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Pediatr Drugs 2007; 9 (1): 47-69
1174-5878/07/0001-0047/$44.95/0
REVIEW ARTICLE
 2007 Adis Data Information BV. All rights reserved.
Management of Postoperative Nausea and
Vomiting in Children
Anthony L. Kovac
Department of Anesthesiology, University of Kansas Medical Center, Kansas City, Kansas, USA
Contents
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
1. Incidence, Pathophysiology, and Etiology of Postoperative Nausea and Vomiting (PONV) and Postoperative Vomiting (POV) 49
1.1 Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
1.2 Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
1.3 Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
1.3.1 Anxiety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
1.3.2 Inhalation Anesthetic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
1.3.3 Other Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
2. Antiemetics for PONV and POV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
2.1 Ondansetron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
2.2 Dolasetron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
2.3 Granisetron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
2.4 Dexamethasone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
2.5 Droperidol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
3. Non-Pharmacologic Antiemetic Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
3.1 Isopropyl Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
3.2 P6 Acupuncture and Acupressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
4. Postoperative Pain, Antiemetic Use, and Patient-Controlled Analgesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
5. Specific Emetogenic Surgical Procedures in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
5.1 Strabismus Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
5.1.1 Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
5.1.2 Muscles Repaired and the Oculocardiac Reflex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
5.1.3 Anesthetic Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
5.1.4 Antiemetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
5.2 Tonsillectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
5.2.1 Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
5.2.2 Anesthetic Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
5.2.3 Antiemetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
5.3 Additional Pediatric Surgeries and Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5.3.1 Tympanoplasty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5.3.2 Ear Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5.3.3 Radiofrequency Catheter Ablation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5.3.4 Burn Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5.3.5 Craniofacial Operations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5.3.6 Neurosurgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
5.3.7 Magnetic Resonance Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
6. Development of PONV and POV Management Guidelines and Algorithms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
7. Guidelines for POV Prophylaxis in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
8. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
48
Abstract
Kovac
Postoperative nausea and vomiting (PONV) continues to be a frequent and important cause of morbidity in
children. Postoperative vomiting (POV) is more commonly studied in children than postoperative nausea
because of a child’s inability to effectively express distress after experiencing nausea. POV is problematic in
children and is one of the leading postoperative complaints from parents and the leading cause of readmission to
the hospital. POV occurs twice as frequently in children as in adults, increasing until puberty and then decreasing
to adult incidence rates. Gender differences are not seen before puberty.
POV remains a main cause of morbidity in children because severe vomiting can be associated with
dehydration, postoperative bleeding, pulmonary aspiration, and wound dehiscence. While children have an
increased potential for dehydration and the resulting physiologic impairments, other associated results such as a
delay in hospital discharge or an overnight or longer hospital admission also must be considered.
The two most common emetogenic surgical procedures evaluated in children are strabismus repair and
adenotonsillectomy. The approach to the management of PONV and POV in children is similar to that in adults.
However, as the rate of POV is more frequent in children than in adults, more children are candidates for
antiemetic prophylaxis. The management approach is multifactorial and involves proper preoperative preparation, risk stratification, rational selection of antiemetic prophylaxis, choice of anesthesia technique, and a plan
for postoperative antiemetic therapy.
It is important to identify children at moderate-to-high risk for POV as prophylactic antiemetic therapy is
useful in these children. Antiemetics of choice for POV in children include dexamethasone, dimenhydrinate,
perphenazine, ondansetron, dolasetron, granisetron, and tropisetron. The serotonin (5-hydroxytryptamine;
5-HT3) antagonists are the antiemetic drugs of first choice for POV prophylaxis in children because as a group
they have greater efficacy for preventing vomiting than nausea. The 5-HT3 antagonists can be effectively
combined with dexamethasone with an increase in efficacy. If possible, regional anesthesia should be considered. For those undergoing general anesthesia, the baseline POV risk should be reduced.
Children at moderate-to-high PONV risk should receive combination therapy with two or three prophylactic
antiemetics from different antiemetic drug classes. Reference to and the use of PONV guidelines and management algorithms help improve cost-effective postoperative care.
It is estimated that following anesthesia and surgery, children
have more complications in the postoperative anesthesia care unit
(PACU) recovery area than adults.[1] The majority of these events
are age related, occurring mostly in neonates and infants, and most
involve the respiratory rather than the cardiovascular system. As
children become older, postoperative effects include nausea, retching, and vomiting. Nausea is an unpleasant, subjective sensation
that may or may not be associated with vomiting. Retching is the
synchronous, rhythmic contraction of the abdominal, diaphragmatic, and intercostal muscles that occurs with a closed mouth and
glottis. Vomiting is the forceful expulsion of gastric contents from
the mouth. Postoperative nausea and vomiting (PONV) and postoperative vomiting (POV) continue to be important causes of
morbidity in adults and children, respectively.[2,3] They are among
the main postoperative complaints from parents, and a leading
cause of delayed discharge and/or re-admission to the hospital for
the pediatric patient. A review[4] of 10 772 children undergoing
day surgery found that PONV was the fourth most common reason
for unplanned hospital admission following pain, surgical complications, and surgery late in the day.
 2007 Adis Data Information BV. All rights reserved.
More PONV clinical trials have been conducted in adults than
in children. The limitations involved in analyzing and comparing
older antiemetic studies has resulted in difficulty in applying the
results of randomized clinical trials to actual clinical situations.
The systematic review is an important method that has been used
to understand the efficacy of an intervention in actual clinical
situations and the likelihood of harm or adverse events. It is
especially useful when there is a large amount of data from
numerous clinical trials but still unresolved questions. Concepts
such as the number needed to treat (NNT; the inverse of the
absolute risk reduction) and the number needed to harm (NNH; the
inverse of the absolute risk increase) have been summarized by
Tramér[5-7] for PONV and are useful concepts that can be used to
compare antiemetic drug efficacy and adverse events, respectively.
The improvement resulting from treatment compared with placebo has been used as a measurement of antiemetic efficacy.
Tramér[5] used the example that a 20% improvement in treatment
efficacy above the placebo response indicated that 20% of patients
who received the antiemetic medication would benefit (absolute
risk reduction) from the treatment. If a perfect response is defined
Pediatr Drugs 2007; 9 (1)
Management of Postoperative Nausea and Vomiting in Children
as a 100% improvement, then a 20% response yields an NNT of
five (100% divided by 20%), i.e. five patients would need to
receive the medication for it to have a positive effect in one
patient. Specifically, for an antiemetic medication, an NNT of five
indicates that five patients at risk for PONV would need to receive
the medication in order for one patient not to vomit that would
have vomited had he or she not received the medication. From
Tramér’s[7] evaluation, in children, intravenous droperidol 75 µg/
kg has an NNT of 5 and 4–5 for early (0–6 hours) and late (0–24
hours) vomiting, respectively. Intravenous ondansetron 100 µg/kg
has an NNT of 4–5 and 2–3 for early (0–6 hours) and late (0–24
hours) vomiting, respectively. Intravenous ondansetron 150 µg/kg
has an NNT of 2–3 for early (0–6 hours) vomiting. Regarding
NNH in children, droperidol has an NNH of 91 for extrapyramidal
symptoms. The oculocardiac reflex in children receiving propofol
has an NNH of 4.
This review summarizes the latest data and information regarding the management of PONV in the pediatric patient specifically
with respect to strabismus surgery and adenotonsillectomy. A
summary of anesthetic techniques and application of the recent
PONV consensus guidelines for pediatric patients is presented.
Study references cited in this article were obtained by an
Internet search of Google, OVID, and Netscape databases using
keywords such as ‘postoperative nausea and vomiting,’ ‘PONV,’
‘postoperative vomiting,’ ‘POV,’ ‘pediatrics,’ ‘antiemetics,’
‘5-HT3 antagonists,’ ‘ondansetron,’ ‘granisetron,’ ‘dolasetron,’
‘dexamethasone,’ ‘droperidol,’ ‘meta-analysis,’ ‘systematic review,’ ‘strabismus repair,’ ‘tonsillectomy,’ and ‘adenotonsillectomy.’
49
Various investigators[8-19] have evaluated the reasons for POV
and PONV in the pediatric population. Kotiniemi et al.[8] evaluated
PONV symptoms in children occurring at home following daycase surgery. PONV occurred in 13% of all children evaluated,
and emetic symptoms were most common following tonsillectomy, occurring in 31% of patients. Specific predictors that PONV
would occur at home were: (i) emetic symptoms in the hospital;
(ii) age >5 years; (iii) pain at home; and (iv) the use of postoperative opioids. However, these authors noted that the intraoperative
use of opioids did not affect the incidence of PONV.
Investigators[8-14,16,17] have reported the overall incidence of
POV in children to be between 8.9% and 42% (table I). Surgeryspecific POV in children ranges from 9% to 80%. Interestingly,
Table I. Incidence of postoperative nausea and vomiting (PONV) and
postoperative vomiting (POV) in children
Study
Year
PONV or
POV
Incidence (%)
1982
POV
42
Overall
Rowley and Brown[10]
Patel and
Hannallah[14]
1988
POV
D’Errico et al.[9]
1989
PONV
19
Schofield and White[16]
1989
POV
14
Karlsson et al.[17]
1990
POV
25
Byers et
al.[12]
8.9
1995
PONV
18.1
Kotiniemi et al.[8]
1997
PONV
13
Villeret et al.[13]
2002
PONV
2005
PONV
28
1983
POV
80
1999
PONV
37
1992
POV
70
2002
POV
15.6
1994
POV
63
2002
PONV
60
McCall et al.[24]
1999
PONV
69
al.[25]
1999
PONV
45 (non-scalp);
100 (scalp)
1996
POV
66
1995
POV
9
Khalil et
al.[11]
9.4
Surgery/procedure specific
Strabismus
1. Incidence, Pathophysiology, and Etiology of
Postoperative Nausea and Vomiting (PONV) and
Postoperative Vomiting (POV)
Abramowitz et al.[21]
Kuhn et
al.[22]
Tonsillectomy
Ferrari and Donlon[19]
1.1 Incidence
Despite the introduction of new antiemetic medications, the
incidence of POV in children is estimated to be twice the incidence
for both nausea and vomiting after surgery in adults. It is difficult
to estimate the true incidence of nausea in children who may not be
able to express their degree of discomfort associated with this
subjective feeling. This is the major reason why antiemetic studies
in children have evaluated POV rather than PONV. However,
failure to report nausea in these studies does not mean that nausea
is not experienced in children. If the true incidence of nausea could
be measured accurately, the incidence of PONV (see table I)
would be even higher in the pediatric age group.[1,8-10]
 2007 Adis Data Information BV. All rights reserved.
Stewart et
al.[20]
Plastic surgery: ears
Ridings et al.[18]
Radiofrequency catheter ablation
Erb et al.[23]
Burn reconstruction surgery
Stubbs et
Craniotomy
Furst et al.[26]
Magnetic resonance imaging
Murray et al.[15]
Pediatr Drugs 2007; 9 (1)
50
Kovac
the study by Stewart et al.[20] in pediatric patients undergoing
tonsillectomy revealed a POV incidence of 15.6% despite the fact
that these children received intraoperative antiemetics.
