Effectiveness of antiemetics on the basis of cause

Clinical question

What is the effectiveness of the administration of antiemetics chosen on the basis of the cause in patients with nausea and/or vomiting as a result of cancer, heart failure, ALS, MS, COPD or renal failure in the palliative phase?


For patients in the palliative phase with nausea and vomiting as a result of other causes than chemotherapy, ileus, brain metastases or vestibular causes, it is recommended to choose an empirical approach with metoclopramide or domperidone as first choice.


There are many causes of nausea and/or vomiting in patients in the palliative phase [Ang 2010; Glare 2011; Gupta 2012; Harris 2010; Wood 2007]. Various neurotransmitters may play a role in this (such as dopamine, serotonin, histamine or acetylcholine), possibly in conjunction with the underlying cause.

Antiemetics (such as dopamine-antagonists, serotonin-antagonists, antihistamines and anticholinergic agents) affect specific neurotransmitters. It is the question whether the effectiveness of antiemetics is dependent on the underlying cause and the neurotransmitters involved. In the following text, the prevention and treatment of nausea and vomiting as a result of chemotherapy will not be addressed.

Literature discussion

Literature research yielded two studies that were directly related to the clinical question [Bentley 2001; Stephenson 2006]. There were also a number of reviews that paid attention to this approach [Ang 2010; Glare 2011; Gupta 2012; Harris 2010; Wood 2007].
Bentley performed a prospective audit on 37 patients (40 admittances, three patients were admitted twice) with an advanced stage of cancer with nausea and vomiting, who were admitted to a palliative care unit [Bentley 2001]. On admittance, a standard questionnaire was filled in for each patient, in which information was filled in about the patient, the disease and treatment, the symptoms and possible causes. The causes were subdivided into seven groups (with an associated choice of antiemetic): chemical/metabolic (haloperidol) (n=12), gastroparesis/obstruction of the gastric outlet (metoclopramide or domperidone) (n=14), regurgitation (various agents) (n=4), ileus (various agents) (n=5), central nervous system/radiotherapy (cyclizine) (n=1), movement related (cyclizine) (n=0) and other causes/cause unknown (various agents) (n=4). Fifty-nine potentially reversible causes were identified: medication (30), constipation (11), renal failure (7), infection (3), fear (3), gastritis (3) and high obstruction (2). The patients scored the level of nausea and vomiting daily. Metoclopramide (n=15) and haloperidol (n=11) were the most commonly used antiemetics. Domperidone (n=2), cyclizine (n=3), levomepromazine (n=5), butylscopolamine (n=1) and octreotide (n=1) were also used in the first line. Medication was administered orally in 37% of cases and subcutaneous in 63% of cases (as a bolus or continuous). Nausea disappeared completely in 82% of patients, vomiting in 84%.

Stephenson performed a prospective study of 61 patients with an advanced stage of cancer with nausea and vomiting, who were admitted to a hospice [Stephenson 2006]. The treating physician was asked to assign the cause of the nausea to one of six categories (with associated treatment): chemical, including medication, metabolic causes and infections (haloperidol, n=20), delayed gastric emptying, including tumour, hepatomegaly, medication, ascites, gastritis (metoclopramide, n=27), visceral/serosal, including ileus, gastric bleeding, enteritis, constipation (cyclizine, n=19), central nervous system, including increased intracranial pressure and leptomeningeal metastases (cyclizine, n=50), vestibular (cyclizine, n=0) and anxiety (benzodiazepines, n=4). If there was insufficient effect with the first antiemetic, levomepromazine and/or dexamethasone were prescribed (independent of the cause). On the last evaluation (after one week), 8% did not use antiemetics, 49% one antiemetic, 33% two antiemetics and 10% three antiemetics. The most common drugs were metoclopramide (n=27), levomepromazine (n=27) and dexamethasone (n=17). Other drugs used were haloperidol (n=5), cyclizine (n=4), octreotide (n=4), hyoscine butylbromide (n=2). After 48 hours 44% of the evaluable patients (n=54) did not suffer from nausea and 69% had no vomiting; after 1 week these percentages were 56% and 89% respectively (n=36).

The studies by Bentley and Stephenson show that the approach used for the choice of antiemetic based on cause is reasonably effective in the treatment of nausea and vomiting in patients with an advanced stage of cancer. However, the lack of a control group implies it cannot be concluded that this approach has added value above a structural empirical approach, in which the choice of antiemetic is independent of the cause. This opinion is shared by Ang, Glare and Gupta [Ang 2010; Glare 2011; Gupta 2012]. Harris and Wood propagate the aetiology-based approach [Harris 2010; Wood 2007]. As an argument for this, Wood states that this approach facilitates a systematic approach, takes all possible causes into account and minimises the chance of overtreatment.

It has not been proven that choosing an antiemetic based on the cause of the nausea and/or vomiting has added value above an empirical approach in which the choice of drug is independent of the cause.
Bentley 2001; Stephenson 2006

While not founded on comparative research, it is rational to choose a prokinetic agent such as metoclopramide or domperidone for nausea and vomiting resulting from a gastroparesis (see also clinical question 11). If an empirical approach is taken it is also rational to choose metoclopramide or domperidone as first choice because these drugs have a broad spectrum of action: they advance gastric emptying (peripheral action) and in addition also have a central antidopaminergic effect.

The treatment of nausea and vomiting due to an ileus or due to brain metastasis, and the prevention and treatment of nausea and vomiting as a result of chemo- or radiotherapy require a different approach. If the cause is vestibular, a scopolamine patch is the agent of first choice; however, this cause is extremely rare in patients in the palliative phase.

Although there is a lack of information about the effect of antiemetics for nausea and vomiting in patients with other diseases than cancer, the recommendation makes no distinction between cancer patients and patients with other life-threatening disorders.

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