AANA Journal Course
Update for nurse anesthetists
1
*6 CE Credits
Antiemetic prophylaxis:
Pharmacology and therapeutics
Carol L. Norred, CRNA, MHS
Denver, Colorado
Postoperative nausea and vomiting (PONV), a common problem with complex causes, may result in substantial complications. This Journal course discusses the pathogenesis of PONV
and reviews antiemetic pharmacology. Corticosteroids, gastrointestinal prokinetics, neuroleptic butyrophenones, phenothiazines, and serotonin receptor antagonists may be prescribed alone or in combination. State-of-the-art anesthetic
techniques for prevention of PONV are described. Multimodal
therapy with combined low-dose antiemetics affecting multiple
receptors is suggested to prevent PONV in high-risk patients
such as nonsmokers, females with a previous history of nausea, and patients with high postoperative narcotic requirements.
Objectives
current pharmacology for antiemetic prophylaxis is followed by a description of therapeutic anesthetic techniques to minimize PONV.
At the completion of this course, the reader should be
able to:
1.
Describe the pathophysiological factors that
may precipitate postoperative nausea and vomiting (PONV).
2.
Compare and contrast the mechanisms of
action of and indications for corticosteroids,
gastrointestinal prokinetics, neuroleptic butyrophenones, phenothiazines, and serotonin
receptor antagonists for prevention and treatment of PONV.
3.
Examine the contraindications, side effects,
and drug interactions of these antiemetic
drugs.
4.
Identify patients, procedures, and anesthetic
techniques that may contribute to an increased
risk of PONV.
5.
Formulate an appropriate anesthetic plan to
minimize PONV in high-risk patients.
Introduction
This Journal course overviews the pathogenesis and
physiological mechanisms of postoperative nausea and
vomiting (PONV). In addition, an extensive review of
Key words: Antiemetics, nausea, vomiting.
Pathogenesis and physiological mechanisms
of nausea and vomiting
Nausea and vomiting pose a substantial postoperative
problem that can result in corporeal complications, such
as aspiration, wound disruption, impaired healing, and
increased surgical bleeding. In addition, intractable nausea and vomiting can minimize patient satisfaction,
delay patient discharge, and increase hospital
costs.1,2(pp14-15),3(p1395) Several studies report an incidence of PONV as high as 60% to 70% after high-risk
procedures, but generally the incidence is around 30%.1
The pathogenesis of PONV is multifactorial. Preoperative (Table 1), intraoperative (Table 2), and postoperative factors (Table 3) may have a role. Physiologically, autonomic stimulation due to nausea and
vomiting results in salivation, cutaneous vasoconstriction, tachycardia, mydriasis, inhibition of gastric parietal cell secretion of acid, and altered gastric motility.
Triggers of nausea and vomiting may occur from multiple sites such as the pharynx, ear, gut, and brain. An
emetic reflex may be elicited from pharyngeal stimula-
* The American Association of Nurse Anesthetists is accredited as a provider of continuing education in nursing by the American Nurses Credentialing
Center Commission on Accreditation. The AANA Journal course will consist of 6 successive articles, each with objectives for the reader and sources for
additional reading. At the conclusion of the 6-part series, a final examination will be printed in the AANA Journal. Successful completion will yield the
participant 6 CE credits (6 contact hours), code number: 25468, expiration date: July 31, 2004.
