Symptom Relief for the Dying Patient

About half of patients dying of cancer have severe pain. Yet, only half of these patients receive reliable pain relief. Many patients dying of organ system failure and dementia also have severe pain. Sometimes pain can be controlled but persists because patients, family members, and physicians have misconceptions about pain and the drugs (especially opioids) that can relieve it, resulting in serious and persistent underdosing.

Patients perceive pain differently, depending partly on whether other factors (eg, fatigue, insomnia, anxiety, depression, nausea) are present. Analgesic choice depends largely on pain intensity and cause, which can be determined only by talking with and observing patients. Patients and physicians must recognize that all pain can be relieved by an appropriately potent drug at sufficient dosage, although aggressive treatment may also cause sedation or confusion. Commonly used drugs are aspirin, acetaminophen, or nonsteroidal anti-inflammatory drugs (NSAIDS) for mild pain; oxycodone for moderate pain; and hydromorphone, morphine, or fentanyl for severe pain (see Treatment of Pain).

In dying patients, oral opioid therapy is convenient and cost-effective. Sublingual administration is also convenient particularly because it does not require patients to swallow. In the unusual case where opioids cannot be given orally or sublingually, they can be given rectally, or by injection (IM, IV, or subcutaneously). Long-acting opioids are best for long-lasting pain. Physicians should prescribe opioids in adequate dosages and on a continuous basis and make additional, short-acting opioids available for breakthrough pain. Concerns by the public and by health care practitioners about addiction may unreasonably limit appropriate use of opioids in dying patients. Pharmacologic dependence may result from regular use but causes no problems in dying patients except the need to avoid inadvertent withdrawal. Prescription opioid risk mitigation strategies, such as prescription drug monitoring programs and opioid reversal drugs like naloxone, are not usually necessary for dying patients.

Adverse effects of opioids include nausea, sedation, confusion, constipation, and respiratory depression. Opioid-induced constipation should be treated prophylactically. Patients usually develop substantial tolerance to the respiratory depressant and sedative effects of morphine but develop much less tolerance for the analgesic and constipating effects. Opioids may also cause myoclonus, agitated delirium, hyperalgesia, and seizures. These neurotoxic effects may result from accumulation of toxic metabolites and usually resolve when another opioid is substituted. Patients with these adverse effects and serious pain often warrant consultation with a palliative care or pain specialist.

When a stable opioid dose becomes inadequate, increasing the dose by 1½ to 2 times the previous dose (eg, calculated based on daily dose) is reasonable. Usually, serious respiratory depression occurs only if the new dose is much more than twice the previously tolerated dose.

Use of adjunctive drugs for pain relief often increases comfort and reduces the opioid dosage and consequent adverse effects. Corticosteroids can reduce the pain of inflammation and swelling. Tricyclic antidepressants (eg, nortriptyline, doxepin) help manage neuropathic pain; doxepin can provide bedtime sedation as well. Gabapentin 300 to 1200 mg orally 3 times a day can help relieve neuropathic pain. Methadone is effective for refractory or neuropathic pain; however, its kinetics vary, and it requires close monitoring. Ketamine can be an effective nonopioid alternative for treating pain. Benzodiazepines are useful for patients whose pain is worsened by anxiety.

For severe localized pain, regional nerve blocks given by an anesthesiologist experienced in pain management may provide relief with few adverse effects. Various nerve-blocking techniques may be used. Indwelling epidural or intrathecal catheters can provide continuous infusion of analgesics, often mixed with anesthetic drugs.

Pain-modification techniques (eg, guided imagery, hypnotherapy, acupuncture, relaxation, biofeedback) help some patients. Counseling for stress and anxiety may be very helpful, as may spiritual support from a chaplain.

Dyspnea is one of the most feared symptoms and is extremely frightening to dying patients. The main causes of dyspnea are heart and lung disorders. Other factors include severe anemia and chest wall or abdominal disorders that cause painful respiration (eg, rib fracture) or that impede respiration (eg, massive ascites). Metabolic acidosis causes tachypnea but does not cause a sensation of dyspnea. Anxiety (sometimes due to delirium or pain) can cause tachypnea with or without a feeling of dyspnea.

Reversible causes should be treated specifically. For example, placing a chest tube for tension pneumothorax or draining a pleural effusion provides quick and definitive relief. Supplemental oxygen can sometimes correct hypoxemia. Nebulized albuterol and oral or injectable corticosteroids may relieve bronchospasm and bronchial inflammation. However, if death is imminent or a definitive treatment for the cause of dyspnea is not available, proper symptomatic treatment assures patients they will be comfortable, regardless of the cause. If death is expected and the goals of care focus on comfort, then pulse oximetry, arterial blood gases, electrocardiography, and imaging are not indicated. Clinicians should use general comfort-oriented treatments including positioning (eg, sitting up), increasing air movement with a fan or open window, and bedside relaxation techniques.

