- Email: [email protected]
Managing respiratory symptoms at the end of life
Clin Geriatr Med 19 (2003) 225 – 239
Managing respiratory symptoms at the end of life Laurie G. Jacobs, MD* Unified Division of Geriatrics, Albert Einstein College of Medicine and Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA
Dyspnea is the most prevalent respiratory symptom described by elderly patients at the end of life. Other respiratory symptoms, including cough (reported in 30– 50% of cancer patients), hiccups, pain, and control of secretions are also common in the elderly at the end of life whether or not they have primary lung disease. In a study of hospice patients who had cancer, 70.2% reported shortness of breath at some time during the last 6 weeks of life during biweekly interviews. Only 33% had lung or pleural involvement [1]. Thus, the assessment, management, and palliation of respiratory symptoms are important parts of care near and at the end of life. Dyspnea is defined by the American Thoracic Society as ‘‘a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity . . . derives from interactions among multiple physiological, psychological, social and environmental factors, and may include secondary physiological and behavioral responses’’ [2]. In hospice patients, dyspnea has been found to be associated with underlying lung disease, low-level performance on the Karnofsky scale, and underlying cardiac disease [1]. In ‘‘the study to understand prognoses and preferences for outcomes and risks of treatments (SUPPORT)’’ [3], the vast majority of patients who had advanced lung disease experienced dyspnea in the last 3 days of life [4]. Dyspnea has been found to peak just before death in terminally ill cancer patients [5]. Lung involvement and anxiety have been independently correlated with the intensity of dyspnea in patients who have advanced cancer [6]. Anxiety has a reciprocal relationship to dyspnea; the sensation of breathlessness can increase anxiety, and anxiety can be expressed as breathlessness [61]. Both symptoms often require palliation. The palliative management of respiratory and other symptoms
* Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA. E-mail address: [email protected] 0749-0690/03/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved. PII: S 0 7 4 9 - 0 6 9 0 ( 0 2 ) 0 0 0 5 4 - X
226
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
at the end of life should be pursued as vigorously and aggressively as lifeprolonging treatments might have been pursued earlier in the course of the disease.
Advanced care planning The care of patients who have advanced and incurable diseases such as chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), malignancy, or neuromuscular diseases (in which the management of respiratory symptoms at the end of life can be anticipated) should include discussions about advanced care planning. The timing of such discussions is often difficult because providers often express concern that such conversations will cause patients to ‘‘lose hope’’ and may hasten deterioration [7]. Patients might also avoid these topics [8]. Discussions about prognosis and the use of life-prolonging interventions, however, can significantly influence their experiences and quality of life. Discussions about advanced care planning should occur prior to a medical crisis, ideally as a routine part of health care planning. When treatment wishes, quality-of-life values, and delegation of decision-making authority can be separated from disclosure of poor prognosis or end-of-life discussions, they tend to be less threatening and anxiety provoking. Raising these issues when patients are stable permits timely and focused deliberation and promotes carefully considered decision making. Nevertheless, it is often unavoidable that advance care planning is introduced during discussions about prognosis, hopes, fears, treatments with a low probability of success [9], or at a time of increased symptoms, particularly when dyspnea occurs at rest [10], because there are few real indications as to when the end is near [10]. Prognosis often is difficult to determine with accuracy. Urgent indications for such discussions include imminent respiratory failure, hospitalization, patients expressing a wish to die, severe suffering, and poor prognosis [9]. In the SUPPORT study [3], recommended clinical prediction criteria for patients who had advanced lung, heart, or liver disease were not able to identify those with a survival prognosis of 6 months or less [11]. One study has indicated that patients with chronic obstructive lung disease with a PaO2 greater than or equal to 50 mmHg have a 1-year mortality of 43% [12]. Thus, the timing of discussions remains difficult, but their importance is clear. Advanced care planning should at a minimum include the identification of patient care preferences and the appointment of a health care proxy (or agent) or durable power of attorney for health care decisions. Such an individual is empowered to make health care decisions in the event the patient loses the capacity to do so. The health care proxy is responsible for making decisions in accordance with the patient’s known or inferred wishes or, if these preferences are unknown, according to what the proxy judges to be the patient’s ‘‘best interest.’’ If the patient is unable or unwilling to delegate decision-making authority to another person, a living will articulating care preferences can provide useful guidance when others must make treatment decisions. In most states, family members are permitted to
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
227
make end-of-life decisions for patients who lack the capacity to do so under the ‘‘substituted judgment standard,’’ which draws on the patient’s probable wishes [13]. Certain states, including New York, Missouri, Michigan, and Wisconsin, require documentation of an incapacitated patient’s actual wish to forgo certain treatments under specific circumstances. Determination of patient preferences for care is critical in guiding decisions made by the patient, their proxy, or their physician. For patients who have respiratory compromise, discussions about when to forgo therapies that carry high risk and little benefit, whether or not to accept mechanical ventilation or further hospitalization, do-not-resuscitate orders, and when to make end-of-life plans should occur [9]. In a study of patients who had advanced COPD, the majority expressed a preference for comfort care rather than life-prolonging measures [14]. Documentation of these discussions and preferences should be made in the patient’s medical record and on advance directive documents such as living wills and proxy designation forms. It is important that the designated proxy and significant others be aware of such preferences for care.
Dyspnea Pathophysiology in the elderly Pulmonary ventilation is largely determined by airflow and chest wall dynamics, which are altered by aging. A higher closing volume is associated with aging, increasing the ventilation –perfusion mismatch and producing a decline in the arterial partial pressure of oxygen, or PaO2 . In addition, calcification of costochondral cartilage might limit chest expansion; inspiration becomes more dependent on abdominal muscles, which might be less effective in opening airways in a supine position. The cough can also be less vigorous and less effective in clearing secretions. Total lung capacity might remain stable, but residual volume increases with age. Dyspnea is a sensation of breathlessness and should not be confused with tachypnea or hyperventilation. It has a functional aspect relating to exercise tolerance or ability. Dyspnea is thought to be due to a disassociation between central respiratory motor activity and incoming afferent information from central and peripheral chemoreceptors (sensing increased PaCO2, decreased PaO2 and pH) and by mechanical receptors in the chest wall. Some patients, however, experience dyspnea with normal blood gas values, whereas others do not feel dyspneic with extremely aberrant values [15]. It has been demonstrated in healthy individuals that the degree of reflex ventilatory activation is an important determinant of the intensity of dyspnea irrespective of the cause of the ventilatory stimulus [16]. Extrathoracic receptors, including those on the face and in the CNS, also affect the sensation of breathlessness. The pathophysiology of dyspnea might be related to several anatomic or physiologic abnormalities related to the underlying disease. These include
228
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
increased ventilatory demand, respiratory muscle weakness, increased ventilatory impedance, abnormal breathing patterns, and blood gas abnormalities. Ventilatory demand relates to the demands of exercise and pulmonary or vascular disease. Severe dyspnea has been correlated with low maximum inspiratory pressures in patients who have advanced cancer; this suggests that severe respiratory muscle weakness contributes significantly to dyspnea in this population [6,17].
Assessment History and symptom scales As in the palliative management of other symptoms, treatment decisions must be based upon an evaluation of the severity of symptoms and their response to interventions. The components of the assessment include the characteristics reported in the history, simple symptom scoring of severity, affect upon function, and anatomic or physiologic cause. The history should include information about what brings on dyspnea, what relieves it, what other symptoms are associated, the primary diagnosis, comorbid conditions (ie, pulmonary or cardiovascular disease, neuromuscular disease, cognition, etc), and medication use. The duration of symptoms might assist in identifying the cause and instituting therapy. Acute dyspnea occurs within hours and might indicate bronchospasm, infection, pneumothorax, pulmonary embolism, heart failure or ischemia, or psychological issues. Subacute dyspnea has generally been present for days to weeks, and might have similar causes, but it additionally includes obstruction and effusion. Chronic dyspnea lasts months to years, and it might result from COPD, bronchial obstruction, motor neuron disease, or psychological problems. Many symptom scales have been used and reviewed [2]. These scales seek to quantify the severity of dyspnea, but they might not be superior to the patient’s own estimation of functional ability limitations due to the complaint. The affect on function is important to quantify. What activities are no longer possible? Patients with advanced COPD can often estimate the level of physical activity that produces a certain level of dyspnea [18]. Verbal categorical scales (none, mild, moderate, or severe) or visual analog scales (a 10-cm line with ‘‘none’’ and ‘‘extreme’’ dyspnea at either end) are usually most useful, and they are similar to scales used to evaluate pain. The Lung Module (QLQ-LC13) [58] of the EORTC Quality of Life Core Questionnaire (EORTC QL-30) [19] uses a verbal rating system and has been standardized and validated. The Chronic Respiratory Disease Questionnaire (CRQ) [20] is a 20-item instrument that evaluates dyspnea, fatigue, emotional function, and mastery. Measures of symptom severity have not been well correlated with pulmonary functional parameters. Pulmonary function testing might not be helpful in patients who have advanced disease.
