CHAPTER 27. DYSPNEA
Kim K. Kuebler, Jerald M. Andry and Shawn Davis
The symptom of dyspnea, or breathlessness, has been defined as an uncomfortable awareness of breathing (Baines, 1978). The American Thoracic Society (ATS) defines dyspnea as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity” (ATS, 1999). The experience is a combination of physiological, social, and environmental factors that potentiate physiological and behavioral response (ATS, 1999). Dyspnea not only is a common companion to pulmonary and cardiac diseases, but also often accompanies the dying process. The clinician providing management for the patient with dyspnea should always consider the underlying pathophysiology contributing to the patient’s breathlessness. Having knowledge related to the cause of dyspnea will direct the clinician on how best to strategize his or her diagnostic evaluation and consideration for specific interventions.
The literature suggests that there is a large variation in the reported prevalence of dyspnea, which ranges from 21% to 79% (Bruera, Sweeney, & Ripamonti, 2002). “These variations are a result of the different natures of patient populations reported by different authors and the lack of a general consensus regarding the assessment and evaluation of dyspnea” (Bruera et al., p. 359, 2002). A number of authors have reported the incidence of dyspnea in different patient populations that include patients in the last month of life, patients with advanced cancer, and patients without intrathoracic malignancies, chronic congestive heart failure, and chronic obstructive pulmonary disease (COPD) (Bruera et al., 2002). Most cancer patients develop progressive dyspnea over days or weeks, yet for those patients who experience a sudden onset of dyspnea, a medical emergency should be considered (Bruera et al., 2002).
ETIOLOGY AND PATHOPHYSIOLOGY
Dyspnea encompasses complex interactions between peripheral and central sensory receptors and cognition, while the underlying causation remains unknown. Physiological, psychological, behavioral, social, and environmental factors play a role in the pathogenesis and perception of dyspnea (Rao & Gray, 2003). Although the underlying medical condition may not be treatable in the palliative care patient, dyspnea almost always responds to intervention or treatment.
Normal Control of Breathing
As simplistic as inhaling and exhaling seems, it is actually a complex of physiological mechanisms that are constantly adapting to a multitude of psychological, social, and environmental factors. The main function associated with the respiratory system is to obtain oxygen from the atmosphere to supply functioning cells and remove carbon dioxide (CO) produced by cellular metabolism (Levitzky, 2003). All respiratory processes are controlled by the central nervous system, which responds to stimuli in order to maintain homeostasis. The primary example is how the respiratory center in the medulla oblongata responds to stimuli from four primary sources (ATS, 1999; Guyton & Hall, 1996):
▪ Chemoreceptors in the aorta, carotid arteries, and medulla sense changes in P o2, P co2, and pH and transmit signals back to the respiratory center to adjust breathing. The peripheral chemoreceptors (i.e., those in the aortic arch and carotid arteries) are most sensitive to changes in P o2. When P o2 decreases, ventilation increases. However, hypoxia must be fairly profound before this change in respiratory pattern is seen. The central chemoreceptors of the medulla are very sensitive to changes in pH. Changes in pH are closely related to P co2. Hypercapnia leads to a decrease in pH, which then stimulates ventilation.
▪ Mechanoreceptors in the diaphragm and chest wall sense changes in the work of breathing. When an increased workload is sensed, the respiratory center stimulates the diaphragm and respiratory muscles and attempts to expand the lungs.
▪ Vagal receptors in the airways and lungs also influence breathing. Afferent impulses are generated when (1) stretch receptors in the lungs are stimulated as the lungs expand, (2) irritant receptors in the bronchial walls are stimulated, or (3) C fibers in the interstitium of the lungs respond to increases in pulmonary interstitial or capillary pressure.
▪ Cortical areas of the brain affect breathing by allowing individuals to consciously increase or decrease their respiratory rate. It also appears that the chemoreceptors, mechanoreceptors, and respiratory center itself send messages to higher brain centers, leading to a cognitive awareness of the ventilatory demand.
Mechanisms Leading to Dyspnea
Patients may describe dyspnea by using several phrases such as “My breathing requires effort,” “I feel a hunger for more air,” or “I feel out of breath” (Harver, Mahler, Schwartzstein et al., 2000). In a palliative care patient, the perception of dyspnea includes several qualitatively distinct sensations that may be caused by one or more pathophysiological mechanisms (Manning & Schwartzstein, 1995). As described, receptors throughout the body will trigger the central nervous system when homeostasis is altered, which can ultimately lead to the feeling of dyspnea. However, specific data are not available to explain how dyspnea is processed by higher brain centers in humans (Guz, 1997). Research has shown that the known dyspnea pathways may be shared by painful stimuli such as heat, cold, and electrical stimulation (von Leupoldt & Dahme, 2005). Thus, there may be a common neural network explaining pain and dyspnea, which are common symptoms in the palliative care patient population. Before the brain can interpret changes and alter breathing patterns, peripheral stimuli must be gathered by various receptors.