AANA Journal/April 2003/Vol. 71, No. 2
133
Table 1. Preoperative factors affecting postoperative nausea and vomiting (PONV)1-6
Factor
Effects
Age
Children and adolescents more likely to have PONV; for people older than 50 y, little association
between age and PONV
Sex
Women more likely, affected by gonadotropin and estrogen; PONV likely during menstrual cycle
History
Likelihood increased if previous PONV or motion sickness
Smoking
Decreases risk of PONV
Anxiety
With high anxiety, increased PONV due to catecholamine release; air swallowing by anxious
patients increases gastric volume
Obesity
Positive correlation due to accumulation of fat-soluble anesthetics; obesity linked with large
gastric volume, increased esophageal reflux, increased gallbladder and gastrointestinal disease
Oral intake
Decreased gastric motility after excessive preoperative intake of fatty foods; vomiting during
induction or emergence stimulated by full stomach; history of heavy alcohol intake associated
with less nausea
Table 2. Intraoperative factors affecting postoperative nausea and vomiting (PONV)1-6
Factor
Effects
Surgery type
Higher PONV incidence in the following types of surgery or anatomic areas: intra-abdominal,
craniotomy, gynecological, laparoscopic, orthopedic, to treat strabismus or ear-nose-throat
disorders, plastic, breast augmentation, or orthopedic shoulder surgery
Duration of surgery
Increased chance of PONV in longer procedures
Anesthetic technique
Greater likelihood with general anesthesia; no effect of gastric emptying during general
anesthesia on the incidence of PONV; spinal associated with less PONV than general anesthesia;
peripheral regional anesthesia least emetogenic
Anesthetic drugs
Occurrence of PONV increased with balanced anesthesia combined with opioids; each drug is very
emetogenic: morphine, meperidine, fentanyl, etomidate, ketamine, thiopental, nitrous oxide, and
neostigmine
Table 3. Postoperative factors affecting postoperative nausea and vomiting (PONV)1-6
Factor
Effects
Pain
Nausea substantially reduced by adequate pain relief
Opioids
Increases PONV by causing direct stimulation of chemoreceptor trigger zone
Movement
May induce PONV through a vestibular component
Orthostatic hypotension
or dehydration
May contribute to PONV
Hypoglycemia
May contribute to PONV from prolonged fasting
Hypoxemia
May contribute to PONV
Oral intake
Premature intake of food or fluid may contribute to PONV
tion. The labyrinthine or vestibular apparatus and
auricular branch of the tympanum of the ear may
detect motion stimuli from histamine or acetylcholine
receptors. Mechanoreceptors of the bladder, gallbladder, or uterus may detect overdistention and disordered
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AANA Journal/April 2003/Vol. 71, No. 2
gastric motility due to disease or surgical trauma.
Hepatic portal vein detectors sense chemical stimuli in
the venous drainage of the gut. Gastric and duodenal
chemoreceptors detect irritation from toxins such as
serotonin (also known as 5-HT).2(pp16-23),7(pp316-317)
Table 4. Antiemetic drugs1-8
Class
Generic name
Trade name
Corticosteroids
Dexamethasone
Decadron
4-10 mg IV on induction
Butyrophenones
Droperidol
Inapsine
0.625-1.25 mg IV preoperatively or
treatment
Gastrointestinal
prokinetics
Metoclopramide
Reglan
10-20 mg IV or PO preoperatively
Serotonin antagonists
Ondansetron
Zofran
4 or 8 mg IV before induction or as
treatment; 8 mg PO 1-2 h preoperatively
Dolasetron
Anzemet
12.5 mg IV 15 min before emergence or as
treatment; 100 mg PO 1-2 h preoperatively
Granisetron
Kytril
1 mg IV on induction or as treatment
Promethazine
Phenergan
12.5-25 mg IV or rectal every 4-6 h
Prochlorperazine
Compazine
5-25 mg PO, rectal, or IV every 4-6 h
Phenothiazines
Dose and timing*
* IV indicates intravenous; PO, by mouth.
From the vagus nerve of the gut, transmitted signals
reach the histamine, cholinergic, or enkephalin receptors in the nucleus tractus solitarius or other centers in
the area postrema and area subpostrema. The chemoreceptor trigger zone (CTZ) located in the area postrema
on the floor of the fourth ventricle of the brain may
identify absorbed toxins or disturbances such as
hypotension or metabolic acid-base changes. The higher
brain centers in the cortex and limbic system may be
affected by emotions, smells, sights, or thoughts. Afferent stimuli detect the need to vomit and coordinate the
response in the vomiting center located in lateral reticular formation of the brainstem close to the fourth ventricle. This area is rich in receptors that have an important role in the transmission of impulses to emetic
centers such as serotonin, opioid, histamine, and muscarinic and dopamine receptors. Other dopamine receptors in the nucleus tractus solitarius and CTZ may be
implicated in the vomiting reflex and are involved in the
control of gastric motility.2(pp16-23),7(pp316-317) Thus, many
physiological and pathological foci contribute to the
cause of PONV. The clinician can use this information
in the administration of the varied pharmacological
treatments for prophylaxis of this complex and recalcitrant problem.
Literature review: Antiemetic pharmacology
The purpose of this course is to discuss the clinically
relevant pharmacology of common antiemetic drugs
such as corticosteroids, gastrointestinal prokinetics,
neuroleptic butyrophenones, phenothiazines, and serotonin receptor antagonists. Table 4 presents the doses
and trade names of pharmaceuticals in each of these
antiemetic classes.
