04 SYMPTOM MANAGEMENT – PART I

 

 

There are many physical and psychological symptoms common at the end of life.  Many symptoms are observed during end of life and it is important that they be assessed and managed effectively.

By assessing and managing symptoms, healthcare professionals can improve the quality of life for patients and their families.

 

Essential elements of symptom management include:

Ø       Assessment and evaluation of symptoms is an essential element in any care setting, requiring diligent ongoing assessment and evaluation of interventions.

Ø       The management of symptoms requires cohesive interdisciplinary teamwork to ensure that optimal care is delivered.  Close collaboration between staff and physicians is essential (Coyne, 2007).

Ø       Financial concerns may be important factors for some families and should be considered in your overall care plan (Coyne et al., 2010). Criteria for ordering diagnostic tests:

w          Each test ordered should help determine an intervention.

w          If no change in management will result, the test should be questioned for its appropriateness.

The Edmonton Symptom Assessment System (ESAS): a simple method for the assessment of palliative care patients.

Bruera E, Kuehn N, Miller MJ, Selmser P, Macmillan K.

Purpose

The ESAS is a tool that was developed to assist in the assessment of nine symptoms that are common in palliative care patients: pain, tiredness, drowsiness, nausea, lack of appetite, depression, anxiety, shortness of breath, and wellbeing (1). There is also a blank scale for patient-specific symptoms.

The ESAS has been revised to improve ease of understanding and completion for patients (2). The revised version of the tool is known as the ESAS-r. Changes include specifying a timeframe of “now”, adding definitions for potentially confusing symptoms, modifying the order of symptoms, adding an example for “other symptom”, and altering the format for improved readability.

The ESAS-r is intended to capture the patient’s perspective on symptoms. However, in some situations it may be necessary to obtain a caregiver’s perspective. The ESAS-r provides a profile of symptom severity at a point in time. Repeated assessments may help to track changes in symptom severity over time. The ESAS-r is only one part of a holistic clinical assessment. It is not a complete symptom assessment in itself.

General Information

How to do the ESAS-r

• It is recommended that the patient complete the ESAS-r with guidance from a health care professional, especially on the first occasion.

• The patient should be instructed to rate the severity of each symptom on a 0 to 10 scale, where 0 represents absence of the symptom and 10 represents the worst possible severity. The number should be circled on the scale.

• The patient should be instructed to rate each symptom according to how he or she feels now. The health care professional may choose to ask additional questions about the severity of symptoms at other time points e.g. symptom severity at best and at worst over the past 24 hours. • Definitions have been added to items that have been found to be more problematic for patients to understand or rate (3); it is recommended to review these with the patient:

Tiredness – lack of energy py

Drowsiness – feeling slee

Depression – feeling sad

Anxiety – feeling nervous

Wellbeing – how you feel overall

• With the previous version of the ESAS, patients often reversed the scale for appetite i.e. they considered “0” as “no appetite” and “10” as “best appetite”. The scale has now been re-labeled as “lack of appetite”. Coaching patients on the correct direction of the scale is still recommended.

• The body diagram on the reverse side of the ESAS-r can be used to indicate sites of pain.

• The circled numbers can be transcribed onto the ESAS-r graph.

When to do the ESAS-r

• In palliative home care, it is a good practice to complete and graph the ESAS-r during each telephone or personal contact. If symptoms are in good control, and there are no predominant psychosocial issues, then the ESAS-r can be completed weekly for patients in the home.

• In hospice and tertiary palliative care units, the ESAS-r should be completed daily. •In other settings, palliative care consultants will utilize this tool upon initial assessment and at each follow-up visit.

 

Who should do the ESAS-r

• It is preferable for the patient to provide ratings of symptom severity by himself/herself.

• If the patient cannot independently provide ratings of symptom severity but can still provide input (e.g. when the patient is mildly cognitively impaired), then the ESAScompleted with the assistance of a caregiver (a family member, friend, or health rofessional closely involved in the patient’s care).

• If the patient cannot participate in the symptom assessment at all, or refuses to do so, the ESAS-r is completed by the caregiver alone. The caregiver assesses the remaining symptoms as objectively as possible. The following are examples of objective indicators:

Pain – grimacing, guarding against painful maneuver

Tiredness – increased amount of time spent

Drowsiness – decreased level of alertness

Nausea – retching or vomiting

Appetite – quantity of food intake

Shortness of breath – increased respiratory rate or effort that appears to causing distress to the patient

Depression – tearfulness, flat affect, withdrawal from social interactions,

irritability, decreased concentration and/or memory, disturbed sleep pattern

Anxiety – agitation, flushing, restlessness, sweating, increased heart rate (intermittent), shortness of breath

Wellbeing – how the patient appears overall

If it is not possible to rate a symptom, the caregiver may indicate “U” for “Unable to assess” on the ESAS-r and ESAS-r Graph.

• The method of completion of the ESAS-r must be indicated in the space provided at the bottom of the ESAS-r and the ESAS-r Graph as follows:

Bottom of ESAS-r Numerical Scale

Completed by (check one):

? Patient

? Family caregiver

? Health care professional caregiver

? Caregiver-assisted

Bottom of ESAS-r Graph

Insert letter from key in date column (date indicated at the top of form)

Key:

P = Patient

F = Family caregiver

H = Health care professional caregiver

A = Caregiver-assisted

Where to document the ESAS-r

• The ESAS-r is always done on the ESAS-r numerical scale and the results later transferred to the ESAS-r Graph. Graphing symptom severity directly onto the ESAS-r Graph without the use of the numerical scale is not a valid use of the ESAS-r, nor a reliable method of symptom assessment (attention to the graphed historical trend may affect the current scores and thus undermine one of the main purposes of the ESAS, i.e. to assess the current symptom profile as accurately as possible).