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
229
Physical examination and diagnostic testing The physical examination should be thorough and include a careful evaluation of vital signs and the pulmonary, cardiac, and vascular systems to identify chest wall, pleural, parenchymal, pericardial, vascular, and cardiac disease. The extent of further evaluation to direct treatment depends on the type and stage of the underlying process (cancer, COPD, etc), the ability to ameliorate further pathology if found (eg, antibiotics for infection), and patient preferences. A limited diagnostic evaluation will usually include a complete blood count, a chest radiograph, and a pulse oxygenation saturation (SpO2). Further testing can include an ultrasound or computed tomography (CT) scan to evaluate pleural or parenchymal disease, a ventilation – perfusion scan to identify pulmonary emboli, an echocardiogram to assess pericardial disease and myocardial function, and pulmonary function tests of dynamic lung volumes (FEV1, FVC) with and without bronchodilators to examine obstruction and bronchospasm and response to therapy.
Management considerations of specific causes of dyspnea at end of life Superior vena cava syndrome Superior vena cava syndrome is the clinical presentation of superior vena cava obstruction, resulting in reduced venous return from the head, neck, and upper extremities. In cases due to malignancy, lung cancer causes 85%, with lymphoma, breast, and solid tumors comprising the other malignant causes. Thrombosis due to central venous catheters can also produce this syndrome, as can some benign pathologies. Patients usually complain of facial and neck swelling, dyspnea, and cough. Symptoms such as hoarseness, headache, nasal congestion, epistaxis, hemoptysis, pain, dizziness, and syncope might be present and might be exacerbated by bending forward or lying down. Pemberton’s sign on physical examination is an increase in facial plethora and edema with elevation of the arms above the head. Superior vena cava syndrome usually presents acutely and should be treated as an emergency. The diagnosis is generally made clinically; it can be confirmed by a vascular duplex and CT scan. The primary treatment is radiation therapy for malignant disease, although corticosteroids can also be administered to reduce edema and to treat possible radiation-induced inflammatory reactions. Chemotherapy can also be administered in patients in whom the syndrome is due to lymphoma, small cell lung cancer, or breast cancer [21]. Diuretics, head elevation, and oxygen might provide short-term symptomatic relief. Bronchial obstruction Bronchogenic carcinoma might cause obstruction and collapse of the pulmonary parenchyma distal to the obstruction. Infection is commonly present beyond the obstruction as well. External beam radiotherapy or endobronchial
230
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
therapies, including radiotherapy, laser therapy, cryotherapy, and the use of endobronchial stents have been used to treat bronchial obstruction. Pleural effusions Pleural effusions form when the rate of formation of fluid in the pleural space is greater than that of removal due to elevated hydrostatic pressure gradients with transudation or increased permeability of pleural vessels in exudation. In patients who have terminal diseases, transudative effusions might be expected in patients who have cirrhosis, CHF, pulmonary embolism, atelectasis, and other pathologies. Exudative effusions can occur with malignancy (particularly lung, lymphoma, mesothelioma, and metastatic disease), infection, lymphatic disease, or inflammatory conditions, or they might be due to radiation or medications used in treatment. Medications such as amiodarone, bleomycin, methotrexate, and mitomycin, among others [22] can cause pleural effusions. A pleural effusion can be suspected on physical examination. A chest radiograph can usually detect fluid greater than 500 cc [23] whereas an ultrasound can accurately detect effusions of 100 cc or greater and a CT scan can detect even smaller volumes while also evaluating the entire pleura and parenchyma. A lateral decubitus radiograph is helpful in identifying whether or not the effusion is free flowing. The decision to perform a thoracentesis for diagnostic reasons depends on the clinical picture, but the procedure is often performed for relief of dyspnea. It allows lung volumes to increase somewhat, although blood gas measurements are not altered significantly [24]. If dyspnea persists, chest tube drainage and pleurodesis can be considered, although this might initially produce significant discomfort and fever, so the potential benefit must be carefully weighed in patients who have terminal disease. Many patients do not live long enough for the fluid to reaccumulate, so only initial drainage might be warranted. There are data suggesting that the pleural fluid characteristics of a malignant effusion can serve as prognostic indicators and can affect subsequent management. Low pH (< 7.30) and low glucose (< 60 mg/dL) are associated with more extensive tumor involvement of the pleura, less successful attempts at pleurodesis, and shorter survival [25,26]. One study indicated that the mean survival of patients whose pleural fluid had a low pH was 2.1 months versus 9.8 months for those whose pleural fluid had a normal pH [26]. Pericardial effusion/tamponade Malignant pericardial disease occurs most often in patients who have lung cancer, breast cancer, leukemia, or lymphoma. Tumors can invade the pericardium or cause pericarditis or pericardial effusion. Pericardial disease might also be due to complications of therapy such as radiation, drug toxicity, or other comorbid diseases (eg, hypothyroidism, rheumatologic disease). Patients might be asymptomatic or present with dyspnea, cough, chest pain, orthopnea, or
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
231
weakness. Physical findings include pleural effusion, pulsus paradoxicus, pulsus alternans, a friction rub, jugular venous distension, tachycardia, diminished heart sounds, hepatomegaly, edema, and cyanosis. Echocardiography can establish the diagnosis. Therapy includes pericardiocentesis, stripping, ablation, irradiation, and chemotherapy. Congestive heart failure Congestive heart failure (CHF) is extremely frequent in older adults at the end of life and contributes significantly to dyspnea. It might be the primary diagnosis or a concurrent problem due to a comorbid disease or adverse effects of medications. More often congestive heart failure is due to left ventricular systolic dysfunction rather than diastolic dysfunction in this scenario, but an echocardiogram will assist with the evaluation along with the physical examination and chest radiograph. CHF is treated with diuretics, angiotensin converting enzyme inhibitors (ACE-I), b-blockers, digoxin, oxygen, and vasodilators, similar to its management in other clinical settings. Digoxin is often poorly tolerated in the elderly due to adverse effects even without toxic levels, although toxicity occurs more commonly as a result of declining renal function. The ACE-Is are more frequently associated with cough in older adults (personal observation). Carcinomatous lymphangitis Carcinomatous lymphangitis can be difficult to differentiate from CHF. It is due to impedance of pulmonary lymphatic drainage, it usually occurs bilaterally due to malignant obstruction of hilar lymph nodes, and it produces parenchymal congestion. It might contribute to muscle fatigue. Patients complain of severe and continuous dyspnea, and might also have a cough. Carcinomatous lymphangitis is most commonly associated with lung, breast, gastrointestinal, or prostatic cancers. The diagnosis is difficult to ascertain because it might develop insidiously, causing few findings on the physical examination other than rales or crackles, and it is often mistaken for disease progression. Chest radiographs can have minimal findings, or can indicate widespread interstitial edema in the middle and lower zones, which is similar to the radiographic appearance of CHF. Further chemotherapy might be considered as well as radiotherapy to the mid-chest. Highdose corticosteroids are often tried but might contribute to fluid overload. Opioids and anxiolytics are usually administered for symptom management.
Pharmacologic treatment General principles Treatment aimed at palliation of dyspnea can combine a number of modalities, some of which are aimed at treating the underlying lung disease or the other conditions that cause it as well as other factors that might contribute, such as
232
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
anxiety. Treatment modalities aimed at the pathophysiologic causes of dyspnea include those aimed at reducing ventilatory impedance, reducing ventilatory demand, improving respiratory muscle function, and altering central perception of breathlessness. Treatments can also be focused on specific pathologies that cause dyspnea, such as superior vena cava syndrome, pleural effusion, pericardial disease, and obstruction, as discussed above. Bronchodilators and corticosteroids Increased ventilatory impedance contributes significantly to dyspnea. This impedance might be most profound in patients who have advanced COPD with narrowed airways and decreased elasticity, but it might also occur in some patients who have lung cancer and pulmonary fibrosis in which the lung parenchyma is infiltrated. Treatment includes b2-agonists, inhaled anticholinergics, methylxanthines, and inhaled and systemic corticosteroids. Because the tachycardia induced by inhaled b2-agonists or methylxanthines might be poorly tolerated by older adults, inhaled anticholinergic agents are preferred initially. Aminophylline and theophylline are the two methylxanthines used in clinical practice. They might have a bronchodilatory effect, but they also stimulate respiration through a central effect on the medullary center of respiration, driving the hypercapnic and hypoxic drive to breathe. This effect can be useful only in respiratory failure due to the irritability they also produce, which can be more profound in the elderly. Although corticosteroids produce symptomatic relief of dyspnea from obstructive disease, they might also induce euphoria, sleeplessness, muscle weakness, and fluid retention, which can be undesirable. Corticosteroids have not been found to slow the rate of decline in lung function in patients who have COPD [10], but they are employed when patients fail to respond to bronchodilators. There is no evidence that one steroid is superior to others. Oxygen Oxygen therapy is often considered to be less invasive than medication use, easily administered, and a direct treatment for dyspnea. This is not always true; however, oxygen is frequently provided for treatment of dyspnea. Long-term oxygen therapy, preferably continuously administered, has been shown to be of benefit in increasing survival for patients who have hypoxemia and long-standing COPD [27,28]. It also improves quality of life through increased exercise tolerance and improved cognition [29,30]. The data supporting the use and benefit for advanced cancer patients [31,32] and those who have end-stage CHF is more limited and less clear. Oxygen might be of benefit for patients with hypoxemia. This can be difficult to determine clinically because terminally ill patients might appear to be cyanotic, or cool, due to vasoconstriction. Pulse oximetry is the preferred method of determining whether or not a patient is hypoxemic in terminal care because it is
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
233
painless and an immediate result is obtained. If this is unavailable, an empiric trial of oxygen therapy might be considered. Oxygen can be administered continuously or intermittently, timed with activity. Administration by nasal cannula is preferred because it interferes less with communication and eating. Nasal dryness can be protected with ointment. Oxygen can also be delivered through conserving devices such as reservoirs, demand pulse systems, transtracheal catheters, and face masks. Treatment should be initiated at 1 to 3 L/minute during activity and monitored and adjusted accordingly, because oxygen can cause an increase in PCO2. The flow rate or the route of administration has not been correlated with effect on dyspnea in clinical trials [33]. Home oxygen therapy is covered by Medicare under durable medical equipment with strict criteria: a PaO2 less than or equal to 55 mmHg, arterial oxygen saturation (SaO2) less than or equal to 88%, PaO2 56 to 59 mmHg, or SaO2 89% with the following conditions: electrocardiographic evidence of cor pulmonale, edema due to CHF, or erythrocytosis with a hematocrit greater than 56%. Oxygen therapy is covered under the hospice benefit without these criteria. Opioids The usefulness of opioids has been demonstrated in the acute treatment of dyspnea associated with COPD [34] and in terminal cancer patients [59]. The mechanism of this effect is not entirely clear, but several mechanisms have been proposed. Morphine has a depressant effect on the central respiratory center that is dose-dependent. Tolerance can develop with chronic use. Morphine might also act by peripheral mechanisms. Metabolic requirements that require a lower level of ventilation might be reduced by the use of morphine. In addition, opioids also act by reducing anxiety, inducing analgesia, and improving cardiac function through vasodilation. The concern about opioids causing respiratory failure and hastening death was addressed by the United States Supreme Court in two 1997 cases [35,36]. The Court, recognizing a protected interest in adequate pain relief, noted that it is both legally and ethically appropriate to give dying patients as much medication as necessary to relieve pain, even if the foreseen but unintended effect is to hasten death. This principle of ‘‘double effect’’ supports the palliative use of opioids to relieve symptoms such as dyspnea or pain, even in the event that the patient dies as an unintended result of this therapy [13,37]. Opioids are often administered orally, although subcutaneous [38], sublingual, intravenous [39], and transcutaneous routes can be used as well. All opioids are hepatically metabolized to active and inactive metabolites that are excreted renally, and metabolism is slowed with aging. The data supporting the use of nebulized, inhaled opioids are more limited and less robust [40,41]. Long-term use of opioids for chronic dyspnea in COPD has been found to be less helpful due to the prevalence of adverse effects, including drowsiness, nausea, and constipation [42].