Chemoreceptors found in the blood and brain detect blood-gas abnormalities. As stated, the central chemoreceptors of the medulla are particularly sensitive to fluctuations in pH. Any condition causing retention of CO 2, such as chronic obstructive pulmonary disease (COPD), leads to hypercapnia, which lowers blood pH. Thus, the respiratory system responds by increasing ventilation in order to “blow off” the excess CO 2. It is not known if the dyspnea caused by hypercapnia is a direct effect of chemoreceptor stimulation to higher brain centers or the cognitive perception of the increased ventilatory demand (ATS, 1999; von Leupoldt & Dahme, 2005).
Respiratory muscle abnormalities lead to a mismatch between the central respiratory motor output and the achieved ventilation. Respiratory muscle weakness, whether caused by generalized weakness or a neuromuscular disorder, is perceived as dyspnea. Many persons with advanced diseases experience anorexia, cachexia, and generalized weakness and are at risk for experiencing dyspnea. In diseases that cause hyperinflation of the lung and overexpansion of the thorax, the muscles of inspiration become weakened, leading to the sensation of dyspnea (ATS, 1999; Guyton & Hall, 1996). This dyspnea may be mediated via mechanoreceptor messages to the cortex.
Abnormal ventilatory impedance (e.g., narrow airways or increased airway resistance) leads to stimulation of increased central respiratory motor output. When the effort expended to breathe is not matched by the level of ventilation, dyspnea is perceived (ATS, 1999). This perception may result from vagal or mechanoreceptor stimulation of the cortex.
Cognitive factors also influence the perception of dyspnea (ATS, 1999; Guyton & Hall, 1996; Kuebler, Dahlin, Heidrich et al., 1996; Twycross, 1999). Although many physiological mechanisms lead to a perception of dyspnea, not all dyspnea is a direct result of pathological structural characteristics. Psychological states are interrelated to the dyspneic experience, which may be caused or exacerbated by anxiety, fear, hopelessness, and depression. Breathlessness precipitates anxiety, leading to increased breathlessness and even more anxiety; commonly called the “snowball effect.” The patient’s perception of dyspnea is decreased when he or she believes that the shortness of breath is treatable and that prompt access to treatment is available.
Dyspnea is predominantly experienced by persons with pulmonary, cardiac, and neuromuscular diseases (Ahmedzai, 1998; Carrieri-Kohlman & Janson-Bjerklie, 1993; Twycross, 1997). Table 27-1 summarizes many of the causes of dyspnea in the terminally ill. Note also that cognitive factors may contribute to all causes of dyspnea; thus, they are not included. Although respiratory muscle abnormality due to weakness may be present in almost all advanced diseases, Table 27-1 lists the diseases in which weakness is most profound.
| Disease Process | Blood Gas Abnormalities | Increased Ventilatory Demand | Respiratory Muscle Abnormality | Ventilatory Impedence |
|---|---|---|---|---|
| Pulmonary Disease | ||||
| Chronic obstructive pulmonary disease | X | X | X | X |
| Asthma | X | X | ||
| Cystic fibrosis | X | X | X | |
| Pneumonia | X | X | ||
| Pleural effusion | X | X | X | |
| Malignancy | X | X | X | X |
| Radiation pneumonitis | X | X | ||
| Pulmonary embolism | X | X | ||
| Cardiovascular Disease | ||||
| Heart failure | X | X | ||
| Myopathies | X | X | ||
| Anemia | X | X | ||
| Superior vena cava syndrome | X | X | ||
| Neuromuscular Disease | ||||
| Muscular dystrophy | X | X | ||
| Myasthenia gravis | X | X | ||
| Amyotrophic lateral sclerosis | X | X | ||
| Paralysis of diaphragm | X | X | ||
ASSESSMENT AND MEASUREMENT
Patients who complain of being breathless will often seek some relief through position changes, pursed lip breathing, use of accessory muscles, and/or use of environmental aids such as a fan or sitting near an open window or refraining from being exposed to humidity. Breathlessness can be easily observed (objective evaluation) in the patient who is struggling to breathe—but is often considered a subjective experience. For the clinician, a simple approach used to assess and evaluate the patient’s dyspnea would be to ask the patient to quantify his or her difficulty in breathing from a numerical scale that is rated from 0 (no breathlessness) to 10 (severe breathlessness). A numerical value provides the clinician with an understanding of the patient’s expression of his or her dyspnea intensity. The Edmonton Symptom Assessment System (ESAS) is an example of a numerical rating scale to evaluate the patient’s intensity associated with multiple symptoms including dyspnea (Bruera, Kuehn, Miller et al.,1991).
There are several psychometrically valid and reliable dyspnea assessment tools that are used in clinical and research settings to assess and evaluate the symptom of dyspnea. The traditional approach to providing care for patients with chronic respiratory disease has primarily relied on pulmonary function tests (PFTs) to quantify the severity of the patient’s disease and/or their response to therapy (Mahler, 2000). However, patients often present for medical attention as a result of their symptoms, particularly dyspnea and an impaired ability to perform activities of daily living, with both contributing to the interference of the patient’s perceived quality of life (Mahler, 2000). The patient’s perception of breathlessness that interferes with quality of life may not always be accurately reflected in the most recent spirometry evaluation (GOLD, 2003). As previously mentioned, simply asking the patient to rate his or her dyspnea or difficulty breathing from a numerical rating scale may serve as a useful indicator of the patient’s self-description of his or her discomfort. Other examples of dyspnea evaluation tools will be briefly described below. The patient’s physical status should be considered in instrument selection, since lengthy instruments are not generally appropriate in palliative care populations.
