative care compared to those that received standard oncologic care?

A) Introduction of early palliative care improved patients' quality of life.

B) Introduction of early palliative care improved patients' mood.

C) Introduction of early palliative care shortened the median survival.

D) Introduction of early palliative care resulted in fewer aggressive therapies at the end-of-life.

The correct answer is "C." Introduction of early palliative care was shown to increase median survival from 8.9 months to 11.6 months, and this occurred despite the intervention group patients receiving fewer aggressive interventions at the end-of-life. Both "A" and "B" are incorrect answers (but true statements) because this study showed that both quality of life and mood were improved when early palliative care was introduced to the standard oncologic care in this patient population. "D" is incorrect (but again a true statement) because 33% of patients who received early palliative care received "aggressive care" (chemotherapy within 2 weeks of death, no hospice care, and/or admission to hospice 3 days or less before death) as compared to 54% of patients in the standard care group. The Temel study applies to a very specific patient population—patients with metastatic nonsmall-cell lung cancer; however, there are ongoing studies in other advanced illnesses to see if these outcomes can be reproduced and applied to larger populations of patients. In fact, there is current research being done at the University of Iowa introducing early palliative care to patients with end-stage-liver disease and measuring the outcomes of mood, quality of life and mortality. Keep an eye out in the literature because the novel therapy of early palliative care may prove to be applicable to more patient populations over the next several years.

A 74-year-old female was diagnosed with adenocarcinoma of the colon 3 years prior to beginning hospice care. She has known metastases to her liver and pelvis. She complains of a cramping pain in her abdomen and a "deep pain" in her groin. She is currently receiving morphine 10 mg orally (PO) every 4 hours (except when asleep) and acetaminophen 650 mg PO TID. She says that her pain is 4 out of 10 on a numeric pain scale. Her past medical history includes hemorrhage secondary to a gastric ulcer 4 years ago (Helicobacter pylori negative on biopsy).

Question 27.2.1 Which of the following strategies is the best next step for improving this patient's pain control?

A) Start gabapentin to treat the neuropathic aspect of her pain.

B) Add a strong nonsteroidal anti-inflammatory drug (NSAID) such as ketorolac (Toradol) to her current regimen.

C) Add scheduled tramadol to try to decrease her morphine use.

D) Start a long-acting morphine (e.g., MS Contin) at a dose 20% higher than her current morphine use.

E) Maximize the dose of acetaminophen to 1,000 mg every 4 hours.

Answer 27.2.1 The correct answer is "D." The patient is taking short-acting opiates around the clock, which can lead to "chasing the pain" (not to be confused with "chasing the dragon," which is inhaling heroin smoke, which leads to a leukoencephalopathy … you never know … it could be on the test!). Patients often receive much better pain control when they are maintained on a long-acting opiate. It is common practice to increase the dose of opiates by 15% to 25% when a patient's pain is only partially controlled. It is then recommended to have the breakthrough dose equivalent to 10% of her 24-hour use. "A" is incorrect as her pain is better described as visceral or somatic rather than neuropathic. Gabapentin is an acceptable choice for neuropathic pain but is not likely to be effective for this patient. "B" is incorrect. Ketorolac is the NSAID with the highest rate of renal disease and gastrointestinal (GI) bleeds and is contraindicated in a patient who has had a GI bleed. If you were to add an NSAID, ibuprofen would be a better choice, and GI protection with a proton pump inhibitor would be advisable for this patient. "C" is incorrect. Tramadol is a weak mu-receptor agonist, possessing some norepinephrine and serotonin reuptake inhibition and is much less efficacious than morphine. Tramadol is not likely to benefit a patient with severe pain from cancer and metastases. Tramadol also has a number of troubling side effects such as an increased risk of seizures and serotonin syndrome. "E" is incorrect because the current recommended daily maximum dose of acetaminophen for elderly patients is 3,000 mg (don't blame us … blame the FDA), and the frequency suggested in "E" would far exceed this amount.

When determining what medications are appropriate for treating pain, it helps to know what type of pain the patient has.

Question 27.2.2 Cancer is known to cause which type(s) of pain?

A) Neuropathic pain.

B) Visceral pain.

C) Soft tissue/bony pain.

D) Pain from increased intracranial pressure.

E) All of the above are types of pain.

