Palliative Sedation in Patients With Terminal Illness

Indications

There is no universal definition for refractory symptoms; thus, it is up to the clinician and the hospital staff's discretion to determine if certain intractable symptoms would warrant the initiation of palliative sedation. However, in general, the following are considered to fit the criteria for palliative sedation:

• The candidate for palliative sedation must have a terminal illness where death is almost certain. 
• The patient's clinical presentation must be such that conventional therapies are incapable of providing relief despite maximal doses, and symptom relief cannot be obtained without affecting consciousness. 
• Alternatively, a scenario can exist when conventional therapies are associated with potential adverse outcomes in patients at high doses or frequent administration of agents and thus warranting the use of palliative sedation, eg, use of frequent and high doses of Ondansetron to relieve nausea and vomiting can be associated with QTc prolongation and cardiac arrhythmias. Using sedating agents such as benzodiazepine (midazolam) might be a suitable alternative that can relieve nausea and avoid the risk of cardiac arrhythmias. 
• Palliative sedation can be considered if traditional therapies cannot provide relief of symptoms in a timely manner, eg, using intravenous or intramuscular antipsychotics in acutely agitated and delirious patients with a terminal illness offers quicker results compared to standard reorientation techniques in patients, and may be necessary for the safety of the patient or caregivers. 
• Well-documented goals of care discussions with the patient or surrogates must be present to outline the plan of care and potential risks of using palliative sedation.[17][18]

Ethical and Legal Issues 

Although there has been a well-demonstrated benefit of better symptom control in patients with a terminal illness treated with palliative sedation, the topic continues to garner some controversy. Most clinicians and organizations' chief concern regarding the administration of palliative sedation is that it may inadvertently hasten or quicken someone's demise. Due to this concern, the practice of palliative sedation is still compared with physician-assisted suicide and euthanasia. Below, we will briefly describe the fundamental concept and differences between these therapies in terminally ill patients.[7][19][20]

Euthanasia

Euthanasia constitutes the process by which a health care worker caring for a patient intentionally uses medications to terminate a patient's life to end their pain and suffering. Euthanasia can either be performed with the patient's consent (voluntary euthanasia) or performed independently by the health care providers (involuntary euthanasia). The practice of involuntary euthanasia is illegal in all countries.[19][21]

Physician-Assisted Suicide

Physician-assisted suicide is the process by which a physician acts as a facilitator for a patient to hasten death by providing lethal doses of prescription medication. It differs from euthanasia in that the healthcare worker assumes a passive role of supervision, and the actual administration of medication that leads to death has to be done by the patients on their own.[22]

In the United States, physician-assisted suicide is legal in some states but not all. In these states, "death with dignity" statutes ensure that the adult is mentally competent, is a state resident who has a terminal illness with a confirmed prognosis of having 6 or fewer months to live, and can voluntarily request a prescription for medication that hastens death.[23]

Differentiating Palliative Sedation from Euthanasia and Physician-assisted Suicide

Palliative sedation as a practice differs from euthanasia and physician-assisted suicide on 2 fronts: intention and the desired outcome. Palliative sedation intends to relieve refractory symptoms in dying patients, whereas the intention of physician-assisted suicide and euthanasia is the termination of a patient's life. Similarly, the desired outcome of palliative sedation is to achieve a level of sedation in patients that controls their symptoms. Whereas in physician-assisted suicide and euthanasia, the desired outcome is always the death of the patient. Although some healthcare workers still raise ethical concerns regarding its use, palliative sedation is legal in most countries, including the United States. 

Preparation

Timing of Palliative Sedation

Determining the most appropriate time to initiate palliative sedation is often a challenging process. Firstly, there are inconsistencies in defining what to label as "refractory symptoms" due to the lack of consensus among clinicians. In general, a refractory symptom is one that has not responded to multiple conventional treatments, and other treatment options that would not cause sedation are unlikely to provide adequate relief within a tolerable time frame or are associated with excessive and intolerable adverse effects.[17] Secondly, as palliative sedation is usually reserved for the end of life of terminally ill patients, determining the prognosis of the disease is an important step in planning for palliative sedation. Prior literature has demonstrated that healthcare workers are not always accurate when predicting the prognosis or estimated timing of decline due to diseases. Thus, labeling a disease as "terminal" and without a cure remains a difficult task for clinicians.[24][25]

Understanding Proportional Treatment and the Doctrine of "Double Effect" 

The goal of palliative sedation is to relieve intractable distressing symptoms, not to keep the patient unresponsive or unconscious. Thus, the concept of proportional treatment must be understood while using palliative sedation. Medications such as benzodiazepines, opiates, and antipsychotics are often used to alleviate patients' respiratory distress, agitation, and anxiety and can also cause sedation. However, the dose and frequency with which benzodiazepines, opiates, and antipsychotics should be titrated and always be proportional to the desired clinical benefit, which is relief from suffering and disturbing symptoms. Extreme cases in which a patient has to be given a high dose of sedatives exist when keeping them obtunded is the only way to alleviate their symptoms, eg, extreme agitation or seizures. However, the goal of treatment is adequate relief of symptoms, not to achieve sedation or unconsciousness in its own right. 

An additional ethical concept that needs to be understood regarding palliative sedation is the doctrine of "double effect." This doctrine originated from Thomas Aquinas in the 13th century and parallels the principles of beneficence and non-maleficence. [26]

This doctrine asserts the following:

"An action in the pursuit of a good outcome is acceptable, even if it is achieved through means with an unintended but foreseeable negative outcome if that negative outcome is outweighed by the good outcome."