• Corticosteroids. Corticosteroids inhibit prostaglandin synthesis and prevent the inflammatory release
of serotonin in the gut, or they sensitize the antiemetic
pharmacotherapy receptors. Dexamethasone has been
found to enhance the effects of other antiemetic drugs.
Alone or combined with serotonin receptor antagonists,
dexamethasone is especially useful for late PONV efficacy.9 For example, in a randomized study of Taiwanese
patients undergoing laparoscopic cholecystectomy, 5 mg
of prophylactic intravenous (IV) dexamethasone was as
effective as 2 mg of IV tropisetron, and significantly
more effective than placebo to reduce the incidence of
PONV (P < .01).10 A study of patients who had undergone hysterectomy and were treated for nausea due to
epidural morphine found that 5 mg of IV dexamethasone effectively reduced nausea and vomiting (P < .01)
and reduced the use of rescue antiemetics (P < .05), but
5 mg of IV tropisetron was not significantly more effective.11 In a randomized, placebo-controlled, doubleblind trial, researchers found that 4 mg of IV dexamethasone combined with 12.5 mg of IV dolasetron,
administered just after induction for laparoscopic cholecystectomy, was associated with significantly shorter
day surgery stay, more rapid discharge, improved patient
satisfaction, and improved quality of recovery, as well as
decreased PONV after discharge (P < .05). However, no
difference in early nausea and vomiting was noted compared with patients who received only 12.5 mg of IV
dolasetron. Administration of dexamethasone at induction may improve antiemetic efficacy.12
Long-term use or large doses of glucocorticoids may
cause considerable adverse effects,13(pp420-422) but studies
do not suggest the occurrence of toxic effects with low
doses.9-12 However, glucocorticoids may exacerbate
AANA Journal/April 2003/Vol. 71, No. 2
135
hypokalemia, metabolic acidosis, edema, myopathy,
peptic ulcer, infections, psychosis, diabetes, or osteoporosis.13(pp420-422) Phenytoin, phenobarbital, ephedrine,
and rifampin speed the clearance of dexamethasone.
Concomitant use of diuretics with glucocorticoids may
result in hypokalemia.14(p2082)
• Gastrointestinal prokinetics. Gastrointestinal prokinetics are often administered preoperatively. Antiemetic
gastrointestinal prokinetic drugs classified as benzamides include metoclopramide, domperidone, and cisapride.13(pp447-450) However, cisapride does not prevent
postoperative vomiting in children and may intensify
the problem.15
Metoclopramide does not alter gastric hydrogen ion
secretion or pH, but speeds gastric emptying and shortens the small intestinal transit time of ingested substances by cholinergic stimulation of the postganglionic nerves of the gastrointestinal tract. It increases
smooth muscle tension of the lower esophagus and
stomach, increases gastrointestinal motility, causes
relaxation of the pylorus and duodenum, and increases
prolactin and aldosterone secretion. It centrally antagonizes dopamine receptors of the CTZ. In high doses,
this drug acts as a serotonin receptor antagonist and
stimulates cholinergic effects on the gastrointestinal
smooth muscle.13(pp447-448) However, a systematic
review found that 10 mg of IV metoclopramide was no
more effective than placebo for prevention of PONV in
adults and children.16
While the antiemetic efficacy is controversial, combined with an H2 receptor antagonist, metoclopramide
effectively reduces both gastric pH and volume.17(p559)
Metoclopramide is indicated to decrease preoperative
gastric volume and to treat heartburn, gastrointestinal
reflux, and gastroparesis. Preoperative metoclopramide
may be beneficial for patients who have fasted for an
insufficient time before surgery or have a full stomach
or after trauma. In addition, maternity patients or
patients who are obese, have diabetes with autonomic
neuropathy, or are at risk for aspiration pneumonia also
may benefit from the administration of metoclopramide.9(p448),17(p559)
Although it is prescribed frequently, metoclopramide
should be used cautiously. Metoclopramide may cause
increased intracranial pressure in head-injured
patients.18 Metoclopramide is contraindicated in
patients with breast cancer, intestinal obstruction, or
pheochromocytoma, and for patients taking medication for Parkinson disease, seizure disorders, or depression. Pediatric and geriatric patients and patients with
renal failure or insufficiency may be more prone to
adverse effects; the dose should be decreased in these
populations. While it does not cause substantial sedation, metoclopramide may cause intestinal cramping. It
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AANA Journal/April 2003/Vol. 71, No. 2
may cause analgesia in patients with gastrointestinal
spasm, biliary or renal colic, uterine cramping, or
prostaglandin-induced pregnancy termination. Metoclopramide is rarely linked with hypotension, dysrhythmia, or extrapyramidal side effects such as dysphoria or agitation.4(p246),13(pp448-450)
Interactions may occur with other antiemetics or anesthetic drugs. Due to potential extrapyramidal effects,
metoclopramide should not be administered with phenothiazines or butyrophenones such as droperidol. Metoclopramide has been linked with dysrhythmia when combined with ondansetron. It may decrease the induction
dose of thiopental and also may increase the sedative
effect of central nervous system depressants.4(p246),13(pp448450)
Anticholinergics4(p246),13(pp448) and opioids4(p449) may
offset the beneficial effects of metoclopramide. Metoclopramide may inhibit plasma cholinesterase and the
metabolism of drugs such as succinylcholine or ester
local anesthetics.13(p450)
• Neuroleptic drugs. Also used to treat psychoses,
neuroleptic drugs are potent sedatives and antiemetics.
