The Advanced Practice Nurse's Role in Palliative Care and the Management of Dyspnea

Rose Anne Indelicato, MSN, APRN-BC, PCM-BC, OCN


Topics in Advanced Practice Nursing eJournal. 2006;6(4) 

In This Article

Pharmacologic Interventions for Dyspnea Management

The APN possesses the advanced clinical knowledge and skills to be able to synthesize the assessment information and create a comprehensive plan -- including pharmacologic and nonpharmacologic interventions -- to address the patient's dyspnea. Depending upon the APN's scope of practice and the state regulations, some of the recommended therapies (such as the use of opioid analgesics) may not be within his or her prescriptive abilities. However, being informed about these interventions will enable the APN to recommend therapies to other members of the interdisciplinary team who have such prescriptive authority.

A number of drugs may affect the intensity of dyspnea in patients with cancer and other life-threatening illnesses. Some may relieve factors that contribute to dyspnea, such as bronchospasm (bronchodilators), or fluid overload (diuretics). Others can help provide symptom relief directly, including opioids, benzodiazepines, phenothiazines, steroids, methylxanthines, and oxygen therapy.

Morphine has been used to treat dyspnea for centuries, although the exact mechanism of action remains unclear. Opioids may diminish the chemoreceptor response to hypercapnia and hypoxia, or they may cause vasodilation, resulting in decreased dyspnea due to the resulting reduction in preload and pulmonary congestion. Additionally, opioids can facilitate a decrease in anxiety and the subjective sensation of dyspnea without reducing respiratory rate or oxygen saturation.[1,2,16]

Most studies have focused on the use of opioids in patients with nonmalignant disease.[31,32,33,34,35,36,37,38] Studies in populations with cancer-related dyspnea have found favorable results, but the optimal type, dose, and mode of administration remain unknown.[32]

Table 2 outlines a step-wise approach to opioid titration in dyspnea similar to that used in pain management. This technique can be the most practical and reliable method for implementing this pharmacologic intervention safely. This table should serve as a guideline. Each patient should be assessed individually and appropriate dose adjustments made based on the patient's current medical condition.

There are no data to suggest that the use of opioids for management of breathlessness is associated with a reduction in a patient's life expectancy. On the contrary, patients who receive aggressive symptom management might actually have a prolonged survival due to a reduction in physical and psychological stress and exhaustion.[24,39] Adverse effects of opioids such as sleepiness, hypercapnia, or nausea are infrequent, and patients quickly develop tolerance to these side effects. In fact, the transient sedation that often occurs may be related to sleep deprivation due to uncontrolled dyspnea.[40]

The most common side effect that patients do not develop a tolerance for is constipation. The APN can provide improved quality of care to patients by educating them about appropriate bowel management (including the need to increase fluid intake, avoid caffeinated beverages, increase dietary fiber, etc) and by implementing a standing bowel regimen that should include a stool softener and laxative. By being proactive with bowel management, the APN can help the patient avoid an uncomfortable and usually preventable side effect.

The use of nebulized opioids in the treatment of dyspnea remains controversial.[17] Although inhaled morphine can have low bioavailability (depending on droplet size), nebulized treatments may be effective for dyspnea due to a local effect. If such an effect existed, it would be a favorable route because of the low incidence of opioid-related side effects.[41] Unfortunately, the data are conflicting. Although one large, uncontrolled study in cancer patients demonstrated positive results in the management of dyspnea,[42] a recent 20-article analysis found a lack of support for the use of nebulized opioids in the treatment of dyspnea in patients with COPD or cancer.[43,44] Other studies have also reached conflicting conclusions.[45,46,47]

If the clinician wishes to implement this therapy, the recommended starting dose is morphine 5 mg or fentanyl 25-50 mcg mixed with 2.5—5.0 mL of sterile normal saline, inhaled over 5-10 minutes every 4 hours with titration to effect.[48,49] Care must be taken as nebulized morphine, unlike fentanyl, may induce bronchospasm in some patients, most likely caused by histamine release into the airways. The first dose should be administered either on an inpatient unit or in an outpatient setting where treatment for severe bronchospasm is immediately accessible.[3,46,49]

A recent case series highlighted the use of oral transmucosal fentanyl citrate (OTFC) in the management of dyspnea in cancer patients. Although only 4 cases were discussed, OTFC was shown to improve dyspnea rapidly, without intolerable side effects. Its use did not reduce oxygen saturation, nor did patients present any clinical signs of respiratory depression.[50]

Although benzodiazepines are commonly used in the treatment of dyspnea, results of clinical trials have been variable.[51] These drugs do not appear to reduce dyspnea directly, but they seem to decrease the anxiety that may accompany dyspnea and contribute to its intensity; therefore, they should not be the only medications used in the management of breathlessness.[1,16]

Since benzodiazepines are metabolized in the liver to long-acting metabolites, short-acting drugs such as lorazepam are preferred, especially in the elderly or in patients with compromised hepatic function.[48] Midazolam, when administered either subcutaneously or intravenously as an addition to an opioid, has been shown to reduce the terminal agitation and anxiety that may be associated with dyspnea.[1,3,27,41,52]

Table 3 provides the APN with guidelines for dosing and scheduling. These doses should be titrated on the basis of the patient's relief and/or the development of intolerable side effects. As with any medication regimen, dose adjustments should be based upon a patient's individual condition and on the APN's clinical assessment.

