Nausea and Vomiting
Nausea and vomiting occur in up to 62% of patients with terminal cancer41 and 27% of patients dying of other causes. There are multiple potential causes for both nausea and vomiting [see Table 4].37 Once the cause has been determined, symptomatic relief is relatively easy to achieve with the appropriate medications [see Table 5J.28 Without an understanding of the underlying etiology, it may be impossible to find the most beneficial form of treatment.
The central nervous system and the gastrointestinal tract are particularly important in nausea and vomiting.42 The gastric lining, the chemoreceptor trigger zone in the base of the fourth ventricle, the vestibular apparatus, and the cortex are all involved in the physiology of nausea. Stimulation of the vomiting center in the brain from one or more of these areas is mediated through the neurotransmitters serotonin, dopamine, acetylcholine, and histamine. Serotonin seems to be important in the gastric lining and the CNS, whereas acetylcholine and histamine are important in the vestibular apparatus. Cortical responses are mediated via both neurotransmitters and learned responses (e.g., nausea related to anxiety or anticipatory nausea with chemotherapy).
The major causes of nausea and vomiting can be classified by the mechanisms' principal site of action. Dopamine-medi-ated nausea is probably the most common form of nausea and the most frequently targeted one for initial symptom management. Antidopamine medications are phenothiazines and butyrophenone neuroleptics (metoclopramide and pro-chlorperazine). They may cause drowsiness and extrapyrami-dal symptoms. Haloperidol is a highly effective antinausea agent and may be less sedating. Antihistamines such as diphenhydramine can be used to control nausea, but they may cause sedation. Antihistamines also have anticholinergic properties. Serotonin has been implicated in chemotherapy-associated nausea. Antiserotonin medications (e.g., odansetron) can be effective, but they are expensive.
Nausea can also result from slow gastric and intestinal motili-ty, so-called squashed stomach syndrome from mechanical compression of the stomach, and constipation. Hence, prokinetic agents (e.g., metoclopramide) and aggressive fecal disimpaction and institution of a bowel regimen (see below) should be considered as therapeutic modalities. In some patients, hyperacidity and mucosal erosion may also be associated with significant nausea. In these patients, consider the use of antacids, histamine2 blockers, proton-pump inhibitors, and misoprostol [see 4:XIV Gastrointestinal Motility Disorders].
Constipation
Constipation can lead to serious complications, such as bowel obstruction, ulceration, or perforation, as well as delirium. Because constipation is so common in terminal illness, appropriate management includes the institution of preventive measures in patients at high risk for this complication.
Diagnosis Assessment of constipation begins with inquiry about the frequency and consistency of stools; possible contributing factors, such as medications, reduced mobility, and a low-fiber diet; and any accompanying symptoms that suggest complications, such as nausea, vomiting, abdominal pain, dis-tention, and discomfort.43 As with any symptom, the search for a reversible cause is primary. A plain x-ray can be useful to evaluate for ileus or bowel obstruction. Invasive evaluation with colonoscopy should be considered in difficult, refractory, or complicated cases.
Many medications can contribute to constipation. These include beta blockers, calcium channel blockers, anticholinergic agents, and diuretics.43,44 First and foremost, however, are opioid analgesics: constipation is a universal side effect of opioid therapy, especially in the terminally ill. For that reason, every terminally ill patient who is placed on opioids should also be started on a preventive regimen for constipation. The bowel regimen in these patients starts with stool softeners and stimulant laxatives and progresses through hyperosmotic agents and enemas, as necessary [see Table 6].45 This regimen can also be utilized for treatment of constipation from other causes, once intestinal obstruction is ruled out.
Treatment Treatment of constipation is with oral agents, rectal suppositories, or enemas and can focus on softening the stool, enlarging stool volume, or promoting bowel peristalsis. Laxative categories include detergents, stimulants, osmotic agents, prokinetic agents, lubricant stimulants, and large-volume enemas [see Table 7]. Polyethylene glycol solution (GoLYTE-LY) or powder (MiraLax) is an osmotic agent that is marketed as a bowel cleanser to prepare patients for colonoscopy, but it is often effective in relieving constipation and may cause less cramping than other laxatives. Whichever laxative is chosen, the clinician should prescribe the maximum therapeutic dose of the agent before switching to another one.