Answer 27.2.2 The correct answer is "E." Physiologic pain is separated into four categories: soft tissue or bony pain (also called somatic pain), neuropathic pain, visceral pain, and the pain of increased intracranial pressure. An example of somatic pain is the musculoskeletal pain (e.g., sports injuries and fractures) that everyone experiences at some point. Neuropathic pain is generally described as burning and results from nerve damage, inflammation, or compression. Visceral pain comes from distention of an organ capsule (e.g., liver enlargement from metastases, and colicky pain from the colon). Depending on where a metastasis or primary tumor is located, it may cause somatic pain (e.g., bone tumors), neuropathic pain (e.g., Pancoast tumor), visceral pain (e.g., peritoneal carcinomatosis), or a headache from increased intracranial pressure.

You decide to increase her morphine dose.

Question 27.2.3 Which of the following statements is TRUE?

A) Intravenous morphine is 10 times more potent than oral morphine.

B) Naloxone should be given if a hospice patient near death demonstrates confusion, decreased responsiveness, a slowed respiratory rate or cool extremities.

C) Patients exhibiting a local rash or intense pruritus at the site of intravenous morphine administration must be considered allergic and given an alternate opiate.

D) Tolerance to morphine does not occur in patients with cancer, so any increased analgesic need is due solely to uncontrolled pain.

E) Renal and hepatic insufficiency both contribute to the accumulation of morphine and its metabolites.

Answer 27.2.3 The correct answer is "E." "A" is incorrect. Intravenous (IV) morphine is about three times as potent as oral morphine. "B" is incorrect. Patients who are within several days or hours of death often exhibit pallor, peripheral vasoconstriction, apneic episodes, and obtundation as part of the physiologic process of dying. Counseling the family and patient is preferable to administering naloxone, which can cause abrupt opiate withdrawal and significant distress and discomfort to the patient (again, don't make her ghost haunt you). "C" is also incorrect. Local histamine release is a known effect of IV morphine administration. Histamine-mediated skin changes proximal to the IV infusion site of morphine do not represent a contraindication to future morphine use. In fact, antihistamines (e.g., diphenhydramine) can be used to counter morphine-related histamine effects, such as rash, itching, and hypotension. But again, if you choose to use an antihistamine you need to monitor for delirium. "D" is incorrect. All patients can develop tolerance to the effects of morphine. Of course, in patients with terminal cancer, increasing opiate requirements are often entirely due to increasing pain. And even if your dying patient develops morphine tolerance, you still need to treat the pain. Finally, "E" is correct. Patients with renal and hepatic insufficiency can accumulate metabolites of morphine, some of which are helpful in pain control and others of which may have an anti-analgesic effect. These patients often need lower doses of opiates. If a patient is actively dying and has evidence of renal failure, opioid doses can often be decreased significantly without a worsening of pain control. Fentanyl and methadone are considered the safest opiates in renal failure although methadone use is complicated by the long half-life.

Question 27.2.4 Which of the following statements is NOT accurate regarding the appropriate use of opiates in end-of-life situations?

A) At times, delirium can be improved with opiate dosage reduction and/or the addition of opioid-sparing analgesics (e.g., acetaminophen).

B) If oral morphine cannot be swallowed, then either an enteral feeding tube or a parenteral route (IM/IV/subcutaneous) must be used.

C) Dosage conversion from one opiate to another is affected by the type of opiate used and the route of administration.

D) Transdermal opiate delivery products are expensive, have a slow onset of action, and have erratic absorption.

E) There is no pre-established ceiling dosage for opiates, and you may increase the opiate dose until adverse side effects occur.

Answer 27.2.4 The correct answer (and the false statement) is "B." Concentrated oral morphine solutions (20 mg/mL) can be given in small amounts to patients who are unable to swallow. While it was previously thought that morphine elixir worked by absorption through the buccal mucosa, it is now believed to trickle down the throat to be absorbed through the gastric mucosa. Fentanyl is the only opiate absorbed via the buccal mucosa (thus, the fentanyl lollipops). A secret that drug companies do not want you to know is that you can avoid the expense of fentanyl lollipops by using fentanyl IV solution orally for control of breakthrough pain. Since concentrated morphine elixir is effective in patients who cannot swallow, feeding tubes or parenteral routes of administration are unnecessary. "A" is true. Delirium is a common and disturbing finding toward the end of life, and it is sometimes precipitated or exaggerated by opiates. On the flip side, untreated pain can cause delirium, and the delirium may improve when opioid doses are escalated. In these situations, it can be helpful to rotate opiates because the lack of cross-tolerance means that the dose can often be decreased while maintaining the same level of pain control. Acetaminophen is the safest opiate-sparing analgesic, and its adjuvant action may allow for opioid dosage reduction without a loss of overall analgesia. In the appropriate patient, NSAIDs may also be used.