The St. George’s Respiratory Questionnaire
The St. George’s Respiratory Questionnaire (SGRQ) contains 76 items that are divided into three sections and include:
▪ Symptoms—affecting normal respirations to include the frequency and severity
▪ Activity—interference with the ability to engage in activities as a result of breathlessness
▪ Impact—influence that breathlessness has on a wide array of social and psychological difficulties:
Each of these sections is scored and then a final score is calculated to discern the severity of patient breathlessness (Jones, Quirk, & Baveystock, 1991). The SGRQ was developed to measure quality of life in patients with airway disease with the intent to exert greater sensitivity and be useful in patients with mild as well as severe disease (Jones et al., 1991).
Baseline and Transition Dyspnea Index
The Transition Dyspnea Index (TDI) was developed to provide a discriminative and evaluative assessment of dyspnea in pharmacotherapy trials for COPD (Witek & Mahler, 2003). This tool is divided into the Baseline Dyspnea Index (BDI) as a discriminative instrument to measure dyspnea at a single point in time (Mahler et al., 2004) and the TDI as an evaluative tool to assess changes in dyspnea from baseline. These tools consist of dyspnea indices that assess breathlessness in domains related to functional impairment, magnitude of task, and magnitude of effort (Mahler, Weinberg, Wells et al., 1998; Mahler, Ward, Fierro-Carrion et al., 2004).
The BDI/TDI evaluation tool has been proved useful in multiple clinical trials seeking to evaluate medication use to relieve dyspnea in patients with chronic lung disease. Successful demonstration of the relief of dyspnea with drug therapy depends on achieving consistent results using valid instruments (Witek & Mahler, 2003). The BDI/TDI, however, has received criticism from the interview process maintaining that the interpretation by the interviewer may introduce bias. Recently, the BDI/TDI was modified to allow patients to perform self-administration through a computerized venue. This has been further validated (Mahler et al., 2004).
Medical Research Council
The Medical Research Council Scale was developed in 1959 to provide patients an opportunity to grade their breathlessness based on a single dimension (i.e., daily tasks). This tool has been tested in patients with dyspnea from a variety of respiratory and cardiovascular origins (Fletcher, Elmes, & Wood, 1959).
HISTORY AND PHYSICAL EXAMINATION
Patients experiencing the sensation of dyspnea or breathlessness will often seek medical attention. The clinician encountering the dyspneic patient should consider asking the patient specifically about his or her shortness of breath. Because dyspnea is considered a subjective complaint, it is important to note that patients may often present with tachycardia and look in distress yet may not describe being dyspneic or distressed versus the patient who is not tachypneic or in apparent distress yet may describe having severe breathlessness (Pereira & Bruera, 2001).
The etiology of dyspnea may be easy to discern in most patients by taking a complete history and performing a physical examination. A detailed examination with a focus on the cardiac and respiratory systems is essential (Bruera et al., 2002). Simple measures such as a chest radiograph, digital oximetry, and a complete blood count and comprehensive metabolic profile tests can help in differentiating the cause of dyspnea (Bruera et al., 2002). Pulmonary function tests (PFTs) are useful for the patient with obstructive and restrictive pulmonary disease. These tests are easy to perform at the bedside and can also provide the clinician with valuable information on how the patient responds to specific interventions. If done appropriately, the patient will use a bronchodilator after the first evaluation and measurements are considered before and after bronchodilator use.
