Assessment and treatment of terminal restlessness in the hospitalized adult patient with cancer
Charles and Claire were married for 54 years when Claire was diagnosed with colon cancer that metastasized to her brain. After undergoing both chemotherapy and radiation treatments, Claire’s body succumbed to the terminal disease. She was admitted to the hospital for palliative pain management when she started hallucinating, moaning, twitching, pulling off her clothes, and trying to climb out of bed. Charles was distraught and felt helpless as he tried to help his wife in her experience of a condition known as terminal restlessness. Had the care providers known more about the condition, perhaps the situation would have been different for Charles and Claire.
Terminal restlessness, or terminal delirium, can be a devastating experience during the end of life, not only for the patient but also for the family, other loved ones, and caregivers. The painful memory of the person’s last days can live on in the hearts and minds of survivors and can interfere with the grieving process (Avery, 2003). While a large number of patients with terminal cancer will die either at home or in a long-term care facility, many will die in the hospital. Registered nurses whose clinical practice is at the bedside in the acute care setting most certainly will care for people with cancer near the end of life. Those who infrequently care for these patients may not understand terminal restlessness fully and may also find it somewhat overwhelming. Caring for someone with this complex and intense condition can consume the emotions of everyone involved. Despite the intensity, appropriate end-of-life care can and must be provided for the comfort of the patient.
In the patient with advanced cancer, terminal restlessness severely affects quality of life and creates additional burden upon family members. It is important for acute care clinical nurses to be educated about the numerous causes of terminal restlessness in the hospitalized adult patient with cancer. The focus is comfort and symptom management strategies. Recognizing and managing terminal restlessness empower nurses to help their patients achieve a peaceful death and to help decrease unnecessary distress for grieving loved ones.
What Is Terminal Restlessness?
A common condition in the dying process is a type of delirium called terminal restlessness, also known as terminal delirium, end-stage restlessness, terminal agitation, or hyperactive delirium (Avery, 2003; Jackson & Lipman, 2004; Lawlor, Fainsinger, & Bruera, 2000; Travis, Conway, Daly, & Larsen, 2001). Delirium of varying severity frequently occurs in the days and weeks prior to death. The delirium during this time may have similar presentations as when the patient previously experienced pain, anxiety, infection, or an adverse drug reaction. Terminal restlessness differs from the delirium frequently seen as a complication in hospitalized elders who have advanced age, pre-existing cognitive impairment, recent surgery, or severe illness (Cobb et al., 2000). For example, elders with urinary tract infections (UTI) often develop confusion and restlessness. Most often delirium is transient and reversible up to the last 48 to 72 hours of life, when tile event is then considered terminal (Lawlor et al., 2000: Travis et al., 2001).
Terminal restlessness is a condition that is under-recognized, under-treated, and underresearched in patients with cancer (Gagnon, Allard, Masse, & DeSerres, 2000; Lawlor et al., 2000). It is known to occur frequently, affecting 25% to 85% of patients with cancer prior to death (Avery, 2003; Brajtman, 2003; Cobb et al., 2000; Morita, You, Tsunoda, Inoue, & Chihara, 2002; Stirling, Kurowska, & Tookman, 1999). This variation may result from different definitions of terminal restlessness, nonstandard diagnostic criteria, or diverse patient populations (Lawlor et al., 2000; Morita, You, Tsunoda, Inoue, & Chihara, 2001). This subtype of delirium has many different presentations, such as agitation, fidgeting, twitching, moaning, confusion, anxiety, and hallucinations (see Table 1). Some symptoms can be alleviated with appropriate interventions if the underlying pathology is identified (Cobb et al., 2000; Gagnon et al., 2000; Morita et al., 2001).
Common Causes and Treatments of Terminal Restlessness
Terminal restlessness is often multifactoral, especially in the older adult patient or the patient with advanced cancer (Inouye, 2000; Lawlor et al., 2000; Travis et al., 2001). The cause may never be confirmed, but the condition usually results from the interaction of precipitating factors and other risk factors. It also can be exacerbated by shut down of the body’s systems during the dying process. Table 2 lists the various factors that place a person at risk for developing terminal restlessness; the risk increases in proportion to the number of factors present (Lawlor et al., 2000).
Causes of terminal restlessness, such as pain, dyspnea, urinary retention, or constipation/impaction, are often identified on initial assessment. Causes that may require more in-depth investigation may be side effects or unexpected reactions from medications, electrolyte imbalance, liver failure, renal failure, infection, or brain metastasis. Emotional, psychological, or spiritual factors also can contribute to terminal restlessness; specifically, fear of dying or losing control, anger, sadness about leaving the family, or spiritual distress can be significant (Avery, 2003). Unresolved issues that usually are associated with guilt can create mental anguish. The nurse can offer spiritual support by chaplain visits, prayer, readings, or other religious rituals appropriate to the patient’s belief (Avery, 2003; Kasper et al., 2005; Sagar, 2001).
