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Palliative care: The last hours and days of life

Palliative care: The last hours and days of life
Authors:
Stephanie M Harman, MD
F Amos Bailey, MD
Anne M Walling, MD, PhD
Section Editor:
Eduardo Bruera, MD
Deputy Editor:
Jane Givens, MD, MSCE
Literature review current through: Feb 2022. | This topic last updated: Oct 11, 2021.

INTRODUCTION — Patients in the last hours and days of life may have physical suffering as well as significant emotional, spiritual, and social distress. Patients in their final days require careful symptom management, and families may need support and coaching as death approaches. Care continues through the death pronouncement, family notification of the death, and bereavement support.

This topic review will cover management of patients with a terminal disease who are in the final days to hours of life.

The comprehensive patient assessment and symptom assessment for palliative care patients, as well as an overview of managing pain and common non-pain symptoms in palliative care patients, hospice care, and issues surrounding stopping enteral and parenteral nutrition and hydration and ventilatory support, are addressed in detail elsewhere.

(See "Overview of comprehensive patient assessment in palliative care".)

(See "Hospice: Philosophy of care and appropriate utilization in the United States".)

(See "Approach to symptom assessment in palliative care".)

(See "Withholding and withdrawing ventilatory support in adults in the intensive care unit" and "Palliative care delivery in the home" and "Overview of managing common non-pain symptoms in palliative care".)

(See "Stopping nutrition and hydration at the end of life".)

(See "Withholding and withdrawing ventilatory support in adults in the intensive care unit" and "Palliative care delivery in the home" and "Overview of managing common non-pain symptoms in palliative care".)

(See "Withholding and withdrawing ventilatory support in adults in the intensive care unit" and "Palliative care delivery in the home" and "Overview of managing common non-pain symptoms in palliative care".)

ASSESSING END-OF-LIFE EXPECTATIONS AND PREFERENCES — Once a patient has begun the transition to the actively dying phase, we bring the patient (as able to participate) and family together to discuss their expectations and preferences for end-of-life care. In many cases, such discussions have already taken place earlier in the illness process; however, we maintain continued communication and dialogue in the dying phase in order to be flexible and responsive to evolving expectations and preferences. Our overall goals are to clarify a comfort-focused plan as appropriate, including a plan to maintain physical comfort and to address emotional, spiritual, and social needs of the patient and family.

Goals of care — We aim to communicate prognostic information with the patient/family in a clear but compassionate way that allows them to express their fears, hopes, and goals for end-of-life care [1-4]. Communication between caregivers and patients/families regarding goals of care is important to ensure that patients receive the care they would like [5,6]. A discussion of advance directives, issues regarding communicating prognosis in palliative care, and conducting family meetings for patients with a critical illness are discussed elsewhere. (See "Advance care planning and advance directives" and "Communication of prognosis in palliative care" and "Communication in the ICU: Holding a meeting with families and caregivers".)

Whenever possible, we ask patients and their families to describe what they consider a good death to facilitate identification of specific goals of care. The available literature suggests that patients and their families desire good symptom management and avoidance of suffering; care that is consistent with clinical, cultural, and ethical standards; and clear decision-making processes [1,7-9]. The Study to Understand Prognosis and Preferences for Outcomes and Risks of Treatments (SUPPORT) trial elucidated elements of quality care at the time of death among older adults (table 1) [10].

Goals of care discussions should address decreased oral intake at the end of life and the lack of evidence to support artificial feeding and hydration, as well as other physiologic changes as appropriate to the particular disease process. (See 'Preparing the family for physiologic changes in the dying process' below and "Stopping nutrition and hydration at the end of life".)

Cardiopulmonary resuscitation — We ensure that discussions about cardiopulmonary resuscitation (CPR) have taken place. Patients who are actively dying should not be subjected to CPR, as this constitutes a non-beneficial and potentially harmful medical treatment. Nonetheless, it may be an intervention that is expected by patients and their families, and as such it should be addressed through proactive communication. (See "Prognosis and outcomes following sudden cardiac arrest in adults" and "Palliative care: Issues in the intensive care unit in adults", section on 'CPR and families bearing witness'.)

Ideally, CPR discussions have occurred prior to the active dying phase, although this is often not the case [11]. Failure to address CPR earlier in the course of illness may force the discussion to take place during a crisis or oblige emergency services personnel to attempt resuscitation if called when the patient dies. Most hospice/home palliative care programs have policies requiring that expectations around CPR be addressed prior to enrollment, although not all programs require that a patient have a do-not-resuscitate (DNR) order to be eligible for hospice/palliative care services.

Deactivation of cardiac implantable electronic devices — For patients with cardiac implantable electronic devices, including permanent pacemakers (PPMs) and implantable cardioverter-defibrillators (ICDs), discontinuation at the terminal phase of illness is appropriate. This is discussed in detail elsewhere. (See "Management of cardiac implantable electronic devices in patients receiving palliative care".)

Place of death — We try to honor patient preferences for place of death and to minimize burdensome transitions between the home, hospital, and nursing home during the last days and weeks of life [12,13]. Timely referral to palliative care or hospice may facilitate a death in the preferred place [14-16].

Surveys indicate that most people would prefer to die at home, although many patients do not manage to do so [13,14,17-23]. Dying at home has been associated with greater family satisfaction, better patient outcomes, a higher “quality of death” as assessed by bereaved family members, and lower overall and financial caregiver burden [7,24-28].

Patients dying at home – For patients dying at home, we ensure that the patient and family are equipped for the physical, emotional, and practical considerations of caring for an actively dying patient. Home hospices can assist patients who are actively dying at the time of admission, although it is preferable to refer patients for home hospice earlier so that they may receive the full benefits of referral including the establishment of therapeutic relationships [1-3,29,30]. The provision of palliative care in the home, including care surrounding death, is discussed in detail elsewhere. (See "Palliative care delivery in the home" and "Palliative care delivery in the home", section on 'Death in the home'.)

Patients dying in the hospital For hospitalized patients who are actively dying, we try to either allow for transfer to home or to provide a private room or setting that will allow maximal family access and privacy as well as attentive nursing support for symptom management. Hospitalized patients who are unstable and likely to die in transport or very shortly afterward may not be good candidates for transfer to home.

Patients dying in the ICU – Death in the intensive care unit (ICU) is common, and although palliative care can be delivered successfully to patients in the ICU, there are some challenges [31]. The general environment, with continual monitoring of vital signs, instrumentation, environmental noise, lights, sleep deprivation, and limited family access, detracts from comfort. Decisions on whether to continue ICU care or not must be individualized, but in general, transfer out of the ICU setting is desirable unless the patient is so unstable that death could occur very quickly, in which case it may be better to liberalize visitation and allow support of the patient/family there.

A paradigm to assist in the delivery of palliative care to patients dying in the ICU has been developed that is termed the “ABCDs (attitudes, behaviors, compassion, and dialogue) of dignity-conserving care,” examples of which are provided in the table (table 2) [32,33]. Practical preparatory procedures to ensure patient comfort and dignity before withdrawal of life support are also available [32].

Palliative care issues in the ICU and the principles underlying withdrawal of life-sustaining treatment such as ventilators, dialysis, and nutritional support are addressed in detail elsewhere. (See "Palliative care: Issues in the intensive care unit in adults" and "Withholding and withdrawing ventilatory support in adults in the intensive care unit" and "Kidney palliative care: Withdrawal of dialysis" and "Stopping nutrition and hydration at the end of life".)

Organ donation — We have a discussion with the patient and family regarding the possibility of organ donation. Organ donation is discussed in detail elsewhere. (See "Evaluation of the potential deceased organ donor (adult)".)

Cultural and religious traditions — Awareness of and respect for the patient’s and family’s cultural traditions is an important aspect of care at the end of life, and it may impact communication about prognosis, symptom management, organ donation, and traditions at death and during bereavement. Cultural aspects of palliative care are discussed elsewhere. (See "Cultural aspects of palliative care".)

