PALLIATIVE CARE
PHYSICAL CARE
Among patients with life-limiting diseases, physical symptoms have been the cause of the most distress [212]. Patients usually have multiple symptoms, and a mean of nine to 11 symptoms per patient has been reported [204,205,206,213]. The presence of multiple symptoms can create challenges in identifying causes, as many symptoms are intricately linked with others, including symptoms in the psychosocial domain.Several tools have been developed to assess factors in the end-of-life experience, including five tools to evaluate physical symptoms (three of which are used to assess pain), four to assess quality of life, and six to assess functional status [214]. However, a systematic review of 99 tools in these three domains plus six others (emotional and cognitive symptoms, advance care planning, continuity of care, spirituality, grief and bereavement, satisfaction and quality of care, and caregiver well-being) showed that data on the reliability and validity were lacking for most of the tools [215]. Assessment of symptoms should include comprehensive documentation of the patient's history and findings on physical examination and should be carried out at regular intervals [5]. To help ensure that patients' physical distress is alleviated, when clinicians ask patients about the presence and severity of symptoms, they should also ask which symptom is most troublesome, as patients do not often specifically state this [216].
Although asking open-ended questions about symptoms is
helpful, systematic assessment of symptoms is also necessary. A study of patients in a
palliative medicine program demonstrated that significantly more symptoms were identified on
systematic assessment than through open-ended questioning (2,075 symptoms compared with 325)
[217]. The missed symptoms were not
inconsequential; 69% of symptoms that patients rated as "severe" and 79% of the symptoms
described as "distressing" were not volunteered by the patients [217]. Studies have demonstrated that patients are
often reluctant to report worsening symptoms because of fear that they indicate progressive
disease. Clinicians should describe potential symptoms to help patients and their family
understand which symptoms can be expected and when it is appropriate to notify a member of the
healthcare team. It is important for the healthcare team to acknowledge the patient's symptoms
as real and to take prompt actions to relieve them adequately. The patient's comfort should
take precedence over the exact cause of the symptom. Diagnostic studies to determine the cause
of symptoms should be undertaken only if the results will substantially help in directing
effective treatment. The risks, benefits, costs, and options for treating an underlying cause
should be discussed with the patient and family and considered within the context of the
patient's culture, belief system, and expectations.
An important distinction of palliative care is the focus on dimensions other than the
physical. Symptoms are accompanied by the patient's thoughts and feelings, and as such,
nonpharmacologic strategies should be used to address the sensory, cognitive, affective, and
functional components [66]. The healthcare
team should talk to the patient and family about priorities for pharmacologic versus
nonpharmacologic treatments. Although data are limited on some nonpharmacologic interventions,
many patients have benefited from these approaches. As research expands in the field of
palliative care, other innovative strategies are being scientifically evaluated, and results
are sometimes conflicting. Nonpharmacologic measures should be carried out in conjunction with
pharmacologic management before medications fail to provide relief, as interventions,
especially cognitive/behavioral techniques, are more effective when symptoms are acute and/or
mild.Once the patient's needs have been assessed, the palliative care team should work with the patient (and family) to develop priorities and goals of care [110]. Continual reassessment of symptoms and periodic review and documentation of the patient's goals and care plan are necessary to ensure that his or her needs are met [110]. It may be helpful for patients or a family member to keep a pain or symptom diary to note which measures have or have not provided relief and the duration of relief. This information will help clinicians determine the efficacy of specific therapeutic options and modify the treatment plan as necessary.
The discussion of interventions that follows focuses on the care of adults. Palliative care for children is addressed later in this course.
PAIN
Issues in Effective Pain Management
The inadequate management of pain is the result of
several factors related to both patients and clinicians. In a survey of oncologists,
patient reluctance to take opioids or to report pain were two of the most important
barriers to effective pain relief [222].
This reluctance is related to a variety of attitudes and beliefs [218,222]:
- Fear of addiction to opioids
- Worry that if pain is treated early, there will be no options for treatment of future pain
- Anxiety about unpleasant side effects from pain medications
- Fear that increasing pain means that the disease is getting worse
- Desire to be a "good" patient
- Concern about the high cost of medications
There are several other ways clinicians can allay patients' fears about pain medication:
- Assure patients that the availability of pain relievers cannot be exhausted; there will always be medications if pain becomes more severe.
- Acknowledge that side effects may occur but emphasize that they can be managed promptly and safely and that some side effects will abate over time.
- Explain that pain and severity of disease are not necessarily related.
Clinicians' attitudes, beliefs, and experiences also influence pain management, with addiction, tolerance, side effects, and regulations being the most important concerns [218,219,222,224,225,226]. A lack of appropriate education and training in the assessment and management of pain has been noted to be a substantial contributor to ineffective pain management [222,224,226,227]. As a result, many clinicians, especially primary care physicians, do not feel confident about their ability to manage pain in their patients [222,224].
Clinicians require a clear understanding of available medications to relieve pain, including appropriate dosing, safety profiles, and side effects. If necessary, clinicians should consult with pain specialists to develop an effective approach.
Legal and Ethical Issues Related to the Treatment of Pain
Fear of license suspension for inappropriate prescribing
of controlled substances is also prevalent, and a better understanding of pain medication
will enable physicians to prescribe accurately, alleviating concern about regulatory
oversight. Physicians must balance a fine line; on one side, strict federal regulations
regarding the prescription of schedule II opioids (morphine, oxycodone, methadone,
hydromorphone) raise fear of Drug Enforcement Agency investigation, criminal charges, and
civil lawsuits [218,228]. Careful documentation on the patient's
medical record regarding the rationale for opioid treatment is essential [228]. On the other side, clinicians must
adhere to the American Medical Association's Code of Ethics, which states that failure to
treat pain is unethical. The code states, in part: "Physicians have an obligation to
relieve pain and suffering and to promote the dignity and autonomy of dying patients in
their care. This includes providing effective palliative treatment even though it may
foreseeably hasten death" [229]. In
addition, the American Medical Association Statement on End-of-Life Care states that
patients should have "trustworthy assurances that physical and mental suffering will be
carefully attended to and comfort measures intently secured" [230].
Physicians should consider the legal ramifications of
inadequate pain management and understand the liability risks associated with both
inadequate treatment and treatment in excess. The undertreatment of pain carries a risk of
malpractice liability, and this risk is set to increase as the general population becomes
better educated about the availability of effective approaches to pain management at the
end of life. Establishing malpractice requires evidence of breach of duty and proof of
injury and damages. Before the development of various guidelines for pain management, it
was difficult to establish a breach of duty, as this principle is defined by nonadherence
to the standard of care in a designated specialty. With such standards now in existence,
expert medical testimony can be used to demonstrate that a practitioner did not meet
established standards of care for pain management. Another change in the analysis of
malpractice liability involves injury and damages. Because pain management can be
considered as separate from disease treatment and because untreated pain can lead to
long-term physical and emotional damage, claims can be made for pain and suffering alone,
without wrongful death or some other harm to the patient [231].
The proper storage and disposal of prescription pain medications should also be
considered. Taking steps to ensure that medications are stored and destroyed securely and
safely can help prevent unintended overdose and substance abuse. In 2010, the U.S. House
of Representatives passed the Safe Disposal Drug Act, which amended the Controlled
Substances Act to permit the take-back disposal of medications by authorized persons
(rather than the patient with the prescription) [486]. As such, healthcare professionals may be required to dispose of drugs
returned by patients in addition to drug samples that have expired or are not being
dispensed. For best practice guidelines on the disposal of medications by patients or
healthcare professionals, please visit the American Academy of Pain Management at http://www.aapainmanage.org/literature/Articles/DisposalOfDrugs.pdf
[487].Patients with History of Substance Abuse
This population of people with a history of substance
abuse presents challenges to the effective use of pain medication, with issues related to
trust, the appropriate use of pain medications, interactions between illicit drugs and
treatment, and compliance with treatment. The issues differ depending on whether substance
abuse is a current or past behavior.
With active substance abusers, it is difficult to know
if patients' self-reports of pain are valid or are drug-seeking behaviors. It has been
recommended that, as with other patients at the end of life, self-reports of pain should
be believed [66,223]. A multidisciplinary approach, involving
psychiatric professionals, addiction specialists, and, perhaps, a pain specialist, is
necessary. To decrease the potential for the patient to seek illicit drugs for pain, an
appropriate pain management plan should be implemented and the patient should be reassured
that pain can be managed effectively [66,223]. When planning treatment, the
patient's tolerance must be considered; higher doses may be needed initially, and doses
can be reduced once acute pain is under control. Long-acting pain medications are
preferred for active substance abusers, and the use of nonopioids and coanalgesics can
help minimize the use of opioids. Setting limits as well as realistic goals is essential
and requires establishing trust and rapport with the patient and caregivers.
Establishing trust is also essential for patients with
former substance abuse behavior, who often must be encouraged to adhere to a pain
management program because of their fears of addiction. Involving the patient's drug
counselor is beneficial, and other psychologic clinicians may be helpful in assuring the
patient that pain can be relieved without addiction. Recurrence of addiction is low,
especially among people with cancer, but monitoring for signs of renewed abuse should be
ongoing [223].
Patients who are following a methadone maintenance program may also fear effective
pain management as a risk for recurrent abuse. Two approaches may be followed for these
patients: they may receive an increased dose of methadone as the pain reliever or they may
be given other opioids along with the same methadone dose, with the dose of the opioid
titrated for effective pain relief [66,223]. Again, involvement of the drug
counselor is important.Prevalence
Etiology
Assessment
As the fifth vital sign, pain should be assessed
routinely, and frequent assessment has become the standard of care [219]. Pain is a subjective experience, and as
such, the patient's self-report of pain is the most reliable indicator. Research has shown
that pain is underestimated by healthcare professionals and overestimated by family
members [219,233]. Therefore, it is essential to obtain a
pain history directly from the patient, when possible, as a first step toward determining
the cause of the pain and selecting appropriate treatment strategies. When the patient is
unable to orally communicate, other strategies must be used to determine the
characteristics of the pain, as will be discussed.
Questions should be asked to elicit descriptions of the
pain characteristics, including its location, distribution, quality, temporal aspect, and
intensity. In addition, the patient should be asked about aggravating or alleviating
factors. Pain is often felt in more than one area, and physicians should attempt to
discern if the pain is focal, multifocal, or generalized. Focal or multifocal pain usually
indicates an underlying tissue injury or lesion, whereas generalized pain could be
associated with damage to the central nervous system. Pain can also be referred, usually
an indicator of visceral pain.
The quality of the pain refers to the sensation experienced by the patient, and it
often suggests the pathophysiology of the pain [219]. Pain that is well localized and described as aching, throbbing,
sharp, or pressurelike is most likely somatic nociceptive pain. This type of pain is
usually related to damage to bones and soft tissues. Diffuse pain that is described as
squeezing, cramping, or gnawing is usually visceral nociceptive pain. Pain that is
described as burning, tingling, shooting, or shocklike is neuropathic pain, which is
generally a result of a lesion affecting the nervous system.Temporal aspects of pain refer to its onset: acute, chronic, or "breakthrough." A recent onset characterizes acute pain, and there are accompanying signs of generalized hyperactivity of the sympathetic nervous system (diaphoresis and increased blood pressure and heart rate). Acute pain usually has an identifiable, precipitating cause, and appropriate treatment with analgesic agents will relieve the pain. When acute pain develops over several days with increasing intensity, it is said to be subacute. Episodic, or intermittent, pain occurs during defined periods of time, on a regular or irregular basis. Chronic pain is defined as pain that persists for at least 3 months beyond the usual course of an acute illness or injury. Such pain is not accompanied by overt pain behaviors (grimacing, moaning) or evidence of sympathetic hyperactivity.
"Breakthrough" is the term used to describe transitory exacerbations of severe pain over a baseline of moderate pain [234]. Breakthrough pain can be incident pain or pain that is precipitated by a voluntary act (such as movement or coughing), or can occur without a precipitating event. Breakthrough pain occurs in as many as 90% of people with cancer or in hospice settings and is often a consequence of inadequate pain management [218].
Documentation of pain intensity is key, as several treatment decisions depend on the intensity of the pain. For example, severe, intense pain requires urgent relief, which affects the choice of drug and the route of administration [3,219]. The numeric rating scale is the tool used most often to assess pain; with this tool, patients rate pain on a scale of 0 to 10 [219]. Visual analogue scales (patients rate pain on a line from 0 to 10) and verbal rating scales, which enable the patient to describe the pain as "mild," "moderate," or "severe," have also been found to be effective. Some patients, however, may have difficulty rating pain using even the simple scales. In an unpublished study involving 11 adults with cancer, the Wong-Baker FACES scale, developed for use in the pediatric setting, was found to be the easiest to use among three pain assessment tools that include faces to assess pain [235].
Functional assessment is important. The healthcare team should observe the patient to see how pain limits movements and should ask the patient or family how the pain interferes with normal activities. Determining functional limitations can help enhance patient compliance in reporting pain and adhering to pain-relieving measures, as clinicians can discuss compliance in terms of achieving established functional goals [223]. The Memorial Pain Assessment Card can be used to evaluate both the severity of pain and the effect of pain on function [219,236].
Physical examination can be valuable in determining an underlying cause of pain. Examination of painful areas can detect evidence of trauma, skin breakdown, or changes in osseous structures. Auscultation can detect abnormal breath or bowel sounds; percussion can detect fluid accumulation; and palpation can reveal tenderness. A neurologic examination should also be carried out to evaluate sensory and/or motor loss and changes in reflexes. During the examination, the clinician should watch closely for nonverbal cues that suggest pain, such as moaning, grimacing, and protective movements. These cues are especially important when examining patients who are unable to verbally communicate about pain.
