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Nausea and vomiting

Definition

Nausea and vomiting are often referred to as a single symptom but are separate physiological conditions (Glare et al. [93], Heskeeth [106]):

Nausea is defined as an unpleasant feeling of the need to vomit and is often accompanied by autonomic symptoms such as pallor, cold sweat, salivation and tachycardia (Heskeeth [106]).
Vomiting (emesis) is defined as the forceful expulsion of gastric contents through the mouth (Twycross and Black [290]).
Retching is defined as the gastric and oesophageal movements of vomiting without the expulsion of vomit (Twycross and Black [290]). It may occur in isolation without discharge of gastric contents from the mouth and is often referred to as ‘dry heaves’.
Chemotherapy‐induced nausea and vomiting (CINV) is one of the most common side‐effects of chemotherapy; however, persistent nausea and vomiting are now fairly rare with the use of the modern antiemetic drugs. CINV is often grouped into three phases, with two additional subclassifications (Molassiotis and Borjeson [185], Nasir and Schwartzberg [192]):
- Acute: within 24 hours of receiving chemotherapy.
- Delayed: from 24 hours after chemotherapy. Seldom persists beyond 1 week.
- Anticipatory: occurs prior to any chemotherapy and is a learned response to previous treatments.
- Breakthrough: development of symptoms (nausea and vomiting) despite standard antiemetic therapy which require treatment with an additional pharmacological agent.
- Refractory: patients who have failed on both standard and rescue medication.

Anatomy and physiology

Several neural structures and a variety of neurotransmitters and receptors have been identified that relate to nausea and vomiting. Most of the relevant receptors are excitatory and induce nausea and vomiting when stimulated (Twycross and Black [290]). The afferent and efferent reflexes that result in nausea and vomiting are thought to be stimulated at brainstem level through the chemotherapy trigger zone and integrative trigger zone (Figure 26.6).

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Figure 26.6 The emetogenic pathway. Source: Harris ([103]). Reproduced with permission of Oxford University Press, permission conveyed through Copyright Clearance Center, Inc.

The chemoreceptor trigger zone (CTZ) is located in the floor of the fourth ventricle and is outside the blood–brain barrier (Pleuvry [233]). As it sits outside the blood–brain barrier it is exposed to various noxious agents such as toxins, biochemical products and drugs, borne in the blood and cerebrospinal fluid (O'Brien [217]). Neural pathways from the CTZ provide the main stimulus to the vomiting centre (Mannix [162], Pleuvry [233]). The CTZ is stimulated by chemicals in cerebrospinal fluid and blood as well as vestibular and vagal afferents and contains receptors for dopamine (D2), serotonin (5‐HT3), acetylcholine (ACH) and opioids (MU2).

The vomiting centre (VC) is situated in the medulla oblongata outside the blood–brain barrier and is thought to co‐ordinate the vomiting process (Mannix [162], Pleuvry [233]). The VC receives input from the CTZ, vestibular apparatus (the part of the internal ear concerned with balance), glossopharyngeal and splanchnic nerves, cerebral cortex, thalamus, hypothalamus and the vagus nerve through the stimulation of stretch of mechanoreceptors and activation of 5‐HT3 receptors in the GI tract (Mannix [162]). These pathways then prompt the vomiting reflex, which stimulates peristalsis in the upper GI tract, the pylorus and oesophagus relax, and the intercostal muscles, diaphragm and abdominal wall contract culminating in the forced expulsion of the gastric contents through the mouth past a closed glottis (Nasir and Schwartzberg [192]).

Evidence‐based approaches

Background

An estimated 60% of patients who receive chemotherapy as part of their treatment experience some degree of nausea and vomiting (Bender et al. [17], Warr [303]). It is reported as one of the most dreaded side‐effects and can have both a physical and psychological effect on the patient (Molassiotis and Borjeson [185]). Cancer itself or the many treatments used can cause nausea and vomiting (Table 26.9). It is therefore important to ascertain what treatment the patient is on in order to rule this out as a cause. Do not assume that nausea and vomiting are chemotherapy related. Many chemotherapies have no significant emetic potential, and chemotherapy will seldom cause nausea and vomiting more than 1 week after administration (London Cancer Alliance [151]).