PREPARING THE FAMILY FOR PHYSIOLOGIC CHANGES IN THE DYING PROCESS — As patients approach death, we engage the family to educate them about the physiologic changes in dying process and to discuss potentially difficult decisions (eg, feeding, hydration) [34-36]. We often include pastoral care and social work providers for an interdisciplinary approach.

Preparation for physiologic changes are particularly important for families planning a home death to prevent surprise or panic. Salient points for education of families/friends who are sitting in vigil with a patient are listed in the table (table 3).

Discussion points include:

Decreased oral intake – The great majority of patients in the terminal phase of an illness experience reduced oral intake and impaired swallowing due to generalized weakness, sedation due to medications, or metabolic disturbances such as hypercalcemia. We attempt to anticipate concerns of the family regarding feeding, as they often experience high levels of emotional distress when the patient becomes unable to take food and fluids orally. We provide education and counseling on the normal dying process, keeping in mind that food and eating have strong cultural and emotional connections, and that the provision of information in a sensitive way reduces distress and potential conflicts.

We encourage families to provide mouth care with sponge sticks or offer sips of water, as these can improve patient symptoms of thirst and mouth irritation and are useful interventions for caregivers and family members who wish to be involved in the care process.

There is no evidence that improving caloric intake will improve strength, energy, or functional status, nor prolong survival in patients in the final days or weeks of advanced terminal illness. Neither parenteral nutrition nor tube feeding is recommended for nutritional support of patients in the dying phase of an advanced terminal illness due to their invasive nature [37].

Similarly, the possibility that dehydration may contribute to suffering and hasten death in patients at the end of life is not supported by the available data [38]. Artificial hydration may be considered on a case-by-case basis.

Dehydration in terminally ill patients may be associated with amelioration of certain symptoms such as choking, coughing, and chest congestion. In addition, there may be a benefit from decreased urine output (with less need for catheterization and bedwetting), decreased gastrointestinal fluid (with less vomiting, bloating, and diarrhea), and less peripheral edema.

Issues surrounding hydration and feeding in palliative care patients are further discussed elsewhere. (See "The role of parenteral and enteral/oral nutritional support in patients with cancer", section on 'End of life and cancer' and "Stopping nutrition and hydration at the end of life", section on 'Use of artificial nutrition' and "Care of patients with advanced dementia", section on 'Eating problems'.)

Breathing changes – We prepare families for changes in the breathing pattern which may indicate significant neurologic compromise and impending death. Breaths may become shallow and frequent with a diminishing tidal volume. Periods of apnea or a Cheyne-Stokes pattern of respirations (which is characterized by cyclic crescendo-decrescendo respiratory effort and airflow during wakefulness or sleep, without upper airway obstruction) may develop. This may be perceived by family members as breathlessness or impending suffocation. (See "Disorders of ventilatory control", section on 'Cheyne-stokes respiration'.)

Accumulation of upper airway secretions – Loss of the ability to swallow may result from weakness and decreased neurologic function. As the gag reflex and reflexive clearing of the oropharynx decline, secretions from the tracheobronchial tree accumulate. The buildup of saliva and oropharyngeal secretions may lead to gurgling, crackling, or rattling sounds with each breath, which some refer to as the “death rattle.” Increased airway secretions may interfere with a patient’s ability to sleep, worsen dyspnea, precipitate uncomfortable coughing spells, and predispose to infections. In addition, in the last stages of life, gurgling and crackling sounds that result from increased secretions can be distressing to the family. Treatment is discussed below. (See 'Airway secretions' below.)

Other physiologic changes include neurologic changes (eg, coma or delirium), signs of diminished perfusion (tachycardia, hypotension, peripheral cooling, cyanosis, mottling of the skin, and loss of peripheral pulses), loss of sphincter control, and the inability to close eyes. (See 'Delirium' below and 'Loss of sphincter control' below.)

We provide explicit encouragement to families to speak to, touch, and comfort their loved one. Although it is not possible to know the patient’s experience, it is often observed that a familiar voice, touch, and music may have a calming presence for some patients.

A helpful handout entitled “Preparing for Your Loved One’s Loss” is provided at the University of Alabama at Birmingham (UAB) BEACON Project website.

NURSING CARE ORDERS — For patients who are in a hospital or other setting where nursing care is provided and care is focused on comfort at the end of life, such care should be redirected from procedures and monitoring to an emphasis on assisting the patient's physical comfort while offering emotional and practical support to the patient/family. Some practical tips include:

Order a diet, as some patients may desire to taste food, along with an order for food to be permitted to be provided by the family. Consider a full liquid diet since it is more palatable (contains ice cream, sherbet, and jello) and easier to swallow than a clear liquid diet. However, once the patient is unable to swallow, oral intake should cease because of the risk of aspiration. (See "Swallowing disorders and aspiration in palliative care: Definition, consequences, pathophysiology, and etiology" and 'Preparing the family for physiologic changes in the dying process' above.)

Attention to mouth care is essential, and the family can be encouraged to give sips of water or moisten the patient’s mouth with a swab. Glycerine is no longer recommended as it is thought to cause drying.

Activity orders can allow for the patient to be up in a chair and use the bedside commode, as they are able. Family can be permitted to stay in the room. Avoid restraints.

Vital signs can be limited to those necessary with a minimum frequency as allowed by that unit’s policy. Alarms and excessive numeric data can distract from attending to the patient’s comfort and can cause unnecessary distress for the family. However, assessment and documentation of symptoms should be routine.

For patients with established intravenous (IV) lines, maintenance of the line can be helpful as a route for medications. One can also utilize a subcutaneous (SC) line for injecting small volumes either as needed or as a continuous infusion.

A bedside fan may aid in improving dyspnea in non-hypoxemic patients. If a hypoxemic patient consistently pulls off supplemental oxygen, and it does not seem to be aiding comfort, consider discontinuing oxygen. (See 'Dyspnea' below.)

Repositioning and hygiene orders can help with comfort. This may include placement of a Foley catheter for select patients. (See 'Loss of sphincter control' below.)

Invasive procedures (eg, enemas, manual disimpaction) for bowel care are rarely needed in the dying phase.

Avoidance of dry eyes can be aided by the use of ophthalmic lubricants such as hydroxypropyl methylcellulose ophthalmic solution or ointment (“artificial tears”) or physiologic saline.

Clinicians should review and discontinue orders that may no longer be necessary such as scheduled laboratory tests, radiographic studies, and telemetry or other monitoring [34,39-44].

RECOGNIZING THE DYING PATIENT — Recognition of the terminal phase of illness and accurate prognostication regarding death are important for patients, families, and health care providers. It allows for realistic expectations and the opportunity to plan for care at life's end. Late recognition of dying results in poor symptom management and suboptimal psychosocial and spiritual care for dying patients and their families [1,29,45,46].

We use clinical signs as the most reliable way to recognize that a patient is actively dying. This process is facilitated by continuous reevaluation of the clinical condition, close communication and sharing of information between caregivers and family members, and recognition of certain signs that tend to be present when patients are within days of death [47,48].

A list of signs and symptoms of the actively dying patient are provided in the table (table 4).

A few key signs include [39]:

The patient becoming bedbound

A change in the level of consciousness

Indifference to food and fluids

Inability to take oral medications

Certain signs are particularly suggestive of death within days. These include alterations in breathing, decreased urine output, nonreactive pupils, decreased response to verbal or visual stimuli, inability to close eyelids, and drooping of the nasolabial folds [49,50].

Prognosis scales can also be used to help identify dying patients. The Palliative Performance Scale (PPS) is an 11-point scale that ranges from 0 (death) to 100 percent (completely asymptomatic), based upon the patient’s function, oral intake, and cognitive status. It is widely used to estimate prognosis in cancer patients. The use of the PPS along with the presence or absence of drooping of the nasolabial folds has been used to predict three-day mortality in cancer patients (table 5) [51]. (See "Survival estimates in advanced terminal cancer".)