Other information about the ESAS-r

• The ESAS-r Graph contains space to add the patient’s Folstein Mini-Mental State Examination score. The “normal” box refers to the cutoff for a normal score for the patient, based on age and education level (see Instructions for MMSE).

• A space for the Palliative Performance Scale (PPS) is also provided.

• The ESAS-r is available in other languages, although most translations have not been validated.

There is a simple method for the assessment of symptoms twice a day in patients admitted to a palliative care unit. Eight visual analog scales (VAS) 0-100 mm are completed either by the patient alone, by the patient with nurse’s assistance, or by the nurses or relatives at 10:00 and 18:00 hours, in order to indicate the levels of pain, activity, nausea, depression, anxiety, drowsiness, appetite, and sensation of well-being. The information is then transferred to a graph that contains the assessments of up to 21 days on each page. The sum of the scores for all symptoms is defined as the symptom distress score. The Edmonton Symptom Assessment System (ESAS) was carried out for 101 consecutive patients for the length of their admission to our unit. Of these, 84% were able to make their own assessment sometime during their admission. However, before death 83% of assessments were completed by a nurse or relative. Mean symptom distress score was 410 +/- 95 during day 1 of the admission, versus 362 +/- 83 during day 5 (p less than 0.01). Mean symptom distress scores throughout the hospitalization were 359 +/- 105, 374 +/- 93, 359 +/- 91 and 406 +/- 81 when the ESAS was completed by the patient alone, patient with nurse’s assistance (p = N.S.), nurse alone (p = N.S.), or relative (p less than 0.01) respectively. We conclude that this is a simple and useful method for the regular assessment of symptom distress in the palliative care setting.

 

The Palliative Performance Scale version 2 is a tool for measurement of performance status in palliative care.

Purpose

 

Use of the PPSv2 allows common language about performance status that is more relevant in palliative care than the Karnofsky Performance scale from which it is based. A succinct reporting of performance status allows us to communicate amount of support the person may need in the home or hospice and decreases in score may indicate a progressing condition. 1996 [J Pall Care 9(4): 26-32].

Instructions

1.  The PPS should be completed on initial assessment at all sites and weekly thereafter.

2.  The PPS can be recorded by staff who are familiar with the person’s functional status, such as rehabilitation, nursing or medical staff.

3.  Recording of the PPS is on the consultation form at initial assessment (?home care), and weekly there is a row near the bottom of the ESAS-r graph.

4.  PPS scores are determined by reading horizontally at each level to find a ‘best fit’ for the patient who is then assigned as the PPS% score.

5. Begin at the left column and read downwards until the appropriate ambulation level is reached, then read across to the next column and downwards again until the activity/evidence of disease is located. These steps are repeated until all five columns are covered before assigning the actual PPS for that patient. In this way,‘  columns (columns to the left of any specific column) are ‘stronger’ determinants and generally take precedence over others.

 

 

Similar to pain, other physical and psychological symptoms create suffering and distress (Ferrell & Coyle, 2008). Psychosocial intervention is key to complement pharmacologic strategies. 

 

·                               Use of chaplains, social workers and psychologists are necessary to address suffering and to evaluate role of clinical intervention. Need to determine with each clinical intervention:

Ø          Benefit (s)

Ø          Burden (s)

Ø          Risk (s)

The following symptoms have been chosen for review in this curriculum because they occur frequently in patients with terminal illnesses and because they are extremely distressing to patients and families. For each of the above-mentioned symptoms, we will review:

Ø       Definition of the symptom

Ø       Causes of the symptom

Ø       Assessment of the symptom

Ø       Treatment of the symptom (pharmacological and nonpharmacological)

 

Common Symptoms at End of Life and Their Treatment

 

 

 

Dyspnea

Dyspnea, described as shortness of breath or air hunger, is a common symptom in people with cancer during the final days or weeks of life. The prevalence of dyspnea in adults diagnosed with cancer varies from 21% to 90%, correlated with lung cancer and advanced disease. Dyspnea may predict shortened survival. Patients with cancer presenting to an emergency center for treatment of dyspnea had a median overall survival of 12 weeks. Patients with lung cancer had a significantly shorter survival (4 weeks) than did patients with breast cancer (22 weeks). In another study, patients presenting to an emergency department with cancer-related dyspnea who were at greatest risk of imminent death were those with an elevated pulse (100 or more beats per minute) and increased respiratory rate (more than 28 breaths per minute), with a predicted mean survival of less than 2 weeks.

There are various causes for dypnea which include:

Ø                       Major pulmonary causes

w       Tumor infiltration

w       Aspiration

w       Pleural effusion –  may be blood, malignant or nonmalignant fluid

w       Superior vena cava syndrome

w       Pneumonia

w       Pulmonary embolism

w       Chronic obstructive pulmonary disease (COPD)

w       Thick secretions caused by an infectious process or dehydration

w       Bronchospasm

w       Ascites, which can impair diaphragmatic excursion

Ø                       Major cardiac causes

w       Congestive heart failure

w       Pulmonary edema and pulmonary hypertension

w       Severe anemia

w       Cardiovascular disease

Ø                       Major neuromuscular causes

w       Amyotrophic lateral sclerosis (ALS)

w       Muscular dystrophy

w       Myasthenia gravis

w       Cerebrovascular disease

w       Trauma as a result of physical injury

The etiology of dyspnea is usually advanced malignant disease, although other risk factors include ascites, chronic obstructive pulmonary disease, deconditioning, and pneumonia. Dyspnea occurs when more respiratory effort is necessary to overcome obstruction or restrictive disease (e.g., tumor or pleural effusions), when more respiratory muscles are required to maintain adequate breathing (e.g., neuromuscular weakness or cachexia), or when there is an increase in ventilatory need (e.g., hypercapnia or metabolic acidosis).

