M E D I C I N E
REVIEW ARTICLE
Nausea and Vomiting After Surgery Under
General Anesthesia
An Evidence-Based Review Concerning Risk Assessment, Prevention, and Treatment
Dirk Rüsch, Leopold H. J. Eberhart, Jan Wallenborn, Peter Kranke
SUMMARY
Background: The German-language recommendations for
the management of postoperative nausea and vomiting
(PONV) have been revised by an expert committee. Major
aspects of this revision are presented here in the form of
an evidence-based review article.
Methods: The literature was systematically reviewed with
the goal of revising the existing recommendations. New
evidence-based recommendations for the management of
PONV were developed, approved by consensus, and
graded according to the scheme of the Scottish Intercol-
legiate Guidelines Network (SIGN).
Results: The relevant risk factors for PONV include female
sex, nonsmoker status, prior history of PONV, motion sick-
ness, use of opioids during and after surgery, use of inha-
lational anesthetics and nitrous oxide, and the duration of
anesthesia. PONV scoring systems provide a rough as-
sessment of risk that can serve as the basis for a risk-
adapted approach. Risk-adapted prophylaxis, however,
has not been shown to provide any greater benefit than
fixed (combination) prophylaxis, and PONV risk scores
have inherent limitations; thus, fixed prophylaxis may be
advantageous. Whichever of these two approaches to
manage PONV is chosen, high-risk patients must be given
multimodal prophylaxis, involving both the avoidance of
known risk factors and the application of multiple vali-
dated and effective antiemetic interventions. PONV should
be treated as soon as it arises, to minimize patient dis-
comfort, the risk of medical complications, and the costs
involved.
Conclusion: PONV lowers patient satisfaction but is treat-
able. The effective, evidence-based measures of prevent-
ing and treating it should be implemented in routine prac-
tice.
►Cite this as
Rüsch D, Eberhart LHJ, Wallenborn J, Kranke P: Nausea
and vomiting after surgery under general anesthesia
—an evidence-based review concerning risk assessment,
prevention, and treatment. Dtsch Arztebl Int 2010;
107(42): 733–41. DOI: 10.3238/arztebl.2010.0733
T he incidence of postoperative nausea and vomit-ing (PONV) after general anesthesia is up to 30%
when inhalational anesthetics are used with no prophy-
laxis. This makes PONV one of the most common
complaints following surgery under general anesthesia,
together with postoperative pain (1).
As anesthesia is administered approximately 8 mil-
lion times per year in Germany for surgery, this means
that up to 2.4 million patients suffer from PONV every
year (e1) if no prophylaxis is provided.
While anesthesia-related mortality and morbidity
have fallen dramatically in recent decades, the outcome
parameters wellbeing and patient satisfaction are be-
coming increasingly important (e2). These are
considerably affected by PONV (2–4, e3). Financial
issues are also significant, as PONV can lead to a sub-
stantial prolongation of time in the recovery room with
increased costs of personal care (e4) and in pediatric
patients PONV is the most common cause of the
approximately 1% to 2% of unplanned hospitalizations
following outpatient surgery (e5, e6). Despite their
rarity, serious complications caused by PONV which
are described in case reports, such as aspiration pneu-
monia, Boerhaave’s syndrome, severe subcutaneous
emphysema, pneumothorax, rupture of the trachea and
loss of vision, provide a warning that this problem is
not to be underestimated (e7–e14).
In the German-speaking world, recommendations for
preventing and treating PONV were first published in
2007. They were based on searches of the literature up to
2005 and therefore require revision due to new findings
(5). Although the recommendations of the Society for
Ambulatory Anesthesia (SAMBA), also published in
2007, were based on searches of the literature up to
2006, they require a high level of abstraction because of
their claim to international validity. For the German-
speaking world, this level of abstraction is difficult to
translate directly into treatment recommendations (6).
This review of PONV prevention and treatment is
based on a systematic review of the literature with sub-
sequent assessment according to the levels of evidence
and grades of recommendations within the framework
of expert consensus dating from 2009 (March 30, 2009,
Frankfurt am Main, Germany). It can be taken as a
Klinik für Anästhesie
und Intensivtherapie
Universitätsklinikum
Gießen und Marburg
GmbH: Priv.-Doz. Dr.
med. Rüsch, Prof. Dr.
med. Eberhart, MA
Klinik für Anästhesiolo-
gie und Intensivther-
apie Universitätsklini-
kum Leipzig: Priv.-Doz.
Dr. med. Wallenborn
Klinik und Poliklinik für
Anästhesiologie Uni-
versitätsklinikum
Würzburg: Univ.-Prof.
