Symptom Control
Physical and mental distress is common during terminal disorders. Patients commonly fear that their suffering will be protracted and that no one will control it. Relief of discomfort enables patients to focus on living as fully as possible and on confronting the issues presented by the approach of death.
Symptom control should be based on etiology when possible. For example, vomiting due to hypercalcemia is treated differently from vomiting due to elevated intracranial pressure. However, diagnosing the cause of a symptom may be inappropriate if testing is burdensome or if a specific treatment (eg, major surgery) has already been ruled out. For dying patients, comfort measures, including nonspecific treatments or short sequential trials of empiric treatments, are often better than an exhaustive diagnostic evaluation.
Because one symptom can have many causes and may respond differently to treatment as the patient's condition deteriorates, treatments must be closely monitored and repeatedly reevaluated. Drug overdosage or underdosage must be avoided, especially as worsening physiology causes changes in drug disposition.
When survival is expected to be brief, symptom severity frequently dictates initial, empiric treatment. Sometimes the fear that a symptom will worsen can be more crippling than the symptom itself, and reassurance that effective treatment is available may be all a patient needs. Other times, a symptom is so severe and the diagnostic alternatives are so nonspecific that immediate symptom suppression is indicated.
Pain: About ½ of patients dying of cancer have severe pain. Yet, only ½ of these patients receive reliable pain relief. Many patients dying of organ system failure or dementia also have severe pain. Sometimes pain could be controlled but persists because patients, their family members and friends, and health care practitioners have misconceptions about pain and the drugs (especially opioids) that can control it, resulting in significant underdosing.
Patients perceive pain differently, depending 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. Most pain can be relieved by an appropriately potent drug at sufficient dosage. Palliative sedation may be the most appropriate treatment for patients whose pain or other troubling symptoms cannot be adequately controlled.
Commonly used drugs are acetaminophen or NSAIDs for mild pain; codeine or hydrocodone for moderate pain; and hydromorphone, oxycodone, morphine, or fentanyl for severe pain or palliative sedation. As long as patients can swallow drugs, oral opioid therapy is convenient and cost-effective. Long-acting opioids are best for long-lasting pain. When opioids are indicated, the health care practitioner should prescribe them in adequate dosages and on a continuous basis to prevent pain. Tragically, unreasonable concerns of the public and of health care practitioners about addiction are often barriers to appropriate opioid use. Drug dependence may result from regular use but causes no problems in dying patients except the need to avoid inadvertent withdrawal. Addictive behaviors are rare and usually easy to control.
When death is imminent, oral analgesic therapy may not be feasible. Giving morphine or oxycodone solutions 20 mg/mL sublingually can often control pain even when patients cannot swallow other tablets or liquids. The usual recommendation when death is imminent is to switch from a long-acting opioid to an immediate-release form because absorption and clearance changes rapidly during the dying process and patients may need the opioid dose adjusted often. Rectal administration provides slower absorption but with very little first-pass effect; morphine suppositories or pills may be given rectally at the same dose used for oral forms and then adjusted as needed. IV or sc opioid therapy is preferred to IM injections, which are painful and result in variable absorption.
Adverse effects of opioids include nausea, sedation, confusion, constipation, and respiratory depression. Constipation should be treated prophylactically with a large-bowel stimulant such as senna or bisacodyl. Patients usually develop substantial tolerance to the respiratory depressant and sedative effects of morphine but do not develop as much tolerance to the analgesic and constipating effects. Rarely, opioids may also cause myoclonus, agitated delirium, hyperalgesia, and seizures. These effects may result from accumulation of toxic metabolites and may be associated with reduced clearance in patients who are near death; the effects usually resolve when another opioid is substituted (opioid rotation).
When patients on a stable opioid dose experience increased pain, the dose should be increased. If pain is mild to moderate, the daily dose should be increased by 25 to 50%; if pain is moderate to severe, the dose may need to be increased by 50 to 100%. Continuous infusions of opioids using IV or sc patient-controlled analgesia (PCA) can be effective when opioid doses are very high. With the support of home hospice, sc opioid PCA pumps with both continuous and bolus functions can be used easily at home. Usually, serious respiratory depression does not occur unless the dose is increased to more than twice the previously tolerated dose.
Using adjunctive drugs for pain control often increases comfort and allows the opioid dosage and consequent adverse effects to be reduced. Corticosteroids are widely used in the terminally ill to reduce pain caused by inflammation and swelling. Gabapentin 300 to 1200 mg po tid or pregabalin 100 to 200 mg po tid (or 300 mg bid) helps relieve neuropathic pain. Tricyclic antidepressants (eg, nortriptyline, doxepin) help manage neuropathic pain; doxepin provides sedation as well. Methadone is effective for refractory or neuropathic pain; however, its metabolism and half-life can vary, and patients must be closely monitored. Benzodiazepines are useful for patients whose pain is worsened by anxiety.