M.C. was a 51-year-old man with end-stage multiple myeloma who was agitated for days despite attempted symptom management. The chaplain was consulted and discovered during his visit that the patient had molested a child many years ago. M.C. was afraid to die because he feared what faced him after death. Once the chaplain prayed with him and granted him forgiveness, the patient’s symptoms subsided and he died peacefully the next day. This case study reinforces the need to assess psychological and spiritual factors while the patient is still alert and able to communicate, and to consult the appropriate disciplines to assist the patient with any needs.
Medications. The most common cause of terminal restlessness in patients with cancer is the result of medications (Avery, 2003). Opioids cause terminal restlessness in approximately 27% of patients with cancer (Morita et al., 2002). Opioid toxicity usually presents as agitation, restlessness, myoclonus, twitching, and tactile hallucinations (Lawlor, Fainsinger et al., 2000; Morita et al., 2002; Morita et al., 2001; Sagar, 2001). A recent study (Morita et al., 2002) showed that the plasma morphine metabolites, M-6-G and M-3-G, increase in terminally ill patients with cancer due to organ failure and dehydration during the dying process. Toxic levels result as liver and renal function deteriorates toward the end of life, impairing the metabolism and excretion of drugs. Tricyclic antidepressants such as amitriptyline (Elavil[R]) and nortriptyline (Pamelor[R]) also are known to increase plasma morphine levels. The study also indicated that the harmful accumulation of morphine metabolites can be avoided by rehydration, opioid rotation, and/or dose reduction. Hypoalbuminemia is common during the dying process due to malnutrition in patients with cancer, but rehydration is a challenge because of excessive fluid retention. Because dehydration is not always a cause of terminal restlessness but rather a facilitator of opioid toxicities, rehydration can also exacerbate increased bronchial secretions, contributing to dyspnea during the dying process (Morita et al., 2001). An alternative to rehydration is opioid rotation or dose reduction. Opioid rotation is accomplished by either alternating opioids and nonopioids or switching to an alternative opioid (for example, from morphine to hydromorphone) (Lawlor, Fainsinger et al., 2000; Morita et al., 2001).
Steroids are another class of drugs that can contribute to metabolic encephalopathies (Avery, 2003; Sagar, 2001). Steroids usually are given to patients with brain metastasis to decrease inflammation and the risk of seizures. Steroid psychosis often develops within 2 weeks of starting the drug but can occur at anytime (Morita et al., 2001). However, this condition is typically associated with higher doses (Avery, 2003).
Another consideration with medications and the contribution to terminal restlessness is the sudden withdrawal of analgesics during hospitalization (Avery, 2003; Travis et al., 2001). Many patients with cancer take analgesics, with higher doses needed as the disease progresses. Sometimes a patient’s medication regimen is not continued during hospitalization, due either to the patient’s declining status or the physician not ordering the medications. For example, a patient routinely taking a high dose of sustained release oxycodone (Oxycontin[R]) is admitted to the hospital and is now unable to swallow pills. This patient should be provided with pain medication using alternative routes such as a hydromorphone (Dilaudid[R]) PCA with a basal rate, a transdermal fentanyl (Duragesic[R]) patch, or sublingual oxycodone (Oxyfast[R]). Other substance withdrawals to consider are illegal narcotics, alcohol, nicotine, or caffeine (Lawlor, Gagnon et al., 2000). Screening for use of these substances should be done upon admission.
Alteration in elimination. Common reversible causes of terminal restlessness are urinary retention or constipation. Urinary retention is treated easily by catheterizing the patient. If a patient already has a catheter in place, the nurse should ensure its patency. Constipation is a common occurrence near the end of life due to effects of opioids, decreased mobility, and decreased oral intake, and it can cause restlessness. Constipation can be treated by giving a laxative either orally or rectally. The patient should also be checked for impaction (Avery, 2003).
Electrolyte and fluid imbalances. Common electrolyte imbalances that contribute to terminal restlessness are hyponatremia, hypercalcemia, hyperglycemia, and hypoglycemia (Travis et al., 2001). The most frequent contributors are hyponatremia and hypercalcemia. Low sodium may result from the disease process (for example, small cell lung cancer) or from side effects of diuretics. High calcium is seen in patients with bone metastasis. Because dehydration can exacerbate both hyponatremia and hypercalcemia, intravenous fluids can be administered as appropriate and if the patient and family desire treatment. Hypercalcemia can also be treated with a bisphosphonate (pamidronate disodium [Aredia[R]])(Morita et al., 2001). Hyperglycemia and hypoglycemia can be seen with patients with diabetes or those who take steroids (Kasper et al., 2005).
