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Palliative sedation

Palliative sedation
Author:
Nathan Cherny, MD
Section Editor:
Thomas J Smith, MD, FACP, FASCO, FAAHPM
Deputy Editor:
Jane Givens, MD, MSCE
Literature review current through: Feb 2022. | This topic last updated: Mar 03, 2021.

INTRODUCTION — Palliative sedation is a measure of last resort used at the end of life to relieve severe and refractory symptoms. It is performed by the administration of sedative medications in monitored settings and is aimed at inducing a state of decreased awareness or absent awareness (unconsciousness). The intent of palliative sedation is to relieve the burden of otherwise intolerable suffering for terminally ill patients in a manner that preserves the moral sensibilities of the patient, the medical professionals involved in their care, and concerned family and friends [1].

This topic will review the indications and administration of palliative sedation in patients nearing the end of life as well as special applications of palliative sedation in other palliative care settings, such as in emergency situations, for respite, and for psychological distress. Other aspects of symptom care in the palliative setting are covered separately. (See "Overview of managing common non-pain symptoms in palliative care" and "Cancer pain management with opioids: Optimizing analgesia" and "Approach to symptom assessment in palliative care".)

INDICATIONS — Palliative sedation may be utilized in both adults and children [2-6] with advanced incurable (ie, terminal) illness in order to alleviate severe symptoms that are refractory to other forms of treatment. It is most commonly utilized for the treatment of refractory pain, dyspnea, agitated delirium, and convulsions. However, there is much variability in the definition of “refractory” symptoms and thus in the prevalence of use of palliative sedation (table 1) [7].

Some emergency situations for which palliative sedation could be considered may include massive hemorrhage, asphyxiation, an overwhelming pain crisis, and severe terminal dyspnea [8-10]. (See 'Emergency sedation' below.)

Still, other than in emergency situations, intermittent or mild sedation should generally be attempted before deep and continuous sedation. For some patients, a state of "conscious sedation," in which the ability to respond to verbal stimuli is retained, may provide adequate relief without total loss of interactive function.

Defining refractory symptoms — A symptom is considered "refractory" when it cannot adequately be controlled by therapies that do not seriously compromise consciousness and when it is associated with intolerable suffering on the part of the patient. The diagnostic criteria for "refractoriness" are based on the clinician’s determination that further invasive and noninvasive interventions meet any of the following [1]:

Incapable of providing inadequate relief

Associated with excessive and intolerable acute or chronic adverse effects

Unlikely to provide relief within a tolerable time frame

CONCERNS OF STAFF, FAMILY, AND OTHERS — Witnessing or just considering palliative sedation can be profoundly distressing to family, other loved ones, and staff. This is particularly true if there is concern regarding the effects and ethics of palliative sedation, if there is lingering disagreement regarding the treatment plan among providers, and in situations where the process is protracted.

Are we hastening death? — Multiple studies have attempted to measure the impact of palliative sedation on patient survival, and their overall conclusion is that survival is the same (or even better) when sedated patients are compared with non-sedated patients [11-18]. These studies, while important, share methodological limitations that detract from the certainty of their conclusions: they are all cohort studies, most did not incorporate cohort matching for prognostic factors, and many did not detail the degree of sedation in the intervention arm.

Other ethical concerns — Some family members, loved ones, or staff may be concerned that palliative sedation is a form of euthanasia.

The discussion of ethical issues with family or other loved ones and care team members should address the distinction from euthanasia. Palliative sedation is distinct from euthanasia in that euthanasia refers to the deliberate termination of the life of a patient by active intervention, usually at the request of the patient (voluntary active euthanasia [VAE]). Palliative sedation, by contrast, is utilized for refractory suffering and the intent of the intervention is to provide symptom relief, not expressly to end the life of the suffering patient [19-27]; the intervention is proportionate to the prevailing symptom, its severity, and the prevailing goals of care; and, unlike euthanasia, death of the patient is not a criterion used to gauge the success of the treatment.

Discussions with family members or other loved ones should emphasize that uncontrolled suffering at the end of life constitutes a critical situation and that the option of palliative sedation, after obtaining informed consent by the patient (or their surrogate) or by previously determined advance directives, constitutes a proportionate and effective response to suffering that is within accepted medical guidelines and supported by the principles of patient autonomy and self-determination [28]. In this context, the decision to offer the use of sedation to relieve intolerable suffering to terminally ill patients presents no new ethical problem [29,30] and is supported by legal precedent [31-33]. (See 'Obtaining consent' below and "Ethical issues in palliative care", section on 'Palliative sedation'.)

Some assume that palliative sedation requires the concurrent discontinuation of nutrition and hydration [34-37]. Therefore, they argue that while palliative sedation for the relief of uncontrolled symptoms may be justifiable, it almost certainly hastens death by allowing for starvation and dehydration. However, it is important to assert that the discontinuation of hydration and nutrition is not an essential element to the administration of sedation in the management of refractory symptoms [38]. (See 'The role of nutrition and hydration' below.)

Ethically problematic practices — Clinicians using palliative sedation need to be aware of the potential for harm from abusive, injudicious, or unskilled use of sedation. Potential harm is illustrated in the following examples:

Sedation as a means of hastening death – This is the most common abuse of palliative sedation. It may occur by the deliberate use of deep sedation in patients who have no refractory symptoms, or in the deliberate use of doses that far exceed what is necessary to provide adequate comfort [19-26].

Sedation applied inappropriately – Palliative sedation may be used for an inappropriate indication due to inadequate patient assessment that may have overlooked a potentially reversible cause of distress [20,39]. For patients in whom palliative sedation is being considered, consultation with palliative care experts or a multidisciplinary team may help identify potential and available alternatives to palliative sedation [20,40].

Sedation given in response to the family’s (or others’) wishes and not in response to the patient themselves (or their advance directives) [41].

Sedation withheld when it is appropriate – This may occur when clinicians rule out or do not offer the option of palliative sedation in favor of other therapeutic options that do not provide adequate relief. This may occur when anxiety about having to deal with all of the difficult discussions about sedation and end-of-life care results in continued futile therapeutic trials of ineffective therapies or when there are reservations based on undue concerns about potentially hastening death.