For severe localized pain, regional nerve blocks, done 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 may be inserted to provide continuous infusion of analgesics, often mixed with anesthetic drugs.
Nondrug pain-modification techniques (eg, guided mental imagery, hypnosis, acupuncture, relaxation) help some patients. Counseling for stress and anxiety may be very helpful, as may spiritual support from a chaplain.
Dyspnea: Dyspnea is one of the most feared symptoms and probably the most distressing to dying patients. Its causes may be treatable. For example, antibiotics for pneumonia or thoracentesis for a pleural effusion may be appropriate. However, if death is imminent, such measures are more burdensome than beneficial; patients can be made comfortable without invasive or aggressive measures, regardless of the cause of dyspnea.
Initially, O2 helps correct hypoxemia. Even when its benefit is no longer certain, O2 may continue to be psychologically comforting to patients, family members, and friends. It is usually most comfortable when given by nasal cannula because masks may be uncomfortable and may make patients feel smothered.
Morphine 2 to 10 mg sublingually or 2 to 4 mg sc q 2 to 4 h prn helps reduce breathlessness without significantly affecting ventilation. The drug must be given continuously so that blood levels remain steady. If levels increase, respiratory drive and ventilation may decrease. If patients are already taking typical doses of opioids for pain, doses for respiratory symptoms may need to be much higher.
Airway congestion is best managed with drugs that dry secretions (eg, scopolamine transdermal patch 1.5 mg applied q 72 h, hyoscyamine 0.125 mg sublingually q 8 h, atropine eye drops 2 drops po q 4 h prn).
Nebulized saline may be used to treat patients with viscous secretions. Bronchospasm and bronchial inflammation may be treated with nebulized albuterol and oral or injectable corticosteroids.
Benzodiazepines often help relieve anxiety associated with dyspnea. Useful nondrug measures include providing a cool draft from a fan or open window and maintaining a calming presence.
Anorexia: Anorexia and marked weight loss are common among dying patients. For family members and friends, accepting the patient's poor oral intake is often difficult because it means accepting that the patient is dying. Sometimes even health care practitioners have trouble accepting a patient's poor oral intake. Patients should be offered their favorite foods whenever possible. Conditions that may cause poor intake and can be easily treated (eg, gastritis, constipation, oral candidiasis, pain, nausea) should be treated. Some patients benefit from appetite stimulants such as oral corticosteroids (eg, dexamethasone 2 to 8 mg bid or prednisone 10 to 30 mg once/day). Dronabinol does not help most patients but may help a subset of patients (eg, those who have used marijuana earlier in life). Megestrol, although commonly used as an appetite stimulant in patients with cancer, is not recommended. It causes only temporary weight gain by increasing fluid retention and body fat; it does not increase lean body mass, prolong survival, or improve quality of life.
IV fluids, TPN, and tube feedings are often begun because family members or health care practitioners cannot tolerate the patient's poor oral intake. These measures do not prolong the life of dying patients, seem to increase discomfort, and may even hasten death. In dying patients who are fed artificially, incidence of pulmonary congestion and pneumonia is increased. Artificial hydration may worsen edema and pain associated with inflammation. Conversely, dehydration and ketosis due to caloric restriction are associated with analgesic effects and absence of discomfort. The only reported discomfort caused by dehydration near death is xerostomia, which is easily relieved with oral swabs or ice chips.
If a patient is close to death, family members and friends should be gently told that the patient is dying and that food does not help the patient's strength nor substantially delay death; they should be reassured that the patient does not suffer from having little or no intake. Suggesting concrete measures (eg, providing favorite foods, small portions, or foods that are easy to swallow) and other ways to show caring and love can help family members and friends.
Even debilitated and cachectic patients may live for several days to weeks after all food and hydration are stopped. Family members and friends should be told that stopping fluids will not result in the patient's immediate death and ordinarily does not hasten death. Supportive care, including good oral hygiene (eg, brushing the teeth, swabbing the oral cavity, applying lip salve, providing ice chips for xerostomia), is imperative for the comfort of the dying patient and can be provided by family members and friends.
Nausea and vomiting: Many seriously ill patients experience nausea, frequently without vomiting. Nausea may be exacerbated by GI problems (eg, constipation, gastritis), metabolic abnormalities (eg, hypercalcemia, uremia), drug adverse effects, increased intracranial pressure secondary to cerebral cancer, and psychosocial stress. Treatment should be guided by the likely cause; for example, NSAIDs are stopped, gastritis is treated with H2 blockers or proton pump inhibitors, and patients with known or suspected brain metastases are treated with a trial of corticosteroids. If nausea is due to gastric distention and reflux, metoclopramide (orally or subcutaneously) is useful because it increases gastric tone and contractions while relaxing the pyloric sphincter.
