NAUSEA & VOMITING

Nausea and vomiting occur in 60% of terminal cancer patients at some stage but tend to be intermittent (in one study 21 % of patients reported nausea and vomiting at each evaluation).

The plan of management is:

1. History and examination

2. Consider causes

3. Choose anti-emetic(s)

4. Choose route

5. Change anti-emetic regime

6. Consider steroids

7. Consider ranitidine

8. Change or reduce opioid

9. Remember anxiety

10. Celiac plexus block (very rarely indicated)

There are usually several causes contributing to nausea (for example, anxiety, a new NSAID, constipation, and the strong smell of cooking all playing a part).

It can be helpful to think in terms of a nausea threshold (analogous to a pain threshold) and to consider several approaches to raising the nausea threshold.

1. History and examination – A past history of peptic ulcer may be relevant - a peptic ulcer may cause nausea with little pain (masked by steroids or analgesics).

Try to discover if there is a pattern to the nausea:

• After certain drugs

• After meals (if so, try metoclopramide)

• On movement (try cyclizine)

• In certain situations (anxiety related)

• With certain smells

Ask about:

• Epigastric pain (?gastritis)

• Pain on swallowing (?oral thrush)

• Pain on standing (?mesenteric traction)

• Thirst (?hypercalcemia)

• Hiccup (?uremia)

• Heartburn (?small stomach syndrome)

• Dysuria (?urinary tract infection)

• Constipation (?constipation!)

«  Nausea can become a conditioned response.

The most dramatic example of a conditioned response is nausea after chemotherapy, then nausea on arriving at the chemotherapy clinic, then finally on seeing the appointment card for the chemotherapy clinic. For this reason, to abolish prolonged nausea may require high doses of anti-emetics for a few days to break the association of events and surroundings with nausea.

«  Palliative radiotherapy does not cause nausea unless the field includes the celiac plexus (anterior to L1).

Examination:

• Mouth (?oral thrush)

• Speech, arms, legs (?brain metastases)

• Abdomen (?hepatomegaly ?obstruction)

• Rectal (?constipation)

• Bloods (urea, calcium, drug levels)

• Mid-stream clean catch urine specimen

«  Neurological signs are usually obvious if nausea or vomiting are due to brain metastases. Papilledema is an unreliable sign of raised intracranial pressure.

2. Causes of nausea (which may respond to treatment other than anti-emetics):

• Drugs

• Oral thrush

• Brain metastases

• Anxiety

• Gastric irritation

• Small stomach syndrome

• Intestinal obstruction

• Constipation

• Hypercalcemia

• Uremia

• Low grade urinary tract or pulmonary infection

It is useful to remember this list and apply it when nausea is a problem in advanced disease. Reversible causes are often found, but it is important to abolish nausea as quickly as possible and to use anti-emetics with other treatments initially.

Drugs that can cause nausea include:

• Opioids

• NSAIDs

• Antibiotics (metronidazole, erythromycin)

• Digoxin (consider drug level)

• Estrogens

• Cytotoxics

• Many others!

Stop as many drugs as possible. Remember, metronidazole and alcohol together will cause headaches and nausea.

It can be important to discover whether uremia is the cause (even though it is untreatable) because it means you can stop looking for other causes, you can explain to the patient and family why nausea and vomiting are present (“Is the cancer spreading, doctor?”), and because chlorpromazine is usually the best drug.

3. Choose an appropriate anti-emetic. Haloperidol is effective as a twice a day regime. Chlorpromazine may be more suitable if sedation is needed, or if hiccups are troublesome. Metoclopramide is useful if poor gastric emptying is a problem. (see Phenothiazines)

Cyclizine is particularly useful if there is an element of motion sickness or as a logical addition to a drug acting at the CTZ. Methotrimeprazine as a continuous subcutaneous infusion is the most powerful anti-emetic but can cause drowsiness. (see Anti-emetics)

4. Choose the appropriate route:

• Oral

• Suppository

• IM injection

• Subcutaneous

The oral route is best for prophylaxis. If a patient is feeling nauseated or vomiting more than two or three times a day, oral absorption is reduced and suppositories or injections are needed for at least 24 hours before trying oral anti-emetics again.

Some patients are well-controlled on suppositories, others dislike them or cannot use them.

A continuous subcutaneous infusion is useful for severe nausea and vomiting to avoid repeated injections. (see Subcutaneous Infusions) 

«  In nausea there is a reflux of duodenal contents into a relaxed stomach, therefore there is poor absorption of oral drugs.