Ischemia. Hypoxia and ischemia also contribute to restlessness. If the patient develops either circumoral or peripheral cyanosis or if dyspnea is present, oxygen administration should be considered. The family should be consulted prior to initiating oxygen therapy because the mask can irritate the patient (Sagar, 2001).
Assessment of Terminal Restlessness
Terminal restlessness requires a thorough assessment to determine precipitating causes. Assessment can be difficult, especially when the patient approaches death and communication is impaired due to decreased consciousness. It should begin with identifying the potentially reversible and treatable causes, because approximately 20% to 30% of symptoms can be reversed if the causes are found early (Avery, 2003; Morita et al., 2001). An early, thorough history and physical provide important data for investigating potential causes if the condition develops. Multiple delirium-specific instruments exist to aid the health care provider in assessing delirium in patients. Such tools are the Mini Mental State Exam (MMSE); Delirium Rating Scale (DRS), which is a 10-item observer-rating scale; Memorial Delirium Assessment Scale (MDAS), which requires patient participation and rates the severity of delirium using a 10-scale; and the Confusion Rating Scale (CRS) (Gagnon et al., 2000; Lawlor, Fainsinger et al., 2000; Lawlor, Gagnon et al., 2000; Morita et al., 2001; Morita, Tel, & Inoue, 2003).
The CRS is a screening instrument used to detect the presence of symptoms of delirium and confusion, and does not require patient participation. The presence and intensity of disorientation, inappropriate behavior, inappropriate communication, and hallucinations are assessed to indicate potential delirium. For each symptom, a score is given of 0 (no symptom), 1 (symptom present at some time, but mild), or 2 (symptom present and pronounced). A CRS score of 2 or greater is considered a positive screening (Gagnon et al., 2000).
The etiology of terminal restlessness is frequently multifactorial, and the condition may be difficult to treat. Often the cause is never found. Even when a cause is found, it may not he reversible, as in the case of primary or metastatic brain cancer or pulmonary cancer (Avery, 2003; Lawlor, Fainsinger et al., 2000). Furthermore, diagnostic work up to discover potential causes may be burdensome to families who do not wish for their loved ones to undergo further procedures such as phlebotomy or radiology.
The risks and benefits must be analyzed when deciding whether or not to investigate causes and initiate treatment. The extent to which the multiple causes of terminal restlessness should be treated is debatable because such efforts may be considered futile in patients who are very close to death (Avery, 2003; Kasper et al., 2005). For example, the benefits of performing a urinalysis on a patient during the last 48 hours of life must be balanced with what will be done with the results. Is an antibiotic going to be administered if a UTI is present? The antibiotic may help the infection and alleviate some symptoms of restlessness, but may place added stress on the body’s ability to metabolize and excrete the drug. In this case, comfort measures as described below may be an appropriate alternative if a UTI is suspected. When a causative factor is identified, corrective action should be taken if it will result in patient comfort (Jackson & Lipman, 2004; Kasper et al., 2005). Treatment must be individualized based on the patient and family wishes. When a causative factor cannot be identified, or the patient or family does not wish to investigate, the goal of treatment is comfort measures by pharmacologic management.
Any unnecessary medications should be discontinued in the hospitalized patient who is near death in order to decrease any interference with the medications necessary to provide comfort. This also will decrease further demands on the body to metabolize unneeded drugs. The medication used most frequently for terminal restlessness is haloperidol (Haldol[R]), a potent dopamine-blocking neuroleptic with relatively low anticholinergic effects (Cobb et al., 2000; Kasper et al., 2005; Jackson & Lipman, 2004; Lawlor, Fainsinger et al., 2000; Travis et al., 2001). Haloperidol is administered by oral, intravenous, intramuscular, and subcutaneous routes, and is safe to titrate hourly to patient comfort. Starting doses range from 0.5 to 2 mg every hour for acute episodes until symptoms are controlled, and then continued every 6 hours around the clock. The dose may need to be titrated depending on the effects to a maximum of 20 mg/day (Avery, 2003).
If haloperidol is ineffective, chlorpromazine (Thorazine[R]) is an alternative that is more sedating. Both chlorpromazine and haloperidol have a low incidence of extrapyramidal symptoms (EPS) at low doses, but EPS should be assessed when higher doses are given (Lawlor, Fainsinger et al., 2000). Because chlorpromazine may lower the seizure threshold and aggravate twitching, lorazepam (Ativan[R]) may be added for relief of anxiety and restlessness. This medication is very sedating and should be used if anxiety, dyspnea, or myoclonus is present. Lorazepam can be given by many routes, including sublingually or bucally, and is supplied in a liquid form if the patient has difficulty swallowing. Another effective benzodiazepine is intravenous midazolam (Versed[R]), one of the best drugs for intractable symptoms. It has a very short half-life and can be titrated frequently to achieve symptom control. Midazolam should be used with caution due to its highly sedating properties (Avery, 2003).