Dyspnea assessment is like pain assessment – the subjective report of the patient is the only reliable indicator of this symptom. 

Ø     The assessment should include:  effect on functional status, factors that improve or worsen this symptom, assessment of breath sounds, presence of chest pain and/or other pain that may compound the problem, and oxygenation status. 

Ø     Consider what, if any, appropriate diagnostic tests will be useful in treating the underlying cause.

Ø     The patient’s respiratory rate and oxygenation status do not always correlate with the symptom of breathlessness.

Ø     The amount of dyspnea present may not be related to the extent of disease. 

 

Impact on function and quality of life

Ø     Evaluate the individual’s ability to sleep, get dressed, talk, eat, etc.

Ø     The patient may report breathlessness in spite of good oxygenation status or limited disease state.

 

Clinical assessment

Ø     The purpose of clinical assessment is to determine any underlying pathophysiology in order to develop the most effective treatment plan. 

Ø     The utilization of any test should be weighed on the risk/benefit ratio, patient’s wishes, and prognosis. 

Ø     The assessment should include history of acute or chronic dyspnea, history of smoking, heart disease, or lung disease, or concurrent medical conditions.  

Ø     Physical examination:  Elevated jugular pressure, bilateral crackles, respiratory rate and depth, use of accessory muscles, pain with respiratory movement, functional status                   

Ø     Diagnostic tests are only done if helpful in diagnosing the cause of dyspnea and should only be used if they will change or guide therapy:  Chest X-Ray, electrocardiogram, pulmonary function tests, arterial blood gas, serum potassium, magnesium, phosphate, oxygen saturation, helical computed tomography scan, complete blood count, etc.

Opioids decrease the perception of air hunger, regardless of the underlying pathophysiology and without causing respiratory depression.[47] This relief is dose related and, experimentally, is reversible by naloxone, an opioid antagonist. Very low doses of opioid, such as morphine 2.5 mg orally, may provide relief in opioid-naïve patients. Higher doses may be indicated in patients who have more intense dyspnea or in patients who are using opioids for pain. As with pain control, gradual upward titration may be needed to provide relief, particularly as symptoms progress.

The use of nebulized opioids for control of dyspnea remains controversial. Nebulized morphine has been administered in the belief that this route would deliver the opioid directly to opioid receptors isolated within the lung. Initial uncontrolled clinical trials and case reports described efficacy using this technique.] However, controlled trials have not confirmed these positive results, and as a result, nebulized morphine is generally not indicated. Initial trials of nebulized fentanyl, a lipophilic opioid, suggest efficacy.

A randomized controlled trial of oxygen delivered versus room air, both delivered by nasal cannula and worn at least 15 hours per day over a 7-day period, demonstrated no differences in breathlessness, with no difference in side effects between the two groups. In light of the lack of benefit of oxygen therapy, the investigators recommended that less burdensome therapies be selected. Supplemental oxygen appears to be useful only when hypoxemia is the underlying cause of dyspnea and is not effective in relieving symptoms of dyspnea in people who do not have hypoxemia. Alternate strategies include positioning a cool fan toward the patient’s face and repositioning the patient into an upright posture. Cognitive behavioral therapies such as relaxation, breathing control exercises, and psychosocial support may be effective in relieving dyspnea, although patients in the final hours of life may have limited capacity to participate in these techniques.

Complementary therapies such as acupuncture and acupressure have been demonstrated to be beneficial for relieving dyspnea, although controlled trials are lacking. Antibiotics may provide relief from infectious sources of dyspnea; however, the use of these agents should be consistent with the patient’s goals of care. If the patient experiences bronchospasm in conjunction with dyspnea, glucocorticoids or bronchodilators can provide relief. Bronchodilators should be used with caution because they can increase anxiety, leading to a worsened sense of dyspnea. In rare situations, dyspnea may be refractory to all of the treatments described above. In such cases, palliative sedation may be indicated, using benzodiazepines, barbiturates, or neuroleptics.

There are many nonpharmacologic treatments/techniques available for dypsnea

(Dudgeon, 2010; Gallagher & Roberts, 2004; Jacobs, 2003; Kravits & Berenson, 2010).  They include:

Ø     Oxygen use ion-hypoxemic patients may have limited benefit.  A trial of oxygen should always be considered. 

Ø     Counseling may include the use of cognitive-behavioral, interpersonal and complementary strategies. 

Ø     Pursed lip breathing slows respiratory rate and decreases small airway collapse.

Ø     Energy conservation techniques can save energy, reduce fatigue, and allow the patient to maintain control of lifestyle changes.

Ø     Fans, open windows and air conditioners circulate air.

Ø     Elevation of the head of the bed and the ability of the patient to sit in a forward and upright position reduces choking sensations and promotes expansion of the lungs. Placing the patients’ arms on pillows may promote air exchange.

Ø     Prayer can promote comfort and relaxation.