Management
According to the American College of Physicians, clinicians should use
specific effective therapies for all palliative care patients with acute and chronic
pain. Strong evidence supports using nonsteroidal anti-inflammatory drugs, opioids, and
bisphosphonates for pain relief in patients with cancer. Bisphosphonates are effective
for bone pain relief in patients with breast cancer and myeloma.
(http://www.guideline.gov/content.aspx?id=12149
Last Accessed: May 24, 2012)
Strength of Recommendation/Level of Evidence:
Strong recommendation based on moderate quality of evidence
Strong evidence supports pain management approaches for
people with cancer, but the evidence base for management of pain in people with other
life-limiting diseases is weak [46,105,183,209,211,237]. Effective pain management involves a multidimensional approach
involving pharmacologic and nonpharmacologic interventions that are individualized to the
patient's specific situation [219].
Pharmacologic Interventions
The pharmacologic management of pain is best achieved
with use of the WHO three-step analgesic ladder, which designates the type of analgesic
agent based on the severity of pain (Figure 6) [238]. Step 1 of the WHO ladder involves the
use of nonopioid analgesics, with or without an adjuvant (coanalgesic) agent, for mild
pain (pain that is rated 1 to 3 on a 10-point scale). Step 2 treatment, recommended for
moderate pain (score of 4 to 6), calls for a weak opioid, which may be used in combination
with a step 1 nonopioid analgesic for unrelieved pain. Step 3 treatment is reserved for
severe pain (score of 7 to 10) or pain that persists after Step 2 treatment. Strong
opioids are the optimum choice of drug at Step 3. At any step, nonopioids and/or adjuvant
drugs may be helpful.
THE WORLD HEALTH ORGANIZATION'S THREE-STEP LADDER OF ANALGESIA
The WHO ladder is also accompanied by five principles:
prescribe analgesics according to the severity of pain (regardless of whether treatment at
a previous step was carried out), use oral formulations (preferably), give analgesics at
regular intervals around the clock (not on an as-needed basis), tailor the dose to the
individual, and prescribe analgesics with attention to detail (document a treatment
program) [238]. The pharmacologic
treatment of pain involves the selecting the right drug(s) at the right dose, frequency,
and route, and managing side effects [219]. A decision pathway was developed for use in the cancer setting and can be applied to
other settings (Figure 7) [219].
DECISION PATHWAY FOR PAIN MANAGEMENT
NSAIDs are most effective for pain associated with inflammation. Among the commonly used NSAIDs are ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), and indomethacin (Indocin). There are several classes of NSAIDs, and the response differs among patients; trials of drugs for an individual patient may be necessary to determine which drug is most effective [66]. NSAIDs inhibit platelet aggregation, increasing the risk of bleeding, and also can damage the mucosal lining of the stomach, leading to gastrointestinal bleeding. There is a ceiling effect to the nonopioid analgesics; that is, there is a dose beyond which there is no further analgesic effect. In addition, many side effects of nonopioids can be severe and may limit their use or dosing.
Moderate pain (Step 2) has often been treated with analgesic agents that are combinations of acetaminophen and an opioid, such as codeine, oxycodone, or hydrocodone. However, it is now recommended that these combination drugs be avoided, as limits on the maximum dose of acetaminophen limits the use of a combination drug [202,219]. Individual drugs in combination is preferred, allowing for increases in the dose of the opioid without increasing the dose of the coanalgesic.
Strong opioids are used for severe pain (Step 3)
[105,183,211,219]. Morphine, buprenorphine, oxycodone,
hydromorphone, fentanyl, and methadone are the most widely used Step 3 opioids in the
United States [239]. Unlike nonopioids,
opioids do not have a ceiling effect, and the dose can be titrated until pain is relieved
or side effects become unmanageable. For an opioid-naïve patient or a patient who has been
receiving low doses of a weak opioid, the initial dose of a Step 3 opioid should be low,
and, if pain persists, the dose may be titrated up daily until pain is controlled. Typical
starting doses for patients who are opioid-naïve have been noted, but these doses should
be used only as a guide, and the initial dose, as well as titrated dosing, should be done
on an individual basis (Table 8).
Guidelines suggest that the most appropriate dose is the one that relieves the patient's
pain throughout the dosing interval without causing unmanageable side effects [183,202,243].
OPIOIDS FOR THE MANAGEMENT OF PAIN IN ADULTS*
| Drug | Typical Starting Dose† | Onset of Action | Duration of Action | ||
|---|---|---|---|---|---|
| Codeine | 15–60 mg | 30 to 60 min | 4 to 6 hrs | ||
| Hydrocodone | 2.5–10 mg | 10 to 20 min | 4 to 8 hrs | ||
| Morphine, immediate release | 15–30 mg |
15 to 30 min 5 to 10 min | 3 to 6 hrs | ||
| Oxycodone, immediate release | 5–10 mg | 10 to 30 min | 3 to 4 hrs | ||
| Oxymorphone, sustained release | 10 mg | 5 to 10 min | 8 to 12 hrs | ||
| Hydromorphone | 2–4 mg | 15 to 30 min | 4 to 5 hrs | ||
| Methadone | 5–10 mg | 30 to 60 min | 4 to 6 hrs | ||
| Tapentadol | 50–100 mg | <60 min | 4 to 6 hrs | ||
| Tapentadol, extended release | 50–100 mg | — | — | ||
| Fentanyl (buccal tablet) | 100–200 mcg | 5 to 15 min | 2 to 4 hrs | ||
| Fentanyl (transdermal patch) | 25 mcg/hr (worn for 3 days) | 12 to 18 hrs | 48 to 72 hrs | ||
| Buprenorphine (transdermal patch) | 5–10 mcg/hr (worn for 7 days) | — | — | ||
| |||||
More than one route of opioid administration will be
needed by many patients during end-of-life care, but in general, opioids should be given
orally, as this route is the most convenient and least expensive. The transdermal route is
preferred to the parenteral route, although dosing with a transdermal patch is less
flexible and so may not be appropriate for patients with unstable pain [219]. Intramuscular injections should be
avoided because injections are painful, drug absorption is unreliable, and the time to
peak concentration is long [219].
Morphine is considered to be the first-line treatment
for a Step 3 opioid [202]. Morphine is
available in both immediate-release and sustained-release forms, and the latter form can
enhance patient compliance. The sustained-release tablets should not be cut, crushed, or
chewed, as this counteracts the sustained-release properties. Morphine should be avoided
in patients with severe renal failure [211].
Buprenorphine (Butrans) has the general structure of morphine but differs from it in
several ways [239]. The transdermal
formulation of the drug was approved in 2010 for moderate-to-severe chronic pain in
patients requiring an around-the-clock opioid for an extended period [219]. It may be used for people with renal
impairment but is contraindicated in patients who have substantial respiratory depression
[239,240].The sustained-release form of oxycodone (OxyContin) has been shown to be as safe and effective as morphine for cancer-related pain, and it may be associated with less common side effects, especially hallucinations and delirium [244]. Oxycodone is also available in an immediate-release form (Roxicodone). Oxycodone should be used in people with advanced chronic kidney disease only if alternative options are not available [211]. If the drug must be used, the intervals between doses should be increased, and the patient should be monitored closely [211].
Hydromorphone and fentanyl are the most potent opioids; neither drug should be given to an opioid-naïve patient. Hydromorphone (Dilaudid), which is four times as potent as morphine, is available in only an immediate-release form. Fentanyl is the strongest opioid (approximately 80 times the potency of morphine) and is available as a transdermal drug-delivery system (Duragesic), and a buccal tablet (Onsolis) was approved in 2009 [240,245]. Both the transdermal patch and buccal tablet have a more rapid onset than other opioids given nonparenterally [219]. Because of its potency, fentanyl must be used with extreme care, as deaths have been associated with its use. Physicians must emphasize to patients and their families the importance of following prescribing information closely, and members of the healthcare team should monitor the use of the drug. Fentanyl, administered subcutaneously, is the recommended choice for patients with advanced chronic kidney disease [211].
The use of methadone (Dolophine) to relieve pain has
increased substantially over the past few years, moving from a second-line or third-line
drug to a first-line medication for severe pain in people with life-limiting diseases
[246]. A systematic review showed that
methadone had efficacy similar to that of morphine [247]. Physicians must be well educated about the pharmacologic properties
of methadone, as the risk for serious adverse events, including death, is high when the
drug is not administered appropriately [247,248]. If the dose of methadone is
increased too rapidly or administered too frequently, toxic accumulation of the drug can
cause respiratory depression and death. Extreme care must be taken when titrating the
drug, and close evaluation of the patient is necessary.
Propoxyphene (Darvon) is an opioid that is chemically similar to methadone. It is not
recommended for use because of toxicity even at therapeutic doses and a lack of efficacy
compared with placebo or acetaminophen [66,223]. Similarly, meperidine (Demerol)
should not be used in the palliative care setting because of limited efficacy and
potential for severe toxicity. Agonist-antagonist opioids (nalbuphine [Nubain],
butorphanol [Stadol], and pentazocine [Talwin]) are not recommended for use with pure
opioids, as they compete with them, leading to possible withdrawal symptoms.Tapentadol (Nucynta) is a short-acting opioid approved for moderate to severe pain in adults; an extended release formulation (Nucynta ER) was approved in 2011 for moderate-to-severe chronic pain when an around-the-clock opioid is needed [240]. The drug is associated with a lower incidence of adverse effects than other opioids, and it has been shown to be highly effective for chronic pain conditions but has not been studied in cancer-related pain or the palliative care setting [249].
The most appropriate option for breakthrough pain is an immediate-release opioid taken in addition to the around-the-clock regimen [219]. The fentanyl buccal tablet has been shown to be effective and safe for relieving breakthrough pain in people who are opioid tolerant [183,250,251]. Between January 2011 and January 2012, three forms of fentanyl were approved for breakthrough pain in people with cancer: fentanyl sublingual tablet (Abstral), fentanyl nasal spray (Lazanda), and fentanyl sublingual spray (Subsys) [240]. For each formula, the initial dose may be repeated once if pain is not relieved adequately after 30 minutes. Patients must wait at least 2 hours before using the sublingual tablet or the nasal spray for another breakthrough pain episode; the interval is 4 hours for the sublingual spray [240].
When pain responds poorly to escalated doses of an opioid, other approaches should be considered, including alternative routes of administration, use of alternate opioids (termed opioid rotation or opioid switching), use of adjuvant analgesics, and nonpharmacologic approaches. A process for opioid switching has been established (Figure 8); the first step is to calculate the equianalgesic dose of the new drug (Table 9) [183,202,219]. Additional care is needed when switching to methadone, and conversion ratios have been established (Table 10) [183]. Evidence suggests that the traditionally recommended equianalgesic doses for the fentanyl transdermal patch are subtherapeutic for patients with chronic cancer-related pain, and more aggressive approaches may be warranted (Table 11) [183,219,252].
PROCESS FOR OPIOID SWITCHING
 |
| *Reduce by a greater percentage if the patient is older, frail, or has significant organ dysfunction. If changing to methadone, reduce the dose by 75%. If changing to transdermal fentanyl, do not reduce the dose and continue the current opioid for 12 to 48 hours. |
OPIOID EQUIVALENT DOSES
| Drug | Oral Dose | Parenteral Dose |
|---|---|---|
| Morphine | 30 mg | 10 mg |
| Codeine | 200 mg | NA |
| Hydromorphone | 7.5 mg | 1.5 mg |
| Hydrocodone | 30–45 mg | NA |
| Oxycodone | 20 mg | NA |
| Oxymorphone | 10 mg | 1 mg |
| Methadone | 20 mg | 10 mg |
| Buprenorphine transdermal patch | 5–0 mcg/hr | NA |
DOSE CONVERSION RATIOS FOR METHADONE
| Oral Morphine | Conversion Ratio (Morphine:Oral Methadone) |
|---|---|
| 30–90 mg | 4:1 |
| 91–300 mg | 8:1 |
| >300 mg | 12:1 |
| 100 mcg/hr | 800 mg |
EQUIANALGESIC ORAL OPIOID DOSES FOR FENTANYL TRANSDERMAL PATCH
| Transdermal Fentanyl | Morphine | Hydromorphone | Oxycodone | Codeine |
|---|---|---|---|---|
| 25 mcg/hr | 60 mg | 7.5 mg | 30 mg | 200 mg |
| 50 mcg/hr | 120 mg | 15 mg | 60 mg | 400 mg |
| 75 mcg/hr | 180 mg | 22.5 mg | 90 mg | 600 mg |
| 100 mcg/hr | 240 mg | 30 mg | 120 mg | 800 mg |
Opioids are associated with many side effects, the most notable of which is constipation, occurring in nearly 100% of patients. The universality of this side effect mandates that once extended treatment with an opioid begins, prophylactic treatment with laxatives must also be initiated. Tolerance to other side effects, such as nausea and sedation, usually develops within 3 to 7 days. Some patients may state that they are "allergic" to an opioid. It is important for the physician to explore what the patient experienced when the drug was taken in the past, as many patients misinterpret side effects as an allergy. True allergy to an opioid is rare [219]. Opioid rotation may also be done to reduce adverse events.
When opioids are prescribed, careful documentation of the patient's history, examinations, treatments, progress, and plan of care are especially important from a legal perspective. This documentation must provide evidence that the patient is functionally better off with the medication than without [66]. In addition, physicians must note evidence of any dysfunction or abuse.
Adjuvant agents are often used in conjunction with opioids and are usually considered after the use of opioids has been optimized [66]. The primary indication for these drugs is adjunctive because they can provide relief in specific situations, especially neuropathic pain. Examples of adjuvant drugs are tricyclic antidepressants, anticonvulsants, muscle relaxants, and corticosteroids (Table 12) [183,219]. A systematic review found that there was limited evidence to support the use of selective serotonin reuptake inhibitors (SSRIs) for neuropathic pain, but one serotonin-norepinephrine reuptake inhibitor, venlafaxine (Effexor), was found to be effective [254].