"C" is true. When a patient chronically taking one opiate switches to another, a dose adjustment calculation must be made. You cannot switch milligram for milligram. Also, some authorities recommend that after the calculation, you slightly reduce the dose of the new opiate due to incomplete cross-tolerance (refer to opioid dose conversion charts available in numerous pharmaceutical texts and handbooks). "D" is true. The transdermal fentanyl patches, though convenient, have fluctuating bioavailability over the three days that each patch is worn, and breakthrough doses of an alternative opiate should be available. Fentanyl is also fat-soluble and absorption/bioavailability is decreased in thin and/or cachectic patients. The fentanyl patches are expensive and initially have a slow onset until a steady state is achieved. For this reason, a fentanyl patch should never be used alone as an initial treatment of acute pain. In fact, if you want to avoid a lawsuit, a fentanyl patch should never be used as the first method to treat pain in an "opiate-naïve" patient. "E" is true. Because of the extraordinarily wide dosage range of opiates, the ceiling dosage cannot be calculated or assumed. Rather, analgesic requirements allow for continual increase unless adverse side effects clearly undermine the use of the drug.

You increase the morphine dose considerably over a 2-week period and your patient begins having escalating pain and muscle twitching.

Question 27.2.5 Which statement is true about opioid-induced hyperalgesia (OIH)?

A) Patients with OIH always become delirious.

B) When a patient has OIH, the pain does not improve when the opioid dose is increased.

C) The pain in OIH is described as a worsening of the original pain being treated.

D) OIH needs to be differentiated from worsening underlying disease.

Answer 27.2.5 The correct answer is "D." Before we presume that a patient has OIH, we need to ensure that the increase in pain is not due to further disease progression. We also need to consider increased pain resulting from increased activity or other exacerbation (such as trips to x-ray or radiation therapy). Additional features that can help distinguish OIH from increased pain include: the development of muscle twitching, presence of allodynia (pain elicited from ordinarily nonpainful stimuli, such as stroking skin with cotton—although this can occur with neuropathic pain syndromes as well), and development of seizures or delirium. However, not all patients with OIH become delirious, making "A" incorrect. The key feature of OIH is that the pain increases as the dose of the opiate is increased and will decrease when the dose is decreased. We are not certain why OIH occurs but several mechanisms have been proposed. One proposed mechanism is upregulation of NMDA receptors from chronic use of high-dose opiates, which is why switching to an opiate with NMDA antagonism could prove helpful (such as methadone or ketamine). However, OIH can still occur in patients new to opiates and on low doses, so there is still more research needed on this subject. "C" is incorrect as well. OIH typically produces diffuse pain, less defined in quality and extending beyond the pre-existing pain distribution.

You are concerned about OIH and you decide to rotate to methadone.

Question 27.2.6 Which of the following statements is FALSE regarding the use of methadone?

A) Methadone can be legally prescribed for pain and addiction by a physician with a current schedule II DEA license.

B) Methadone is more easily absorbed by those with bowel problems than is sustained-release morphine.

C) The half-life of methadone is 22 hours.

D) Methadone may be useful for neuropathic pain because it inhibits receptors in the dorsal horn of the spine.

E) Methadone is primarily excreted in the stool and thus drug dosages do not need to be modified in those with mild to moderate renal disease.

Answer 27.2.6 The correct answer (and false statement) is "A." Methadone can be prescribed for pain control by physicians with a schedule II DEA license but cannot be prescribed for addiction or opiate withdrawal without a special license. "B" and "C" are true. Methadone has a long half-life, and sustained-release preparations are not needed. Sustained-release morphine may pass unabsorbed in patients with short gut or dysfunctional gut, whereas methadone would be absorbed. "D" is true; methadone may be especially useful in treating neuropathic pain. "E" is also true. Methadone is primarily excreted into the GI tract. Patients with liver disease should have doses adjusted. However, those with renal disease may tolerate "normal" doses since renal excretion is a minor part of methadone elimination.