Studies have produced some evidence that phenothiazines can be beneficial in the treatment of breathlessness. In addition to reducing anxiety, these agents also possess anticholinergic properties that can be useful in managing increased respiratory secretions or in controlling nausea.[53]

One controlled study in patients with chronic obstructive airway disease demonstrated a reduction in dyspnea with the use of promethazine.[54] Chlorpromazine has been found to be effective for the relief of dyspnea in advanced cancer patients.[55] Promethazine dosing can start at 12.5 mg orally, and chlorpromazine dosing can begin at 10 mg orally.[53] Both preparations can be administered every 4-6 hours and as needed, with titration to symptom relief. Side effects include hypotension and extrapyramidal effects, which may limit tolerability in some patients.

Corticosteroids are highly effective in the treatment of dyspnea related to carcinomatous lymphangitis, superior vena cava syndrome, tracheal obstruction, and bronchospasm associated with COPD and asthma.[2,41] They often are delivered via inhalation and by systemic routes in patients with end-stage disease.[56]

These medications should be used cautiously, as steroids may cause muscular weakness, which can involve the diaphragm and chest wall muscles, potentially exacerbating dyspnea.[17] The APN should also be mindful of other potential side effects, including but not limited to hypertension, fluid retention, and hyperglycemia. For systemic therapy, the usual dosage range is prednisone 20-40 mg/day or dexamethasone 4-8 mg/day.[3] On occasion, higher doses may be seen in clinical practice.

Bronchodilators are used in the management of bronchospasm and may provide relief for dyspneic patients who present with airflow obstruction by relaxing the muscles around airways and increasing muscle tone.[57,58,59] Common bronchodilators include the short-acting agents albuterol sulfate, levalbuterol, and pirbuterol acetate, and the long-acting agents ipratropium bromide, salmeterol xinafoate, formoterol, tiotropium, and terbutaline sulfate.[59,60] Terbutaline is delivered by subcutaneous injection. Albuterol sulfate and ipratropium bromide are frequently the bronchodilators of choice for the palliation of dyspnea.[53,61]

The APN should spend time educating the patient and family on the use of these medications, as inhalation devices vary. Metered-dose inhalers should be used with a spacer to improve the patient's ability to receive the full dose.

Proper dosing is often dependent on perfect technique of these technically challenging devices. Dry powder inhalers often ensure more dependable dosing, but instructions must be followed correctly for each type of inhaler.

Many medication errors have occurred or patients have not received therapeutic doses due to a lack of understanding or a lack of the manual dexterity required to use a delivery system correctly. Medication administration via nebulizer may be a more reliable alternative, but it requires special equipment, and not all medications are available in a nebulized formulation.

Aminophylline and theophylline have been found to dilate bronchi and improve diaphragmatic contractility in COPD patients.[3] Theophylline can be useful in managing dyspnea when combined with albuterol and ipratropium.[61] Dosing of theophylline should be between 200 and 400 mg per day in order to maintain a therapeutic blood level of 8-12 mcg/mL.[62]

In addition to monitoring plasma levels, the APN should be attentive to the development of side effects, which may include vomiting, hypokalemia, hyperglycemia, tachycardia, cardiac dysrhythmias, neuromuscular irritability, and seizures.[62] Given the side-effect profile, these agents are often not well tolerated in patients with advanced illness.[3]

Diuretics may be useful in the treatment of dyspnea related to congestive heart failure and in treating breathlessness due to edema that occurs with superior vena cava syndrome.[3] Standard dosing for furosemide is 20-40 mg orally or intravenously once or twice a day.[63]

Diuretics must be used cautiously, however, given the potential for hypovolemia and electrolyte disturbances.[64] Nebulized furosemide, delivered at 20 mg 4 times a day, may be an effective treatment for dyspnea.[65] In one study, patients demonstrated a decrease in breathlessness, alleviation of tachypnea, and a reduction of cough, without an increase in diuresis or side effects.[65]

Oxygen therapy continues to be very controversial in the management of dyspnea, as there are few data supporting its use in the nonhypoxic patient.[66] In patients who are hypoxic on room air, the benefit of supplemental oxygen is most likely related to a decrease in the chemoreceptor input to the respiratory center and the brain cortex.[41] Currently, most practitioners recommend oxygen for dyspneic patients, even with increasing hypercapnia, to achieve and maintain a PaO2 of 55-60 mm Hg and oxygen saturation of 88% to 90%.[67,68]

The role of oxygen therapy in patients with nonhypoxic dyspnea is not well defined. While Woodcock's work demonstrated a reduction in breathlessness and an increase in the walking distance of patients with nonhypoxic COPD treated with oxygen, Bruera and colleagues[69,70] found no significant difference in dyspnea or walking distance in patients who received oxygen therapy during exercise. Jantarakupt and Porock[21] recommend a trial of oxygen therapy in patients with nonhypoxic dyspnea to ascertain whether there is any symptomatic relief.

Patients often best tolerate oxygen that is humidified and is administered via nasal cannula. The APN who wants to consider a trial of oxygen therapy should initiate a starting dose of 1-3 liters (L)/min, with titration up to 6 L/min if necessary.[3,53,71]


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