Approach to the care team — The care team should recognize the potential for staff distress [42,43]. All participating staff members need to understand the rationale for sedation and goals of care. Whenever possible, this should be addressed at team meetings or case conferences, both before and after the event, to discuss the professional and emotional issues related to such decisions. Distress can be mitigated by fostering a culture of sensitivity to the emotional burdens involved in care, participating in the deliberative processes leading up to a treatment decision, sharing information, and engaging in multidisciplinary discussions that offer the group or individuals opportunities to express their feelings.

Approach to the patient's family and friends — Palliative sedation can be a welcomed method to assure patient comfort but can also be profoundly distressing to the patient’s family members and/or friends [28]. A few principles are useful when considering the approach to a patient’s loved ones:

They should be allowed and encouraged to be with the patient. In many situations, an opportunity to say good-bye is of critical importance.

They often need repeated reassurance that other methods have been sufficiently tried and/or carefully considered but were ineffective and that sedation is unlikely to shorten the patient’s life. The conversation should also emphasize the importance of comfort and our obligation to prevent or alleviate suffering.

They should be kept informed about the patient’s wellbeing and what to expect.

The care team must provide supportive care to the members of the patient’s family and/or friends. This includes listening to their concerns, attention to grief and physical/psychological burdens, and awareness for any perceived feelings of guilt. In addition, they should be offered advice as to ways to be of help to the patient (eg, by being with, talking to, and touching the patient, providing mouth care, and managing the atmosphere of the patient’s care).

The care team should provide regular information updates to the family or other loved ones including information about the patient’s condition, degree of suffering, anticipated changes, or, when appropriate, notification that death is approaching and what can be expected in the dying process.

After the death of the patient, the family or other loved ones should be offered the opportunity to meet with his or her care providers to give them the opportunity to ventilate grief and to discuss any outstanding concerns that they may harbor about the care delivered in the last days of life.

PROCESS

Advanced care planning — Palliative sedation may be discussed as a component of a “goals of care” discussion when death is not imminent but a patient with advanced illness is at risk of intolerable suffering, and the clinician anticipates a potential need for it in the future. The discussion of this option should include review of the aims, benefits, and risks of palliative sedation, as well as the alternatives to its use (see "Discussing goals of care"). When the potential for catastrophic events such as bleeding or extreme distress is foreseen, contingency plans for the management of these events should be discussed, including the potential role of palliative sedation.

Patient assessment — However, most often the discussion about palliative sedation takes place because of a symptom crisis.

Terminally ill patients suffering from severe distress should be evaluated urgently, preferably by a palliative care clinician. This evaluation is to determine whether reversible (or treatable) factors may be playing a role in the patient’s deterioration or severe distress (eg, acute bowel obstruction, elevated intracranial pressure, or a previously undiagnosed pulmonary infection). In addition, this allows for a re-evaluation of the patient’s prognosis, which is essential in order to allow for the discussion of appropriate therapy.

In general, if palliative sedation is under consideration, review of the case by a multidisciplinary team (eg, involving a palliative care team or such specialists as psychiatrists or pain specialists) should be conducted in order to assure that all other reasonable treatments have been provided and that palliative sedation meets the patient’s goals [44,45]. When local expertise is limited, telephone consultation with experts in palliative medicine is strongly encouraged.

Obtaining consent — When patients with advanced illness are at risk of intolerable suffering, clinicians should discuss the option of palliative sedation at a time before the patient is in a crisis situation. The discussion of this option should include review of the aims, benefits, and risks of palliative sedation, as well as the alternatives to its use.

For patients experiencing severe or refractory distress but who are still conscious, alert, and communicative, a discussion on palliative sedation should be a part of a more comprehensive conversation that includes the following:

The patient’s general condition and the cause of the distress

Acknowledgement that prior treatments have not been successful

Current prognosis, including predictions about survival

Rationale, aims, and methods available for the use of palliative sedation, including the depth of planned sedation, patient monitoring, and, if appropriate, the possibility of planned weaning from sedation and even discontinuation

Alternative treatment options, the likelihood that they may relieve distress, and the expected survival associated with each

Anticipated effects of sedation, including degree of reduction in consciousness levels and the estimated effects on mental activities, communication, and oral intake

Potential risks such as paradoxical agitation, delayed or inadequate relief, and the possibility of hastened death

For patients who lack decisional capacity, the advance care plan of the patient should be followed. If there is no advance directive, the discussion regarding palliative sedation (including consent) must be obtained from a legally recognized proxy. When the patient is a child, consent of a parent or other guardian is required; however, care options might be discussed in an age-appropriate manner for older children to facilitate their agreement (or assent) [6,46]. (See "Pediatric palliative care".)

For terminally ill patients who are actively dying and in severe distress, an opportunity to obtain consent by the patient or their health care proxy may not be present. In the absence of an advance directive or health care proxy, the provision of comfort measures (including, if necessary, the use of sedation) should be considered standard of practice and the default strategy for clinician treatment decisions.

Regardless of whether the patient has decisional capacity or not, patients, their families and loved ones should be reassured that they will receive the best possible care during this time, irrespective of decisions to proceed with palliative sedation or an alternative treatment. In addition, patients should be informed that medical treatments and nursing care will be provided to ensure that the patient’s comfort is maintained and that the patient’s and family or other loved one’s wishes are respected.

Sedative medications

Opioids — Many patients are already taking sedating opioids for pain or dyspnea and can be treated simply with upward dose titration. These medications should not be discontinued even when comfort is achieved. (See 'Administration of previous medications' below.)

Benzodiazepines and other agents — Midazolam is a short half-life benzodiazepine with a rapid onset of action and, administered parenterally, it is the most commonly used medication for palliative sedation [18,47-49]. In one prospective study, 24 of 176 patients (14 percent) receiving palliative care at home underwent palliative sedation using a stepwise administration of midazolam [50], which was administered predominantly due to agitated delirium. Based on the home care team and the individual patient’s relative's experience, the use of midazolam was felt to be effective at minimizing distress and most expressed satisfaction with the procedure.

An alternative to benzodiazepine option is lorazepam, which has a slower onset of action (10 minutes) compared with midazolam (two minutes).