Your nurse calls you about your patient and reports that her pain level has been rising, and despite significant increases in both basal and breakthrough opiate therapy, the patient's pain is uncontrolled. The nurse asks you if there is something else that can be added to the opiates as an adjunctive treatment for pain. For no explicable reason, you cannot get gabapentin out of your head—even though you know it's probably useless for this patient.

Question 27.2.7 Which of the following is TRUE regarding the use of the gabapentin?

A) Gabapentin is hepatically cleared and dose adjustment is needed in patients with liver disease.

B) The primary utility of gabapentin is in neuropathic pain.

C) Gabapentin primarily works via the μ-opiate receptors.

D) The most common side effects of gabapentin are supraventricular arrhythmias (thus limiting its utility in heart failure patients).

E) If a patient does not respond to gabapentin, she will also not respond to pregabalin.

Answer 27.2.7 The correct answer is "B." Gabapentin has proven to be a marginally effective (NNT = 7) therapy for a number of diseases that manifest with neuropathic pain, including postherpetic neuralgia, diabetic neuropathy, and cancer-related neuropathic pain. "A" is incorrect because gabapentin is excreted unchanged through the kidneys—a plus for patients with working kidneys on multiple drugs. Why do we like drugs that are not hepatically cleared? They do not interact in any of the cytochrome P450 pathways and therefore have few drug–drug interactions. "C" is incorrect. The mechanism of gabapentin is complex and not fully understood, but we are fairly certain that it does not work through the μ-opiate receptors. The literature suggests there is an intricate interplay with multiple receptors, including voltage-dependent calcium channels and increasing synthesis of GABA (more than you wanted to know, right?). "D" is incorrect. The most common side effect of gabapentin is its effect on cognition, causing dizziness and somnolence. Gabapentin can also cause edema, which can be problematic for patients with heart failure. "E" is incorrect. Although gabapentin and pregabalin are thought to have the same mechanism of action, it appears that patients that some patients will respond to one but not the other. Another important distinction between gabapentin and pregabalin is the time needed to titrate to an effective dose. With gabapentin we typically start at 100 to 300 mg and escalate the dose over the course of weeks up to 3,600 mg divided three times a day; alternatively, pregabalin starts at 75 mg daily and reaches a max dose of 300 mg BID within a week of initiation.

As time goes on, the patient has other concerns, including constipation, weight loss of 20 pounds over 2 months, sleeplessness, nausea, and anxiety. In addition, she expresses how her loss of functional abilities is a hardship for her and her adult daughter who serves as her primary caregiver. Her guilt for losing her health is a continual source of frustration and anger.

Question 27.2.8 What is true regarding her social and emotional pain?

A) It will not affect the patient's analgesic requirements.

B) It will likely complicate treatment adherence.

C) Active treatment of emotional sources of pain should only occur after the physical source has been addressed and treated.

D) Prophylactic antidepressants in patients within 6 months of death decrease the probability of developing depression.

Answer 27.2.8 The correct answer is "B." Adherence, always an issue, is especially compromised in those dying patients whose social, spiritual, and emotional problems are not effectively addressed. Similarly, analgesic control of somatic pain is complicated when social, emotional, and spiritual sources of pain exacerbate the patient's response and perception to somatic pain. Concurrent treatment of all sources of pain is necessary. Antidepressant therapy in dying patients who do not have clinical depression offers no prophylaxis against the development of depression.

You estimate your patient's life expectancy to be 2 months or less. Her frailty has progressed to the point where she is bedbound and utterly dependent for all of her ADLs. You have made some adjustments, and she is now on stable doses of the following medications:

• Hydromorphone (Dilaudid) 20 mg PO Q 4 hours

• Acetaminophen 1,000 mg PO TID

• Sorbitol 30 mL PO TID

• Metoclopramide 20 mg PO TID

You want to optimize her medications.

Question 27.2.9 Which of the following is the most appropriate medication adjustment to make at this time?

A) Hydromorphone → scheduled controlled release morphine.

B) Hydromorphone → scheduled immediate release morphine.

C) Hydromorphone → scheduled controlled release morphine and immediate release morphine as needed.

