Systemic metoclopramide to prevent postoperative nausea and vomiting: A meta-analysis without Fujii's studies

Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, 251 E Huron St, F5-704, Chicago, IL 60611, USA.
BJA British Journal of Anaesthesia (Impact Factor: 4.85). 09/2012; 109(5):688-97. DOI: 10.1093/bja/aes325
Source: PubMed
ABSTRACT
Previous evidence suggested that 10 mg systemic metoclopramide is not effective to prevent postoperative nausea and/or vomiting (PONV) in patients receiving general anaesthesia. However, the evidence included data with questioned validity by the author Yoshitaka Fujii. The objective of the current study was to examine the effect of a systemic dose of 10 mg metoclopramide to prevent PONV. This quantitative systematic review was performed according to the PRISMA guidelines. A wide search was performed to identify randomized clinical trials that evaluated systemic 10 mg metoclopramide as a prophylatic agent to reduce PONV. Meta-analysis was performed using a random-effect model. Thirty trials evaluating the effect of 10 mg systemic metoclopramide in 3328 subjects on PONV outcomes were included. Metoclopramide reduced the incidence of 24 h PONV compared with control, odds ratio (OR) [95% confidence interval (CI)] of 0.58 (0.43-0.78), number needed to treat (NNT)=7.8. When evaluated as separate outcomes, metoclopramide also decreased the incidence of nausea over 24 h, OR (95% CI) of 0.51 (0.38-0.68), NNT=7.1, and vomiting over 24 h, OR (95% CI) of 0.51 (0.40-0.66), NNT=8.3. A post hoc analysis examining three studies with questioned validity performed by the author Yoshitaka Fujii that would meet criteria for inclusion in the current study did not demonstrate a significant benefit of metoclopramide compared with control on the incidence of 24 h PONV. Our findings suggest that metoclopramide 10 mg i.v. is effective to prevent PONV in patients having surgical procedures under general anaesthesia. Metoclopramide seems to be a reasonable agent to prevent PONV.

Full-text

Available from: Edward Yaghmour, Mar 06, 2016
Systemic metoclopramide to prevent postoperative nausea
and vomiting: a meta-analysis without Fujii’s studies
G. S. De Oliveira Jr
*
, L. J. Castro-Alves, R. Chang, E. Yaghmour and R. J. McCarthy
Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital,
251 E Huron St, F5-704, Chicago, IL 60611, USA
* Corresponding author. E-mail: g-jr@northwestern.edu
Editor’s key points
Previous evidence of
ineffectiveness of
metoclopramide in
preventing postoperative
nausea and vomiting (PONV)
included studies co-authored
by Yoshitaka Fujii.
Recently, the credibility of
data from Fujii’s studies has
been seriously questioned.
In this meta-analysis, the
authors have re-analysed
data after excluding the data
from Fujii’s studies.
Importantly, the authors
have consolidated evidence
showing the effectiveness of
metoclopramide in treating
PONV.
Summary. Previous evidence suggested that 10 mg systemic metoclopramide is not
effective to prevent postoperative nausea and/or vomiting (PONV) in patients
receiving general anaesthesia. However, the evidence included data with questioned
validity by the author Yoshitaka Fujii. The objective of the current study was to
examine the effect of a systemic dose of 10 mg metoclopramide to prevent PONV.
This quantitative systematic review was performed according to the PRISMA
guidelines. A wide search was performed to identify randomized clinical trials that
evaluated systemic 10 mg metoclopramide as a prophylatic agent to reduce PONV.
Meta-analysis was performed using a random-effect model.