234
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
Psychotropic agents Benzodiazepines have also been used to reduce dyspnea in patients who have COPD by depressing the ventilatory drive, the perception of breathlessness, and anxiety [43]. These drugs can cause sedation and ataxia, particularly in the elderly, in whom they might be more slowly metabolized and might have an increased pharmacodynamic effect.
Complementary and alternative medicine modalities Positioning might also be helpful in the relief of dyspnea in patients who have COPD. Body positions such as leaning forward, which increases abdominal pressure, might enhance respiratory muscle and diaphragm function in patients who have COPD [44,45]. Fans have also been found to relieve dyspnea in patients who have severe COPD. The mechanism is thought to be due to stimulation of mechanoreceptors on the face or a decrease in the temperature of facial skin, which are mediated through the trigeminal nerve [2]. A review of the use of complementary and alternative medicine in symptom management at the end of life describes the use of several modalities that have undergone limited testing [46]. Two trials evaluating the use of acupuncture, one in patients with COPD [47] and the other in cancer patients [48], demonstrated symptomatic improvements. One study of the use of acupressure during pulmonary rehabilitation showed that dyspnea was significantly reduced in patients who had COPD [60]. Mechanical vibration of the chest wall inspiratory muscles during inspiration using vibrators has been found to reduce dyspnea in patients who have advanced COPD and hypercapnia [49]. Behavioral and psychological therapy has been used in the treatment of dyspnea for patients with COPD [25,50] and lung cancer [51] with some benefit.
Cough, hiccups, and control of secretions Pathophysiology Cough Cough is a normal respiratory mechanism designed to protect the airway by clearing secretions and inhaled material. Cough can be voluntary or involuntary. It can also be produced by abnormal stimulation of the irritant receptors in the airways. Illnesses associated with inflammation, constriction, infiltration, or compression of airways can cause cough. Chronic cough might be a symptom that causes significant suffering for elderly patients at the end of life. The cough reflex is normally diminished with aging, and it might be reduced further by muscle weakness, cognitive dysfunction, and sedation. It is also often associated with other symptoms, including chest tightness, dyspnea, and pain.
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
235
Hiccups Hiccups are produced by contraction of the inspiratory muscles, which is terminated abruptly by closure of the glottis. Hiccups can occur transiently with gastric distension, sudden changes in temperature, alcohol, smoking, or excitement. Persistent hiccups can be disturbing, and they might have several etiologies, including infection or structural lesions of the central nervous system, diaphragmatic irritation by tumor or inflammation, metabolic abnormalities, vascular lesions, intra-abdominal processes, or systemic infection [52]. Assessment It is useful to determine the cause of cough to optimize therapy? Is the cough acute or chronic? Are the increased secretions due to aspiration or infection or an inability to clear saliva and secretions due to weakness or motor neuron disease? Is the cough a symptom of CHF or an obstructive airway disease? Is cough an adverse effect of a medication such as an ACE-I or an inhaled drug? Common causes of cough include pulmonary or sinus infection, airway diseases (including COPD or obstruction due to malignant disease), CHF, gastroesophageal reflux or aspiration, and drug-induced cough due to ACE-Is or inhaled medications. The history, physical examination, chest (and perhaps sinus) radiographs, and an examination of sputum along with a complete blood count might be sufficient to determine the cause of cough and institute therapy. The mental status, examination of the oropharynx, chest, heart, and vasculature might indicate evidence of heart failure, infection, or aspiration. The elderly are often unable to expectorate sputum due to weakness, so evaluation of sputum is often not possible. More invasive testing is rarely required in the management of cough at the end of life. Management Cough and management of secretions Treatment should be aimed at the underlying pathology inducing the cough, if possible. Respiratory infections are managed in the usual manner with appropriate but often empiric antibiotic coverage appropriate to the community, nursing home, or hospital setting. The patient might be immune suppressed due to disease or prior therapy, requiring broader coverage than might have otherwise been required. Adjunctive therapy with an expectorant and cough suppressant can be given. Agents containing opioids are most effective at suppression, but they might cause sedation, confusion, and constipation in older adults. Physiotherapy with cupping and drainage can provide some assistance with clearing secretions, as can nebulized saline. Cough due to COPD or CHF is managed in the usual fashion, as described previously. Physiotherapy might also provide some relief. Aspiration or gastroesophageal reflux occurs normally, and might increase due to sedation from medications or disease, weakness, confusion, food inadequately cleared from the mouth, inhalation of liquids, supine position, or the use of nasogastric or percutaneous gastrostomy tubes for feeding. Management includes
236
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
maintenance of an upright posture, use of thickened liquids or pureed foods, drinking through straws, H2-blockers, and anti-reflux agents. If aspiration of saliva is due to motor neuron disease, the use of anticholinergic agents to reduce saliva might help, although they can induce confusion and agitation in older adults [53]. The ‘‘death rattle’’ occurs when semiconscious or deeply unconscious patients are unable to swallow saliva or cough secretions reflexively. It usually occurs during the final hours of life. These secretions vibrate noisily in the airway with respiration producing a ‘‘rattle’’ that can be disturbing to family and staff. Gentle suctioning can help, but it might also be disturbing. Anticholinergic agents such as hyoscine can be administered as a single dose or continuous infusion to prevent or treat this condition. Hiccups Initial treatment of hiccups is often aimed at reduction of gastric distension, because this often initiates sporadic episodes. Antiflatulent agents such as simethecone can be tried initially, and prokinetc agents can be added if needed. Peppermint water has been used, which is reported to relax the lower esophageal sphincter, but it opposes the action of prokinetic agents. Baclofen [54], nifedipine [55,56], and haloperidol [57] have been used to treat intractable hiccups.
Summary Early and clear discussion and articulation of preferences about interventions with increasing burdens and diminishing benefits is helpful in identifying the goals of care and planning management for patients who have unremitting terminal illnesses. The development of respiratory symptoms such as dyspnea, cough, and hiccups is common and can often be anticipated. Aggressive evaluation and treatment should be pursued and offered to palliate symptoms at the end of life.
References [1] Reuben DB, Mor V. Dyspnea in terminally ill cancer patients. Chest 1986;89:234 – 6. [2] American Thoracic Society. Dyspnea. Mechanisms, assessment and management: a consensus statement. Am J Respir Crit Care Med 1999;159:321 – 40. [3] The SUPPORT Principal Investigators. A controlled trial to improve care for seriously ill hospitalized patients. The study to understand prognoses and preferences for outcomes and risks of treatments (SUPPORT). JAMA 1995;274:1591 – 8. [4] Lynn J, Teno J, Phillips R, et al. Perceptions by family members of the dying experience of older and seriously ill patients. Ann Intern Med 1997;126:97 – 106. [5] Mercadante S, Casuccio A, Fulfaro F. The course of symptom frequency and intensity in advanced cancer patients followed at home. J Pain Symptom Manage 2000;20:104 – 12. [6] Bruera E, Schmitz B, Pither J, et al. The frequency and correlates of dyspnea in patients with advanced cancer. J Pain Symptom Manage 2000;19:357 – 62. [7] Larson DG, Tobin DR. End-of-life conversations: evolving practice and theory. JAMA 2000; 284:1573 – 8.