Ø     Education of patient/family reduces anxiety. 

Ø     Music as a form of relaxation and distraction also reduces dyspnea.

Ø     Calm room environment.

Ø     Cold air directed against the cheek may reduce the perception of breathlessness (Elia & Thomas, 2008).

Ø                 Other techniques may include blood transfusions, thoracentesis, stent tube placement to open an occluded airway, endobronchial laser therapy, radiation therapy to shrink tumor, paracentesis.

 

Cough

In some patients, chronic coughing at the end of life may contribute to suffering. Chronic cough can cause pain, interfere with sleep, aggravate dyspnea, and worsen fatigue. At the end of life, aggressive therapies are not warranted and are more likely to cause increased burden or even harm. Symptom control rather than treatment of the underlying source of the cough is warranted at this time of life. Opioids are strong antitussive agents and are frequently used to suppress cough in this setting. Corticosteroids may shrink swelling associated with lymphangitis. Antibiotics may be used to treat infection and reduce secretions leading to cough. Patients with cancer may have comorbid nonmalignant conditions that can lead to cough. For example, bronchodilators are useful in the management of wheezing and cough associated with chronic obstructive pulmonary disease, and diuretics may be effective in relieving cough due to cardiac failure. Additionally, a review of medications is warranted because some drugs (e.g., ACE inhibitors) can cause cough.

Anecdotal evidence suggests a role for inhaled local anesthetics, which should be utilized judiciously and sparingly; they taste unpleasant and suppress the gag reflex, and anaphylactic reactions to preservatives in these solutions have been documented. In cases of increased sputum production, expectorants and mucolytics have been employed, but the effects have not been well evaluated. Inhaled sodium cromoglycate has shown promise as a safe method of controlling chronic coughing related to lung cancer.

 

Coughing is a common symptom in advanced disease.  Cough, like dyspnea can be very frustrating and debilitating for the patient, causing pain, fatigue, vomiting and insomnia.

Thirty-nine (39) to 80 percent of palliative care patients will experience cough-related problems (Dudgeon, 2010; Estfan & LeGrand, 2004).

An ongoing cough is also a constant reminder of the evolving disease process. Cough is frequently present in advanced diseases such as bronchitis, congestive heart failure, HIV/AIDS and various cancers, however lung cancer patients most commonly experience this symptom (Dudgeon, 2010).

Causes of cough can be numerous.  Possible causes can include post-nasal drip, bronchitis, obstruction, asthma, pleural effusion, pulmonary embolism, pneumothorax, etc).

 

Identify the types of coughs:

Ø     Acute: may be caused by exposure to allergens, environmental irritants, post-nasal drip, aspiration of gastric contents, pulmonary lesions, pneumonia, TB, or presence of foreign objects.

Ø     Chronic: may result from exposure to allergens or other chronic diseases (i.e. bronchitis/airway inflammation).

Ø     Nocturnal: suggests gastro-esophageal reflux disease, asthma or congestive heart failure.

 

·        Assessment should include (Dudgeon, 2010):

Ø     A history and physical should be obtained that includes information about precipitating and relieving factors, associated symptoms, presence of sputum production which includes observation of color, consistency, presence of blood. 

 

·         It may be appropriate to order chest or sinus X-Rays.  However, the choice of tests will be determined by prognosis and patient’s wishes.

·                       There are many different pharmacologic interventions used for coughing.

 

·                       Suppressants/expectorants:

Ø     Opiates (morphine sulfate)

Ø     Local anesthetics (benzonatate, nebulized lidocaine)

Ø     Cough expectorant/antitussive (guaifenesin), dextromethorphan)

 

·                       Antibiotics:

Ø     Penicillin

 

·                       Steroids:

Ø     Dexamethasone

 

·                       Anticholinergics:

Ø     Atropine, hyoscyamine, hydrobromide

·                       Non-pharmacologic interventions should be considered when treating a cough. Non-pharmacologic techniques include:

Ø     Chest physical therapy has ability to help a frail patient mobilize secretions.

Ø     Humidifier, typically cool, can help comfort a rapid breathing state and thin secretions.

Ø     Elevating the head of the bed/positioning to allow the patient the ability to clear or manage secretions more effectively.

Ø     Caffeinated beverages have been reported to have an effect in dilating pulmonary vessels.

Radiation may be utilized, especially with hemoptysis.

 

CONSTIPATION

Constipation can be defined as a reduced frequency of bowel movements and an increased stool consistency. In defining constipation in people with life-limiting disease, measurable symptoms, as well as the person’s perception of constipation and the level of discomfort, are factors. The condition may be accompanied by cramps and a bloating feeling as well as discomfort while defecating, due to straining and rectal pressure. Constipation should be fundamentally defined by the patient.

Prevalence

The prevalence of constipation among adults with life-limiting disease ranges from 8% to 70%, and constipation occurs in almost all patients taking opioids.

Etiology

Opioids are the primary factor in constipation in the palliative care setting, and many other prescribed drugs can contribute to constipation, including tricyclic antidepressants, antacids, antiepileptic drugs, anticholinergic agents, and antihypertensives. Additional factors that may contribute to constipation are diverticuli, inflammatory bowel disease, metabolic conditions (hypercalcemia, hypokalemia, hypothyroidism, uremia), cerebral tumors, dehydration, and radiation fibrosis. For patients with cancer, constipation may be directly due to tumor involvement that causes intestinal obstruction. A diet low in fiber and decreased physical activity also increase the likelihood of constipation.