Thirty trials evaluating the effect of 10 mg systemic metoclopramide in 3328
subjects on PONV outcomes were included. Metoclopramide reduced the incidence of
24 h PONV compared with control, odds ratio (OR) [95% confidence interval (CI)] of
0.58 (0.43 0.78), number needed to treat (NNT)¼ 7.8. When evaluated as separate
outcomes, metoclopramide also decreased the incidence of nausea over 24 h, OR
(95% CI) of 0.51 (0.380.68), NNT¼ 7.1, and vomiting over 24 h, OR (95% CI) of 0.51
(0.400.66), NNT¼ 8.3. A post hoc analysis examining three studies with questioned
validity performed by the author Yoshitaka Fujii that would meet criteria for inclusion
in the current study did not demonstrate a significant benefit of metoclopramide
compared with control on the incidence of 24 h PONV. Our findings suggest that
metoclopramide 10 mg i.v. is effective to prevent PONV in patients having surgical
procedures under general anaesthesia. Metoclopramide seems to be a reasonable
agent to prevent PONV.
Keywords: anaesthesia, general; PONV; premedication, metoclopramide
Postoperative nausea and/or vomiting (PONV) can affect up
to 80% of patients undergoing surgical procedures.
1
Clinically
significant PONV can substantially decrease patient’s quality
of postsurgical recovery and result in serious consequences
to patient’s health including dehydration with electrolyte dis-
turbance, bleeding, and oesophageal laceration.
23
Drug
shortages around the world have recently limited the
access to commonly used medications to prevent PONV
such as ondansetron and dexamethasone.
4
Metoclopramide is a safe and inexpensive medication that
has been used to prevent PONV worldwide. A previous system-
atic review did not find a clinically meaningful effect of 10 mg
systemic metoclopramide to prevent PONV.
5
The current
Society of Ambulatory Anaesthesia guidelines to prevent
PONV do not recommend metoclopramide as an efficacious
agent to prevent PONV.
6
It is important to note that much of
the evidence for the lack of efficacyof metoclopramide included
studies with questioned validity originated by the author Yoshi-
taka Fujii.
7
It has been recently recommended that systematic
reviews should exclude data originated from Yoshitaka Fujii.
8
Therefore, it remains unknown if a common 10 mg dose of sys-
temic metoclopramide is efficacious to prevent PONV.
The main objective of the current investigation was to
evaluate the effect of systemic metoclopramide in the pre-
vention of PONV. A secondary objective was to examine if
the effect of metoclopramide in the prevention of PONV
changed when the medication was administered as a
single agent or as part of a combination therapy.
Methods
This quantitative systematic review was conducted following
the guidelines of the PRISMA statement.
9
Systematic search
Published reports of randomized trials evaluating the effects
of metoclopramide on surgical PONV were searched using
the National Library of Medicine’s Pubmed database,
British Journal of Anaesthesia 109 (5): 68897 (2012)
Advance Access publication 25 September 2012
.
doi:10.1093/bja/aes325
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Embase, the Cochrane Database of Systematic Reviews and
Google Scholar inclusive to March 1, 2012. Free text and
MeSH terms ‘metoclopramide’, ‘nausea’, ‘vomiting’, and
‘postoperative’ were used individually and in various combi-
nations. No language restriction was used. The search was
limited to randomized controlled clinical trials in subjects
older than 18 yr of age. An attempt to identify additional
studies not found by the primary search methods was
made by reviewing the reference lists from identified
studies. No search was performed for unpublished studies.
This initial search yielded 159 randomized clinical trials.
Selection of included studies
The study’s inclusion and exclusion criteria were determined
before the systematic search. Two authors (G.S.D.O. and
L.J.C.-A. or R.C.) independently evaluated the abstract and
results of the 159 articles obtained by the initial search. Articles
that were clearly not relevant based on our inclusion and exclu-
sion criteria were excluded at this phase. Disagreements on in-
clusion of the articles were resolved by discussion among the
evaluators. If an agreement could not be reached, the dispute
was resolved with the help of a fourth investigator (E.Y.).