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
237
[8] Hinton J. An assessment of open communication between people with terminal cancer, caring relatives, and others during home care. J Palliat Care 1998;14:15 – 23. [9] Quill TE. Initiating end-of-life discussions with seriously ill patients. Addressing the ‘‘elephant in the room.’’ JAMA 2000;284:2502 – 7. [10] Luce JM, Luce JA. Management of dyspnea in patients with far-advanced lung disease. ‘‘Once I lose it, it’s kind of hard to catch it. . .’’ JAMA 2001;285:1331 – 7. [11] Fox E, Landrum-McNiff K, Zhong Z, et al. Evaluation of prognostic criteria for determining hospice eligibility in patients with advanced lung, heart or liver disease. JAMA 1999;282: 1638 – 45. [12] Connors AF, Dawson NV, Thomas C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. Am J Respir Crit Care Med 1996;154:959 – 67. [13] Meisel A, Snyder L, Quill T. Seven legal barriers to end-of-life care. Myths, realities, and grains of truth. JAMA 2000;284:2495 – 501. [14] Lynn J, Ely EW, Zhong Z, et al. Living and dying with chronic obstructive pulmonary disease. J Am Geriatr Soc 2000;48:S91 – S100. [15] Kikuchi Y, Okabe S, Tamura G, et al. Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma. N Engl J Med 1994;330:1329 – 34. [16] Lane R, Adams L. Metabolic acidosis and breathlessness during exercise and hypercapnia in man. J Physiol 1993;461:47 – 61. [17] Dudgeon D, Lertzman M. Dyspnea in the advanced cancer patient. J Pain Symptom Manage 1998;16:212 – 9. [18] Jefia R, Ward J, Lentine T, Mahler DA. Target dyspnea ratings predict expected oxygen consumption as well as target heart rate values. Am J Respir Crit Care Med 1999;159:1485 – 9. [19] Aaronson N, Bullinger M, Ahmedzai S. A modular approach to quality of life assessment in cancer clinical trials. Cancer Res 1988;111:231 – 49. [20] Guyatt GH, Berman LB, Townsend M, et al. A measure of quality of life for clinical trials in chronic lung disease. Thorax 1987;42:773 – 8. [21] Ahmedzai S. Palliation of respiratory symptoms. In: Doyle D, Hanks GWC, MacDonald N, editors. Oxford textbook of palliative medicine, 2nd edition. Oxford: Oxford University Press; 1998. p. 583 – 616. [22] Bartter T, Akers SM, Pratter MR. The evaluation of pleural effusion. Chest 1994;106:1209 – 14. [23] Gryminski J, Krakowda P, Lypacewicz G. The diagnosis of pleural effusion by ultrasonic and radiologic techniques. Chest 1976;70:33 – 7. [24] Estenne M, Yernault JC, Troyer A. Mechanism of relief of dyspnea after thoracentesis in patients with large pleural effusions. Am J Med 1983;74:813 – 9. [25] Rodriquez-Panadero F, Lopez-Mejias J. Survival time of patients with pleural metastatic carcinoma predicted by glucose and pH studies. Chest 1989;95:320 – 4. [26] Sahn SA, Good JT. Pleural fluid pH in malignant effusions. Ann Intern Med 1988;108: 345 – 9. [27] Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med 1980;93:391 – 8. [28] The Medical Research Council Working Party. Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet 1981;1: 681 – 5. [29] Heaton RK, Grant I, McSweeney AJ, et al. Psychologic effects of continuous and nocturnal oxygen therapy in hypoxemic chronic obstructive pulmonary disease. Arch Intern Med 1983; 143:1941 – 7. [30] Petty TL, Finigan MM. Clinical evaluation of prolonged ambulatory oxygen therapy in chronic airway obstruction. Am J Med 1968;45:242 – 52. [31] Bruera E, de Stoutz N, Velasco-Leiva A, et al. Effects of oxygen on dyspnoea in hypoxaemic terminal-cancer patients. Lancet 1993;342:13 – 4. [32] Booth S, Kelly MJ, Cox MP, et al. Does oxygen help dyspnoea in patients with cancer? Am Rev Resp Crit Care Med 1996;153:1515 – 8. [33] Dewan NA, Bell CW. Effect of low flow and high flow oxygen delivery on exercise tolerance
238
[34] [35] [36] [37]
[38] [39] [40] [41] [42]
[43] [44] [45] [46]
[47] [48] [49]
[50] [51] [52]
[53] [54] [55] [56] [57]
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239 and sensation of dyspnea: a study comparing the transtracheal catheter and nasal prongs. Chest 1994;105:1061 – 5. Light RW, Muro JR, Sato RI, et al. Effects of oral morphine on breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease. Am J Respir Dis 1989;139:126 – 33. Vacco v Quill, 117 S.Ct. 606 (1997). Washington v Glucksberg, 117 S.Ct. 735 (1997). Luce JM, Alpers A. Legal aspects of withholding and withdrawing life support from critically ill patients in the United States and providing palliative care to them. Am J Respir Crit Care Med 2000;162:2029 – 32. Bruera E, MacEachern T, Ripamonti C, et al. Subcutaneous morphine for dyspnea in cancer patients. Ann Intern Med 1993;119:906 – 7. Cohen MH, Anderson AJ, Krasnow SH, et al. Continuous intravenous infusion of morphine for severe dyspnea. South Med J 1991;84:229 – 34. Noseda A, Carpiaux J-P, Markstine C, et al. Disabling dyspnoea in patients with advanced disease: lack of effect of nebulized morphine. Eur Respir J 1997;10:1079 – 83. Young IH, Daviskas E, Keena VA. Effect of low dose nebulized morphine on exercise endurance in patients with chronic lung disease. Thorax 1989;44:387 – 90. Poole PJ, Veale AG, Black PN. The effect of sustained-release morphine on breathlessness and quality of life in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157:1877 – 80. Man GCW, Hsu K, Sproule BJ. The effect of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease. Chest 1986;9:832 – 6. Barach AL. Chronic obstructive pulmonary disease: postural relief of dyspnea. Arch Phys Med Rehabil 1974;55:494 – 503. O’Neil S, McCarthy DS. Postural relief of dyspnea in severe chronic airflow limitation: relationship to respiratory muscle strength. Thorax 1983;38:585 – 600. Pan CX, Morrison RS, Ness J, et al. Complementary and alternative medicine in the management of pain, dyspnea, and nausea and vomiting near the end of life: a systematic review. J Pain Symptom Manage 2000;20:374 – 87. Jobst K, Chen JH, McPherson J, et al. Controlled trial of acupuncture for disabling breathlessness. Lancet 1986;2:1416 – 8. Filshie J, Penn K, Ashley S, et al. Acupuncture for the relief of cancer related breathlessness. Palliat Med 1996;10:145 – 50. Cristiano LM, Schwartzstein RM. Effect of chest wall vibration on dyspnea during hypercapnia and exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;155: 1552 – 9. Renfroe KL. Effect of progressive relaxation on dyspnea and state anxiety in patients with chronic obstructive pulmonary disease. Heart Lung 1988;17:408 – 13. Corner J, Plant H, A’Hern R, Bailey C. Non-pharmacological intervention for breathlessness in lung cancer. Palliat Med 1996;10:299 – 305. Friedman LS, Isselbacher KJ. Nausea, vomiting, and indigestion. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, editors. Harrison’s principles of internal medicine. 14th edition. New York: McGraw-Hill; 1998. p. 230 – 6. Tune LE. Anticholinergic effects of medication in elderly patients. J Clin Psychiatry 2001;62 (Suppl 21):11 – 4. Ramirez FC, Graham DY. Treatment of intractable hiccup with baclofen: results of a doubleblind randomized, controlled crossover study. Am J Gastro 1992;87:1789 – 91. Mukhopadhyay P, Osman MR, Wajima T, Wallace TI. Nifedipine for intractable hiccups. N Engl J Med 1986;314:1256. Lipps DC, Jabbari B, Mitchell MH, Daigh JD. Nifedipine for intractable hiccups. Neurology 1990; 40:531 – 2. Ives TJ, Fleming MF, Weart CW, Block D. Treatment of intractable hiccups with intramuscular haloperidol. Am J Psych 1985;142:1368 – 9.
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
239
[58] Bergman B, Aaronson NK, Ahmedzai S, et al. The EORTC QLQ-LC13: a modular supplement to the EORTC core quality of life questionnaire (QLQ-C30) for use in lung cancer clinical trials. Eur J of Ca 1994;30A:635 – 42. [59] Bruera E, Macmillan K, Pither J, MacDonald RN. Effects of morphine on the dyspnea of terminal cancer patients. J Pain Symptom Manage 1990;5:341 – 4. [60] Maa SH, Gauthier D, Turner M. Acupressure as an adjunct to a pulmonary rehabilitation program. J Cardiopulm Rehab 1997;17:268 – 76. [61] Rosser R, Denford J, Heslop A, et al. Breathlessness and psychiatric morbidity in chronic bronchitis and emphysema: a study of psychotherapeutic management. Psychol Med 1983;13: 93 – 110.