Prevention

Prevention of constipation is key, as prophylaxis is more effective than treatment after constipation has been identified. As such, all treatment guidelines strongly recommend that a prophylactic bowel regimen be initiated when treatment with opioids (or other constipation-causing drugs) begins. The recommended prophylaxis is an osmotic and/or a stimulant laxative. Many nonpharmacologic approaches are recommended, and patients should be encouraged to plan a diet with adequate fiber, to increase fluid intake, and to engage in physical activity, as appropriate. Family members should be asked to help the patient comply with these measures. Ensuring that the patient has sufficient privacy and comfort with toileting is also recommended.

Assessment

Issues of personal privacy often lead to a reluctance of patients to discuss constipation, so clinicians and other healthcare professionals must initiate the discussion and talk honestly about what to expect and measures to prevent and manage the symptom. The assessment tools used most often are the Bristol Stool Form Scale and the Constipation Assessment Scale. Assessment should include a review of the list of medications, a history of bowel habits, and abdominal and rectal examination. In addition to checking the list of prescribed medications to determine if constipation is a side effect, the physician should ask the patient about over-the-counter drugs and herbal remedies, as constipation can be a consequence of aluminum-containing antacids, ibuprofen, iron supplements, antidiarrhea drugs, antihistamines, mulberry, and flax. A detailed history of bowel habits helps to establish what is considered normal for the individual patient. The patient should be asked about frequency of stool, the appearance and consistency of stools, use of bowel medications, and previous occurrence of constipation. In general, physical examination of the abdomen for tenderness, distention, and bowel sounds can rule out intestinal obstruction as the cause of constipation. A rectal examination can identify the presence of stool, fecal impaction, or tumor. Imaging of the abdomen (by plain x-ray or computerized tomography) may be appropriate to confirm the presence of obstruction. Consideration of the patient’s prognosis and preferences for care should be factored into a decision to carry out diagnostic testing. As with assessment of all symptoms, constipation should be reassessed frequently; assessment at least every 3 days is recommended.

Management

The goal of treatment should be relief of symptoms related to constipation and re-establishment of bowel habits to the patient’s comfort and satisfaction; some recommend a goal of one nonforced bowel movement every 1 to 2 days. Systematic reviews have demonstrated that data are insufficient to support one laxative or combination of laxatives over others.

Many laxatives are FDA approved for occasional constipation, and much of the evidence on their efficacy has come from studies of chronic constipation, not patients with life-limiting disease. In its guidelines for the management of chronic constipation, the American College of Gastroenterology notes the following:

·                     Polyethylene glycol (PEG) and lactulose (both osmotic) improve stool frequency and stool consistency.

·                    

·                     Data are insufficient to make a recommendation about the efficacy of stool softeners (docusate [Colace or Surfak]); stimulant laxatives (senna [Senokot, Ex-lax] or bisacodyl [Dulcolax, Correctol]); milk of magnesia; herbal supplements (aloe); lubricants (mineral oil); or combination laxatives (psyllium plus senna).

The results of a systematic review of studies in the palliative care setting also demonstrated insufficient data for recommendations because of a lack of direct comparisons of laxatives. Researchers have concluded that the choice of a laxative should be made on an individual basis, with considerations of patient preferences and the side-effect profile. For all patients, oral formulations are recommended over rectal suppositories.

European and Canadian consensus groups and the NCCN have developed practice guidelines for constipation in the palliative care setting on the basis of the available data and expert opinion. First-line recommended treatment is a stimulant laxative plus a stool softener (PEG or lactulose). A small study of senna with and without docusate for hospitalized patients with cancer showed no significant benefit to the addition of docusate; docusate is specifically not recommended in the Canadian consensus recommendations. If constipation persists, other options are bisacodyl, magnesium hydroxide, or sorbitol. Methylnaltrexone (Relistor) was approved by the FDA in 2008 for the treatment of opioid-induced constipation. Although data are still limited, a systematic review indicated that the subcutaneous drug is effective in the palliative care setting, and is especially useful for patients with constipation refractory to conventional laxatives. Practice recommendations note that methylnaltrexone should be considered for patients taking opioids after failure of other laxatives. Withdrawal of opioids should never be a strategy to manage constipation.

 

ALGORITHM FOR THE MANAGEMENT OF CONSTIPATION IN PALLIATIVE CARE PATIENTS

Figure 11

Source: Reprinted, with permission from Larkin PJ, Sykes NP, Centeno C, et al. The management of constipation in palliative care: clinical practice recommendations. Palliat Med. 2008;22(7):796-807.

Nonpharmacologic interventions are important adjuncts to laxatives, and the interventions used as prophylaxis are recommended for ongoing management.

 

NAUSEA AND VOMITING

Nausea may occur alone or with vomiting, a neuromuscular reflex. Nausea and vomiting can exacerbate pain and contribute to insomnia, fatigue and weakness, and anorexia. It can also limit activities and cause distress for the patient and family. Nausea is the result of stimulation of one of several pathways: the chemoreceptor trigger zone (located in the medulla), the cortex of the brain, the vestibulocochlear nerve, or the gastrointestinal tract.

Pathways of Nausea & Vomiting

v

Prevalence

Nausea alone affects approximately 6% to 68% of adults with life-limiting disease, and vomiting affects 40%. The rate of nausea and vomiting is highest among patients with cancer.