A study by D’Errico et al.[9] evaluating the incidence and
reasons for prolonged PACU stay and unplanned hospital admission determined that the most common cause of prolonged length
of PACU stay was due to PONV (19% of children), followed by
respiratory complications (16%). Unplanned hospital admissions
following outpatient surgery were primarily due to respiratory and
surgical reasons (32% and 30%, respectively), and these outcomes
had a significant impact on hospital staffing, institutional costs,
family convenience, and patient satisfaction; PONV accounted for
8%.
A lower incidence of POV of 22–40% was observed by Rowley
and Brown[10] in children aged <3 years compared with 42–51% in
children >3 years. This was supported by Khalil et al.[11] who
reported a POV incidence of 27% and 28% in children aged 1–12
months and 13–24 months, respectively. Byers et al.[12] found that
the highest incidence occurred in children undergoing ear, nose,
and throat (ENT) procedures and increased with age. Avoidance of
intraoperative opioids and the use of local anesthesia and/or
NSAIDs for pain control were found to reduce the incidence of
PONV.
Villeret et al.[13] evaluated the incidence of PONV during the
first 24 hours following elective ambulatory pediatric surgery,
specifically excluding head and neck procedures. PONV occurred
most frequently in the hospital during the first 3 hours after
anesthesia but rarely during the journey home and was associated
with: (i) increasing age; (ii) previous history of PONV;
(iii) tracheal intubation; (iv) use of the laryngeal mask airway;
(v) controlled or manual ventilation; and (vi) opioids. The type of
surgery, premedication, type of anesthesia induction, regional
anesthesia, use of nitrous oxide, anesthesia duration, length of
PACU stay, and duration of the journey home after discharge were
not found to be significantly associated with PONV.
1.2 Pathophysiology
Mechanisms of PONV and POV in children are similar to those
in adults. However, they appear to be more procedure specific in
children as a result of swallowing of blood in adenotonsillectomy
patients, stimulation of extraocular muscles in strabismus surgery,
and labyrinthine, otic, and vestibular stimulation in ear surgery.
The vomiting areas in the CNS include the emetic center,
nucleus of the solitary tract, area postrema, and chemoreceptor
trigger zone. The chemoreceptor trigger zone is located in the area
postrema near the emetic center at the bottom of the fourth
ventricle (figure 1). The process of nausea, retching, and vomiting
 2007 Adis Data Information BV. All rights reserved.
Cerebellum
Area postrema
and chemoreceptor
trigger zone
Nucleus of the
solitary tract
Fourth ventricle
Vomiting centre
Fig. 1. Anatomic location of the brain postoperative nausea and vomiting
receptor area: vomiting center, nucleus of the solitary tract, area postrema,
and chemoreceptor trigger zone (reproduced from Kovac,[29] with permission).
is coordinated by the vomiting center. Stimulation can be initiated
from peripheral areas such as the oropharynx, mediastinum, gastrointestinal tract, renal pelvis, peritoneum, or genitalia, and from
central areas such as the cerebral cortex, and labyrinthine, otic, or
vestibular apparatus.[27-29]
It is hypothesized that PONV after strabismus surgery may be
due to an altered visual perception and afferent impulses causing
the oculoemetic reflex, which is analogous to the oculocardiac
reflex. An increase in the number of ocular muscles that are
repaired is reported to increase the risk of POV. Afferent stimuli
are relayed from peripheral to central vomiting centers and the
area postrema via the glossopharyngeal and vagal nerves, which
may help explain the cause of PONV following adenotonsillectomy and hernia repair.[27,28,30-33]
Patients who have a history of motion sickness have a higher
incidence of PONV, as stimulation of the vestibular apparatus of
the inner ear due to movement of endolymph in the semicircular
canals stimulates otolith cells in the utricle. Transmission of
impulses to the chemoreceptor trigger zone and vomiting center
occurs, causing the sensation of motion sickness with the occurrence of nausea and vomiting. Motion sickness or vertigo as a
result of vestibular stimulation also can be a consequence of
middle ear surgery.[32,33]
Sensory stimuli causing PONV include tactile stimulation of
the posterior pharynx (from oral or nasal airway devices, and
nasogastric or endotracheal tubes), operations on extraocular muscles (stimulating the oculocardiac reflex), as well as stretching and
inflammation or injury to the airway, upper abdomen, gastrointestinal tract, renal pelvis, bladder, or testes.[32-36]
Pediatr Drugs 2007; 9 (1)
Management of Postoperative Nausea and Vomiting in Children
The close proximity of areas associated with balance, vasomotor activity, salivation, respiration, and bulbar control to the vomiting center corresponds to the physiologic reactions often seen with
POV and PONV, such as salivation, increased swallowing, sweating, pallor, tachypnea, tachycardia, cardiac dysrhythmias, and
motion sickness.[36,37]
Metabolic, biochemical, and environmental factors that are
mediated by the vomiting center and the chemoreceptor trigger
zone include uremia, diabetes mellitus (hypo- or hyperglycemia),
electrolyte disturbances (sodium, potassium), hormonal imbalances (estrogen, progesterone), chemotherapy, and radiation therapy.[33,36,37]
The chemoreceptor trigger zone contains high concentrations
of enkephalin, opioids, and dopamine (D2) receptors. The area
postrema has high concentrations of opioids, D2, serotonin
(5-hydroxytryptamine; 5-HT), and neurokinin-1 (NK-1) receptors
(table II). The nucleus of the solitary tract has a predominance of
enkephalin, histamine, muscarinic, cholinergic, and NK-1 receptors. These emetic neuroreceptor areas serve as sensors and are
stimulated by drugs, electrolytes, and metabolic chemicals, causing impulses to be relayed to the vomiting center, thereby initiating the vomiting reflex. The mechanism of action of the antiemetic
medications commonly used for PONV involves blockade of these
multiple neurochemical receptor sites; this helps explain why a
combination or multimodal antiemetic approach may be necessary
in some high-risk patients.[20,28,32,37-42]
1.3 Etiology
Table III. Simplified risk score for postoperative vomiting (POV) in children[44]
No. of risk factorsa
POV risk (%)
0
10
1
10
2
30
3
50
4
a
70
Risk factors include: strabismus surgery; age ≥3y; surgery >30 min;
history of POV or postoperative nausea and vomiting in relatives
(mother, father, siblings).
These include: (i) strabismus surgery; (ii) duration of anesthesia
>30 minutes; (iii) history of POV or previous history of POV,
PONV, or motion sickness in relatives; (iv) age ≥3 years; and
(v) use of postoperative opioids. When 0, 1, 2, 3, or 4 of these risk
factors were present, the POV risk was 10%, 10%, 30%, 50%, or
70%, respectively (table III). A variety of authors have also
evaluated the effects of other patient- and anesthetic-related factors.[45-59]
1.3.1 Anxiety
The relationship between anxiety and PONV appears to be
minimal. Wang and Kain[46] determined that preoperatively controlling for anxiety had no predictive value for the occurrence of
PONV in children in the PACU or during the first postoperative
day.
1.3.2 Inhalation Anesthetic Agents
Similar to adults, surgical-, patient-, and anesthesia-related
factors play an important part in the etiology of PONV and POV in
children. Lerman[37] noted that while a greater incidence of PONV
is reported in children compared with adults, this must be interpreted with caution; postoperative follow-up data were not collected prospectively for 24 hours in all patients. However, as previously determined in adults by Apfel et al.,[43] Eberhart et al.[44]
prospectively determined risk factors for POV in pediatric surgery.
Table II. Mid-brain neurochemical emetogenic receptor locations (reproduced from Kovac,[29] with permission)
Mid-brain location
Receptorsa
Area postrema
Opioid, dopamine, serotonin
(5-hydroxytryptamine), neurokinin-1
Chemoreceptor trigger
zone
Enkephalin, opioid, dopamine
Nucleus of solitary tract
Enkephalin, histamine, neurokinin-1,
muscarinic, cholinergic
a
51
The vomiting center is the coordinator for these receptors to initiate
the vomiting reflex.
 2007 Adis Data Information BV. All rights reserved.
Numerous studies have evaluated the effect of anesthetic technique and inhalation agents on PONV.[45-56,59] In an attempt to
quantify the relative importance of operative anesthetic and patient-specific factors for the development of PONV, Apfel et al.[43]
conducted a randomized controlled trial of 1180 children and adult
patients at high risk for PONV. They concluded that inhalation
anesthetic agents caused early but not delayed PONV, and that this
effect was more significant than the effects of other risk factors.
Their conclusion was that in adult and pediatric patients at high
risk for PONV, it makes better sense to avoid inhalation anesthesia
rather than simply adding an antiemetic, which may still be needed
to prevent or treat delayed PONV. A similar conclusion was
reached by Elliott et al.[48] who compared inhalation versus intravenous anesthesia techniques and determined that there was a
higher incidence of pre-discharge PONV and resulting higher
costs if sevoflurane was used for anesthesia induction and maintenance compared with using propofol.
Goa et al.[49] reviewed the use of sevoflurane in pediatric
anesthesia. While sevoflurane provided a more rapid induction and
anesthesia emergence than halothane, postoperative pain and
Pediatr Drugs 2007; 9 (1)
52
Kovac
PONV were more frequent with sevoflurane. This review brings
attention to the possible correlation between pain and PONV or the
treatment of pain with opioids and PONV.
Use of regional anesthesia has been suggested to decrease
PONV. Oddby et al.[50] evaluated the use of sevoflurane alone
versus spinal anesthesia combined with propofol for sedation in
pediatric ambulatory surgery. While a reduced number of POV
episodes and better immediate postoperative analgesia were found
with spinal anesthesia than with propofol sedation, there was no
difference between the two regimens regarding time to discharge
or overall patient satisfaction.
Two studies[10,44] determined that length of surgery >30 minutes
has a positive increased correlation with POV in children.