Managing respiratory symptoms at the end of life Laurie G. Jacobs, MD* Unified Division of Geriatrics, Albert Einstein College of Medicine and Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA
Dyspnea is the most prevalent respiratory symptom described by elderly patients at the end of life. Other respiratory symptoms, including cough (reported in 30– 50% of cancer patients), hiccups, pain, and control of secretions are also common in the elderly at the end of life whether or not they have primary lung disease. In a study of hospice patients who had cancer, 70.2% reported shortness of breath at some time during the last 6 weeks of life during biweekly interviews. Only 33% had lung or pleural involvement [1]. Thus, the assessment, management, and palliation of respiratory symptoms are important parts of care near and at the end of life. Dyspnea is defined by the American Thoracic Society as ‘‘a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity . . . derives from interactions among multiple physiological, psychological, social and environmental factors, and may include secondary physiological and behavioral responses’’ [2]. In hospice patients, dyspnea has been found to be associated with underlying lung disease, low-level performance on the Karnofsky scale, and underlying cardiac disease [1]. In ‘‘the study to understand prognoses and preferences for outcomes and risks of treatments (SUPPORT)’’ [3], the vast majority of patients who had advanced lung disease experienced dyspnea in the last 3 days of life [4]. Dyspnea has been found to peak just before death in terminally ill cancer patients [5]. Lung involvement and anxiety have been independently correlated with the intensity of dyspnea in patients who have advanced cancer [6]. Anxiety has a reciprocal relationship to dyspnea; the sensation of breathlessness can increase anxiety, and anxiety can be expressed as breathlessness [61]. Both symptoms often require palliation. The palliative management of respiratory and other symptoms
* Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA. E-mail address: [email protected] 0749-0690/03/$ – see front matter D 2002, Elsevier Science (USA). All rights reserved. PII: S 0 7 4 9 - 0 6 9 0 ( 0 2 ) 0 0 0 5 4 - X
226
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
at the end of life should be pursued as vigorously and aggressively as lifeprolonging treatments might have been pursued earlier in the course of the disease.
Advanced care planning The care of patients who have advanced and incurable diseases such as chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), malignancy, or neuromuscular diseases (in which the management of respiratory symptoms at the end of life can be anticipated) should include discussions about advanced care planning. The timing of such discussions is often difficult because providers often express concern that such conversations will cause patients to ‘‘lose hope’’ and may hasten deterioration [7]. Patients might also avoid these topics [8]. Discussions about prognosis and the use of life-prolonging interventions, however, can significantly influence their experiences and quality of life. Discussions about advanced care planning should occur prior to a medical crisis, ideally as a routine part of health care planning. When treatment wishes, quality-of-life values, and delegation of decision-making authority can be separated from disclosure of poor prognosis or end-of-life discussions, they tend to be less threatening and anxiety provoking. Raising these issues when patients are stable permits timely and focused deliberation and promotes carefully considered decision making. Nevertheless, it is often unavoidable that advance care planning is introduced during discussions about prognosis, hopes, fears, treatments with a low probability of success [9], or at a time of increased symptoms, particularly when dyspnea occurs at rest [10], because there are few real indications as to when the end is near [10]. Prognosis often is difficult to determine with accuracy. Urgent indications for such discussions include imminent respiratory failure, hospitalization, patients expressing a wish to die, severe suffering, and poor prognosis [9]. In the SUPPORT study [3], recommended clinical prediction criteria for patients who had advanced lung, heart, or liver disease were not able to identify those with a survival prognosis of 6 months or less [11]. One study has indicated that patients with chronic obstructive lung disease with a PaO2 greater than or equal to 50 mmHg have a 1-year mortality of 43% [12]. Thus, the timing of discussions remains difficult, but their importance is clear. Advanced care planning should at a minimum include the identification of patient care preferences and the appointment of a health care proxy (or agent) or durable power of attorney for health care decisions. Such an individual is empowered to make health care decisions in the event the patient loses the capacity to do so. The health care proxy is responsible for making decisions in accordance with the patient’s known or inferred wishes or, if these preferences are unknown, according to what the proxy judges to be the patient’s ‘‘best interest.’’ If the patient is unable or unwilling to delegate decision-making authority to another person, a living will articulating care preferences can provide useful guidance when others must make treatment decisions. In most states, family members are permitted to
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
227
make end-of-life decisions for patients who lack the capacity to do so under the ‘‘substituted judgment standard,’’ which draws on the patient’s probable wishes [13]. Certain states, including New York, Missouri, Michigan, and Wisconsin, require documentation of an incapacitated patient’s actual wish to forgo certain treatments under specific circumstances. Determination of patient preferences for care is critical in guiding decisions made by the patient, their proxy, or their physician. For patients who have respiratory compromise, discussions about when to forgo therapies that carry high risk and little benefit, whether or not to accept mechanical ventilation or further hospitalization, do-not-resuscitate orders, and when to make end-of-life plans should occur [9]. In a study of patients who had advanced COPD, the majority expressed a preference for comfort care rather than life-prolonging measures [14]. Documentation of these discussions and preferences should be made in the patient’s medical record and on advance directive documents such as living wills and proxy designation forms. It is important that the designated proxy and significant others be aware of such preferences for care.
Dyspnea Pathophysiology in the elderly Pulmonary ventilation is largely determined by airflow and chest wall dynamics, which are altered by aging. A higher closing volume is associated with aging, increasing the ventilation –perfusion mismatch and producing a decline in the arterial partial pressure of oxygen, or PaO2 . In addition, calcification of costochondral cartilage might limit chest expansion; inspiration becomes more dependent on abdominal muscles, which might be less effective in opening airways in a supine position. The cough can also be less vigorous and less effective in clearing secretions. Total lung capacity might remain stable, but residual volume increases with age. Dyspnea is a sensation of breathlessness and should not be confused with tachypnea or hyperventilation. It has a functional aspect relating to exercise tolerance or ability. Dyspnea is thought to be due to a disassociation between central respiratory motor activity and incoming afferent information from central and peripheral chemoreceptors (sensing increased PaCO2, decreased PaO2 and pH) and by mechanical receptors in the chest wall. Some patients, however, experience dyspnea with normal blood gas values, whereas others do not feel dyspneic with extremely aberrant values [15]. It has been demonstrated in healthy individuals that the degree of reflex ventilatory activation is an important determinant of the intensity of dyspnea irrespective of the cause of the ventilatory stimulus [16]. Extrathoracic receptors, including those on the face and in the CNS, also affect the sensation of breathlessness. The pathophysiology of dyspnea might be related to several anatomic or physiologic abnormalities related to the underlying disease. These include
228
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
increased ventilatory demand, respiratory muscle weakness, increased ventilatory impedance, abnormal breathing patterns, and blood gas abnormalities. Ventilatory demand relates to the demands of exercise and pulmonary or vascular disease. Severe dyspnea has been correlated with low maximum inspiratory pressures in patients who have advanced cancer; this suggests that severe respiratory muscle weakness contributes significantly to dyspnea in this population [6,17].
Assessment History and symptom scales As in the palliative management of other symptoms, treatment decisions must be based upon an evaluation of the severity of symptoms and their response to interventions. The components of the assessment include the characteristics reported in the history, simple symptom scoring of severity, affect upon function, and anatomic or physiologic cause. The history should include information about what brings on dyspnea, what relieves it, what other symptoms are associated, the primary diagnosis, comorbid conditions (ie, pulmonary or cardiovascular disease, neuromuscular disease, cognition, etc), and medication use. The duration of symptoms might assist in identifying the cause and instituting therapy. Acute dyspnea occurs within hours and might indicate bronchospasm, infection, pneumothorax, pulmonary embolism, heart failure or ischemia, or psychological issues. Subacute dyspnea has generally been present for days to weeks, and might have similar causes, but it additionally includes obstruction and effusion. Chronic dyspnea lasts months to years, and it might result from COPD, bronchial obstruction, motor neuron disease, or psychological problems. Many symptom scales have been used and reviewed [2]. These scales seek to quantify the severity of dyspnea, but they might not be superior to the patient’s own estimation of functional ability limitations due to the complaint. The affect on function is important to quantify. What activities are no longer possible? Patients with advanced COPD can often estimate the level of physical activity that produces a certain level of dyspnea [18]. Verbal categorical scales (none, mild, moderate, or severe) or visual analog scales (a 10-cm line with ‘‘none’’ and ‘‘extreme’’ dyspnea at either end) are usually most useful, and they are similar to scales used to evaluate pain. The Lung Module (QLQ-LC13) [58] of the EORTC Quality of Life Core Questionnaire (EORTC QL-30) [19] uses a verbal rating system and has been standardized and validated. The Chronic Respiratory Disease Questionnaire (CRQ) [20] is a 20-item instrument that evaluates dyspnea, fatigue, emotional function, and mastery. Measures of symptom severity have not been well correlated with pulmonary functional parameters. Pulmonary function testing might not be helpful in patients who have advanced disease.
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
229
Physical examination and diagnostic testing The physical examination should be thorough and include a careful evaluation of vital signs and the pulmonary, cardiac, and vascular systems to identify chest wall, pleural, parenchymal, pericardial, vascular, and cardiac disease. The extent of further evaluation to direct treatment depends on the type and stage of the underlying process (cancer, COPD, etc), the ability to ameliorate further pathology if found (eg, antibiotics for infection), and patient preferences. A limited diagnostic evaluation will usually include a complete blood count, a chest radiograph, and a pulse oxygenation saturation (SpO2). Further testing can include an ultrasound or computed tomography (CT) scan to evaluate pleural or parenchymal disease, a ventilation – perfusion scan to identify pulmonary emboli, an echocardiogram to assess pericardial disease and myocardial function, and pulmonary function tests of dynamic lung volumes (FEV1, FVC) with and without bronchodilators to examine obstruction and bronchospasm and response to therapy.