If no cause for mild nausea is identified, patients may benefit from nonspecific treatment with a phenothiazine (eg, promethazine 12.5 to 25 mg po qid; prochlorperazine 5 to 10 mg po before meals or, for patients who cannot take oral drugs, 25 mg rectally bid). Anticholinergic drugs such as scopolamine and the antihistamines meclizine and diphenhydramine prevent recurrent nausea in many patients but increase risk of delirium. Because nausea has multiple simultaneous causes in many patients, combining drugs that work via different mechanisms often improves efficacy. Second-line drugs for intractable nausea include haloperidol, started at 0.5 to 1 mg po or sc q 8 to 12 h, then increased to as much as 15 mg/day. The serotonin (5-HT3) receptor antagonists ondansetron and granisetron and the neurokinin antagonist aprepitant often dramatically relieve chemotherapy-induced nausea but frequently do not work as well in patients with chronic nausea.
Nausea and pain due to intestinal obstruction are common among patients with widespread abdominal cancer. Surgery, which can relieve symptoms and prolong survival, may be appropriate, even for certain patients whose prognosis is poor otherwise and, rarely, even for hospice patients. If surgery is not appropriate for a hospice patient (eg, because health is poor, an obstruction is inaccessible, or there are multiple obstructions), IV fluids and nasogastric suction are usually not useful. Symptoms of nausea, pain, and intestinal spasm may be controlled with hyoscyamine 0.125 to 0.25 mg sublingually or sc q 4 h, scopolamine 1.5 mg topically q 72 h, morphine (sc, sublingually, or rectally), or any antiemetic (eg, diphenhydramine, granisetron, haloperidol, meclizine, ondansetron, prochlorperazine, promethazine, scopolamine). Octreotide 150 µg sc or IV q 8 to 12 h inhibits GI secretions and peristalsis, effectively calming the bowel and dramatically reducing nausea and painful distention. Given with antiemetics, octreotide usually eliminates the need for nasogastric suctioning.
Corticosteroids (eg, dexamethasone 40 mg/day for 4 days and then 4 to 6 mg IV, sc, or rectally tid) may decrease obstructive inflammation at the tumor site and temporarily relieve the obstruction. IV fluids may exacerbate obstructive edema.
Constipation: Constipation is common among dying patients because of inactivity, opioid and anticholinergic drug use, and decreased fluid and dietary fiber intake. Laxatives help prevent fecal impaction, especially in patients receiving opioids. All patients should be asked about bowel function. Most patients do well on a twice/day regimen of stool softener (eg, docusate) plus a mild stimulant laxative (eg, casanthranol, senna, bisacodyl). If stimulant laxatives cause cramping discomfort, patients may respond to increased doses of docusate alone or an osmotic laxative such as lactulose or sorbitol (which is much cheaper and equally effective) started at 15 to 30 mL po bid and increased as needed.
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 rigorous bowel regimen to avoid recurrence. Regular bowel movements are essential for a dying patient's comfort, at least until the last day or two.
Diarrhea: If diarrhea occurs, an examination is done to rule out impaction. All laxatives, including stool softeners, are stopped. If diarrhea is severe, the patient should be given clear liquids and bland carbohydrates. Other foods can be added as symptoms permit. For severely dehydrated patients, electrolytes may be given po, IV, or sc to make the patient comfortable more quickly. Sports drinks, which contain electrolytes and carbohydrates, are similar to IV fluids and can be used in oral rehydration plans.
Often, diarrhea must be suppressed with nonspecific treatment (eg, opioids; loperamide 4 mg po initially, then 2 mg after each diarrheal stool [up to 16 mg/day]; diphenoxylate-atropine 5 mg [2 tablets of 2.5 mg diphenoxylate] po after each diarrheal stool, up to qid). However, more specific treatment may be needed: for carcinoid tumors or dumping syndrome after gastrectomy, octreotide 150 to 300 µg sc bid or 300 µg continuous IV infusion given over 24 h; for Clostridium difficile colitis due to recent antibiotic treatment, metronidazole 250 to 500 mg po tid for 10 days; for fungal infection due to immunosuppression, clotrimazole 10 to 20 mg po tid or fluconazole (first dose is 200 mg po, then 100 mg po once/day for 14 days); and for pancreatic insufficiency, pancreatic enzymes such as pancreatin 1 to 2 tablets with meals and ½ the dose with any snack. Zinc oxide helps relieve irritation around the anus, and corticosteroid cream (for as few as 1 to 2 days) helps relieve maceration or inflammation.
Pressure ulcers: Many dying patients are immobile, poorly nourished, incontinent, and cachectic and thus are at risk of developing pressure ulcers. Prevention requires relieving pressure by rotating patients every 2 h; a specialized mattress or continuously inflated air-suspension bed may be used. Incontinent patients should be kept as dry as possible. Generally, using an indwelling catheter, with its inconvenience and risk of infection, is justified only when bedding changes cause pain or when patients, family members, or caregivers strongly prefer it.