Differential diagnostics are important as dyspnea is a complex symptom that may arise from multiple insults. Common contributions to dyspnea can include the following (Bruera et al., 2002; Pereira & Bruera, 2001):
▪ Primary lung malignancy
▪ Pleural or pericardial effusion
▪ Carcinomatous lymphangitis
▪ Pulmonary embolism
▪ Chemotherapy-induced fibrosis
▪ Superior vena cava syndrome
▪ Depression and anxiety
▪ Pneumonia
▪ Muscle deconditioning (cachexia)
▪ COPD, neuromuscular disease
▪ Anemia
▪ Congestive heart failure (cor pulmonale)
DIAGNOSTICS
Diagnostic procedures can provide assistance in identifying the causes of dyspnea and monitoring the course of the illness, but the practitioner must evaluate the appropriateness of such diagnostic tests in palliative care. A diagnosis can sometimes be made based solely on the clinical presentation alone; thus, the burden and cost incurred by the patient must be considered. When a diagnosis is more complicated, a clinician may have a clinical history, physical examination, laboratory tests (complete blood cell count, metabolic panel), and possibly a chest radiograph as an initial work-up. Pulmonary diagnostics, such as spirometry and PFTs (outlined later), provide supporting information to help the clinician make the diagnosis (West, 2003). Additionally, spirometry and PFTs are valuable in following the progress of a patient’s dyspnea over time. Other diagnostic tests that may not be used in palliative care include the following (Karnani, Reisfield, & Wilson, 2005; West, 2003):
▪ Pulse oximetry
▪ Echocardiography
▪ Brain natriuretic peptide
▪ Arterial blood gas
▪ Ventilation-perfusion ( 
/ 
) scan
/ ) scan▪ Bronchoscopy
▪ Lung biopsy
Spirometry
Spirometry is a highly effort-dependent diagnostic test that measures the volume of air (liters) exhaled or inhaled by a patient as a function of time (Evans & Scanlon, 2003; Karnani et al., 2005). Spirometry allows clinicians to distinguish between obstructive (i.e., asthma and COPD) and restrictive (i.e., fibrosis, chest wall limitation, pleural diseases, neuromuscular disorders) diseases, in which patients experience dyspnea (Karnani et al., 2005; West, 2003). The typical end points measured via spirometry are the forced expiratory volume in 1 second (FEV 1), the forced vital capacity (FVC), and/or the forced expiratory volume in 6 seconds (FEV 6). FVC can be extremely challenging in older or impaired patients, so FEV 6 has been shown to be an acceptable surrogate alternative that is available in most newer spirometers. Spirometry has limitations because it does not allow clinicians to measure lung volumes; other PFTs are used to potentially identify the underlying cause of the patient’s dyspnea (Karnani et al., 2005).
Pulmonary Function Tests
PFTs are used in addition to spirometry to determine the volume of air in the lungs at any given time. Such volumes include the total amount of air in the lungs at full inspiration (total lung capacity [TLC]), the amount of air left in the lungs at the end of normal expiration (functional residual capacity [FRC]), and the amount of air remaining after maximal expiration (residual volume [RV]) (Evans & Scanlon, 2003; Karnani et al., 2005). A clinician will may also order a diffusing capacity (D Lco) to estimate the patient’s ability to absorb alveolar gases in the lung. The DL co substitutes CO as a surrogate for oxygen in order to measure the amount of oxygen that is absorbed into the bloodstream (Evans & Scanlon, 2003). By knowing lung volumes and the amount of oxygen absorbed, clinicians are able to narrow the pathophysiology associated with dyspnea.
Radiography: Computed Tomography and Magnetic Resonance Imaging
Clinicians do not typically order radiographs, high-resolution computed tomography (CT) scans, and/or MRI for each patient who presents with dyspnea. However, such diagnostics are ordered to rule in and rule out underlying pathologies that are seen in palliative patients. High-resolution CT could be used to diagnose bronchiectasis and identify pulmonary embolism or idiopathic pulmonary fibrosis (Evans & Scanlon, 2003).
INTERVENTIONS AND TREATMENT
The treatment of dyspnea begins with determining and treating the underlying cause. This includes the appropriate selection of disease-specific and palliative therapies, taking into account prognosis, adverse events, costs, and potential outcomes to the patient. The most common reversible causes of dyspnea are bronchospasm, hypoxia, and anemia (Dudgeon & Lertzman, 1998). Appropriate management of dyspnea requires pharmacological and nonpharmacological treatments. Two types of drugs that have proved useful in alleviating dyspnea in palliative care are opioids and drugs that decrease anxiety. Table 27-2 summarizes pharmacological options for the management of dyspnea based on cause. Many of the other medications described in this chapter concerning dyspnea relief have primarily been studied in other disease states such as asthma, COPD, and cancer.
| Causes | Management |
|---|---|
| Respiratory infection | Antibiotics |
| Expectorants | |
| Physiotherapy | |
| Chronic obstructive pulmonary disease and asthma | Bronchodilators |
| Corticosteroids | |
| Theophylline | |
| Physiotherapy | |
| Hypoxia | Trial of oxygen |
| Bronchial obstruction and lung collapse | Corticosteroids |
| Mediastinal obstruction | Radiotherapy |
| LASER therapy | |
| Stent | |
| Lymphangitis carcinomatosa | Corticosteroids |
| Diuretics | |
| Bronchodilators | |
| Pleural effusion | Paracentesis |
| Pleurodesis | |
| Ascites | Diuretics |
| Paracentesis | |
| Pericardial effusion | Paracentesis |
| Corticosteroids | |
| Anemia | Blood transfusion |
| Erythropoietin | |
| Cardiac failure | Diuretics |
| Digoxin | |
| Angiotensin-converting enzyme inhibitors | |
| Pulmonary embolism | Anticoagulants (if appropriate) |
Opioids
Opioids are commonly used medications to treat dyspnea in palliative care. The mechanisms of action by which opioids alleviate dyspnea are unclear but may include decreasing the central perception of dyspnea (similar to pain), decreasing anxiety, decreasing sensitivity to hypercapnia, reduction in oxygen consumption, and improved cardiovascular effects (Ahmedzai, 1998; Twycross, 1999; Vismara, Leaman, & Zelis, 1976). Because opioids are respiratory depressants, there are safety concerns. The risk of causing severe respiratory depression with opioid use depends on the prior exposure to opioids, route of administration, rate of titration, and underlying pathophysiology.