Management considerations of specific causes of dyspnea at end of life Superior vena cava syndrome Superior vena cava syndrome is the clinical presentation of superior vena cava obstruction, resulting in reduced venous return from the head, neck, and upper extremities. In cases due to malignancy, lung cancer causes 85%, with lymphoma, breast, and solid tumors comprising the other malignant causes. Thrombosis due to central venous catheters can also produce this syndrome, as can some benign pathologies. Patients usually complain of facial and neck swelling, dyspnea, and cough. Symptoms such as hoarseness, headache, nasal congestion, epistaxis, hemoptysis, pain, dizziness, and syncope might be present and might be exacerbated by bending forward or lying down. Pemberton’s sign on physical examination is an increase in facial plethora and edema with elevation of the arms above the head. Superior vena cava syndrome usually presents acutely and should be treated as an emergency. The diagnosis is generally made clinically; it can be confirmed by a vascular duplex and CT scan. The primary treatment is radiation therapy for malignant disease, although corticosteroids can also be administered to reduce edema and to treat possible radiation-induced inflammatory reactions. Chemotherapy can also be administered in patients in whom the syndrome is due to lymphoma, small cell lung cancer, or breast cancer [21]. Diuretics, head elevation, and oxygen might provide short-term symptomatic relief. Bronchial obstruction Bronchogenic carcinoma might cause obstruction and collapse of the pulmonary parenchyma distal to the obstruction. Infection is commonly present beyond the obstruction as well. External beam radiotherapy or endobronchial
230
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
therapies, including radiotherapy, laser therapy, cryotherapy, and the use of endobronchial stents have been used to treat bronchial obstruction. Pleural effusions Pleural effusions form when the rate of formation of fluid in the pleural space is greater than that of removal due to elevated hydrostatic pressure gradients with transudation or increased permeability of pleural vessels in exudation. In patients who have terminal diseases, transudative effusions might be expected in patients who have cirrhosis, CHF, pulmonary embolism, atelectasis, and other pathologies. Exudative effusions can occur with malignancy (particularly lung, lymphoma, mesothelioma, and metastatic disease), infection, lymphatic disease, or inflammatory conditions, or they might be due to radiation or medications used in treatment. Medications such as amiodarone, bleomycin, methotrexate, and mitomycin, among others [22] can cause pleural effusions. A pleural effusion can be suspected on physical examination. A chest radiograph can usually detect fluid greater than 500 cc [23] whereas an ultrasound can accurately detect effusions of 100 cc or greater and a CT scan can detect even smaller volumes while also evaluating the entire pleura and parenchyma. A lateral decubitus radiograph is helpful in identifying whether or not the effusion is free flowing. The decision to perform a thoracentesis for diagnostic reasons depends on the clinical picture, but the procedure is often performed for relief of dyspnea. It allows lung volumes to increase somewhat, although blood gas measurements are not altered significantly [24]. If dyspnea persists, chest tube drainage and pleurodesis can be considered, although this might initially produce significant discomfort and fever, so the potential benefit must be carefully weighed in patients who have terminal disease. Many patients do not live long enough for the fluid to reaccumulate, so only initial drainage might be warranted. There are data suggesting that the pleural fluid characteristics of a malignant effusion can serve as prognostic indicators and can affect subsequent management. Low pH (< 7.30) and low glucose (< 60 mg/dL) are associated with more extensive tumor involvement of the pleura, less successful attempts at pleurodesis, and shorter survival [25,26]. One study indicated that the mean survival of patients whose pleural fluid had a low pH was 2.1 months versus 9.8 months for those whose pleural fluid had a normal pH [26]. Pericardial effusion/tamponade Malignant pericardial disease occurs most often in patients who have lung cancer, breast cancer, leukemia, or lymphoma. Tumors can invade the pericardium or cause pericarditis or pericardial effusion. Pericardial disease might also be due to complications of therapy such as radiation, drug toxicity, or other comorbid diseases (eg, hypothyroidism, rheumatologic disease). Patients might be asymptomatic or present with dyspnea, cough, chest pain, orthopnea, or
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
231
weakness. Physical findings include pleural effusion, pulsus paradoxicus, pulsus alternans, a friction rub, jugular venous distension, tachycardia, diminished heart sounds, hepatomegaly, edema, and cyanosis. Echocardiography can establish the diagnosis. Therapy includes pericardiocentesis, stripping, ablation, irradiation, and chemotherapy. Congestive heart failure Congestive heart failure (CHF) is extremely frequent in older adults at the end of life and contributes significantly to dyspnea. It might be the primary diagnosis or a concurrent problem due to a comorbid disease or adverse effects of medications. More often congestive heart failure is due to left ventricular systolic dysfunction rather than diastolic dysfunction in this scenario, but an echocardiogram will assist with the evaluation along with the physical examination and chest radiograph. CHF is treated with diuretics, angiotensin converting enzyme inhibitors (ACE-I), b-blockers, digoxin, oxygen, and vasodilators, similar to its management in other clinical settings. Digoxin is often poorly tolerated in the elderly due to adverse effects even without toxic levels, although toxicity occurs more commonly as a result of declining renal function. The ACE-Is are more frequently associated with cough in older adults (personal observation). Carcinomatous lymphangitis Carcinomatous lymphangitis can be difficult to differentiate from CHF. It is due to impedance of pulmonary lymphatic drainage, it usually occurs bilaterally due to malignant obstruction of hilar lymph nodes, and it produces parenchymal congestion. It might contribute to muscle fatigue. Patients complain of severe and continuous dyspnea, and might also have a cough. Carcinomatous lymphangitis is most commonly associated with lung, breast, gastrointestinal, or prostatic cancers. The diagnosis is difficult to ascertain because it might develop insidiously, causing few findings on the physical examination other than rales or crackles, and it is often mistaken for disease progression. Chest radiographs can have minimal findings, or can indicate widespread interstitial edema in the middle and lower zones, which is similar to the radiographic appearance of CHF. Further chemotherapy might be considered as well as radiotherapy to the mid-chest. Highdose corticosteroids are often tried but might contribute to fluid overload. Opioids and anxiolytics are usually administered for symptom management.
Pharmacologic treatment General principles Treatment aimed at palliation of dyspnea can combine a number of modalities, some of which are aimed at treating the underlying lung disease or the other conditions that cause it as well as other factors that might contribute, such as
232
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
anxiety. Treatment modalities aimed at the pathophysiologic causes of dyspnea include those aimed at reducing ventilatory impedance, reducing ventilatory demand, improving respiratory muscle function, and altering central perception of breathlessness. Treatments can also be focused on specific pathologies that cause dyspnea, such as superior vena cava syndrome, pleural effusion, pericardial disease, and obstruction, as discussed above. Bronchodilators and corticosteroids Increased ventilatory impedance contributes significantly to dyspnea. This impedance might be most profound in patients who have advanced COPD with narrowed airways and decreased elasticity, but it might also occur in some patients who have lung cancer and pulmonary fibrosis in which the lung parenchyma is infiltrated. Treatment includes b2-agonists, inhaled anticholinergics, methylxanthines, and inhaled and systemic corticosteroids. Because the tachycardia induced by inhaled b2-agonists or methylxanthines might be poorly tolerated by older adults, inhaled anticholinergic agents are preferred initially. Aminophylline and theophylline are the two methylxanthines used in clinical practice. They might have a bronchodilatory effect, but they also stimulate respiration through a central effect on the medullary center of respiration, driving the hypercapnic and hypoxic drive to breathe. This effect can be useful only in respiratory failure due to the irritability they also produce, which can be more profound in the elderly. Although corticosteroids produce symptomatic relief of dyspnea from obstructive disease, they might also induce euphoria, sleeplessness, muscle weakness, and fluid retention, which can be undesirable. Corticosteroids have not been found to slow the rate of decline in lung function in patients who have COPD [10], but they are employed when patients fail to respond to bronchodilators. There is no evidence that one steroid is superior to others. Oxygen Oxygen therapy is often considered to be less invasive than medication use, easily administered, and a direct treatment for dyspnea. This is not always true; however, oxygen is frequently provided for treatment of dyspnea. Long-term oxygen therapy, preferably continuously administered, has been shown to be of benefit in increasing survival for patients who have hypoxemia and long-standing COPD [27,28]. It also improves quality of life through increased exercise tolerance and improved cognition [29,30]. The data supporting the use and benefit for advanced cancer patients [31,32] and those who have end-stage CHF is more limited and less clear. Oxygen might be of benefit for patients with hypoxemia. This can be difficult to determine clinically because terminally ill patients might appear to be cyanotic, or cool, due to vasoconstriction. Pulse oximetry is the preferred method of determining whether or not a patient is hypoxemic in terminal care because it is
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
233
painless and an immediate result is obtained. If this is unavailable, an empiric trial of oxygen therapy might be considered. Oxygen can be administered continuously or intermittently, timed with activity. Administration by nasal cannula is preferred because it interferes less with communication and eating. Nasal dryness can be protected with ointment. Oxygen can also be delivered through conserving devices such as reservoirs, demand pulse systems, transtracheal catheters, and face masks. Treatment should be initiated at 1 to 3 L/minute during activity and monitored and adjusted accordingly, because oxygen can cause an increase in PCO2. The flow rate or the route of administration has not been correlated with effect on dyspnea in clinical trials [33]. Home oxygen therapy is covered by Medicare under durable medical equipment with strict criteria: a PaO2 less than or equal to 55 mmHg, arterial oxygen saturation (SaO2) less than or equal to 88%, PaO2 56 to 59 mmHg, or SaO2 89% with the following conditions: electrocardiographic evidence of cor pulmonale, edema due to CHF, or erythrocytosis with a hematocrit greater than 56%. Oxygen therapy is covered under the hospice benefit without these criteria. Opioids The usefulness of opioids has been demonstrated in the acute treatment of dyspnea associated with COPD [34] and in terminal cancer patients [59]. The mechanism of this effect is not entirely clear, but several mechanisms have been proposed. Morphine has a depressant effect on the central respiratory center that is dose-dependent. Tolerance can develop with chronic use. Morphine might also act by peripheral mechanisms. Metabolic requirements that require a lower level of ventilation might be reduced by the use of morphine. In addition, opioids also act by reducing anxiety, inducing analgesia, and improving cardiac function through vasodilation. The concern about opioids causing respiratory failure and hastening death was addressed by the United States Supreme Court in two 1997 cases [35,36]. The Court, recognizing a protected interest in adequate pain relief, noted that it is both legally and ethically appropriate to give dying patients as much medication as necessary to relieve pain, even if the foreseen but unintended effect is to hasten death. This principle of ‘‘double effect’’ supports the palliative use of opioids to relieve symptoms such as dyspnea or pain, even in the event that the patient dies as an unintended result of this therapy [13,37]. Opioids are often administered orally, although subcutaneous [38], sublingual, intravenous [39], and transcutaneous routes can be used as well. All opioids are hepatically metabolized to active and inactive metabolites that are excreted renally, and metabolism is slowed with aging. The data supporting the use of nebulized, inhaled opioids are more limited and less robust [40,41]. Long-term use of opioids for chronic dyspnea in COPD has been found to be less helpful due to the prevalence of adverse effects, including drowsiness, nausea, and constipation [42].