5. Change anti-emetic regime – Try full doses of one anti-emetic before changing to another. Sometimes the patient needs two (and rarely three) anti-emetics for good control. It is logical to combine anti-emetics that act at different sites, for example, haloperidol (CTZ) with cyclizine (vomiting center). (The combination of haloperidol with metoclopramide is likely to result in dystonia and stiffness, and should be avoided.)

6. Consider steroids – A trial of high dose steroids is considered in three situations which can cause nausea and vomiting:

• Raised intracranial pressure

• Hypercalcemia

• Malignant pyloric stenosis

Apart from these, steroids can have a direct anti-emetic effect. The mechanism of action is unknown but the usefulness of steroids in cytotoxic-induced sickness is documented. It is common for steroids to reduce or abolish nausea in advanced malignancy, and they should be tried for severe nausea resistant to anti-emetics. (see Steroids)

7. Consider an H2 receptor antagonist – Gastric irritation can occur with NSAIDs. Epigastric discomfort may be masked by steroids and analgesics. H₂ receptor antagonists should be considered for nausea especially if there is a history of peptic ulceration or if nausea is associated with heartburn. The usual dose is ranitidine 150mg 2 times a day. A trial of ranitidine may be indicated in nausea resistant to anti-emetics.

8. Consider changing or reducing the opioid drug – Nausea related to morphine can occur because the patient is taking more morphine than required. A reduction in pain occurs (either spontaneously, or following radiotherapy or a nerve block) and the previous dose of morphine is now too high, commonly causing drowsiness, but also occasionally nausea.

30% of patients experience mild nausea for a few days after starting morphine. An anti-emetic (such as thiethylperazine 10mg 2 to 3 times a day, prochlorperazine 5mg 3 times a day, or haloperidol 0.5mg to 1.5mg at bedtime) can be prescribed to prevent this nausea.

About 1% of patients are intolerant of morphine, which causes severe, persistent nausea and vomiting despite treatment with anti-emetics. These patients require an alternative opioid analgesic (hydromorphone, oxycodone, buprenorphine, methadone).

All these drugs can themselves cause nausea (particularly buprenorphine in about 20% of cases) but true morphine-related nausea can be abolished in an individual by changing to one of these opioids. (see Analgesics)

9. Nausea and anxiety – Anxiety can cause nausea. Nausea can cause anxiety. (“Is the cancer spreading?”) Some people react to anxiety by feeling nauseated. Relieving anxiety (often by sharing worries and fears) can help to reduce or abolish nausea.

10. Celiac plexus block – A celiac plexus nerve block should be considered for intractable nausea resistant to other treatments. It can abolish nausea - possibly because the trunk of the left vagus passes through the plexus. In fact, intractable nausea is extremely rare if the regimes described in this section are applied. (Intractable nausea may very rarely be due to a brainstem metastasis involving the vomiting center.) (see Celiac Plexus Block)

Vomiting with little or no nausea can occur in:

1. Regurgitation

2. High intestinal obstruction

3. Raised intracranial pressure

1. Regurgitation is usually seen in carcinoma of the esophagus with total dysphagia. It is usually obvious from the history of food sticking and coming back (the food contains no acid). A pharyngeal pouch can also cause regurgitation.

2. High intestinal obstruction – Malignant pyloric stenosis is associated with vomiting of large volumes (300ml to 600ml) of undigested food some hours after a meal, with little preceding nausea. The force of the vomit can make it come down the nose. There is no bile in the vomit. Duodenal obstruction (due to carcinoma of the pancreas) produces a similar pattern. A “vomit chart” is occasionally helpful to see the typical pattern if the patient is a poor historian. A palliative gastro-enterostomy can prevent the problem. High dose steroids (dexamethasone 8mg per day – initially by IM injection) can reduce peri-tumor edema and improve gastric emptying.

3. Raised intracranial pressure is classically said to cause early morning headaches and vomiting, with little or no nausea. In fact, in advanced disease due to cerebral primary tumors or cerebral metastases both headache and vomiting are uncommon.

«  It may not be possible to abolish vomiting, but patients can accept occasional vomiting provided they are free of nausea.

The author and publisher have taken precautions to ensure that the information in this book is error-free. However, readers must be guided by their own personal and professional standards of good practice in evaluating and applying recommendations made herein. The contents of this book represent the views and experience of the author, and not necessarily those of the publisher.