The effect of nitrous oxide on PONV in adults and children has
been controversial, and most clinical data have come from adult
studies. The results of three systematic reviews[51-53] concluded
that omitting nitrous oxide from general anesthesia decreases
PONV (NNT = 5). In other words, five high-risk patients would
need to undergo a nitrous oxide-free anesthetic for one to not
vomit who would have done so if they had received nitrous oxide.
Nevertheless, the results in children are controversial as two other
studies reached different conclusions. Splinter and Komocar[54]
studied the effects of nitrous oxide on POV in children who
underwent outpatient dental restorations under halothane anesthesia. Even though the POV rate in the PACU was slightly less for
the no nitrous oxide versus the nitrous oxide group (15% vs 24%),
they concluded that nitrous oxide did not significantly affect POV.
Similarly, another study[55] concluded that nitrous oxide in combination with sevoflurane was not associated with an increase in
POV; the incidence of POV for the nitrous oxide and no nitrous
oxide groups was similar (14.3% and 15.5%, respectively).
Hannallah et al.[56] evaluated speed and quality of recovery,
comparing propofol with thiopentone or halothane for induction
and maintenance of anesthesia. Children who received propofol
had a faster recovery, were discharged home earlier, and had a
lower POV incidence. However, it should be stressed that the risk
of propofol-related bradycardia is particularly high in children
undergoing strabismus surgery, due to stimulation of the oculocardiac reflex. The NNH of propofol causing the oculocardic
reflex in children has been estimated to be four despite the prophylactic use of anticholinergics.[60]
1.3.3 Other Factors
Withholding oral fluids postoperatively from children undergoing day surgery has significantly reduced the incidence of POV.
This difference was seen whether or not a patient was at high risk
for POV (including operations for strabismus, adenoidectomy,
and/or tonsillectomy). Interestingly, the greatest effect of with 2007 Adis Data Information BV. All rights reserved.
holding oral fluids was seen in patients who received opioids, in
whom POV was reduced from 73% to 36%.[57] Similarly, another
study[58] determined that not requiring pediatric patients aged 1
month to 18 years to consume clear fluids postoperatively decreased the incidence of POV and time to discharge from the
PACU.
Murat et al.[61] determined an increased correlation with POV in
the PACU in children aged ≥8 years who were intubated for ENT
surgery.
2. Antiemetics for PONV and POV
2.1 Ondansetron
As ondansetron is relatively free of adverse events, numerous
researchers[62-65] have concluded that ondansetron is a safe firstline antiemetic for children. Ondansetron is the only 5-HT3 antagonist with US FDA approval for use in children as young as 1
month.[11]
Ondansetron has been determined to have good antiemetic
efficacy for the prevention of POV in children, particularly when
combined with dexamethasone. In several large, dose-ranging, and
placebo-controlled trials,[63-67] intravenous ondansetron 0.05–0.15
mg/kg or oral ondansetron 0.1 mg/kg was significantly more
effective than placebo for the prevention of emesis in children
undergoing highly emetogenic surgery, which included tonsillectomy or strabismus repair. Intravenous ondansetron 0.05 mg/kg
was determined to be the lowest effective dose.[66] Prophylactic
ondansetron 0.1 mg/kg (up to a total dose of 4mg) reduced POV in
pediatric patients regardless of surgical or anesthesia factors.[67]
The ondansetron-treated children reached the criteria for home
readiness 30 minutes earlier than the placebo-treated patients.
Rapid intravenous administration of ondansetron 0.15 mg/kg or
metoclopramide 0.25 mg/kg was not associated with changes in
vital signs or oxygen saturation.[68]
In children undergoing strabismus surgery, a POV prophylactic
intravenous study[69] concluded that ondansetron 0.1 mg/kg and
droperidol 0.075 mg/kg had similar antiemetic efficacy and were
significantly more effective compared with placebo or
metoclopramide 0.25 mg/kg. A meta-analysis[70] of 54 studies
compared the efficacy and safety of ondansetron, droperidol, or
metoclopramide for preventing PONV in adults and POV in
children. While ondansetron was determined to be more effective
than droperidol, both antiemetics alone were found to be more
effective than metoclopramide in preventing POV in children.
Antiemetic studies in children have been limited in study
design and have had low power, as these studies have been
powered to detect differences between an antiemetic drug and
Pediatr Drugs 2007; 9 (1)
Management of Postoperative Nausea and Vomiting in Children
placebo and not between anesthetic regimens. Prophylactic PONV
antiemetic studies are easier to conduct than treatment studies.
Consequently, as in adults, there have been fewer POV treatment
studies in children. A large treatment study[71] evaluated the use of
intravenous ondansetron in established POV in 2720 pediatric
outpatients undergoing general anesthesia with nitrous oxide. A
single intravenous dose of ondansetron 0.1 mg/kg (up to a maximum dose of 4mg) was concluded to be effective and well tolerated (as rescue medication) for prevention of further episodes of
POV and resulted in a shorter time to PACU discharge.
Ummenhofer et al.[72] conducted a double-blind, prospective
prophylactic study on the effect of intravenous ondansetron
0.1 mg/kg or placebo administered before surgical incision, and
the effect of rescue antiemetics in patients in whom prophylaxis
failed. For rescue medication, patients received either intravenous
ondansetron 0.1 mg/kg or droperidol 0.02 mg/kg. As ondansetron
was found to be effective for the prevention of PONV for the first
4 hours after general anesthesia with lower sedation scores compared with droperidol, this was judged to be advantageous, especially in ambulatory surgery. Interestingly, the incidence of lateonset PONV occurring >4 hours postoperatively was not found to
be influenced by the preoperative prophylactic administration of a
one-time dose of ondansetron.
2.2 Dolasetron
Dolasetron has been recommended for POV prophylaxis in
children aged 2 years and older. An intravenous equivalence doseranging study[73] determined the lowest effective dose of dolasetron (45, 75, 350, or 700 µg/kg) that was equivalent to the US
FDA-approved ondansetron intravenous dose of 100 µg/kg. Intravenous dolasetron 350 µg/kg was determined to be the lowest
effective dose providing acceptable equivalent efficacy and patient
satisfaction scores to those with the intravenous ondansetron
100 µg/kg dose.
In a strabismus study, Wagner et al.[74] determined that the
efficacy of intravenous dolasetron 350 µg/kg in preventing PONV
in children was equivalent to that of an intravenous dolasetron
12.5mg fixed dose. In a prophylactic intravenous study[75] of
pediatric patients undergoing tonsillectomy who also received
intravenous dexamethasone 1 mg/kg (up to 25mg), dolasetron 500
µg/kg (up to 25mg) plus intravenous dexamethasone 1 mg/kg (up
to 25mg) was found to be equivalent to a prophylactic ondansetron
dose of 150 µg/kg (up to 4mg).
2.3 Granisetron
Granisetron has also been recommended for POV prophylaxis
in children aged 2 years and older. Numerous studies[76-80] have
 2007 Adis Data Information BV. All rights reserved.
53
evaluated the effectiveness of granisetron for the prevention of
POV following pediatric surgery with most clinical studies conducted in Japan by Fujii et al.[76-79]
An oral dose of granisetron 40 µg/kg was determined to be the
lowest effective dose for the prevention of POV following inguinal hernia and phimosis-circumcision surgery.[76] A dose-ranging
study[77] determined that intravenous granisetron 40 µg/kg was the
minimally effective dose for POV prevention. After inhalation
anesthesia induction, intravenous granisetron 40 µg/kg was found
to be effective for preventing POV in children with a history of
motion sickness.[78] Intravenous granisetron 40 µg/kg was also the
lowest effective dose for preventing POV and retching following
strabismus repair and tonsillectomy surgery.[79] This conclusion
was also reached by Cieslak et al.[80] who studied pediatric outpatients and determined that intravenous granisetron 40 µg/kg was
more effective than intravenous granisetron 10 µg/kg or placebo,
but that this dose had a higher acquisition cost.
Kranke et al.[81] evaluated the influence of a dominating center
in a quantitative systematic review of granisetron for preventing
PONV. A total of 27 randomized clinical trials were assessed;
2938 patients including children and adolescents were included in
the analysis. In the dominating center, low-dose granisetron was
determined to be ineffective, while high-dose granisetron was
found to be effective. In contrast, the other centers showed both
low- and high-dose granisetron to be effective. These researchers[81] concluded that the overall results and dose-response characteristics of meta-analyses may be significantly altered by one
dominating center. A cautious statistical analysis was previously
conducted by Kranke et al.[82] on the distribution of side effects of
comparative groups reported by the dominating center and suggested that the reported data are idealized.
With these data in mind, the safety and efficacy of granisetron
has not been established in children for the prevention and treatment of PONV and does not have US FDA approval for PONV in
children. The 2003 Consensus Guidelines[83] contained no granisetron dosing recommendations for PONV in children.
2.4 Dexamethasone
A quantitative, systematic review[84] on the use of dexamethasone for the prevention of PONV evaluated data from 1946 adult
and pediatric patients studied in 17 randomized controlled trials in
which 16 different dexamethasone dose regimens were used. An 8
or 10mg intravenous dose in adults and a 1 or 1.5 mg/kg intravenous dose in children were the most frequently used dexamethasone doses. Using these doses, the NNT to prevent early
(0–6 hours) and late (0–24 hours) POV was seven and four,
respectively. Late efficacy with dexamethasone was a more proPediatr Drugs 2007; 9 (1)
54
Kovac
nounced effect in children than in adults. A single prophylactic
dose of dexamethasone was a more effective antiemetic compared
with placebo without any clinically relevant evidence of toxicity
or adverse effects in otherwise healthy patients. While the best
PONV prophylaxis was achieved with the combination of dexamethasone and a 5-HT3 receptor antagonist, the authors noted
that optimal doses of this combination requires further investigation. However, other studies[63,64] determined that intravenous
ondansetron 50 µg/kg when combined with intravenous dexamethasone 150 µg/kg was significantly more effective at reducing POV than either medication used alone.
2.5 Droperidol
Henzi et al.[85] systematically reviewed the efficacy, doseresponse, and adverse effects of droperidol for the prevention of
PONV in 76 randomized controlled trials involving 5351 patients
receiving 24 different antiemetic regimens. The average incidence
of early and late PONV in the control groups was 34% and 51%,
respectively. Droperidol was determined to be more efficacious
than placebo in preventing PONV in children with an NNT of four
and five to prevent early and late vomiting, respectively. Two
children were noted to have had extrapyramidal symptoms, and
the NNH in children was determined to be 91. The effect of
droperidol on nausea was short-lived but was more pronounced
than its effect on vomiting, with sedation and drowsiness being
dose dependent, and a small risk for extrapyramidal symptoms
being present.
