Nausea and vomiting causes and complications

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Nausea and vomiting
— causes and complications
By Alan Worsley, MRPharmS, PhD, and Andrew Husband, MRPharmS, MSc

Nausea and vomiting are biological
defence mechanisms, associated
with a variety of stimuli and
conditions. This article explains
some of the common causes of
nausea and vomiting and the
complications that can arise

DAVID MACK/SPL
Computer artwork of the vomiting reflex

N
ausea is the word used to a result, the stomach expels the vomitus with aspiration of the stomach contents into the
describe the sensation of discom- great force into the mouth and out of the lung, potentially leading to aspiration pneu-
fort and unease in the stomach body. monitis and pneumonia.
and is derived from the Greek This sequence may be repeated in co-
word for sea-sickness (naus means ship). ordination with respiratory cycles, and The vomiting process
Nausea itself is not an illness but a symptom retrograde peristalsis from the small intestine
associated with a variety of conditions. Nau- to the stomach may refill the stomach sever- The act of vomiting is a complex physiolog-
sea and vomiting are produced by the same al times. Retching is a similar process to ically co-ordinated sequence. It is said to be
stimuli and can be viewed as a progressive vomiting, where the movements involved controlled by the vomiting centre in the
response to increased stimulus. are less severe and do not result in ejection brain. Generally, this is no longer considered
The act of vomiting (emesis) is caused by a of vomitus. to be a distinct anatomical structure, but is
series of changes within the gastrointestinal believed to involve a central pattern genera-
tract, in co-ordination with respiratory Complications If vomiting is left untreat- tor, similar to that which co-ordinates
movements. Generally, salivation precedes ed, in addition to causing distress, ventilation. The vomiting process is closely
the ejection of vomitus and there is a simul- hypokalaemic hypo-chloraemic alkalosis associated with the salivary, vagal and respi-
taneous increased volume of inspiration into (volume depletion, loss of gastric hydrogen ratory centres of the brain, and has several
the lungs, which increases abdominal pres- ions and alterations in the renin- excitatory inputs (see Panel 1, p186).
sure.The epiglottis closes and the soft palate angiotensin-aldosterone system) can result. Among these is the chemoreceptor trigger
of the mouth rises to prevent vomitus enter- Vomiting can also cause mucosal damage zone, as described in Panel 2 (p186).
ing the lungs. The pyloric region of the such as Mallory-Weiss tears, or rupture the The remainder of this article explains
stomach undergoes a strong contraction, oesophagus (eg, Boerhaave syndrome).A fall common causes of nausea and vomiting
while the fundus, cardiac sphincter and in haemocrit and subsequent endoscopy likely to be encountered in hospital practice.
oesophagus remain relaxed and the external should identify any bleed and associated
muscles of the anus and urethra contract. As physical damage. Gastrointestinal rupture as Treatment-induced
a result of vomiting is particularly dangerous
in alcoholics who have developed Chemotherapy-induced nausea and
Alan Worsley and Andrew Husband are senior
oesophageal varices. vomiting Chemotherapy-induced nausea
lecturers in pharmacy practice at the University of
Another complication associated with and vomiting (CINV) can be classified as
Sunderland
uncontrolled vomiting is the possible acute, delayed or anticipatory. Two further