Dr. med. Kranke, MBA
Deutsches Ärzteblatt International | Dtsch Arztebl Int 2010; 107(42): 733–41 733
M E D I C I N E
basis for incorporation into Standard Operating Pro-
cedures (SOPs) in the German-speaking world.
Methods
The recommendations were developed by an expert
committee. All participants had many years’ clinically-
oriented scientific experience in the subject. Before
beginning the work, relevant key subjects were
presented to the participants for their expert opinions.
The subjects were researched using Medline, entering
search terms related to each subject in combination with
established search algorithms for PONV (including
“PONV”; “postoperative” AND [“nausea” OR “vomiting”
OR “retching”]). They were then presented and discussed
at the plenum, taking the available evidence (published
up to and including February 2009) into account. State-
ments on which agreement had been reached were given
a grade of recommendation according to the stipulations
of the Scottish Intercollegiate Guidelines Network
(SIGN) (Table 1; e15). Where there was disagreement,
repeat discussions were held using iterative round emails
to the participants (modified Delphi technique). In the
event of any further disagreement, the disputes were
recorded in the manuscript.
PONV risk factors and PONV prognosis systems
The pathogenesis of PONV is still largely unclear.
However, in recent years it has been possible to identify
a number of risk factors for the occurrence of PONV in
adults using multivariate methods (1, 7–11, e16–e22).
An overview of the risk factors confirmed by several
independent studies is provided in Table 2. Results re-
garding the effect of the type of operation on the risk of
PONV are varied, and discussion of them both at the
plenum and in the literature therefore includes conflict-
ing opinions (5, 6).
As none of the risk factors listed in Table 2 alone is
sufficiently able to predict PONV, various prognosis
systems have been developed. These have a prediction
accuracy rate of approximately 70% (1, 7, 12, e18,
e23). Due to the heterogeneous nature of the values of
the available scores, and given that the predictive value
depends on the decision-making criterion in question
(number of risk factors) and the prevalence of the dis-
order (PONV), we refer to further reading in the litera-
ture for more detailed description (8, 9). Simplified
PONV prognosis systems (Table 3) have been shown to
have the same prediction ability as more complex
PONV prognosis systems (grade B). They are therefore
TABLE 1
Levels of evidence and grades of recommendations according to the Scottish Intercollegiate Guidelines Network (SIGN)
(e15)
Level of evidence
1++
1 +
1 –
2++
2 +
2 –
3
4
Requirements
High quality meta-analyses, systematic reviews of
RCTs, or RCTs with a very low risk of bias
Well-conducted meta-analyses, systematic reviews,
or RCTs with a low risk of bias
Meta-analyses, systematic reviews, or RCTs with a
high risk of bias
High quality systematic reviews of case control or
cohort or studies
High quality case control or cohort studies with a very
low risk of confounding or bias and a high probability
that the relationship is causal
Well-conducted case control or cohort studies with a
low risk of confounding or bias and a moderate prob-
ability that the relationship is causal
Case control or cohort studies with a high risk of con-
founding or bias and a significant risk that the relation-
ship is not causal
Non-analytic studies, e.g. case reports, case series
Expert opinion
Grade of recommendation
A
B
C
D
Requirements
At least one meta-analysis, systematic review, or RCT
rated as 1++, and directly applicable to the target
population; or
A body of evidence consisting principally of studies
rated as 1+, directly applicable to the target popu-
lation, and demonstrating overall consistency of results
A body of evidence including studies rated as 2++,
directly applicable to the target population, and
demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
A body of evidence including studies rated as 2+,
directly applicable to the target population and demon-
strating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
734 Deutsches Ärzteblatt International | Dtsch Arztebl Int 2010; 107(42): 733–41
M E D I C I N E
to be used in preference to more complex systems to as-
sess the risk of PONV, as they are more practicable
(grade D; e20, e24).
PONV prevention
An essential part of PONV prevention is the avoidance
of confirmed emetogenic factors. Where possible, re-
gional anesthesia should be used, as it is associated
with a significantly lower risk of PONV in adults than
general anesthesia (grade B; [10, e25]). If general anes-
thesia is administered, using propofol rather than
volatile anesthetics to maintain anesthesia is an effec-
tive way of reducing the incidence of PONV (relative
risk reduction [RRR] of approximately 19%; grade A;
[13, 14]). Not using nitrous oxide is another option for
risk reduction (RRR = approximately 12%; grade A;
[14, e26]). Avoidance or reduced doses of opioids dur-
ing (grade B) and after surgery (grade B) also leads to a
lower incidence of PONV (1, 13, e27, e28). To this end,
non-opioids and/or regional anesthesia, among other
options, can be used.