In 1994 it was reported that droperidol caused a dose-dependent
prolongation of the QT interval.[86] While previously there was
warning of potential sudden cardiac death regarding the use of
droperidol when administered at high doses (>25mg) to psychiatric patients, in December 2001 a ‘black box’ warning[87] of cardiac
effects regarding the use of droperidol for PONV, issued by the US
FDA, was included in the package insert. The revised warning
cautioned that even low droperidol doses such as 0.625mg for
PONV should be used only when other first-line antiemetic medications are not effective. Data regarding the NNH of cardiac
effects with droperidol were not available because of the low
number of adverse events previously reported. The majority of the
reports of cardiovascular events with droperidol were in adults;
however, cardiovascular effects have also been observed in children.
Stuth et al.[88] conducted a retrospective analysis of 20 children
of whom 18 had undergone cardiopulmonary bypass. An intravenous droperidol 100 µg/kg bolus was given for perioperative
sedation. Droperidol caused a significant but transient increase in
the QTc interval; it was still present at 15 minutes but had resolved
 2007 Adis Data Information BV. All rights reserved.
within 30 minutes of the bolus dose. No associated arrhythmias
were observed. These researchers followed the ECG for a minimum of 1 hour and were able to evaluate the length of time (15–30
minutes) in which there was a dose-dependent prolongation of the
QT interval. The authors noted that a large prospective study is
needed to identify the true risk of arrhythmias in the pediatric
population.
The US FDA ‘black box’ recommendation indicated that all
surgical patients should undergo 12-lead ECG monitoring prior to
the administration of droperidol to determine if a prolonged QTc
interval was present and to continue ECG monitoring for 3 hours
after droperidol administration.[87] Because of these recommendations, this situation places the practising anesthesiologist in a
dilemma, as there can be a significant difference between standard
clinical practice and the package insert recommendation for
droperidol.
An editorial by Berry[89] noted that the Stuth et al.[88] study cast
doubt about the recommendations in the ‘black box’ warning for
ECG monitoring. Reasonable practice suggests that proper evaluation of patients for potential problems should allow the use of a
drug such as droperidol in an appropriate manner while monitoring for expected potential complications.
Further research must be completed to resolve the role of lowdose droperidol as an antiemetic. The US FDA is exploring
options to obtain data that satisfy regulatory standards for the
demonstration of safety and efficacy at doses lower than 2mg.
Chang and Rappaport[90] urged practitioners to participate in the
postmarketing safety assessment process by reporting all potential
drug-related adverse events. The website www.fda.gov/
medwatch[91] contains information on ‘reporting adverse events’.
3. Non-Pharmacologic Antiemetic Approaches
3.1 Isopropyl Alcohol
Isopropyl alcohol is a novel alternative method to alleviate
PONV in children who are scheduled to undergo elective outpatient surgery under general anesthesia. One study[92] randomized
children to inhale an isopropyl alcohol wipe versus saline, repeating this for up to three times. After three sequences, 65% in the
isopropyl group versus 26% in the saline group had a significant
reduction of either nausea or vomiting. However, this reduction
was transient in children with established PONV; recurrent nausea
or vomiting occurred within 20–60 minutes.
3.2 P6 Acupuncture and Acupressure
A meta-analysis[93] was conducted of 19 randomized trials on
the efficacy of preventing PONV with acupuncture, acupressure,
Pediatr Drugs 2007; 9 (1)
Management of Postoperative Nausea and Vomiting in Children
acupoint stimulation, electro-acupuncture, and transcutaneous
electrical nerve stimulation in children and adults. The primary
outcomes for the incidence of nausea, vomiting, or both were
evaluated at 0–6 hours (early efficacy) or 0–48 hours (late efficacy) after surgery. While the results of these techniques in adults
were found to be statistically significant, no benefit was found in
children.
In contrast, Wang and Kain[94] evaluated P6 acupoint injections
versus droperidol for control of early PONV in children and
concluded that the P6 acupoint injections were as effective as
droperidol in controlling early PONV. Similarly, another study[95]
concluded that laser P6 stimulation, when administered 15 minutes before anesthesia induction for strabismus surgery and 15
minutes after arriving in the PACU, resulted in a significantly
lower incidence of POV. In addition, another study[96] evaluated
the effect of P6 electroacupuncture prophylaxis following pediatric tonsillectomy with or without adenoidectomy and concluded
that perioperative P6 stimulation in awake children significantly
reduced nausea, but there was no reduction in emetic episodes or
the need for rescue antiemetics.
While the efficacy of P6 acupuncture for PONV prevention is
believed to be similar to that of commonly used pharmacotherapies, its appropriate role in the prevention and treatment of PONV
in children requires further study.
4. Postoperative Pain, Antiemetic Use, and
Patient-Controlled Analgesia
Similar to adults, nausea and vomiting in children related to
opioids is difficult to treat, and the effectiveness of antiemetics for
opioid-induced nausea and vomiting is controversial.
Children who received intravenous tropisetron 0.1 mg/kg (up to
a maximum of 5mg) had a lower incidence and severity of vomiting during patient-controlled opioid analgesia, with only one child
vomiting more than twice, compared with nine children in the
control group.[97] Prophylactic intravenous dixyrazine was found
to significantly reduce the incidence and severity of PONV in
children who used patient-controlled analgesia with morphine
after major surgery.[98] In contrast, another study[99] evaluated the
effectiveness of adding antiemetics to the morphine solution in
patient-controlled analgesia syringes used by children after appendectomy, and determined that addition of prophylactic antiemetics
such as ondansetron or droperidol did not reduce the incidence of
PONV. Thus, this continues to be a controversial topic.
 2007 Adis Data Information BV. All rights reserved.
55
5. Specific Emetogenic Surgical Procedures
in Children
5.1 Strabismus Surgery
5.1.1 Incidence
Over the last 20 years the incidence of POV in children having
strabismus surgery has ranged from 37% to 80%.[21,22] The effects
of various anesthetic techniques and antiemetics (see also section
5.1.3) on POV in children undergoing strabismus surgery are
summarized in tables IV and V, respectively.[69,100-119]
5.1.2 Muscles Repaired and the Oculocardiac Reflex
In an evaluation of children who received no prophylactic
antiemetic medication for strabismus surgery, the overall incidence of nausea and vomiting was determined as 37% and 32%,
respectively.[115] Splinter et al.[115] determined that while the incidence of POV was not affected by the use of intravenous midazolam, droperidol 50 µg/kg, or duration of anesthesia, the number of
repaired eye muscles was a significant predictor of POV, with an
incidence of POV 2.5-fold higher with surgery performed on both
eyes compared with one eye.
The relationship between the oculocardiac reflex and PONV
was studied in children receiving a prophylactic dose of intravenous atropine 0.02 mg/kg, alfentanil, and no nitrous oxide. The
investigators concluded that while a thiopental-isoflurane technique with alfentanil resulted in a moderate risk for POV, adding
intravenous ondansetron 4mg significantly decreased this risk.
The NNT in the early postoperative period was six (six children
needed to be treated for one to benefit). Propofol and the combination of intravenous propofol and lidocaine (lignocaine) 2 mg/kg
demonstrated no benefit in decreasing POV but increased the risk
of the oculocardiac reflex despite a high dose of prophylactic
intravenous atropine 0.02 mg/kg.[117]
5.1.3 Anesthetic Techniques
Diazepam
The combination of diazepam and atropine 0.015 mg/kg has
been shown to decrease POV following strabismus surgery.[101]
The overall incidence of POV and the need for rescue antiemetics
was significantly higher for the first 24 hours after using a
sevoflurane-nitrous oxide technique compared with a propofolnitrous oxide technique. However, there was a significantly higher
incidence of bradycardia from the oculocardiac reflex, using a
propofol-nitrous oxide technique.[102]
Opioids
Several studies[100,103,104] have evaluated anesthetic techniques
combined with opioids for strabismus surgery. Rectal diclofenac
Pediatr Drugs 2007; 9 (1)
56
Kovac
Table IV. Effects of anesthetic techniques on postoperative vomiting (POV) in children
Study
Surgery No. of
type
pts
Age
(y)
Anesthetic technique
Conclusions (effect of technique on POV)
Wennstrom and
Reinsfelt[100]
S
50
4–16
Rectal diclofenac vs morphine
Diclofenac < morphine
Ozcan et al.[101]
S
50
4–15
Diazepam + atropine premedication vs
placebo
Diazepam + atropine ↓ POV vs placebo
Gurkan et al.[102]
S
40
3–15
Propofol-nitrous oxide vs sevofluranenitrous oxide
Propofol-nitrous oxide < sevoflurane-nitrous oxide
Standl et al.[103]
S
90
3–10
Propofol-sufentanil vs propofol-isoflurane
Propofol-sufentanil < propofol-isoflurane
Eltzschig et al.[104]
S
81
2–12
Fentanyl vs remifentanil
Fentanyl = remifentanil (no change in POV)
Pandit et al.[105]
T
60
4–12
Nitrous oxide vs no nitrous oxide
Nitrous oxide = no nitrous oxide
Ved et al.[106]
T
80
3–10
Halothane + nitrous oxide vs propofol
Halothane + nitrous oxide = 3-fold ↑ POV vs propofol
Zestos et al.[107]
T
252
2–12
Subhypnotic propofol 0.2 mg/kg dose
No effect on POV (subhypnotic dose)
Chhibber et al.[108]
T
93
3–16
Atropine-neostigmine vs glycopyrrolateneostigmine for muscle relaxant reversal
Atropine-neostigmine < glycopyrrolate-neostigmine
pts = patients; S = strabismus repair; T = tonsillectomy; < indicates significantly less effect; > indicates significantly greater effect; = indicates similar effect;
↑ indicates increase; ↓ indicates decrease.
1 mg/kg was associated with less POV than intravenous morphine
0.05 mg/kg in children aged 4–16 years.[100] A propofol-sufentanil
anesthetic technique compared with propofol-isoflurane resulted
in less POV requiring fewer antiemetic rescues during the early
postoperative phase in the PACU, irrespective of the use of nitrous
oxide.[103] One study[104] determined that the number of children
who experienced POV did not differ significantly between groups
irrespective of whether or not they received fentanyl. The effects
of ketorolac and fentanyl on POV and analgesic requirements
were evaluated in children who received no antiemetic prophylaxis.[120] It was concluded by the study investigators that opioids such
as fentanyl should be avoided as intravenous fentanyl 1 µg/kg had
a greater incidence of POV compared with intravenous ketorolac
0.9 mg/kg.
This gives further proof of the emetogenic effects of opioids
and how the use of NSAIDs such as ketorolac help decrease
PONV.