ORAL ADJUVANT ANALGESICS
| Drug Class | Drug | Typical Starting Dose | Usual Effective Dose |
|---|---|---|---|
| Anticonvulsants | Gabapentin | 100–300 mg once daily | 300–1200 mg (2 or 3 divided doses) |
| Pregabalin | 25–75 mg twice daily | 75–200 mg (3 divided doses) | |
| Carbamazepine | 100 mg twice daily | 300–800 mg twice daily | |
| Topiramate | 25–50 mg daily | 50–200 mg twice daily | |
| Oxcarbazepine | 150–300 mg twice daily | 150–600 mg twice daily | |
| Tiagabine | 4 mg at bedtime | 4–12 mg twice daily | |
| Tricyclic antidepressants | Amitriptyline Nortriptyline Desipramine | 10–25 mg at bedtime | 50–150 mg at bedtime |
| Serotonin-norepinephrine reuptake inhibitors | Venlafaxine | 37.5 mg daily | 150–350 mg daily |
| Skeletal muscle relaxants | Baclofen | 5 mg twice daily | 10–20 mg 2 or 3 times daily |
| Cyclobenzaprine | 5 mg 3 times daily | 10–20 mg 3 times daily | |
| Metaxalone | 400 mg 3 times daily | Not defined | |
| Corticosteroids | Dexamethasone | 1–2 mg | Not defined |
Nonpharmacologic Interventions
Several nonpharmacologic approaches are therapeutic complements to pain-relieving medication, lessening the need for higher doses and perhaps minimizing side effects. These interventions can help decrease pain or distress that may be contributing to the pain sensation. Approaches include palliative radiotherapy, complementary/alternative methods, manipulative and body-based methods, and cognitive/behavioral techniques. The choice of a specific nonpharmacologic intervention is based on the patient's preference, which, in turn, is usually based on a successful experience in the past.Palliative radiotherapy is effective for managing cancer-related pain, especially bone metastases [46,255,256]. Bone metastases are the most frequent cause of cancer-related pain; 50% to 75% of patients with bone metastases will have pain and impaired mobility [255]. External-beam radiotherapy is the mainstay of treatment for pain related to bone metastases. At least some response occurs in 70% to 80% of patients, and the median duration of pain relief has been reported to be 11 to 24 weeks [255]. It takes 1 to 4 weeks for optimal therapeutic results [255,256].
However, palliative radiotherapy has become a controversial issue. Although the benefits of palliative radiotherapy are well documented and most hospice and oncology professionals believe that palliative radiotherapy is important, this treatment approach is offered at approximately 24% of Medicare-certified freestanding hospices, with less than 3% of hospice patients being treated [74,75,76]. As previously noted, reimbursement issues present a primary barrier to the use of palliative radiotherapy [74,75,76]. Among other barriers are short life expectancy, transportation issues, patient inconvenience, and lack of knowledge about the benefits of palliative radiotherapy in the primary care community [74,75,256,257].
More than half (54%) of people use complementary/alternative medicine therapies at the end of life [258]. The most commonly used therapies are massage, relaxation techniques, and acupuncture [258,259,260].
Massage, which can be broadly defined as stroking, compression, or percussion, has led to significant and immediate improvement in pain in the hospice setting [261]. Both massage and vibration are primarily effective for muscle spasms related to tension or nerve injury, and massage can be carried out with simultaneous application of heat or cold. Massage may be harmful for patients with coagulation abnormalities or thrombophlebitis [223].
Focused relaxation and breathing can help decrease pain by easing muscle tension. Progressive muscle relaxation, in which patients follow a sequence of tensing and relaxing muscle groups, has enabled patients to feel more in control and to experience less pain and can also help provide distraction from pain. [223]. This technique should be avoided if the muscle tensing will be too painful.
Acupuncture typically provides pain relief 15 to 40 minutes after stimulation. Relief seems to be related to the release of endorphins and a susceptibility to hypnosis [223]. The efficacy of acupuncture for relieving pain has not been proven, as study samples have been small. However, acupuncture has been found to be of some benefit for cancer-related pain when the therapy is given in conjunction with analgesic therapy [262].
Other nonpharmacologic interventions that have been helpful for some patients but lack a strong evidence base include manipulative and body-based methods (such as application of cold or heat, and positioning), yoga, distraction, and music or art therapy. The application of cold and heat are particularly useful for localized pain and have been found to be effective for cancer-related pain caused by bone metastases or nerve involvement, as well as for prevention of breakthrough incident pain [223]. Alternating application of heat and cold can be soothing for some patients, and it is often combined with other nonpharmacologic interventions.
Cold can be applied through wraps, gel packs, ice bags, and menthol. It provides relief for pain related to skeletal muscle spasms induced by nerve injury and inflamed joints. Cold application should not be used for patients with peripheral vascular disease. Heat can be applied as dry (heating pad) or moist (hot wrap, tub of water) and should be applied for no more than 20 minutes at a time, to avoid burning the skin. Heat should not be applied to areas of decreased sensation or with inadequate vascular supply, or for patients with bleeding disorders.
Changing the patient's position in the bed or chair may help relieve pain and also helps minimize complications such as decubitus ulcers, contractures, and frozen joints. Members of the healthcare team as well as family members and other informal caregivers can help reposition the patient for comfort and also perform range-of-motion exercises. Physical and occupational therapists can recommend materials, such as cushions, pillows, mattresses, splints, or support devices.
Hatha yoga is the branch of yoga most often used in the medical context, and it has been shown to provide pain relief for patients who have osteoarthritis and carpal tunnel syndrome but it has not been studied in patients at the end of life. Yoga may help relieve pain indirectly in some patients through its effects on reducing anxiety, increasing strength and flexibility, and enhancing breathing [263]. Yoga also helps patients feel a sense of control.
Methods to provide distraction from pain come in a wide variety of methods, including reciting poetry, meditating with a calm phrase, watching television or movies, playing cards, visiting with friends, or participating in crafts.
Music therapy and art therapy are also becoming more widely used as nonpharmacologic options for pain management. Listening to music has been shown to decrease the intensity of pain and reduce the amount of opioids needed, but the magnitude of the benefit was small [264]. Research suggests that art therapy contributes to a patient's sense of well-being [265]. Creating art helps patients and families to explore thoughts and fears during the end of life. An art therapist can help the creators reflect on the implications of the art work. Art therapy is especially helpful for patients who have difficulty expressing feelings with words, for physical or emotional reasons.
FATIGUE
Fatigue is often part of a cluster of symptoms that may also include pain, depression, sleep disturbances, and anxiety/depression, especially at the end of life [183,268,269,270]. Analysis of 25 symptoms among 922 patients with advanced cancer demonstrated seven clusters. One of those clusters, referred to as the fatigue/anorexia-cachexia cluster, was composed of easy fatigue, weakness, lack of energy, anorexia, early satiety, weight loss, dry mouth, and taste changes [271]. Fatigue has often been reported to be the symptom that causes patients the most distress [272].
Prevalence
Etiology
Prevention
Assessment
An easy-to-use instrument is the Brief Fatigue Inventory, which includes four items that ask the patient to rate the severity of fatigue on a scale of 0 (no fatigue) to 10 ("as bad as you can imagine") [275]. The patient is asked to consider the current level of fatigue as well as fatigue experienced within the past 24 hours and to indicate the degree to which fatigue has interfered with activities, mood, relations with other people, and enjoyment of life.
Assessment should also include a physical examination to detect an underlying cause of fatigue, a focused history-taking, and laboratory tests, as appropriate, to rule out suspected causes (Figure 9) [266].
ALGORITHM FOR THE DIAGNOSIS OF FATIGUE IN PALLIATIVE CARE PATIENTS
 |
| ACTH = adrenocorticotropic hormone, Ca = calcium, CRP = C-reactive protein, Mg = magnesium, NRS = numerical rating scale, Phos = phosphate, TSH = thyroid-stimulating hormone. |
Management
Little evidence is available to support guidelines for
the management of fatigue during the end of life. Most of the research on nonpharmacologic
and pharmacologic treatment options has been conducted with subjects receiving active
cancer treatment or long-term follow-up care after cancer treatment. Fatigue in the
palliative care setting is addressed specifically by the European Association for
Palliative Care (EAPC) (all settings) and the NCCN (cancer setting) and is noted in
guidelines for palliative care for advanced heart failure [105,183,266]. In addition, the
AHRQ has addressed fatigue in the cancer setting, and systematic reviews have been done to
help determine effective pharmacologic and nonpharmacologic interventions [268,276,277,278,279]. Management of fatigue should include treatment of an underlying
cause, if one can be identified, but symptomatic relief should also be provided (Figure
10) [105,183,266].
ALGORITHM FOR THE MANAGEMENT OF FATIGUE IN PALLIATIVE CARE PATIENTS
When medications are the underlying cause of the
fatigue, nonessential medications should be discontinued, and changing medications or the
time of dosing may reduce tiredness during the day. Appropriate management of infection,
cachexia, depression, and insomnia may also help reduce fatigue [266,273]. The patient's life expectancy and preferences should be considered
before carrying out treatment of an underlying cause [266]. Fatigue may provide a protective effect for patients in the last days
or hours of life [266]. As such, the
patient may be more comfortable without aggressive treatment of fatigue during that period
[266].
The treatment of anemia as an underlying cause of
fatigue (and other symptoms) is a complex issue. Many studies have provided evidence to
recommend the use of erythropoiesis-stimulating agents (erythropoietin [Epogen],
darbepoetin [Procrit]) for anemia in people with cancer, HIV/AIDS, chronic kidney disease,
and heart failure because of benefit in increasing the hemoglobin level, improving
exercise tolerance, reducing symptoms, and decreasing the need for blood transfusions
[266; 276; 280; 281; 282]. However, safety concerns led the U.S. Food and Drug
Administration (FDA) to require a boxed warning on the label of erythropoiesis-stimulating
agents regarding the increased risk of several adverse events (death, myocardial
infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor
progression or recurrence) among people with chronic kidney disease or cancer [240]. The
FDA recommends using the lowest dose sufficient to avoid red blood cell transfusion [240].
Recommendations for these agents in these populations have been withdrawn or revised [277;
283; 284]. A 2010 systematic review and meta-analysis (11 studies, 794 subjects)
demonstrated benefit of erythropoiesis-stimulating agents among people with heart failure
and mild anemia (>10 g/dL) with no increase in adverse events [282].
Most patients will try to manage fatigue by resting
and/or sleeping more often, and many healthcare professionals will also recommend this
strategy. However, additional rest and/or sleep usually does not restore energy in
patients who have fatigue related to a life-limiting disease; continued lack of exercise
may even promote fatigue [266]. Aerobic
exercise has been found to alleviate fatigue, although much of the research in this area
has been conducted with cancer survivors. For example, a meta-analysis (28 studies, 2,083
subjects) demonstrated a significant effect of exercise in the treatment of fatigue during
and after cancer treatment [279]. Some
small studies of fatigue have been done in the palliative care setting, and exercise was
found to be beneficial [285,286,287].
Although an exercise program is recommended, decreasing activity to conserve energy is
also encouraged [105,183,266]. Clinicians should talk to the patient and family about the importance
of the patient conserving energy by adjusting daily activities to correspond to times of
peak energy, setting priorities for activities, following a normal wake-sleep cycle, and
using assistive devices, and delegating less important tasks [183,266]. Encouraging adequate nutrition, stress reduction through meditation
or relaxation techniques, and engagement in enjoyable activities can help restore energy
[183,266]. Counseling about setting realistic goals for activities and function
may also help patients and family members adapt to new daily routines.Pharmacologic treatment of fatigue should be undertaken only after potential causes of fatigue have been ruled out [183,266]. The EAPC notes that methylphenidate (Ritalin) and modafinil (Provigil) may reduce fatigue, and the NCCN recommends these two drugs as first-line options in the cancer palliative care setting [183,266]. These recommendations are based on systematic reviews showing a significant effect of methylphenidate for the treatment of fatigue in people with cancer or HIV/AIDS or for opioid-induced sedation [266,276,277,278,288]. An optimal dose of methylphenidate has not been defined, but an initial dose of 5–10 mg (given in the morning) has been used, with the dose titrated to 40–60 mg per day (given once in the morning and once at midday) [266]. Among the side effects are nervousness, jitteriness, agitation, arrhythmia, and tachycardia [266]. The initial recommended dose of modafinil is 200 mg per day [266]. Major side effects have included agitation, nervousness, sleep disturbances, nausea, and diarrhea. Since the publication of these recommendations, researchers conducting a systematic review concluded that the evidence was insufficient to recommend a specific drug for the treatment of fatigue in the palliative care setting [278].
Corticosteroids (prednisone and dexamethasone) have been used frequently to treat fatigue in the palliative care setting, but no research on their effectiveness is available [278]. These agents have provided short-term relief of fatigue and improved quality of life among people with cancer, but because of the toxicity associated with their long-term use, they should be considered only at the end life or to alleviate fatigue for a well-defined goal (such as allowing the patient to attend a special event) [183,266].
DYSPNEA
Prevalence
Etiology
Prevention
Assessment
Physical assessment of the patient should include evaluation of breath sounds, heart rate, respiratory rate, jugular pressure, and functional status. Testing should be done to identify a suspected underlying cause of dyspnea [119,237].
Management
According to the American College of Physicians, clinicians should use
therapies of proven effectiveness to manage dyspnea in patients with serious illness at
the end of life, which include opioids in patients with unrelieved dyspnea and oxygen
for short-term relief of hypoxemia.
(http://www.guideline.gov/content.aspx?id=12149
Last Accessed: May 24, 2012)
Strength of Recommendation/Level of Evidence:
Strong recommendation based on moderate quality of evidence
The American College of Physicians, the American College
of Chest Physicians, the American Thoracic Society, and the NCCN have developed
evidence-based guidelines for the management of dyspnea [46,119,183,210,237]. In addition,
evidence-based recommendations for managing dyspnea in people with advanced heart failure
are available [105]. A stepwise approach
to managing dyspnea should be taken, with the first step being treatment of the underlying
cause, if one can be identified [237].