JUNE 2007 • VO L . 1 4 H O S P I TA L P H A R M AC I S T • 185
are those cases where symptoms occur Post-operative nausea and vomiting
during subsequent cycles when control Post-operative nausea and vomiting
Panel 1: Excitatory inputs had been incomplete in previous (PONV) is a common condition associated
controlling the vomiting process chemotherapy treatment cycles.3 with general anaesthetic use and surgery. As
The pathophysiology of CINV is com- with all types of nausea and vomiting,
The vomiting centre is associated with plex. The vomiting centre receives input PONV is ultimately associated with dehy-
several excitatory inputs coming from: from the CTZ via 5-HT3, dopamine D2, dration, electrolyte disturbance and, rarely,
neurokinin-1 and muscarinic receptors; aspiration pneumonitis, all of which can
■ Receptors in the gastrointestinal from the gastrointestinal tract through vagal delay patient recovery. In addition, various
tract, responding to either chemical and visceral afferent pathways via 5-HT3 and post-surgical complications can occur as a
(5-hydroxytryptamine [5-HT] neurokinin-1 receptors; and from the result of severe PONV, such as wound dehis-
receptors) or intramuscular forces vestibular apparatus of the inner ear, which cence (where the force of retching causes
(histamine and acetylcholine controls motion sickness. Increasing evi- stitched wounds or anastomoses to burst)
receptors) dence has suggested that the gastrointestinal and problems for faciomaxillary patients
■ The labyrinths of the vestibular tract may initiate the emetic response, with wired jaws.
centres of the inner ear via cranial through a bundle of nerve fibres near the The causes of PONV are believed to be
nerve VIII (the vestibulocochlear vomiting centre called the nucleus tractus multiple, including the use of anaesthetics,
nerve) solitarius. drugs such as opiates and surgical factors. In
■ Intracranial pressure receptors The incidence of acute emesis is deter- terms of induction anaesthetics, etomidate is
■ The cerebral cortex, as a result of mined by the emetogenic potential of the associated with an increase in PONV
conscious stimuli to smells, tastes and chemotherapy used, the dose and efficacy of compared with propofol. For inhalation
conditioned reflexes antiemetic drug therapy, and patient vari- anaesthetics, halothane and enflurane are
■ Pain receptors (eg, within the ables. Patient variables include age (there is a associated with a higher rate of PONV than
genitourinary tract) lower incidence of CINV in patients under sevoflurane and desflurane.
■ The chemoreceptor trigger zone six years and over 50 years of age), sex Intubation is also thought to increase the
■ Cranial nerve X (the vagus nerve) (females are more prone to CINV), alcohol rate of PONV, by stimulating the pharyngeal
from pharynx irritation, resulting in consumption (there is a greater incidence of mechanoreceptor. Gastric distension sec-
the gag reflex CINV in patients consuming more than 10 ondary to mask ventilation is also associated
units of alcohol per week), anxiety levels, with an increased risk of PONV, as a result of
and any previous cycles of poorly controlled mechanoreceptor stimulation within the
categories apply to uncontrolled CINV — chemotherapy. stomach and small intestine.5
breakthrough and refractory nausea and Surgical procedures such as intra-
vomiting. CINV is the single most feared Radiation-induced nausea and vomiting abdominal, middle ear, ophthalmic and
adverse effect for patients undergoing The intestinal tract is highly sensitive to gynaecological surgery are associated with
chemotherapy and has regularly resulted in ionising radiation, as a result of its rapid cell the highest rates of PONV. Management
patients refusing treatment or physicians turnover. Thus, one of the most common of PONV is among the topics covered in
having to withhold it. If inadequately con- side effects of radiation therapy is diarrhoea the second article in this special feature
trolled, CINV can lead to dehydration, with associated nausea and vomiting. (p189).
electrolyte imbalance and physical damage Whole body doses of radioactivity will
(such as Mallory-Weiss tears of the oesopha- affect the gastrointestinal tract. Almost 80 Vestibular disorders
gus).Acute CINV occurs within 12 hours of per cent of the total body 5-HT3 is con-
chemotherapy and late-acute CINV occurs tained within the gastrointestinal tract, in The vestibular system is responsible for sen-
within 12–24 hours. Delayed CINV occurs the enterochromaffin cells, the enteric sory input to provide information relating to
after 24 hours and may persist for six to nerves and mucosal mast cells. Changes in movement and orientation in space. It com-
seven days. intestinal 5-HT3 tissue content in animal prises the semicircular canals which detect
Depending on its emetic potential, models with total body irradiation have rotational movement and the otoliths which
chemotherapy is divided into three classes been demonstrated, which may contribute detect linear movement. Disorders of the
— highly emetogenic, moderately emeto- to enteric neuronal innervation and nausea vestibular system are often accompanied by
genic or low emetogenic. Treatment and vomiting.4 nausea.
protocols are based on this classification.
Examples of highly emetogenic agents
include cisplatin, cyclophosphamide, doxo- Panel 2: Chemoreceptor trigger zone
rubicin, dacarbazine and carboplatin, all of
which have an emetogenic potential of The chemoreceptor trigger zone (CTZ) is a small collection of cells based in the medulla.
greater than 90 per cent.2 It is located outside the blood-brain barrier and therefore responds to chemical stimuli
Anticipatory nausea and vomiting can present in the blood or cerebrospinal fluid. The CTZ responds to a number of drugs (eg,
occur before, during and after (but before apomorphine) and is also involved in vomiting in conditions such as uraemia and radia-
acute symptoms would normally be expect- tion sickness.
ed to occur) administration of a The CTZ has a number of receptors, namely dopamine (D2) receptors (believed to be
chemotherapeutic agent. This is a condi- the most important in CTZ stimulation), 5-hydroxytryptamine (5-HT) receptors, opioid
tioned response to visual, olfactory, receptors, acetylcholine receptors and neurokinin-1 receptors. Receptor stimulation
gustatory and environmental stimuli occurs via different afferent pathways, all of which stimulate a common substance P
associated with previously administered pathway.1
chemotherapy. The CTZ is not separated from the blood by the blood-brain barrier and is therefore
Breakthrough nausea and vomiting susceptible to drugs and metabolites. Communication between circulatory compounds
refers to cases where prophylactic and the CTZ is thought to be via astrocytes (star-shaped glial cells) which release
antiemetic treatment has been given, dopamine that connects with neurones in the CTZ.
whereas refractory nausea and vomiting