Delirium: Mental changes that can accompany the terminal stage of a disorder may distress patients, family members, and friends. Patients may appear distressed, often becoming agitated and crying out; however, if delirium resolves, patients forget what happened during the delirium. Confusion is common; causes include drugs, hypoxia, metabolic disturbances, and intrinsic CNS disorders. Confusion in debilitated patients is worsened by sleep deprivation. Agitation and restlessness often result from urinary retention, which resolves promptly with urinary catheterization.
If the cause can be determined, simple treatment may be worthwhile provided it enables 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 health care practitioner should ascertain the preferences of patients, family members, and friends and use them to guide treatment.
In dying patients, the goal is to control agitation and relieve confusion while maintaining alertness and consciousness as much as possible (for some patients, alertness is not a goal). Thus, if drugs are needed, those with relatively mild sedative effects are preferred. Agitated patients may benefit from low doses of antipsychotics such as haloperidol 0.5 to 2 mg po or sc titrated as needed to control delirium. Atypical antipsychotics such as risperidone and quetiapine have been recommended for the elderly, but they must be given orally. If patients are unable or unwilling to take the drugs orally, having an sc or IV option (eg, haloperidol) is helpful.
Benzodiazepines are sometimes given for agitation associated with delirium and for exacerbated delirium. In terminal delirium not adequately controlled with haloperidol, adding a benzodiazepine to increase sedation may be the most appropriate next step. Patients with severe terminal agitation resistant to other measures may respond best to continuous sedation with midazolam, a short-acting benzodiazepine.
Family members and visitors may help lessen confusion by frequently holding the patient's hand, saying where the patient is, and letting the patient know what is happening. Supportive therapy, including listening and talking to the patient, should precede and supplement drug therapy. Sometimes symptoms of anxiety and agitation can be managed with gentle reassurance. Meditation, guided imagery, prayer, music therapy, and massage are often helpful.
Depression: Most dying patients experience some depressive symptoms. Providing psychologic support and allowing patients to express concerns and feelings are usually the best approaches. A skilled social worker, physician, nurse, other health care practitioner, or chaplain can help with these concerns.
A trial of antidepressants is often appropriate for patients who have persistent, clinically significant depression. SSRIs are useful for patients likely to live beyond the 4-wk period usually needed for onset of the antidepressant effect. A possible alternative for patients with depression and significant insomnia is trazodone 25 to 50 mg po daily at bedtime, increased in 25- to 50-mg/day increments every 3 days as tolerated, to a maximum of 300 mg/day. For patients who are withdrawn or who have vegetative signs, methylphenidate may be started at 2.5 mg po once/day and increased to 2.5 to 5 mg bid (given at breakfast and lunch) as necessary. Methylphenidate (same dose) is sometimes used to provide a few days or weeks of increased energy for patients who are fatigued or somnolent because of disease progression or analgesics. Methylphenidate has a rapid effect but occasionally precipitates agitation. Because its duration of action is short, adverse effects are also short-lived.
Stress: A few people approach death peacefully, but most patients, family members, and friends experience stress. Death is particularly stressful when interpersonal conflicts keep patients, family members, and friends from sharing their last moments together in peace. Such conflicts can lead to excessive guilt or pathologic or dysfunctional grieving in survivors and to anguish in patients. A family member or friend who is caring for a dying patient at home may experience physical and emotional stress. Usually, stress in patients and in family members and friends is best treated with compassion, information, counseling, and sometimes brief psychotherapy. Social services may be needed to help increase home support and relieve caregiver burden. Sedatives should be used sparingly and briefly.
When a loved one dies, the survivor may be overwhelmed by having to make decisions about legal or financial matters or having to manage the household; these responsibilities can compound grief. For an elderly couple, the death of one may reveal the survivor's cognitive impairment, for which the deceased partner had compensated. Health care practitioners should identify such high-risk situations, usually with the help of social workers, so that they can mobilize the resources needed to prevent undue suffering and dysfunction.
Grieving: Grieving is a normal process that usually begins before an anticipated death. For patients, grief often starts with denial caused by fears about loss of control, separation, suffering, an uncertain future, and loss of self. Staff members can help patients accept their prognosis by listening to their concerns, helping them understand that they can still control important elements of their life, explaining how the disorder will progress and how death will come, and assuring them that their physical symptoms will be controlled. Printed educational materials that provide information about the illness, dying process, grief, or other important topics are helpful and can be reviewed later.
Family members and friends may need support in expressing grief. Any health care team member who has come to know the patient, family members, and friends can help them through this process and direct them to professional services if needed. Team members need to develop regular procedures that ensure follow-up of grieving family members and friends.
This topic was last updated July 2006.
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