Alternative agents used in this context include levomepromazine [51,52], chlorpromazine [53,54], phenobarbital [55,56], and propofol [57-61]. These medications are reviewed in a table (table 2).

Administration — Sedation for the management of refractory symptoms is most commonly performed in an inpatient setting. However, substantial experience has been reported in home care settings [62-65], which may be a preferred alternative for some patients.

Administration of the selected medication initially requires dose titration to achieve adequate relief, followed by ongoing therapy to ensure maintenance of the effect. In general, the level of sedation should be the least necessary to provide adequate relief of suffering. Regular, "around the clock" administration can be maintained by continuous infusion or intermittent bolus.

The route of administration can be intravenous, intramuscular, subcutaneous, or rectal; in some situations, drugs can also be administered via a stoma or gastrostomy. In all cases, provision for emergency bolus therapy to manage breakthrough symptoms is recommended.

If mild sedation is ineffective, deeper levels of sedation should be performed. This is especially true in cases of refractory suffering when death is imminent and in the case of a catastrophic event (eg, massive hemorrhage or asphyxia). (See "Palliative care: Overview of cough, stridor, and hemoptysis in adults", section on 'Management'.)

Patient monitoring — Once adequate relief has been achieved, the parameters for patient monitoring and the role of further dose titration are determined by the clinical situation:

Patient is imminently dying – We do not perform routine monitoring of vital signs (eg, pulse, blood pressure, and temperature) for patients nearing death. The only critical parameters for ongoing observation are those pertaining to comfort. Since downward titration of drug doses places the patient at risk for recurrent distress, it is not recommended in most instances. Respiratory rate is monitored primarily to ensure the absence of respiratory distress and tachypnea. A gradual deterioration of respiration is expected as patients near death and this alone should not constitute a reason to decrease sedation.

Patient is not imminently dying – Monitoring may be undertaken to preserve physiological stability for terminally ill patients who are not imminently dying. This may include repeat assessment of the level of sedation and routine physiological parameters such as heart rate, blood pressure, and oxygen saturation. If life-threatening obtundation with respiratory depression occurs, a lower treatment dose may be required. If patients become more unstable, the careful administration of a benzodiazepine antagonist (flumazenil) may be appropriate. IV flumazenil 0.2 mg can be administered over one to two minutes and repeated up to every 15 minutes (maximum total dose 1 mg) until obtundation is reversed. Since its duration effect is short (0.7 to 1.3 hours), relapse may be treated in adults by using additional 0.2 mg doses until the desired effect is achieved or by a continuous flumazenil infusion (0.25 to 1 mg per hour) [66].

Once sedation and symptom control is achieved, doses can be titrated down to reestablish lucidity if appropriate, if this was desired by the patient prior to sedation. This enables an opportunity to reevaluate the patient's condition and their preferences regarding sedation. It may also allow for patient to communicate with family or other loved ones. However, lucidity may not be restored, symptoms may reoccur, and death may intervene.

The role of nutrition and hydration — Decisions regarding the administration of hydration and/or artificial nutrition therapy are independent of the decision about whether to administer palliative sedation. Although sedation is clearly beneficent in terms of providing relief of otherwise intolerable suffering, the beneficence of withdrawal of nutrition and hydration in the already sedated and comfortable patient is not self-evident, and indeed it may be perceived as harmful.

Medically, there are few data to support the clinical benefit of hydration or artificial nutrition in the imminently dying, or to suggest that it prolongs life or contributes to comfort. Despite this, the withdrawal of potentially death-deferring treatments (such as hydration) among dying patients is, for some, controversial. Opinions and practices vary and reflect the heterogeneity of attitudes of involved clinicians, ethicists, patients, families, and local norms of good clinical and ethical practice. In cases where there are religious or culturally based reservations regarding the discontinuation of nutritional support, it should be maintained unless there is evidence of direct patient harm by the intervention. The topic of nutrition and hydration as part of end-of-life care is discussed separately. (See "Stopping nutrition and hydration at the end of life".)

Administration of previous medications — Medications for symptom palliation used before sedation should be continued unless they are ineffective or have distressing side effects. Medications that are either inconsistent with or irrelevant to the goal of patient comfort can be discontinued. Special caution must be exercised regarding medications that may be associated with withdrawal responses, and in general such medication should not be discontinued [67]. (See "Palliative care: The last hours and days of life", section on 'Eliminating non-essential medications'.)

In most cases, patients who were on pain medications (eg, opioids) prior to sedation should be continued on them unless adverse effects or signs of overdose (eg, respiratory suppression) are observed, in which case dose modifications may be necessary. If symptoms of an overdose are observed, opioid doses should be reduced but should not be rapidly withdrawn because of the risk of withdrawal.

SPECIAL APPLICATIONS OF SEDATION IN PALLIATIVE CARE

Emergency sedation — Emergency sedation refers to the use of sedation to provide urgent relief of overwhelming symptoms in dying patients. Emergency situations may include massive hemorrhage, asphyxiation, severe terminal dyspnea, or overwhelming pain crisis [8-10]. If a catastrophic situation is anticipated, advance care directives should be discussed with the patient, family members, other loved ones, and health care providers. (See 'Obtaining consent' above.)

For patients who are at home and at risk of a catastrophic event, sedating medications should be prepared in advance and accompanied by a clear plan for emergency administration. In situations in which family members or other home carers feel that they would be unable to administer emergency medications, consideration should be given to inpatient care.

Respite sedation — Respite sedation refers to the transient use of sedation to relieve severe symptoms (eg, malaise, pain, agitation, and nausea) that are not necessarily refractory, to provide adequate relief before continuing with further trial of nonsedating palliative approaches. After such respite, some patients will be sufficiently rested to consider further trials of symptomatic therapy [55,56,68].

Since the aim of respite sedation is to ultimately restore the patient to their pretreatment state of consciousness, precautions are required to ensure patient safety and to minimize risks. These include:

Administration of the lowest effective dose of the sedative agent chosen that provides adequate comfort

Monitoring routine physiological parameters

If midazolam is used, flumazenil should be readily available in case of inadvertent overdose. Despite these precautions, this approach is associated with significant risks (including the risk that level of consciousness may not be completely restored) that should be considered in the consent process. (See 'Obtaining consent' above.)