Neuroleptic butyrophenones act peripherally on the
gastrointestinal tract and block dopamine receptors in
the CTZ.13(p373) Although droperidol does not affect
histamine receptors and is not effective for motion
sickness,13(p376) it inhibits the activation of g -aminobutyric acid, serotonin, norepinephrine, and neuronal
nicotinic acetylcholine receptors,19 and it exhibits mild
peripheral a -adrenoreceptor antagonism.4(p174),13(p374)
Because droperidol does not alter carotid body hypoxic
drive, it also is indicated for the sedation of patients
with chronic obstructive pulmonary disease and to
decrease blood pressure.13(pp373-374)
Several studies illustrate the antiemetic efficacy of
droperidol. In a randomized, double-blind study of adult
general surgery patients, when given 30 minutes before
emergence from general anesthesia, low dose 0.625 mg of
IV droperidol, was significantly more effective than
placebo (P < .001) and as effective as 12.5 mg of IV
promethazine and as effective as 4 mg of IV ondansetron,
without significant differences in adverse events.20 A
meta-analysis found the efficacy and safety for the prevention of PONV to be similar with droperidol (pooled
odds ratio [OR], 0.68; 95% confidence interval [CI],
0.54-0.85; P < .001) and ondansetron (pooled OR, 0.43;
95% CI, 0.31-0.61; P < .001), with both drugs being more
effective than metoclopramide.21 Similar patient satisfaction and rates of adverse effects were found in adult outpatients (pooled OR, 0.87; P = .45).21 Still, a multicenter,
randomized, double-blind, placebo-controlled study
found that prophylactic 1.25 mg of IV droperidol was
more efficacious than 0.625 mg IV, less costly than 4 mg
of IV ondansetron (P = .001), and associated with similar
patient satisfaction (P < .05).22
Although droperidol is less expensive,22 it may cause
clinically significant adverse effects. High-dose droperidol may be more effective as an antiemetic, but doses
greater than 50 to 75 µg/kg may cause extrapyramidal
effects.23(p864) When administered preoperatively,
droperidol may cause dysphoria and agitation without
decreasing anxiety. Sedation without amnesia, lethargy,
and dry mouth may occur. Treatable with dyphenhydramine,13(p373) extrapyramidal reactions are more
common in middle-aged women and children.24(p51S)
Due to a -adrenergic blockade, droperidol may cause
hypotension due to vasodilation, but it does not alter
myocardial contractility or depress respirations.
Droperidol decreases cerebral blood flow and intracranial pressure, which may be an adverse effect for elderly patients but does not affect cerebral metabolic oxygen consumption. Droperidol also is contraindicated in
patients with Parkinson disease or pheochromocytoma.