D) Acetaminophen → immediate release morphine.

E) Acetaminophen → nortriptyline.

Answer 27.2.9 The correct answer is "C." A patient who has reached a stable dose of short-acting opiate, such as hydromorphone, should subsequently be switched to a long-acting opioid agent. An immediate release medication should be available for acute "breakthrough" pain. There is no reason to change the acetaminophen. Nortriptyline is sometimes useful as an adjuvant medication and is particularly helpful when treating neuropathic pain.

The hospice nurse calls you. Your patient is at home and has become restless with slow respirations (6/min) along with paroxysmal coughing and gagging with a large amount of secretions.

Question 27.2.10 The following are all appropriate orders for this patient EXCEPT:

A) Obtain subcutaneous access through placement of a subcutaneous button or butterfly needle.

B) Lorazepam 1 to 2 mg PO or SL every hour PRN.

C) Glycopyrrolate 2 mg PO or SL every 4 hours PRN.

D) Midazolam 0.4 to 4 mg SC every hour PRN.

E) Naloxone 2 mg SC every 2 hours PRN.

Answer 27.2.10 The correct answer is "E." Naloxone is a potent opioid receptor antagonist. Although the sudden change in the patient's status could be partly due to opiate accumulation, the risks of naloxone antagonism are great and include severe pain, cardiac arrhythmias, and seizures (remember, you don't want that ghost haunting you). Withholding or reducing the next dose of opiates is a safer approach. A subcutaneous infusion pump ("A") may allow effective administration of medications and fluids in patients who cannot tolerate oral administration. The use of hydration at the end of life is controversial. Withholding fluids and nutrition has strong merit, but the evidence is not compelling enough to declare that fluid infusion is futile and possibly harmful in this setting. In addition, dehydration is a common cause of delirium at the end of life, and her confusion may improve with gentle hydration. It is more important to review the patient's goals and only administer fluids if consistent with her goals. Glycopyrrolate ("C") has been shown to decrease oral/pulmonary secretions that lead to the "death rattle" in the final days and hours of life. Such treatment benefits the patient and her grieving family and friends. "B" and "D" may also be useful. Benzodiazepines have the potential to reduce anxiety, agitation, and insomnia; however, any benzodiazepine can worsen confusion and cause delirium. Benzodiazepines with an extended half-life (e.g., diazepam and chlordiazepoxide) should generally be avoided because of the potential for toxic accumulation.

Objectives: Did you learn to…

• Define major physiologic pain categories?

• Describe the pharmacology of pain control?

• Prescribe opiate pain medications and adjuvant therapies for pain?

• Identify emotional, social, and spiritual symptoms and recognize how they can affect pain management?

Regarding the subcutaneous administration of fluids and medications, which of the following is true?

A) Not more than 500 cc of saline per day can be given by hypodermoclysis (subcutaneous administration).

B) Only medication with low lipid solubility can be delivered via subcutaneous administration.

C) Most drugs used in end-of-life care can be given subcutaneously.

D) In general, subcutaneous administration dosage conversion is closer to oral dosage than to IV dosage.

The correct answer is "C." The subcutaneous route can be quite effective. Adverse events such as local irritation, pulmonary edema, and local edema are less frequent with subcutaneous administration when compared with IV administration. In general, most drugs used in end-of-life care can be given subcutaneously. "A" is incorrect. Evidence demonstrates that up to 3,000 cc of crystalloid solution can be given subcutaneously in a 24-hour period with limited adverse effects. Experience suggests that even greater volumes can be given. "B" is incorrect. Lipid solubility is not a clinically relevant aspect of bioavailability during subcutaneous administration. "D" is also not true. Subcutaneous doses are generally very close to, but lower than, the IV dose of a drug. As with IV administration, the onset of action is more rapid than with enteral dosing.

You assume care for the 84-year-old father of one of your patients. He has severe dementia, which has caused him to require nursing home care for the last 5 years. He has stable heart failure due to ischemic cardiomyopathy. He requires full assistance to eat, which the staff members spend an hour doing at each meal. He has lost 20 lb in the last 6 months (BMI now is 21 kg/m²). A facility nurse calls you worried about his weight.

Question 27.3.1 What would be the best intervention for weight gain in this patient?

A) Megestrol.

B) Nutritional supplements.