Use of sedation in the management of refractory existential or psychological distress — Sedation in the management of refractory psychological symptoms and existential distress is controversial and is different from the use of palliative sedation in other situations for several reasons [69-72]:

Due to the nature of the symptoms being addressed, it is much more difficult to establish that they are truly refractory.

The severity of distress of some symptoms may be very dynamic and idiosyncratic (ie, difficult to predict); in such cases, psychological adaptation and coping are common.

The standard treatment approaches to address severe psychological symptoms or existential distress are not intrinsically life-threatening, such as the use of psychotherapy, religious counseling, and spiritual support [70].

Unlike physical symptoms such as pain or dyspnea, the presence of these severe psychological symptoms or existential distress does not necessarily indicate a far-advanced state of physiological deterioration.

The European Association for Palliative Care (EAPC) has provided a framework for addressing the use of palliative sedation in these circumstances [73]:

This approach should be reserved for patients in advanced stages of a terminal illness.

The designation of such symptoms as refractory should only be made following a period of repeated assessment by clinicians skilled in psychological care who have established a relationship with the patient and their family or other loved ones along with trials of routine approaches for anxiety, depression, and existential distress.

Because of the complexity and frequently multifactorial nature of this situation, the evaluation should be made in the context of a multidisciplinary case conference, including representatives from psychiatry, chaplaincy, and ethics as well as those providing care at the bedside.

In the rare situations that this strategy is indeed appropriate and proportionate to the situation, it should be initiated on a respite basis for 6 to 24 hours with planned downward titration after a pre-agreed interval.

Only after repeated trials of respite sedation with intensive intermittent therapy have been performed should continuous sedation be considered.

GUIDELINES FROM MEDICAL GROUPS — For palliative sedation to be used humanely and appropriately, appropriate attention to these processes is essential. While acknowledging that specific best practices have not been rigorously developed, procedural guidelines at the institutional level are necessary for clinicians to have a framework for decision-making and implementation. This promotes and protects the interests of patients, their families or other loved ones, and the health care providers administering care. Sound procedural guidelines such as checklists can reduce the risk of adverse outcomes in medicine [74,75].

Representative guidelines have been developed at a national, local, and institutional level [49,73,76-90]. There are several inconsistencies throughout the positions taken by organizations on palliative sedation, most notably the timing of initiating palliative sedation, the level and pattern of sedation, whether or not existential distress is an indication, and the continuation versus discontinuation of life-sustaining therapies [89,90]. Discrepancies in these areas are largely due to a number of ethical and clinical factors that make these decisions very difficult.

However, several core factors are in agreement among most position statements on palliative sedation:

The patient must have a terminal illness where death is imminent (though the definition of imminent is variable).

The physical symptoms that the patient is experiencing are intractable and refractory to the most aggressive interventions, with no other options for treatment that would be effective within the estimated time left before expected death.

The intention of the intervention is symptom relief.

The plan of sedation and the risk-benefit profile should be made explicitly in an informed consent obtained from the patient or, if incapable, the surrogate, family, or other loved ones prior to initiation of palliative sedation.

The decision to use palliative sedation must be discussed among an interdisciplinary team, ideally led by an experienced palliative care clinician.

Documentation of the informed consent and the provision of sedation must be thorough.

The European Association for Palliative Care (EAPC) has developed a 10-item framework that addresses the key clinical issues to be considered when institutions are developing guidelines for palliative sedation in the management of refractory physical symptoms at the end of life. These are summarized in a table (table 3).

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

Palliative sedation is the monitored use of sedating medications to induce a state of decreased awareness or complete unconsciousness in order to relieve the burden of otherwise intolerable suffering at the end of life. (See 'Introduction' above.)

Palliative sedation may be utilized in both adults and children with advanced incurable (ie, terminal) illness in order to alleviate severe symptoms that are refractory to other forms of treatment. The most common symptoms include pain, dyspnea, agitated delirium, and convulsions. (See 'Indications' above.)

Although the data are limited, compared with patients at the end of life who did not receive palliative sedation, the use of palliative sedation does not appear to shorten survival in this setting. (See 'Are we hastening death?' above.)

Patients who are acutely suffering should be evaluated urgently, preferably by a clinician with experience and expertise in palliative care. (See 'Advanced care planning' above.)

Irrespective of the agent selected for palliative sedation, administration initially requires dose titration to achieve adequate relief, followed by ongoing therapy to ensure maintenance of effect. In general, the level of sedation should be the least necessary to provide adequate relief of suffering. (See 'Administration' above.)

For patients undergoing palliative sedation, monitoring should be tailored to their clinical status (see 'Patient monitoring' above):

For patients who are actively dying, we do not perform routine monitoring of vital signs (eg, pulse, blood pressure, and temperature). The only critical parameters for ongoing observation are those pertaining to comfort.

For patients who are not actively dying, monitoring is reasonable, including repeat assessment of the level of sedation and routine physiological parameters such as heart rate, blood pressure, and oxygen saturation.

The decision about artificial hydration and/or nutrition therapy is made independently of the decision about palliative sedation itself. (See 'The role of nutrition and hydration' above.)

Medications for symptom palliation used before initiating palliative sedation should be continued, unless they are ineffective or have distressing side effects. Medications that are either inconsistent with, or irrelevant to, the goal of patient comfort can generally be discontinued. (See 'Administration of previous medications' above.)

Loved ones often need repeated reassurance that other methods have been sufficiently trialed but were ineffective in alleviating suffering and that palliative sedation is unlikely to shorten the patient’s life. (See 'Approach to the patient's family and friends' above.)

The care team should recognize the potential for staff distress. All participating staff members need to understand the rationale for sedation and goals of care. Whenever possible this should be addressed at team meetings or case conferences, both before and after the event, to discuss the professional and emotional issues related to such decisions. (See 'Approach to the care team' above.)

Special applications of palliative sedation include (see 'Special applications of sedation in palliative care' above):

The use of sedation to provide urgent relief of overwhelming symptoms in dying patients (emergency palliative sedation)

Transient use of sedation to relieve severe symptoms that are not necessarily refractory (respite palliative sedation)

The use of sedation to manage refractory psychological symptoms and existential distress is controversial but may be appropriate.