Nonpharmacologic interventions should be used first; if the response is inadequate,
pharmacologic interventions may be added.
Supplemental oxygen is commonly used to treat dyspnea.
The ACCP notes that strong evidence supports the use of oxygen and pulmonary
rehabilitation for dyspnea, and supplemental oxygen may provide relief of dyspnea for
people with advanced lung or heart disease who have hypoxemia at rest or with minimal
activity [46,183,209,210,237]. However, data suggest that oxygen
offers no benefit to patients who do not have hypoxemia [105].
A variety of nonpharmacologic interventions have been
suggested in several practice guidelines, although the evidence base varies (Table
13) [119,183,210,237,292]. In a systematic
review of nonpharmacologic interventions for dyspnea in people with advanced malignant and
nonmalignant diseases, there was strong evidence for chest wall vibration and
neuroelectrical muscle stimulation and moderate evidence for walking aids and breathing
training [293]. The data were insufficient
to recommend the use of a fan, music, relaxation, counseling and support, and
psychotherapy [293]. A subsequent small
randomized controlled trial demonstrated that a handheld fan directed at the face reduced
breathlessness [292].
NONPHARMACOLOGIC INTERVENTIONS FOR DYSPNEA RECOMMENDED IN PRACTICE
GUIDELINES
|
Opioids represent the primary recommended pharmacologic
intervention for severe dyspnea in people with advanced cancer and lung disease [46,210,237]. A systematic
review and meta-analysis (18 randomized controlled trials) demonstrated a significant
positive effect of opioids on breathlessness [294]. Guidelines recommend that oral or parenteral opioids be considered
for all patients with severe and unrelieved dyspnea; nebulized opioids have not had an
effect when compared with placebo [46,209,210,237]. Oral morphine is the most commonly prescribed opioid, but other
opioids, such as diamorphine, dihydrocodeine, fentanyl, hydromorphone, and oxycodone, may
be used [210]. The dose should be selected
and titrated according to such factors as renal, hepatic, and pulmonary function and past
use of opioids [210]. An oral dose of
morphine of 2.5–10 mg every 4 hours as needed (1–5 mg intravenously) has been recommended
for opioid-naïve patients [119,183]. Although respiratory depression is a
side effect associated with opioids, especially morphine, this effect has not been found
with doses used to relieve dyspnea [119,295]. Evidence-based recommendations
for palliative care for people with heart failure note that diuretics represent the
cornerstone of treatment of dyspnea [105].
Nitrates may also provide relief, and inotropes may be appropriate in select patients
[105]. The recommendations also include
the use of low-dose opioids [105].
Anxiolytics are often a recommended option for relief of breathlessness because of the
association between anxiety and dyspnea. However, anxiolytic agents have not been found to
be effective for the management of dyspnea. A systematic review published in 2010 (seven
studies, 200 subjects) showed that benzodiazepines had no beneficial effect on
breathlessness in people with advanced cancer or COPD [296]. Bronchodilators and systemic corticosteroids may be helpful in
relieving dyspnea in people with lung cancer and underlying obstructive airway disease
[237]. In addition, analgesics may help
relieve dyspnea associated with pain [237].CONSTIPATION
Prevalence
Etiology
Prevention
Assessment
Issues of personal privacy often lead to a reluctance of
patients to discuss constipation, so clinicians and other healthcare professionals must
initiate the discussion and talk honestly about what to expect and measures to prevent and
manage the symptom. The assessment tools used most often are the Bristol Stool Form Scale
and the Constipation Assessment Scale [297,298]. Assessment should include a
review of the list of medications, a history of bowel habits, and abdominal and rectal
examination. In addition to checking the list of prescribed medications to determine if
constipation is a side effect, the physician should ask the patient about over-the-counter
drugs and herbal remedies, as constipation can be a consequence of aluminum-containing
antacids, ibuprofen, iron supplements, antidiarrhea drugs, antihistamines, mulberry, and
flax. A detailed history of bowel habits helps to establish what is considered normal for
the individual patient. The patient should be asked about frequency of stool, the
appearance and consistency of stools, use of bowel medications, and previous occurrence of
constipation. In general, physical examination of the abdomen for tenderness, distention,
and bowel sounds can rule out intestinal obstruction as the cause of constipation. A
rectal examination can identify the presence of stool, fecal impaction, or tumor. Imaging
of the abdomen (by plain x-ray or computerized tomography) may be appropriate to confirm
the presence of obstruction. Consideration of the patient's prognosis and preferences for
care should be factored into a decision to carry out diagnostic testing. As with
assessment of all symptoms, constipation should be reassessed frequently; assessment at
least every 3 days is recommended [298].
Management
The goal of treatment should be relief of symptoms
related to constipation and re-establishment of bowel habits to the patient's comfort and
satisfaction; some recommend a goal of one nonforced bowel movement every 1 to 2 days
[183,298]. Systematic reviews have demonstrated that data are insufficient to
support one laxative or combination of laxatives over others [297,299,300].
Many laxatives are FDA approved for occasional
constipation, and much of the evidence on their efficacy has come from studies of chronic
constipation, not patients with life-limiting disease. In its guidelines for the
management of chronic constipation, the American College of Gastroenterology notes the
following [300]:
- Polyethylene glycol (PEG) and lactulose (both osmotic) improve stool frequency and stool consistency.
- Data are insufficient to make a recommendation about the efficacy of stool softeners (docusate [Colace or Surfak]); stimulant laxatives (senna [Senokot, Ex-lax] or bisacodyl [Dulcolax, Correctol]); milk of magnesia; herbal supplements (aloe); lubricants (mineral oil); or combination laxatives (psyllium plus senna).
European and Canadian consensus groups and the NCCN have developed practice guidelines for constipation in the palliative care setting on the basis of the available data and expert opinion (Figure 11) [183,297,298]. First-line recommended treatment is a stimulant laxative plus a stool softener (PEG or lactulose) [183,297,299]. A small study of senna with and without docusate for hospitalized patients with cancer showed no significant benefit to the addition of docusate; docusate is specifically not recommended in the Canadian consensus recommendations [298,301]. If constipation persists, other options are bisacodyl, magnesium hydroxide, or sorbitol [183]. Methylnaltrexone (Relistor) was approved by the FDA in 2008 for the treatment of opioid-induced constipation. Although data are still limited, a systematic review indicated that the subcutaneous drug is effective in the palliative care setting, and is especially useful for patients with constipation refractory to conventional laxatives [302]. Practice recommendations note that methylnaltrexone should be considered for patients taking opioids after failure of other laxatives [183,297,298]. Withdrawal of opioids should never be a strategy to manage constipation.
ALGORITHM FOR THE MANAGEMENT OF CONSTIPATION IN PALLIATIVE CARE PATIENTS
NAUSEA AND VOMITING
Prevalence
Etiology
- Medications (chemotherapy agents, opioids, antidepressants, antibiotics)
- Radiation therapy (especially to the abdomen or lumbosacral spine)
- History of peptic ulcer disease or gastroesophageal reflux
- Delayed gastric emptying
- Primary or metastatic brain tumor
- Gastrointestinal tract obstruction
- Constipation
- Renal failure
- Hepatic failure
- Pancreatitis
- Hypercalcemia
- High serum levels of dioxin or anticonvulsants
CAUSES OF NAUSEA AND VOMITING ACCORDING TO PATHWAY STIMULATED AND CLASS OF
ANTIEMETICS
| Pathway Stimulated | Causes | Class of Antimetics |
|---|---|---|
| Chemoreceptor trigger zone | Metabolic disorders (hypercalcemia, hyponatremia, hepatic/renal failure) | Dopamine antagonists |
| Opioids | Prokinetic agent, dopamine antagonists | |
| Malignant bowel obstruction | Prokinetic agent, dopamine antagonists, corticosteroids | |
| Cortex of brain | Increased intracranial pressure, anxiety, five senses | Corticosteroids, anxiolytics |
| Peripheral pathways (gastrointestinal tract) | Gastroparesis | Prokinetic agent |
| Vestibular system | Motion | Muscarinic acetylcholine receptor, antihistamine |
Prevention
Assessment
Nausea is often not reported; patients should be asked if they have experienced nausea even if they have not vomited [243].
Management
Several classes of pharmacologic agents can be used to
manage nausea and vomiting; the main classes used in the end-of-life setting are
prokinetic agents, dopamine receptor antagonists, antihistamines, anticholinergics, 5-HT3
receptors, and corticosteroids (Table 15) [303,304,308]. The prokinetic
agent metoclopramide (Reglan) has been recommended as a first-line treatment because of
its central and peripheral actions and its effectiveness for many chemical causes of
nausea [202,243,303]. The drug should be used with caution in patients with heart failure,
diabetes, and kidney or liver disease, and the dose should be reduced by half for older
patients and those with moderate-to-severe renal impairment [304]. Octreotide (Sandostatin),
dexamethasone, and hyoscine hydrobromide (Scopolamine) are recommended for bowel
obstruction [89,303,304,306]. Ondansetron
(Zofran) has been suggested for chronic nausea, but in September 2011, the FDA issued a
safety announcement about the drug, noting that it may increase the risk of QT
prolongation on electrocardiogram; more research is being done [240,304]. Haloperidol (Haldol) is recommended for uremia-induced nausea in
people with end-stage chronic kidney disease [211]. Dexamethasone is used for nausea and vomiting related to increased
intracranial pressure and, although the evidence is limited, it is also used as
second-line treatment for intractable nausea and vomiting and as an adjuvant antiemetic
[243,303,304]. Olanzapine
(Zyprexa), an atypical antipsychotic, has also been effective for nausea that has been
resistant to other traditional antiemetics, as well as for opioid-induced nausea [309]. A benzodiazepine (such as lorazepam
[Ativan]) may be of benefit if anxiety is thought to be contributing to nausea or vomiting
[304].
PHARMACOLOGIC MANAGEMENT OF NAUSEA AND VOMITING
| Drug Class | Drug | Typical Starting Dose and Frequency |
|---|---|---|
| Prokinetic agents | Metoclopramide | 10–20 mg PO/IV/SC, every 6 to 8 hrs |
| Dopamine antagonists | Haloperidol | 1.5–5 mg PO/IV/SC 2 or 3 times daily |
| Prochlorperazine | 5–10 mg PO 3 or 4 times daily | |
| Chlorpromazine | 10–25 mg PO/IV every 4 to 6 hrs | |
| Olanzapine | 5–10 mg PO daily | |
| Levomepromazine | 6.25–25 mg SC twice daily | |
| Antihistamines | Promethazine | 25 PO 4 to 6 hrs |
| Anticholinergics | Hyoscine hydrobromide | 0.1–0.4 mcg PO/IV/SC every 4 hrs |
| 5-hydroxytryptamine type 3 receptor antagonists | Ondansetron | 4–8 mg PO/IV 1 or 2 times daily |
| Granisetron | 1 mg twice daily | |
| Dolasetron | 200 mg daily | |
| Palonosetron | 0.25 mg IV daily | |
| Mirtazapine | 15–45 mg PO, every night | |
| Corticosteroids | Dexamethasone | 4–8 mg daily |
| PO = orally, IV = intravenously, SC = subcutaneously. | ||
ANOREXIA AND CACHEXIA
Cachexia is associated with a poor prognosis in many life-limiting diseases. In fact, unintentional, progressive weight loss of more than 10% of body weight over the past 6 months, with an albumin level less than 2.5 mg/dL is a prognostic indicator for hospice referral [73]. Despite this relationship between cachexia and poor prognosis, the condition is underrecognized and underdiagnosed [313].
Cachexia has also been challenging to define. The lack of an operational definition led to a consensus conference at which a definition was crafted [311]. This definition joins others for disease-specific cachexia (Table 16). The diagnosis and management of anorexia/cachexia has been studied the most in the settings of cancer and HIV infection.
DEFINITIONS AND DIAGNOSTIC CRITERIA FOR CACHEXIA
| Condition | Definition and/or Diagnostic Criteria | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| All patients with chronic disease |
| |||||||||
| Cancer cachexia | A multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterized by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. | |||||||||
| Cardiac cachexia | 6% non-edematous, nonvoluntary weight loss over 6 months | |||||||||
| HIV-associated wasting |
|
Prevalence
Etiology
Studies have shown that multiple factors contribute to cachexia. Abnormal metabolism is thought to lead to a negative protein and energy balance, with subsequent loss of muscle mass [197,311,314,315]. Inflammation, increased neurohormonal activity, insulin resistance, and increased muscle protein breakdown are often associated with cachexia [311,315,319]. The role these factors play in the development of cachexia may differ according to the underlying chronic condition.
Prevention
Assessment
- Determination of the rate and severity of weight loss
- Examination of the oral cavity (the mucous membranes, teeth, gingiva, and lips)
- Review of the medications list for drugs that interfere with intake
- Evaluation of symptoms that have the potential to interfere with eating and drinking
- Evaluation for endocrine abnormalities that may be an underlying cause
- Assessment of social and economic factors
- Thorough and complete history and physical examination, with specific questions related to the patient's nutritional status, caloric intake, appetite, and gastrointestinal and physiologic functioning
- Measurements of body composition (considering the following factors: age, height, weight, ideal body weight, body cell mass (by BIA), and body mass index
- Laboratory tests (plasma HIV RNA, CD4 cell count, free and total serum testosterone, and serum albumin and thyroid function (if clinically warranted)
- Psychosocial evaluation
- Dietary assessment
Management
Two drugs are FDA approved as appetite stimulants for
anorexia associated with life-limiting disease (Table
17). Megestrol acetate is FDA approved for the treatment of
anorexia, cachexia, or unexplained weight loss in patients with AIDS [323]. It has become the most widely used drug
for these indications for people with other life-limiting diseases, and a meta-analysis of
data from studies (involving people with a variety of life-limiting illnesses)
demonstrated that megestrol acetate was beneficial, especially with respect to improving
appetite and weight gain in people with cancer [323]. The data were insufficient to recommend megestrol acetate for
conditions other than cancer or to recommend an optimal dose [323]. Dronabinol (Marinol), an oral
cannabinoid, is FDA approved for anorexia associated with weight loss in people with AIDS
[240]. Because of its effects,
dronabinol should be used with caution for people with cardiac disorders, depression, or a
history of substance abuse; people taking concomitant sedatives or hypnotics; and older
individuals [240].
