3. Postoperative Nausea and Vomiting Flashcards
Neural Pathways Which Mediate Nausea and Vomiting
Nausea and vomiting are reflexes, with afferent and efferent pathways which are
mediated by a number of anatomically ill-defined structures in the medulla oblongata
of the brain stem
vomiting centre,
the chemoreceptor trigger zone
and the nucleus tractus solitarius
Vomiting centre (VC):
afferents from a large number of sources,
including the cerebral cortex,
the viscera and the
chemoreceptor trigger zone (CTZ).
Its receptors are primarily cholinergic (muscarinic M3),
but it also contains some histaminic (H1) receptors.
Cortical afferents
: nausea and vomiting may be provoked by
pain, fear and anxiety, as well as by association
and by other psychological factors.
It may also be precipitated by visual and olfactory stimuli.
Cortical stimulation of the vomiting centre may also result from
organic disturbance such as
raised or lowered ICP,
hypoxia (of which nausea is a sensitive early sign)
and the vascular derangement that accompanies migraine.
Visceral afferents:
the vomiting centre responds to stimuli such as peritoneal irritation,
as well as a variety of visceral disorders,
including inflammation,
distension and ischaemia.
Obvious causes include
intestinal obstruction or perforation,
gastric stasis and gastric irritation.
Cardiac pain is also a potent stimulus to vomiting.
Chemoreceptor trigger zone (CTZ):
this is also located in the medulla,
in the area postrema on the floor of the fourth ventricle.
It lies outside the blood–brain barrier and responds
both to afferents from various sources as well as to emetogenic
substances in blood and cerebrospinal fluid.
Its receptors are primarily dopaminergic (D2) and serotoninergic (5-HT3).
Inputs to CTZ
- Gastrointestinal and vagal afferents:
enterochromaffin cells in the gut produce
5-HT and vagal input is mediated by 5-HT3 receptors. - Vestibular afferents:
inputs are received from the vestibular apparatus via the
cerebellum. Its receptors are cholinergic (muscarinic M3) and histaminic (H1). - Drug effects:
numerous drugs exert a direct action on the CTZ.
These include opioids (which also sensitize the vestibular apparatus to motion),
cytotoxic drugs,
cardiac glycosides,
volatile anaesthetic agents
drugs with sympathomimetic effects.
Nucleus tractus solitarius (NTS):
This is also found in the area postrema
in the lower pons and receives afferents from the CTZ
(dopamine D2 receptors),
from the vagus,
from the vestibular apparatus and from the limbic system.
It precipitates vomiting by stimulation of several nuclei: the dorsal motor nucleus of the vagus, the nucleus
ambiguous, the ventral respiratory nuclei and the rostral nucleus.
Factors related to patients
female gender is the most reliable predictive factor (OR 3).
(unreliable evidence around phase menstruation)
A positive history of PONV is another predictive
factor, which doubles its likelihood (OR 2)
as does a history of motion sickness
if ambulation after surgery is premature
+
Smoking appears to exert a protective effect with an odds ratio of 2 (theory acting as a potent inducer of the cytochrome P450 system)
PONV is increased by preoperative anxiety.
Body habitus has no impact on the incidence of PONV, and
there is no association with obesity, as formerly was believed. There is an inverse
relationship with increasing age in adults.
Factors related to surgery
intra-abdominal, intracranial, middle ear and squint
surgery have all been associated with a higher incidence of PONV,
as have laparoscopic and gynaecological procedures.
Multivariate analysis in large trials, however,
suggests that there is no direct causation and that these operations
(with the exception of squint surgery in children)
do not represent independent risk factors for PONV.
Empirical experience across this range of surgical procedures nonetheless
suggests that the need for rescue antiemetic therapy does appear to be greater than for
some others.
Moderate to severe postoperative pain can also be a potent precipitant.
Factors related to anaesthesia:
- volatile anaesthetics
at least double the incidence of PONV,
and as would be expected the risk is dose- and duration-dependent.
It is believed that the emetic potential of volatiles
(which is similar for all the halogenated hydrocarbons)
is related to a decrease in serum concentrations of anandamide.
it is a neurotransmitter with a wide spectrum of activity, including
the suppression of emesis, and whose effects are mediated via CB1 and CB2
cannabinoid receptors.
- Nitrous Oxide
The increased risk of PONV of which nitrous oxide is frequently accused is actually modest (OR 1.4)
The ENIGMA II trial (Myles
et al. Lancet 2014, 384: 1446–54) showed that this risk is nullified with concomitant
anti-emetic therapy
Factors related to disease:
Factors related to disease: the list of potential causes is long and includes intestinal
obstruction, hypoglycaemia, hypoxia, uraemia and hypotension
Management of PONV
- prevention by avoidance of emetic drugs
(this need not include nitrous oxide, as long as an anti-emetic is given), - by the use of total intravenous anaesthesia (TIVA),
- by vigorous hydration and (contentiously)
- by high-inspired oxygen concentrations.
- There are also complementary techniques such as acupressure
on the P6 acupuncture point at the wrist.
Drug Tx
A multimodal approach uses combinations of
- H1-antagonists
(phenothiazines such as prochlorperazine), - anticholinergic M3-antagonists (atropine, glycopyrrolate),
- anti-dopaminergic D2-antagonists
(domperidone, metoclopramide, haloperidol, droperidol), - 5-HT3 antagonists
(ondansetron, granisetron) - NK1-antagonists (aprepitant
This is necessary because the efficacy of single agents is disappointing,
and the numbers needed to treat (NNT) are relatively high. The NNT for ondansetron,
for example, is quoted as between 5 and 6. Other drugs with anti-emetic effects
include corticosteroids, cannabinoids and propofol.