Palliative sedation is not synonymous with voluntary active euthanasia (VAE). VAE refers to the deliberate termination of the life of a patient by active intervention, usually at the request of the patient. Palliative sedation is not meant to be a means of hastening the patient’s death. (See "Physician-assisted dying" and 'Other ethical concerns' above.)

We encourage the development of guidelines on a local level to establish criteria for the use of palliative sedation. We agree with the European Association for Palliative Care (EAPC)’s 10-item framework that addresses the key clinical issues in palliative sedation for the management of refractory physical symptoms at the end of life. (See 'Guidelines from medical groups' above.)

REFERENCES

  1. Cherny NI, Portenoy RK. Sedation in the management of refractory symptoms: guidelines for evaluation and treatment. J Palliat Care 1994; 10:31.
  2. Anghelescu DL, Hamilton H, Faughnan LG, et al. Pediatric palliative sedation therapy with propofol: recommendations based on experience in children with terminal cancer. J Palliat Med 2012; 15:1082.
  3. Pousset G, Bilsen J, Cohen J, et al. Continuous deep sedation at the end of life of children in Flanders, Belgium. J Pain Symptom Manage 2011; 41:449.
  4. Kuhlen M, Schneider K, Richter U, et al. Palliative sedation in 2 children with terminal cancer - an effective treatment of last resort in a home care setting. Klin Padiatr 2011; 223:374.
  5. Kiman R, Wuiloud AC, Requena ML. End of life care sedation for children. Curr Opin Support Palliat Care 2011; 5:285.
  6. Postovsky S, Moaed B, Krivoy E, et al. Practice of palliative sedation in children with brain tumors and sarcomas at the end of life. Pediatr Hematol Oncol 2007; 24:409.
  7. Roy DJ. Need they sleep before they die? J Palliat Care 1990; 6:3.
  8. Bishop MF, Stephens L, Goodrich M, Byock I. Medication kits for managing symptomatic emergencies in the home: a survey of common hospice practice. J Palliat Med 2009; 12:37.
  9. Falk S, Fallon M. ABC of palliative care. Emergencies. BMJ 1997; 315:1525.
  10. Nauck F, Alt-Epping B. Crises in palliative care--a comprehensive approach. Lancet Oncol 2008; 9:1086.
  11. Maltoni M, Scarpi E, Rosati M, et al. Palliative sedation in end-of-life care and survival: a systematic review. J Clin Oncol 2012; 30:1378.
  12. Beller EM, van Driel ML, McGregor L, et al. Palliative pharmacological sedation for terminally ill adults. Cochrane Database Syst Rev 2015; 1:CD010206.
  13. Daly BJ, Thomas D, Dyer MA. Procedures used in withdrawal of mechanical ventilation. Am J Crit Care 1996; 5:331.
  14. Campbell ML, Bizek KS, Thill M. Patient responses during rapid terminal weaning from mechanical ventilation: a prospective study. Crit Care Med 1999; 27:73.
  15. Wilson WC, Smedira NG, Fink C, et al. Ordering and administration of sedatives and analgesics during the withholding and withdrawal of life support from critically ill patients. JAMA 1992; 267:949.
  16. Maeda I, Morita T, Yamaguchi T, et al. Effect of continuous deep sedation on survival in patients with advanced cancer (J-Proval): a propensity score-weighted analysis of a prospective cohort study. Lancet Oncol 2016; 17:115.
  17. Rietjens JA, van Zuylen L, van Veluw H, et al. Palliative sedation in a specialized unit for acute palliative care in a cancer hospital: comparing patients dying with and without palliative sedation. J Pain Symptom Manage 2008; 36:228.
  18. Schur S, Weixler D, Gabl C, et al. Sedation at the end of life - a nation-wide study in palliative care units in Austria. BMC Palliat Care 2016; 15:50.
  19. Levy MH, Cohen SD. Sedation for the relief of refractory symptoms in the imminently dying: a fine intentional line. Semin Oncol 2005; 32:237.
  20. Hasselaar JG, Reuzel RP, van den Muijsenbergh ME, et al. Dealing with delicate issues in continuous deep sedation. Varying practices among Dutch medical specialists, general practitioners, and nursing home physicians. Arch Intern Med 2008; 168:537.
  21. Kuhse H, Singer P, Baume P, et al. End-of-life decisions in Australian medical practice. Med J Aust 1997; 166:191.
  22. Shapiro RS, Derse AR, Gottlieb M, et al. Willingness to perform euthanasia. A survey of physician attitudes. Arch Intern Med 1994; 154:575.
  23. Willems DL, Daniels ER, van der Wal G, et al. Attitudes and practices concerning the end of life: a comparison between physicians from the United States and from The Netherlands. Arch Intern Med 2000; 160:63.
  24. Meier DE, Emmons CA, Wallenstein S, et al. A national survey of physician-assisted suicide and euthanasia in the United States. N Engl J Med 1998; 338:1193.
  25. Douglas CD, Kerridge IH, Rainbird KJ, et al. The intention to hasten death: a survey of attitudes and practices of surgeons in Australia. Med J Aust 2001; 175:511.
  26. Rietjens JA, van der Heide A, Vrakking AM, et al. Physician reports of terminal sedation without hydration or nutrition for patients nearing death in the Netherlands. Ann Intern Med 2004; 141:178.
  27. Materstvedt LJ. Distinction between euthanasia and palliative sedation is clear-cut. J Med Ethics 2020; 46:55.
  28. Tursunov O, Cherny NI, Ganz FD. Experiences of Family Members of Dying Patients Receiving Palliative Sedation. Oncol Nurs Forum 2016; 43:E226.
  29. Miller FG, Fins JJ, Bacchetta MD. Clinical pragmatism: John Dewey and clinical ethics. J Contemp Health Law Policy 1996; 13:27.
  30. Fins JJ, Bacchetta MD, Miller FG. Clinical pragmatism: a method of moral problem solving. Kennedy Inst Ethics J 1997; 7:129.
  31. Gevers S. Terminal sedation: a legal approach. Eur J Health Law 2003; 10:359.
  32. Easing the Passing, Devlin P (Ed), Bodley Head, London 1985.
  33. Burt RA. The Supreme Court speaks--not assisted suicide but a constitutional right to palliative care. N Engl J Med 1997; 337:1234.
  34. Craig GM. On withholding artificial hydration and nutrition from terminally ill sedated patients. The debate continues. J Med Ethics 1996; 22:147.
  35. Craig GM. On withholding nutrition and hydration in the terminally ill: has palliative medicine gone too far? J Med Ethics 1994; 20:139.
  36. Craig G. Is sedation without hydration or nourishment in terminal care lawful? Med Leg J 1994; 62:198.
  37. Orentlicher D. The Supreme Court and physician-assisted suicide--rejecting assisted suicide but embracing euthanasia. N Engl J Med 1997; 337:1236.
  38. Hahn MP. Review of palliative sedation and its distinction from euthanasia and lethal injection. J Pain Palliat Care Pharmacother 2012; 26:30.
  39. Fainsinger RL, De Moissac D, Mancini I, Oneschuk D. Sedation for delirium and other symptoms in terminally ill patients in Edmonton. J Palliat Care 2000; 16:5.
  40. Murray SA, Boyd K, Byock I. Continuous deep sedation in patients nearing death. BMJ 2008; 336:781.
  41. Higgins PC, Altilio T. Palliative sedation: an essential place for clinical excellence. J Soc Work End Life Palliat Care 2007; 3:3.
  42. Ziegler S, Merker H, Schmid M, Puhan MA. The impact of the inpatient practice of continuous deep sedation until death on healthcare professionals' emotional well-being: a systematic review. BMC Palliat Care 2017; 16:30.
  43. Leboul D, Aubry R, Peter JM, et al. Palliative sedation challenging the professional competency of health care providers and staff: a qualitative focus group and personal written narrative study. BMC Palliat Care 2017; 16:25.
  44. Feldman HA, McKinlay JB, Potter DA, et al. Nonmedical influences on medical decision making: an experimental technique using videotapes, factorial design, and survey sampling. Health Serv Res 1997; 32:343.
  45. Christakis NA, Asch DA. Biases in how physicians choose to withdraw life support. Lancet 1993; 342:642.
  46. Fraser J, Harris N, Berringer AJ, et al. Advanced care planning in children with life-limiting conditions - the Wishes Document. Arch Dis Child 2010; 95:79.