Guidelines for identifying the actively dying patient are available from the University of Alabama at Birmingham (UAB) BEACON Project website.

MANAGEMENT OF THE DYING PATIENT

Integrated care pathways — We encourage the use of integrated care pathways (ICPs), which are a method of implementing and monitoring best practice and incorporating accepted guidelines and protocols into health care settings; they detail the essential elements of care required to manage a specific clinical problem, and they ensure that the best available evidence is systematically integrated into care delivery [52,53]. Clinicians should be aware of whether their institution has a pathway for end-of-life care and make use of it if available.

The earliest widely used end-of-life ICP was the Liverpool Care Pathway [54-56]. Additional end-of-life care pathways have been developed and implemented in the United States [41,57-60] and Australia [61].

Our group has developed a set of comfort care plans (referred to as a Comfort Care Order Set [CCOS]) for care in the last hours or days of life as practiced in the home hospice setting, and modified for use in the acute care inpatient setting [62]. The order set is available at the University of Alabama at Birmingham (UAB) BEACON Project website.

The benefits of ICPs were addressed in a 2016 Cochrane review, which analyzed only one trial and concluded that there was limited evidence concerning the clinical, physical, psychological, or emotional effectiveness of end-of-life care pathways [63].

Benefits from use of the CCOS developed by our group (BEACON Project) were evaluated in a multisite implementation trial using a stepped wedge design in which the intervention was initiated sequentially between 2005 and 2011 in six United States Veterans Affairs (VA) Medical Centers [62]. Data were abstracted from the medical records of 6066 veterans dying in a 12-month period before (n = 3243) and after (n = 2824) implementation of the order set. Following the implementation of the order set, orders for opioid medication increased from 62 to 73 percent (odds ratio [OR] 1.39, 95% CI 1.09-1.76), more patients had palliative care consultations (31 versus 17 percent), and there were more orders for antipsychotic medications, benzodiazepines, medications to reduce airway secretions, and sublingual drug administration. There were also more advance directives (OR 1.47, 95% CI 1.15-1.88) and fewer nasogastric tubes (OR 0.71, 95% CI 0.53-0.96) at the time of death. However, the intervention did not decrease the proportion of deaths occurring in intensive care units (41 versus 37 percent), the proportion of deaths in which there was a do-not-resuscitate (DNR) order (70 versus 75 percent), or the use of restraints at the time of death (16 versus 13 percent).

Medication management

Eliminating non-essential medications — Polypharmacy is common in patients at the end of life and increases the possibility of drug-drug interactions, patient burden, and adverse events [64-68]. Non-essential and potentially inappropriate medications should be discontinued, particularly those being administered for primary and secondary prevention [42,43,69-76]. (See "Deprescribing", section on 'Goals of deprescribing'.)

Most medications can be stopped abruptly; however, certain medications should be gradually stopped (tapered) to prevent complications. As a general rule, this includes cardiovascular medications and those affecting the central nervous system (eg, beta blockers, clonidine, antidepressants, benzodiazepines). (See "Deprescribing", section on 'Approach to deprescribing'.)

Strategies for specific medication categories include the following:

Antihypertensives can usually be discontinued, as hypertension is usually not an issue with diminishing fluid intake.

Continuation of medications for angina or heart failure should be guided by clinical assessment of need; poor control of these conditions may adversely impact quality of life during the final weeks, although unlikely in the final days.

Management of patients with diabetes at the end of life must be tailored to the individual patient’s needs and the severity of the illness. In general, the risks and consequences of hypoglycemia are greater than those of hyperglycemia in patients at the end of life [77]; looser control of blood sugars is appropriate. Palliative care experts and the American Diabetes Association recommend relaxing glycemic control target levels for patients with diabetes and advanced disease, and eventual discontinuation of medications as patients near death to avoid hypoglycemia [78,79]. Sliding scale insulin, which requires painful finger sticks to assess blood sugars, should not be used in dying patients.

Anticonvulsants are generally maintained; however, the need for the initial prescription should be scrutinized; ongoing treatment may not be needed if the anticonvulsant was started for neuropathic pain or seizure prophylaxis. If the patient has a documented seizure disorder, it is imperative that an alternative route of such as intravenous (IV)/subcutaneous (SC) for lorazepam and levetiracetam or diazepam per rectum be instituted if and when the oral route is lost to prevent recurrence of seizures.

Non-oral routes of medication administration — We utilize non-oral routes to ensure timely access to needed medications, as dying patients may not be able to take medications by mouth.

Removal of existing central venous access devices or gastrostomy tubes should be carefully considered, as they may represent a very effective means of administered medications if the oral route is no longer feasible. On the other hand, a backup plan should be in place in case the gastrostomy tube is dislodged or IV access is lost, so that medications can be continued with minimal interruption.

In home or inpatient hospice settings, we generally use the sublingual route for most medications. In the hospital setting, institutional culture may dictate the use of SC route as the preferred option [80]. However, there are many non-oral routes for medication administration, which differ in their availability across care settings, acceptance by the patient and family, and in the specific drugs that can be administered by that route. In general, the least invasive route of administration should be chosen. The choice of route for pain medications is discussed in detail elsewhere. (See "Cancer pain management with opioids: Optimizing analgesia", section on 'Selecting the route of administration'.)

Some considerations regarding specific routes include the following:

Subcutaneous – A wide variety of medications can be administered SC using the parenteral formulation, either intermittently or by continuous infusion using a syringe driver. A site in the abdominal wall is preferred over an extremity site because there is a larger space for fluids to disperse, and peripheral absorption is less dependable as perfusion declines [81].

Continuous SC infusional drug administration has not been widely adopted in United States acute care hospitals, but it may be more common, especially for administration of analgesics, in home hospice [82-85]. This route is safe and just as effective as IV delivery but with a lower risk for infection and less cost [86]. Although many essential drugs, including opioids, anxiolytics, and antiemetics, can be converted to the SC route, SC options for some medications, such as anticonvulsants, are limited. Oral to SC equivalences for opioids are variable depending on the specific agent (table 6). We generally consider SC and IV administration of opioids as having the same potency but a difference in peak of effect (15 to 20 minutes for SC versus 6 to 10 minutes for IV).

Gastrostomy tube – If already in place, a gastrostomy tube is a convenient and well-tolerated means of administering medication. Many medications are available in liquid form, and some tablets can be crushed (but not long-acting formulations of opioids, and only some enteric coated medications).

Intravenous – If available, the IV route provides a reliable means of administering a medication with minimal patient burden. For this reason, central venous access lines should be left in place if the chosen site of care can support them. Oral to IV equivalences for opioids are variable depending on the specific agent (table 6).

Nasal and oral transmucosal – When patients are unable to swallow, liquid preparations may be given sublingually. Some medications are specifically formulated for buccal or sublingual use, such as fentanyl (table 7), buprenorphine, lorazepam, prochlorperazine, and the atypical antipsychotic olanzapine.

Medications whose injectable formulations can be absorbed by the buccal, sublingual, and nasal routes include the opioids fentanyl and sufentanil, midazolam, lorazepam, ketamine, and methadone [87-91].

Given that bioavailability will never exceed the IV route of administration, a general guideline for buccal, sublingual, or nasal dosing of a parenteral preparation is to start with the recommended IV dose and titrate to response [81].

Rectal – With the increasing numbers of medications that can be given by SC injection, transmucosally (buccal, sublingual, or nasal), and transdermally, the rectal route is used less often. Furthermore, turning the patient and inserting the medication may be physically uncomfortable and socially awkward for the family. Nonetheless, a variety of medications can be administered rectally (table 8), and for some medications, such as acetaminophen or diazepam for control of seizures in patients at home, the rectal route may be preferable [81].