PHARMACOLOGIC MANAGEMENT OF ANOREXIA AND CACHEXIA
| Drug | Dose Range | Findings | FDA Approval |
|---|---|---|---|
| Megestrol acetate | 400–800 mg/day | Increased appetite, food intake, and weight | For the treatment of anorexia, cachexia, or unexplained weight loss in patients with AIDS |
| Dronabinol | 2.5–20 mg, twice daily (before lunch and dinner) | Stimulated appetite and improved body weight | For anorexia associated with weight loss in people with AIDS |
| Metoclopramide | 10 mg, 3 times daily | Enhanced appetite in people with early satiety | For nausea and vomiting |
| Recombinant human growth hormone | 0.1 mg/kg SC at bedtime (max: 6 mg) | Increased lean body mass and improved physical endurance and quality of life among people with HIV-related cachexia | For HIV-related wasting or cachexia (with concomitant antiretroviral therapy) |
| Oxandrolone (anabolic steroid) | 5–20 mg/day | Increased body weight and lean body mass in cachexia related to HIV and COPD | Adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infection, or severe trauma and for some patients without a definitive pathophysiologic cause of weight loss |
| Ghrelin | Not defined | Increased lean body mass in people with end-stage renal disease, COPD, and heart failure | Not approved |
| AIDS = acquired immune deficiency syndrome, COPD = chronic obstructive pulmonary disease, HIV = human immunodeficiency virus, SC = subcutaneous. | |||
The treatment of cachexia is more challenging because its pathophysiology is poorly understood and because treatments may differ according to the life-limiting disease. According to the guidelines for cachexia related to cancer and HIV infection, management includes improving nutritional intake, treating disease-related causes of cachexia, treating anorexia, and addressing psychosocial or lifestyle issues [183,320].
Currently, there is no one treatment or combination of treatments that is effective for all patients with cachexia [322]. Increasing oral intake alone is not sufficient, and reversal of wasting may not always be possible; the goal should be to prevent or delay further wasting and functional decline [183,320,322]. As noted, the use of megestrol acetate is effective in increasing weight, but increased nutrition and weight are not sufficient to effectively manage cachexia, and more research is needed to identify agents to increase body mass and to define a multimodal strategy to stop and/or reverse wasting. These strategies may differ according to the underlying chronic disease.
Studies have indicated that recombinant human growth hormone (rhGH) significantly increases lean body mass and improved physical endurance and quality of life in people with HIV [324,325]. In addition, rhGH has shown benefit in cachexia related to pulmonary and cardiac disease [326]. Recombinant somatropin (Serostim) is approved for the treatment of people with HIV with wasting or cachexia; concomitant antiretroviral therapy is necessary [240]. The drug is contraindicated in active neoplasia [240].
The anabolic steroid oxandrolone (Oxandrin) is FDA approved as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infection, or severe trauma and for some patients without a definitive pathophysiologic cause of weight loss [240]. The drug has shown benefit in increasing body weight and lean body mass in cachexia related to HIV and COPD [327,328]. The drug is safe and well tolerated, but more studies are needed to determine its risk-benefit ratio before it can be used more widely [329].
Ghrelin has been evaluated for the treatment of cachexia, and its anti-inflammatory properties may address the proposed role of inflammation in the development of cachexia [330]. The results of small studies have demonstrated that ghrelin increases lean body mass in people with end-stage renal disease, COPD, and heart failure [326]. Again, more research is needed before this agent can become part of clinical practice.
For people with a limited life expectancy (weeks to days), the clinician should assess the importance of anorexia and cachexia to the patient and the family before prescribing interventions [183]. The clinician should also talk to the patient and family about the risks of artificial nutrition and should consider consulting a spiritual counselor or bioethicist about discontinuing nutrition [183].
DIARRHEA
Prevalence
The prevalence of diarrhea among adults with
life-limiting disease varies widely, ranging from 3% to 90%, with the highest rates
reported among people with HIV infection or AIDS [208].
Etiology
Prevention
Assessment
If infectious diarrhea is suspected, a stool sample should be evaluated to identify the causative organism [332,333].
Management
Treatment of an underlying condition is the optimal approach to managing diarrhea. The clinician should review the medication list and discontinue or reduce the dose of any medication that may be the cause [331,332].
Nonpharmacologic approaches to managing diarrhea include avoiding gas-forming and bulky foods, hot spices, fats, alcohol, and milk until diarrhea is controlled. The patient should be encouraged to drink plenty of fluids to avoid dehydration; beverages with added electrolytes, such as sports drinks, can help maintain proper electrolyte balance.
Pharmacologic management includes the use of bulk-forming agents, adsorbents, and opioids [332]. Kaolin and pectin (Kaopectate), available over the counter, is a combination of adsorbent and bulk-forming agents. However, it provides modest relief and it may take up to 48 hours to be effective [332]. Loperamide (Imodium) is the drug of choice for diarrhea because its side effect profile is better than that for codeine or diphenoxylate (Lomotil) [332]. The initial dose of loperamide is 4 mg, with an additional 2 mg after each loose stool [332]. The package insert for loperamide notes that the maximum daily dose in a 24-hour period is 16 mg, but doses of up to 54 mg a day have been used as part of palliative care with few adverse events [332]. Octreotide has been effective for profuse secretory diarrhea associated with HIV infection and can be used to treat refractory diarrhea [332]. The use of octreotide for diarrhea in the palliative setting is usually off-label, as the drug is FDA approved for the treatment of diarrhea and flushing associated with metastatic carcinoid tumors [240]. Octreotide is administered as a continuous subcutaneous infusion at a rate of 10–80 mcg/hr until improvement of symptoms [332]. Infectious diarrhea should be treated with an appropriate antibiotic. A systematic review found probiotic agents to be of benefit in the management of acute infectious diarrhea [334].
INSOMNIA
Prevalence
Etiology
The primary difference between insomnia in the general
population and in people with life-limiting diseases is that insomnia in the latter group
is usually secondary to the life-limiting disease or its symptoms [336]. Overall, uncontrolled pain is the most
common contributor to the inability to sleep well [336,337]. Other common
physical symptoms such as dyspnea, nocturnal hypoxia, nausea and vomiting, pruritus, and
hot flashes are also causes of insomnia. Restless legs syndrome may be a substantial
contributor to the disruption of sleep in persons with end-stage renal disease [207,338,339].
In addition, many psychologic conditions associated with a life-limiting disease can
cause insomnia; depression, anxiety, delirium, spiritual distress, and grief can make it
difficult to fall or remain asleep [336].
Insomnia is a side effect of many drugs, most notably corticosteroids, antidepressants,
decongestants, opioids, and some antiemetics [335,340]. Patients also
may have difficulty sleeping because of disruptions in the normal sleep-wake cycle that
result from inactivity and napping during the day. Lastly, stimulants, such as caffeine,
and alcohol may keep patients from falling asleep easily.Prevention
Assessment
QUESTIONS TO OBTAIN A SLEEP HISTORY
|
Management
The nonpharmacologic approaches used to prevent insomnia are also the primary management strategies. Among the recommended behavioral strategies are the following [335,342]:
- Stimulus control therapy: Training the patient to reassociate the bed and bedroom with sleep and to re-establish a consistent sleep-wake cycle
- Relaxation training: Progressive muscle relaxation and reducing thoughts that interfere with sleep
- Sleep restriction: Limiting the time spent in bed to time spent sleeping
Several drugs have been approved by the FDA for the treatment of insomnia; the classes of these drugs are sedative-hypnotics and benzodiazepines Table 19. In addition, antidepressants and antihistamines are often used for insomnia, but this use is off-label.
PHARMACOLOGIC MANAGEMENT OF INSOMNIA
| Drug | Typical Dose (mg)* | Comments |
|---|---|---|
| Sedative-Hypnotics (FDA approved for insomnia) | ||
| Zolpidem | 5–20 mg | Useful for sleep-onset insomnia; lower dose should be used for older or debilitated individuals or those with impaired hepatic function |
| Zaleplon | 5–20 mg | Useful for sleep-onset insomnia; lower dose should be used for older or debilitated individuals, patients with impaired hepatic function, and patients taking cimetidine |
| Eszopiclone | 1–3 mg | Has favorable side-effect profile in older individuals; FDA approved for long-term use |
| Benzodiazepines (FDA approved for insomnia) | ||
| Flurazepam | 15–30 mg | Lower dose should be used for older or debilitated individuals; long-acting effect increases risk of daytime drowsiness |
| Estazolam | 0.5–2 mg | Lower dose should be used for older or debilitated individuals |
| Temazepam | 7.5–30 mg | Lower dose should be used for older or debilitated individuals |
| Triazolam | 0.125–0.25 mg | Lower dose should be used for older or debilitated individuals |
| Quazepam | 7.5–15 mg | — |
| Melatonin Receptor Agonists (FDA approved for insomnia) | ||
| Ramelteon | 8 mg | Useful for sleep-onset insomnia; FDA approved for long-term use |
| Antidepressants (Not FDA approved for insomnia) | ||
| Trazodone | 50–150 mg | — |
| Amitriptyline | 10–100 mg | — |
| Doxepin | 75–150 mg | — |
| Trimipramine | 25–100 mg | — |
| Nonprescription (Not FDA approved for insomnia) | ||
| Diphenhydramine | 25–50 mg | — |
| *Doses are given as guidelines; actual doses should be determined on an individual basis. | ||
A systematic search of the literature found no evidence from randomized controlled trials regarding the use of benzodiazepines in palliative care [344]. However drugs in this class are the most commonly used drugs for the treatment of short-term insomnia in people with life-limiting disease [336]. Benzodiazepines are effective in decreasing the time needed to fall asleep as well as the likelihood of waking up during the night [336,343]. Their use should be short term, as their long-term efficacy has not been clearly defined, although this issue is not as important for patients with a limited life expectancy [336]. Lorazepam (Ativan) is a recommended drug for insomnia in people with cancer [183]. The long-acting effect of flurazepam (Dalmane) may be of benefit for some patients [336].
The antidepressant trazodone (Desyrel) is the preferred antidepressant for insomnia (although it is not FDA approved for this indication) [336]. It is the drug of choice among tricyclic antidepressants because of its shorter half-life and its milder anticholinergic side effects [336]. Antidepressants are especially useful for people who have anxiety or depression.
The most recently FDA-approved drug for insomnia is ramelteon (Rozerem), a melatonin receptor agonist. This drug is short acting and used primarily for sleep-onset insomnia [343]. Ramelteon is FDA approved for long-term use [335].
For insomnia related to restless legs, a systematic review showed that dopamine agonists are effective, with cabergoline (Dostinex) and pramipexole (Mirapex) often having a greater efficacy than levodopa (L-Dopa) [345].
Barbiturates are not recommended for insomnia because of the rapid development of tolerance [336]. Two supplements promoted for sleep enhancement—melatonin and valerian—have not been shown to be effective for managing insomnia [336,346].
Several factors must be considered when treating older patients with insomnia. For example, it has been recommended that benzodiazepines be avoided in older individuals because of side effects such as increased risk for falls, confusion, and "hangover" [343]. However, these side effects must be considered in light of an individual's particular situation and weighed against the benefits [343,336]. Eszopiclone and ramelteon have been studied in older individuals and have a favorable side-effect profile for that population [343]. Lower doses are often recommended for older individuals [335].
DELIRIUM
Delirium can be extremely distressful for the patient and even more so for family members. The healthcare team can help alleviate family members' distress by educating them about the nature and cause of the syndrome and the potential for reversal. Encouraging them to participate in nonpharmacologic interventions may also help to provide a positive experience.
Prevalence
Etiology
Prevention
Because of the substantial influence of unrelieved pain,
adequate pain management can help prevent delirium. Prevention strategies are directed at
minimizing precipitating factors, which include a high number of medications (more than
six), dehydration, decreased sensory input, psychotropic medications, and a change in
environment.
Assessment
- Ask the patient "Do you feel 100% awake?" If they do not, ask "How awake do you feel?"
- Evaluate whether the patient is easily distracted.
- Test registration and immediate recall.
- Assess psychomotor disturbances by noting whether the patient is restless and agitated or slow and hypoactive.
- Ask the patient if he or she is seeing or hearing strange things.
- Ask the patient to state the days of the week or months backward, or to give a span of numbers frontward and backward.
- Ask the patient open-ended questions, and listen for incoherent speech or tangential thought processes.