  47. Lux MR, Protus BM, Kimbrel J, Grauer P. A Survey of Hospice and Palliative Care Physicians Regarding Palliative Sedation Practices. Am J Hosp Palliat Care 2017; 34:217.
  48. Vivat B, Bemand-Qureshi L, Harrington J, et al. Palliative care specialists in hospice and hospital/community teams predominantly use low doses of sedative medication at the end of life for patient comfort rather than sedation: Findings from focus groups and patient records for I-CAN-CARE. Palliat Med 2019; 33:578.
  49. Imai K, Morita T, Akechi T, et al. The Principles of Revised Clinical Guidelines about Palliative Sedation Therapy of the Japanese Society for Palliative Medicine. J Palliat Med 2020; 23:1184.
  50. Mercadante S, Porzio G, Valle A, et al. Palliative sedation in patients with advanced cancer followed at home: a prospective study. J Pain Symptom Manage 2014; 47:860.
  51. Oliver DJ. The use of methotrimeprazine in terminal care. Br J Clin Pract 1985; 39:339.
  52. Dietz I, Schmitz A, Lampey I, Schulz C. Evidence for the use of Levomepromazine for symptom control in the palliative care setting: a systematic review. BMC Palliat Care 2013; 12:2.
  53. McIver B, Walsh D, Nelson K. The use of chlorpromazine for symptom control in dying cancer patients. J Pain Symptom Manage 1994; 9:341.
  54. LeGrand SB. Dyspnea: the continuing challenge of palliative management. Curr Opin Oncol 2002; 14:394.
  55. Greene WR, Davis WH. Titrated intravenous barbiturates in the control of symptoms in patients with terminal cancer. South Med J 1991; 84:332.
  56. Truog RD, Berde CB, Mitchell C, Grier HE. Barbiturates in the care of the terminally ill. N Engl J Med 1992; 327:1678.
  57. Collins P. Prolonged sedation with midazolam or propofol. Crit Care Med 1997; 25:556.
  58. Tobias JD. Propofol sedation for terminal care in a pediatric patient. Clin Pediatr (Phila) 1997; 36:291.
  59. Krakauer EL, Penson RT, Truog RD, et al. Sedation for intractable distress of a dying patient: acute palliative care and the principle of double effect. Oncologist 2000; 5:53.
  60. Mercadante S, De Conno F, Ripamonti C. Propofol in terminal care. J Pain Symptom Manage 1995; 10:639.
  61. Moyle J. The use of propofol in palliative medicine. J Pain Symptom Manage 1995; 10:643.
  62. Mercadante S, Porzio G, Valle A, et al. Palliative sedation in advanced cancer patients followed at home: a retrospective analysis. J Pain Symptom Manage 2012; 43:1126.
  63. Setla J, Pasniciuc SV. Home Palliative Sedation Using Phenobarbital Suppositories: Time to Death, Patient Characteristics, and Administration Protocol. Am J Hosp Palliat Care 2019; 36:871.
  64. Caraceni A, Speranza R, Spoldi E, et al. Palliative Sedation in Terminal Cancer Patients Admitted to Hospice or Home Care Programs: Does the Setting Matter? Results From a National Multicenter Observational Study. J Pain Symptom Manage 2018; 56:33.
  65. Mercadante S, Masedu F, Mercadante A, et al. Attitudes of palliative home care physicians towards palliative sedation at home in Italy. Support Care Cancer 2017; 25:1615.
  66. Zaporowska-Stachowiak I, Szymański K, Oduah MT, et al. Midazolam: Safety of use in palliative care: A systematic critical review. Biomed Pharmacother 2019; 114:108838.
  67. Laroche JP. Subcutaneous dexmedetomidine for baclofen withdrawal during palliative sedation. BMJ Support Palliat Care 2020; 10:7.
  68. Morita T, Inoue S, Chihara S. Sedation for symptom control in Japan: the importance of intermittent use and communication with family members. J Pain Symptom Manage 1996; 12:32.
  69. Rousseau P. Existential distress and palliative sedation. Anesth Analg 2005; 101:611.
  70. Taylor BR, McCann RM. Controlled sedation for physical and existential suffering? J Palliat Med 2005; 8:144.
  71. Ciancio AL, Mirza RM, Ciancio AA, Klinger CA. The Use of Palliative Sedation to Treat Existential Suffering: A Scoping Review on Practices, Ethical Considerations, and Guidelines. J Palliat Care 2020; 35:13.
  72. Voeuk A, Nekolaichuk C, Fainsinger R, Huot A. Continuous Palliative Sedation for Existential Distress? A Survey of Canadian Palliative Care Physicians' Views. J Palliat Care 2017; 32:26.
  73. Cherny NI, Radbruch L, Board of the European Association for Palliative Care. European Association for Palliative Care (EAPC) recommended framework for the use of sedation in palliative care. Palliat Med 2009; 23:581.
  74. Haynes AB, Weiser TG, Berry WR, et al. A surgical safety checklist to reduce morbidity and mortality in a global population. N Engl J Med 2009; 360:491.
  75. Hoffman GM, Nowakowski R, Troshynski TJ, et al. Risk reduction in pediatric procedural sedation by application of an American Academy of Pediatrics/American Society of Anesthesiologists process model. Pediatrics 2002; 109:236.
  76. Dean MM, Cellarius V, Henry B, et al. Framework for continuous palliative sedation therapy in Canada. J Palliat Med 2012; 15:870.
  77. Ghafoor VL, Silus LS. Developing policy, standard orders, and quality-assurance monitoring for palliative sedation therapy. Am J Health Syst Pharm 2011; 68:523.
  78. Verkerk M, van Wijlick E, Legemaate J, de Graeff A. A national guideline for palliative sedation in the Netherlands. J Pain Symptom Manage 2007; 34:666.
  79. Morita T, Bito S, Kurihara Y, Uchitomi Y. Development of a clinical guideline for palliative sedation therapy using the Delphi method. J Palliat Med 2005; 8:716.
  80. Royal Dutch Medical Association Committee on National Guideline for Palliative Sedation. Available at http://www.scribd.com/doc/100581822/KNMG-Guideline-for-Palliative-Sedation-2009-2 (Accessed on March 16, 2013).
  81. Kirk TW, Mahon MM, Palliative Sedation Task Force of the National Hospice and Palliative Care Organization Ethics Committee. National Hospice and Palliative Care Organization (NHPCO) position statement and commentary on the use of palliative sedation in imminently dying terminally ill patients. J Pain Symptom Manage 2010; 39:914.
  82. National Ethics Committee, Veterans Health Administration. The ethics of palliative sedation as a therapy of last resort. Am J Hosp Palliat Care 2006; 23:483.
  83. Braun TC, Hagen NA, Clark T. Development of a clinical practice guideline for palliative sedation. J Palliat Med 2003; 6:345.
  84. Hospice and Palliative Care Federation of Massachusetts. Palliative Sedation Protocol: A Report of the Standards and Best Practices Committee, Hospice and Palliative Care Federation of Massachusetts 2004, Norwood, MA.
  85. Quill TE, Byock IR. Responding to intractable terminal suffering: the role of terminal sedation and voluntary refusal of food and fluids. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians-American Society of Internal Medicine. Ann Intern Med 2000; 132:408.
  86. HPNA Position Statement: Palliative sedation at end of life; 2003 Hospice and Palliative Nurses Association Web site: http://hpna.advancingexpertcare.org/wp-content/uploads/2015/08/Palliative-Sedation.pdf (Accessed on November 05, 2015).
  87. American Academy of Hospice and Palliative Medicine. Statement on palliative sedation; 2013. http://aahpm.org/positions/palliative-sedation (Accessed on November 05, 2015).
  88. American Medical Association. Opinnion 2.201-sedation to unconsciousness in end of life care; 2008. http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion2201.page (Accessed on November 05, 2015).
  89. Gurschick L, Mayer DK, Hanson LC. Palliative Sedation: An Analysis of International Guidelines and Position Statements. Am J Hosp Palliat Care 2015; 32:660.
  90. Abarshi E, Rietjens J, Robijn L, et al. International variations in clinical practice guidelines for palliative sedation: a systematic review. BMJ Support Palliat Care 2017; 7:223.
Topic 83710 Version 26.0