186 • H O S P I TA L P H A R M AC I S T JUNE 2007 • VO L . 1 4
Vertigo Vertigo, specifically benign Migraine Migraine is a neurological with ovarian cancer have a 25–40 per cent
paroxysmal positional vertigo, is thought to condition, with the most common symptom risk of obstruction. Other patients who may
be caused by sections of the otoliths having being headache. The headache is charac- experience intestinal obstruction are those
cleaved off and passed into the semicircular terised by pain on either side of the head, with metastatic abdominal or pelvic cancer,
canals. Vertigo may potentially have other photophobia and nausea. The condition is which may lead to obstruction at multiple
underlying causes, such as certain tumours, thought to result from cortical spreading sites. Occlusion is generally caused by:
vascular insufficiencies, or the early stages of depression, releasing inflammatory media- extrinsic compression from the primary
multiple sclerosis. tors which cause irritation of the cranial tumour; malignant adhesions; post- radio-
nerve roots, in particular the trigeminal therapy fibrosis and mobility disorder due to
Vestibular neuronitisVestibular neuronitis nerve, causing face and head pain. tumour infiltration into the musculature of
is associated with nausea and vomiting of Approximately 90 per cent of migraine the bowel (specifically the intestinal linitis
sudden and rapid onset. It is normally associ- sufferers experience nausea. It is suggested plastica).
ated with a viral infection of the inner ear. that nausea and vomiting associated with Obstruction usually manifests itself as
Prolonged dizziness, without deafness, may migraine result from gastric stasis or gastro- severe vomiting and is dependent upon the
persist for several weeks.6 paresis (delayed stomach content emptying). severity and site of the occlusion. Symptoms
Consequently the absorption of orally may worsen and become continuous or may
Labyrinthitis Labyrinthitis is a disorder administered anti-migraine medicines may be intermittent with periods of relief. Radi-
similar to vestibular neuronitis affecting bal- be delayed. Some antiemetics such as ological investigation will often differentiate
ance, usually resulting from a viral upper metoclopramide also exhibit prokinetic between malignant obstruction and consti-
respiratory tract infection. Inflammation of properties, which is especially effective in pation and will be useful in determining the
the labyrinth results in dizziness, nausea, patients with migraine associated with gas- site of occlusion.
vomiting, loss of balance, tinnitus, and some troparesis.
deafness. It can also manifest as rapid unco- Endocrine disorders
ordinated eye movements (nystagmus) in Gastrointestinal disorders
response to perceived rotational motion. Nausea and vomiting during pregnancy
This will often exacerbate the feeling of The most common causes of nausea and “Morning sickness”, is believed to affect
nausea and vomiting. vomiting are duodenal ulcers, dyspepsia, 70–90 per cent of pregnant women. It is
Labyrinthitis is normally divided into three irritable bowel syndrome, often associated normally a self-limiting condition which
phases — the acute period, which can often with anorexia and pain. Other causes begins between weeks 4 and 7 of pregnancy
manifest as periods of nausea and vomiting, include gastric ulcer, gall-stones, gastro- and usually resolves after week 20. However,
the recovery phase and then a final phase of oesophageal reflux disease, gastric cancer, in approximately 10 per cent of pregnant
sensory compensation.The condition can last colon cancer, Crohn’s disease and pancreati- women, the condition persists and becomes
from one to six weeks, with residual dysequi- tis. The probability of organic disease known as hyperemesis gravidarum. The
librium occurring many months after inner increases with age in comparison to func- aetiology of hyperemesis gravidarum is
ear inflammation has resolved.7 tional disease. Similarly, the incidence of unknown. A number of causes have been
Labyrinthitis is often associated with anxi- ulceration due to Helicobacter pylori infection suggested, including delayed gastric empty-
ety, which can lead to palpitations, tremor increases with age. ing and H pylori (found in 60 per cent of
and panic attacks. antiemetics and anxiolyt- Chemoreceptors and mechanoreceptors women with hyperemesis gravidarum.)