Inclusion and exclusion criteria
We included randomized controlled trials of a single peri-
operative 10 mg i.v. metoclopramide administration with an
inactive (placebo or ‘no treatment’) control group. Excluded
were trials reporting nausea and vomiting after emergency
medicine and non-surgical patients. Trials evaluating multiple
perioperative metoclopramide doses or that evaluated meto-
clopramide to treat PONV were excluded to maximize clinical
homogeneity. Studies containing a concurrent use of an alter-
native multimodal anti-emetic regimen were excluded if a
direct comparison of metoclopramide and placebo could not
be established. Included studies had to report at least on the
incidence of early (1 6 h) or 24 h PONV. No minimum
sample size was required for inclusion in the meta-analysis.
The studies performed by the author Yoshitaka Fujii were
excluded, as recently recommended, due to the questioned
validity of the data originated in those studies (Fig. 1).
78
Validity scoring
Two authors (G.S.D.O. and L.J.C.-A. or R.C.) independently
read the included reports and assessed their methodological
validity using a modified Jadad five-point quality scale.
10
The
scale evaluates the study for the following: randomization,
double-blind evaluation, concealment of study group to
evaluator, valid randomization method, and completeness
of data at follow-up. Discrepancies in rating of the trials
were resolved by discussion among the evaluators. If an
agreement could not be reached, the dispute was resolved
with the help of a fourth investigator (E.Y.). As only rando-
mized trials were included in the analysis, the minimum pos-
sible score of an included trial was 1 and the maximum was
5. Trials were not excluded or weighted in the analysis based
on quality assessment scores.
Data extraction
Two authors (G.S.D.O. and L.J.C.-A. or R.C.) independently
evaluated the full manuscripts of all included trials and
performed data extraction using a data collection form spe-
cifically developed for this review. Discrepancies were
resolved by discussion between the two investigators. If an
agreement could not be reached between two investigators,
the decision was made by a fourth investigator (E.Y.). Data
extracted from trials included metoclopramide dose and
time of administration, sample size, number of subjects in
treatment groups, follow-up period, type of surgery, nausea
and/or vomiting over 24 h, early nausea and/or vomiting
(16 h), need for rescue anti-emetic, type of drug interven-
tion (single regimen vs combination therapy), and adverse
events.
Data were initially extracted from tables or text. For data
not available in tables, attempts to contact authors were
made; if the authors did not respond or did not have
current contact information, the data were abstracted from
available figures. Dichotomous data on the presence or
absence of adverse effects were extracted and converted
to incidence.
159 abstracts
57 potential
studies
Included 27 studiesNo
Ye s
30 randomized
controlled trials
Fig 1 Flow chart outlining retrieved, excluded, and evaluated
randomized controlled trials.
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Definition of relevant outcome data
Primary outcomes
Twenty-four hour incidence of PONV (defined as nausea and/
or vomiting), early (up to 6 h after operation) incidence of
PONV, early and 24 h incidence of nausea, and early and
24 h incidence of vomiting (including retching) were the
primary outcomes.
Secondary outcomes
These were the need for rescue anti-emetic, and adverse
events including headache, dizziness, postoperative sedation,
and extrapyramidal symptoms.
Meta-analyses
For dichotomous data, odds ratio (OR) and 95% confidence
interval (CI) are reported. For dichotomous adverse effects
data, the Peto OR (to account for the potential of zero
counts in the cells for low-frequency outcomes) and 95%
CI are reported. For a significant effect compared with
placebo required for dichotomous data, the confidence inter-
val did not include 1.0. We calculated the number needed to
treat (NNT), based on the absolute risk reduction, as an esti-
mate of a beneficial effect. Owing to the different surgical
procedures, a random-effect model was used in an attempt
to generalize our findings to studies not included in our
meta-analysis.
11
Publication bias was evaluated by examin-
ing for the asymmetry of funnel plots using Egger’s regres-
sion test.
12
A one-sided P,0.05 was considered as an
indication of an asymmetric funnel plot. A file drawer ana-
lysis described by Rosenthal
13
was performed in the case of
an asymmetric funnel plot. The test estimates the lowest
number of additional studies that if they became available
would reduce the combined effect to non-significance, as-
suming that the average Z-score of the combined P-values
of these missing studies would be 0. A separate post hoc
analysis of the studies performed by the author Yoshitaka
Fujii that would meet criteria for inclusion in the current ana-
lysis was also performed.
