A. Definition

1. "The study and management of patients with active, progressive, far advanced disease, for whom the prognosis is limited and the focus of care is the quality of life" [2]
2. World Health Organization (WHO) defines it as: [3]
   1. The active total care of patients whose disease is not responsive to curative treatment
   2. Control of pain, of other symptoms, and of psychological, social, and spiritual problems, is paramount
3. The goal of palliative care is the relief of suffering and the improvement of the quality of life for patients with advanced illness and their families

B. Philosophy and Purpose of Palliative Care

1. Represents a significant departure from curative/heroic medicine paradigm in which every effort is made to extend life regardless of its quality [4]
2. Palliative care for terminal patients acknowledges death as a natural, normal stage in life
3. Recognizes the end of life as a time to reconcile with loved ones and bring closure to relationships
4. Such reconciliation and closure requires the patient to be as comfortable as possible on physical, psychological, and spiritual levels
5. Caregivers can help patients "die a good death", with dignity, by providing care that enhances physical, psychological and spiritual comfort
6. As pailliative care is considered or instituted, establishing goals of care is crucial [1]
   1. Open-ended questions are very useful
   2. "What makes life worth living to you?"
   3. "Given the severity of your illness, what are the most important things for you to achieve?"

C. Where Palliative Care is Provided [5]

1. Medical/surgical or intensive care unit of acute care hospital
2. Dedicated hospice unit of acute care hospital
3. Residential free-standing hospice
4. At patient's or relative's home
5. Site of care should be identified based on availability, patient preferences and resources, family preferences, abilities, and resources

D. Issues Palliative Care Providers Must Address

1. Communication with patient is of critical importance
   1. Eye contact with patients
   2. Ask open-ended questions
   3. Respond to patient's affect
   4. Demonstrate empathy
2. Excellent commication reduces anxiety and improves patients' and families' satisfaction
3. Most patients are mainly concerned with pain reduction and quality of life
4. Key Focus Areas [10,11]
   1. Pain Management - caregivers must regularly assess level of pain
   2. Management of symptoms causing discomfort but not pain - particularly dyspnea
   3. Treatment of Depression
   4. Discontinuation of unnecessary therapies and interventions
   5. Environment
   6. Hydration and Nutrition
5. Timely use of medical care (procedures and medications) which improve patient comfort
6. Focus on psychological and spiritual state of both patient and family
7. Ensure that advance care planning, including completion of advance directes, occur

E. Pain Management - Background

1. Patients have an intense fear of unrelieved pain
2. Fear is grounded in reality [6]
   1. 40% of patients in one study died in severe pain
   2. 63% had difficulty tolerating physical or emotional symptoms
3. This suffering is Unnecessary
   1. Most pain at the end of life can be managed
   2. Opioids must not be withheld because of fears that agents may accelerate death [9]
4. Goals of pain management
   1. Adequate pain relief with least amount of sedation possible
   2. This permits patient to interact with family and friends

F. General Pain Management

1. For verbal patients, their perception of pain should guide therapy
2. For nonverbal patients, therapy is guided by distress signs including:
   1. Restlessness, agitation
   2. Moaning, grimacing
   3. Tachypnea and tachycardia
3. Physicians must set aside the following concerns:
   1. Addicting patients to pain medications
   2. Hastening death by administering an excessive dose of pain medications [9,10,11]
4. Family and friends must be advised as follows:
   1. Addiction is very uncommon among terminal patients with pain
   2. Pain medication has not been found to hasten death [2,7]

G. Specific Pain Management [7]

1. Approach must be tailored to source and type of pain
2. Consultation with pain management specialist may be very helpful
3. Pain medications should be administered regularly, not just as needed
   1. This will help prevent resistant pain syndromes
   2. Best to wake patient to administer pain medications
   3. Pain should not awaken patient
4. Patient should have constant access to additional pain medication for breakthrough pain
5. Pain management therapies include the following drug classes (may use in combination):
   1. Opioids - intravenous or subcutaneous or oral
   2. no maximum dose exists
      1. titrate to achieve good control of pain
   3. Nonsteroidal anti-inflammatory drugs (NSAIDs)
   4. Antidepressants
   5. Tricyclic Antidepressants (TCA) - pain control, increase appetite, adverse effects
      1. Selective serotonin reuptake inhibitors (SSRI) - rapid acting, reduce appetite
   6. Benzodiazepines - usually oral; intravenous forms available
   7. to prevent accumulation of toxic metabolites use short acting agents
      1. these include lorazepam, alprazolam, oxazepam
   8. Neuroleptics - haloperidol
   9. Mexilitine oral or intravenous lidocaine - appear effective for neuropathic pain [9]
6. For cancer pain, also consider the following interventions
   1. Radiation - external beam or implants
   2. Chemotherapy
   3. Surgical debulking
   4. Intravenous bisphosphonates for bone pain
   5. Radioactive strontium isotopes for bone pain
7. Treating certain infections may reduce pain
   1. Thrush
   2. Perirectal and vaginal candidiasis
   3. Perirectal herpes
   4. Wound infections

