INTRODUCTION — Many patients suffer from untreated pain at the end of life. This topic review will focus on the ethical issues surrounding pain management in patients receiving end-of-life care. Other ethical issues that arise in patients receiving palliative care (eg, advance care planning, withholding and withdrawing of life-sustaining treatments, medical aid in dying), principles of pain management, and palliative sedation for control of refractory symptoms at the end of life are discussed elsewhere. (See "Advance care planning and advance directives" and "Ethical issues in palliative care" and "Kidney palliative care: Withdrawal of dialysis" and "Medical aid in dying: Ethical and legal issues" and "Kidney palliative care: Principles, benefits, and core components", section on 'Pain' and "Palliative sedation".)
SCOPE OF THE ISSUE — Failure to treat pain effectively can result from a lack of clinician training in palliative care or from the fear of violating ethical, moral, and legal tenets in the administration of pain medication to the dying patient. Clinicians may have an exaggerated perception of the risk of hastening death when treating patients with opioids. Furthermore, some clinicians may be unclear about the distinctions between pain management, sedation for intractable symptoms, medica aid in dying, and euthanasia. Clinicians are faced with balancing these concerns with their legal duty and moral obligation to treat pain in the suffering patient, as well as their obligation to educate themselves on the differences between these approaches. (See "Palliative sedation" and "Medical aid in dying: Ethical and legal issues".)
Studies of dying patients reveal that up to 47 percent describe moderate or severe pain in the last month of life and 25 percent experience uncontrolled pain in the last week of life [1,2]. Some experts define the escalation of pain that is uncontrolled at the end of life as a “medical emergency” . Untreated pain can be devastating to the patient and family or other loved ones not only because of the suffering it produces but also because it interferes with the ability to complete important tasks at the end of life, such as getting legal affairs in order, grieving the loss of their life, making amends in strained relationships, and saying goodbye to loved ones.
Pain management at the end of life is the right of the patient and the duty of the clinician. The World Health Organization states that patients have a right to have their pain treated, as does the United States Supreme Court [4,5]. (See "Legal aspects in palliative and end-of-life care in the United States".)
UNITED STATES LEGAL CONSIDERATIONS — Some clinicians may be unclear about how aggressive symptom management in palliative care differs from medical aid in dying and voluntary active euthanasia. Palliative care is a comprehensive approach to treating physical, spiritual, and psychological suffering in a patient at any stage of a serious illness, including at the end of life. While this may include prescribing pain medication that carries with it a very small risk of hastening death, any hastening of death is not the intention of the treating clinician. The use of medication intended to treat pain or relieve discomfort is legal in all US states.
By contrast, medical aid in dying involves supplying a patient with the means to end their life when desired. In the United States, medical aid in dying is legal in some states. Voluntary active euthanasia, which requires a clinician to physically administer a medication with the intent of causing death, is illegal in all states but is permitted in certain other countries. (See "Medical aid in dying: Ethical and legal issues".)
In the United States, no legal barrier exists to treating pain; in fact, there is a legal risk to clinicians who do not effectively treat pain. For example, in 2021, a woman in Kentucky successfully sued a pain clinic and its physicians for improperly reducing her husband’s opioid dose, which, she contended, led to his death by suicide. The jury found that the physicians and clinic were at fault and awarded the man’s family almost USD $7 million in damages .
RELIGIOUS VIEWS — Ethical consensus exists in the standard treatment of pain at the end of life . Religious groups have also addressed this issue . For example, the Catechism of the Catholic Church states, “Even if death is thought imminent, the ordinary care owed to a sick person cannot be legitimately interrupted. The use of painkillers to alleviate the sufferings of the dying, even at the risk of shortening their days, can be morally in conformity with human dignity if death is not willed as either an end or a means, but only foreseen and tolerated as inevitable. Palliative care is a special form of disinterested charity. As such, it should be encouraged” .
