Chapter 11: Symptom control and care towards the end of life
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Source: Adapted from Twycross et al. ([156]).
Nausea and vomiting
Definition
Nausea
Sanger and Andrews ([132]) describe nausea as a ‘warning’ to inhibit any further ingestion of potentially harmful substances. Nausea (and vomiting) is primarily a defence mechanism; however, it also occurs as a side‐effect of both disease and treatment.
Vomiting
Vomiting (or emesis) is an objective experience that involves the forceful movement and elimination of the contents of the stomach by the constant action of the abdominal muscles with the opening of the gastric cardia (Sanger and Andrews [132]). Vomiting and the associated sensation of nausea are significant and distressing symptoms that patients may experience as a result of either disease or treatment (Bennett [11]). Vomiting can also be a warning sign of deterioration (Frese et al. [50]), a defence mechanism against ingested toxins or poisons, or a symptom of bowel obstruction. The most common causes are outlined in Table 11.4.
Table 11.4 Common causes of nausea and vomiting in palliative care
| Cause | Examples |
|---|---|
| Toxins |
|
| Metabolic conditions |
|
| Organ failure/disorders of viscera |
|
| Neurological conditions |
|
| NSAIDs, non‐steroidal anti‐inflammatory drugs. |
Anatomy and physiology
The pathophysiology of nausea and vomiting is complex (Figure 11.8); two main centres within the brainstem are involved: the chemoreceptor trigger zone (CTZ) and the vomiting centre (Kelly and Ward [73]). Vomiting is ultimately controlled by the vomiting centre, which receives input from a wide range of sources. Some of these inputs are directly connected to the vomiting centre but most are directed through the CTZ (Kelly and Ward [73]). The CTZ is an area of the brain that is not fully separated from the blood by the blood–brain barrier, allowing it to detect chemicals in the blood and cerebrospinal fluid and initiate vomiting where necessary. It is also stimulated by the vagus and vestibular nerves, which receive signals from the gut and inner ear respectively (Bennett [11], Kelly and Ward [73]).
Figure 11.8 The emetic pathway.
Source: Reproduced from Kelly and Ward ([73]) with permission of EMAP Publishing Ltd.
The causes of vomiting are often multifactorial and therefore thorough assessment of the risk factors, precipitating factors and alleviating factors is key to identifying effective strategies for managing this symptom.
Related theory
Post‐operative nausea and vomiting affect up to 30% of surgical patients (Gan et al. [52]) (this is further described in Chapter c16: Perioperative care). Around 40–80% of cancer patients receiving chemotherapy experience nausea and vomiting (dependent on the regime and agents used) (Del Fabbro et al. [34]). Nausea and vomiting are unpleasant symptoms and a systematic review demonstrated that in patients with advanced disease the prevalence of this symptom is between 6% and 68%. Less is known about the prevalence of vomiting; however, while these symptoms are separate, they often occur together (Hardy et al. [58], Solano et al. [142]). Twycross et al. ([157]) report that nausea and vomiting are experienced by up to 70% of patients in their last week of life.
Evidence‐based approaches
Anticipated patient outcomes
The patient will be free of symptoms that are distressing and/or having an impact on their quality of life.
Assessment
Assessment may either focus on risk factors (in the case of post‐operative nausea and vomiting, in order to prevent or minimize the symptom occurring) or focus on identifying causative factors. Risk assessment tools for post‐operative nausea and vomiting consider a range of factors relating to the patient themselves (e.g. gender, age, history of motion sickness, smoker status), the surgical procedure (e.g. duration, open versus laparoscopic, type of surgery) and the anaesthetic (e.g. type of agent, duration, premedication, use of opioids) (Hambridge [57]). In those patients who are experiencing nausea and vomiting associated with other causes, a consistent and systematic approach should be used to assess symptoms and determine the cause (Kelly and Ward [73]). It is helpful to consider reversible causes alongside goals of care to determine the right treatment actions (Walsh et al. [160]). Anticipatory, acute or delayed chemotherapy‐induced nausea and vomiting can be reported using self‐assessment tools (Molassiotis et al. [96]), although strict adherence to pharmacological guidelines is paramount for optimal management irrespective of the phase (Molassiotis et al. [96]).
Assessment of nausea and vomiting at the end of life primarily requires detailed history taking and physical assessment. The most common causes of nausea and vomiting at the end of life are outlined in Table 11.4. Further diagnostic tests may be required to confirm the cause; however, the risks and benefits of carrying out such tests should be considered, especially at the end of life. Del Fabbro et al. ([34]) suggest that, when the cause of nausea and vomiting cannot be confirmed, an empirical approach (treatment initiated based on a ‘best guess’ of the cause) may be more suitable.
Vomiting is a significant yet complex symptom that requires a multifactorial approach to assess, prevent and manage it effectively.