Heterogeneity of the included studies was considered to
be present if the I
2
statistic was .30%. Further analysis
was planned a priori to explore relevant heterogeneity. Sub-
group analysis was performed to investigate the effect of
type of anti-emetic intervention (single therapy vs combin-
ation therapy). A Q statistic was used to compare the
effects between subgroups. The proportion of the total vari-
ance explained by the covariates (R
2
) was calculated by
dividing random effects pooled estimates of variance
(tau-squared) within studies by total variance (total
tau-squared). The value obtained was then subtracted from
1. When values decrease outside the range of 0100%,
they were set to the closest value (0% or 100%).
Analysis was performed using Stata version 11 (College
Station, TX, USA) and Comprehensive Meta-analysis software
version 2 (Biostat, Englewood, NJ, USA).
Results
Of the 159 initially evaluated abstracts, 57 studies initially
met the inclusion criteria. Twenty-seven studies were subse-
quently excluded: seventeen did not provide a direct com-
parison between metoclopramide and placebo or did not
report the evaluated outcomes,
14 30
five evaluated weight-
based responses of the evaluated outcomes,
31 35
two
examined patients undergoing regional anaesthesia,
36 37
two were retracted, (Piper SN, Suttner SW, Ro
¨
hm KD,
Maleck WH, Larbig E, Boldt J. Dolasetron, but not metoclopra-
mide prevents nausea and vomiting in patients undergoing
laparoscopic cholecystectomy. Can J Anaesth 2002; 49:
10218 and Abou Zeid H, Al-Gahamdi A, Abdul-Hadi M. Dola-
setron decreases postoperative nausea and vomiting after
breast surgery. Breast J 2002; 8: 21621) and one examined
metoclopramide administered after operation.
38
The charac-
teristics of included studies are listed in Supplementary Table
S1. The evaluated trials included data from 3328 subjects
and were published between 1967 and 2011.
39 68
The
median number of patients in the included studies receiving
metoclopramide was 36.5. The median modified Jadad scale
score was 4. The trials tested a single dose of 10 mg i.v.
metoclopramide given either before operation or intraopera-
tively in a large variety of surgical procedures under general
anaesthesia. All 30 studies included reported on nausea and/
or vomiting.
Twenty-four hours nausea and/or vomiting
(PONV)
The aggregated effect of 13 studies (14 comparisons)
39 67
examining the effect of 10 mg systemic metoclopramide
on the 24 h incidence of nausea and/or vomiting compared
with placebo showed a beneficial effect of metoclopramide,
OR (95% CI) of 0.58 (0.43 0.78), NNT¼ 7.8. The funnel plot
did not demonstrate asymmetry (P¼ 0.38). Heterogeneity
was low (I
2
¼ 0) (Fig. 2).
Only one study
44
examined metoclopramide used as a com-
bination therapy, but it did not achieve a significant benefit
compared with placebo, OR (95% CI) of 0.49 (0.141.62).
The combined effect of three studies
69 71
performed by
the author Yoshitaka Fujii that would meet inclusion criteria
in the current meta-analysis did not show a significant bene-
ficial effect of 10 mg i.v. metoclopramide compared with
placebo on the incidence of 24 h PONV, OR (95% CI) of
0.72 (0.391.31).
Early (16 h) nausea and/or vomiting
The overall effect of 11 studies (12 comparisons)
41 44 45 47 49 62 63 65 68
examining 10 mg i.v. metoclopramide on the incidence of early
nausea and/or vomiting compared with placebo favoured
metoclopramide, OR (95% CI) of 0.52 (0.360.75), NNT¼ 7.6
(Fig. 3). The funnel plot did not demonstrate asymmetry
(P¼ 0.08). Heterogeneity was low (I
2
¼ 24).