Jewish religious law upholds both the sanctity of life and a duty to alleviate suffering. When the two seem to conflict at the end of life, most rabbinical authorities agree that it is acceptable to treat pain and to allow the natural dying process to take place . According to a 2017 systematic review, in Islam, pain is seen as a means through which patients connect with Allah (God) and atone for their sins. While pain control is theologically permitted, it is not to be at the expense of ongoing medical treatment. At the same time, Islamic teaching does acknowledge death as a part of life and therefore that one should not stand in the way of the dying process when death is imminent . For Buddhists, mindfulness and mental clarity are key values. Therefore, some Buddhists may prefer not to take analgesics that could sedate them, even if it causes them to be in more pain .
Understanding risks — Opioids have multiple desirable and undesirable effects (see "Cancer pain management: General principles and risk management for patients receiving opioids" and "Prevention and management of side effects in patients receiving opioids for chronic pain"). Opioids provide analgesia but, at increased doses, may cause sedation and even respiratory depression. Respiratory depression does not occur in isolation but always in the context of sedation and mental clouding. These precursors to respiratory depression allow for a careful reversal of the opioid with naloxone (an opioid antagonist) if necessary. That said, the use of naloxone often falls outside of the scope of end-of-life care when clinicians and families focus on comfort and allowing a natural death.
Best practices for the use of opioids to treat end-of-life pain include the use of intermittent doses as needed for intermittent symptoms and careful titration of long-acting opioid preparations or continuous infusion of opioids for continuous pain or dyspnea. By contrast, the practice of initiating opioid therapy with continuous infusion of opioids with a broad range of “as needed” doses for titration in opioid-naïve patients is discouraged.
While the data are mixed, most studies demonstrate no association between opioid use and mortality in seriously ill populations. For example, appropriately dosed opioids and other sedating medications were not associated with decreased survival in a study of terminally ill patients with cancer . The risk of respiratory depression is of greatest concern in patients with comorbid cardiac, pulmonary, kidney, or hepatic dysfunction, as well as in those also prescribed other central nervous system depressant medications [14,15]. The simultaneous use of opioids and benzodiazepines carries an increased risk, particularly in older patients [16,17]. Caution is also warranted in opioid-naïve patients . With continuous use of opioids, sedation and respiratory depression are effects to which patients quickly develop tolerance. Nevertheless, it is important not to gloss over this risk, which, while rare, is not nonexistent. (See "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Sleep-disordered breathing'.)
The risks associated with the use of opioids are best thought of in the same way clinicians weigh the risks and benefits of any intervention. Let us consider, for example, a patient who requires a thoracentesis to alleviate dyspnea related to a pleural effusion. The patient has a risk of pneumothorax and possible death as a result of the procedure. This is a very uncommon adverse event when the procedure is done by a skilled clinician. The benefit of the procedure may be to greatly decrease the dyspnea caused by the pleural effusion. Clinicians would not avoid the thoracentesis because it carries with it a small risk of an adverse event when the benefits to relieve suffering are so great. They would, however, attempt to reduce the chance of these events as much as possible and inform the patient of these risks. The same is true of the treatment of pain at the end of life. Treatment with opioids carries with it a very small but real chance of respiratory depression. This risk, however, does not outweigh the benefit of giving the drug.
Principle of double effect — The position of the Catholic Church and the United States Supreme Court is that aggressive treatment of pain at the end of life is legally and morally acceptable, even in the rare circumstance that death is hastened, provided the intention of the action (administering sedating medication) is to relieve pain and not to cause death. This is the principle of double effect (PDE), a concept that originated in the Catholic Church. This principle stipulates that the action taken (administering medication to relieve pain) is morally good or neutral, the intended outcome (relief of pain) is important enough to justify the unlikely but possible bad effect (death), efforts are undertaken to minimize risk of the bad effect, and the unintended effect is not the means to achieve the desired effect .
A classic example of PDE is the following: a clinician may find it morally unacceptable to directly abort a fetus, yet they may find it morally acceptable to remove a diseased uterus that may contain a fetus to save the life of a pregnant woman. The clinician does not intend to cause the death of the fetus, although it is expected. The key element of PDE is that the intentions of the actor are only good, even if the bad effect is foreseen . PDE is often invoked in writings about the treatment of pain at the end of life.