Drug-based PONV prevention
Many different substances belonging to different drug
groups are available for drug-based PONV prevention.
Today most substances are understood to act as antag-
onists on specific receptors in the area postrema and on
free nerve endings of the vagus nerve. A summary of
the most widely-used drugs available in Germany today
is provided in Table 4.
Adjuvants and non-drug-based PONV prevention
According to the results of a recent meta-analysis, in-
creased inhaled oxygen concentration has no signifi-
cant effect in preventing PONV (grade A; [e46]). This
is also true of ginger and ginger extracts (grade A;
[e47]). The panel considered the data on the effect of
aromatherapy involving isopropyl alcohol in prevent-
ing PONV to be insufficient for providing recommen-
dations (grade D; [e48]).
Studies that have investigated the effect of perioper-
ative fluid replacement on the incidence of PONV are
too heterogeneous in terms of both different fluid re-
placement regimens and results to serve as a valid basis
for PONV-prevention recommendations at present
(grade D; [e49–e52]).
According to the results of a Cochrane Review,
stimulation of acupuncture point P6 on the wrist has
been shown to be superior to a placebo (e.g. sham acu-
puncture) in preventing both nausea (relative risk [RR]
0.72; 95% confidence interval [95% CI] 0.58–0.89) and
vomiting (RR 0.71; 95% CI 0.56–0.91) (e53). How-
ever, due to study design and its weaknesses regarding
treatment blinding, and considerable heterogeneity
(e.g. regarding the time of treatment), these conclusions
must be interpreted with care (e54). An update of the
Cochrane Review on P6 stimulation which included
better-designed studies shows again that these treat-
ments achieve a significant reduction in nausea (RR
0.71; 95% CI 0.61–0.83) and vomiting (RR 0.7; 95%
CI 0.59–0.83) as compared to a placebo, with minimum
side effects in adults and children (grade B; [16]),
which ultimately led to a positive overall assessment of
this method for PONV prevention in adults and
children. Nevertheless, P6 stimulation was awarded a
SIGN grade B recommendation in the face of continu-
ing uncertainty regarding its mechanism of action and
data which remain very heterogeneous.
Combination prophylaxis and multimodal antiemetic treatment
When deciding on PONV prophylaxis, the following
key aspects must be considered:
● For dexamethasone, droperidol and ondansetron,
a comparable antiemetic efficacy with a relative
risk reduction (RRR) for PONV of approximately
26% has been demonstrated (grade A; [14]).
● Total intravenous anesthesia (TIVA) with propo-
fol instead of volatile anesthetics and air instead
of nitrous oxide has been shown to be comparably
effective (RRR 31%) (grade A; [14]).
● The effects of a combination of these antiemetic
measures (dexamethasone, droperidol, ondanse-
tron and TIVA) are cumulative (grade A; [14]).
● It can be assumed that the results showing a com-
parable risk reduction for antiemetic measures
and the cumulative nature of the efficacy of anti-
emetic treatment (combinations of antiemetics
from different classes) are also valid for the other
drug-based measures described in Table 4
(grade B).
● There is no evidence to date that a specific anti-
emetic is especially effective for a particular pa-
tient profile or a particular operation (grade B;
[13]).
TABLE 2
Risk factors for PONV
*1The risk factors listed in each group are ordered according to severity
(from most to least severe)
Group
Patient-dependent
Anesthesia-dependent
Surgery-dependent
General
Risk factor*1
Female sex
History of PONV
Motion sickness
Nonsmoker status
Volatile anesthetics
Duration of anesthesia
(risk increases relatively by
approx. 60% every 30 min)
Nitrous oxide
Type of operation
Postoperative opioid
administration
Intraoperative opioid
administration
Recommendation grade
B
B
B
B
A
B
A
D
A
A
Deutsches Ärzteblatt International | Dtsch Arztebl Int 2010; 107(42): 733–41 735
M E D I C I N E
The higher the underlying risk of PONV, the more
components from the available antiemetic portfolio are
needed to achieve a PONV risk of less than 20%
(grade A; [14]). By using a multimodal approach
(grade A), it has been possible to achieve a dramatic re-
duction in the incidence of PONV (less than 10%) and
an increase in patient satisfaction, even for high-risk
patients with an underlying PONV risk of more than
80% (2, e55).
PONV treatment
When PONV occurs, prompt treatment is indicated, as
the likelihood of PONV to persist or to recur is at least
65% (grade A; [11, 17]).