Etiology

The potential causes of nausea and vomiting near the end of life vary according to life-limiting disease:

·                     Medications (chemotherapy agents, opioids, antidepressants, antibiotics)

·                     Radiation therapy (especially to the abdomen or lumbosacral spine)

·                     History of peptic ulcer disease or gastroesophageal reflux

·                     Delayed gastric emptying

·                     Primary or metastatic brain tumor

·                     Gastrointestinal tract obstruction

·                     Constipation

·                     Renal failure

·                     Hepatic failure

·                     Pancreatitis

·                     Hypercalcemia

·                     High serum levels of dioxin or anticonvulsants

The causes also differ according to the pathway stimulated. Most often the cause is multifactorial, but sometimes no cause can be determined.

 

CAUSES OF NAUSEA AND VOMITING ACCORDING TO PATHWAY STIMULATED AND CLASS OF ANTIEMETICS

Table 14

 

Prevention

The prevention of nausea and vomiting has focused on prophylactic treatment for patients receiving chemotherapy or radiation therapy for cancer. Although most patients at the end of life do not receive anticancer treatment, chemotherapy may be given as part of palliative care. ASCO classifies chemotherapy drugs according to their emetigenic potential: high (>90% incidence of emesis without an antiemetic), moderate (30% to 90% incidence), low (10% to 30% incidence), and minimal (<10% incidence). According to ASCO guidelines, a 5-hydroxytryptamine type 3 (5-HT₃) antagonist, dexamethasone (Decadron), and a neurokinin 1 (NK1) receptor antagonist (such as aprepitant [Emend]) should be used as prophylaxis for a highly emetic chemotherapy agent or combination (such as an anthracycline and cyclophosphamide) [305]. Palonosetron (Aloxi), in combination with dexamethasone, is recommended for chemotherapy agents with moderate emetic risk, and dexamethasone is recommended before the first dose of chemotherapy with a low emetic risk. For nausea and vomiting not related to chemotherapy, treatment with regular dosing of an antiemetic will help prevent subsequent episodes of the symptoms.

Assessment

A detailed history, physical examination, and review of the medication list are essential for planning effective management of nausea and vomiting. In talking with the patient, the clinician should ensure that the patient is actually experiencing nausea, as patients have used the term nausea to describe other feelings, such as pain, distention, abdominal discomfort, and early satiety. The clinician should ask about the onset of the nausea, how frequently it occurs, if there are precipitating factors, and if there is a relationship to food intake. It may be helpful to ask the patient to rate the intensity of nausea on a scale similar to a pain scale (a 10-point numerical scale). Because the cause of nausea and vomiting is often multifactorial, a multidimensional assessment is beneficial, with particular attention paid to such other symptoms as pain, appetite, fatigue, depression, and anxiety. The physical examination should include evaluation for signs of cachexia or malnutrition, assessment of the abdomen for evidence of bowel obstruction, increased bowel sounds, and abdominal distention. In addition, a neurologic examination should be done to determine if there are signs of increased intracranial pressure, papilledema, or autonomic insufficiency. Diagnostic testing may include laboratory studies to rule out metabolic disorders, renal impairment, or liver failure, or radiographs of the abdomen to determine if there is obstruction.

Nausea is ofteot reported; patients should be asked if they have experienced nausea even if they have not vomited.

Management

Evidence-based guidelines for the management of nausea and vomiting unrelated to chemotherapy and radiation are lacking. In addition, most studies of these symptoms and recommendations are related to the cancer setting. In general, experts have recommended that antiemetics be selected on the basis of the emetic pathway and the etiology of the nausea and/or vomiting, but systematic reviews have found that the evidence for recommendations is weak to moderate at best. One systematic review found no evidence that the choice of antiemetic according to etiology or multiple antiemetics was better than a single antiemetic.

Several classes of pharmacologic agents can be used to manage nausea and vomiting; the main classes used in the end-of-life setting are prokinetic agents, dopamine receptor antagonists, antihistamines, anticholinergics, 5-HT3 receptors, and corticosteroids. The prokinetic agent metoclopramide (Reglan) has been recommended as a first-line treatment because of its central and peripheral actions and its effectiveness for many chemical causes of nausea. The drug should be used with caution in patients with heart failure, diabetes, and kidney or liver disease, and the dose should be reduced by half for older patients and those with moderate-to-severe renal impairment. Octreotide (Sandostatin), dexamethasone, and hyoscine hydrobromide (Scopolamine) are recommended for bowel obstruction . Ondansetron (Zofran) has been suggested for chronic nausea, but in September 2011, the FDA issued a safety announcement about the drug, noting that it may increase the risk of QT prolongation on electrocardiogram; more research is being done. Haloperidol (Haldol) is recommended for uremia-induced nausea in people with end-stage chronic kidney disease. Dexamethasone is used for nausea and vomiting related to increased intracranial pressure and, although the evidence is limited, it is also used as second-line treatment for intractable nausea and vomiting and as an adjuvant antiemetic. Olanzapine (Zyprexa), an atypical antipsychotic, has also been effective for nausea that has been resistant to other traditional antiemetics, as well as for opioid-induced nausea. A benzodiazepine (such as lorazepam [Ativan]) may be of benefit if anxiety is thought to be contributing to nausea or vomiting [304].

 

PHARMACOLOGIC MANAGEMENT OF NAUSEA AND VOMITING

Table 15

In addition to pharmacologic management of nausea and vomiting, other supportive approaches include maintenance of oral hygiene, regular baths to reduce unpleasant odors, and small meals at regular intervals. Cold foods may be better tolerated than hot foods because of decreased smells.