Cautions include ensuring that the rectum is not blocked by stool or tumor and avoiding rectal administration of drugs in patients with severe thrombocytopenia, coagulopathy, or profound neutropenia with risk of infection.

A rectal medication delivery system, the Macy catheter [92], has been developed that permits medications (including tablets, which can be crushed and instilled into the catheter followed by a fluid “flush”) to be given without repositioning the patient; it is designed to come out easily when the patient has a bowel movement, and can be replaced by a trained nurse. If a Macy catheter is not available, medications may be administered similarly with a small bladder catheter. Care should be taken to ensure that the catheter does not interfere with bowel movements.

Transdermal – Transdermal systems are less useful in dying patients as absorption is reduced when circulation is centralized or patients are very cachectic. In addition, the use of a transdermal administration approach may not be optimal if dose changes are needed quickly. Some medications with potential transdermal use include fentanyl, buprenorphine, and scopolamine.

Management of specific symptoms — The following sections provide an overview of our approach to treating common symptoms. Further details on how to manage patients in the last hours to days of life is available at the University of Alabama at Birmingham (UAB) BEACON Project website.

Weakness and functional decline — Increasing overall burden of disease and diminishing functional reserve results in weakness and fatigue as well as a decreased tolerance for physical activity.

Practical approaches to address these changes include the following:

Patients may no longer be able to climb stairs in order to access a bedroom or toilet. Options include creating space for care on an accessible level or providing a portable toilet (commode), urinal, or bedpan.

Assistive equipment may be needed in the transition period between independent mobility and bed confinement to prevent falls. In the inpatient setting, encouraging and allowing family to stay with the patient may be comforting and promote safety. Call buttons and bed alarms may help staff respond to patients’ needs promptly so that falls can be avoided. In some patients, one-to-one sitters may be needed.

Once patients are less mobile or become bedbound, adequate cushioning on the bed and scheduled turning or repositioning can reduce the risk of skin ischemia and pain due to continued pressure on the same area, particularly over bony prominences.

We discuss with family members how to assist the patient with aspects of personal hygiene such as bathing or help with toileting, recognizing that these tasks may be socially uncomfortable. In the home, a home health aide is a major resource to the patient and family in assisting with these tasks. However, even if a home health care is available, it is best if family members are educated regarding transfers, turning, changing, feeding, and other personal care issues in order to ensure safety. Many family members want to provide some or even most personal care in the home and to assist in the inpatient settings. Therefore, basic instruction and a culture of permission to participate are important to foster.

Pain — Opioids are the mainstay of treating pain. We use a short-acting oral/sublingual opioid, usually morphine in the liquid concentrate form (20 mg/mL). Equivalent dosing for other mu-opioid agonists are provided in the table (table 6). Because patients who need opioids for symptom control may be unable to request them, the opioid order should be written as “offer, may refuse” or “as scheduled for symptoms” as opposed to "as needed.”

We generally stop sustained release opioids in the dying phase, as they may accumulate excessively. In addition, some patients may become increasingly sedated as they enter the dying process and no longer need these medications.

For opioid-naïve dying patients, we use a starting dose of 2.5 mg of morphine sulfate orally or sublingually or 2 mg morphine sulfate SC every two hours (offer, patient may refuse). Most patients will not need every dose.

For older or frail patients with pain, we start with a lower dose (1 mg morphine sulfate SC every two hours) but increase the dose quickly within the constrictions of appropriate dose escalation parameters (ie, no more than a 100 percent dose increase at a time) if symptom control is not provided, at which point oral or sublingual forms also can be used.

For patients who have been on chronic opioids, higher doses will likely be needed. We start with a dose of 10 to 15 percent of the basal daily requirement of opioid, calculated in morphine equivalents, given in oral, sublingual, or SC form every two hours on an “offer, may refuse” basis.

If a patient accepts every dose or still seems to be in pain, we increase the dose or even starting a morphine infusion if needed.

Morphine dosing every one hour orally or every 30 minutes for IV or SC routes may be used for patients who require dose escalation or careful titration. However, such frequent dosing may not be available in many clinical settings.

In general, we do not use intermittent IV dosing of opioids, even if an indwelling central venous line is available, since the half-life is very short and continuous infusion is often needed. Another issue with reliance on the IV route is that it is easy to lose peripheral access and then have a long delay in pain management because of difficulty regaining access.

Glucocorticoids can also be used to manage end-of=-life pain, especially in patients who have other systemic symptoms such as nausea and fever. (See 'Glucocorticoids for multiple symptoms' below.)

Additional information on the use of opioids to control cancer pain in palliative care patients, and the ethical issues that occasionally arise in patients who need strong analgesics at the end of life, is provided elsewhere. (See "Cancer pain management with opioids: Optimizing analgesia", section on 'Pure mu agonists commonly used for cancer pain' and "Cancer pain management with opioids: Optimizing analgesia", section on 'Management of breakthrough pain' and "Ethical considerations in effective pain management at the end of life".)

Dyspnea — The most common treatments for dyspnea include oxygen and opioids. Fan therapy (which uses a fan to blow air toward the patient’s face) has also been found to be effective at reducing dyspnea in patients with terminal cancer [93].

Oxygen – The use of supplemental oxygen should ideally be restricted to dyspneic patients who are hypoxemic as the routine administration of oxygen to patients who are near death is not supported by clinical evidence [94,95]. However, the administration of oxygen is a symbol of medical care for both patients and their families and may be associated with a placebo effect for both.

Some patients who are not initially hypoxemic may become so during the dying process. Since measurement of oxygen saturation is not routinely performed in the home hospice setting, a therapeutic trial of oxygen is not unreasonable for patients who become dyspneic.

If oxygen is used, nasal cannula are preferred over oxygen masks which are uncomfortable and restrictive and interfere with patient communication.

Opioids – For opioid-naïve dying patients with dyspnea, we use a starting dose of 2 mg of morphine sublingually or 2 mg morphine sulfate SC every two hours as needed. Nursing orders are written so that the morphine is offered to the patient (“offer, may refuse”), rather than as a “as needed” where the patient must ask for the medication. If a patient accepts every dose or still seems to be dyspneic, the dose should be increased.

For patients who have been on chronic opioids, we start with a dose that is 10 to 15 percent of the basal daily requirement of opioid, calculated in morphine equivalents, and offered every two hours. If a patient accepts every dose or still seems to be dyspneic, the dose is increased.

The general management of dyspnea in palliative care patients is discussed in detail elsewhere. (See "Assessment and management of dyspnea in palliative care".)

Nausea — In general, the new development of intractable nausea is uncommon in the dying phase; patients who have nausea at the end of life generally have a known condition causing the symptom. The management of nausea and vomiting based on patient characteristics and underlying illness is discussed in detail elsewhere. (See "Assessment and management of nausea and vomiting in palliative care", section on 'Management'.)

For patients with opioid-related nausea, opioid rotation is an appropriate choice. (See "Cancer pain management with opioids: Optimizing analgesia", section on 'How to perform opioid rotation'.)

For patients with gastroparesis, metoclopramide is a reasonable first choice. (See "Malignancy-associated gastroparesis: Pathophysiology and management", section on 'Management'.)

For patients with malignant bowel obstruction, symptomatic improvement may be seen with glucocorticoids, octreotide, and anticholinergics. (See "Palliative care of bowel obstruction in cancer patients".)

Radiation and chemotherapy-induced nausea is discussed elsewhere. (See "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults" and "Radiotherapy-induced nausea and vomiting: Prophylaxis and treatment".)

For treatment of patients who have nausea without an identifiable cause, we use haloperidol 1 mg orally or 0.5 mg SC/IV every six to eight hours as needed. For patients over age 65, we use a lower dose (0.5 mg orally or 0.25 mg SC/IV every eight hours). The total dose in 24 hours (for any patient) should be limited to no more than 6 mg oral or 3 mg IV/SC.