The only study examining the effect of metoclopramide
used in a combination regimen on the incidence of early
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690
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PONV
44
did not demonstrate a significant benefit, OR (95%
CI) of 0.63 (0.162.42).
Twenty-four hour incidence of nausea
The combined effect of 10 studies (11 comparisons)
40 44 46 47
51 53 55 59 60
examining the effect of 10 mg i.v. metoclopra-
mide on the incidence of 24 h nausea compared with
placebo favoured metoclopramide, OR (95% CI) of 0.51
(0.380.68), NNT¼ 7.1 (Fig. 4). Heterogeneity was low
(I
2
¼ 8). The funnel plot demonstrated some asymmetry, indi-
cating the possibility of publication bias (P¼ 0.03). Rosenthal
analysis estimated that 92 missing studies would be required
to change the analysis.
The only study examining the effect of metoclopramide
used in a combination therapy on the incidence of 24 h
nausea
40
did not show a significant benefit, OR (95% CI) of
0.34 (0.061.99).
The combined effect of three studies
69 71
performed by
the author Yoshitaka Fujii that would meet inclusion criteria
in the current meta-analysis did not show a significant bene-
ficial effect of 10 mg i.v. metoclopramide compared with
placebo on the incidence of nausea over 24 h, OR (95% CI)
of 0.76 (0.361.57).
Study name Comparison Outcome Statistics for each study Events/Total Odds ratio and 95% Cl
Odds
ratio
Lower
limit
Upper
limit
Z-value P-value Metoclopramide Control
Ekinci
Kaki
Nasek-adam
Nasek-adam 2
Nasek-adam 2004
Huang
Muhammad
Sharma
Rusch 1999
Pertusa
Naguib
Desilva
Bone
Waldmann
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
PONV 24h
PONV 24h
PONV 24h
PONV 24h
PONV 24h
PONV 24h
PONV 24h
PONV 24h
PONV 24h
PONV 24h
PONV 24h
PONV 24h
PONV 24h
PONV 24h
0.441
1.000
0.545
0.492
0.632
0.648
0.818
0.844
0.254
0.260
0.925
0.758
0.429
0.619
0.585
0.123
0.291
0.224
0.149
0.246
0.259
0.208
0.270
0.090
0.073
0.279
0.365
0.117
0.158
0.439
1.573
3.437
1.325
1.626
1.623
1.621
3.216
2.644
0.720
0.921
3.069
1.574
1.568
2.429
0.780
0.207
1.000
0.181
0.245
0.340
0.354
0.774
0.771
0.010
0.037
0.899
0.457
0.201
0.492
0.000
9 / 20
7 / 25
18 / 40
5 / 40
15 / 35
20 / 38
9 / 16
13 / 24
13 / 33
9 / 22
17 / 24
29 / 58
10 / 20
5 / 20
179 / 415
13 / 20
7 / 25
24 / 40
9 / 40
19 / 35
24 / 38
11 / 16
14 / 24
23 / 33
16 / 22
21 / 24
33 / 58
14 / 20
7 / 20
235 / 421
0.01 0.1
Metoclopramide Control
1 10 100
–1.262
0.000
–1.338
–1.163
–0.954
–0.927
–0.287
–0.291
–2.580
–2.088
–0.127
–0.744
–1.280
–0.688
–3.652
Fig 2 Pooled data evaluating the effect of systemic metoclopramide on the 24 h incidence of PONV compared with control. Data were eval-
uated by calculating OR. The point estimate (95% CI) for the overall effect was 0.58 (0.430.78). OR for individual studies represented by the
square on the Forrest plot with 95% CI of the difference shown as a solid line. Larger sized squares denote larger sample size. The diamond
represents the pooled estimate and uncertainty for the combined effect.