Clonidine
The effect of oral clonidine on POV following strabismus
surgery is controversial. While Handa and Fujii[112] concluded that
oral clonidine 4 mg/kg enhanced the antiemetic effect of propofol,
a study by Gulhas et al.[113] reported that premedication with oral
clonidine 4 mg/kg 1 hour prior to surgery did not reduce POV.
5.1.4 Antiemetics
Dixyrazine
Karlsson et al.[114] concluded that avoidance of opioids and the
use of intravenous prophylactic dixyrazine 0.25 mg/kg significant 2007 Adis Data Information BV. All rights reserved.
ly reduced the incidence of POV following strabismus surgery
compared with opioid use.
Dimenhydrinate
Numerous studies have evaluated the effectiveness of
dimenhydrinate in the management of POV.[109-111,121] Two studies[109,110] comparing the efficacy of rectal dimenhydrinate 50mg
administered 30 minutes before the start of strabismus surgery and
placebo reported the incidence of POV to be significantly lower
with dimenhydrinate than placebo (15–30% vs 60–75%). However, the dimenhydrinate-treated patients tended to be more sedated
and required observation in the PACU for a longer period than the
placebo group.[109] Another study[111] determined that even though
children who received intravenous dimenhydrinate 0.5 mg/kg had
less POV compared with those who received placebo, the time to
arousal and hospital discharge did not differ between groups.
Kranke et al.[121] conducted a meta-analysis of dimenhydrinate
and determined that it was an inexpensive, older antiemetic that
was effective clinically. However, these researchers also concluded that the dose-response curve, estimation of adverse effects,
optimal time of administration, and benefit of repetitive doses
remains unclear.
Ondansetron
Intravenous ondansetron 75 µg/kg has been determined to be
the optimum, lowest effective dose and to be as effective as
150 µg/kg in preventing PONV and improving outcomes for
strabismus surgery.[119] Antiemetic efficacy was similar with administration of intravenous ondansetron 100 µg/kg either before
(at induction) or after surgical manipulation of extraocular musPediatr Drugs 2007; 9 (1)
Management of Postoperative Nausea and Vomiting in Children
cles (at the end of surgery).[122] Children given ondansetron had
less than half the risk of POV compared with those given placebo,
with no difference between groups in the incidence of side effects.
There was a significant decrease in POV with a corresponding
increase in dose (0.04, 0.1, or 0.2 mg/kg) of ondansetron.[117]
While intravenous ondansetron 100 µg/kg and droperidol
75 µg/kg have been determined to be more effective than intravenous metoclopramide 250 µg/kg, as compared with placebo, in
decreasing the incidence of pre-hospital discharge vomiting in
children undergoing strabismus surgery, no antiemetic was found
57
to be more effective than placebo in decreasing the incidence of
post-discharge vomiting.[69] The efficacy and safety of intraoperative intravenous droperidol followed by an oral dose of
dimenhydrinate at home did not differ from the use of intravenous
ondansetron administered in the operating room followed by oral
ondansetron at home.[123]
Splinter et al.[124] evaluated the effect of intravenous ondansetron 0.15 mg/kg (up to a maximum of 8mg) versus intravenous
propofol 2.5–3.5 mg/kg on POV after strabismus surgery in children. Inhalation halothane, nitrous oxide, oxygen, or propofol was
Table V. Effects of antiemetics on postoperative vomiting (POV) in children undergoing strabismus surgery
Study
No. of
pts
Age (y)
Antiemetic
Conclusions
Wennstrom and
Reinsfelt[100]
50
4–16
Diclofenac 1 mg/kg
Morphine sulfate 0.05 mg/kg
Diclofenac < morphine sulfate
Welters et al.[109]
30
4–10
Rectal dimenhydrinate 0.50mg
Placebo
Dimenhydrinate > placebo. ↑ sedation with dimenhydrinate
Schlager et al.[110]
40
3–12
Dimenhydrinate 50mg
Placebo
Dimenhydrinate < placebo
Vener et al.[111]
80
1–12
Dimenhydrinate 0.5 µg/kg
Placebo
Dimenhydrinate > placebo
Handa and Fujii[112]
60
2–12
Diazepam 0.45 mg/kg
Clonidine 4 µg/kg
Clonidine > placebo
Gulhas et al.[113]
80
3–12
Clonidine 4 µg/kg
Placebo
Clonidine = placebo
Karlsson et al.[114]
58
2–16
Dixyrazine
Placebo
Dixyrazine > placebo
Splinter et al.[115]
393
1.5–14
Midazolam 50 µg/kg
Droperidol 50 µg/kg
Midazolam = droperidol
↑ in the number of eye muscles → ↑ POV
Bowhay et al.[117]
131
2.5–12.5
Ondansetron 0.4 mg/kg
Ondansetron 0.1 mg/kg
Ondansetron 0.2 mg/kg
Placebo
Ondansetron 0.4 > ondansetron 0.2 > ondansetron 0.1 >
placebo
Scuderi et al.[69]
160
1–12
Predischarge vs postdischarge
Placebo
Metoclopramide 250 µg/kg
Ondansetron 100 µg/kg
Droperidol 75 µg/kg
Predischarge: droperidol = ondansetron > metoclopramide =
placebo
Postdischarge: droperidol = ondansetron = metoclopramide
= placebo
Sadhasivam et al.[118]
180
2–12
Ondansetron
Ondansetron
Ondansetron
Ondansetron
Ondansetron
Placebo
Shende et al.[119]
240
1–15
Droperidol 15 µg/kg
Ondansetron 0.1 mg/kg
Droperidol + ondansetron
25 µg/kg
50 µg/kg
75 µg/kg
100 µg/kg
150 µg/kg
Ondansetron 75 = ondansetron 100 = ondansetron 150 >
ondansetron 25 = ondansetron = placebo
Droperidol + ondansetron > droperidol = ondansetron
pts = patients; < indicates significantly less efficacy; > indicates significantly greater efficacy; = indicates similar efficacy; ↑ indicates increase; → indicates
results in.
 2007 Adis Data Information BV. All rights reserved.
Pediatr Drugs 2007; 9 (1)
58
Kovac
used for anesthesia induction. The incidence of POV in both
groups was similar pre- and post-hospital discharge. Each episode
of in-hospital vomiting prolonged hospital discharge by approximately 17 minutes. Prophylactic ondansetron shortened fast-tracking time and duration of PACU stay, improving parental satisfaction and therapeutic outcomes at a lower direct overall treatment
cost. Sennaraj et al.[125] noted that the propofol-based technique
had a higher acquisition cost.
Granisetron
Oral granisetron 20 and 40 µg/kg administered prior to anesthesia induction was found to be more effective than placebo in
reducing the incidence of POV for the first 24 hours after strabismus surgery; patients were discharged home earlier, with no
difference between the granisetron groups.[126]
Ramosetron
Antiemetic therapy with intravenous ramosetron 6 µg/kg was
determined to be comparable to granisetron 40 µg/kg at the end of
strabismus surgery for the prevention of POV during the early 0to 24-hour period, but significantly more effective than granisetron
during the later 24- to 48-hour postoperative period.[127]
Multimodal Antiemetic Anesthetic Technique
Smith and Walton[135] reported the use of a multimodal anesthesia technique for the prevention of POV following general anesthesia in children aged 2 weeks to 18 years undergoing ophthalmologic surgery. General anesthesia was induced with nitrous oxide
and halothane in 83% of study patients and intravenous propofol in
17%. Gastric aspiration was performed after endotracheal intubation. Anesthesia was maintained either with halothane or isoflurane, oxygen, and air. Intravenous morphine, up to a dose of 0.1
mg/kg, was administered for pain relief. Combination antiemetic
therapy (intravenous metoclopramide 0.15 mg/kg and intravenous
ondansetron 0.1 mg/kg) was administered before the end of the
operation. These researchers concluded that the incidence of POV
was 7.3% with the use of their multimodal protocol. Limited use of
nitrous oxide (for mask induction only), gastric emptying, and
administration of combination antiemetics were believed to be
effective methods to reduce POV in a variety of pediatric
ophthalmic procedures.
5.2 Tonsillectomy
5.2.1 Incidence
Combination Antiemetics
therapies[63,119,123,128-134]
Numerous combination
have been
compared with monotherapy for POV prophylaxis in strabismus
patients (table VI).
Splinter[128] determined that patients who received intravenous
dexamethasone 150 µg/kg alone had more POV compared with
the intravenous combination of dexamethasone 150 µg/kg plus
ondansetron 50 µg/kg. Each episode of POV increased the inhospital length of stay by 29 minutes. Similarly, another study[129]
also concluded that the combination of dexamethasone plus lowdose ondansetron was effective in decreasing POV. Shende
et al.[119] concluded that intravenous droperidol 15 µg/kg plus
ondansetron 100 µg/kg was more effective in reducing the incidence of POV than either drug given alone.
Nearly all the strabismus combination therapy studies determined that antiemetic combinations had a better effect in decreasing the incidence of nausea and vomiting than a single antiemetic
alone. However, this depended on which antiemetics are combined. When the antiemetic was combined with either droperidol
or dexamethasone, the combined effect was better than with either
antiemetic used alone. However, if metoclopramide was one of the
combination antiemetics, the combined effect was not better than
with either agent alone. Children who are at moderate-to-high risk
for POV are recommended to receive combination therapy with
two or three prophylactic antiemetics from different drug classes.[63,119,123,130-134]
 2007 Adis Data Information BV. All rights reserved.
As recently as 2002, Roberts and Jones[136] noted that PONV
following tonsillectomy continues to be a “big little problem”. In
an audit of a pediatric day-stay tonsillectomy service, Stewart
et al.[20] estimated that the overall incidence of POV following
tonsillectomy was 15.6% even in children who received combination intraoperative antiemetic therapy consisting of intravenous
dexamethasone 0.4 mg/kg (maximum of 8mg) and ondansetron
0.1–0.2 mg/kg for POV prophylaxis. This was in contrast to the
findings of Ferrari and Donlon[19] who reported a 70% incidence in
children undergoing tonsillectomy who received no POV prophylaxis. The Stewart et al.[20] study illustrates the fact that POV
continues to be a problem despite current antiemetic prophylaxis
with combination therapy.
5.2.2 Anesthetic Techniques
Inhalation Agents: Nitrous Oxide and Halothane
Tables IV and VII, respectively, list anesthetic techniques and
antiemetics that have been evaluated for their effectiveness in
decreasing POV and PONV following tonsillectomy.