234
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
Psychotropic agents Benzodiazepines have also been used to reduce dyspnea in patients who have COPD by depressing the ventilatory drive, the perception of breathlessness, and anxiety [43]. These drugs can cause sedation and ataxia, particularly in the elderly, in whom they might be more slowly metabolized and might have an increased pharmacodynamic effect.
Complementary and alternative medicine modalities Positioning might also be helpful in the relief of dyspnea in patients who have COPD. Body positions such as leaning forward, which increases abdominal pressure, might enhance respiratory muscle and diaphragm function in patients who have COPD [44,45]. Fans have also been found to relieve dyspnea in patients who have severe COPD. The mechanism is thought to be due to stimulation of mechanoreceptors on the face or a decrease in the temperature of facial skin, which are mediated through the trigeminal nerve [2]. A review of the use of complementary and alternative medicine in symptom management at the end of life describes the use of several modalities that have undergone limited testing [46]. Two trials evaluating the use of acupuncture, one in patients with COPD [47] and the other in cancer patients [48], demonstrated symptomatic improvements. One study of the use of acupressure during pulmonary rehabilitation showed that dyspnea was significantly reduced in patients who had COPD [60]. Mechanical vibration of the chest wall inspiratory muscles during inspiration using vibrators has been found to reduce dyspnea in patients who have advanced COPD and hypercapnia [49]. Behavioral and psychological therapy has been used in the treatment of dyspnea for patients with COPD [25,50] and lung cancer [51] with some benefit.
Cough, hiccups, and control of secretions Pathophysiology Cough Cough is a normal respiratory mechanism designed to protect the airway by clearing secretions and inhaled material. Cough can be voluntary or involuntary. It can also be produced by abnormal stimulation of the irritant receptors in the airways. Illnesses associated with inflammation, constriction, infiltration, or compression of airways can cause cough. Chronic cough might be a symptom that causes significant suffering for elderly patients at the end of life. The cough reflex is normally diminished with aging, and it might be reduced further by muscle weakness, cognitive dysfunction, and sedation. It is also often associated with other symptoms, including chest tightness, dyspnea, and pain.
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
235
Hiccups Hiccups are produced by contraction of the inspiratory muscles, which is terminated abruptly by closure of the glottis. Hiccups can occur transiently with gastric distension, sudden changes in temperature, alcohol, smoking, or excitement. Persistent hiccups can be disturbing, and they might have several etiologies, including infection or structural lesions of the central nervous system, diaphragmatic irritation by tumor or inflammation, metabolic abnormalities, vascular lesions, intra-abdominal processes, or systemic infection [52]. Assessment It is useful to determine the cause of cough to optimize therapy? Is the cough acute or chronic? Are the increased secretions due to aspiration or infection or an inability to clear saliva and secretions due to weakness or motor neuron disease? Is the cough a symptom of CHF or an obstructive airway disease? Is cough an adverse effect of a medication such as an ACE-I or an inhaled drug? Common causes of cough include pulmonary or sinus infection, airway diseases (including COPD or obstruction due to malignant disease), CHF, gastroesophageal reflux or aspiration, and drug-induced cough due to ACE-Is or inhaled medications. The history, physical examination, chest (and perhaps sinus) radiographs, and an examination of sputum along with a complete blood count might be sufficient to determine the cause of cough and institute therapy. The mental status, examination of the oropharynx, chest, heart, and vasculature might indicate evidence of heart failure, infection, or aspiration. The elderly are often unable to expectorate sputum due to weakness, so evaluation of sputum is often not possible. More invasive testing is rarely required in the management of cough at the end of life. Management Cough and management of secretions Treatment should be aimed at the underlying pathology inducing the cough, if possible. Respiratory infections are managed in the usual manner with appropriate but often empiric antibiotic coverage appropriate to the community, nursing home, or hospital setting. The patient might be immune suppressed due to disease or prior therapy, requiring broader coverage than might have otherwise been required. Adjunctive therapy with an expectorant and cough suppressant can be given. Agents containing opioids are most effective at suppression, but they might cause sedation, confusion, and constipation in older adults. Physiotherapy with cupping and drainage can provide some assistance with clearing secretions, as can nebulized saline. Cough due to COPD or CHF is managed in the usual fashion, as described previously. Physiotherapy might also provide some relief. Aspiration or gastroesophageal reflux occurs normally, and might increase due to sedation from medications or disease, weakness, confusion, food inadequately cleared from the mouth, inhalation of liquids, supine position, or the use of nasogastric or percutaneous gastrostomy tubes for feeding. Management includes
236
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
maintenance of an upright posture, use of thickened liquids or pureed foods, drinking through straws, H2-blockers, and anti-reflux agents. If aspiration of saliva is due to motor neuron disease, the use of anticholinergic agents to reduce saliva might help, although they can induce confusion and agitation in older adults [53]. The ‘‘death rattle’’ occurs when semiconscious or deeply unconscious patients are unable to swallow saliva or cough secretions reflexively. It usually occurs during the final hours of life. These secretions vibrate noisily in the airway with respiration producing a ‘‘rattle’’ that can be disturbing to family and staff. Gentle suctioning can help, but it might also be disturbing. Anticholinergic agents such as hyoscine can be administered as a single dose or continuous infusion to prevent or treat this condition. Hiccups Initial treatment of hiccups is often aimed at reduction of gastric distension, because this often initiates sporadic episodes. Antiflatulent agents such as simethecone can be tried initially, and prokinetc agents can be added if needed. Peppermint water has been used, which is reported to relax the lower esophageal sphincter, but it opposes the action of prokinetic agents. Baclofen [54], nifedipine [55,56], and haloperidol [57] have been used to treat intractable hiccups.
Summary Early and clear discussion and articulation of preferences about interventions with increasing burdens and diminishing benefits is helpful in identifying the goals of care and planning management for patients who have unremitting terminal illnesses. The development of respiratory symptoms such as dyspnea, cough, and hiccups is common and can often be anticipated. Aggressive evaluation and treatment should be pursued and offered to palliate symptoms at the end of life.
References [1] Reuben DB, Mor V. Dyspnea in terminally ill cancer patients. Chest 1986;89:234 – 6. [2] American Thoracic Society. Dyspnea. Mechanisms, assessment and management: a consensus statement. Am J Respir Crit Care Med 1999;159:321 – 40. [3] The SUPPORT Principal Investigators. A controlled trial to improve care for seriously ill hospitalized patients. The study to understand prognoses and preferences for outcomes and risks of treatments (SUPPORT). JAMA 1995;274:1591 – 8. [4] Lynn J, Teno J, Phillips R, et al. Perceptions by family members of the dying experience of older and seriously ill patients. Ann Intern Med 1997;126:97 – 106. [5] Mercadante S, Casuccio A, Fulfaro F. The course of symptom frequency and intensity in advanced cancer patients followed at home. J Pain Symptom Manage 2000;20:104 – 12. [6] Bruera E, Schmitz B, Pither J, et al. The frequency and correlates of dyspnea in patients with advanced cancer. J Pain Symptom Manage 2000;19:357 – 62. [7] Larson DG, Tobin DR. End-of-life conversations: evolving practice and theory. JAMA 2000; 284:1573 – 8.