Data from several clinical studies reveal that 80% to 95% of terminal cancer patients achieved significant relief of dyspnea through the use of morphine (Bruera, Sala, Spruyt et al., 2005; Harwood, 1999; Mahler, 1990). A systematic review of 18 studies on the use of opioids in the management of dyspnea has been conducted (Jennings, Davies, Higgins et al., 2002). Most of the patients in the meta-analysis had COPD. The authors concluded that there is a significant positive effect of opioids in the treatment of breathlessness. In addition, oral or parenteral opioids showed a greater effect than nebulized formulations. Low-dose sustained-release oral morphine has been shown to provide significant improvements in refractory dyspnea in patients with COPD (Abernethy, Currow, Frith et al., 2003).
Nebulized formulations of opioids deliver medication directly to the airways and pulmonary circulation, avoiding first-pass metabolism by the liver. Studies evaluating the effectiveness of nebulized opioids have been inconclusive and predominantly negative; however, positive case reports have been published (Sarhill, Walsh, Khawam et al., 2000). Nebulized morphine was shown to be no more effective at reducing dyspnea than nebulized saline solution (Davis, 1996). Results of several small studies of nebulized morphine do not support its use to treat dyspnea (Brown, Eichner, & Jones, 2005). It has been suggested that nebulized opioids may not be delivered in a high enough concentration to affect dyspnea (Baydur, 2004). A recent preliminary study evaluating nebulized versus subcutaneous morphine to treat dyspnea in cancer patients showed that both routes of administration offered similar relief of dyspnea, but due to the low number of patients in the study, a difference between routes could not be determined (Bruera et al., 2005). Due to the number of conflicting studies and lack of large clinical trials, the utility of nebulized opioids to treat dyspnea remains controversial. They may be beneficial in some patient populations or when other therapies have failed.
The required dose of morphine to alleviate dyspnea is influenced by the patient’s current opioid regimen. The opioid-naïve patient may begin with 5 to 6 mg of morphine every 4 hours as a starting dose. If a patient is receiving morphine for pain and remains dyspneic, increasing the dose by 25% to 50% is recommended (Thomas & von Gunten, 2003). The usual starting dose for nebulized morphine is 2 to 2.5 mg of preservative-free morphine in 3 ml of sterile saline solution. The dosage may be titrated up to 10 to 20 mg of morphine; however, a greater risk of bronchospasm is seen with higher doses. Once an effective dose is determined, both a sustained-release opioid for baseline control and an immediate release opioid for breakthrough can be used for chronic dyspnea.
Anxiolytics
Because fear and anxiety can be a large component of the sense of breathlessness, anxiolytics are often used to alleviate these causes. Benzodiazepines and phenothiazines have the ability to reduce respiratory drive, may reduce pulmonary ventilation, and may better control the emotional component of dyspnea.
Randomized controlled trials evaluating benzodiazepines versus placebo in COPD patients have yielded conflicting results regarding breathlessness and have shown that the medications are poorly tolerated in long-term studies (ATS, 1999; Mitchell-Heggs, Murphy, & Minty, 1980; Woodcock, Gross, & Geddes, 1981). In addition, alprazolam has been shown to be ineffective in treating dyspnea in COPD patients (Man, Hsu & Sproule, 1986). Despite the lack of evidence that anxiolytics reduce dyspnea, they are widely used. The use of these medications may be most beneficial when anxiety is prominent and when they are combined with an opioid (Thomas & von Gunten, 2003).
Phenothiazines have been poorly studied in dyspnea. Chlorpromazine has been shown to reduce breathlessness after exercise in healthy subjects (O’Neill, Morton, & Stark, 1985) and in COPD patients experiencing anxiety-associated dyspnea (McIver, Walsh, & Nelson, 1994). The combination of morphine with chlorpromazine or promethazine has been shown to be effective at reducing dyspnea (Dudgeon, 1997).
Various routes of administration of the anxiolytics are available, including oral, parenteral, and sublingual. Anxiolytics should be started at very low doses and titrated to dyspnea reduction. The following anxiolytics have been used to treat dyspnea (Thomas & von Gunten, 2003):
▪ Lorazepam, 0.5 to 1 mg every hour until dyspnea resides and then every 4 to 6 hours
▪ Diazepam, 5 to 10 mg every hour until dyspnea is settled and then every 6 to 8 hours; 2 to 5 mg in the elderly
▪ Clonazepam, 0.25 to 2 mg every 12 hours
▪ Midazolam, 0.5 mg intravenously every 15 minutes until dyspnea settles and then continuous subcutaneous or intravenous infusion
▪ Chlorpromazine (titrated to effect), 10 mg every 4 to 6 hours and as needed
▪ Promethazine (titrated to effect), 12.5 mg every 4 to 6 hours and as needed
Corticosteroids
In patients with advanced cancer, corticosteroids have been used to relieve dyspnea caused by superior vena cava syndrome and the inflammation induced by chemotherapy or radiation (LeGrand & Walsh, 1999; Wickham, 1998). The corticosteroids used are typically dexamethasone and prednisolone. Corticosteroids are used in the management of asthma, severe COPD, and fibrotic lung diseases as inhaled preparations, because these diseases have an inflammatory component in the lungs. Corticosteroids also cause bronchodilation, which may help relieve dyspnea (Barnes, 1995). This effect is enhanced when combined with a long-acting β 2 agonist, such as salmeterol or formoterol (Palmqvist, Arvidsson, Beckman et al., 2001). Possible side effects of corticosteroids include fluid retention, gastric toxicity, hyperglycemia, bruising, and decreased bone density (Calverley, 2005).