H. Management of Symptoms Causing Discomfort But Not Pain

1. Dyspnea
   1. Oxygen to reduce sense of dyspnea
   2. Opioids - improve pulmonary oxygenation and reduce sense of suffocation
   3. Benzodiazepines
   4. Titrate dose to achieve good response (not simply "adequate" response)
   5. Titration may require physician presence until control has been achieved
2. Gastrointestinal
   1. Diarrhea - unlikely to be a problem if opioids are used,
   2. Diarrhea may be treated with diphenoxylate 2.5-5.0 mg qid
   3. Constipation - much more common, especially with opioid therapy
   4. Malignant gastroduodenal obstruction - endocopic luminal stenting is very effective [9]
3. Constipation Treatment
   1. Wetting agents (detergent laxatives)
   2. Softening agents (mineral oil)
   3. Osmotic and stimulatory/secretory agents: lactulose, sorbitol, Mg2+, bisacodyl, cascara
   4. Avoid bulking agents
   5. Treat preemptively if constipation seems likely
   6. If impaction occurs, use softening and osmotic agents
   7. Use manual disimpaction only if necessary
4. Gastritis and/or Heartburn
   1. First line treatment with antacids and H2 blockers (famotidine, ranitidine, others) [7]
   2. Resistant disease treated with proton pump inhibitors (omeprazole or lansoprazole)
5. Nausea and Vomiting
   1. Treat aggressively with anti-emetics
   2. First line: chlorpromazine, metoclopramide (may cause dystonic reactions)
   3. Second line: scopolamine patch, droperidol
   4. Antihistamines- diphenhydramine, meclizine, promethazine (concern for disorientation)
   5. Very effective: ondansetron, granisetron [7]
   6. Dronabinol - also stimulates appetite
   7. If caused by obstruction, consider surgery to reverse
   8. Acupuncture treatments may help
6. Itching
   1. Topical moisturizers, steroid creams, colloidal oatmeal baths or compresses
   2. Antihistamines
   3. Systemic corticosteroids - may have adjunctive antinausea activity
   4. Cholestatic Pruritis: cholestyramine, ursodiol, naloxone, phenobarbital
7. Anxiety
   1. Benzodiazepines
   2. Selective serotonin reuptake inhibitors (SSRI) - particularly sertraline, escitalopram
   3. Reassurance
   4. Increased contact with loved ones
   5. Discussion of how pain or discomfort will be managed
   6. Spiritual counseling
   7. Discuss how death may occur and what it will be like
   8. Consider neuroleptics in very difficult cases
8. Depression / Dysphoria [10,11]
   1. Antidepressants should be used liberally to manage depression and anxiety
   2. Tricyclic antidepressants (mainly secondary amines) or SSRIs are used
   3. May have pain reduction and benzodiazepine reduction potential
9. Dry mouth
   1. Ice chips, popsicles, hard candy or throat lozenges
   2. Oral fluids as desired
   3. Lip balm
   4. Glycerine swabs
   5. Artificial saliva
   6. Review medications to see if any that cause / contribute to dry the mouth can be replaced
   7. Consider pilocarpine (cholinergic agent) in severe cases
10. Oral inflammation
    1. Ice chips, popsicles
    2. Viscous lidocaine
    3. Anesthetic spray
    4. Treat underlying infection, such as candida
    5. Analgesics
    6. Topical oral steroids
    7. Some oral steroids are available in a bioadhesive base that protect inflamed area from further irritation, such as Orabase®
11. Fever [2,6,7]
    1. Treat with antipyretics every two hours
    2. Alternate acetaminophen and nonsteroidal anti-inflammatory drugs
    3. For very severe fevers, oral or parenteral glucocorticoids may be used