Fecal impaction Although impaction of stool in the rectum is a complication of constipation, the typical clinical manifestation is so-called overflow diarrhea from leakage of unformed stool around the obstruction. A digital rectal examination may confirm fecal impaction in the distal rectum, but abdominal x-rays may be required for the diagnosis of more proximal im-paction. Treatment of fecal impaction is from below, utilizing digital disimpaction and rectal laxatives (suppositories, enemas, or both); only if those fail should oral treatment be attempted.43
Bowel Obstruction
The prevalence of bowel obstruction is as high as 40% in bowel and pelvic cancers.46 Constipation and fecal impaction are the most common causes of bowel obstruction in terminal illness. Symptoms of bowel obstruction include anorexia, confusion, nausea and vomiting, constipation, and pain. Diagnosis is made on the basis of the clinical presentation and abdominal x-rays.
Consultation with a surgeon is advisable to establish a treatment plan. In addition to aggressive measures to prevent or treat constipation and fecal impaction (see above), treatment of bowel obstruction may involve surgical relief of obstruction, nasogas-tric suction, and pharmacologic measures. Colicky or cramping pain may respond to dicyclomine, opioids (parenteral or rectal), and warm soaks to the abdomen. The obstruction and associated nausea and vomiting may respond to metoclopramide, haloperi-dol, or dexamethasone. Parenteral octreotide is also useful in this setting to decrease the volume of bowel secretions.
Diarrhea
Diarrhea, which is often secondary to fecal impaction or antibiotic-associated colitis, is a particularly distressing and exhausting symptom in the terminally ill patient.43 Once impaction, overgrowth, and other causes (e.g., gastrointestinal bleeding, malabsorption, and medications) have been ruled out, kaolin-pectin, psyllium, loperamide, or tincture of opium may be tried.
Figure 1 Shown are the drug treatments for productive cough and nonproductive cough.28
Table 4 Management of Nausea and Vomiting37
|
Etiology |
Pathophysiology |
Therapy |
|
Mechanical obstruction— intraluminal |
Constipation, obstipation |
Laxatives; disimpaction |
|
Mechanical obstruction— extraluminal |
Tumor, fibrotic stricture |
Surgery, fluid management, steroids, octreotide, scopolamine |
|
Medications—chemotherapy |
Chemoreceptor trigger zone, GI tract |
Antiserotonin, antidopamine, steroids |
|
Medications—NSAIDs |
GI tract irritation |
Cytoprotective agents, antacids |
|
Medications—opioids |
Chemoreceptor trigger zone, vestibular effect, GI tract |
Antidopamine, anticholinergic, proki-netic agents, stimulant cathartics |
|
Medications—other |
Chemoreceptors |
Antidopamine, antihistamine |
|
Meningeal irritation |
Increased intracranial pressure |
Steroids |
|
Mentation (e.g., anxiety) |
Cortical |
Anxiolytics |
|
Metabolic—hypercalcemia |
Chemoreceptor trigger zone |
Antidopamine, antihistamine |
|
Metabolic—hyponatremia |
Chemoreceptor trigger zone |
Antidopamine, antihistamine |
|
Metabolic—hepatic/renal failure |
Chemoreceptor trigger zone |
Rehydration, steroids |
|
Metastases—cerebral |
Increased intracranial pressure |
Steroids, mannitol |
|
Chemoreceptor trigger zone |
Antidopamine, antihistamine |
|
|
Metastases—liver |
Toxin buildup |
Antidopamine, antihistamine |
|
Microbes—gastroenteritis |
GI tract |
Anti-infectives, antacids |
|
Microbes—sepsis |
Chemoreceptor trigger zone |
Antidopamine, antihistamine, anti-infectives |
|
Movement |
Vestibular stimulation |
Anticholinergic |
|
Mucosal irritation |
GI hyperacidity, GERD |
Cytoprotective agents, antacids |
|
Myocardial—ischemia, CHF |
Vagal stimulation, cortical, chemore-ceptor trigger zone |
Oxygen, opioids, antidopamine, antihistamine, anxiolytics |
CHF—congestive heart failure
GERD—gastroesophageal reflux disease
NSAIDs—nonsteroidal anti-inflammatory drugs
Octreotide (see above) is an effective means of reducing gastrointestinal secretions.