Opioids are the drugs of choice for dyspnea near the end of life. Low doses of morphine 2 to 10 mg sublingually or 2 to 4 mg subcutaneously every 2 hours as needed helps reduce breathlessness in an opioid-naive patient. Morphine may blunt the medullary response to CO2 retention or O2 decline, reducing dyspnea and decreasing anxiety without causing harmful respiratory depression. If patients are already taking opioids for pain, dosages that relieve the new onset of dyspnea must often be more than double the patient’s usual dosages. Benzodiazepines often help relieve anxiety caused by dyspnea and the fear of a return of dyspnea.

Oxygen may also give psychologic comfort to patients and family members even if it does not correct hypoxemia. Patients usually prefer oxygen via nasal cannula. An oxygen face mask may increase agitation of a dying patient. Nebulized saline may help patients with viscous secretions.

The death rattle is noisy breathing that results from air moving across pooled secretions in the oropharynx and bronchi and often portends death in hours or days. The death rattle is not a sign of discomfort in the dying patient but can disturb family members and caregivers. To minimize the death rattle, caregivers should limit patients' fluid intake (eg, oral, IV, enteral) and position patients on their side or semi-prone. Oropharyngeal suctioning is generally ineffective in reaching the pooled secretions and may cause discomfort. Airway congestion is best managed with an anticholinergic drug such as scopolamine, glycopyrrolate, or atropine (eg, glycopyrrolate beginning with 0.2 mg subcutaneously every 4 to 6 hours or 0.2 to 0.4 mg orally every 8 hours, with dose increases as needed). Adverse effects mostly occur with repeated doses and include blurred vision, sedation, delirium, palpitations, hallucinations, constipation, and urinary retention. Glycopyrrolate does not cross the blood-brain barrier and results in fewer neurotoxic adverse effects than other anticholinergics.

Anorexia and marked weight loss are common among dying patients. For family members, accepting the patient’s poor oral intake is often difficult because it means accepting that the patient is dying. Patients should be offered their favorite foods whenever possible. Conditions that may cause poor intake and that can be easily treated—gastritis, constipation, toothache, oral candidiasis, pain, and nausea—should be treated. Some patients benefit from appetite stimulants such as oral corticosteroids (dexamethasone 2 to 8 mg 2 times a day or prednisone 10 to 30 mg once a day) or megestrol 160 to 480 mg orally once a day. However, if a patient is close to death, family members should be helped to understand that neither food nor hydration is necessary to maintain the patient’s comfort.

IV fluids, total parenteral nutrition, and tube feedings do not prolong the life of dying patients, may increase discomfort, and even hasten death. Adverse effects of artificial nutrition in dying patients can include pulmonary congestion, pneumonia, edema, and pain associated with inflammation. Conversely, dehydration and ketosis due to caloric restriction correlate with analgesic effects and absence of discomfort. The only reported discomfort due to dehydration near death is xerostomia, which can be prevented and relieved with oral swabs or ice chips.

Even debilitated and cachectic patients may live for several weeks with no food and minimal hydration. Family members should understand that stopping medically supplied fluids does not result in the patient’s immediate death and ordinarily does not hasten death. Supportive care, including good oral hygiene, is imperative for patient comfort during this time.

Many seriously ill patients experience nausea, frequently without vomiting. Nausea may arise with gastrointestinal problems (eg, constipation, gastritis), metabolic abnormalities (eg, hypercalcemia, uremia), drug adverse effects, increased intracranial pressure secondary to cerebral cancer, and psychosocial stress. When possible, treatment should match the likely cause—eg, stopping NSAIDs, treating gastritis with proton pump inhibitors, and trying corticosteroids for patients with known or suspected brain metastases. If nausea is due to gastric distention and reflux, metoclopramide (eg, 10 to 20 mg orally or subcutaneously 4 times a day as needed or given on a scheduled basis) is useful because it increases gastric tone and contractions while relaxing the pyloric sphincter.

The 5-hydroxytryptamine (5-HT)3 antagonists ondansetron and granisetron often dramatically relieve nausea. Patients with no specific cause of nausea may benefit from treatment with a phenothiazine (eg, promethazine 25 mg orally 4 times a day; prochlorperazine 10 mg orally before meals or, for patients who cannot take oral drugs, 25 mg rectally 2 times a day). Anticholinergic drugs such as scopolamine and the antihistamines meclizine and diphenhydramine prevent recurrent nausea in many patients. Combining lower doses of the previously mentioned drugs often improves efficacy. Second-line drugs for intractable nausea include haloperidol (started at 1 mg orally or subcutaneously every 6 to 8 hours, then titrated to as much as 15 mg/day).

Nausea and pain due to intestinal obstruction are common among patients with widespread abdominal cancer. Generally, IV fluids and nasogastric suction are more burdensome than useful. Symptoms of nausea, pain, and intestinal spasm respond to hyoscyamine (0.125 to 0.25 mg every 4 hours sublingually or subcutaneously), scopolamine (1.5 mg topically), morphine (given sc or rectally), or any of the other previously mentioned antiemetics. Octreotide 150 mcg subcutaneously or IV every 12 hours inhibits gastrointestinal secretions and dramatically reduces nausea and painful distention. Given with antiemetics, octreotide usually eliminates the need for nasogastric suctioning. Corticosteroids (eg, dexamethasone 4 to 6 mg IV, IM, or rectally 3 times a day) may decrease obstructive inflammation at the tumor site and temporarily relieve the obstruction. IV fluids may exacerbate obstructive edema.