C) Dronabinol.

D) Mirtazapine.

E) Feeding tube.

Answer 27.3.1 The correct answer is "B." The most effective means to maintain weight in elderly patients with dementia is hand feeding and providing favorite foods (yes, ice cream with every meal is OK!) and frequent offerings. Hand feeding is expensive and often problematic in nursing homes with limited staff. When hand feeding is not possible, nutritional supplements are the least invasive alternative with minimal side effects and have been shown to be modestly effective in promoting weight gain in elderly patients with dementia. Other important considerations related to nutrition in dementia patients is being aware of effective ways to decrease aspiration risk, including sitting upright, eating small portions, use of thickened liquids, and hand feeding. "A," megestrol (Megace), is minimally effective in improving appetite and increasing weight in patients with cancer cachexia and weight loss related to AIDS, but there is sparse evidence for use in geriatric patients. Trials are of short duration (1–2 months) using widely varying amounts of megestrol (240–1,600 mg/day), and the weight gained is typically fluid and not muscle mass. With such poor evidence for benefit but well-known side effects, there is no role for megestrol in this setting. In fact, there is no role for hormones or steroids in the treatment of weight loss in the elderly patient with dementia. "B," dronabinol, is synthetic derivative of cannabis (known to cause "the munchies" … we've heard). It increases appetite and improves nausea, but again the studies are small and exploratory in nature and focused mainly on patients with AIDS and cancer. "D" is incorrect. If the patient were depressed and losing weight as a result, mirtazapine might be a reasonable choice since it may stimulate appetite. However, mirtazapine has not been shown to boost appetite in nondepressed subjects (and like the SSRIs, does not improve depression in the demented elderly anyway; Lancet. 2011;378:403–411). Some antidepressants, such as SSRIs and bupropion, are associated with weight loss. Finally, a feeding tube is invasive with numerous side effects (cellulitis, leakage, and increased fecal incontinence which can contribute to bed sores). While enteric tube feeds may improve caloric intake, they do not extend life, increase weight, improve functional status, or reduce the incidence of pressure sores or aspiration in dementia patients (exceptions to this are ALS and gastrointestinal cancers with proximal obstruction with a good functional status). Thus, "E" is incorrect.

Your nutrition shakes are not doing the trick. The patient continues to lose weight. To further stage his dementia, you attempt a Folstein Mini Mental Status Exam, but he cannot participate. The nurse reports that he needs assistance with all ADLs, he is incontinent, and he is unable to speak more than six intelligible words (and although you remember a couple of post-call days when you were in the same condition, you say nothing). The nursing staff asks you if the patient is appropriate for hospice care.

Question 27.3.2 Which of the following is TRUE?

A) The life trajectory of terminally demented patients is unclear. Wait until his cardiac disease worsens.

B) He does not yet meet Medicare hospice benefit criteria for dementia.

C) A history from the nursing staff or family regarding the rate of his functional loss is the best predictor of death.

D) The nursing home staff can provide all of the end-of-life services provided by hospice, so hospice is not needed.

E) Presence of a stage 2 pressure ulcer and aspiration risk is sufficient for referral to hospice.

Answer 27.3.2 The correct answer is "C." Predicting death in patients with dementing illness is difficult which is why it is one of most underutilized diagnoses for referral to hospice care. In fact, dementia has the greatest variability among hospice diagnoses when it comes to predicting survival. However, waiting until a more predictable organ system failure occurs is not a reason for delaying a hospice referral, which makes "A" incorrect. "B" is incorrect because he does meet criteria for hospice enrollment. The National Hospice and Palliative Care Organization (NHPCO) hospice guidelines for eligibility in dementia include three components: (1) demonstrating severity of dementia (e.g., an inability to walk or dress or bathe without assistance, urinary/fecal incontinence, or inability to speak 6 different intelligible words per day); (2) evidence of a severe comorbid condition within the past 6 months (e.g., aspiration pneumonia, pyelonephritis, sepsis, stage ≥3 decubitus ulcer, or fever despite antibiotics); (3) inability to maintain fluid/caloric intake (by demonstrating weight loss >10% in 6 months or albumin <2.5 g/dL). "E" is incorrect. Aspiration risk and stage 2 pressure ulcers alone are not sufficient for referral to hospice. If the patient had stage 3 or 4 pressure ulcers, he would likely meet NHPCO hospice criteria for severe dementia. It is the extrapolation of the patient's loss of basic functions over time that best predicts death, as in "C." "D" is incorrect because while most nursing homes routinely care for dying patients without the assistance of hospice, they are typically not able to offer the full range of services or the end-of-life expertise that hospice offers.