Non‐pharmacological approaches
There are a range of non‐pharmacological strategies available to manage nausea and vomiting. First, consideration needs to be given to any precipitating factors that can be controlled or removed, such as exposure to food smells or malodour, or large meals. Complementary therapies, such as acupressure and acupuncture (Abraham [1], Lee et al. [82]) and aromatherapy (Hines et al. [62]), may be used but the evidence base for their effectiveness is relatively weak. Interventions including progressive muscle relaxation techniques (Charalambous et al. [24]) and hypnosis (Richardson et al. [126]) have been found to be effective in reducing nausea and vomiting associated with chemotherapy, but more research is required to establish the wider effectiveness of these approaches.
Pharmacological approaches
There is a wide variety of antiemetic drugs available, all of which act on one or more type of neuroreceptor, resulting in a central and/or peripheral effect. Antiemetics and their receptor affinity sites can be found in Table 11.5. A Cochrane review in 2015 looked into the use of cannabinoids for chemotherapy‐induced nausea and vomiting, and it confirmed that the use of cannabinoids may be helpful in the management of this refractory symptom (Smith et al. [141]). Bennett ([11]) identifies nine categories of antiemetics, a summary of which can be found in Box 11.5.
Table 11.5 Receptor affinity sites of selected anti‐emetics
| Drug | D2 | H1 | Muscarinic | 5HT2 | 5HT3 | NK1 | 5HT4 | CB1 | GABAmimetic |
|---|---|---|---|---|---|---|---|---|---|
| Aprepitant and fosaprepitant | – | – | – | – | – | +++ | – | – | – |
| Chlorpromazine | +++ | +++ | ++ | ++ | – | – | – | – | – |
| Cyclizine | – | ++ | ++ | – | – | – | – | – | – |
| Domperidone (does not normally cross the blood–brain barrier) | ++ | – | – | – | – | – | – | – | – |
| Haloperidol | +++ | – | – | – | +/− | – | – | – | – |
| Hyoscine hydrobromide | – | – | +++ | – | – | – | – | – | – |
| Levomepromazine | ++ | +++ | ++ | +++ | – | – | – | – | – |
| Lorazepam | – | – | – | – | – | – | – | – | +++ |
| Metoclopramide | ++ | – | – | – | + | – | ++ | – | – |
| Nabilone | – | – | – | – | – | – | – | +++ | – |
| Ondansetron and granisetron | – | – | – | – | +++ | – | – | – | – |
| Olanzapine | ++ | + | ++ | ++ | + | – | – | – | – |
| Prochlorperazine | +++ | ++ | + | +/++ | – | – | – | – | – |
| Promethazine | +/++ | ++ | ++ | – | – | – | – | – | – |
| +++, marked pharmacological activity; ++, moderate; +, slight; –, no or insignificant activity. |
Box 11.5
Classes of antiemetics
Antihistamines
Antihistamines block the histamine H1 receptor and are widely used. The main side‐effects are the sedative potential and anticholinergic effects (e.g. dry mouth, constipation). Cyclizine tends to be less sedating than other antihistamines and is commonly used as a first‐line treatment for post‐operative nausea and vomiting or motion sickness.
Dopamine antagonists
These act by blocking the dopamine D2 receptors in the chemoreceptor trigger zone (CTZ). Some antipsychotic drugs, such as the phenothiazines, have a strong affinity for these receptors but also block D2 receptors elsewhere, leading to side‐effects such as restlessness and tremors, which may limit their use as antiemetics, particularly in very young or older patients (Bennett [11]). Metoclopramide and domperidone act on D2 receptors in the CTZ but also on receptors in the gastrointestinal tract, which can reduce abdominal bloating. There is a particular risk of neurological side‐effects with longer‐term use and higher doses (BNF [14]). Levomepromazine is a broad‐spectrum antiemetic, which means it acts on a range of receptors; it also has sedating and analgesic effects and so is often used in the palliative care setting.
5‐HT3 antagonists
These are regarded as highly effective antiemetics that block 5‐HT3 receptors in the CTZ and the gastrointestinal tract. They are commonly used to prevent chemotherapy‐induced nausea and vomiting.
Steroids
Dexamethasone, a corticosteroid, is recognized for its antiemetic effect (Warren and King [161]), and is often used in conjunction with other antiemetics, although its mechanism of action is not clear.
Other antiemetics
Other categories of antiemetic include:
- benzodiazepines, which work in the central nervous system to inhibit the GABA (gamma‐aminobutyric acid) neurotransmitter
- anticholinergics, such as hyoscine hydrobromide, which acts directly on the vomiting centre
- cannabinoids, which inhibit nausea and vomiting caused by substances that irritate the CTZ, although the precise mechanism of action is not clearly understood.
Neurokinin‐1 antagonists are a relatively new category of antiemetic that act on NK1 receptors in the CTZ. They have been found to be most effective in the treatment of chemotherapy‐induced nausea and vomiting when used in conjunction with an HT3 antagonist and dexamethasone (BNF [14], Dikken and Wildman [40]).
Procedure guideline 11.2