Management
Several nonpharmacologic interventions have been successful in preventing and managing delirium Table 20 [183,349,351]. If delirium is refractory to nonpharmacologic measures, medications may be prescribed. The American Psychiatric Association developed guidelines in 1999 for the treatment of delirium with antipyschotics [355]. Level 1 evidence supports the use of haloperidol and chlorpromazine (Thorazine) (typical antipsychotics), and these drugs have the advantage of being available in formulations that allow for multiple routes of administration and of being the most cost-effective [349]. Several systematic reviews have been done to determine the efficacy of antipsychotics for delirium, and although each review has identified only a few well-designed trials, the results have supported the continued use of these drugs (Table 21) [183,349,351,356,357,358]. One of these reviews focused on patients with terminal illness; the review identified only one small study (30 subjects) eligible for analysis; haloperidol and chlorpromazine were equally effective, but the risk for cognitive impairment was slightly greater with chlorpromazine [356]. In the other reviews, the efficacy of haloperidol was found to be similar to that of olanzapine, risperidone (Risperdal), and quetiapine (Seroquel) (atypical antipsychotics) [357,358]. In two small nonrandomized studies—one involving hospitalized patients with cancer—aripiprazole (Abilify) was safe and effective for the treatment of delirium, especially the hypoactive subtype [359,360]. Mild-to-moderate delirium can be managed with low oral doses of antipsychotics, titrating the dose to optimum relief; higher doses can be used for severe delirium [183,351]. For older patients and those with multiple comorbidities, treatment should begin with lower doses and titration should be slow [349]. Factors to consider when selecting a drug include the side-effect profile, the patient's age and baseline mental status, the time to response, and the subtype of delirium [349].
NONPHARMACOLOGIC TREATMENT OPTIONS FOR DELIRIUM
|
PHARMACOLOGIC OPTIONS FOR DELIRIUM
| Drug | Dose Range | Routes of Administration | Comments |
|---|---|---|---|
| Haloperidol | 0.5–2 mg every 2 to 12 hrs | PO, IV, IM, SC | Considered to be first-line treatment. |
| Chlorpromazine | 12.5–50 mg every 4 to 6 hrs | PO, IV, IM, SC, PR | Has more sedative effect than haloperidol, thus is preferred for patients with agitation. |
| Olanzapine | 2.5–5 mg every 12 to 24 hrs | PO | Sedation has been a dose-limiting effect; poorer response has been associated with older age, pre-existing dementia, and hypoactive subtype. |
| Risperidone | 0.25–1 mg every 12 to 24 hrs | PO | Response may be better with hypoactive subtype; orthostatic hypotension is possible adverse effect. |
| Quetiapine | 12.5–100 mg every 12 to 24 hrs | PO | Sedation and orthostatic hypotension are possible adverse effects. |
| Aripiprazole | 5–30 mg every 24 hrs | PO | Response may be better with hypoactive subtype. |
| Lorazepam | 0.5–2 mg every 2 to 4 hrs | IV, SC | May be added to treatment with haloperidol if agitation is refractory to high doses. |
| PO = orally, IV = intravenously, IM = intramuscularly, SC = subcutaneously, PR = rectally. | |||
PSYCHOSOCIAL CARE
The prevalence of psychologic suffering is high during the last year of life, and addressing this aspect of care is integral to the patient's overall comfort and quality of life. Anxiety and depression are the most common psychologic symptoms at the end of life, yet they are among the most underdiagnosed and untreated symptoms [66,361]. Psychologic suffering exacerbates pain and other symptoms, limits the patient's capacity for pleasurable activities, and causes distress for both the patient and the family [202,362].
The word "distress" has become standard to describe the
psychologic suffering experienced by patients with life-limiting disease. The NCCN notes that
the word "distress" is more acceptable and is associated with less stigma than words such as
"psychosocial" or "emotional" [183]. In its
guidelines on distress management, the NCCN defines distress as existing "along a continuum,
ranging from common normal feelings of vulnerability, sadness, and fears to problems that can
become disabling, such as depression, anxiety, panic, social isolation, and existential and
spiritual crisis" [183]. According to a study
of patients in a palliative care program, the answers to the question "What bothers you most?"
included [212]:
- Emotional, spiritual, existential, or nonspecific distress (16%)
- Relationships (15%)
- Concerns about the dying process and death (15%)
- Loss of function and normalcy (12%)
As with physical symptoms, assessment of distress and the psychosocial and spiritual well-being of the patient must be ongoing, as changes occur over time [5,66]. In addition, worsening symptoms and disease progression can affect patients' coping mechanisms [223]. One study found significant correlations between the will to live and existential, psychologic, and social sources of distress. In that study, hopelessness, burden to others, and dignity were the variables with the most influence [363]. Other studies have consistently shown that psychosocial suffering has a stronger association than pain with a desire to hasten death [364,365,366,367,368,369].
How a patient responds to his or her disease and care is strongly influenced by attitudes and values learned through family interactions, and social workers should evaluate the patient and family to assess psychosocial as well as practical problems and recommend and/or carry out interventions [5,183]. For many patients, the primary concern about their illness is its impact on the family. The need for palliative care raises issues regarding power, structure, and roles among the patient and his or her family [66]. The impact of a life-limiting disease and the ensuing care threatens the structure and integrity of the family, as family roles are reassigned, the rules of daily living are altered, and methods of problem-solving are revised. Families vary in their ability to adapt to such restructuring, and dysfunction can result from either limited or excessive adaptation. At one end of this spectrum, family members have difficulty breaking away from coping mechanisms, even though they are ineffective. At the other end of the spectrum, family members continually try new coping strategies to meet each crisis, resulting in chaos [66]. Both types of dysfunction can lead to increased demands on the healthcare team and can interfere with the delivery of appropriate care.
ANXIETY
Prevalence
Etiology
One of the primary causes of anxiety is inadequate pain
relief. Anxiety may also be the result of a patient's overwhelming concern about his or
her illness, the burden of the illness on the family, and the prospect of death. In
addition, anxiety is a potential side effect of many medications, including
corticosteroids, metoclopramide, theophylline, albuterol, antihypertensives, neuroleptics,
psychostimulants, antiparkinsonian medications, and anticholinergics. Lastly, withdrawal
from opiates, alcohol, caffeine, and sedatives can result in anxiety.
Prevention
Effective pain management is the best way to prevent
anxiety. Also, educating the patient and the family about what to expect over the course
of the illness and providing adequate psychologic and spiritual support can help comfort
the patient, thereby preventing anxiety.
Assessment
Family members and friends may be able to provide
information about the level of anxiety experienced by the patient currently and in past
situations. All members of the healthcare team should evaluate the patient and the
clinical record for reversible causes of anxiety, such as those caused by medications or
withdrawal syndromes, and should try to distinguish anxiety from delirium, depression, or
bipolar disorder [370,371].
Anxiety manifests itself through physical as well as
psychologic and cognitive signs and symptoms. These signs and symptoms include dyspnea,
paresthesias, tachycardia, chest pain, urinary frequency, pallor, restlessness, agitation,
hyperventilation, insomnia, tremors, excessive worrying, and difficulty
concentrating.
Management
Nonpharmacologic approaches are essential for managing
anxiety, and the addition of pharmacologic treatment depends on the severity of the
anxiety [66,372]. Effective management of pain and other
distressing symptoms, such as constipation, dyspnea, and nausea, will also help to relieve
anxiety. If the anxiety is thought to be caused by medications, they should be replaced by
alternate drugs. Other strategies include psychologic support that allows the patient to
explore fears and concerns and to discuss practical issues with appropriate healthcare
team members. Relaxation and guided imagery may also be of benefit [373]. A consult for psychologic therapy may
be needed for patients with severe anxiety.
When pharmacologic management is deemed necessary, benzodiazepines are generally
preferred, and administration on an as-needed basis is usually sufficient [66]. Neuroleptics and tricyclic
antidepressants may also be effective (Table 22). For all
medications, the initial dose should be low and subsequently titrated to produce the
desired effect within the level of tolerance. Benzodiazepines should be given with caution
in older patients, as these drugs may harm memory or cause confusion and agitation in
patients who have cognitive impairment [375].
PHARMACOLOGIC MANAGEMENT OF ANXIETY AND DEPRESSION
| Condition | Drug Class, Drugs | Typical Starting Oral Dose* | Titration Recommended | Maximum Daily Dose | Comments |
|---|---|---|---|---|---|
| Anxiety | Benzodiazepines | ||||
| Lorazepam | 0.5–2 mg, every 1 to 6 hrs | May titrate upward | — | First choice | |
| Diazepam | 2.5–10 mg, every 3 to 6 hrs | May titrate upward | — | ||
| Midazolam | 2–10 mg/day (SC) | May titrate upward | — | ||
| Clonazepam | 0.5–1.0 mg, 3 times per day | May titrate upward 4 mg | — | ||
| Neuroleptics | |||||
| Haloperidol | 0.5–4.0 mg, every 4 to 6 hrs | May titrate upward | — | — | |
| Thioridazine | 10 mg, 3 times per day | May titrate upward | — | — | |
| Tricyclic Antidepressant | |||||
| Imipramine | 10–25 mg, 3 times per day | May titrate upward | — | — | |
| Depression | SSRIs | ||||
| Fluoxetine | 20 mg/day | Increase by 10 mg every 1 to 2 wks | 20–60 mg | First choice when immediate onset not needed (onset at 4 to 6 wks) | |
| Paroxetine | 10 mg/day | Increase by 10 mg every 1 wk | 10–50 mg | ||
| Sertraline | 50 mg/day | Increase by 25 mg every 1 wk | 50–150 mg | ||
| Escitalopram | 10 mg/day | — | 20 mg | ||
| Venlafaxine | 18.75 mg/day | Increase by 75 mg every 1 wk | 75–225 mg | ||
| Tricyclic Antidepressants | |||||
| Amitriptyline | 25 mg/day | Increase by 25 mg every 1 to 2 days | 50–150 mg | Less useful because of side effects; slow onset of action (3 to 6 wks) | |
| Nortriptyline | 25 mg/day | 50–150 mg | |||
| Desipramine | 25 mg/day | 50–150 mg | |||
| Doxepin | 25 mg/day | 50–200 mg | |||
| *Doses are given as guidelines; actual doses should be determined on an individual basis. | |||||
DEPRESSION
Prevalence
Etiology
Unrelieved pain is one of the primary risk factors for
depression. Other causes within the physical domain include metabolic disorders
(hyponatremia or hypercalcemia), lesions in the brain, insomnia, or side effects of
medications (corticosteroids or opioids). Many patients with heart failure have
comorbidities and polypharmacy, both of which can increase the risk of depression [377,378]. Psychosocial causes include despair about progressive physical
impairment and loss of independence, financial stress, family concerns, lack of social
support, and spiritual distress.
Prevention
Adequate management of pain, attention to psychosocial
and spiritual well-being, and early referral for mental health or pastoral counseling are
the best strategies to prevent depression.
Assessment
The diagnosis of depression is complicated, as the usual
somatic signs of depression—anorexia, sleep disturbances, weight loss, and fatigue—are
often symptoms related to the underlying disease or part of the constellation of symptoms
experienced by patients with life-limiting disease [223]. Because of this, assessment should focus on psychologic and cognitive
symptoms, such as:
- Persistent dysphoria
- Loss of pleasure in activities
- Frequent crying
- Loss of self-esteem
- Sense of worthlessness
- Excessive guilt
- Pervasive despair
- Thoughts of suicide
A diagnosis of depression requires the presence of at
least five depression-related symptoms within the same 2-week period, and the symptoms
must represent a change from a previous level of functioning [347]. A simple screening tool that has been
found to be effective is to ask the patient, "Are you depressed?" or, "Do you feel
depressed most of the time?" [223,379,380]. The physician should also discuss the patient's mood and behavior
with other members of the healthcare team and family to help determine a diagnosis.
Patients who have thoughts of suicide must be assessed carefully. The physician should
differentiate between depression and a desire to hasten death because of uncontrolled
symptoms [66]. Psychologic counseling
should be sought, as well as measures to enhance the management of symptoms.
Management
The American College of Physicians asserts that clinicians should
assess for and manage symptoms of depression in patients with serious chronic diseases.
For patients with cancer, strong evidence shows that depression should be treated with
generally effective therapies, including tricyclic antidepressants, selective serotonin
reuptake inhibitors, or psychosocial interventions.
(http://www.guideline.gov/content.aspx?id=12149
Last Accessed: May 24, 2012)
Strength of Recommendation/Level of Evidence:
Strong recommendation based on moderate quality of evidence
The effective management of depression requires a
multimodal approach, incorporating supportive psychotherapy, cognitive strategies,
behavioral techniques, and antidepressant medications [46]. Patients with depression should be referred to mental health services
for evaluation, and resultant approaches may include formal therapy sessions with
psychiatrists or psychologists or counseling from social workers or pastoral advisors. In
addition, physicians can help by having discussions with the patient to enhance his or her
understanding of the disease, treatments, and outcomes, and to explore expectations,
fears, and goals. Behavioral interventions, such as relaxation techniques, distraction
therapy, and pleasant imagery have been effective for patients with mild-to-moderate
depression [46].
Strong evidence supports the use of tricyclic antidepressants or SSRIs, along with
psychosocial interventions, for the management of depression in patients with cancer [46,209]. Evidence to support the use of specific pharmacologic agents to treat
depression in patients with noncancer diagnoses is not as strong, but psychostimulants may
also be helpful [46,66,223,381]. The choice of
medication depends on the time available for treatment. The most immediate effect (within
days) is achieved with a rapid-acting psychostimulant; longer times to therapeutic effect
are associated with SSRIs (2 to 4 weeks) and tricyclic antidepressants (3 to 6
weeks).SPIRITUAL NEEDS
According to the National Consensus Project for Quality Palliative Care,
whenever possible, a standardized instrument should be used to assess and identify
religious or spiritual/existential background, preferences, and related beliefs, rituals,
and practices of the patient and family.
(http://www.guideline.gov/content.aspx?id=14423
Last Accessed: May 24, 2012)
Level of Evidence: Consensus
Statement/Expert Opinion
Spirituality is unique to each person. It is founded in
cultural, religious, and family traditions and is modified by life experiences. Spirituality
is considered to be separate from religious faith, and many surveys have shown that
spirituality or religion is an integral component of people's lives [66,382]. Spirituality also plays a significant role in health and illness.
Studies have shown spirituality to be the greatest factor in protecting against end-of-life
distress and to have a positive effect on a patient's sense of meaning [376,383]. Thus, a spiritual assessment and spiritual care to address individual
needs are essential components of the multidimensional evaluation of the patient and family
[202,384].