The following dosages are recommended for the treatment of dyspnea with corticosteroids (Ahmedzai, 1998; LeGrand & Walsh, 1999)
▪ Prednisolone, 30 to 60 mg/day
▪ Dexamethasone, 4 to 8 mg two to four times daily
Bronchodilators
Bronchodilators may significantly reduce the symptoms of dyspnea by treating reversible bronchospasm and decreasing important lung volumes (Barnes, 2000). Bronchodilators are standard therapy in asthma and COPD and have been used for symptomatic relief of dyspnea in cancer patients (Wickham, 1998). It is suggested that this class of medications is most beneficial for patients with cancer who also have obstructive lung disease and a history of smoking (Wickham, 1998).
The classes of medications that fall under bronchodilators include β agonists and anticholinergics. β Agonists are classified according to their receptor binding selectivity (α and β receptors) and their duration of action. They are termed sympathomimetics because they stimulate adrenergic receptors. Epinephrine and isoproterenol cause more cardiac stimulation (mediated by β 1 receptors) and are typically reserved for special circumstances. Short-acting β 2 agonists such as albuterol and the anticholinergic ipratropium are used for acute and maintenance therapy. Newer, long-acting bronchodilators are now available and include the β 2 agonists salmeterol and formoterol, used twice daily, and the anticholinergic tiotropium bromide, used once daily (Gross, 2004; Weder & Donohue, 2005). Tiotropium was found to decrease exertional dyspnea and enhance exercise endurance in COPD patients (O’Donnell, Fluge, Gerken et al., 2004). Table 27-3 highlights the most frequently used bronchodilators, with attention to usefulness, dose, and route.
| Prototype | Clinical Usefulness | Dosage/Route |
|---|---|---|
| Nonselective Agonist | ||
| Epinephrine |
Acute
Bronchospasm
Sus-Phrine
Longer-acting bronchodilation, acute asthma, anaphylaxis
Epinephrine inhaler, Primatene, Vaponefrin Wheezing, bronchoconstriction, asthma
|
Subcutaneous: titrate 0.2 to 1 mg as needed
Subcutaneous: titrate 0.5 to 1.5 mg every 6 hr as needed
Inhaler: 1 puff (200 mcg) every 3 to 4 hr as needed
|
| Nonselective β Agonists | ||
| Isoproterenol |
Isuprel
Intraoperative bronchospasm
Isuprel
Chronic bronchoconstriction, asthma
Isuprel inhaler
Bronchoconstriction in asthma/COPD
|
Intravenous push: 0.2 mg (1 ml) in 10 ml of NaCl or 5% dextrose; titrate 0.01 to 0.02 mg
SL: titrate 10- to 15-mg tablet as needed
Inhaler: 1 to 2 puffs (130 mcg each) up to five times daily as needed
|
| Ethylnorepinephrine | Acute bronchospasm |
Nebulizer: 5 to 15 deep inhalations of 10 mg/ml solution
Subcutaneous, intramuscular: 1 to 2 mg (0.5 to 1 ml) as needed
|
| Selective β 2 Agonists | ||
|
Albuterol sulfate
Salmeterol
Xinofoate
Formoterol
Fumerate
|
Proventil/Ventolin
Bronchodilation in asthma and COPD
Alupent
Bronchodilation for COPD
Serevent Diskus
Maintenance of asthma/COPD
Foradil Aerolizer
Maintenance of asthma/COPD
|
Inhaler: 1 to 2 puffs (90 mcg each) every 4 to 6 hr
Orally: 2 to 4 mg every 3 to 4 hr; maximum 8 mg qid
Inhaler: 3 to 4 puffs every 3 to 4 hr as needed; maximum 12 puffs daily
Nebulizer: 10 deep inhalations of undiluted 5% solution every 4 hr as needed
Orally: 10- to 20-mg tablets three to four times daily
Inhaler: 1 puff (50 mcg) twice daily
Inhaler: 1 capsule inhaled twice daily
|
| Anticholinergics | ||
| Ipratropium bromide |
Atrovent
Maintenance of COPD
|
Inhaler: 2 puffs (18 mcg each) four times daily |
| Tiotropium bromide |
Spiriva
Maintenance of COPD
|
Inhaler: 1 capsule inhaled daily |
| Methylxanthines | ||
| Theophylline |
Elixophyllin, Slo-Phyllin, Uniphyl, Theo-Dur, Theo-24
Treat wheeze, shortness of breath from asthma and COPD
|
Orally: tablets (100, 200, 300, 400, and 450 mg), syrups, solutions
Initial dose 400 to 600 mg/day, titrate to serum concentration of 10 to 20 mg/L
Intravenous: infusion to serum concentration of 10 to 20 mg/L
|
Side effects of β 2 agonists include palpitations, tachycardia, tremor, and hypokalemia (Sears, 2002). Possible side effects of anticholinergics include dry mouth, urinary retention, and glaucoma (Weder & Donohue, 2005). Side effects from inhaled anticholinergics are low because the molecules are positively charged and have little systemic absorption from the lungs (Gross, 2004). Their utility in palliative care must be weighed against potential side effects and practicality of use.