Some recent studies have shown that palliative sedation is safe in terminally ill patients and is not associated with an increased risk of death. However, it is important to highlight the use of potential risks of excess sedation. Palliative sedation can be associated with an increased risk of aspiration, respiratory depression, and worsening agitation due to delirium. These adverse outcomes are unintended effects of therapy and not the primary intended outcome of palliative sedation. Thus, as per the doctrine of "double effect," as long as the patient, family, and physicians are aware of the potential adverse effects coupled with palliative sedation, it can be administered without any hesitation.[27][28][29][28]

Initiating Goals of Care Discussion with Patients, Family Members, or Surrogates

Initiating conversations regarding goals of care with patients with terminal illness and their family members can be challenging. Clinicians and healthcare workers benefit from additional training, including communication skills and navigating challenging and often emotional conversations. They need to identify patients with poor prognoses and refractory symptoms who are likely to benefit from palliative sedation. Prior studies have demonstrated several communication barriers and misconceptions regarding end-of-life issues in physicians and patients/family members.[13][14] There is ample evidence that shows that there is room for improvement when it comes to discussing issues such as reviewing the code status of patients, conveying poor prognosis of the disease, converting to hospice care, and initiating palliative sedation. Due to a lack of consensus regarding the definition of palliative sedation and its indications, there are often misconceptions among patients and family members regarding the use of palliative sedation.[15][16] 

Given its close resemblance to euthanasia and physician-assisted suicide, every attempt must be made to delineate the patient's/family's wishes and manage expectations properly. Often, interdisciplinary teams can assist these challenging conversations and will often include the medical providers (including palliative care providers, specialists, and primary care providers), patients, family members (or surrogates), social workers, and chaplains. These conversations need to address the prognosis of the disease and define the specific symptoms that have not abated with standard therapy. The pros and cons of palliative sedation should be explained during this meeting. Potential adverse effects, such as the risk of inadvertently hastening death, aspiration, and excess sedation, must be addressed while clearly expressing the treatment goals, including the relief of intolerable symptoms and suffering. 

Discussing Ongoing Care and Obtaining Consent

After a thorough goals-of-care discussion, written or verbal consent must be documented from the patient or surrogate decision-maker regarding their willingness to initiate palliative sedation. For patients who cannot communicate their wishes due to a decreased level of cognitive capacity, consciousness, or nonverbal state, we must follow the patient's advance directives, or if there is no advance directive, consent must be obtained from a legally recognized proxy. Patients and families should be assured that being started on palliative sedation does not imply that any ongoing medical or nursing care that has been beneficial to the patient will be withdrawn by default. Detailed goals of care should address what therapies would be added or continued for the patient's care and those that can be discontinued. For example, there should be a detailed discussion regarding issues such as feeding and artificial nutrition in terminally ill patients. Clinicians should clearly explain the prognosis and life expectancy and discuss with patients/family members whether it is prudent to continue feeding tubes and nutrition or to discontinue it entirely to limit patient distress (mainly if life expectancy is in the range of hours to days).

Technique or Treatment

Pharmacology

The following are the common pharmacological agents that can be used in palliative sedation.[30][31][32][33] 

Respite Sedation vs Continuous Sedation

Respite sedation refers to the temporary use of sedative agents to relieve symptoms such as pain, nausea, and agitation. These symptoms may or may not be refractory. Patients are typically started on sedative agents for a brief, predetermined period (eg, 1 to 48 h) with frequent reassessment. The dose of the sedating agent is then decreased until the patient is fully conscious after the predetermined period.

Most patients with a terminal illness and refractory pain who have shown poor response to conventional therapy are placed on continuous sedation. As the name suggests, with this form of sedation, no attempt is made to wean the sedative medication off, and it is typically continued until the patient's demise. 

Complications

The use of palliative sedation continues to be a controversial topic, given that its use can potentially hasten death. As such, the pros and cons of palliative sedation should be clearly outlined to the patient/family to manage expectations. Excess sedation can theoretically cause an increased risk of aspiration pneumonia and respiratory suppression. However, contrary to this belief, recent studies have demonstrated that palliative sedation can be safely administered without any disproportionate increase in the incidence of aspiration pneumonia or respiratory failure.[34][35][34] Additionally, other studies have demonstrated that the time till death is not significantly shortened in patients receiving palliative sedation compared to patients receiving standard or alternative therapy.[36][37]

Clinical Significance

Identifying terminally ill patients with refractory symptoms and the timely initiation of goals-of-care discussions are paramount to patient care. This will not only ensure that the patient's wishes are honored but also assist in withholding any redundant therapies or invasive procedures that are unlikely to improve the patient's symptoms or delay disease progression. Prior studies have demonstrated that palliative care has enormous benefits in patients beyond just pain control. These studies reveal that providing interprofessional care and family meetings enhances the bond between the patient, family, and caregivers and relieves stress, anxiety, and frustration.[38][39]

Enhancing Healthcare Team Outcomes

Providing palliative care requires an interprofessional team approach. It includes managing a broad range of refractory symptoms, including shortness of breath, agitation, delirium, and pain. Currently, most healthcare institutions have a palliative care management team that assesses patients for their palliative care needs. The team usually consists of a physician, nurse, pharmacist, pain specialist, religious figure, and ethics committee members. Palliative care should be individualized for each patient based on goals of care discussions with the patient and family. Nurses and pharmacists are vital team members as they closely monitor the patient for adverse effects and effectiveness of the sedative medications. In addition to pharmacological methods to relieve pain, several nonpharmacological methods are available. Some of these nonpharmacological methods are radiation therapy, radiofrequency ablation, heat, ice, or coolant sprays, and may warrant the inclusion of other specialties such as pain medicine and radiation oncology.