As in strabismus surgery (see section 5.1), the use of nitrous
oxide has been controversial. Pandit et al.[105] concluded that,
although a high incidence of POV was noted, there was no
difference in either the incidence or severity of POV between
children who did or did not receive nitrous oxide.
Pediatr Drugs 2007; 9 (1)
Management of Postoperative Nausea and Vomiting in Children
59
Table VI. Combination antiemetic therapy in children undergoing strabismus surgery
Author
Antiemetics
Kymer et al.[130]
Placebo
Droperidol 0.3 mg/kg PO
Droperidol 0.15 mg/kg PO
Both metoclopramide + droperidol
Klockgether-Radke
et al.[131]
Placebo
Droperidol 0.075 mg/kg
Ondansetron 0.1 mg/kg
Ondansetron + droperidol (dose
as above)
Splinter and
Rhine[63]
Ondansetron 0.15 mg/kg
Ondansetron 0.05 mg/kg +
dexamethasone 0.15 mg/kg
Kathirvel et al.[132]
Study endpoint
Results
(% of pts)
Conclusions
34
41
42
37
Emesis
56
26
62
22
Metoclopramide + droperidol = droperidol >
metoclopramide = placebo (metoclopramide
ineffective)
40
40
40
40
Emesis
98
32.5
40
45
Ondansetron + droperidol = droperidol =
ondansetron > placebo (all three groups better
than placebo but no one regimen was superior to
the other)
150
150
Emesis
28
9
Low-dose ondansetron + dexamethasone > highdose ondansetron
Placebo
Ondansetron 0.1 mg/kg
Metoclopramide 0.25 mg/kg
Ondansetron + metoclopramide
(dose as above)
25
25
25
25
Emesis
72
40
60
44
Ondansetron + metoclopramide = ondansetron >
metoclopramide > placebo
Fujii et al.[133]
Granisetron 0.05 mg/kg
Droperidol 0.05 mg/kg
Granisetron + droperidol (dose as
above)
40
40
40
No emesis
80
No rescue
45
medications required 98
Granisetron + droperidol > granisetron >
droperidol
Shende et al.[119]
Placebo
Droperidol 0.25 mg/kg
Ondansetron 0.1 mg/kg
Droperidol 0.15 mg/kg +
ondansetron 0.1 mg/kg
60
60
60
60
Emesis
62.5
32
37
13
Ondansetron + droperidol > ondansetron =
droperidol > placebo
Splinter[128]
Ondansetron 0.05 mg/kg +
dexamethasone 0.15 mg/kg
111
Emesis
5
Caron et
al.[123]
Bhardwaj et al.[134]
No. of
pts
Ondansetron + dexamethasone > ondansetron
Ondansetron 0.05 mg/kg
82
23
Ondansetron
Droperidol + dimenhydrinate
88
84
Nausea and vomiting 25.3
31.6
Ondansetron > droperidol + dimenhydrinate.
More emesis during ride home in droperidol
group (12.6% vs 3.6%)
Placebo
Ondansetron 0.15 mg/kg
Ondansetron 0.15 +
dexamethasone 0.2 mg/kg
31
39
30
Vomiting – early and 64.5
24hr
33.3
10
Ondansetron + dexamethasone > ondansetron >
placebo
Low power for intergroup difference. Both groups
better than placebo but no difference between
groups
PO = oral; pts = patients; > indicates significantly greater efficacy; = indicates similar efficacy.
Propofol
Use of propofol for anesthesia maintenance helps decrease
PONV. Ved et al.[106] compared the effects of four anesthetic
techniques using nitrous oxide with halothane or propofol on POV
and recovery after outpatient tonsillectomy and adenoidectomy in
children aged 3–10 years. The anesthetic techniques evaluated
were: (i) halothane for induction and maintenance; (ii) propofol
for induction and maintenance; (iii) halothane induction and propofol maintenance; and (iv) propofol induction and halothane
 2007 Adis Data Information BV. All rights reserved.
maintenance. The incidence of POV occurred 3.5 times more
frequently when halothane was used for maintenance of anesthesia
compared with when propofol was used for maintenance. However, these authors concluded there was no difference in the
endpoints of unplanned admissions or discharge times, despite a
reduced rate of POV using propofol rather than halothane plus
nitrous oxide for maintenance. The main factor that delayed hospital discharge beyond 6 hours was POV that occurred within the
first 6 postoperative hours.
Pediatr Drugs 2007; 9 (1)
60
Kovac
Table VII. Effects of antiemetics in children undergoing tonsillectomy on postoperative vomiting and postoperative nausea and vomiting
Author
No. of
pts
Age (y)
Antiemetic
Conclusions
Rose et al.[137]
136
2–12
Midazolam 0.5 mg/kg PO
Dexamethasone 0.1 mg/kg
Ondansetron 0.15 mg/kg
Ondansetron 0.075 mg/kg
Placebo
Ondansetron 0.15 = dexamethasone 0.1 > midazolam >
ondansetron 0.075 = placebo
Splinter and Rhine[138]
240
2–12
Ondansetron 0.15 mg/kg
Ondansetron 0.05 mg/kg
Ondansetron 0.15 > ondansetron 0.05
Splinter and Rhine[139]
216
2–12
Ondansetron 0.15 mg/kg
Perphenazine 0.07 mg/kg
Ondansetron = perphenazine
Sukhani et al.[75]
149
2–12
Dexamethasone 1 mg/kg
Ondansetron 0.15 mg/kg
Dolasetron 0.5 mg/kg
Placebo
Ondansetron = dolasetron = dexamethasone > placebo
Stene et al.[140]
132
2–12
Metoclopramide 0.25 mg/kg IV
Ondansetron 0.15 mg/kg
Placebo
Ondansetron > metoclopramide = placebo
Hamid et al.[141]
74
2–10
Ondansetron 0.1 mg
Dimenhydrinate 0.5 mg/kg
Placebo
Ondansetron > dimenhydrinate > placebo
Fujii et al.[142]
90
4–10
Granisetron 40 µg/kg IV
Ramosetron 6 µg/kg
Ramosetron > granisetron
Jensen et al.[143]
71
2–14
Tropisetron 0.2 mg/kg
Placebo
Tropisetron > placebo
143
2–10
Tropisetron 0.1 mg/kg
Tropisetron 0.1 + dexamethasone 0.5mg/kg
Tropisetron + dexamethasone > tropisetron
Holt et al.[144]
IV = intravenous; PO = oral; pts = patients; > indicates significantly greater efficacy; = indicates similar efficacy.
For the treatment of POV in the PACU following tonsillectomy, a subhypnotic intravenous propofol bolus dose of 0.2 mg/kg
was not effective and caused sedation and pain on injection.[107]
Neuromuscular Blockade
Reversal of neuromuscular blockade with intravenous atropine
15 µg/kg and neostigmine was associated with a lower incidence
of POV compared with the combination of glycopyrrolate (glycopyrronium bromide) 10 µg/kg and neostigmine. However, there
was no significant difference in the number of patients who
required rescue antiemetics or additional analgesics.[108]
NSAIDs
A systematic review[145] of 25 studies involving 1853 patients
was conducted on the use of NSAIDs and the risk of operative-site
bleeding after tonsillectomy; 970 patients received an NSAID and
883 received a non-NSAID or placebo. While NSAIDs and
opioids had similar analgesic efficacy, the risk of emesis was
significantly decreased with the use of NSAIDs.
 2007 Adis Data Information BV. All rights reserved.
5.2.3 Antiemetics
Ondansetron
The incidence of POV during the first 24 hours’ post-tonsillectomy was significantly reduced by the use of preoperative oral
ondansetron 0.15 mg/kg compared with oral ondansetron 0.075
mg/kg or placebo in preadolescent children premedicated with oral
midazolam 0.5 mg/kg and intravenous dexamethasone 0.1 mg/
kg.[137] Similarly, Splinter and Rhine[138] compared high-dose
(0.15 mg/kg) versus low-dose (0.05 mg/kg) intravenous ondansetron and concluded that a high dose was more effective than a low
dose. While traditional, inexpensive antiemetics such as
perphenazine have overall not been well studied in children, a
study by Splinter and Rhine[139] concluded that intravenous ondansetron 0.15 mg/kg and intravenous perphenazine 0.07 mg/kg had
similar effects on POV after tonsillectomy in day-case surgery.
Sukhani et al.[75] compared the effect of intravenous ondansetron and dolasetron on POV after ambulatory tonsillectomy in
dexamethasone pretreated children aged 2–12 years. All children
received intravenous dexamethasone 1 mg/kg (up to a maximum
Pediatr Drugs 2007; 9 (1)
Management of Postoperative Nausea and Vomiting in Children
of 25mg) and were randomized to receive before the start of
surgery intravenous ondansetron 0.15 mg/kg (maximum 4mg),
dolasetron 0.5 mg/kg (maximum 25mg), or saline placebo. Both
ondansetron and dolasetron were more effective than placebo and
had similar effects on the incidence of POV and the need for
rescue antiemetics.
Stene et al.[140] evaluated intravenous metoclopramide 0.25 mg/
kg, ondansetron 0.15 mg/kg, or placebo administered after an
inhalation induction of halothane, nitrous oxide, and oxygen.
Prophylactic ondansetron was found to be more effective than
metoclopramide or placebo.
Hamid et al.[141] concluded that intravenous ondansetron
0.1 mg/kg was superior to intravenous dimenhydrinate 0.5 mg/kg
or placebo. Of special importance was that two children who had
received ondansetron vomited large volumes of bloody fluid 9 and
22 hours after surgery without previous signs of occult bleeding.
The authors concluded that, while ondansetron was more effective
than dimenhydrinate or placebo, antiemetics may mask the presence of bleeding and blood in the stomach by preventing vomiting,
and that this should be appreciated when adenotonsillectomy is
performed on an outpatient basis. A similar comment was noted by
Courtman et al.[146] who emphasized the importance of early
diagnosis of bleeding in this patient population who may be
receiving antiemetics such as ondansetron.
Ramosetron versus Granisetron
Fujii et al.[142] compared intravenous granisetron 40 µg/kg
versus intravenous ramosetron 6 µg/kg for prevention of POV
administered at the end of tonsillectomy surgery. These researchers concluded that ramosetron was a significantly better antiemetic
than granisetron for the long-term prevention of POV.
Tropisetron
Jensen et al.[143] evaluated the effectiveness of reducing POV in
children undergoing tonsillectomy after administering either placebo or intravenous tropisetron 0.2 mg/kg (maximum of 5mg) at
the time of anesthesia induction with halothane, nitrous oxide, and
oxygen. Tropisetron had significantly better POV efficacy compared with placebo.