I. Discontinuation of Unnecessary Therapies and Interventions

1. When patient has reached a stage at which cure is extremely unlikely, discuss discontinuation of therapies and interventions with patient and/or family
2. If therapy or intervention causes pain or discomfort but offers no palliative benefit, strongly consider discontinuing it
3. If intervention interferes with patient's ability to interact with family and friends, consider discontinuing (but do not compromise pain control or other comfort measures)
4. Therapies and interventions to consider discontinuing:
   1. Mechanical ventilation
   2. Dialysis
   3. Tube feeding
   4. Transfusions
   5. Blood draws for lab tests
   6. Radiologic examination
   7. Weighing patient
   8. Frequent turning
   9. Frequent monitoring of vital signs
   10. Intravenous and central lines
   11. Antibiotic therapy
   12. Use of cardiac monitor
   13. Use of pulse oximeter
   14. Aggressive respiratory or physical therapy [7]
5. Prepare patient and family for discontinuation of therapies or interventions
   1. Describe sequence of events leading to and following discontinuation
   2. Discuss likely effects on patient and how they will be managed
   3. Reassure patient and family frequently that they have made good decisions [3,4]

J. Hydration and Nutrition

1. Most patients report that they do not experience hunger or thirst at the end of their lives
2. This may be the result of endogenous opioids or metabolic ketosis
3. If a patient does not wish to eat or drink, he or she should not be forced to do so
4. Families may have conflicting feelings about having the patient eat and drink as they struggle with the imminent loss. This is normal and should be discussed openly
5. Hydration may contribute to bloating, and excessive secretions, which can give patient an unpleasant sensation of dyspnea, drowning or choking
6. Intravenous hydration may make it difficult for patient to interact as desired with family and friends, because tubes get in the way and "medicalize" the situation [2,7]

L. Environment

1. An environment as home-like as possible is desirable
2. Live green plants will soften a room and add a soothing focus for the patient
3. Offensive odors can be managed with
   1. Good hygiene
   2. Room sprays or potpourris that smell pleasant to the patient
   3. Sickness and medications may alter a patient's sense of smell
   4. Therefore, a pre-sickness favorite fragrance may actually now smell bad
   5. Elicit the patient's preferences
   6. Lavender, citrus, and peppermint essential oils may comfort and reduce nausea
4. Low lighting may reduce patient discomfort and anxiety
5. Music may be a distraction to pain and other discomfort and is highly recommended
6. Objects from home, such as pictures and clothing, contribute to a homelike environment
7. The family and friends of a dying person should be made comfortable
   1. This improves their ability to support the patient
   2. Also alleviates patient's concerns about comfort of family and friends

M. Psychological and Spiritual State of the Patient and Family

1. Provide multiple opportunities for patient and family to talk about what will happen as the patient dies
2. Provide opportunities for patient to speak with social workers, psychologists, clergy
3. Provide family and friends with opportunities to speak with social workers, psychologists, clergy
4. Introduce family (and friends) to bereavement counselors prior to the patient's death
5. Respect the need for friends and family to spend uninterrupted time with the patient but assure them that you are available if needed
6. Assess and accommodate patient's desire for time alone
7. Be willing to spend time with the patient yourself, during which you will do what the patient needs - sitting quietly, talking, touching or massaging, listening
8. Promise not to abandon the friends and family as the patient nears death
9. Promise the patient that he or she will not die alone

N. Persistent Suffering Despite Optimal Palliative Care [8]

1. 10-50% of patients in palliative care programs have significant pain in last week of life
2. In many cases, unrelieved pain is accompanied by loss of meaning, dignity, independence
3. Patients experiencing these conditions may request help to hasten death
4. Approaches include discontinuing hydration and nutrition, terminal sedation, physician- assisted suicide, and voluntary active euthanasia

O. Discontinuing Hydration and Nutrition [8]

1. Voluntary - patient is physically capable of oral intake but chooses to discontinue
2. Physician must ensure patient understands that discontinuing food and liquid will result in death
3. Physician must rule out depression
4. Physician must ensure that sedation and analgesia remain adequate
5. Death generally occurs within 1 to 3 weeks
6. See "Hydration and Nutrition" comments above (J)
7. Patient should occassionally be offered food and drink but refusal should be respected
8. Such opportunities to restart oral intake reinforce the voluntary nature of the act
9. A decision to discontinue food and liquid falls within the patient's right to refuse treatment
10. Poses no legal or ethical dilemma as long as patient is competent and not depressed