Alternatively, for treatment of nausea in patients with other systemic symptoms such as pain and fever, we use glucocorticoids. (See 'Glucocorticoids for multiple symptoms' below.)

The approach to nausea is limited by lack of high-quality evidence to support a specific antiemetic approach, with the exception of chemotherapy and radiation-related emesis [96].

Delirium — Delirium can present as confusion, restlessness, agitation, and/or day-night reversal [34,97]. Moaning, groaning, and grimacing may accompany the agitation and restlessness and may be misinterpreted as physical pain. A hypoactive form of delirium may present with decreased psychomotor activity.

The first step in management is to identify and eliminate any specific causes. Medications used in the dying patient may be contributory (eg, opioids, benzodiazepines, glucocorticoids, neuroleptics, and medications to manage secretions) [98]. Delirium can also be caused by withdrawal from certain medications or substances (opioids, benzodiazepines, selective serotonin reuptake inhibitors [SSRIs], alcohol). Delirium prevention and treatment are discussed in detail elsewhere. (See "Delirium and acute confusional states: Prevention, treatment, and prognosis".)

For most patients with terminal delirium, it is not possible to find a reversible cause. Addressing the delirium involves educating the family about what to expect and offering strategies for caregivers to provide a calming presence and gentle redirection. For patients in whom delirium manifests with agitation or distress, we typically recommend pharmacologic treatment, despite limited evidence of benefit from high-quality clinical trials to inform the optimal drug therapy [99-101].

In patients with terminal delirium, we use haloperidol as standard therapy, especially when there is evidence of psychomotor agitation, delusions, or hallucinations. Typical doses are 1 to 2 mg of oral haloperidol or 1 mg SC/IV with repeat doses every two hours until settled, then every six to eight hours as needed, titrated against symptoms. A 50 percent dose reduction is appropriate for older or very frail adults.

Alternative therapies include olanzapine or risperidone, both of which are available in an oral dissolving formulation. However, the regular oral formulation is available in a lower dose, and we would initiate therapy with this in patients who can take oral medications (olanzapine 2.5 mg, risperidone 0.25 mg).

For patients with persistent agitated delirium despite the use of haloperidol (or other antipsychotic), we add lorazepam (1 mg orally or 0.5 mg SC/IV every four to six hours as needed) [102,103].

For patients with Parkinson disease or parkinsonian side effects from antipsychotics, quetiapine is the preferred antipsychotic. We use a reduced dose of 12.5 mg daily, or 25 mg if the patient is very agitated. Alternatively, we use lorazepam (1 mg orally or 0.5 mg SC/IV every four to six hours as needed) rather than any antipsychotic.

Further discussion of delirium management is provided elsewhere. (See "Overview of managing common non-pain symptoms in palliative care", section on 'Delirium' and "Management of psychiatric disorders in patients with cancer", section on 'Delirium'.)

Anxiety and agitation — In our experience, most patients with anxiety or terminal agitation can be comfortably managed with lorazepam, with intermittent doses titrated up as needed (starting at 1 mg orally or SC/IV every six hours as needed) or even as a continuous infusion.

In patients with restlessness or agitation, it may be difficult to discern whether symptoms are due to a terminal delirium or arise from other psychological or physical distress. For practical purposes, if a patient has been treated for delirium and is still agitated and distressed, the addition of a benzodiazepine such as lorazepam may be helpful.

Continuous IV infusion of midazolam has been popular among some palliative care practitioners for severe sustained symptoms, allowing for rapid titration of doses, but institutional policies prohibit its use in many settings. (See "Palliative sedation".)

There is insufficient evidence in the literature to draw any conclusions about the effectiveness of drug therapy for treatment of anxiety at the end of life [104-106].

Seizures — Seizures may occasionally occur as a new symptom at the end of life, such as in patients who have brain metastases or other neurologic injury that results in a new seizure focus. For those who are imminently dying, parenteral lorazepam (1 mg SC/IV every four to six hours as needed) can be used to control seizures and to prevent them over the next hours or days.

For patients with a known seizure disorder, we recommend continuing known, effective anticonvulsants as long as the patient is able to swallow medication. However, clinicians should be prepared to transition to non-oral routes of medication. This plan should be individualized but can include IV or SC lorazepam, rectal diazepam, or rectal or SC phenobarbital. The choice of management will be guided by what the location of care can support. (See "Seizures in patients with primary and metastatic brain tumors", section on 'Seizures at the end of life'.)

Nonconvulsive status epilepticus, a potentially reversible cause of altered mental status, is discussed elsewhere [107]. (See "Nonconvulsive status epilepticus: Classification, clinical features, and diagnosis".)

Airway secretions — For many patients, troublesome airway secretions occur late in the dying process. Discontinuing non-essential IV fluids or enteral feedings, combined with positioning the patient on their side, may help to move the secretions out of the airway. This can be a distressing symptom for caregivers and loved ones, and discussion and reassurance that this is part of the natural dying process can often address these concerns. Despite limited evidence of pharmacologic treatment efficacy, it is reasonable to consider a trial of pharmacologic treatment while carefully watching for side effects particularly if the symptom is bothersome [108-110]. Appropriate agents are listed in the table (table 9).

If a trial of pharmacologic treatment is undertaken, we use glycopyrrolate (0.2 mg SC every four to six hours). Providers should be aware that the drying side effects of anticholinergic agents may contribute to added discomfort, and these medications should be reconsidered if side effects are noted.

Glycopyrrolate, a quaternary amine, is preferred over atropine, scopolamine hydrobromide, or other tertiary amines because of fewer central effects as the quaternary structure impedes entry across the blood brain barrier [111-113].

Outside of the United States, scopolamine (hyoscine) butylbromide may be used; like glycopyrrolate, it is also a quaternary compound and has fewer central side effects compared with scopolamine (hyoscine) hydrobromide. Scopolamine (hyoscine) butylbromide doses are not equivalent to those of scopolamine (hyoscine) hydrobromide.

Some patients (eg, those with advanced head and neck cancer) may benefit from suctioning to clear excessive secretions if they have a lot of drooling. However, we avoid deep suctioning.

The evidence demonstrating benefit from pharmacologic interventions to dry secretions had been limited due in part to the challenges with conducting randomized controlled trials at the end of life. A 2008 Cochrane review, a subsequent trial of sublingual atropine versus placebo, and two systematic reviews concluded that there is no evidence that any intervention is superior to placebo for the treatment of “death rattle” [105,108,114,115]. However, in a 2021 trial conducted in six hospices in the Netherlands, patients (n = 162) entering the dying phase were randomized to receive either prophylactic subcutaneous scopolamine butylbromide 20 mg four times a day, or placebo [116]. The primary outcome of death rattle occurred in a smaller percentage of patients in the scopolamine group than the placebo group (13 versus 27 percent, 95% CI 2-27). These more recent data support the practice of using anticholinergics for the management of death rattle as described above.

Loss of sphincter control — Loss of sphincter control in the last hours of life may lead to incontinence of urine and/or stool, which may be distressing to patients and family members. A urinary catheter may minimize the need for frequent changing and cleaning and reduce demand on caregivers. However, catheters can be viewed as a form of restraint, and their use should be carefully considered. Use of a catheter may not be necessary if urine flow is minimal and can be managed with absorbent pads.

In older men, urinary retention from benign prostatic hyperplasia (BPH) may be exacerbated by the use of medications with anticholinergic effects, and use of a catheter may prevent pain and distress. Ultrasound bladder scanners may be used by nursing staff to determine if urinary retention is present, thus avoiding diagnostic catheterization.

Profuse intractable diarrhea may be managed with a rectal tube, although this is rarely necessary.

Glucocorticoids for multiple symptoms — Glucocorticoids are ideal medications for pain, fever, or nausea in dying patients within the last week of life and may reduce the need for other medications [41].