The bioethical PDE is important to patients and to the clinicians who care for these individuals. As Quill states, “To the extent that the principle allows patients, families, and clinicians to respond in an ethically and clinically responsible way to palliative care emergencies without violating the fundamental values of any of the participants, it (PDE) should be used and protected”  The PDE would only need to be invoked if the treatment of pain frequently carried with it a substantial risk of hastened death. In truth, opioids are unlikely to hasten death if used in an appropriate manner by a skilled clinician.
Balancing pain control and alertness — While opioids are unlikely to cause respiratory depression when dosed appropriately, patients may become sedated and less able to interact with loved ones, friends, and family. In these situations, our practice is to ask patients how they prioritize pain control and alertness. In some cases, patients choose pain control, recognizing that their time awake may be shorter. In other cases, patients choose alertness, recognizing that their pain may be under less control.
Clinicians also have a role in educating families and other clinicians and staff about appropriate titration of opioids and other medications at the end of life. Well intentioned loved ones or less experienced clinicians may advocate for the administration of inappropriately high doses of opioids to alleviate suffering, particularly for patients who are no longer able to communicate. Here we recommend aligning with their goal of ensuring the patient’s comfort while also gently educating them on the importance of appropriate titration of medications .
PALLIATIVE SEDATION FOR INTRACTABLE PAIN — With aggressive palliative care, acceptable pain relief can be provided to 85 percent of patients at the end of life . Unfortunately, there is a minority of patients, 2 to 5 percent, in which adequate pain control cannot be achieved despite expert pain management. For these patients, palliative sedation may successfully alleviate severe, refractory pain. Medications (typically short-acting benzodiazepines) are administered in increasingly higher doses to achieve maximum relief from physical symptoms, such as pain, that cannot be otherwise controlled.
The intent of palliative sedation is to relieve the burden of otherwise intolerable suffering for patients at the end of life and to do so in such a manner so as to preserve the moral sensibilities of the patient, medical professionals involved in their care, and concerned family and friends. The decision to use sedation to relieve intolerable suffering at the end of life is legally and morally acceptable according to the principle of double effect (PDE), even if death is hastened (see 'Principle of double effect' above). Notably, professional organizations such as the American Medical Association, American Academy of Hospice and Palliative Medicine, and American College of Physicians endorse palliative sedation for pain control when it is used as a last resort for symptom control at the end of life, thereby relying on the PDE’s “proportionality” clause .
An in-depth discussion of palliative sedation is provided separately. (See "Palliative sedation".)
SUMMARY AND RECOMMENDATIONS
●Importance of treatment – The treatment of pain at the end of life is the right of the patient and a moral duty, as well as legal obligation, of the clinician caring for the suffering. (See 'Scope of the issue' above and 'United States legal considerations' above.)
●Understanding risk of opioid use – Myths and misconceptions about the risks associated with the use of opioids exist in the literature and in clinical practice as well as in the lay public. The small risk of respiratory depression that opioids carry when used appropriately does not justify withholding their use in treatment of pain and other intractable symptoms at the end of life. (See 'Understanding risks' above.)
•The risk of respiratory depression is greatest in patients with comorbid cardiac, pulmonary, kidney, or hepatic dysfunction and in those simultaneously prescribed other central nervous system depressant medications.
●Principle of double effect – Aggressive treatment of pain at the end of life is legally and morally acceptable, even if death is hastened by treatment, provided the intention of the action (administering sedating medication) is to relieve pain and not to cause death. This concept is referred to as the principle of double effect (PDE) and is an important underlying treatment principle in end-of-life care. (See 'Principle of double effect' above.)
●Palliative sedation as last option – For the minority of patients for whom adequate pain control cannot be achieved despite expert pain management, palliative sedation may successfully alleviate severe, refractory pain. (See 'Palliative sedation for intractable pain' above and "Palliative sedation".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Lida Nabati, MD, who contributed to an earlier version of this topic review.
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