Palliative Care and Pain Management at the End of Life ___________________________________________
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 cor- ticosteroids ( Table 15 ) [328; 329; 334]. A first antiemetic should be scheduled and titrated to efficacy, maximum recom- mended dose, or dose-limiting side effects. If a first drug does not adequately control nausea and vomiting, a second (and perhaps subsequent agents) with different receptor binding can be added in a stepwise manner [331]. Oral antiemetics are recommended unless the patient is vomiting or has symp- tomatic gastric stasis. Drugs that block several receptors (e.g., olanzapine) may be advantageous if the nausea and vomiting seems refractory [331]. The prokinetic agent metoclopramide (Reglan) has been rec- ommended as a first-line treatment because of its central and peripheral actions and its effectiveness for many chemical and undetermined causes of nausea [206; 246; 328; 331]. The drug should be used with caution in patients with heart failure, dia- betes, and kidney or liver disease; the dose should be reduced by 50% for older patients and those with moderate-to-severe renal impairment [329; 331]. Chronic use of prokinetic agents and dopamine receptor antagonists may be associated with the development of tardive dyskinesia, especially in frail, elderly patients [187]. Octreotide (Sandostatin), dexamethasone, and hyoscine hydrobromide (Scopolamine) are recommended for bowel obstruction [92; 328; 329; 331; 332]. Ondansetron (Zofran) has been suggested for chronic nausea, but in Septem- ber 2011, the FDA issued a safety announcement about the drug, noting that it may increase the risk of QT prolongation on electrocardiogram. [329; 335]. In 2012, the FDA updated the safety information specifically for the 32-mg IV dose of the
drug, and the manufacturer subsequently announced changes to the drug label removing this dose [336]. Haloperidol (Hal- dol) is recommended for uremia-induced nausea in people with end-stage chronic kidney disease [214]. 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 [246; 328; 329]. 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 [337]. A benzodiazepine (such as lorazepam [Ativan]) may be of benefit if anxiety is thought to be contributing to nausea or vomiting [329]. 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 [206; 246]. 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 tan- dem. While anorexia encompasses decreased appetite and food intake, cachexia is defined as physical wasting with loss of skeletal and visceral muscle mass accompanied by asthenia and autonomic failure. The two conditions are often linked by the term “anorexia-cachexia syndrome,” but the exact relation- ship between the two conditions is unclear [338]. For example, decreased food intake may lead to weight loss, but the body wasting of cachexia is not solely the result of decreased intake [339]. “Wasting” is often used as a synonym for cachexia, but wasting indicates weight loss due to inadequate nutritional
PHARMACOLOGIC MANAGEMENT OF NAUSEA AND VOMITING
Drug Class
Drug
Typical Starting Dose and Frequency 10–20 mg PO/IV/SC, every 6 to 8 hours 0.5–1.5 mg PO/IV/SC every 6 to 8 hours
Prokinetic agents
Metoclopramide
Dopamine antagonists
Haloperidol
Prochlorperazine Chlorpromazine
5–10 mg PO every 6 hours
10–25 mg PO/IV every 4 to 6 hours
Olanzapine
5–10 mg PO daily
Levomepromazine
6.25–25 mg SC twice daily 25 mg PO 4 to 6 hours
Antihistamines Anticholinergics
Promethazine
Hyoscine hydrobromide
0.1–0.4 mcg PO/IV/SC every 4 hours 4–8 mg PO/IV 1 or 2 times daily
5-hydroxytryptamine type 3 receptor antagonists
Ondansetron Granisetron Dolasetron Palonosetron Mirtazapine Dexamethasone
1 mg twice daily
200 mg daily
0.25 mg IV daily
15–45 mg PO, every night
Corticosteroids
4–8 mg daily
PO = orally, IV = intravenously, SC = subcutaneously. Source: [187; 206; 329]
Table 15
42
MDCA1525
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