Administration of medications to reduce consciousness or induce sleep in patients suffering from refractory symptoms that are difficult to control is becoming more common in the palliative care setting, particularly in the end-of-life care. Palliative sedation refers to the intentional administration of medications that reduce the patient’s level of consciousness in situations where death is imminent (hours to days) in order to relieve their intolerable and intractable suffering. It involves the use of appropriate, carefully selected and dosed medications and is aimed at relieving suffering—not shortening or ending the patient’s life. This sedation may be intermittent (the patient desires the ability to rouse) or continuous. By contrast, medical assistance in dying (MAiD) (as it is referred to in Canada) refers to the prescription and administration of medications with the explicit intent of ending a patient’s life in order to relieve their suffering. Palliative sedation can be performed in the hospital and community settings with sufficient family and nursing support.
From the Canadian professional and ethical standpoints, medical practitioners have the obligation to offer or use palliative sedation in justified situations, when the patient’s suffering is intolerable and symptoms are refractory to other palliative treatment options. This responsibility is often neglected either for fear of being accused of shortening the patient’s life (ie, palliative sedation is confused with MAiD) or due to the lack of skills in administering sedation. Nevertheless, palliative sedation may have 2 kinds of effects: beneficial, of relieving refractory symptoms, and adverse, as deep sedation makes it impossible for patients to communicate, maintain interpersonal contacts, eat, or drink.
When used in the last days and hours of life, palliative sedation has not been shown to shorten life. However, if implemented early in the disease process, it has the potential to contribute to an unintended shortening of a patient’s life if no artificial nutrition or hydration is offered. Timing of palliative sedation should be discussed explicitly as part of the informed consent process (see below).
Indications for sedation in palliative care:
1) Relief of distressing and intolerable symptoms that are refractory to all other forms of treatment. Such symptoms may include dyspnea, anxiety or panic attacks, agitated delirium, pain, persistent nausea and hiccups, myoclonus, or seizures. This sedation is typically continuous but may still be intermittent if the patient desires the ability to rouse up.
2) Respite from brief painful procedures such as insertion of a central venous catheter or some nursing interventions (eg, painful dressing changes) or while awaiting another treatment option (eg, epidural for pain control). This sedation is typically intermittent and timed around the required procedure.
1. The decision to administer sedation should be preceded by a thorough clinical assessment, which includes the patient’s general clinical status, possible alternative therapies, reversibility of symptoms, and life expectancy.
2. In competent and conscious patients informed consent must be obtained. This requires holding a frank discussion with the patient to explain the aims and methods used in sedation. It is important to make the patient aware that sedation impairs consciousness, induces deep sleep (making communication with family or caregivers impossible), prohibits any involvement in making decisions or in further preparations for the end of life. Any decisions around other aspects of care, such as artificial hydration or nutrition, must be made prior to initiating sedation. Goals of care have to be focused on comfort. Do-not-resuscitate (DNR) and allow-natural-death (AND) orders have to be documented. The patient should be aware of imminent death and have the opportunity to say goodbye to family or caregivers before continuous palliative sedation is instituted. If the patient’s condition makes obtaining informed consent impossible, the consent should be sought from a substitute decision-maker (SDM), such as the family or an appointed power of attorney, who needs to be fully aware of the consequences of sedation. If the patient requires urgent suppression of consciousness (in case of a massive hemorrhage or choking/respiratory distress), sedation may be used for the immediate relief of suffering without the consent of the patient, family, or caregivers.
3. It is recommended that all patients being considered for palliative sedation have a consultation with a palliative care physician to ensure that all possible treatment strategies have been tried prior to the initiation of sedation. The administration of palliative sedation should be guided by a physician experienced in this procedure. This is typically a palliative care physician, anesthesiologist, or critical care physician.
4. Pain management should be continued (usually with opioids [see Pain Management: Basic Principles]) throughout sedation.
5. Sedatives are administered in a continuous IV or continuous subcutaneous infusion or via intermittent or repeated injections (every 4 hours and as needed) to maintain sedation.
6. The degree of sedation should be proportional to the degree of refractory symptom being managed. sedation should be re-assessed regularly, usually several times a day. Particular focus should be paid to the depth of sedation (the patient being roused by painful stimuli) and effectiveness (presence of distressing symptoms). The goal of sedation with any medication is to ensure comfort. There is usually no need for routine administration of oxygen, monitoring oxygen saturation (SaO2), or routine vital sign checks.
The dosages below are examples only. Individual patients may respond to smaller or may require higher doses.
1. Midazolam: A short-acting benzodiazepine with sedative, anxiolytic, hypnotic, and skeletal muscle relaxing properties. For continuous sedation start with an IV or subcutaneous injection of 0.25 to 1 mg followed by a continuous infusion at the rate of 0.25 to 1 mg/h (or higher if needed). Higher initial doses (2.5-5 mg) may be required in severely distressed patients (eg, with agitated delirium). For intermittent sedation start with 0.5 to 2 mg subcutaneously every 2 to 4 hours. Patients who have been receiving benzodiazepines prior to initiation of sedation should start at doses at least equivalent to their baseline dose. The onset of action is within 1 to 3 minutes (IV) or 10 to 15 minutes (subcutaneous administration). The duration of action is 15 to 30 minutes after discontinuation of infusion. Depending on dose and infusion rate, midazolam may lead to central respiratory depression, particularly when used in combination with opioids. The duration of action may be markedly prolonged with repeated intermittent injections.
2. Methotrimeprazine: A sedating neuroleptic useful for agitated delirium. The initial dose is 6.25 to 12.5 mg in subcutaneous injections every 4 to 8 hours and then titrated as needed; the dose may need to be titrated up to 25 to 50 mg. The agent suppresses nausea and vomiting and may have weak analgesic properties, but it also lowers the seizure threshold and has potential extrapyramidal adverse effects.
3. Phenobarbital: A sedating anticonvulsant useful for all types of seizures and as a third-line sedating agent. Doses range between 30 and 120 mg subcutaneously every 8 to 12 hours and then titrated as needed.
4. Propofol: An anesthetic agent recommended in patients not responding to other therapies. Propofol should be used in a monitored setting (in many hospitals it can be used exclusively in critical care areas). Initial doses of 5 to 20 mg are administered every 90 seconds to 2 minutes and followed by a continuous IV infusion at the rate of 10 to 70 mg/h. The onset of action is within several seconds and duration of action is 2 to 3 minutes. Propofol also suppresses vomiting and hiccups.
5. Haloperidol: Haloperidol may be used in addition to midazolam for delirium or for other symptoms such as nausea or emesis. The initial doses are 0.5 to 2 mg in subcutaneous intermittent injections every 4 to 6 hours. Haloperidol is not recommended as a single agent for palliative sedation as it is not a sedating neuroleptic and with high doses potentially increases the risk of extrapyramidal adverse effects.
Opioids should not be used for sedation. While it is important to initiate and continue them along with sedatives to ensure comfort and analgesia, opioids are not appropriate as the single agent for inducing palliative sedation because sedating doses cause many adverse effects.