DALLAS – Haloperidol is, perhaps surprisingly to many, the drug of choice for nausea and vomiting caused by stimulation of the chemoreceptor trigger zone–the No. 1 mechanism for nausea in patients nearing the end of life, Dr. Steven Pantilat said at the annual meeting of the Society of Hospital Medicine.
“Haloperidol is the most potent dopamine-2 antagonist at the chemoreceptor trigger zone. We don't think of it that way. We don't think of it for this purpose. But it actually is a terrific drug, and it's the one we use now as our first-line agent,” said Dr. Pantilat, director of the palliative care program at the University of California, San Francisco.
He advocated selecting antiemetics for palliative care patients based on the probable mechanism underlying the symptoms. Clues as to the likely mechanisms come from the history, along with an evaluation that may involve an oral inspection, an abdominal exam, a rectal exam to rule out fecal impaction, laboratory tests, and in some cases brain or abdominal imaging.
Here are the chief mechanisms for nausea and vomiting in end-of-life patients, and the drugs of choice for each:
P Chemoreceptor trigger zone. This can be activated by drugs including opioids, digoxin, NSAIDs, and antibiotics. It can also be activated by metabolic derangements including hypercalcemia and hepatic failure, or by chemotherapy. Dopamine and serotonin are the main mediators.
The dosing of haloperidol is 0.5-2 mg intravenously every 6 hours. Oral prochlorperazine at 10 mg every 6 hours works well, too, provided a patient can take it.
For chemotherapy-induced nausea and vomiting, the 5-HT3 antagonists ondansetron and granisetron are very effective. Good data support their use in this setting as well as in postoperative nausea, but patients seem to get these drugs for all sorts of other types of nausea, too. Dr. Pantilat said he used to frown on this practice because it's not evidence based and the drugs are very expensive; however, he has seen so many anecdotal good results that he has recently become more open to turning to ondansetron and granisetron when first-line drugs for various forms of nausea aren't working.
Lorazepam is effective for prevention of anticipatory nausea in patients preparing to return to the chemotherapy infusion center. But it won't help unless it is given before the anticipatory nausea has set in.
P Vagal afferent nerve. This prominent mechanism for nausea and vomiting is mediated by histamine receptors in the brain. Common underlying causes include GI stretch due to constipation or bowel obstruction, mucosal irritation due to thrush, and peritoneal carcinomatosis or other external causes of nerve irritation.
Dr. Pantilat considers the drug of choice to be promethazine at 12.5-25 mg every 6 hours intravenously, orally, or rectally. It's a highly potent binder of the histamine receptor but is also quite sedating, so caution is warranted in giving it to patients who might vomit. Metoclopramide is useful when the underlying cause of vagal afferent nerve irritation is gastroparesis or partial bowel obstruction.
P Higher cortical structures. When metastases, infection, or edema press on the brain, directly stimulating the medullary vomiting center, the treatment of choice is dexamethasone at a typical starting dose of 2-4 mg intravenously or orally every 6 hours to reduce swelling. If necessary, Dr. Pantilat will go as high as 10 mg.
Dexamethasone is also the drug of choice for intractable, unrelenting nausea and vomiting unresponsive to other antiemetics, although that's not common in palliative care.
“Many palliative care programs use steroids very freely to make people feel good, to try to stimulate appetite, for pain–particularly in the setting of metastases, and for nausea. There are a lot of good reasons, particularly at the end of life, to see this as a drug that can make people feel better in a lot of ways,” he said.
Resources on Palliative Care
Here are several resources on palliative care that Dr. Pantilat recommends as particularly helpful:
P Fast Facts. One-page reports for clinicians on roughly 175 palliative care issues including dyspnea management, running a family conference, and how to use methadone. Available free for downloading onto a PDA through the Medical College of Wisconsin at
www.eperc.mcw.edu/ff_index.htm
P Primer of Palliative Care, fourth edition. Available for purchase from the American Academy of Hospice and Palliative Medicine at
P Perspectives on Care at the Close of Life. An ongoing JAMA series coedited by Dr. Pantilat available free online at
http://jama.ama-assn.org/cgi/collection/endoflife_care_palliative_medicine