Study name Comparison Outcome Statistics for each study Events/Total Odds ratio and 95% Cl
Odds
ratio
Lower
limit
Upper
limit
Z-value P-value Metoclopramide Control
Bilgin
Nasek-adam
Nasek-adam 2
Nasek-adam 2004
Huang
Muhammad
Lim
Madej Out Gyne
Madej Inpat gyne
Waldmann
Handley
Dimich
Meto-saline Early PONV
Early PONV
Early PONV
Early PONV
Early PONV
Early PONV
Early PONV
Early PONV
Early PONV
Early PONV
Early PONV
Early PONV
0.179
0.643
0.630
0.600
0.424
0.480
0.835
0.180
0.395
1.207
0.750
0.125
0.526
0.068
0.255
0.163
0.221
0.169
0.121
0.411
0.008
0.171
0.169
0.021
0.369
0.472
1.623
2.427
1.627
1.066
1.897
1.698
4.009
0.913
2.714
3.333
0.737
0.750
–3.483
–0.935
–0.672
–1.004
–1.824
–1.047
–0.498
–1.082
–2.172
0.455
–0.378
–2.297
–3.551
0.000
0.350
0.502
0.316
0.068
0.295
0.619
0.279
0.030
0.649
0.705
0.022
0.000
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
10 / 40
12 / 40
4 / 40
10 / 35
14 / 38
6 / 16
22 / 58
0 / 20
13 / 50
30 / 48
4 / 20
2 / 26
127 / 431
26 / 40
16 / 40
6 / 40
14 / 35
22 / 38
10 / 18
30 / 71
2 / 20
24 / 51
29 / 50
5 / 20
6 / 15
190 / 438
0.01 0.1
Metoclopramide Control
1 10 100
0.537
Fig 3 Pooled data evaluating the effect of systemic metoclopramide on the early incidence of PONV compared with control. Data were eval-
uated by calculating OR. The point estimate (95% CI) for the overall effect was 0.52 (0.360.75). OR for individual studies represented by the
square on the Forrest plot with 95% CI of the difference shown as a solid line. Larger sized squares denote larger sample size. The diamond
represents the pooled estimate and uncertainty for the combined effect.
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Early (16 h) incidence of nausea
The aggregated effect of 13 studies (14 comparisons)
40 45 47
48 52 54 61 64 65 68
evaluating 10 mg i.v. metoclopramide on
the incidence of early nausea compared with placebo
favoured metoclopramide, OR (95% CI) of 0.49 (0.350.68),
NNT¼ 5.9 (Fig. 5). Heterogeneity was low (I
2
¼ 7). The funnel
plot demonstrated asymmetry, suggesting the possibility of
publication bias (P¼ 0.001). Eighty-nine missing studies
would be required in order to change the analysis.
The combined effect of three studies
40 44 54
evaluating
the effect of 10 mg i.v. metoclopramide as part of a combin-
ation therapy on the incidence of early nausea suggested a
benefit of metoclopramide compared with placebo, OR (95%
CI) of 0.32 (0.120.87), NNT¼ 10.6. Heterogeneity was low
(I
2
¼ 0). Funnel plot did not demonstrate asymmetry (P¼ 0.35).
Vomiting over 24 h
The aggregated effect of 10 studies (11 comparisons)
40 45 47
51 53 55 59 60
evaluating metoclopramide on the incidence of
vomiting over 24 h demonstrated a beneficial effect of meto-
clopramide, OR (95% CI) of 0.51 (0.400.66), NNT¼ 8.3
(Fig. 6). Heterogeneity was low (I
2
¼ 0). The funnel plot did
not demonstrate asymmetry (P¼ 0.07).