References

1 : Sedation in the management of refractory symptoms: guidelines for evaluation and treatment.

2 : Pediatric palliative sedation therapy with propofol: recommendations based on experience in children with terminal cancer.

3 : Continuous deep sedation at the end of life of children in Flanders, Belgium.

4 : Palliative sedation in 2 children with terminal cancer - an effective treatment of last resort in a home care setting.

5 : End of life care sedation for children.

6 : Practice of palliative sedation in children with brain tumors and sarcomas at the end of life.

7 : Need they sleep before they die?

8 : Medication kits for managing symptomatic emergencies in the home: a survey of common hospice practice.

9 : ABC of palliative care. Emergencies.

10 : Crises in palliative care--a comprehensive approach.

11 : Palliative sedation in end-of-life care and survival: a systematic review.

12 : Palliative pharmacological sedation for terminally ill adults.

13 : Procedures used in withdrawal of mechanical ventilation.

14 : Patient responses during rapid terminal weaning from mechanical ventilation: a prospective study.

15 : Ordering and administration of sedatives and analgesics during the withholding and withdrawal of life support from critically ill patients.

16 : Effect of continuous deep sedation on survival in patients with advanced cancer (J-Proval): a propensity score-weighted analysis of a prospective cohort study.

17 : Palliative sedation in a specialized unit for acute palliative care in a cancer hospital: comparing patients dying with and without palliative sedation.

18 : Sedation at the end of life - a nation-wide study in palliative care units in Austria.

19 : Sedation for the relief of refractory symptoms in the imminently dying: a fine intentional line.