ics or selective serotonin re-uptake inhibitors are located in the stomach, jejunum and Reduced levels of thyrotropin stimulating
are often prescribed in labyrinthitis although ileum. These are associated with the detec- hormone have been shown in women with
treatment is not always recommended.8 tion of emetic stimuli. Mechanoreceptors the condition and rises in oestrogen, proges-
are fundamentally tension receptors that ini- terone and prostaglandin E2 have also been
Motion sickness Motion sickness is a nor- tiate emesis in response to distension and implicated.10 Vomiting during pregnancy is
mal response to an abnormal environment. contraction, as in the case of bowel obstruc- not teratogenic and babies born to mothers
Five per cent of the general population suf- tion.Thus, one possible cause of nausea and with hyperemesis gravidarum tend to be the
fer heavily from motion sickness, 5 per cent vomiting associated with the gastrointestinal same weight as other babies.
hardly experience it at all, and the rest expe- tract is intestinal obstruction. Another condition associated with nausea
rience moderate symptoms. and vomiting during pregnancy is acute fatty
The condition is often described as a sen- Intestinal obstruction Intestinal obstruc- liver of pregnancy. In about week 35 of preg-
sory conflict between the vestibular system tion is caused by an occlusion of the nancy some women experience nausea,
and other senses, but this does not explain intestinal lumen. It prevents or delays nor- vomiting, headache and general malaise. Ele-
why exposure to certain forms of motion, mal propulsion of the contents of the vated aminotransferases and microvesicular
such as linear oscillation, also causes sickness. intestine along the tract. Intestinal obstruc- fat (from biopsy) indicate fatty liver of preg-
Another theory is that motion sickness is tion occurs in approximately 3 per cent of nancy.11 HELLP syndrome, (haemolysis,
caused by the brainstem’s mechanism of ori- patients with advanced cancer, and patients elevated liver enzymes, low platelet count) is
entation and motion in response to the also associated with nausea and vomiting
body’s position being in conflict with senso- Suggestions for future special features during the latter stages of pregnancy and
ry information.9 may complicate delivery.12
The signs and symptoms of motion sick- If you would like to suggest a topic for a
ness are nausea and vomiting, malaise, pallor, future special feature in Hospital Pharmacist, Systemic metabolic disorders Acute
cold sweats and abdominal discomfort. The or if you are a specialist clinical pharmacist exacerbations of chronic diseases, such as
mildest form of motion sickness, Sopite syn- interested in writing about your area of diabetes mellitus, endometriosis and renal
drome, manifests as some gasping, practice, please contact Hannah Pike (e-mail insufficiency, may cause nausea and vomit-
drowsiness and decreased interest in sur- hannah.pike@pharmj.org.uk, telephone ing. Severe nausea and vomiting is a clinical
roundings. Behaviour modification 020 7572 2425) or Rachel Graham (e-mail symptom of diabetic ketoacidosis.
techniques (as well as medicines — see rachel.graham@pharmj.org.uk, telephone Acute adrenal insufficiency is also associ-
p189) can be used in the treatment of 020 7572 2419). ated with nausea and vomiting, as is uraemia.
motion sickness. Other non-specific symptoms include

JUNE 2007 • VO L . 1 4 H O S P I TA L P H A R M AC I S T • 187
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Hypercalcaemia (serum calcium >3.5 reactions. Complications of vomiting vestibular disease. Current Opinion in Neurology
mmol/L) can alter gut motility, which may include metabolic disturbances and mucosal 2002;15:1–3.
induce nausea and vomiting. Other gas- damage. Treatment options, which often 8. Staab J and Ruckenstain M. Chronic dizziness and
trointestinal symptoms include anorexia and depend on the cause of the nausea and vom- anxiety. Archives of Otolaryngology — Head and
abdominal pain. Primary hyperparathy- iting, are discussed in the next article in this Neck Surgery 2005;131:675–79.
roidism and malignancy are the two most special feature (p189). 9. Treisman M. Motion sickness: an evolutionary
common causes of hypercalcaemia. hypothesis. Science 1977;197:29.
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