Gunnar Baatrup (ed.)Multidisciplinary Treatment of Colorectal Cancer10.1007/978-3-319-06142-9_26

26. Nausea

Rune Svensen¹

(1)

Department of Gastroenterological and Acute Surgery, Haukeland University Hospital, NO-5021 Bergen, Norway

Rune Svensen

Abstract

Nausea and vomiting represent major challenges in the management of the patient with advanced cancer. An understanding of possible underlying causes as well as basic knowledge of the various receptors most commonly involved will prove useful in tailoring an effective symptomatic treatment of the individual patient. After having identified and corrected any underlying cause, a systematic use of the available antiemetics should be tried while at the same time paying attention to the environment surrounding the patient, removing as many of the emetic stimuli as possible.

Nausea is a frequent problem in palliative care, occurring in 20–30 % overall, with an increasing tendency in the terminal phase, when approximately 70 % will be affected. It is quite frequently highly distressing to the patient and at times notoriously difficult to treat. Nausea is a complex phenomenon. A number of different organs are involved, and the symptom is mediated through a large number of receptors, many of which are most likely yet to be identified [1, 2].

Nausea may be considered a central nervous problem more than a visceral one. Several key locations exist:

The vomiting centre in the brainstem with its chemoreceptors.
The chemoreceptor trigger zone. Interestingly this is located in an area of the brain not protected by the blood-brain barrier, thus enabling circulating chemical substances to affect the brain directly.
The medullary area postrema and the solitary tract receiving signals from both chemo- and mechanoreceptors from distant organs, including the GI tract.
Cerebral cortex, reacting to conscious stimuli such as anxiety, taste, smell and visual impulses.
Meninges with its mechanoreceptors reacting to pressure changes and stretching.
The inner ear with the vestibular system reacting to motion.
Gastrointestinal tract with mechano- and chemoreceptors on both mucosal and serosal surfaces.

Chemoreceptors Simplified [3]

A number of chemoreceptors involved in nausea and vomiting have been identified. Furthermore, several drugs have become available to address some of these receptors, making them useful tools in the treatment of the nauseous patient. However, the complexity of the problem and the multitude of potential culprits make the choice of the ideal drug a challenge for the physician.

The serotonin (5-hydroxytryptamine, 5-HT) receptors in the chemoreceptor trigger zone and GI tract:
- 5-HT₂
- 5 HT₃
- 5-HT₄
Dopamine (D₂) receptors in the area postrema, solitary tract, chemoreceptor trigger zone and GI tract
Muscarinic acetylcholine receptors in the vomiting centre and the vestibular system
Gamma-aminobutyric acid (GABA) receptors in the cerebral cortex
Histamine receptors in the vomiting centre

Approaching the Problem

When faced with a nauseous cancer patient, the physician will find himself far less aided by well-founded therapeutic algorithms than if the patient complained of pain. There is, for example, no parallel to the WHO pain ladder for nausea. Instead the handling of the patient will depend on the physician’s ability to analyze and understand the patient’s total situation, utilize knowledge of basic nausea physiopathology and act accordingly. Although the problem of nausea in the cancer patient is a challenge, a systematic approach will in most cases enable us to solve the problem, at least alleviate it.

Identify and Treat Underlying Cause, if Possible

Biochemical Disorders

Hypercalcaemia is not uncommon in advanced cancer cases and may be caused by the release of parathyroid hormone-related peptides (PTHrP) or through the release of calcium from skeletal metastases. Hypercalcaemia produces a nausea which is notoriously resistant to antiemetics and should be treated by reducing the levels of serum ionized calcium, for example, by rehydration, diuretics and bisphosphonates.

Uraemia.

Ketoacidosis.

Infection.

Tumour toxins.

Dehydration, for example, caused by fistulas and high output stomas or reduced intake.

Adverse drug reactions. Be especially aware of opioids, NSAIDs, digitalis and antibiotics. In cases with liver or renal deficiency, drug metabolism may be altered, and the patient might develop adverse effects even when the drug has been taken for a long period of time.

Treatment related (irradiation, chemotherapy, immunotherapy, hormone therapy).

Effects of cachexia and anorexia, which are mostly cytokine mediated [4].

Gastrointestinal Disorders and Disturbances

Poor oral hygiene, oral ulcerations, fungal infection or altered taste

Constipation, for example, caused by opioids

Autonomous dysfunction causing dysphagia, delayed gastric emptying and intestinal pseudo-obstruction, for example, caused by peritoneal, retroperitoneal or mesenteric metastases

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