The elimination of droperidol is prolonged in patients
with diminished hepatic blood flow or liver disease.13(pp373-374)
Before a recent warning from the US Food and Drug
Administration about the potential for Q-T interval
prolongation and torsades de pointes, droperidol commonly was administered as a low-cost antiemetic.25
Drugs that may interact with droperidol by prolonging
the Q-T interval include class Ia antiarrhythmics
(disopyramide, procainamide, and quinidine), class III
antiarrhythmics (amiodarone, dofetilide, ibutilide, and
sotalol), antihistamines (terfenadine and astemizole),
phenothiazines, tricyclic antidepressants, corticosteroids, chloral hydrate, cisapride, clarithromycin,
erythromycin, thiazide diuretics, tamoxifen,26(pp277279,295-296)
sevoflurane,4(p145) and dolasetron.27 In addition, droperidol prolongs the duration of action of fentanyl,13(p375) antagonizes the action of levodopa, and
interferes with dopamine’s renal effects. Droperidol also
may minimize ketamine’s cardiovascular effects or precipitate rebound hypertension with clonidine.4(p175)
• Phenothiazines. Similar to butyrophenones, phenothiazine antiemetics block the CTZ dopaminergic
receptors and a -adrenergic receptors.7(p318) Phenothiazines also have anti–motion-sickness, antipruritic, and
anxiolytic effects because they antagonize H1 and cholinergic receptors.28(p273) Phenothiazine agents include
prochlorperazine and promethazine. 7(p318),13(p370)
Promethazine is indicated for the treatment of allergic
blood reaction, anaphylaxis, sedation, labor, motion
sickness, and PONV and is indicated as an adjunct to
analgesics.14(p3553) Phenothiazines are potent sedatives
and may delay discharge after day surgery.7(p318) They
also may cause blurred vision, dizziness, tremors, nervousness, and extrapyramidal effects. Phenothiazines
have minimal effects on the cardiovascular system
except potential for hypotension or a prolonged Q-T
interval. These drugs may lower the seizure threshold
and should be used cautiously in patients with altered
cognition, sleep apnea, bone marrow depression, narrow
angle glaucoma, prostatic hypertrophy, peptic ulcer, or
duodenal or bladder obstruction.13(pp371-372),14(pp15051506,3553-3558)
Extrapyramidal effects of prochlorperazine
may be exacerbated with monoamine oxidase inhibitor
drugs.14(p1506) Like many other antiemetics, phenothiazines augment the sedative effects of central nervous
system depressants.13(p372)
• Selective serotonin receptor antagonists. Antiemetic
serotonin receptor blockers are expensive, but their use
is established because they have few side effects such as
sedation and respiratory depression and few extrapyramidal effects because they do not affect histamine,
dopamine, or cholinergic receptors.7(p319),13(p406) Seven
types of serotonin receptors exist; they are found in the
central and peripheral nervous systems, smooth muscle, and platelets. Serotonin receptor antagonists block
serotonin receptors peripherally in the gastrointestinal
tract and centrally in the medulla and area postrema
where the vomiting center, nucleus tractus solitarius,
and CTZ are located.29 Selective serotonin receptor
antagonists include drugs such as ondansetron,
dolasetron, and granisetron.1(p1233),2(p78)
Selective serotonin receptor antagonists work well to
prevent PONV. However, serotonin receptor antagonists do not effectively prevent or treat motion-induced
nausea and vomiting.13(p406) Numerous randomized,
double-blind studies found that ondansetron and
dolasetron were significantly more effective than
placebo for prevention of PONV in high-risk groups.5,30
A meta-analysis reported that ondansetron was more
effective than droperidol and metoclopramide for preventing PONV in children (pooled OR, 0.49; P =
.004).21 However, in a double-blind study of patients
undergoing otolaryngologic surgery, 12.5 mg of IV
dolasetron administered 30 minutes before emergence
was found as effective as 25 mg of IV dolasetron and
more cost effective than and similar in efficacy to 4 and
8 mg of IV ondansetron, with no difference in patient
satisfaction.31 Metabolism to hydrodolasetron is attributed to the antiemetic effect of dolasetron.5
Serotonin receptor blocker drugs may be associated
with a low incidence of headache, diarrhea, light-headedness, warm epigastrium sensations, flushing, and
constipation.7(p319),13(p406) But to avoid torsades de
pointes arrhythmias, dolasetron should not be administered with drugs that can prolong the Q-T interval.
Although it does not significantly alter blood pressure,
dolasetron can prolong the P-R and Q-Tc intervals and
widen the QRS interval by blocking sodium channels,
and it can prolong myocardial depolarization.27
AANA Journal/April 2003/Vol. 71, No. 2
137
Dolasetron and ondansetron do not cause sedative drug
interactions,4(p248),7(p319),13(p406) but ondansetron reduces
the overall analgesic effect of tramadol.32
A great formulary is available to the clinician for
effective management of PONV. To understand the
dynamic intricacies of pharmacological treatments, the
astute anesthetist also should be cognizant of the impact
of anesthetic technique on antiemetic prophylaxis.