Mouth symptoms
Oral problems can cause altered taste, pain, and difficulty swallowing, which may lead to reduced food and fluid intake. Good hy-dration, hygiene, and regular observation can keep oral problems to a minimum. The patient’s teeth should be brushed twice daily with toothpaste. Daily observation of the oral mucosa is recommended.
Dentures also require regular cleansing. Dentures may cease to fit properly in patients who lose a significant amount of weight. Some of those patients may wish to have their dentures refitted; others (especially those nearing death) will choose to forgo this arduous process.
Key questions to ask regarding the mouth include the following: Is the mouth dry? Is infection present? Is the mouth dirty? Is the mouth painful? Are oral ulcerations present? [see Table 8]47
Dry Mouth
The presence of saliva is usually taken for granted, but the lack of it can seriously damage the quality of life. Xerostomia (the subjective sensation of dry mouth) may result from salivary gland disease or systemic conditions such as Sjogren syndrome, Parkinson disease, AIDS, or diabetes48; it may also be a side effect of medications, including those with anticholinergic action, ben-zodiazepines, diuretics, and interleukin-2.49 Regardless of the cause, xerostomia almost always requires symptomatic treatment. The goal of therapy is to moisten the oral mucosa, and the best, simplest way is for the patient to sip water frequently. However, mouth moisteners and artificial salivas exist and may be preferred by some patients.47,49 Pilocarpine tablets may be used, at a dosage of 5 to 10 mg every 8 hours, if the above measures fail. Side effects may include nausea, diarrhea, urinary frequency, and dizziness. Other nonpharmacologic treatments include eating ice chips and sucking on hard candy.
Oral Ulcers/Mucositis
Oral infection can have multiple causes. Aphthous ulcers are common and can be eased by topical corticosteroids, tetracycline mouthwash, or thalidomide. Oral candidiasis usually presents as adherent white plaques but can also present as erythema or angular cheilitis. Nystatin suspension is the usual treatment, but a 5-day course of oral ketoconazole, 200 mg daily, can also be used. Severe viral infection (herpes simplex or zoster) requires treatment with acyclovir, 200 mg every 4 hours for 5 days. Malignant ulcers are often associated with anaerobic bacteria and may respond to metronidazole, 400 to 500 mg orally or rectally every 12 hours or as a topical gel.47
Pressure Ulcers
Pressure ulcers typically result from both intrinsic and extrinsic factors [see Table 9]. Major sites of pressure ulcers in terminally ill patients include the ear and the skin overlying the spine (apex of kyphosis), sacrum, greater femoral trochanter, head of the fibula, and malleolus. Prevention should emphasize these sites and should include daily visual inspection of them in patients at risk for pressure sores.
Prevention and treatment of pressure sores require targeting risk factors and minimizing them. Caregivers need to minimize pressure by turning and repositioning the patient frequently and avoiding shear (sliding movement) and friction. They should be aware that even crumpled bedclothes can impair circulation.