We use dexamethasone 4 to 16 mg orally, SC, or IV daily, equivalent to prednisone 15 to 60 mg daily. Given the long half-life, doses can be given once daily in the morning or in divided doses early in the day to avoid insomnia at night. Compared with other glucocorticoids, dexamethasone is less likely to cause fluid retention since it has no mineralocorticoid effects.

A daily dose of 4 to 8 mg is reasonable for most patients; however, if needed for maximal antiinflammatory effect, such as for patients with brain metastases or epidural spinal cord compression, a higher dose may be used. (See "Management of vasogenic edema in patients with primary and metastatic brain tumors", section on 'Dexamethasone dose and schedule' and "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Glucocorticoids'.)

In patients who have been on chronic glucocorticoids for other illnesses such as chronic obstructive pulmonary disease (COPD) or chronic immunosuppression, we generally continue their treatment, with conversion to dexamethasone because of the availability of multiple routes of administration.

Managing infections and use of antimicrobials — Infections and febrile episodes are common complications experienced by terminally ill patients, and they may represent a terminal event. Antimicrobials are commonly prescribed to dying patients, at times in the absence of clinical symptoms, to support bacterial infection [117-121].

Potential benefits such as prolongation of survival and/or symptom relief may motivate the prescribing of antimicrobials to terminally ill patients. However, the available evidence to support either benefit is sparse [122,123].

Possible adverse consequences of antimicrobials include drug reactions, drug-drug interactions, infection with Clostridioides difficile, the acquisition of multidrug-resistant organisms (an increasing public health concern), and the burden imposed by evaluation and treatment of suspected infections at the end of life.

To the extent possible, decision-making about antimicrobial use at end of life should be undertaken as a component of advance care planning and treatment preferences documented in advance directives, and/or while discussing goals of care. (See "Advance care planning and advance directives" and "Discussing goals of care".)

In the absence of advance directives, the decision to use antimicrobials at the end of life must be individualized, and the approach taken should align with the patient’s stated goals of care. The risks and burdens of evaluating and treating an infection should be discussed, along with the possible benefits, while acknowledging the lack of high-quality outcomes data. If the patient’s goal is to live as long as possible or to live to a specific date (a life event like a graduation, birth of a child, etc), and the potential benefits of antimicrobial use are felt to outweighs its burdens, a clinical assessment for suspected infection, with administration of antimicrobials by the least invasive route, is reasonable if there is adequate evidence to support a bacterial infection. If the decision is made not to pursue antibiotics, around-the-clock acetaminophen or glucocorticoids may be beneficial if the patient has rigors or chills. (See 'Glucocorticoids for multiple symptoms' above.)

Patients dying in isolation — Patients with highly contagious illnesses (eg, ebola, coronavirus disease 2019 [COVID-19]) or patients who are hospitalized in the context of strict visitation policies, as has been common during the COVID-19 pandemic, may be forced to spend time at the end of life in isolation, separated from their loved ones, and with limited clinical staff presence. Important goals for palliative care clinicians in such situations include maintaining a therapeutic connection with the patient and the family and facilitating ways for patients to communicate with their loved ones, especially as death approaches. Bereavement support for the family is also critical, as the stress of having a loved one die alone may increase the risk of complicated grief [124,125].

COVID-19 communication resources — The COVID-19 pandemic has led to the development of approaches and resources to meet the challenges of providing support to patients and families in isolation. Many of these rely on the use of telecommunication.

VitalTalk has created a COVID communication resource (with translation into many languages) which includes information on how to coach a family member to say goodbye over the telephone or over video-based forms of telecommunication (zoom, Skype, FaceTime, etc). In addition, they have created training videos to help clinicians learn or improve these skills.

Strategies for addressing potential communication barriers in telephone or video encounters include [126]:

Prepare for the interaction by assessing the patient’s ability to communicate, establishing a preferred language, and addressing any technical, hearing, or visual impairments prior to the visit to ensure successful participation.

Invite family or other loved ones to the meeting, as appropriate.

As the clinician, find a quiet space to hold the conversation, one in which it is safe to remove any masks or face shields. If using video, look directly at the camera. Silence any beepers or other noisemaking devices.

Consider acknowledging the difficulties of the situation, including the limitations inherent in the chosen method of communication, and express the wish to be present with the patient in person.

Further information on discussing serious news is presented elsewhere. (See "Discussing serious news".)

Palliative sedation for patients with refractory symptoms — Palliative sedation refers to use of non-opioid drugs, including benzodiazepines, barbiturates, and propofol, to control refractory symptoms (eg, pain, dyspnea, agitated delirium) that have been assessed and treated by an interdisciplinary team (palliative physician, pain expert, psychosocial counselor, and chaplain) and have not responded to conventional symptom management. Palliative sedation may also be considered for acute symptoms that are of sufficient severity and/or trajectory as to require prompt intervention to relieve distress in patients who are actively dying (death expected in hours to days). Cases where acute distressing events might occur include massive bleeding, grand mal seizures, or acute airway obstruction; refractory symptoms that may require the use of palliative sedation include nausea, agitated delirium, pain, or refractory dyspnea. Further discussion on palliative sedation is covered separately. (See "Palliative sedation".)

WHEN DEATH OCCURS — In the United States, local regulations generally require that a physician or nurse pronounce death and complete a death certificate. For patients who die in the hospital, the covering physician is generally summoned to pronounce the patient. The family should be notified if they are not present, and if appropriate they can be approached about autopsy or organ donation. (See 'Organ donation' above.)

If hospice is involved, the family should be directed to call the hospice, and a nurse will generally come to the home and pronounce the patient. A local coroner may investigate any death and may perform an autopsy but generally will not become involved when the death was expected and was managed by a hospice.

Most patients who have an anticipated death in the home are cared for by a home hospice agency. At the time of death, families are instructed to call the hospice program instead of 911. Despite these instructions, emergency medical services (EMS) may be called by a distraught family member or caregiver. Most states have implemented a POLST (Physician Orders for Life-Sustaining Treatment) or similar system to document patient preferences and have medical orders regarding life-sustaining treatments that can be honored in any location. EMS and other first responders are trained to look for this kind of documentation on the refrigerator door. Alternatively, the family could present the documents to EMS when they arrived. We recommend family/caregivers take photos of these documents with their phone for easy retrieval. If a patient/family has not completed such a document, they should be encouraged to do so.

Different procedures are used in other countries.

Guidelines for pronouncement of a death are provided at the University of Alabama at Birmingham (UAB) BEACON project website. Information regarding death certificates and death investigations is provided elsewhere. (See "Death certificates and death investigations in the United States".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Palliative care".)

SUMMARY AND RECOMMENDATIONS

Patients in the last hours and days of life may have physical suffering as well as emotional, spiritual, and social needs. Assessing end-of-life expectations and determining goals of care with the patient and family is critical to providing appropriate care. A discussion of cardiopulmonary resuscitation (CPR), if not already addressed, is essential. (See 'Assessing end-of-life expectations and preferences' above.)

We aim to honor patient preferences for place of death. For patients dying at home, we ensure that the patient and family are equipped for the physical, emotional and practical considerations. Palliative care can be delivered to patients who are dying in the hospital or intensive care unit (ICU), although there are inherent challenges. (See 'Place of death' above and "Palliative care: Issues in the intensive care unit in adults" and "Palliative care delivery in the home", section on 'Death in the home'.)

We educate the family about the normal dying process, such as changes in breathing patterns, airway secretions, and other physiologic changes, to assist them in being emotionally prepared to stay with their loved one through the time of death (table 3). A helpful guide to preparing for the death of a loved one is available at the University of Alabama at Birmingham (UAB) BEACON Project website. (See 'Preparing the family for physiologic changes in the dying process' above.)

We discuss the normal decrease in oral intake at the end of life and the lack of evidence supporting artificial feeding or hydration. (See 'Preparing the family for physiologic changes in the dying process' above.)

We discontinue all non-essential medications and ensure that necessary medications are delivered by non-oral routes of administration. (See 'Medication management' above.)