P. Terminal Sedation [8]

1. Patient is sedated to unconsciousness with barbiturates or benzodiazepines
2. Hydration, nutrition and all other interventions are withheld
3. Death generally occurs within days to weeks, depending on patient's condition
4. May be used when intolerable suffering cannot be relieved
5. Terminal sedation is intended to relieve suffering, not cause death
6. Because primary intent is to relieve suffering, the US Supreme Court has recognized it as ethical and legal
7. Can be used when patient is not competent, provided that family or surrogate agrees

Q. Physician-Assisted Suicide (PAS)

1. At patient's request, physician provides a prescription for drugs that can cause death
2. Drug of choice is usually a barbiturate
3. Patient must be able to make such a request
4. Physician has some moral responsibility because he or she provided prescription, but patient must fill prescription and take the drugs
5. Many patients who request such prescriptions never fill them but gain great comfort from the potential permanent relief of suffering that they can control
6. Illegal in most states but no physician has ever been successfully prosecuted for PAS
7. Legal in Oregon
8. Laws prohibiting PAS were not found unconstitutional by the Supreme Court in New York and Washington
9. Court encouraged public discussion of PAS through legislative and referendum processes

R. Voluntary Assisted Euthanasia (VAE)

1. Physician not only prescribes drugs to cause death but is also present to administer them
2. In the Netherlands, VAE is legal
3. Usually involves sedation to point of unconsciousness, then lethal injection of muscle- paralyzing agent such as curare
4. Advantages include a quick, controlled, dignified death, even for patients who have lost manual dexterity or ability to swallow
5. Presence of physician has several advantages
   1. Family feels less directly responsible
   2. Scheduled nature of procedure means family members can arrange to be present
   3. No suffering from unsuccessful suicide attempts can be avoided
6. Disadvantages - physicians may feel conflicted between doing no harm and causing death
7. Illegal in the United States and most other countries, with exception of Netherlands
8. Could be performed on patient involuntarily if patient was unable to communicate and family advocated for procedure

S. Safeguarding Against Abuse of Process and Physician Prosecution [8]

1. Society and the medical community are conflicted by desire to alleviate suffering but not cause death
2. System-wide scarcity of health care resources may result in pressure on patients or families without economic resources to hasten death
3. Families or other heirs may have a financial motivation to hasten death
   1. May want enquire about patient's estate
   2. Particularly if patient desires death less than family or guardians
4. Optimizing SItuation
   1. Avoid pressuring patients or families to hasten death
   2. Physicians avoid prosecution for relieving suffering by hastening or causing death
   3. The following conditions must exist:
   4. The patient must be receiving excellent palliative care but still be suffering
   5. Patient or guardian (for incompetent patients) must give true informed consent about options for ending unrelieved suffering
   6. Patient's diagnosis and prognosis must be clear
   7. Patient should be evaluated by at least 1 other physician specializing in palliative medicine
5. Patient should be evaluated by a psychiatrist if there are any doubts about the patient's mental health or competence
6. Documentation of each step along the decision path should be comprehensive
7. May want to bring case before hospital ethics committee
   1. Particularly where the right path is unclear
   2. To validate decisions

References

1. Morrison RS and Meier DE. 2004. NEJM. 350(25):2582
2. Meier DE, Morrison RS, Cassel CK. 1997. Ann Intern Med. 127(3):225
3. Billings JA and Block S. 1997. JAMA. 278(9):733
4. Fox E. 1997. JAMA. 278(9):761
5. Zerzan J, Stearns S, Hanson L. 2000. JAMA. 284(19):2489
6. Lynn J, Teno L, Joan M, et al. 1997. Ann Intern Med. 126(2):97
7. Brody H, Campbell ML, Faber-Langendoen K, Ogle KS. 1997. NEJM. 336(9):652
8. Quill TE, Lo B, Brock DW. 1997. JAMA. 278(23):2099
9. Goldstein NE. 2008. Ann Intern Med. 148(2):135
10. Qaseem A, Snow V, Shekelle P, et al. 2008. Ann Intern Med. 148(2):141
11. Lorenz KA, Lynn J, DySM, et al. 2008. Ann Intern Med. 148(2):147