Table 26.9 Potential causes of nausea and vomiting in cancer patients

System	Possible causes
Gastrointestinal	Intestinal obstruction Gastric outlet obstruction Constipation Gastroparesis Ileus Gastritis/dyspepsia Ascites
Metabolic	Hypercalcaemia Renal failure Electrolyte disturbance Liver failure
Toxic	Chemotherapy Radiotherapy Infection
Drugs	Gastrointestinal irritation	Non‐steroidal anti‐inflammatory drugs Iron supplements Antibiotics Tranexamic acid
	Gastric stasis	Opioids Tricyclic antidepressants Phenothiazines Anticholinergics
	Chemoreceptor trigger zone stimulation	Opioids Digoxin Anticonvulsants Antibiotics Imidazoles Cytotoxics
	5‐HT3 receptor stimulation	Cytotoxics Selective serotonin reuptake inhibitors
Other	Raised intracranial pressure, e.g. brain metastases Vestibular problems Pain Cough Pharyngeal irritation, e.g. Candida Psychological – fear, anxiety

Source: Adapted from Warr ([303])

Within this section nausea and vomiting will be referred to as ‘emesis’ as this incorporates both symptoms along with retching. CINV will be discussed, however the assessment and management of emesis in the acutely unwell patient is the same. The pharmacological management will differ according to the cause.

Also, as part of the global assessment, the following risk factors can contribute to a greater experience of emesis for some patients (Molassiotis and Borjeson [185]):

below the age of 40
female
susceptibility to nausea when eating food
taste of the drug during administration
low alcohol use
history of labyrinthitis and vestibular disturbance
susceptibility to motion sickness
a desire to control the choice of antiemetic used.

Chemotherapy regimens can be classified according to their emetic potential and treatment recommended accordingly (National Comprehensive Cancer Network [NCCN] [197]). Several types of CINV exist (Janelsins et al. [119]). CINV can result in altered nutritional and performance status and poor quality of life, which may affect patients’ ability and desire to receive additional treatment. Prevention or effective treatment of CINV is, therefore, an important aspect of successful therapy. Owing to the potential side‐effects associated with antiemetic agents themselves (e.g. constipation, headaches), use of the lowest possible effective antiemetic dose is desirable. Antiemetic regimens should be chosen based on the emetogenic potential of the chemotherapy regimen as well as patient‐specific risk factors (London Cancer Alliance [151], Nasir and Schwartzberg [192]).

Assessment

When treatment‐induced emesis is suspected, initial assessment follows as outlined in the introduction to this chapter but with the addition of the following specific questions:

History of presenting complaint

What chemotherapy is the patient on and when was the last treatment?
1. Are any of these drugs commonly associated with CINV?
Are they receiving any radiotherapy and to which area – when was their last treatment?
Frequency and nature of emesis?
1. Any blood noted in the vomit?
2. Does anything make it better or worse?
Any associated symptoms?
1. Is the emesis associated with any particular time of the day?
2. Any change in bowel movement?
  Signs of constipation, diarrhoea or bowel obstruction?
3. Any evidence of reflux or gastritis?
4. Abdominal pain?
Are they able to eat and drink as usual?
1. How much fluid are they able to drink and what type?
Any signs of dehydration – decreased urine output, fever, thirst, dry mouth?
Current medications – are they taking any antiemetics and how are they taking them?
What is the extent of their disease – known brain, bone or liver metastases?

Identify

Is the patient at risk of immunosuppression (chemotherapy or radiotherapy within the last 6 weeks, bone marrow transplant or disease‐related immunosuppression) as there may also be an underlying sepsis (± neutropenia)?

Obtain baseline observations

These should include temperature, pulse, blood pressure, respiration rate, oxygen saturations and the Early Warning Score. If the patient is showing signs of sepsis (see Neutropenic sepsis section), fluid resuscitation should be started before investigations are performed.

Initial investigations include FBC, U&Es, LFTs and bone profile. If sepsis is suspected add CRP, lactate and blood cultures.

Management

Pharmacological support

As previously stated, for many patients this is one of the worst side‐effects; providing a calm and dignified environment will help to calm them. The causes of nausea and vomiting in cancer patients can be multifactorial, therefore careful assessment is essential to explore the cause and identify any reversible causes (Roila et al. [254]). The basic principles of managing emesis with medication (as outlined in Tables 26.10 and 26.11) are as follows (Warr [303]).

Identify and treat underlying causes if possible.
If possible, discontinue any drugs thought to be responsible for nausea and vomiting.
Give antiemetics regularly.
Consider route – give parenterally if the patient is likely to vomit or has poor absorption.
Tailor antiemetic according to likely cause of nausea/vomiting and receptors involved.
Maximize dose before switching.
In a third of patients, there may be more than one cause of nausea/vomiting.
- Any added antiemetic should have a different mode of action.
- Use a broad‐spectrum antiemetic.
- Consider adding a second agent.
- Consider a broad‐spectrum antiemetic (e.g. levomepromazine) if CINV is multifactorial
Use the non‐oral route if vomiting prevents drug absorption (e.g. in bowel obstruction).