A life-limiting disease will lead patients to ask
questions that may give way to spiritual conflicts, such as "Why would God let me suffer
this way?" Patients may also carry out life review in search of meaning for their illness;
some may view their illness as punishment for past "sins." Left unanswered, spiritual
questions and concerns lead to spiritual distress and suffering, which can cause or
exacerbate pain and other physical and psychosocial symptoms. It then becomes critical for
the healthcare team to facilitate pastoral services to address patients' spiritual concerns
[5]. In general, the spiritual and
existential concerns of patients at the end of life relate to four areas: the past, the
present, the future, and religion (Table 23) [202].
SPIRITUAL AND EXISTENTIAL CONCERNS OF PATIENTS AT THE END OF LIFE
| Relation of Concern | Concerns | |||||
|---|---|---|---|---|---|---|
| Past |
| |||||
| Present |
| |||||
| Future |
| |||||
| Religion |
|
The need for spirituality at the end of life is
heightened, and patients will search for meaning as a way to cope with emotional and
existential suffering [385]. Spirituality
helps patients cope with dying through hope. At the time of diagnosis, patients hope for
cure, but over time, the object of hope changes and the patient may hope for enough time to
achieve important goals, personal growth, reconciliation with loved ones, and a peaceful
death [13,66]. Spirituality can also help a patient gain a sense of control,
acceptance, and strength. As a result, greater spiritual well-being has been associated with
decreased rates of anxiety and depression among people with advanced disease [204,386].
There has been a growing emphasis on the need for
physicians to discuss spirituality with their patients [384,387]. A spiritual
history should be obtained to elicit answers to such questions as:
- Do you consider yourself spiritual or religious?
- Do you have spiritual beliefs that help you cope with stress?
- What importance does your faith or belief have in your life?
- Are you part of a spiritual or religious community?
One recommended mnemonic for the components of a spiritual
history is SPIRIT: spiritual belief system; personal spirituality; integration with a
spiritual community; ritualized practices and restrictions; implications for medical care;
and terminal events planning [388].
Although spiritual care is an essential component of
palliative care, what patients and families perceive to be spiritual care and how it should
be delivered have not been well-defined [382]. Patients and families have found spiritual comfort with friends and family, clergy and
other pastoral care providers, and healthcare professionals [382]. Among healthcare professionals, barriers
to providing spiritual care are time; social, religious, or cultural discordance; and lack
of privacy and care continuity [382].
FAMILY-CENTERED PSYCHOSOCIAL NEEDS
Family caregivers can become overwhelmed with added responsibilities. Often, the caregiver is a spouse who is older and may also have illnesses. In addition, children and teenagers are frequently forgotten, but addressing their concerns and needs is essential for their psychologic well-being and appropriate grieving [66]. Young children will realize that the family structure has been disrupted. They should be encouraged to ask questions, and they usually need time to interpret answers. Adolescence is a challenging time in itself, and dealing with the illness and loss of a parent or close family member may result in aggressive behavior, isolation, or sexuality. Frequent evaluation of family members' coping strategies, moods, and behaviors can help to determine if early referral for individual counseling or family therapy is necessary. Support should be provided to ensure that the patient and family has access to resources to help with finances, that the home environment is safe, that caregivers are available, and that adequate transportation is available [183].
Family roles are also important to understand, and these roles are strongly influenced by culture. Many cultures highly value family, with strong family ties across many generations. Patients from such cultures will often have many visitors at one time. The palliative care team should accommodate such visits when possible. In addition, family hierarchy may dictate behavior of family caregivers. For example, in traditional Vietnamese families, a female member of the family is expected to stay at the bedside of the patient for comfort and support [390]. In Asian families, elders are revered and a young person cannot tell an older person what to do [391]. This may make it difficult for a healthcare professional who is younger than the patient. Patients and families who adhere to Native American cultures have unique traditions and rituals that should be respected [392].
All members of the healthcare team should become familiar with the cultural context of their patients and provide resources from within the cultural community if possible. A bilingual healthcare worker can provide an important link to a community [393].
IMMINENT DEATH AND LOSS
THE PATIENT'S NEEDS
INTERVENTIONS FOR PATIENTS WHO ARE IMMINENTLY DYING
|
Anticholinergic medications can eliminate the so-called
"death rattle" brought on by the build-up of secretions when the gag reflex is lost or
swallowing is difficult. Specific drugs recommended include scopolamine, glycopyrrolate,
hyoscyamine, and atropine (Table 25) [66,183,394,396]. For patients with advanced kidney
disease, the dose of glycopyrrolate should be reduced 50% (because evidence indicates that
the drug accumulates in renal impairment) and hyoscine butylbromide should not be used
(because of a risk of excessive drowsiness or paradoxical agitation) [211]. Some evidence suggests that treatment is
more effective when given earlier; however, if the patient is alert, the dryness of the
mouth and throat caused by these medications can be distressful. Repositioning the patient
to one side or the other or in the semiprone position may reduce the sound. Oropharyngeal
suctioning is not only often ineffective but also may disturb the patient or cause further
distress for the family. Therefore, it is not recommended.
TREATMENT OF EXCESSIVE RESPIRATORY SECRETIONS CAUSING "DEATH RATTLE"
| Drug | Dose |
|---|---|
| Scopolamine (transdermal patch) | 1 or 2 (1.5-mg) patches applied behind the ear and changed every 48 to 72 hours; if ineffective, switch to 50 mcg/hr continuous IV or SC infusion and double the dose every hour, up to 200 mcg/hr |
| Glycopyrrolate (Robinul) | 1–2 mg PO or 0.1–0.2 mg SC/IV, every 4 to 8 hrs, as needed; or 0.4–1.2 mg/day continuous infusion |
| Hyoscyamine (Levsin) | 0.125–0.5 mg PO/SL/SC/IV every 4 hrs as needed |
| Atropine (1%) eye drops | 1 or 2 drops PO/SL, titrate every 8 hrs; 0.4 mg SL every 15 min, as needed |
| PO = orally, IV = intravenously, SC = subcutaneously, SL = sublingually, PR = rectally. | |
Seizures at the end of life may be managed with high doses of benzodiazepines. Other antiepileptics such as phenytoin (administered intravenously), fosphenytoin (administered subcutaneously), or phenobarbital (60–120 mg rectally, intravenously, or intramuscularly every 10 to 20 minutes as needed) may become necessary until control is established.
A calm and peaceful environment should be maintained for the patient. Family and spiritual leaders should be allowed to carry out traditional rites and rituals associated with death.
Palliative Sedation
Palliative sedation may be considered when an imminently
dying patient is experiencing suffering (physical, psychologic, and/or spiritual) that is
refractory to the best palliative care efforts. Terminal restlessness and dyspnea have
been the most common indications for palliative sedation, and thiopental and midazolam are
the typical sedatives used [183,397,398]. For patients who have advanced kidney disease, midazolam is
recommended, but the dose should be reduced because more unbound drug becomes available
[211]. Before beginning palliative
sedation, the clinician should consult with a psychiatrist and pastoral services (if
appropriate) and talk to the patient, family members, and other members of the healthcare
team about the medical, emotional, and ethical issues surrounding the decision [66,183,223,399,400]. Formal informed consent should be obtained from the patient or from
the healthcare proxy.
Physician-Assisted Suicide
Physician-assisted suicide, or hastened death, is
defined as active euthanasia (direct administration of a lethal agent with a merciful
intent) or assisted suicide (aiding a patient in ending his or her life at the request of
the patient) [66]. The following are not
considered to be physician-assisted suicide: carrying out a patient's wishes to refuse
treatment, withdrawal of treatment, and the use of high-dose opioids with the intent to
relieve pain. The American Medical Association Code of Ethics explicitly states,
"Physician-assisted suicide is fundamentally incompatible with the physician's role as
healer, would be difficult or impossible to control, and would pose serious societal
risks" [401]. Position statements against
the use of physician-assisted suicide have been issued by many other professional
organizations, including the NHPCO, the AAHPM, and the NCCN [183,402,403]. The basis for
these declarations is that appropriate hospice care is an effective choice for providing
comfort to dying patients.
In 2010, in a first-of-its-kind comprehensive consensus
statement, the Heart Rhythm Society in collaboration with the major cardiology,
geriatrics, and palliative care societies, emphasized that deactivation of implantable
cardioverter-defibrillators is neither euthanasia nor physician-assisted suicide [404]. The organizations urged clinicians to
respect the right of patients to request deactivation.
The NCCN guidelines recommend that physicians explore requests for assisted suicide
and explain to the patient the distinctions among assisted suicide, treatment withdrawal,
and aggressive symptom management [183].
Some states have enacted assisted suicide statutes. State laws vary, and knowledge of your
local statutes is necessary.THE FAMILY'S NEEDS
The altered breathing patterns that are present as death is imminent are distressful for family members, as they believe that the patient is experiencing a sense of suffocation. Also distressful to family is the sound of the death rattle. The healthcare team should assure family that these signs do not indicate that the patient is suffering and explain that additional therapy will not be of benefit.
Families often misinterpret the early signs of terminal delirium as signs of uncontrollable pain. However, if pain has been adequately managed throughout the delivery of palliative care, such pain will not begin during the last hours. As the patient slips in and out of consciousness, family members may become increasingly distressed about not being able to communicate anymore with their loved one. Although it is unknown what a dying patient can hear, other experiences in medicine suggest that awareness may be greater than the ability to respond. Family members should be encouraged to continue talking with their loved one to help them attain a sense of closure.
Despite the best efforts to prepare the family, reactions are unpredictable when death occurs. The clinician should take time to answer questions from family members, including children, and perhaps provide information on the physiologic events associated with death [66]. For family members who were not present during the death, the clinician should describe the event, while reassuring them that the patient died peacefully.
Many experts believe that people can handle grief better if they spend time with a loved one immediately after death. Family members should be allowed to touch, hold, and kiss their loved one as they feel comfortable. The healthcare team should respect the needs of the family to conduct personal, cultural, or religious traditions, rites, and rituals.
GRIEF, MOURNING, AND BEREAVEMENT
Grief
Grief counseling for the family and patient should begin
when the patient is alive, with a focus on life meaning and the contributions from the
patient's family. An understanding of the mediators of the grief response can help
physicians and other members of the healthcare team recognize the family members who may
be at increased risk for adapting poorly to the loss [406]. These mediators are:
- Nature of attachment (how close and/ or dependent the individual was with regard to the patient)
- Mode of death (the suddenness of the death)
- Historical antecedents (how the individual has handled loss in the past)
- Personality variables (factors related to age, gender, ability to express feelings)
- Social factors (availability of social support, involvement in ethnic and religious groups)
- Changes and concurrent stressors (number of other stressors in the individual's life, coping styles)
Clinical assessment should be carried out for
individuals at risk of complicated grief. Distinguishing between grief and depression can
be challenging, as many signs and symptoms are similar. However, the hallmarks of
depression are constant and unremitting feelings of worthlessness, hopelessness,
helplessness, anhedonia, and suicidal ideation [202].
Mourning
Satisfactory adaptation to loss depends on "tasks" of
mourning [406]. Previous research referred
to "stages" of mourning, but the term "task" is now used because the stages were not
clear-cut and were not always followed in the same order. The tasks include:
- Accepting the reality of the loss
- Experiencing the pain of the loss
- Adjusting to the environment in which the deceased is missing (external, internal, and spiritual adjustments)
- Finding a way to remember the deceased while moving forward with life
After the patient's death, members of the palliative
care team should encourage the family to talk about the patient, as this promotes
acceptance of the death. Explaining that a wide range of emotions is normal during the
mourning process can help family members understand that experiencing these emotions is a
necessary aspect of grieving. Frequent contact with family members after the loved one's
death can ensure that the family is adjusting to the loss. Referrals for psychosocial and
spiritual interventions should be made as early as possible to optimize their
efficacy.
Bereavement
The National Consensus Project for Quality Palliative Care recognizes
bereavement services as a core component of the palliative care program. Bereavement
services and follow-up should be made available to the family for at least 12 months, or
as long as is needed, after the death of the patient.
(http://www.guideline.gov/content.aspx?id=14423
Last Accessed: May 24, 2012)
Level of Evidence: Consensus
Statement/Expert Opinion
Bereavement support should begin immediately with a
handwritten condolence note from the clinician. Such notes have been found to provide
comfort to the family [407,408]. The physician should emphasize the
personal strengths of the family that will help them cope with the loss and should offer
help with specific issues. Attendance at the patient's funeral, if possible, is also
appropriate.
How bereavement services are provided through a hospice/palliative care program vary.
Programs usually involve contacting the family at regular intervals to provide resources
on grieving, coping strategies, professional services, and support groups [183,223]. When notes are sent, family members should be invited to contact the
physician or other members of the healthcare team with questions. Notes are especially
beneficial at the time of the first holidays without the patient, significant days for the
family (patient's birthday, spouse's birthday), and the anniversary of the patient's
death. Bereavement services should extend for at least 1 year after the patient's death,
but a longer period may be necessary [5,223].PALLIATIVE CARE FOR SPECIFIC POPULATIONS
OLDER PATIENTS AND NURSING FACILITY RESIDENTS
The primary issues for this population at the end of life are the variation in care settings, a high level of comorbidities, inadequate management of pain and suffering, and a high prevalence of dementia [101].
The majority of older individuals receive hospice care at home, but up to 25% are residents at a nursing facility at the time of death [1,410]. Each setting presents different issues. For patients at home, caregiver burden is high, as the long disease trajectory requires an extended need for family caregivers. In addition, the primary caregiver may be a spouse who is older than 75 years of age and may have multiple health issues. For patients in nursing facilities, care may be fragmented and staff often lack an appropriate understanding of pharmacology, drug addiction and dependence, management of side effects, and effective nonpharmacologic therapies [411,412,413]. Also, family members often have grief symptoms before the death of the patient; the most frequent grief symptom is yearning (separation distress) [414]. Thus, early psychosocial support and bereavement services for family are important.