Constipation is common among dying patients because of inactivity, use of opioids and drugs with anticholinergic effects, and decreased intake of fluids and dietary fiber. Regular bowel movements are essential to the comfort of dying patients, at least until the last day or two of life. Laxatives help prevent fecal impaction, especially in patients receiving opioids. Monitoring bowel function regularly is essential. Most patients do well on a twice daily regimen of a mild stimulant laxative (eg, casanthranol, senna). If stimulant laxatives cause cramping discomfort, patients may respond to an osmotic laxative, such as lactulose or sorbitol started at 15 to 30 mL orally 2 times a day and titrated to effect. However, there are a wide variety of appropriate laxatives with none that has proven superior in this clinical situation (1).

Soft fecal impaction may be treated with a bisacodyl suppository or saline enema. For a hard fecal impaction, a mineral oil enema may be given, possibly with an oral benzodiazepine (eg, lorazepam) or an analgesic, followed by digital disimpaction. After disimpaction, patients should be placed on a more aggressive bowel regimen to avoid recurrence.

Many dying patients are immobile, poorly nourished, incontinent, and cachectic and thus are at risk of pressure injuries. Prevention requires relieving pressure by rotating the patient or shifting the patient’s weight every 2 hours; a specialized mattress or continuously inflated air-suspension bed may also help. Incontinent patients should be kept as dry as possible. Generally, use of an indwelling catheter, with its inconvenience and risk of infection, is justified only when bedding changes cause pain or when patients or family members strongly prefer it.

Mental changes that can accompany the terminal stage of a disorder may distress patients and family members; however, patients are often unaware of them. Delirium is common. Causes include drugs, hypoxia, metabolic disturbances, and intrinsic central nervous system disorders. If the cause can be determined, simple treatment may enable patients to communicate more meaningfully with family members and friends. Patients who are comfortable and less aware of their surroundings may do better with no treatment. When possible, the physician should ascertain the preferences of patients and family members and use them to guide treatment.

Simple causes of delirium should be sought. Agitation and restlessness often result from urinary retention, which resolves promptly with urinary catheterization. Confusion in debilitated patients is worsened by sleep deprivation. Agitated patients may benefit from antipsychotics or benzodiazepines; however, benzodiazepines may also cause confusion. Poorly controlled pain may cause insomnia or agitation. If pain has been appropriately controlled, a nighttime sedative may help.

Family members and visitors may help lessen confusion by frequently holding the patient’s hand and repeating where the patient is and what is happening. Patients with severe terminal agitation resistant to other measures may respond best to barbiturates. However, family members should be told that after these drugs are used, patients may not regain the capacity for coherent interaction. Pentobarbital, a rapid-onset, short-acting barbiturate, may be given as 100 to 200 mg IM every 4 hours as needed. Phenobarbital, which is longer-acting, may be given orally, subcutaneously, or rectally.

Most dying patients experience some depressive symptoms. Providing psychologic support and allowing patients to express concerns and feelings are usually the best approach. A skilled social worker, physician, nurse, or chaplain can help with these concerns.

A trial of antidepressants is often appropriate for patients who have persistent, clinically significant depression. Selective serotonin reuptake inhibitors (SSRIs) are useful for patients likely to live beyond the 4 weeks usually needed for onset of the antidepressant effect. Depressed patients with anxiety and insomnia may benefit from a sedating tricyclic antidepressant given at bedtime. For patients who are withdrawn or who have vegetative signs, methylphenidate may be started at 2.5 mg orally once a day and increased to 2.5 to 5 mg 2 times a day (given at breakfast and lunch) as necessary. Methylphenidate (same dosage) can provide a few days or weeks of increased energy for patients who are fatigued or somnolent because of analgesics and advanced illness. Methylphenidate has a rapid effect but may precipitate agitation. Although its duration of action is short, adverse effects are also short-lived.

Some people approach death peacefully, but more people and family members have stressful periods. Death is particularly stressful when interpersonal conflicts keep patients and family members from sharing their last moments together in peace. Such conflicts can lead to excessive guilt or inability to grieve in survivors and can cause anguish in patients. A family member who is caring for a dying relative at home may experience physical and emotional stress. Usually, stress in patients and family members responds to compassion, information, counseling, and sometimes brief psychotherapy. Community services may be available to help relieve caregiver burden. Sedatives should be used sparingly and briefly.

When a partner dies, the survivor may be overwhelmed by having to make decisions about legal or financial matters or household management. For an elderly couple, the death of one may reveal the survivor’s cognitive impairment, for which the deceased partner had compensated. The clinical team should identify such high-risk situations so that they can mobilize the resources needed to prevent undue suffering and dysfunction. In the US, hospice programs that receive Medicare funds are required to provide bereavement services to family and friends for at least a year after the death of the hospice patient.