Certain clinical signs can be used to identify patients within days of death (table 4). (See 'Recognizing the dying patient' above.)

Common symptoms at the end of life include pain, dyspnea, anxiety or agitation, delirium, and difficulty handling airway secretions. These symptoms can usually be treated with a short list of medications. An end-of-life integrated care pathway (ICP) such as a Comfort Care Order Set (CCOS) may be available at health care institutions and can support optimal management. (See 'Management of specific symptoms' above and 'Integrated care pathways' above.)

Rarely, for patients with refractory symptoms (eg, pain, dyspnea, agitated delirium), that have been assessed and treated by an interdisciplinary team (palliative physician, pain expert, psychosocial counselor, and chaplain) and have not responded to conventional symptom management, palliative sedation can be considered. (See 'Palliative sedation for patients with refractory symptoms' above and "Palliative sedation".)

Nursing care for the actively dying with a comfort-oriented medical plan should be redirected from uncomfortable procedures and unnecessary monitoring to an emphasis on assisting the patient's physical comfort while offering emotional and practical support to the patient/family. (See 'Nursing care orders' above.)

Guidelines for pronouncement of a death are available at the UAB BEACON Project website.

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  74. van Nordennen RT, Lavrijsen JC, Vissers KC, Koopmans RT. Decision making about change of medication for comorbid disease at the end of life: an integrative review. Drugs Aging 2014; 31:501.
  75. Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontinuation of multiple medications in older adults: addressing polypharmacy. Arch Intern Med 2010; 170:1648.
  76. Graham J. End-of-Life medications draw more attention, greater scrutiny. JAMA 2015; 313:231.
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  78. Angelo M, Ruchalski C, Sproge BJ. An approach to diabetes mellitus in hospice and palliative medicine. J Palliat Med 2011; 14:83.
  79. Standards of Medical Care in Diabetes-2017: Summary of Revisions. Diabetes Care 2017; 40:S4.
  80. Bartz L, Klein C, Seifert A, et al. Subcutaneous administration of drugs in palliative care: results of a systematic observational study. J Pain Symptom Manage 2014; 48:540.
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  83. Herndon CM, Fike DS. Continuous subcutaneous infusion practices of United States hospices. J Pain Symptom Manage 2001; 22:1027.
  84. Hunt R, Fazekas B, Thorne D, Brooksbank M. A comparison of subcutaneous morphine and fentanyl in hospice cancer patients. J Pain Symptom Manage 1999; 18:111.
  85. Paix A, Coleman A, Lees J, et al. Subcutaneous fentanyl and sufentanil infusion substitution for morphine intolerance in cancer pain management. Pain 1995; 63:263.
  86. Justad M. Continuous subcutaneous infusion: an efficacious, cost-effective analgesia alternative at the end of life. Home Healthc Nurse 2009; 27:140.
  87. Gardner-Nix J. Oral transmucosal fentanyl and sufentanil for incident pain. J Pain Symptom Manage 2001; 22:627.
  88. McDonough JH, Van Shura KE, LaMont JC, et al. Comparison of the intramuscular, intranasal or sublingual routes of midazolam administration for the control of soman-induced seizures. Basic Clin Pharmacol Toxicol 2009; 104:27.
  89. Anderson GD, Saneto RP. Current oral and non-oral routes of antiepileptic drug delivery. Adv Drug Deliv Rev 2012; 64:911.
  90. Davis MP. Recent development in therapeutics for breakthrough pain. Expert Rev Neurother 2010; 10:757.
  91. Spaner D. Effectiveness of the buccal mucosa route for methadone administration at the end of life. J Palliat Med 2014; 17:1262.
  92. Indformation on the Macy catheter available online at http://hospicorp.com/the-macy-catheter/about-the-macy-catheter (Accessed on March 25, 2015).
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  94. Campbell ML, Yarandi H, Dove-Medows E. Oxygen is nonbeneficial for most patients who are near death. J Pain Symptom Manage 2013; 45:517.
  95. Abernethy AP, McDonald CF, Frith PA, et al. Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial. Lancet 2010; 376:784.
  96. Davis MP, Hallerberg G, Palliative Medicine Study Group of the Multinational Association of Supportive Care in Cancer. A systematic review of the treatment of nausea and/or vomiting in cancer unrelated to chemotherapy or radiation. J Pain Symptom Manage 2010; 39:756.
  97. Moyer DD. Review article: terminal delirium in geriatric patients with cancer at end of life. Am J Hosp Palliat Care 2011; 28:44.
  98. Clegg A, Young JB. Which medications to avoid in people at risk of delirium: a systematic review. Age Ageing 2011; 40:23.
  99. Boettger S, Jenewein J, Breitbart W. Haloperidol, risperidone, olanzapine and aripiprazole in the management of delirium: A comparison of efficacy, safety, and side effects. Palliat Support Care 2015; 13:1079.
  100. Crawford GB, Agar M M, Quinn SJ, et al. Pharmacovigilance in hospice/palliative care: net effect of haloperidol for delirium. J Palliat Med 2013; 16:1335.
  101. Agar MR, Lawlor PG, Quinn S, et al. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial. JAMA Intern Med 2017; 177:34.
  102. Hui D, Frisbee-Hume S, Wilson A, et al. Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial. JAMA 2017; 318:1047.
  103. Hui D, Hess K, Dibaj SS, et al. The minimal clinically important difference of the Richmond Agitation-Sedation Scale in patients with cancer with agitated delirium. Cancer 2018; 124:2246.
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  108. Lokker ME, van Zuylen L, van der Rijt CC, van der Heide A. Prevalence, impact, and treatment of death rattle: a systematic review. J Pain Symptom Manage 2014; 47:105.
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Topic 14241 Version 62.0

References

1 : In search of a good death: observations of patients, families, and providers.

2 : How does the timing of hospice referral influence hospice care in the last days of life?

3 : What impact do setting and transitions have on the quality of life at the end of life and the quality of the dying process?

4 : Palliative care in the final days of life: "they were expecting it at any time".

5 : A controlled trial to improve care for seriously ill hospitalized patients. The study to understand prognoses and preferences for outcomes and risks of treatments (SUPPORT). The SUPPORT Principal Investigators.

6 : Difficult end-of-life treatment decisions: do other factors trump advance directives?

7 : Factors important to patients' quality of life at the end of life.

8 : Factors important to patients' quality of life at the end of life.

9 : A good death from the perspective of palliative cancer patients.

10 : Factors considered important at the end of life by patients, family, physicians, and other care providers.

11 : Do-not-resuscitate orders in the last days of life.

12 : End-of-life transitions among nursing home residents with cognitive issues.

13 : Site of Death, Place of Care, and Health Care Transitions Among US Medicare Beneficiaries, 2000-2015.

14 : The Determinants of Dying Where We Choose: An Analysis of Coordinate My Care.

15 : Recognising patients who will die in the near future: a nationwide study via the Dutch Sentinel Network of GPs.

16 : Association between referral-to-death interval and location of death of patients referred to a hospital-based specialist palliative care service.

17 : Place of care in advanced cancer: a qualitative systematic literature review of patient preferences.

18 : The preferred place of last days: results of a representative population-based public survey.

19 : The preferred place of last days: results of a representative population-based public survey.

20 : The preferred place of last days: results of a representative population-based public survey.

21 : Place of death and its determinants for patients with cancer in Singapore: an analysis of data from the Singapore Cancer Registry, 2000-2009.

22 : Place of death for people with noncancer and cancer illness in South Australia: a population-based survey.

23 : Did Ontario's end-of-life care strategy reduce acute care service use?

24 : Good death inventory: a measure for evaluating good death from the bereaved family member's perspective.

25 : Place of death and the differences in patient quality of death and dying and caregiver burden.

26 : Family satisfaction with end-of-life care for cancer patients in a cluster randomized trial.