Dexamethasone
As corticosteroids have been used for their anti-inflammatory
effect in ENT surgery,[144] numerous studies[52,144,147-152] have evaluated the effectiveness of corticosteroids for POV following tonsillectomy.
Holt et al.[144] compared the effectiveness of tropisetron 0.1 mg/
kg (maximum of 2mg) alone versus the combination of tropisetron
0.1 mg/kg (maximum of 2mg) plus dexamethasone 0.5 mg/kg
(maximum of 8mg) for the prevention of PONV in children
 2007 Adis Data Information BV. All rights reserved.
61
undergoing tonsillectomy. With both drugs administered intravenously during the time of anesthesia induction, these authors
concluded that the combination was significantly more effective
than tropisetron alone in reducing PONV. The effectiveness of
dexamethasone used in combination with other antiemetics has
been reviewed by Splinter et al.[63,64] and by Henzi et al.[84]
Steward et al.[147] conducted a systematic review on the effectiveness of corticosteroids as antiemetics for POV following tonsillectomy. They determined that children who received a single
intraoperative intravenous dose of dexamethasone 0.15–1 mg/kg,
with a maximum dose range of 8–25mg, were two times less likely
to have POV in the first 24 hours than children receiving placebo.
Their review stated an NNT of four, which indicated that routine
use of dexamethasone in four children would be expected to result
in one less patient experiencing post-tonsillectomy emesis. Additionally, children receiving dexamethasone were found to be more
likely to advance to a soft and solid diet on the first post-tonsillectomy day than those who received placebo. No adverse events
were reported in these trials that could be attributed to the singledose administration of dexamethasone.
Another meta-analysis by Steward et al.[153] concluded that a
single intravenous dose of dexamethasone was an effective, safe,
and inexpensive treatment for reducing POV following pediatric
tonsillectomy. Given the frequency of tonsillectomy procedures,
the relative safety and low cost of dexamethasone, and the reduction in postoperative morbidity, the use of a single intravenous
dose of dexamethasone during pediatric tonsillectomy was recommended. These conclusions were further substantiated in studies
conducted by Aouad et al.,[149] Pappas et al.,[150] and Vosdoganis
and Baines.[151]
Aouad et al.[149] determined that the effect of a single dose of
intravenous dexamethasone 0.5 mg/kg in children significantly
decreased the incidence of POV during the first 24 hours, shortened the time to first oral intake, and decreased the duration of
intravenous fluid hydration, which in turn improved patient satisfaction. Pappas et al.[150] determined that intravenous dexamethasone 1 mg/kg (maximum dose of 25mg) significantly decreased the incidence of PONV in the 24 hours’ post-discharge,
improved oral intake, decreased the frequency of parental phone
calls, and resulted in no returns to the hospital for PONV management or poor oral intake. Vosdoganis and Baines[151] similarly
determined that dexamethasone substantially reduced POV after
tonsillectomy.
The precise mechanism of action by which corticosteroids such
as dexamethasone decrease PONV is not known. Several theories[152-154] have been proposed and include membrane stabilization, anti-inflammatory effect, prostaglandin antagonism, tryptophan depletion, endorphin release, inhibition of arachidonic acid
Pediatr Drugs 2007; 9 (1)
62
Kovac
release, and modulation of the by-products of arachidonic acid
metabolism (i.e. lipoxygenase and a decrease in the amount of
available serotonin). Of importance is the timing of administration
of corticosteroids as studied by Wang et al.[155] who reported that
to have maximal effect in the PACU (early PONV) and in the
ward/at home (late PONV), dexamethasone should be administered before anesthesia induction, rather than at the end of surgery.
Administration of dexamethasone at the end of surgery had no
effect on PONV at postoperative hours 0–2 in the PACU, but was
effective at hours 2–24 in the ward/at home. However, because
pre-induction dexamethasone has reportedly caused perineal discomfort due to the injection solution containing phosphate,[156,157]
administration of dexamethasone either in diluted form or postinduction has been recommended.
5.3 Additional Pediatric Surgeries and Procedures
5.3.4 Burn Surgery
In a study on the prevention of PONV in children undergoing
reconstructive burn surgery, the effectiveness of ondansetron 0.1
mg/kg and dimenhydrinate 0.5 mg/kg was found to be similar.[24]
A retrospective chart review[25] of 38 pediatric patients aged 5–12
years undergoing a total of 46 burn procedures concluded that
100% of children with reconstructive surgeries of the scalp experienced PONV compared with only 45% of children whose surgeries did not involve the scalp. Consequently, an increased time
to oral intake was also seen in pediatric patients who underwent
operations involving the scalp.
5.3.5 Craniofacial Operations
Gurler et al.[160] determined that the prophylactic use of intravenous ondansetron 0.15 mg/kg versus placebo significantly reduced
POV after craniofacial operations in children.
5.3.6 Neurosurgery
5.3.1 Tympanoplasty
Berg[158]
van den
compared the use of intravenous ondansetron
versus intramuscular prochlorperazine for the prevention of
PONV after tympanoplasty in pediatric and adult patients, and
reported that the incidence of PONV in the PACU was similar
between children and adults. While the onset of PONV was
delayed in patients given intramuscular prochlorperazine, vomiting was less severe in patients who received intravenous ondansetron. The author concluded that while prophylactic intramuscular
prochlorperazine 0.2 mg/kg and intravenous ondansetron 0.06 mg/
kg had similar effectiveness in reducing PONV after tympanoplasty, intramuscular prochlorperazine 0.01 mg/kg was less
effective.
5.3.2 Ear Surgery
Woodward et al.[159] evaluated the effectiveness of a propofol
infusion versus a thiopental/isoflurane anesthesia technique for
prominent ear correction surgery. In the propofol infusion group,
significantly fewer children complained of nausea or emesis, and
significantly more children were considered to be fit for discharge
on the day of surgery.
5.3.3 Radiofrequency Catheter Ablation
Radiofrequency catheter ablation is considered to be a high-risk
procedure for PONV. Erb et al.[23] reported that in children and
adolescents undergoing radiofrequency catheter ablation, the incidence of PONV was high (60%) with an isoflurane-based technique, whereas the incidence of POV was significantly reduced to
a very low level (5%) with a propofol-based infusion technique.
While the prophylactic use of ondansetron and droperidol was
ineffective, a propofol-based infusion technique was highly effective in preventing PONV in these children.
 2007 Adis Data Information BV. All rights reserved.
Neufeld[161] reviewed the role of ondansetron in the management of PONV in children following posterior fossa neurosurgical
procedures, noting that the proximity of brain stem emetogenic
centers to the surgical site added to the usual PONV risk factors.
Ondansetron was believed to be more effective than the traditionally used antiemetics such as dimenhydrinate and metoclopramide
in this patient population.
Furst et al.[26] studied the effect of ondansetron versus placebo
in children undergoing craniotomies for resective procedures. In
the first 8 hours postoperatively, the incidence of POV was significantly less with intravenous ondansetron 0.15 mg/kg compared
with placebo. However, for the 24-hour postoperative time interval, the incidence of POV was not significantly different between
the ondansetron and placebo groups.
5.3.7 Magnetic Resonance Imaging
A retrospective review[15] evaluated 234 consecutive cases of
POV in children undergoing anesthesia for magnetic resonance
imaging. At an incidence rate of 9%, it was concluded that POV
was an infrequent complication of inhalation anesthesia during
magnetic resonance imaging.
6. Development of PONV and POV Management
Guidelines and Algorithms
Darkow et al.[162] in 2001 evaluated the impact of antiemetic
selection on PONV and patient satisfaction in a prospective observational study. The prophylactic antiemetic that was most often
administered to 292 patients was droperidol (200 patients), followed by metoclopramide (134 patients) or dexamethasone (55
patients). This study was conducted prior to the US FDA ‘black
box’ warning on droperidol. Nevertheless, these authors deterPediatr Drugs 2007; 9 (1)
Management of Postoperative Nausea and Vomiting in Children
mined that the choice of antiemetic drug given for PONV prophylaxis had little impact on clinical outcome or patient satisfaction.
They concluded that traditional antiemetics should form the core
of antiemetics selected and used for PONV prophylaxis in an
ambulatory surgery setting.
Drake et al.[163] further evaluated the impact of an antiemetic
protocol on PONV in children in an attempt to demonstrate a
decreased incidence of PONV with the use of an antiemetic
protocol. PONV was recorded in 272 children aged from 1.5 to 15
years following inpatient surgery under general anesthesia. Study
groups were determined based on one group having surgery
1 month before the introduction of a formalized antiemetic protocol (group 1 = 138 patients) and the other having surgery 2 months
after introduction of the protocol (group 2 = 134 patients). The
overall incidence of postoperative nausea (PON) and POV following introduction of the protocol was 36% and 34%, respectively.
Moderate-to-severe PON significantly decreased after introduction of the protocol (18% vs 9%), but the change in moderate-tosevere POV failed to reach statistical significance (19% vs 11%).
The proportion of children who had repeat PON decreased after
introduction of the protocol, but the proportion who had repeated
episodes of POV remained unchanged. The authors concluded that
the introduction of a postoperative antiemetic protocol improved
prescribing frequency resulting in a decreased incidence of moderate-to-severe PON and a reduction in the number of patients with
repeated PON, but not POV.
De Negri and Ivani[164] reviewed the management of PONV in
children, stating that, while there is little evidence to support
routine prophylactic administration of antiemetics in children at
low risk of PONV, populations at higher risk, such as children
undergoing strabismus surgery or tonsillectomy, could benefit
from the use of adequate prophylactic antiemetics.
Initial recommendations for the use of antiemetic guidelines for
chemotherapy-induced nausea and vomiting and PONV have appeared in reviews about the American Society of Hospital Pharmacists Therapeutic Guidelines on the Pharmacologic Management
of Nausea and Vomiting.[165] Advocacy of a particular antiemetic
treatment requires knowledge of high-risk groups, accurate assessment, timely intervention, and thorough evaluation of pharmacologic and non-pharmacologic measures.
Rose and Watcha,[166] in a review of PONV in pediatric patients, stated that based on current knowledge, the anesthetic plan
for a child with a previous history of severe PONV and undergoing
a procedure known to be associated with a high incidence of
PONV should include premedication with a benzodiazepine or
clonidine and preferential use of regional anesthetic techniques. If
general anesthesia was necessary, anesthesia providers should
consider the use of protocols for induction and maintenance,
 2007 Adis Data Information BV. All rights reserved.
63
avoiding nitrous oxide, opioids, and neuromuscular antagonists.