Theophylline
Theophylline is a methylxanthine that weakly inhibits the enzyme phosphodiesterase leading to bronchodilation, improved gas exchange, reduced inflammation, improved length-tension relationship of the diaphragm, and many other effects (Carrieri-Kohlman & Janson-Bjerklie, 1993; Hansel, Tennant, Tan et al., 2004). Theophylline is used as adjunct therapy in asthma and COPD, and most studies have included patients with nonmalignant disease. Therefore, similar to β 2 agonists and anticholinergics, theophylline is typically reserved for those patients with obstructive lung disease and those who smoke (Wickham, 1998).
The clinical use of theophylline is limited to its narrow therapeutic range and many drug-drug interactions (Hansel et al., 2004). Side effects of theophylline include nausea, headache, insomnia, palpitations, diuresis, and arrhythmias (Hansel et al., 2004). When used as a bronchodilator, doses that give a plasma concentration of 10 to 20 mg/L are optimal.
Oxygen
Oxygen therapy for the treatment of dyspnea in palliative patients is commonly performed by clinicians (Jantarakupt & Porock, 2005). In addition to the relief of breathlessness, therapeutic indications for oxygen use include hypoxemia or a tendency to develop pulmonary hypertension. If a patient’s O 2 saturation falls below 90% at room air, the practitioner may consider starting oxygen by nasal cannula at 1 to 3 L/min, rechecking the patient’s O 2 saturation in 20 to 30 minutes, and titrating up to 6 L/min if necessary (Ahmedzai, 1998; Luce & Luce, 2001, Pereira & Bruera, 1997). The results of O 2 titration are difficult to predict because neither the flow rate nor the route of administration has been shown to determine its effect on dyspnea in clinical trials. In fact, the published data are mixed regarding the use of oxygen for dyspnea. Oxygen was found to increase patients’ oxygen saturation (Sa o2), thus reducing dyspnea, respiratory rate, and respiratory effort in patients with primary lung cancer and advanced disease (Bruera, de Stoutz, Velasco-Leiva et al., 1993; Swinburn, Mould, Stone et al., 1991). A separate controlled study by Davis (1999) showed no advantage of oxygen over compressed air in a separate controlled study. Due to inconclusive data, health care professionals should consider oxygen therapy on a case-by-case basis with the goal of making the patient as comfortable as possible.
Nonpharmacological Interventions
Palliative patients experiencing dyspnea typically have several comorbidities that may require numerous procedures and/or medications. Therefore, the clinician must use nonpharmacological interventions to maximize treatment benefit while trying to minimize potential side effects. Combined approaches (some discussed in depth later in the chapter) such as breathing retraining, exercise counseling, relaxation, and coping and adaptation strategies significantly improved breathlessness and the ability to perform activities of daily living in patients with advanced lung cancer (Dudgeon, 2005). Most of these and subsequent interventions can be taught and implemented easily into patients’ daily activities by all levels of practitioners.
Clinician Demeanor
All clinicians who have interaction with the patient are instrumental therapeutic instruments, because patients react to the demeanor of the clinician. Thus, a calm, confident demeanor will reassure the patient and family and may diminish the anxiety associated with dyspnea and/or the underlying pathology (Thomas & von Gunten, 2003). As a patient’s condition worsens, communication has been identified as a requirement for high-quality end-of-life care. Specifically, one group of patients surveyed would like to receive information regarding diagnosis and disease process, treatment, prognosis, advanced care planning, and what dying might be like (Curtis, Weinrich, Carline et al., 2002).
Breathing Techniques
Numerous dyspneic patients have experienced benefits from pursed-lip and diaphragmatic breathing techniques because they are able to decrease the air trapped in the lung (FRC), increase muscle productivity (recruitment) during inspiration and expiration, and increase the air consumed with each breath (tidal volume and alveolar ventilation), thus improving effective coughing and improving blood gases (Jantarakupt & Porock, 2005). Pursed-lip breathing (inhalation through the nose) allows for patients to slowly exhale through their lips, which allows for increased lung expansion and improved gas exchange by decreasing the time the airway is constricted (Jantarakupt & Porock, 2005).