Table 26.10 Common causes of nausea and vomiting in cancer patients and treatment options

Cause	Treatment options
Anxiety	Lorazepam; antidepressants in the longer term: seek advice from the patient's GP or from the oncology team
Bowel obstruction	Levomepromazine or haloperidol or cyclizine
Chemotherapy	Treat according to emetogenic potential of drugs: Mild (level 1): domperidone or metoclopramide (do not use together) Moderate (level 2): levomepromazine (6.25 mg BD PO) or cyclizine or prochlorperazine (25 mg rectally). These agents replace metoclopramide/domperidone Severe (level 3): ondansetron (effective in acute – maximum use 3 days) or lorazepam (effective in anticipatory – 1 mg PO, IV or sublingual) or levomepromazine (SC infusion) or haloperidol (1–2 mg QDS PO or 1–3 mg TDS IV)
Constipation	Treat cause
Delayed gastric emptying	Metoclopramide
Drugsc26-note-0007 (non‐chemotherapy)	Stop drug if possible Haloperidol or levomepromazine
Gastric irritation	Treat cause (e.g. proton pump inhibitor) Metoclopramide if needed
Metabolic causes including hypercalcaemia	Treat cause Haloperidol or levomepromazine
Renal failure	Haloperidol or levomepromazine
Raised intracranial pressure	Treat cause Dexamethasone and cyclizine

^*	Common culprits include antibiotics, antidepressants, non‐steroidal anti‐inflammatory drugs and opiates. Source: LCA (2015). Reproduced with permission of London Cancer Alliance.
BD PO, twice a day per os, by mouth; IV, intravenous(ly); QDS, four times a day; SC, subcutaneous(ly); TDS, three times a day.

Table 26.11 Drugs used to control emesis and their classification. This list is not exhaustive; each trust may have local clinical guidelines

Putative site of action	Class	Example
Central nervous system
Vomiting centre	Anticholinergic Antihistamine 5‐HT2 antagonist	Hyoscine hydrobromide Cyclizine, dimenhydrinate Phenothiazines Levomepromazine
Central nervous system	Neurokinin‐1 antagonist	Aprepitant
Chemoreceptor trigger zone	Dopamine (D2) antagonist 5‐HT3 antagonist	Haloperidol, phenothiazines, metoclopramide, domperidone Levomepromazine Granisetron, ondansetron, tropisetron
Cerebral cortex	Benzodiazepine Cannabinoid Corticosteroid	Lorazepam Nabilone Dexamethasone
Gastrointestinal tract
Prokinetic	5‐HT4 agonist Dopamine (D2) antagonist	Metoclopramide Metoclopramide, domperidone levomepromazine
Antisecretory	Anticholinergic Somatostatin analogue	Hyoscine butylbromide, glycopyrronium Octreotide
Vagal 5‐HT3 receptor blockade	5‐HT3 antagonist	Granisetron, ondansetron, tropisetron
Anti‐inflammatory	Corticosteroid	Dexamethasone

Source: Adapted from Collis and Mather ([44]), Twycross and Black ([290]).

Non‐pharmacological support

It is important to acknowledge the place of non‐drug treatments (e.g. control of malodour, avoidance of large meals, avoidance of exposure to food smells that may precipitate nausea). It is key for the nurse to facilitate this. Some dietary considerations include:

Eating foods cold or at room temperature as they often smell less strongly than hot foods.
Avoiding fatty foods.
Eating carbohydrates.
Eating small, frequent meals.
Avoiding foods that increase the patient's nausea.
Educating family members who, in their desire to ‘do the right thing’, encourage the patient to eat more than they can comfortably manage.

It can be argued that the patient's favourite food should be avoided during episodes of nausea in case it provides a future stimulus for nausea and vomiting, so depriving the patient of a pleasurable experience.

Avoiding the sight and smell of food may reduce episodes of nausea. The inpatient should be protected from unpleasant odours, for example from bedside commodes, episodes of incontinence or malodorous wounds. Once the patient has finished eating, any remaining food should be quickly cleared away. Any used receptacles should be removed promptly after episodes of vomiting.

Other measures include the use of acupressure bands (see Chapter c23) and acupuncture (see Chapter c22) (Ezzo et al. [71], Pan et al. [223]).

Education

Non‐pharmacological interventions are based around educating the patient and their family in techniques that may help reduce the frequency and severity of symptoms, enhance the effect of antiemetics and increase the patient's sense of control.