 

ANOREXIA AND CACHEXIA

The symptoms of anorexia and cachexia often occur in tandem. While anorexia encompasses decreased appetite and food intake, cachexia involves loss of skeletal mass, with accompanying asthenia and autonomic failure. The two conditions are often linked by the term “anorexia-cachexia syndrome,” but the exact relationship between the two conditions is unclear. For example, decreased food intake may lead to weight loss, but the body wasting of cachexia is not solely the result of decreased intake. “Wasting” is often used as a synonym for cachexia, but wasting indicates weight loss due to inadequate nutritional intake, whereas cachexia refers to a loss of lean body mass resulting metabolic derangement rather thautritional deficiency.

Cachexia is associated with a poor prognosis in many life-limiting diseases. In fact, unintentional, progressive weight loss of more than 10% of body weight over the past 6 months, with an albumin level less than 2.5 mg/dL is a prognostic indicator for hospice referral. Despite this relationship between cachexia and poor prognosis, the condition is underrecognized and underdiagnosed.

Cachexia has also been challenging to define. The lack of an operational definition led to a consensus conference at which a definition was crafted. This definition joins others for disease-specific cachexia. The diagnosis and management of anorexia/cachexia has been studied the most in the settings of cancer and HIV infection.

 

DEFINITIONS AND DIAGNOSTIC CRITERIA FOR CACHEXIA

Table 16

Prevalence

Anorexia occurs in 21% to 92% of adults with life-limiting disease, with the highest rates found among patients with cancer. Cachexia has been reported in 16% to 57%, again with the highest rates found among people with cancer.

Etiology

Across life-limiting diseases, anorexia can occur as a result of several other symptoms, such as fatigue, constipation, xerostomia, dysphagia, mucositis, and nausea. Endocrine abnormalities may also be the cause, and psychologic, social, and spiritual distress can affect the desire to eat. Changes in taste sensations (leading to food aversions), altered sense of smell, and early satiety have been common among people with cancer and anorexia.

Studies have shown that multiple factors contribute to cachexia. Abnormal metabolism is thought to lead to a negative protein and energy balance, with subsequent loss of muscle mass. Inflammation, increased neurohormonal activity, insulin resistance, and increased muscle protein breakdown are often associated with cachexia. The role these factors play in the development of cachexia may differ according to the underlying chronic condition.

Prevention

Preventive measures for anorexia include effective management of symptoms that are known to have a potential impact on the desire and/or ability to eat. No appropriate measures to prevent cachexia are available.

Assessment

Guidelines for assessing anorexia and cachexia have been developed for the cancer and HIV settings. According to NCCN guidelines, assessment of anorexia and cachexia in patients with cancer include the following:

·          Determination of the rate and severity of weight loss

·          Examination of the oral cavity (the mucous membranes, teeth, gingiva, and lips)

·          Review of the medications list for drugs that interfere with intake

·          Evaluation of symptoms that have the potential to interfere with eating and drinking

·          Evaluation for endocrine abnormalities that may be an underlying cause

·          Assessment of social and economic factors

The guidelines for the assessment of HIV-related wasting recommend the following:

·                     Thorough and complete history and physical examination, with specific questions related to the patient’s nutritional status, caloric intake, appetite, and gastrointestinal and physiologic functioning

·          Measurements of body composition (considering the following factors: age, height, weight, ideal body weight, body cell mass (by BIA), and body mass index

·          Laboratory tests (plasma HIV RNA, CD4 cell count, free and total serum testosterone, and serum albumin and thyroid function (if clinically warranted)

·          Psychosocial evaluation

·          Dietary assessment

Management

Few evidence-based guidelines for the treatment of anorexia and cachexia are available, primarily because of the lack of studies on these underrecognized conditions and the still-emerging understanding of the causes of cachexia. The first step in managing anorexia is to treat symptoms that interfere with appetite and/or the ability to eat. In addition, nonpharmacologic interventions should be directed at improving enjoyment of food, increasing the sense of well-being, and enhancing a sense of normalcy in daily activities. The patient should be encouraged to try favorite foods, to eat small frequent meals, and to drink high-calorie nutritional supplements. Other interventions include an exercise program and consultation with a nutritionist. For people with end-stage liver disease and an inadequate caloric intake, protein restriction (to prevent hepatic encephalopathy) should be avoided.

Two drugs are FDA approved as appetite stimulants for anorexia associated with life-limiting disease. Megestrol acetate is FDA approved for the treatment of anorexia, cachexia, or unexplained weight loss in patients with AIDS. It has become the most widely used drug for these indications for people with other life-limiting diseases, and a meta-analysis of data from studies (involving people with a variety of life-limiting illnesses) demonstrated that megestrol acetate was beneficial, especially with respect to improving appetite and weight gain in people with cancer. The data were insufficient to recommend megestrol acetate for conditions other than cancer or to recommend an optimal dose. Dronabinol (Marinol), an oral cannabinoid, is FDA approved for anorexia associated with weight loss in people with AIDS. Because of its effects, dronabinol should be used with caution for people with cardiac disorders, depression, or a history of substance abuse; people taking concomitant sedatives or hypnotics; and older individuals.

 

PHARMACOLOGIC MANAGEMENT OF ANOREXIA AND CACHEXIA

Table 17

In addition to appetite stimulants, metoclopramide, a drug approved for treatment of nausea and vomiting, is recommended for anorexia related to early satiety in people with cancer.