Only 5HT3 receptor antagonists have been fully re-
searched for PONV treatment and confirmed as being
effective (grade A; [18]). They are, therefore, first-line
drugs for treatment of PONV, especially when no
prophylaxis has been administered beforehand
(grade D). The data available on all the other drug-
based and non-drug-based methods described above is
less extensive, although dexamethasone (grade A), ha-
loperidol (grade A), dimenhydrinate (grade B) and
promethazine (grade C) have been shown to be effec-
tive in treating PONV (19, e56, e57).
As those interventions that have proven to be effec-
tive (grade A) for treatment of PONV have also been
shown to be similarly effective (grade A) for prophy-
laxis of PONV, there is consensus that the reverse is
also true: All interventions for which it has been pos -
sible to demonstrate the highest level (grade A) of vali-
dated efficacy in preventing PONV, efficacy in treating
PONV can also be assumed, and these measures can
therefore also be recommended as treatment (grade B).
Drug-based measures associated with slow onset of
effect (e.g. dexamethasone, scopolamine) should not be
used as monotherapy, but only in combination with a
fast-acting substance as part of treatment (grade D).
For reasons of practicability, the same doses as those
used for prevention are also recommended for treat-
ment (grade D), even though for some substances (e.g.
ondansetron) it has been shown that lower doses are
also effective for treatment (18).
If PONV occurs despite prophylaxis, the primary
recommendation (particularly in the immediate post -
operative phase) is to administer a substance from
another drug group (grade A; [20, e56, e57]).
In PONV treatment, combination therapy should be
considered, as despite treatment the recurrence rate of
PONV over the subsequent 24 hours is 35% to 50%,
and the combination of dexamethasone plus dolasetron
or haloperidol has already been shown to be superior to
monotherapy (grade A; [17–19]). A comparable effec-
tiveness as part of combination therapy can also be
assumed for other combinations of established anti -
emetics (grade D).
PONV in children
The incidence of PONV is strongly age-dependent.
While children under 3 years of age are rarely affected,
TABLE 3
Validated, simplified PONV prognosis systems for adults and children, stating the risk factors involved and calculated
incidences of PONV
Prognosis system
Patient population
Risk factors
Calculated incidence of PONV with n risk factors present (sum of the risk factors listed above)
n
0
1
2
3
4
5
Koivuranta et al. (7)
Adults
Female sex
Prior history of PONV
Prior history of motion sickness
Nonsmoker status
Length of operation >60 min
%
17
18
42
54
74
87
Apfel et al. (1)
Adults
Female sex
History of PONV
History of motion sickness
Nonsmoker status
Expected postoperative
administration of opioids
%
10
21
39
61
79
Not stated
Eberhart et al. (12)
Children
Age >3 years
History of PONV or motion sickness
in the child or a first- degree relative
Strabismus surgery
Length of operation >30 min
%
9
10
30
55
70
Not stated
736 Deutsches Ärzteblatt International | Dtsch Arztebl Int 2010; 107(42): 733–41
M E D I C I N E
TABLE 4
Overview of available antiemetics with well-researched efficacy in preventing PONV
The receptors stated in brackets in the second column are the receptors on which the drug groups indicated in the first line have antiemetic effects. Doses stated are for intravenous
administration (except for aprepitant). Side effects listed are the symptoms frequently reported in PONV studies. Level and grade of recommendations according to SIGN criteria; AE: adverse
effect; CI: contraindication; BG: blood glucose; ECG: electrocardiogram; IV: intravenous.
Active
substance
Dexametha-
sone
Granisetron
Ondansetron
Palonosetron
Tropisetron
Droperidol
Haloperidol
Metoclopramide
Dimenhydrinate
Scopolamine
Aprepitant
Substance
g roup
Corticosteroids
Serotonin antag-
onists (5-HT3 re-
ceptors)
Dopamine antag-
onists: butyrophe-
none (D2 recep-
tors)
Dopamine antag-
onists: benzamide
(D2 receptors)
Histamine antag-
onists (H1 recep-
tors)
Anticholinergics
(muscarinergic
acetylcholine
receptors)
Neurokinin antag-
onists (NK1 recep-
tors)
Dose for
adults
4–8 mg
1 mg
4 mg
0.075 mg
2 mg
0.625–1.25
mg
1–2 mg
25–50 mg
62 mg
1 mg/24 hrs
40 mg (avail-
able only as
80 and 125
mg capsules
in Germany)
Dose for
children
0.1–0.15 mg
0.02 mg/kg
0.1 mg/kg
No data
0.1 mg/kg
0.01–0.015
mg/kg
No data
0.15 mg/kg
0.5 mg/kg
No data
No data
Recommen-
dation grade
(literature)
A
(14, 15, e29
–e31)
A
(14, 15, e33
–e36)
A
(14, 15, e33,
e38)
A
(e39, e40)
A
(11, 15)
A
(13, e42)
A
(e43)
A