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Symptom Relief for the Dying Patient

by Elizabeth L. Cobbs, MD, Karen Blackstone, MD; Joanne Lynn, MD, MA, MS

Physical, psychologic, emotional, and spiritual distress is common among patients living with fatal illness, and patients commonly fear protracted and unrelieved suffering. Health care providers can reassure patients that distressing symptoms can often be anticipated and prevented and, when present, can be treated.

Symptom treatment should be based on etiology when possible. For example, vomiting due to hypercalcemia requires different treatment from that due to elevated intracranial pressure. However, diagnosing the cause of a symptom may be inappropriate if testing is burdensome or risky or if specific treatment (eg, major surgery) has already been ruled out. For dying patients, comfort measures, including nonspecific treatment or a short sequential trial of empiric treatments, often serve patients 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, the clinical team must monitor and reevaluate the situation frequently. Drug overdosage or underdosage is harmful, and both become more likely as worsening physiology causes changes in drug metabolism and clearance.

When survival is likely to be brief, symptom severity frequently dictates initial treatment.

Pain

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 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. 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. Unreasonable concerns by the public and by health care practitioners about addiction often limit appropriate use of opioids. Pharmacologic 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. In the unusual case where opioids cannot be given orally or sublingually, they can be given rectally, IM, IV, or sc.

Adverse effects of opioids include nausea, sedation, confusion, constipation, and respiratory depression. Opioid-induced constipation should be treated prophylactically (see Symptom Relief for the Dying Patient : Constipation). 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 does not occur unless 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 (see Neuropathic Pain); doxepin can provide bedtime sedation as well. Gabapentin 300 to 1200 mg po tid can relieve neuropathic pain. Methadone is effective for refractory or neuropathic pain; however, its kinetics vary, and it requires close monitoring. 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 mental imagery, hypnosis, acupuncture, relaxation, biofeedback) help some patients (see Mind-Body Medicine). 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 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 O 2 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, ABGs, ECG, 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 sc q 2 h prn helps reduce breathlessness in an opioid-naive patient. Morphine may blunt the medullary response to CO 2 retention or O 2 decline, reducing dyspnea and decreasing anxiety without causing harmful respiratory depression. If patients are already taking opioids for pain, dosages that relieve dyspnea must often be more than double the patient’s usual dosages. Benzodiazepines often help relieve anxiety associated with dyspnea and with fear of a return of dyspnea.

O 2 may also give psychologic comfort to patients and family members even if it does not correct hypoxemia. Patients usually prefer O 2 via nasal cannula. An O 2 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 sc q 4 to 6 h or 0.2 to 0.4 mg po q 8 h, with dose increases prn). 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

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 bid or prednisone 10 to 30 mg once/day) or megestrol 160 to 480 mg po once/day. However, if a patient is close to death, family members should understand that neither food nor hydration is necessary to maintain the patient’s comfort.

IV fluids, TPN, 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 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.

Nausea and Vomiting

Many seriously ill patients experience nausea, frequently without vomiting. Nausea may arise with GI 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 H 2 blockers, 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 po or sc qid prn or given on a scheduled basis) is useful because it increases gastric tone and contractions while relaxing the pyloric sphincter.

Patients with no specific cause of nausea may benefit from treatment with a phenothiazine (eg, promethazine 25 mg po qid; prochlorperazine 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. Combining lower doses of the previously mentioned drugs often improves efficacy. Second-line drugs for intractable nausea include haloperidol (started at 1 mg po or sc q 6 to 8 h, then titrated to as much as 15 mg/day). The 5-hydroxytryptamine (5-HT) 3 antagonists ondansetron and granisetron often dramatically relieve chemotherapy-induced nausea. Cost often makes these antagonists 2nd-line drugs for more complex causes of nausea in dying patients.

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 q 4 h sublingually or sc), scopolamine (1.5 mg topically), morphine (given sc or rectally), or any of the other previously mentioned antiemetics. Octreotide 150 mcg sc or IV q 12 h inhibits GI 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 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, 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 stool softener (eg, docusate) plus a mild stimulant laxative (eg, casanthranol, senna). If stimulant laxatives cause cramping discomfort, patients may respond to increased doses of docusate alone or an osmotic laxative, such as lactulose or sorbitol started at 15 to 30 mL po bid and titrated to effect.

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.

Pressure Ulcers

Many dying patients are immobile, poorly nourished, incontinent, and cachectic and thus are at risk of pressure ulcers (see also Pressure Ulcers). Prevention requires relieving pressure by rotating the patient or shifting the patient’s weight every 2 h; 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.

Delirium and Confusion

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 CNS 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 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; family members should be made aware that when near death, patients do not usually wake up much after starting these drugs. Pentobarbital, a rapid-onset, short-acting barbiturate, may be given as 100 to 200 mg IM q 4 h prn. Phenobarbital, which is longer-acting, may be given po, sc, or rectally. Midazolam, a short-acting benzodiazepine, also is often effective.

Depression and Suicide

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. SSRIs are useful for patients likely to live beyond the 4 wk 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 (see Vegetative State and Minimally Conscious State : Symptoms and 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 dosage) can provide a few days or weeks of increased energy for patients who are fatigued or somnolent because of analgesics. Methylphenidate has a rapid effect but may precipitate agitation. Although its duration of action is short, adverse effects are also short-lived.

Suicide

Serious medical illness is a significant risk factor for suicidality. Other risk factors for suicide are common among sick enough to die; they include advanced age, male sex, psychiatric comorbidity, an AIDS diagnosis, and uncontrolled pain. Cancer patients have nearly twice the incidence of suicide than the general population, and patients with lung, stomach, and head and neck cancers have the highest suicide rates among all patients with cancer. Clinicians should routinely screen seriously ill patients for depression and suicidal thoughts. Psychiatrists should urgently evaluate all patients who seriously threaten self-harm or have serious suicidal thoughts.

Stress and Grief

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.

Grief

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. Traditionally, the stages after grief were thought to occur in the following order: denial, anger, bargaining, depression, and acceptance. However, the stages that patients go through and their order of occurrence vary. Members of the clinical team can help patients accept their prognosis by listening to their concerns, helping them understand that they can control important elements of their life, explaining how the disorder will worsen and how death will come, and assuring them that their physical symptoms will be controlled. If grief is still very severe or causes psychosis or suicidal ideation or if the patient has a previous severe mental disorder, referral for professional evaluation and grief counseling may help the person cope.

Family members may need support in expressing grief. Any clinical team member who has come to know the patient and family members can help them through this process and direct them to professional services if needed. Physicians and other clinical team members need to develop regular procedures that ensure follow-up of grieving family members.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • DOLOPHINE
  • OXYCONTIN
  • NEURONTIN
  • DILAUDID
  • AVENTYL
  • No US brand name
  • ZONALON
  • DURAMORPH PF, MS CONTIN
  • TYLENOL
  • ACTIQ, DURAGESIC, SUBLIMAZE
  • ATROPEN
  • TRANSDERM SCOP
  • ROBINUL FORTE, ROBINUL
  • PROVENTIL-HFA, VENTOLIN-HFA
  • MEGACE
  • OZURDEX
  • RAYOS
  • REGLAN
  • COMPRO
  • PROMETHEGAN
  • ANTIVERT
  • HALDOL
  • No US trade name
  • SANCUSO
  • ZOFRAN
  • SANDOSTATIN
  • CHOLAC
  • DULCOLAX
  • ATIVAN
  • NEMBUTAL SODIUM
  • CONCERTA, RITALIN

* This is a professional Version *