Older patients, especially those with end-stage organ disease, often have substantial comorbidities and take multiple medications, both of which add to the complexity of care [101,377,415]. One study of patients with heart failure found that approximately 33% had COPD, 40% had diabetes, and more than 50% had coronary heart disease or hypertension [416]. With respect to multiple medications, a study found that older patients took an average of 6.5 medications and that 29% of the patients were taking a medication that was considered to be "never appropriate" [417]. Polypharmacy increases the likelihood of drug interactions, and clinicians should review the medication list and eliminate those drugs that are not providing clear benefit [415]. Knowledge of pharmacokinetics, pharmacodynamics, and pathophysiology are needed in making decisions to stop or adjust drugs [418]. Consulting with a pharmacist can be valuable.
As with the overall population of patients at the end of life, pain management is inadequate for older patients, with pain experienced by more than 50% of patients at home and as many as 80% of patients in nursing facilities [419,420,421]. Studies have confirmed that older patients receive less pain medication at the end of life than younger patients and that pain management is inadequate for residents of nursing facilities [422,423,424,425]. The American Geriatrics Society has issued guidelines for the management of chronic pain for older patients, and physicians and nursing facility staff should become familiar with this resource and other guidelines for pain [421]. Improvement is also needed in the treatment of patients who have psychosocial symptoms, such as depression, agitation, anxiety, and loneliness [426].
Perhaps the greatest issue is the need for better
palliative care for patients with dementia [100,411,427]. The prevalence of dementia has been
reported to be 40% to 50% among persons older than 80 years of age [409]. Underlying dementia makes it difficult to
identify symptoms, especially pain and psychosocial disorders. As a result, suffering is
prevalent among patients with dementia. In fact, one study showed that 93% of patients with
dementia died with an intermediate or high level of suffering [428]. The assessment of pain can be
particularly challenging when the patient is unable to communicate. This situation calls for
a multipronged approach consisting of observation, discussion with family and caregivers,
and evaluation of the response to pain medication or nonpharmacologic measures.
Recommendations for assessing pain in nonverbal patients have been developed by the American
Society for Pain Management Nursing [429].
As dementia progresses, behavioral disturbances become more frequent, and symptoms
include hallucinations, sleep disorders, agitation, paranoia, delusions, anxiety, and
combativeness. Care should be taken to differentiate these symptoms from those associated
with the underlying disease or as an adverse effect of drugs. In addition, dementia can
affect the prognosis of other chronic diseases, and health events or complications such as
hip fracture, pneumonia, febrile episodes, or eating problems can substantially reduce the
life span for patients with advanced dementia [170,422].The understanding of advanced dementia is limited, and as noted, the uncertainty of the disease course makes it difficult for advance care planning and referral to hospice care [170,411,430,431,432]. The progressive nature of dementia adds importance to the need for advance directives, and involvement of the family in decision making is crucial [170,433]. Educational resources about palliative care and hospice can help family and patients better understand the language needed in advance directives and the benefit of hospice services [410,433].
In an effort to enhance the quality of care at the end of life for older patients, the CAPC published the report Improving Palliative Care in Nursing Homes [21]. Based on their research, the authors of this report identified four different models for integrating preferred practices for palliative and hospice care for patients in nursing homes [21,434]:
- Palliative Care Consult Service: Palliative care services are provided by healthcare professionals as requested by the nursing home Medical Director or Director of Nursing or the patient's attending physician.
- Hospice-based Palliative Care Consult Service: Palliative care services are provided by healthcare professionals employed at a local hospice as requested by the nursing home Medical Director or Director of Nursing or the patient's attending physician.
- Nursing Home Services Integrated Palliative Care: Palliative care services are provided by staff employed directly by a nursing home that incorporates one or more of the NQF's domains of care.
- Hospice Care: Specialized end-of-life palliative care services are provided by contracted hospice providers to hospice-eligible residents.
CHILDREN/ADOLESCENTS
One factor contributing to inadequate palliative/hospice care referral may be availability of appropriate services. A survey of institutions participating in Children's Oncology Group clinical trials found that a palliative care team was available in 58% of institutions and hospice care in 60% [440]. Furthermore, even when available, most services were not well used by patients [440]. In addition, many healthcare professionals are inexperienced with pediatric palliative care, and the availability of sufficiently trained pediatric hospice professionals is limited [87,435,438].
Research has identified several additional barriers to palliative care at the end of life for children/adolescents, many of which differ from those in the adult setting (Table 26) [14,87,438,439]. The sense of failure or of "giving up" may be heightened among both pediatric healthcare professionals and family members because the potential death of a child goes against the natural order. Compared with pediatric oncology professionals, parents are more likely to favor the use of aggressive treatment near the end of the child's life and consider hope a more important factor in treatment decision making [441]. As with adults, integrating palliative care early in the disease continuum can help overcome conflicts in treatment goals related to uncertainty of the prognosis [87]. Although aggressive treatment should be discontinued when it is of no benefit, the Patient Protection and Affordable Care Act of 2010 now allows for disease-directed treatment to be given concurrently with hospice [442]. (A life expectancy of 6 months is still a criterion for eligibility.) Clinicians usually recognize the lack of a realistic chance for cure before parents do and should talk openly with parents about discontinuing aggressive treatment and directing attention to enhancing the quality of life that remains for the child [443]. Members of the palliative care team should discuss treatment goals with the family, outline choices for interventions as the end of life draws near, and establish limits of care as the health status changes [435,444,445].
BARRIERS TO EFFECTIVE PALLIATIVE CARE FOR CHILDREN
|
The involvement of the young patient in discussions about
diagnosis, prognosis, and treatment goals is another important issue in the pediatric
population. Members of the healthcare team should collaborate with parents to determine how
much information should be shared with the child and how involved the child should be with
decision making; these determinations should be based on the child's intellectual and
emotional maturity [14,446]. Many parents wish to protect their child
by withholding information, but studies have shown that children often recognize the
seriousness of their illness and prefer open communication about their disease and prognosis
[447,448]. Such open exchange of information can help to avoid the fear of the
unknown and preserve the child's trust in his or her parents and/or family and caregivers
[448]. Thus, as much as possible and
appropriate, the child should be allowed to participate in discussions about the direction
of care [446].
When parents and clinicians involve the child in discussions, the language used should
be developmentally appropriate for the child and the clinician should check often to make
sure the child understands. Having the child repeat the information in his or her own words
is one way to assess comprehension. When the child demonstrates an understanding of the
illness and the prognosis, the emphasis should be on his or her preferences for care, and
the child's preferences should be given equal weight in the decision making [434,449,450]. The physician
should be an advocate for the child's preferences and decision [451].Symptom management is a key issue in the pediatric setting. One study indicated that 89% of dying children suffered "a lot" or "a great deal" from at least one symptom in their last month of life, and other end-of-life symptoms have often been intractable [443,452]. These problems are compounded by the fact that many clinicians who provide components of pediatric palliative care do not have confidence in their ability to manage end-of-life symptoms [437]. Inadequate training and the paucity of data on symptoms in children/adolescents contribute to this lack of confidence. Few studies have been done to determine the prevalence of symptoms in children/adolescents with life-limiting diseases, the studies that do exist are in the cancer setting, and evidence-based recommendations for interventions are not available.
According to reports of parents, the most common symptoms
during the last month of life are similar to those among adults; fatigue (weakness) and pain
have been the most frequently reported Table 27
[443,452,453]. When evaluating
fatigue in children, age is a consideration in how fatigue is discussed. Children think
about fatigue as a physical sensation, and adolescents think about fatigue as either
physical and/or mental tiredness [454].
Parents or other caregivers tend to report fatigue in terms of how it interferes with the
child's activities [454].
PREVALENCE OF SYMPTOMS AMONG CHILDREN IN THE LAST MONTH OF LIFE
| Symptom | Range in Prevalence |
|---|---|
| Pain | 73% to 92% |
| Fatigue/weakness | 86% to 91% |
| Anorexia | 68% to 81% |
| Reduced mobility | 61% to 76% |
| Nausea/vomiting | 57% to 63% |
| Constipation | 55% to 59% |
| Anxiety/depression | 45% to 48% |
| Dyspnea | 41% to 81% |
BEHAVIORS TO EVALUATE IN ASSESSING PAIN IN CHILDREN AND ADOLESCENTS
| Age of Child | Behaviors | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Infants (<1 year) |
| ||||||||
| Children (1 year and older) |
|
Pain management according to the WHO ladder has been found
to be effective for children/adolescents, and the NCCN has developed guidelines for
pediatric pain management [183,463,464]. Acetaminophen or NSAIDs, codeine, or oxycodone is recommended for pain
rated as 0-3 on a scale of 0 to 10; an acetaminophen/opioid combination, NSAIDs, oxycodone,
or morphine is recommended for pain rated as 4-6; and morphine or oxycodone is recommended
for pain rated as 7-10 [183]. It is
important to note that codeine may not be metabolized in 35% of children, and analgesia will
be ineffective in those children [183].
Pharmacokinetic data for pediatric medications are lacking, and physicians should consult
pediatric specialists for appropriate dosing of medications for symptom relief. Pain
medication should be complemented by age-appropriate nonpharmacologic interventions; touch,
massage, stroking, and rocking are effective for infants, toddlers, and young children, and
guided imagery, music and art therapy, play therapy, controlled breathing, and relaxation
techniques are beneficial for older children [455,465,466].
Attention to psychosocial support for the patient,
parents, and other family members is crucial in the pediatric setting. Although most parents
think that psychosocial issues should be discussed with the child's physician and would find
that discussion to be valuable, fewer than half of parents raise such topics [467]. Furthermore, parents report that only 15%
to 20% of physicians assess the family's psychosocial issues [467]. Among the psychosocial issues common in
children/adolescents and their families are ineffective family coping strategies, the
patient's relationships with peers, psychologic adjustment of healthy siblings, and
long-term psychologic adjustment for parents [446,465,468,469,470,471,472]. The palliative care team must carefully evaluate the patient and family
and provide resources and appropriate referrals.
CRITICAL CARE SETTING
Nearly 50% of patients who die in the hospital are in the
ICU for some period of time during the last 3 days of life [473,474]. In addition, 13% of patients admitted to the ICU with traumatic injury
will die [473]. The abruptness of a
traumatic injury is vastly different from the illness trajectories of life-limiting
diseases, and palliative care seems incongruous in the ICU, a high-technology environment of
the most aggressive life-prolonging treatments. The effective delivery of palliative care is
challenged by many factors inherent in the ICU setting, including inadequate training of
healthcare professionals, unrealistic expectations of patients and families,
misunderstanding of lifesaving measures, and a greater need for surrogate decision making
[473,475,476]. As these factors
gain greater recognition, there is a growing emphasis on integrating palliative care
elements into the care of patients with traumatic injury and/or patients in an ICU [119,473,475,476,477,478].
The focus on complex, lifesaving care in the ICU creates a
gap in providing relief of patients' symptoms. As in all settings, symptom assessment and
management must be a priority for ICU patients. It has been suggested that an
interdisciplinary palliative care assessment be carried out early in an ICU stay, preferably
within 24 hours after admission, with documentation of a comprehensive care plan within 72
hours after admission [476,479].
ICU patients are often young, and families expect
lifesaving procedures to be effective [476].
Misunderstanding of lifesaving measures has been reported to be an obstacle to high-quality
palliative care [480]. Clinicians and other
members of the team should maintain open, ongoing communication about the patient's
prognosis, the feasibility of recovery, and the burden of treatment. The sudden, often
catastrophic events that bring patients to the ICU compound stress and grief in family
members, whose psychosocial needs peak earlier than in other palliative care settings [476]. As a result, psychosocial and bereavement
support for families must begin early in the course of the patient's stay in ICU, preferable
within 24 hours after the patient's admission to the ICU [476].
The abruptness of traumatic injury or catastrophic illness
is also associated with the lack of preparation of advance directives for many patients.
There is often no time for planning during the short end-of-life process, and approximately
95% of patients are unable to participate in their care [476]. As a consequence, surrogates must make decisions, and such decisions
have been shown to correlate poorly with the preferences of patients [481,482].
The most critical decision in the ICU setting is the withdrawal of life-support
technologies. Withdrawal of mechanical ventilator support should be discussed with the
family or surrogate when they (or the patient) raise the issue or when the clinician
believes that the ventilator is no longer meeting the patient's goals or is more burdensome
than beneficial [119]. To ease the
discussion for families, the clinician should review the patient's status and care goals
before discussing withdrawal of support [119]. Once the decision has been made to withdraw life support, the physician should review
the process with family members, clarify the decision, ensure that the patient's spiritual
and cultural context are considered, and reassure the family that comfort measures will be
carried out [119,476]. Withdrawal of life support should then be
immediate, not carried out over hours or days, and established protocols for withdrawal of
mechanical ventilation should be followed [476,483].Recognizing the importance of palliative care in critical care settings, the Society of Critical Care Medicine developed recommendations calling for, among other improvements, [473]:
- Increased competency in all aspects of palliative care, including the use of sedatives, analgesics, and nonpharmacologic approaches to manage symptoms
- Improved communication with family
- Better understanding of the practical and ethical aspects of withdrawing life-sustaining treatment
- Development of comprehensive bereavement programs to support both families and the needs of the clinical staff
Many other initiatives have focused on improving palliative care in the ICU, primarily by having a palliative care team screen patients for potential consultation and increasing communication between the team and attending physicians. This approach increased the use palliative care consultation 113% in one study and from 5% to 21% in another study [24,485]. Another model that integrates palliative care into the ICU improved the quality of care and led to a higher rate of formalization of advance directives, better utilization of hospice, and a decreased use of nonbeneficial life-prolonging treatments [474].
CONCLUSION
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