27 : Effectiveness and cost-effectiveness of home palliative care services for adults with advanced illness and their caregivers.

28 : Place of death: correlations with quality of life of patients with cancer and predictors of bereaved caregivers' mental health.

29 : Older persons' preferences for site of terminal care.

30 : Determinants of congruence between the preferred and actual place of death for terminally ill cancer patients.

31 : Determinants of congruence between the preferred and actual place of death for terminally ill cancer patients.

32 : Dying with dignity in the intensive care unit.

33 : Dignity and the essence of medicine: the A, B, C, and D of dignity conserving care.

34 : Competency in end-of-life care: last hours of life.

35 : A systematic review of the prevalence of signs of impending death and symptoms in the last 2 weeks of life.

36 : Supporting relatives and carers at the end of a patient's life.

37 : The last days of life: symptom burden and impact on nutrition and hydration in cancer patients.

38 : Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebo-controlled randomized trial.

39 : Care of the dying patient: the last hours or days of life.

40 : ABC of palliative care. The last 48 hours.

41 : Improving processes of hospital care during the last hours of life.

42 : Terminal care: the last weeks of life.

43 : End-of-life care for the hospitalized patient.

44 : Symptom prevalence, characteristics and distress in a cancer population.

45 : Dying in an acute hospital setting: the challenges and solutions.

46 : End-of-life decision making for cancer patients in different clinical settings and the impact of the LCP.

47 : Importance of functional measures in predicting mortality among older hospitalized patients.

48 : Risk factors for early and late mortality in hospitalized older patients: the continuing importance of functional status.

49 : Clinical signs of impending death in cancer patients.

50 : Bedside clinical signs associated with impending death in patients with advanced cancer: preliminary findings of a prospective, longitudinal cohort study.

51 : A diagnostic model for impending death in cancer patients: Preliminary report.

52 : Integrated care pathways: effective tools for continuous evaluation of clinical practice.

53 : Integrated care pathways.

54 : Achieving a good death for all.

55 : Achieving a good death for all.

56 : The end of the Liverpool Care Pathway?

57 : Improving end-of-life care: development and pilot-test of a clinical pathway.

58 : Pilot of a pathway to improve the care of imminently dying oncology inpatients in a Veterans Affairs Medical Center.

59 : Missed opportunities: use of an end-of-life symptom management order protocol among inpatients dying expected deaths.

60 : Impact of standardized palliative care order set on end-of-life care in a community teaching hospital.

61 : The development and implementation of the pathway for improving the care of the dying in general medical wards.

62 : Intervention to improve care at life's end in inpatient settings: the BEACON trial.

63 : End-of-life care pathways for improving outcomes in caring for the dying.

64 : Continuation of non-essential medications in actively dying hospitalised patients.

65 : The Burden of Polypharmacy in Patients Near the End of Life.

66 : Polypharmacy in patients with advanced cancer and the role of medication discontinuation.

67 : Analysis of drug interactions at the end of life.

68 : Inappropriate prescribing of preventative medication in patients with life-limiting illness: a systematic review.

69 : Reducing potentially inappropriate medications in palliative cancer patients: evidence to support deprescribing approaches.

70 : Futile medication use in terminally ill cancer patients.

71 : Patients with advanced lung cancer: is there scope to discontinue inappropriate medication?

72 : Patients with advanced lung cancer: is there scope to discontinue inappropriate medication?

73 : Integrating palliative medicine into the care of persons with advanced dementia: identifying appropriate medication use.

74 : Decision making about change of medication for comorbid disease at the end of life: an integrative review.

75 : Feasibility study of a systematic approach for discontinuation of multiple medications in older adults: addressing polypharmacy.

76 : End-of-Life medications draw more attention, greater scrutiny.

77 :

78 : An approach to diabetes mellitus in hospice and palliative medicine.

79 : Standards of Medical Care in Diabetes-2017: Summary of Revisions.

80 : Subcutaneous administration of drugs in palliative care: results of a systematic observational study.

81 : Subcutaneous administration of drugs in palliative care: results of a systematic observational study.

82 : Continuous subcutaneous infusion of opiates at end-of-life.

83 : Continuous subcutaneous infusion practices of United States hospices.

84 : A comparison of subcutaneous morphine and fentanyl in hospice cancer patients.

85 : Subcutaneous fentanyl and sufentanil infusion substitution for morphine intolerance in cancer pain management.

86 : Continuous subcutaneous infusion: an efficacious, cost-effective analgesia alternative at the end of life.

87 : Oral transmucosal fentanyl and sufentanil for incident pain.

88 : Comparison of the intramuscular, intranasal or sublingual routes of midazolam administration for the control of soman-induced seizures.

89 : Current oral and non-oral routes of antiepileptic drug delivery.

90 : Recent development in therapeutics for breakthrough pain.

91 : Effectiveness of the buccal mucosa route for methadone administration at the end of life.

92 : Effectiveness of the buccal mucosa route for methadone administration at the end of life.

93 : Effectiveness of the buccal mucosa route for methadone administration at the end of life.

94 : Oxygen is nonbeneficial for most patients who are near death.

95 : Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial.

96 : A systematic review of the treatment of nausea and/or vomiting in cancer unrelated to chemotherapy or radiation.

97 : Review article: terminal delirium in geriatric patients with cancer at end of life.

98 : Which medications to avoid in people at risk of delirium: a systematic review.

99 : Haloperidol, risperidone, olanzapine and aripiprazole in the management of delirium: A comparison of efficacy, safety, and side effects.

100 : Pharmacovigilance in hospice/palliative care: net effect of haloperidol for delirium.

101 : Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial.

102 : Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial.

103 : The minimal clinically important difference of the Richmond Agitation-Sedation Scale in patients with cancer with agitated delirium.

104 : Drug therapy for symptoms associated with anxiety in adult palliative care patients.

105 : Safety and Effectiveness of Palliative Drug Treatment in the Last Days of Life-A Systematic Literature Review.

106 : Safety and Effectiveness of Palliative Drug Treatment in the Last Days of Life-A Systematic Literature Review.

107 : Nonconvulsive status epilepticus in a palliative care unit: when delirium is a seizure.

108 : Prevalence, impact, and treatment of death rattle: a systematic review.

109 : Death rattle is not associated with patient respiratory distress: is pharmacologic treatment indicated?

110 : Care strategy for death rattle in terminally ill cancer patients and their family members: recommendations from a cross-sectional nationwide survey of bereaved family members' perceptions.

111 : Anticholinergic medications for managing noisy respirations in adult hospice patients.

112 : Pharmacokinetics and related pharmacodynamics of anticholinergic drugs.

113 : Anticholinergics in palliative medicine: an update.

114 : Interventions for noisy breathing in patients near to death.

115 : Randomized double-blind trial of sublingual atropine vs. placebo for the management of death rattle.

116 : Effect of Prophylactic Subcutaneous Scopolamine Butylbromide on Death Rattle in Patients at the End of Life: The SILENCE Randomized Clinical Trial.

117 : Frequency of outpatient antibiotic prescription on discharge to hospice care.

118 : Infection management and multidrug-resistant organisms in nursing home residents with advanced dementia.

119 : Antimicrobial use at the end of life among hospitalized patients with advanced cancer.

120 : Patterns of antimicrobial use among nursing home residents with advanced dementia.

121 : A nationwide analysis of antibiotic use in hospice care in the final week of life.

122 : Antimicrobial use for symptom management in patients receiving hospice and palliative care: a systematic review.

123 : Survival and comfort after treatment of pneumonia in advanced dementia.

124 : Complicated grief and post-traumatic stress symptom profiles in bereaved earthquake survivors: a latent class analysis.

125 : Prolonged grief disorder following the Coronavirus (COVID-19) pandemic.

126 : The New Normal: Key Considerations for Effective Serious Illness Communication Over Video or Telephone During the Coronavirus Disease 2019 (COVID-19) Pandemic.