The treatment of cachexia is more challenging because its pathophysiology is poorly understood and because treatments may differ according to the life-limiting disease. According to the guidelines for cachexia related to cancer and HIV infection, management includes improving nutritional intake, treating disease-related causes of cachexia, treating anorexia, and addressing psychosocial or lifestyle issues.

Currently, there is no one treatment or combination of treatments that is effective for all patients with cachexia. Increasing oral intake alone is not sufficient, and reversal of wasting may not always be possible; the goal should be to prevent or delay further wasting and functional decline. As noted, the use of megestrol acetate is effective in increasing weight, but increased nutrition and weight are not sufficient to effectively manage cachexia, and more research is needed to identify agents to increase body mass and to define a multimodal strategy to stop and/or reverse wasting. These strategies may differ according to the underlying chronic disease.

Studies have indicated that recombinant human growth hormone (rhGH) significantly increases lean body mass and improved physical endurance and quality of life in people with HIV. In addition, rhGH has shown benefit in cachexia related to pulmonary and cardiac disease. Recombinant somatropin (Serostim) is approved for the treatment of people with HIV with wasting or cachexia; concomitant antiretroviral therapy is necessary. The drug is contraindicated in active neoplasia.

The anabolic steroid oxandrolone (Oxandrin) is FDA approved as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infection, or severe trauma and for some patients without a definitive pathophysiologic cause of weight loss. The drug has shown benefit in increasing body weight and lean body mass in cachexia related to HIV and COPD. The drug is safe and well tolerated, but more studies are needed to determine its risk-benefit ratio before it can be used more widely.

Ghrelin has been evaluated for the treatment of cachexia, and its anti-inflammatory properties may address the proposed role of inflammation in the development of cachexia. The results of small studies have demonstrated that ghrelin increases lean body mass in people with end-stage renal disease, COPD, and heart failure. Again, more research is needed before this agent can become part of clinical practice.

For people with a limited life expectancy (weeks to days), the clinician should assess the importance of anorexia and cachexia to the patient and the family before prescribing interventions. The clinician should also talk to the patient and family about the risks of artificial nutrition and should consider consulting a spiritual counselor or bioethicist about discontinuing nutrition.

 

DIARRHEA

Diarrhea is characterized by the frequent passage of loose, watery stools, usually defined as more than three unformed stools within a 24-hour period. Diarrhea is most often acute, lasting for a few days; diarrhea is chronic when it persists for more than 3 weeks. Left unchecked, diarrhea can result in dehydration, electrolyte imbalance, and fatigue.

Prevalence

The prevalence of diarrhea among adults with life-limiting disease varies widely, ranging from 3% to 90%, with the highest rates reported among people with HIV infection or AIDS.

Etiology

The most frequent cause of diarrhea in patients receiving palliative care is overuse of laxatives and leakage around a fecal impaction. Other causes are infectious disease or underlying disease in people with HIV/AIDS or metastatic colorectal cancer. Diarrhea is also a side effect of many drugs, including antihypertensives, antacids containing magnesium, some NSAIDs, potassium supplements, quinidine, thiazide diuretics, retroviral agents, prokinetic agents (metoclopramide), and antibiotics.

Prevention

No appropriate measures to prevent diarrhea are available.

Assessment

A detailed history is the cornerstone of assessing patients for diarrhea. The condition is distressful, yet embarrassing, and direct questions should be asked because the patient may not be forthcoming about the symptom. The clinician should ask the patient about the onset of diarrhea, dietary habits and food intolerances, timing of diarrhea in relation to eating, and medications. The patient should also describe bowel movements in terms of frequency, color, and consistency. If possible, a stool specimen should be evaluated.

If infectious diarrhea is suspected, a stool sample should be evaluated to identify the causative organism.

Management

The American Gastroenterological Association developed guidelines for the treatment of chronic disease in the general clinical setting, but no guidelines are available for the management of diarrhea in palliative care.

Treatment of an underlying condition is the optimal approach to managing diarrhea. The clinician should review the medication list and discontinue or reduce the dose of any medication that may be the cause.

Nonpharmacologic approaches to managing diarrhea include avoiding gas-forming and bulky foods, hot spices, fats, alcohol, and milk until diarrhea is controlled. The patient should be encouraged to drink plenty of fluids to avoid dehydration; beverages with added electrolytes, such as sports drinks, can help maintain proper electrolyte balance.

Pharmacologic management includes the use of bulk-forming agents, adsorbents, and opioids. Kaolin and pectin (Kaopectate), available over the counter, is a combination of adsorbent and bulk-forming agents. However, it provides modest relief and it may take up to 48 hours to be effective. Loperamide (Imodium) is the drug of choice for diarrhea because its side effect profile is better than that for codeine or diphenoxylate (Lomotil). The initial dose of loperamide is 4 mg, with an additional 2 mg after each loose stool. The package insert for loperamide notes that the maximum daily dose in a 24-hour period is 16 mg, but doses of up to 54 mg a day have been used as part of palliative care with few adverse events. Octreotide has been effective for profuse secretory diarrhea associated with HIV infection and can be used to treat refractory diarrhea. The use of octreotide for diarrhea in the palliative setting is usually off-label, as the drug is FDA approved for the treatment of diarrhea and flushing associated with metastatic carcinoid tumors. Octreotide is administered as a continuous subcutaneous infusion at a rate of 10–80 mcg/hr until improvement of symptoms. Infectious diarrhea should be treated with an appropriate antibiotic. A systematic review found probiotic agents to be of benefit in the management of acute infectious diarrhea.