Positioning
Several studies have shown that dyspneic patients with COPD have benefited by sitting in the “tripod” position. An example of the tripod is having sitting with feet wide apart and elbows resting on the knees (Jantarakupt & Porock, 2005). Such a position allows the abdominal wall to move outward, increasing transdiaphragmatic pressure, which provides more space for lung expansion and gas exchange (Sharp, Drutz, Moisan et al., 1980). Patients should learn numerous techniques that can improve patients’ quality of life. Such positions include leaning on the banister when climbing stairs and leaning on a shopping cart while shopping. Patients should be encouraged to try various positions to determine which position works best for them (Sexton, 1990).
Exercise
The extent of exercise that palliative patients can tolerate will vary from patient to patient. However, practitioners should encourage patients to exercise leg and arm muscles using multiple techniques such as lifting weights, climbing small sets of stairs, walking on a treadmill, and using a cycle ergometer (Jantarakupt & Porock, 2005). Upper-extremity exercise is more beneficial to improving respiratory muscle strength and reducing dyspnea compared with lower-extremity exercise. Clinicians should consult with a physical therapist prior to beginning an exercise regimen. Additionally, patients should start with a low level of intensity, increase the level as the patient can tolerate, and maintain exercise for a minimum of 8 weeks (Jantarakupt & Porock, 2005).
Environmental Adjustments
Small, crucial changes to a patient’s daily breathing technique can help improve a patient’s dyspnea. Cold and dry air can stimulate the irritant receptors that provoke the cough reflex and allergic reactions, making dyspnea worse. Thus, patients should breathe through their mouth to warm and humidify the air before it passes the trachea. Additionally, patients should cover their mouth with a warm scarf when in cold conditions and use a humidifier when the air is extremely dry indoors. Dry air can impair cilia, which can lead to mucous plugging and dyspnea (Sexton, 1990). The ideal conditions for a dyspneic patient are a cool environment with gentle air movement. Dyspnea may be lessened by cool air from an open window or an oscillating fan set on low speed directed toward the patient’s face (Jantarakupt & Porock, 2005; Manning & Schwartzstein, 1995). The cool air blown against the patient’s cheek and nose is thought to affect the thermal and mechanical receptors in the distribution of the trigeminal nerve, resulting in a decreased perception of breathlessness (Dudgeon, 2005).
Relaxation Techniques
Complete muscle relaxation decreases oxygen consumption, decreases carbon dioxide production, and decreases the respiratory rate, which are all typically increased in a dyspneic patient (Sexton, 1990). Thus, relaxation techniques, such as Tai Chi, yoga, and/or controlled breathing techniques may help patients control dyspnea and decrease anxiety and possibly stop the vicious cycle of anxiety and dyspnea (Jantarakupt & Porock, 2005).
PATIENT AND FAMILY EDUCATION AND FOLLOW-UP
Dyspnea is a frightening experience for the patient and for those who observe the patient struggling to breathe. Once an etiology contributing to dyspnea has been established, it is important for the clinician to teach the patient and family how to utilize the appropriate interventions to manage this symptom. Patients may not always understand how to adequately navigate the medication delivery systems used in pulmonary medicine. Metered inhalers, dry powder inhalers, nebulized medications, and oral preparations may be overwhelming. Taking the time to evaluate how the patient demonstrates his or her use of these devices and learning the frequency of use will affect the compliance and adequate medication delivery to assist in symptom management. Exploring the emotional or psychological aspects associated with this symptom is also key as depression and anxiety may also require evaluation and management.
Asking the patient to record his or her incidence of dyspnea, the intensity of dyspnea that they experience, and the use of interventions and how these can interface with the dyspnea intensity score may also be useful when following up with the patient and evaluating the effectiveness of specific interventions.
M.W., a 58-year-old woman with an 8-month history of weight loss and increasing fatigue, recently noted severe shortness of breath and fever. She also has joint pain in her back, knees, and elbows. A chest radiograph and computed tomography scan reveal a central mass in the upper right lobe of her lung as well as mediastinal lymphadenopathy. Bronchoscopy washings and cytology are positive for stage IV metastatic squamous cell carcinoma of the right lung. Explorative thoracotomy reveals an unresectable tumor of the right lung with possible metastatic nodules in the left lung. M.W. is offered chemotherapy and radiation for treatment. M.W. decides not to pursue any aggressive therapies and enters a local hospice program. Initial medications include around-the-clock hydrocodone/APAP, which does not manage her pain or dyspnea appropriately. Pain is rated at a 9/10 and dyspnea is very severe, making it difficult to talk. Respiratory rate is currently 32, and M.W. is very anxious. She has discussed with the clinician the need to feel more comfortable at this stage of her life. After a complete physical examination, the clinician makes the following changes and interventions:
▪ Begin administration of equianalgesic sustained-release morphine and equivalent breakthrough dose. Pain should be adequately controlled 24 hours a day.
▪ Add prednisone, 20 mg/day, for both somatic pain and the inflammatory effects of dyspnea.
▪ Add chlorpromazine, up to 25 mg, three times daily for the relief of anxiety that M.W. is experiencing, which is having additional effects on her dyspnea—titrate as indicated.
▪ Consult the interdisciplinary team to support recent diagnosis and functional limitations.
▪ Provide oxygen therapy for palliation of breathlessness as needed.
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