Your patient develops nausea and vomiting and on examination you feel a large abdominal mass. He is still having bowel movements, which are guaiac positive. You inform the family that you suspect he has colon cancer, and they elect for no further evaluation but want his symptoms aggressively managed.

Question 27.3.3 Which of the following drugs is the best initial choice for treatment of this patient's nausea and vomiting?

A) Octreotide.

B) Metoclopramide.

C) Diphenhydramine.

D) Ondansetron (Zofran).

E) Aprepitant (Emend).

Answer 27.3.3 The correct answer is "D." "B" is not correct. Using a pro-peristaltic agent in a patient who may have an obstruction is not a good idea in general. Also, metoclopramide has central anti-dopaminergic properties and can cause confusion and extrapyramidal side effects. By understanding the pathophysiology of nausea and targeting antiemetics to specific receptors, therapy can be optimized and side effects minimized. An easy way to remember the causes of vomiting is to use the "VOMIT" mnemonic. In Table 27-1, pathophysiologic mechanisms causing nausea are described using the letters of the mnemonic. Blockade of these receptors allows rational, focused therapy.

Using Table 27-1, another reasonable alternative would be promethazine, although promethazine is not a great antiemetic. "A" is incorrect. Octreotide works by slowing the GI track, and its main use is found in patients with nausea and vomiting due to malignancy-related intestinal obstruction. However, it does not rapidly treat nausea and is not easily administered (usually continuous IV infusion but it can be given subcutaneously or intramuscularly). "C" is incorrect because diphenhydramine alone is a weak antiemetic, mostly used for motion sickness, and it can cause confusion, particularly in the elderly. Aprepitant (Emend) is a neurokinin receptor antagonist that is most effective when used with serotonin receptor antagonists; its primary use is in the management of chemotherapy induced nausea, and it is very expensive.

The patient's nausea is ultimately controlled with scheduled low-dose promethazine and ondansetron (See? Two drugs instead of a large dose of one!). He is continuing to lose weight and has been coughing after eating. He spikes a fever and you suspect he has developed aspiration pneumonia.

Question 27.3.4 Which is true regarding the use of antibiotics for pneumonia in patients with terminal dementia?

A) Antibiotic use is considered the standard of care and should be initiated without discussing with the family.

B) Antibiotics might prolong patients' lives but treatment comes with significant risks that need to be weighed.

C) Antibiotics given in a controlled setting such as a nursing home, where compliance can be ensured, lead to less antibiotic resistance.

D) Parenteral antibiotics are more successful at treating aspiration pneumonia in patients with dementia (compared with oral antibiotics).

Answer 27.3.4 The correct answer is "B." The previous prevailing belief of carte blanche use is being challenged. Currently, antibiotic use is very common in nursing homes, and a majority of nursing home residents will receive antibiotics in the 2 weeks before their death. Most of those antibiotics will be given intravenously, which increases patient discomfort. But more importantly, patients are often admitted to a hospital, placing demented patients at risk for delirium, restraints, and exposure to hospital acquired organisms. The reason we emphasize "might prolong" patients' lives is that the literature shows that in the extremes of advanced dementia plus advanced illness (such as bacteremia) antibiotics may not provide improved survival. In fact, in patients with advanced dementia, infections often characterize the final stage of their illness. "A" is incorrect because antibiotic use in patients with dementia (specifically in patients with dementia who are hospice appropriate) should always be discussed with the surrogate decision maker, and antibiotic use should be based on an informed choice and the patient's wishes/goals. While antibiotics have been shown to prolong life in patients with dementia, they do so with the cost of increasing discomfort, making "B" the correct answer. Families need this information when deciding if antibiotics should be used. "C" is incorrect because nursing homes have been shown to harbor drug-resistant bacteria, likely due in part to the frequent use of antibiotics in these patients. Oral antibiotics have been shown to be as effective as other more invasive administration routes in patients with dementia, making "D" incorrect.