State-of-the-art anesthetic techniques for
PONV prevention
Clinicians may debate the best treatment plan for prevention of PONV. No single drug is without inextricable side effects and costs, is completely efficacious for
prevention of PONV, or is innocuous. The overall risk
of adverse effects may not be different among various
drug combinations.33 Arbitrary or global administration of prophylactic antiemetic medications is not recommended. Although PONV is a very unpleasant experience, data suggest little difference in outcomes
including time to discharge, unanticipated admission,
patient satisfaction, and time to return to normal activities when nausea was treated symptomatically rather
than prophylactically.34 Yet, in identified at-risk
patients undergoing emetogenic procedures, techniques to prevent PONV are indicated. Anesthetists are
encouraged to minimize administration of anesthetic
drugs known to stimulate nausea and strategically
administer antiemetics before emergence from general
anesthesia if indicated. Multimodal antiemetic therapy,
total intravenous anesthesia with propofol, adequate
hydration, anxiolytics, effective nonopioid analgesia,
supplemental oxygen, and nonpharmacological techniques such as acupuncture, acupressure, and hypnosis
may improve efficacy. A treatment algorithm for PONV
prophylaxis appropriate for medium- to high-risk
patients is given in the Figure.1
Narcotics, especially morphine, are notorious for
precipitating nausea and vomiting.7(p317) Surprisingly, a
randomized, double-blind study of outpatients found
no statistical difference of PONV in patients given 0.25
mg of IV nalbuphine, 20 µg/kg of IV alfentanil, 2 µg/kg
of IV fentanyl, or placebo for induction of general anesthesia.35 But a subsequent randomized, double-blind
study of outpatients found that 150 µg/mL of alfentanil
caused less nausea and vomiting than 50 µg/mL of fentanyl and 5 µg/mL of sufentanil (12%, 34%, and 35%,
respectively; P < .005) when administered in equipotent
concentrations for general anesthesia.36 Cyclooxygenase inhibitors and local anesthetics may provide nonopioid analgesia without increasing the risk of PONV.1
Neostigmine may be implicated as a cause of nausea
and vomiting.13(p230) Yet, a study of ambulatory surgical
patients who received 2.5 mg of IV neostigmine and 0.5
mg of IV glycopyrrolate for reversal of rocuronium or
mivacurium muscle relaxant showed no association
with an increased incidence of nausea. A total of 18% of
patients given reversal with neostigmine and glycopy-
Figure. Risk factors for postoperative nausea and vomiting (PONV) and guidelines for prophylactic antiemetic therapy1
Patient factors
Female sex
History of PONV
or motion sickness
Nonsmoker
Postoperative opioid use
Mild to moderate risk
20%-40%
1-2 factors present
Moderate to high risk
40%-80%
3-4 factors present
Any of the following:
Droperidol
Dexamethasone
Scopolamine
Serotonin antagonist
Droperidol plus
Serotonin antagonist
or
Dexamethasone plus
serotonin antagonist
1
(Reproduced with permission from Gan. )
138
Surgical factors
Laparoscopy
Laparotomy
Plastic surgery
Major breast surgery
Craniotomy
Otolaryngologic procedures
Strabismus surgery
AANA Journal/April 2003/Vol. 71, No. 2
Very high risk
> 80%
> 4 factors present
Combination antiemetics
plus
Total intravenous
anesthesia with propofol
rrolate had nausea vs 15% of patients who did not.