Table 5 Medications for Nausea and Vomiting28
|
Administration |
Category |
Drug (Trade Name) |
Dosage |
|
Oral |
Corticosteroid |
Dexamethasone |
2-8 mg q. 6-12 hr |
|
Antidopamine |
Haloperidol (Haldol) |
0.5-5 mg q. 6-8 hr |
|
|
Prochlorperazine (Compazine) |
5-10 mg q. 4-6 hr |
||
|
Prochlorperazine SR |
10-15 mg b.i.d. |
||
|
Antihistamine |
Diphenhydramine (Benadryl) |
25-50 mg q. 4-6 hr |
|
|
Hydroxyzine (Atarax) |
25-50 mg t.i.d.-q.i.d. |
||
|
Promethazine (Phenergan) |
12.5-25 mg t.i.d.-q.i.d. |
||
|
Anticholinergic |
Hyoscyamine (Levsin) |
0.125-0.25 S.L. q. 4 hr |
|
|
Meclizine (Antivert) |
12.5-25 mg b.i.d.-q.i.d. |
||
|
Anxiolytic |
Lorazepam (Ativan) |
1-2 mg q. 2-4 hr |
|
|
Prokinetic |
Metoclopramide (Reglan) |
10-40 mg q.i.d. |
|
|
Antiserotonin |
Ondansetron (Zofran) |
8 mg p.o., t.i.d.-q.i.d. |
|
|
Other |
Dronabinol (Marinol) |
2.5-10 mg b.i.d., t.i.d. |
|
|
Thiethylperazine (Torecan) |
10 mg q.d.-t.i.d. |
||
|
Trimethobenzamide (Tigan) |
250 mg t.i.d.-q.i.d. |
||
|
Rectal suppositories |
Antidopamine |
Prochlorperazine (Compazine) |
25 mg q. 6 hr |
|
Antihistamine |
Promethazine (Phenergan) |
12.5, 25, 50 mg t.i.d.-q.i.d. |
|
|
Other |
Trimethobenzamide (Tigan) |
200 mg t.i.d.-q.i.d. |
|
|
Continuous intravenous infusion |
Corticosteroids |
Dexamethasone |
8-100 mg/24 hr |
|
Antidopamine |
Haloperidol (Haldol) |
2.5-10 mg/24 hr |
|
|
Anticholinergic |
Hyoscyamine (Levsin) |
1-2 mg/24 hr |
|
|
Scopolamine |
0.8-20 mg/24 hr |
||
|
Antiserotonin |
Odansetron (Zofran) |
0.45 mg/kg/24 hr |
|
|
Prokinetic |
Metoclopramide (Reglan) |
20-80 mg/24 hr |
|
|
Intermittent intravenous infusion |
Corticosteroids |
Dexamethasone |
2-8 mg q. 4-6 hr |
|
Antidopamine |
Haloperidol (Haldol) |
0.5-2 mg q. 4-6 hr |
|
|
Prochlorperazine (Compazine) |
5-10 mg q. 4-6 hr |
||
|
Antihistamine |
Diphenydramine (Benadryl) |
25-50 mg q. 6 hr |
|
|
Anxiolytic |
Lorazepam (Ativan) |
1-2 mg q. 6-8 hr |
|
|
Prokinetic |
Metoclopramide (Reglan) |
10-20 mg q. 6 hr |
|
|
Antiserotonin |
Ondansetron (Zofran) |
4-8 mg q. 8 hr |
|
|
Granisetron (Kytril) |
10 ^g/kg q.d. |
||
|
Other |
Dronabinol (Marinol) |
5 mg/m2 q. 4 hr (maximum, six doses/day) |
How a patient moves or is moved by caregivers needs to be assessed and monitored. Even with regular turning and careful lifting and positioning, special pressure surfaces or mattresses are sometimes needed.47 Fragile skin that is at risk for breakdown should be covered with clear, occlusive dressings; pressure points should be covered with thin, hydrocolloid dressings.
Caregivers must keep the patient’s skin clean and dry. Absorbent surfaces, urinary catheters, and rectal tubes may be helpful, but they must be used carefully because of their attendant complications.37
Nutrition is an important factor in both prevention and treatment. Good hydration, a diet that is high in protein and carbohydrates, and vitamin C supplements help maintain skin integrity and encourage healing.
If pressure ulcers develop, they should be covered with gel or colloid dressings, which keep the area moist, reduce pain, and can be left in place for several days. The pain of dressing changes can be eased by extra analgesia before each change.47 The clinician should instruct caretakers to give oral pain medication one-half hour before the dressing change. The dose is determined by whether or not the patient is on regular opioid medications. If the patient is not on regular pain medications, start with 15 mg of immediate-release morphine. If the patient is on a regular opioid regimen, the predressing dose should be the same as the rescue dose.
Pressure ulcer management needs to be consistent with the overall goals of care. If maintenance or improvement of function is the goal and the patient’s life expectancy is weeks to months, the ulcer should be treated according to the usual management guidelines. If life expectancy is very limited (e.g., days), the intent should be to optimize quality of life and minimize pain and discomfort (such as from excessive dressing changes or debridement).