Pain control was believed to be extremely important, and the use
of regional blocks was recommended if possible. Double- or
triple-combination prophylactic antiemetic therapy with dexamethasone, a 5-HT3 antagonist, and an antiemetic of a different
class, such as perphenazine or dimenhydrinate, should also be
administered. Non-pharmacologic measures such as acupressure
should be considered, along with ensuring that the patient avoids
sudden movement, providing a quiet environment, administering
adequate intravenous fluids, and not forcing oral fluids before
discharge. All these measures have been found to decrease the
possibility of PONV in children. The authors stated that administration of effective prophylactic antiemetics should be encouraged,
as emetic symptoms in the hospital were the most significant
predictor of nausea and vomiting at home. Treatment of pain and
instructions for antiemetic treatment at home were believed to be
important needed improvements in PONV therapy.[166]
7. Guidelines for POV Prophylaxis in Children
Because of the initial suggestions for PONV guidelines (section
6) and the belief that an evidence-based analysis of the PONV
literature would be beneficial, a panel of pediatric and adult
‘PONV experts’ met as an independent panel in February 2002
and November 2005 to summarize the literature and develop
evidence-based guidelines for the management of PONV in adult
and pediatric patients. This multispecialty panel consisted of anesthesiologists, a nurse anesthetist, a pharmacist, a nurse, a statistician, and a surgeon.
According to the revised 2006 Consensus Guidelines for Managing PONV,[167-170] an initial approach to the management of
PONV or POV in children is to identify children at high risk.
Because of the difficulty in diagnosing nausea in younger children,
Table VIII.
dren[167-170]
Recommended antiemetic intravenous doses for chil-
Drug
Dose
Ondansetron[11,171] a
50–100 µg/kg up to 4mg
Dolasetron[73,74]
350 µg/kg up to 12.5mg
Dexamethasone[84,172,173]
150 µg/kg up to 5mg
Droperidol[85] b
50–75 µg/kg up to 1.25mg
Dimenhydrinate[121]
0.5 mg/kg up to 1.2mg
Perphenazine[139,174]
70 µg/kg up to 5mg
Granisetron[80]
40 µg/kg up to 0.6mg
Tropisetron[175]
0.1 mg/kg up to 2mg
a
Approved for postoperative vomiting in pediatric patients aged 1
month or older.
b
US FDA black box warning.
Pediatr Drugs 2007; 9 (1)
64
Kovac
Evaluate risk of
PONV in
surgical patient
Low
efficacy in the prevention of vomiting rather than nausea, they are
considered to be the antiemetic drugs of first choice for prophylaxis in children at moderate-to-high risk for POV.[83]
Moderate
No prophylaxis
unless there is
risk of medical
sequelae from
vomiting
High
Consider regional
anesthesia
Not indicated
If general anesthesia is
used, reduce baseline risk
factors and consider using
non-pharmacologic therapies
Patients at
moderate risk
Patients at
high risk
Consider antiemetic
prophylaxis with
monotherapy (adults)
or combination
therapy (children
and adults)
Initiate combination
therapy with 2 or 3
prophylactic agents
from different classes
Fig. 2. Algorithm for the management of postoperative nausea and vomiting (PONV) [reproduced from Gan et al.,[83] with permission].
it was noted that studies in children are often limited to POV and
not nausea. It is important to identify children at high risk for POV
as candidates for prophylactic antiemetic therapy. The risk factors
for POV in children are similar to those in adults, but with
differences such as: (i) vomiting occurs twice as frequently in
children as in adults; (ii) differences between boys and girls are not
observed before puberty (after puberty females have 2- to 3-fold
the incidence of PONV as males); (iii) as children grow older, the
POV risk increases until puberty, then decreases; and (iv) strabismus repair and tonsillectomy are specific surgeries that have a
high POV risk.[83,168]
As the POV rate in children is estimated to be twice as frequent
as in adults, more children than adults are candidates for POV
prophylaxis. Table VIII lists recommended doses of antiemetics
for children.[167,169] Ondansetron has been studied very extensively
for POV prophylaxis in children at an intravenous dose range of
50–100 µg/kg up to a maximum of 4mg. Ondansetron 0.1 mg/kg
has been shown to be effective in children aged <2 years. Compared with placebo, the NNT of ondansetron to prevent early (0–6
hours) and late (0–24 hours) vomiting in children is between two
and three. Ondansetron is US FDA approved in children aged 1
month and older. The optimal intravenous dose for POV prophylaxis with dolasetron in children is 350 µg/kg up to a maximum of
12.5mg. Because the 5-HT3 antagonists as a group have greater
 2007 Adis Data Information BV. All rights reserved.
When dexamethasone is used in children at an intravenous dose
of 150 µg/kg, the NNT to prevent early and late vomiting is
approximately four. Droperidol has been used for POV prophylaxis, administered in an intravenous dose range of 50–75 µg/kg. The
NNT of droperidol for prevention of early vomiting is approximately five, and for late vomiting is between four and five.
However, because of the increased risk of extrapyramidal symptoms, high levels of sedation found with the use of droperidol, and
the US FDA’s ‘black box’ warning, droperidol was recommended
to be reserved for patients in whom all other therapies have failed
and who are being admitted to the hospital.[83] More research needs
to be performed to find the best antiemetic for the treatment of
nausea in children to replace the previously used best anti-nausea
medication, droperidol.
An algorithm that can be used for the management of PONV in
children is shown in figure 2.[83] A new algorithm from the
Revised PONV Consensus guidelines is about to be released. As in
the 2003 guidelines, one should evaluate children for their level of
PONV risk and reduce baseline PONV risk factors. Patient preferences, cost effectiveness and the level of risk as low, medium or
high should be considered. A portfolio of antiemetics for prophylaxis and treatment as in table VIII is recommended. Droperidol
should be used in children only if other antiemetic therapy has
failed and the patient is being admitted to the hospital.[167,169]
Prophylaxis is believed to be useful only for children at moderateto-high risk for PONV and, if possible, regional anesthesia should
be considered in these patients. If general anesthesia is planned,
one should try to use strategies to reduce the baseline PONV risk
factors (table IX) whenever possible, including the use of nonpharmacologic therapies such as acupuncture or acupressure. In
general, combination antiemetic therapy is superior to monotherapy for PONV prophylaxis, as antiemetics with different
Table IX. Strategies to reduce baseline postoperative nausea and vomiting risk factors (reproduced from Gan et al.,[83] with permission)
Use of regional anesthesia
Use of propofol for induction and maintenance of anesthesia
Use of intraoperative supplemental oxygen
Use of hydration
Avoidance of nitrous oxide
Avoidance of volatile anesthetics
Minimization of intraoperative and postoperative opioids
Minimization of neostigmine
Pediatr Drugs 2007; 9 (1)
Management of Postoperative Nausea and Vomiting in Children
Table X. Antiemetic treatment for patients with postoperative nausea and
vomiting (PONV) who did not receive prophylaxis or in whom prophylaxis
failed – excluding inciting medication or mechanical causes of PONV (reproduced from Gan et al.,[83] with permission)
Initial therapy
Treatment
No prophylaxis or dexamethasone
Administer small-dose serotonin
(5-hydroxytryptamine; 5-HT3)
antagonist
5-HT3 antagonista plus second
agentb
Use drug from different class
Triple therapy with 5-HT3
antagonista plus two other agentsb
when PONV occurs <6h after
surgery
Do not repeat initial therapy
Use drug from different class or
propofol 20mg as needed in
postanesthesia care unit (adults)
Triple therapy with 5-HT3
antagonista plus two other agentsb
when PONV occurs >6h after
surgery
Repeat 5-HT3 antagonista and
droperidolc (not dexamethasone or
transdermal scopolamine)
Use drug from different class
a
Ondansetron, granisetron, dolasetron.
b
Dexamethasone, transdermal scopolamine.
c
US FDA black box warning.
65
because of the inability of children to effectively express distress
after surgery, often leading to the ineffective treatment of PONV
as well as pain. Strabismus surgery and tonsillectomy are the more
frequent and emetogenic surgeries performed in children. The
5-HT3 receptor antagonists, ondansetron, dolasetron, granisetron,
and tropisetron, as well as dexamethasone have been effective
treatments when used alone and as combination and multimodal
antiemetic therapy. PONV guidelines and algorithms help clinical
practitioners evaluate and treat children in a cost-effective manner.
Acknowledgments
In the past Dr Kovac has received grant support from GlaxoWellcome
(now GlaxoSmithKline), Roche Pharmaceuticals, Hoechst Marion Roussel
(now Sanofi-Aventis), Helsinn, and Merck and has participated in the Speakers Bureau for GlaxoSmithKline, Roche Pharmaceuticals, Abbott Laboratories, and Baxter Healthcare. Dr Kovac has served as an advisor for Merck,
GlaxoSmithKline, Roche Pharmaceuticals, Sanofi-Aventis, Adolor, and Helsinn. No sources of funding were used to assist in the preparation of this
article.
References
neuroemetogenic receptors and sites of action can be used to
optimize efficacy.
Children who are at moderate-to-high risk for PONV should
receive combination therapy with two or three prophylactic drugs
from different drug classes. The 5-HT3 antagonists can be effectively combined with dexamethasone to significantly reduce both
the frequency and severity of PONV. It has been suggested that in
children, the dexamethasone dose should not exceed 150 µg/kg
(maximum intravenous dose of 5mg); droperidol should not exceed 75 µg/kg (intravenous 1.25mg); dolasetron should not exceed
350 µg/kg (intravenous 12.5mg); and ondansetron should not
exceed 0.1 mg/kg (intravenous 4mg). Useful combination antiemetic therapies in children are: (i) ondansetron 0.05 mg/kg plus
dexamethasone 0.15 mg/kg[63,128]; (ii) ondansetron 0.1 mg/kg plus
droperidol 0.15 mg/kg[119]; and (iii) tropisetron 0.1 mg/kg plus
dexamethasone 0.5 mg/kg.[144] Smaller doses such as intravenous
ondansetron 50 µg/kg have been found to be effective in combination with other antiemetics in children. Further guidelines for the
treatment of PONV in patients who did not receive prophylaxis or
in whom prophylaxis failed are shown in table X.[83] Transdermal
scopalamine is not US FDA approved for use in children.
8. Conclusions
Despite our increased understanding of the etiology of nausea
and vomiting, POV and PONV continue to be problems in children. POV is more commonly studied in children than PONV
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Correspondence and offprints: Dr Anthony L. Kovac, Department of Anesthesiology, University of Kansas Medical Center, Mail Stop 1034, 3901
Rainbow Boulevard, Kansas City, KS 66160, USA.
E-mail: [email protected]
Pediatr Drugs 2007; 9 (1)