Eight percent of patients who were reversed vomited vs
12% of patients who did not receive reversal. Additionally, no difference was noted for the need for antiemetics (13% in both groups) between patients who received
neostigmine and patients who did not.37
Nitrous oxide may contribute to PONV by stimulating the CTZ and vomiting center or by stimulating opioid receptors. Nitrous oxide is 35 times more soluble
than nitrogen in the blood; consequently, air-filled cavities such as the gut or middle ear may expand due to
nitrous oxide absorption, resulting in increased size and
pressure and contributing to PONV.4(p138),13(p26) Due to
etherizing airway irritation, desflurane was associated
with a higher incidence of PONV than isoflurane in a
study using a laryngeal mask airway and standardized
anesthetics for outpatient arthroscopy.38 In a study of
patients undergoing laparoscopic cholecystectomy,
although time to awakening was prolonged, a subhynotic dose of propofol (0.5 mg/kg IV) given before
emergence more effectively prevented vomiting and the
need for rescue antiemetics after sevoflurane than after
desflurane anesthesia.39
Total intravenous anesthesia with propofol is more
efficacious than ondansetron for preventing PONV.13(p142)
Although it is 3 times more expensive, total intravenous
anesthesia with propofol and oxygen, compared with
isoflurane–nitrous oxide–oxygen anesthesia, reduced the
absolute risk of PONV for 72 hours postoperatively by
15% among inpatients (from 61% to 46%; P < .001) and
by 18% among outpatients (from 46% to 28%; P <
.001).40 In the postanesthesia care unit, a subhypnotic
dose of propofol may be given as antiemetic or antipruritic treatment.4(p940),13(p142) Although the specific
antiemetic action of propofol is unknown, it is not due to
dopaminergic 13(p142) or prokinetic effects. 41 The
antiemetic effect of propofol may be related to a
decreased serotonin level in the area postrema.1
Due to the multiplicity of triggering factors for
PONV, combination therapy may be useful for high-risk
patients.1 A randomized, double-blind study of female
outpatients undergoing laparoscopic surgery found that
multimodal management was associated with a 98%
complete response rate and a 0% incidence of vomiting,
compared with 7% in the groups receiving prophylaxis
with 4 mg of IV ondansetron (P = .07) or placebo (22%;
P = .0003). In the multimodal therapy group, 2%
required postoperative antiemetic treatment compared
with 24% in the ondansetron group (P < .0001) and
41% in the placebo group (P < .0001). Nevertheless,
multimodal therapy was not associated with increased
patient satisfaction compared with prophylaxis or rescue treatment for PONV.8 Effective preemptive treatment of PONV may enhance the use of combined treat-
ment with antiemetics that affect several receptors such
as a serotonin antagonist combined with a corticosteroid or a dopamine antagonist.1
Summary
Because PONV has multiple causes, prevention has
been problematic. Prophylactic antiemetic therapy
must be tailored to the level of risk. Anesthetists should
inquire about the patient history of postoperative emesis to design a therapeutic plan to minimize noxious
stimuli. Anesthetic drugs that are implicated as emetogenic should be avoided when possible. Simple anesthetic techniques such as preventing hypotension and
providing adequate hydration, anxiolysis, nonopioid
analgesia, and high inspired oxygen may decrease the
incidence of PONV not only in identified high-risk
patients but also in other surgical patient populations.
Antiemetics should be chosen by considering the
mechanism of action, indications, contraindications,
side effects, and drug interactions that may preclude
administration. Lower cost antiemetic drugs may be
associated with potent sedative effects that prolong
emergence or have potential adverse drug interactions.
Sedative drug interactions may occur with gastrointestinal prokinetics, neuroleptic butyrophenones, and
phenothiazines. Although they do not augment the
sedative effects of anesthetics, serotonin receptor antagonists are costly. Corticosteroids provide increased
antiemetic efficacy, but the potential of toxic effects may
impede acceptance of corticosteroids as a therapeutic.
Consequently, these drugs may be reserved for highrisk patients. Low-dose therapy may minimize adverse
and toxic effects of the drugs. A multimodal approach
of combined low-dose antiemetic drugs that affect multiple receptors is a logical and effective strategy to provide a more pleasant emergence for at-risk surgical
patients by preventing PONV.
REFERENCES
1. Gan TJ. Postoperative nausea and vomiting: can it be eliminated?
JAMA. 2002;287:1233-1236.
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AUTHOR
Carol L. Norred, CRNA, MHS, is a nurse anesthetist researcher and clinical instructor in the Department of Anesthesiology at the University of
Colorado Health Sciences Center (UCHSC), Denver, Colo. She also is a
doctoral student in the UCSHC School of Nursing. Norred works clinically as a locum tenens nurse anesthetist licensed in Virginia, Kentucky,
and Colorado.
ACKNOWLEDGMENTS
Carol Norred’s institutional predoctoral training is provided through a
National Research Service Award funded by the National Center for
Complementary and Alternative Medicine and the National Heart, Lung,
and Blood Institute (HL T32 07085).