20 : Dealing with delicate issues in continuous deep sedation. Varying practices among Dutch medical specialists, general practitioners, and nursing home physicians.

21 : End-of-life decisions in Australian medical practice.

22 : Willingness to perform euthanasia. A survey of physician attitudes.

23 : Attitudes and practices concerning the end of life: a comparison between physicians from the United States and from The Netherlands.

24 : A national survey of physician-assisted suicide and euthanasia in the United States.

25 : The intention to hasten death: a survey of attitudes and practices of surgeons in Australia.

26 : Physician reports of terminal sedation without hydration or nutrition for patients nearing death in the Netherlands.

27 : Distinction between euthanasia and palliative sedation is clear-cut.

28 : Experiences of Family Members of Dying Patients Receiving Palliative Sedation.

29 : Clinical pragmatism: John Dewey and clinical ethics.

30 : Clinical pragmatism: a method of moral problem solving.

31 : Terminal sedation: a legal approach.

32 : Terminal sedation: a legal approach.

33 : The Supreme Court speaks--not assisted suicide but a constitutional right to palliative care.

34 : On withholding artificial hydration and nutrition from terminally ill sedated patients. The debate continues.

35 : On withholding nutrition and hydration in the terminally ill: has palliative medicine gone too far?

36 : Is sedation without hydration or nourishment in terminal care lawful?

37 : The Supreme Court and physician-assisted suicide--rejecting assisted suicide but embracing euthanasia.

38 : Review of palliative sedation and its distinction from euthanasia and lethal injection.

39 : Sedation for delirium and other symptoms in terminally ill patients in Edmonton.

40 : Continuous deep sedation in patients nearing death.

41 : Palliative sedation: an essential place for clinical excellence.

42 : The impact of the inpatient practice of continuous deep sedation until death on healthcare professionals' emotional well-being: a systematic review.

43 : Palliative sedation challenging the professional competency of health care providers and staff: a qualitative focus group and personal written narrative study.

44 : Nonmedical influences on medical decision making: an experimental technique using videotapes, factorial design, and survey sampling.

45 : Biases in how physicians choose to withdraw life support.

46 : Advanced care planning in children with life-limiting conditions - the Wishes Document.

47 : A Survey of Hospice and Palliative Care Physicians Regarding Palliative Sedation Practices.

48 : Palliative care specialists in hospice and hospital/community teams predominantly use low doses of sedative medication at the end of life for patient comfort rather than sedation: Findings from focus groups and patient records for I-CAN-CARE.

49 : The Principles of Revised Clinical Guidelines about Palliative Sedation Therapy of the Japanese Society for Palliative Medicine.

50 : Palliative sedation in patients with advanced cancer followed at home: a prospective study.

51 : The use of methotrimeprazine in terminal care.

52 : Evidence for the use of Levomepromazine for symptom control in the palliative care setting: a systematic review.

53 : The use of chlorpromazine for symptom control in dying cancer patients.

54 : Dyspnea: the continuing challenge of palliative management.

55 : Titrated intravenous barbiturates in the control of symptoms in patients with terminal cancer.

56 : Barbiturates in the care of the terminally ill.

57 : Prolonged sedation with midazolam or propofol.

58 : Propofol sedation for terminal care in a pediatric patient.

59 : Sedation for intractable distress of a dying patient: acute palliative care and the principle of double effect.

60 : Propofol in terminal care.

61 : The use of propofol in palliative medicine.

62 : Palliative sedation in advanced cancer patients followed at home: a retrospective analysis.

63 : Home Palliative Sedation Using Phenobarbital Suppositories: Time to Death, Patient Characteristics, and Administration Protocol.

64 : Palliative Sedation in Terminal Cancer Patients Admitted to Hospice or Home Care Programs: Does the Setting Matter? Results From a National Multicenter Observational Study.

65 : Attitudes of palliative home care physicians towards palliative sedation at home in Italy.

66 : Midazolam: Safety of use in palliative care: A systematic critical review.

67 : Subcutaneous dexmedetomidine for baclofen withdrawal during palliative sedation.

68 : Sedation for symptom control in Japan: the importance of intermittent use and communication with family members.

69 : Existential distress and palliative sedation.

70 : Controlled sedation for physical and existential suffering?

71 : The Use of Palliative Sedation to Treat Existential Suffering: A Scoping Review on Practices, Ethical Considerations, and Guidelines.

72 : Continuous Palliative Sedation for Existential Distress? A Survey of Canadian Palliative Care Physicians' Views.

73 : European Association for Palliative Care (EAPC) recommended framework for the use of sedation in palliative care.

74 : A surgical safety checklist to reduce morbidity and mortality in a global population.

75 : Risk reduction in pediatric procedural sedation by application of an American Academy of Pediatrics/American Society of Anesthesiologists process model.

76 : Framework for continuous palliative sedation therapy in Canada.

77 : Developing policy, standard orders, and quality-assurance monitoring for palliative sedation therapy.

78 : A national guideline for palliative sedation in the Netherlands.

79 : Development of a clinical guideline for palliative sedation therapy using the Delphi method.

80 : Development of a clinical guideline for palliative sedation therapy using the Delphi method.

81 : National Hospice and Palliative Care Organization (NHPCO) position statement and commentary on the use of palliative sedation in imminently dying terminally ill patients.

82 : The ethics of palliative sedation as a therapy of last resort.

83 : Development of a clinical practice guideline for palliative sedation.

84 : Development of a clinical practice guideline for palliative sedation.

85 : Responding to intractable terminal suffering: the role of terminal sedation and voluntary refusal of food and fluids. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians-American Society of Internal Medicine.

86 : Responding to intractable terminal suffering: the role of terminal sedation and voluntary refusal of food and fluids. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians-American Society of Internal Medicine.

87 : Responding to intractable terminal suffering: the role of terminal sedation and voluntary refusal of food and fluids. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians-American Society of Internal Medicine.

88 : Responding to intractable terminal suffering: the role of terminal sedation and voluntary refusal of food and fluids. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians-American Society of Internal Medicine.

89 : Palliative Sedation: An Analysis of International Guidelines and Position Statements.

90 : International variations in clinical practice guidelines for palliative sedation: a systematic review.