Paradoxical reactions may occur with any of these medications, causing more agitation than sedation. If this occurs, phenobarbitone (Solfoton[R]) may be effective. Stifling et al. (1999) showed phenobarbitone to be well-tolerated and effective in controlling physical and psychological agitation at the end of life. This barbiturate depresses central nervous system activity, has a half-life of 50 to 150 hours, and comes in a suppository or a liquid (for subcutaneous or intramuscular injection). Due to its sedating nature, phenobarbitone usually is used only if symptom control cannot be achieved by the other first-line medications. Barbiturates do not have analgesic or antiemetic properties; however, their concurrent use with opioids or antiemetics must be considered carefully due to risk of sedation. The intention of using sedating medications is solely to control symptoms of restlessness and to ease suffering, not for sedation (Stirling et al., 1999). All these medications may be available in the hospital setting, but nurses must check hospital policy for administering these drugs in their practice areas.
Just being in the hospital can cause restlessness in patients because the environment is unfamiliar. Strategies can be used to manipulate the environment in this situation so that the patient feels more comfortable and safe, which can in itself ease the patient’s symptoms. The presence of familiar relatives or caregivers, either in person or in the form of pictures, can be effective. The nurse should encourage the family to provide verbal assurances and touch the patient. Even for the unconscious patient, holding hands or gently speaking may provide some calming effects (Travis et al., 2001). Additional interventions to soothe symptoms of restlessness include limiting staff changes, playing soft music, reducing excess noise, reading personal passages from a favorite book, using aromatherapy or therapeutic touch, and providing a well-lit room at a comfortable temperature with a calendar and clock (Avery, 2003; Lawlor, Fainsinger et al., 2000; Sagar, 2001; Travis et al., 2001).
Educating the family about the dying process and terminal restlessness is crucial (Brajtman, 2003; Sagar, 2001). Explaining that confusion and agitation are expressions of brain malfunctioning, not suffering, can help relieve grief. Also explaining that it may take up to 3 to 4 days to control symptoms may help prevent family frustration.
Terminal restlessness can be extremely distressing to the patient, family members, and caregivers. Preventing and managing terminal restlessness without delay are priorities to reduce the burden associated with advanced cancer and to maintain the quality of the patient’s remaining life. Keen assessment is critical to managing restlessness, along with identifying and reversing the causes. Assessment can be a difficult process because of the multiple causes. The acronym MEDICINE (see Figure 1) developed by the author may be a helpful guide in finding a possible reversible cause. The acronym can be used as a quick reference for the multiple causes of terminal restlessness such as reminding the health care provider to check an agitated patient for fecal impaction. If the causes cannot be found or reversed, then the symptoms must be treated by a combination of pharmacological, environmental, social, and spiritual interventions.
Because nurses are with the patient longer than the physician and see the range of symptoms throughout the day, thorough communication and collaboration with the physician are necessary. Hospital nurses can help their patient to have a peaceful and comfortable death by being patient advocates. Supporting a quality end-of-life experience is essential not only for the patient, but for the family and loved ones who will carry the experience in their memories. To do this, nurses must expand their knowledge of assessment and management of terminal restlessness.
Signs and Symptoms of Terminal Restlessness
Physical Cognitive Affective
Agitation Hallucinations/paranoia Irritability
Fidgeting Confusion/disorientation Anxiety/worry
Tossing and turning Impaired consciousness Sleep-wake
Myoclonic jerks/twitching disturbance
Moaning or crying out
Sources: Avery, 2003; Brajtman, 2003; Cobb, 2000; Morita et al., 2001;
Risk Factors for Terminal Restlessness
Prior history of dementia Malnutrition
Advancing age Drug or alcohol use
Dehydration Recent use of opioids or antidepressants
Brain tumor Poor pain control
Renal failure Guilt or remorse
Sources: Avery, 2003; Inouye, 2000; Lawlor, Fainsinger et al., 2000;
Lawlor, Gagnon et al., 2000; Morita et al., 2001
Guide in Finding a Possible Reversible
Cause for Terminal Restlessness
E Electrolyte imbalance
I Infection (mostly of urinary tract)
N Neoplasm of brain
E Effects from liver or renal failure
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Heather Blanchette, BSN, RN, OCN, is an Oncology Certified Staff Nurse, Morton Plant Hospital, Clearwater, Fl.
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