The patient is enrolled in hospice and 3 weeks later you are called by a nurse reporting an acute condition change. You go to see the patient and he is unresponsive, breathing is labored, and his feet are mottled.

Question 27.3.5 All of the following can be signs of impending death EXCEPT:

A) Cheyne–Stokes breathing.

B) Fever.

C) Cyanosis and mottling.

D) Aldosterone escape phenomenon with increased urinary output.

E) Talking to someone who is already dead (and not via medium at Coney Island).

Answer 27.3.5 The correct answer is "D." Most dying patients have a decrease in urinary output prior to death. The other options describe changes that are commonly seen in patients who are actively dying. Respiratory changes in the active dying phase include Cheyne–Stokes breathing, terminal secretions (the "death rattle"), and periods of apnea. Dying is often accompanied by decreased circulation, which can result in cool extremities and mottling (the skin turning blue and patchy particularly in the fingers and toes). It is not uncommon for a dying patient to have a fever in the last 24 to 48 hours of life, typically thought to be secondary to aspiration pneumonia or another serious infection. It is not uncommon for someone who is dying to talk about going on a journey or talk about seeing someone who is dead. This is typically believed to be part of the normal dying process and in the absence of other symptoms should not be confused with delirium or psychosis.

You need to call the son to tell him of his father's decline.

Question 27.3.6 Which of the following should you say when giving the son an update?

A) "There have been some changes in your father's condition. I think you should go to see him. Call me if you have any questions after you have seen your dad."

B) "Good news, your dad will soon be out of his misery and released from this mortal world."

C) "I'm afraid I have some bad news for you regarding your dad. Would you like to talk over the phone or meet at my office later today to discuss it?"

D) "Your dad is dying. If you want to see him alive again you had better go today."

E) Don't call at all. Ask the nurse to inform the son of his father's condition while you duck out quietly.

Answer 27.3.6 The correct answer is "C." It gives a warning shot and allows the person receiving the bad news some control by allowing him to determine how and where he wants to receive the bad news. "A" avoids giving the bad news at all. "B" is inappropriately flippant and uses euphemisms. "D" is inappropriately blunt and sounds awful (believe it or not, we are very caring doctors; it is just that we have amused ourselves with this book). "E" avoids having the discussion at all and is only appropriate if you will be unable to reach the son in a timely fashion. Besides, you will be forever after known to the nurses as "Dr. Wuss." A common format for giving bad news is to use the SPIKES six-step protocol in Table 27-2.

Breaking bad news is difficult in person and can be more difficult over the phone.

Question 27.3.7 Which suggestion below is NOT recommended when breaking bad news over the phone?

A) Take time to prepare what you are going to say and find a quiet place to make the call.

B) If no one answers the phone, it is acceptable to leave a message or voicemail detailing the bad news.

C) Identify yourself and avoid answering any direct questions until you are sure of the identity of the person to whom you are talking.

D) Ask if the person is alone.

E) Speak clearly and slowly, allow time for questions; be empathetic.

Answer 27.3.7 The correct answer is "B." When breaking bad news over the phone, steps similar to breaking bad news in person should be used. You should obtain the full name, address, and phone number(s) of the person(s) you are calling. If you are not calling the patient, try to establish from the chart and nursing staff the relationship of the contact to the patient. In addition, it can be helpful to write down the key information you need and review what you will say and find a quiet area with a phone. Don't delay in making the call. When you do call, clearly identify yourself and ensure you are able to speak with the person closest to the patient (ideally, the healthcare proxy or the contact person indicated in the chart). Avoid responding to any direct question until you have verified the identity of the person to whom you are speaking. Not only is it morally risky but it also violates HIPPA. Ask if the contact person is alone. Do not give death notification to minor children. If you do not have a prior relationship with the person you are speaking to, ask what they know about the patient's condition. Provide a warning shot. Never deliver the news of death to an answering machine or voice mail. Instead, leave specific contact information. Allow time for questions; be empathetic and ask if you can contact anyone for them. Assess their emotional reaction and follow up as indicated.

Objectives: Did you learn to…

• Generate a management plan for a patient with weight loss due to a terminal disease?

• Describe criteria for hospice admission in patients with severe dementia?

• Identify and treat causes of nausea and vomiting at the end of life?

• Identify signs of the active dying process?

• Recognize the proper steps for breaking bad news?