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
237
[8] Hinton J. An assessment of open communication between people with terminal cancer, caring relatives, and others during home care. J Palliat Care 1998;14:15 – 23. [9] Quill TE. Initiating end-of-life discussions with seriously ill patients. Addressing the ‘‘elephant in the room.’’ JAMA 2000;284:2502 – 7. [10] Luce JM, Luce JA. Management of dyspnea in patients with far-advanced lung disease. ‘‘Once I lose it, it’s kind of hard to catch it. . .’’ JAMA 2001;285:1331 – 7. [11] Fox E, Landrum-McNiff K, Zhong Z, et al. Evaluation of prognostic criteria for determining hospice eligibility in patients with advanced lung, heart or liver disease. JAMA 1999;282: 1638 – 45. [12] Connors AF, Dawson NV, Thomas C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. Am J Respir Crit Care Med 1996;154:959 – 67. [13] Meisel A, Snyder L, Quill T. Seven legal barriers to end-of-life care. Myths, realities, and grains of truth. JAMA 2000;284:2495 – 501. [14] Lynn J, Ely EW, Zhong Z, et al. Living and dying with chronic obstructive pulmonary disease. J Am Geriatr Soc 2000;48:S91 – S100. [15] Kikuchi Y, Okabe S, Tamura G, et al. Chemosensitivity and perception of dyspnea in patients with a history of near-fatal asthma. N Engl J Med 1994;330:1329 – 34. [16] Lane R, Adams L. Metabolic acidosis and breathlessness during exercise and hypercapnia in man. J Physiol 1993;461:47 – 61. [17] Dudgeon D, Lertzman M. Dyspnea in the advanced cancer patient. J Pain Symptom Manage 1998;16:212 – 9. [18] Jefia R, Ward J, Lentine T, Mahler DA. Target dyspnea ratings predict expected oxygen consumption as well as target heart rate values. Am J Respir Crit Care Med 1999;159:1485 – 9. [19] Aaronson N, Bullinger M, Ahmedzai S. A modular approach to quality of life assessment in cancer clinical trials. Cancer Res 1988;111:231 – 49. [20] Guyatt GH, Berman LB, Townsend M, et al. A measure of quality of life for clinical trials in chronic lung disease. Thorax 1987;42:773 – 8. [21] Ahmedzai S. Palliation of respiratory symptoms. In: Doyle D, Hanks GWC, MacDonald N, editors. Oxford textbook of palliative medicine, 2nd edition. Oxford: Oxford University Press; 1998. p. 583 – 616. [22] Bartter T, Akers SM, Pratter MR. The evaluation of pleural effusion. Chest 1994;106:1209 – 14. [23] Gryminski J, Krakowda P, Lypacewicz G. The diagnosis of pleural effusion by ultrasonic and radiologic techniques. Chest 1976;70:33 – 7. [24] Estenne M, Yernault JC, Troyer A. Mechanism of relief of dyspnea after thoracentesis in patients with large pleural effusions. Am J Med 1983;74:813 – 9. [25] Rodriquez-Panadero F, Lopez-Mejias J. Survival time of patients with pleural metastatic carcinoma predicted by glucose and pH studies. Chest 1989;95:320 – 4. [26] Sahn SA, Good JT. Pleural fluid pH in malignant effusions. Ann Intern Med 1988;108: 345 – 9. [27] Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med 1980;93:391 – 8. [28] The Medical Research Council Working Party. Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet 1981;1: 681 – 5. [29] Heaton RK, Grant I, McSweeney AJ, et al. Psychologic effects of continuous and nocturnal oxygen therapy in hypoxemic chronic obstructive pulmonary disease. Arch Intern Med 1983; 143:1941 – 7. [30] Petty TL, Finigan MM. Clinical evaluation of prolonged ambulatory oxygen therapy in chronic airway obstruction. Am J Med 1968;45:242 – 52. [31] Bruera E, de Stoutz N, Velasco-Leiva A, et al. Effects of oxygen on dyspnoea in hypoxaemic terminal-cancer patients. Lancet 1993;342:13 – 4. [32] Booth S, Kelly MJ, Cox MP, et al. Does oxygen help dyspnoea in patients with cancer? Am Rev Resp Crit Care Med 1996;153:1515 – 8. [33] Dewan NA, Bell CW. Effect of low flow and high flow oxygen delivery on exercise tolerance
238
[34] [35] [36] [37]
[38] [39] [40] [41] [42]
[43] [44] [45] [46]
[47] [48] [49]
[50] [51] [52]
[53] [54] [55] [56] [57]
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239 and sensation of dyspnea: a study comparing the transtracheal catheter and nasal prongs. Chest 1994;105:1061 – 5. Light RW, Muro JR, Sato RI, et al. Effects of oral morphine on breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease. Am J Respir Dis 1989;139:126 – 33. Vacco v Quill, 117 S.Ct. 606 (1997). Washington v Glucksberg, 117 S.Ct. 735 (1997). Luce JM, Alpers A. Legal aspects of withholding and withdrawing life support from critically ill patients in the United States and providing palliative care to them. Am J Respir Crit Care Med 2000;162:2029 – 32. Bruera E, MacEachern T, Ripamonti C, et al. Subcutaneous morphine for dyspnea in cancer patients. Ann Intern Med 1993;119:906 – 7. Cohen MH, Anderson AJ, Krasnow SH, et al. Continuous intravenous infusion of morphine for severe dyspnea. South Med J 1991;84:229 – 34. Noseda A, Carpiaux J-P, Markstine C, et al. Disabling dyspnoea in patients with advanced disease: lack of effect of nebulized morphine. Eur Respir J 1997;10:1079 – 83. Young IH, Daviskas E, Keena VA. Effect of low dose nebulized morphine on exercise endurance in patients with chronic lung disease. Thorax 1989;44:387 – 90. Poole PJ, Veale AG, Black PN. The effect of sustained-release morphine on breathlessness and quality of life in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998; 157:1877 – 80. Man GCW, Hsu K, Sproule BJ. The effect of alprazolam on exercise and dyspnea in patients with chronic obstructive pulmonary disease. Chest 1986;9:832 – 6. Barach AL. Chronic obstructive pulmonary disease: postural relief of dyspnea. Arch Phys Med Rehabil 1974;55:494 – 503. O’Neil S, McCarthy DS. Postural relief of dyspnea in severe chronic airflow limitation: relationship to respiratory muscle strength. Thorax 1983;38:585 – 600. Pan CX, Morrison RS, Ness J, et al. Complementary and alternative medicine in the management of pain, dyspnea, and nausea and vomiting near the end of life: a systematic review. J Pain Symptom Manage 2000;20:374 – 87. Jobst K, Chen JH, McPherson J, et al. Controlled trial of acupuncture for disabling breathlessness. Lancet 1986;2:1416 – 8. Filshie J, Penn K, Ashley S, et al. Acupuncture for the relief of cancer related breathlessness. Palliat Med 1996;10:145 – 50. Cristiano LM, Schwartzstein RM. Effect of chest wall vibration on dyspnea during hypercapnia and exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;155: 1552 – 9. Renfroe KL. Effect of progressive relaxation on dyspnea and state anxiety in patients with chronic obstructive pulmonary disease. Heart Lung 1988;17:408 – 13. Corner J, Plant H, A’Hern R, Bailey C. Non-pharmacological intervention for breathlessness in lung cancer. Palliat Med 1996;10:299 – 305. Friedman LS, Isselbacher KJ. Nausea, vomiting, and indigestion. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, editors. Harrison’s principles of internal medicine. 14th edition. New York: McGraw-Hill; 1998. p. 230 – 6. Tune LE. Anticholinergic effects of medication in elderly patients. J Clin Psychiatry 2001;62 (Suppl 21):11 – 4. Ramirez FC, Graham DY. Treatment of intractable hiccup with baclofen: results of a doubleblind randomized, controlled crossover study. Am J Gastro 1992;87:1789 – 91. Mukhopadhyay P, Osman MR, Wajima T, Wallace TI. Nifedipine for intractable hiccups. N Engl J Med 1986;314:1256. Lipps DC, Jabbari B, Mitchell MH, Daigh JD. Nifedipine for intractable hiccups. Neurology 1990; 40:531 – 2. Ives TJ, Fleming MF, Weart CW, Block D. Treatment of intractable hiccups with intramuscular haloperidol. Am J Psych 1985;142:1368 – 9.
L.G. Jacobs / Clin Geriatr Med 19 (2003) 225–239
239
[58] Bergman B, Aaronson NK, Ahmedzai S, et al. The EORTC QLQ-LC13: a modular supplement to the EORTC core quality of life questionnaire (QLQ-C30) for use in lung cancer clinical trials. Eur J of Ca 1994;30A:635 – 42. [59] Bruera E, Macmillan K, Pither J, MacDonald RN. Effects of morphine on the dyspnea of terminal cancer patients. J Pain Symptom Manage 1990;5:341 – 4. [60] Maa SH, Gauthier D, Turner M. Acupressure as an adjunct to a pulmonary rehabilitation program. J Cardiopulm Rehab 1997;17:268 – 76. [61] Rosser R, Denford J, Heslop A, et al. Breathlessness and psychiatric morbidity in chronic bronchitis and emphysema: a study of psychotherapeutic management. Psychol Med 1983;13: 93 – 110.