Study name Comparison Outcome Statistics for each study Events/Total Odds ratio and 95% Cl
Odds
ratio
Lower
limit
Upper
limit Z-value P-value Metoclopramide Control
Entezariasl
Entezariasl 2
Nasek-adam 2004
Nasek-adam 2
Nasek-adam
Rauers
Huang
Wilson
Loo
Helmy
Joshi
Bone
Madej Out Gyne
Handley
Bilgin
Meto-saline
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Early nausea
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
0.318
0.457
0.009
0.715
0.731
0.474
0.698
0.578
0.600
0.181
0.630
0.148
0.538
0.600
0.102
0.493
0.090
0.076
0.000
0.311
0.243
0.082
0.214
0.205
0.310
0.036
0.163
0.035
0.151
0.240
0.005
0.357
1.120
2.755
0.167
1.645
2.201
2.746
2.275
1.630
1.160
0.901
2.427
0.623
1.917
1.503
2.276
0.681
0.075
0.393
0.002
0.430
0.577
0.405
0.551
0.300
0.129
0.037
0.502
0.009
0.339
0.276
0.150
0.000
–1.783
–0.855
–3.162
–0.790
–0.558
–0.833
–0.596
–1.036
–1.518
–2.087
–0.672
–2.605
–0.955
–1.090
–1.441
–4.298
5 / 25
2 / 25
8 / 40
13 / 59
7 / 40
2 / 40
6 / 35
8 / 38
23 / 72
2 / 40
4 / 40
3 / 25
7 / 20
10 / 50
0 / 26
100 / 575
11 / 25
4 / 25
14 / 14
17 / 60
9 / 40
4 / 40
8 / 35
12 / 38
36 / 82
9 / 40
6 / 40
12 / 25
10 / 20
15 / 51
2 / 15
169 / 550
0.01 0.1
Metoclopramide Control
1 10 100
Fig 5 Pooled data evaluating the effect of systemic metoclopramide on the early incidence of nausea compared with control. Data were eval-
uated by calculating OR. The point estimate (95% CI) for the overall effect was 0.49 (0.350.68). OR for individual studies represented by the
square on the Forrest plot with 95% CI of the difference shown as a solid line. Larger sized squares denote larger sample size. The diamond
represents the pooled estimate and uncertainty for the combined effect.
Study name Comparison Outcome Statistics for each study Events/Total Odds ratio and 95% Cl
Odds
ratio
Lower
limit
Upper
limit
Z-value P-value Metoclopramide Control
Entezariasl
Entezariasl 2
Nasek-adam 2004
Huang
Rusch
Rusch 1999
Helmy
Morris
Ascaso
Paxton
Rust
Meto-saline Nausae 24 h
Nausae 24 h
Nausae 24 h
Nausae 24 h
Nausae 24 h
Nausae 24 h
Nausae 24 h
Nausae 24 h
Nausae 24 h
Nausae 24 h
Nausae 24 h
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
0.231
0.348
0.755
0.599
0.888
0.260
0.513
0.606
0.376
0.052
0.613
0.513
0.066
0.061
0.267
0.230
0.341
0.093
0.201
0.355
0.141
0.006
0.359
0.387
0.810
1.993
2.139
1.559
2.313
0.728
1.308
1.035
1.002
0.441
1.047
0.681
0.022
0.236
0.597
0.294
0.807
0.010
0.162
0.067
0.050
0.007
0.073
0.000
–2.289
–1.186
–0.528
–1.050
–0.244
–2.564
–1.398
–1.834
–1.956
–2.714
–1.790
–4.625
5 / 25
2 / 25
9 / 35
16 / 33
12 / 38
12 / 33
11 / 40
350 / 462
6 / 51
17 / 29
351 / 462
791 / 1233
13 / 25
5 / 25
11 / 35
22 / 36
13 / 38
22 / 32
17 / 40
98 / 117
22 / 84
27 / 28
98 / 117
348 / 577
0.01 0.1
Metoclopramide Control
1 10 100
Fig 4 Pooled data evaluating the effect of systemic metoclopramide on the 24 h incidence of nausea compared with control. Data were eval-
uated by calculating OR. The point estimate (95% CI) for the overall effect was 0.51 (0.380.68). OR for individual studies represented by the
square on the Forrest plot with 95% CI of the difference shown as a solid line. Larger sized squares denote larger sample size. The diamond
represents the pooled estimate and uncertainty for the combined effect.
BJA De Oliveira Jr et al.
692
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The only study evaluating the effect of metoclopramide
when used as part of a combination therapy
40
did not
show a significant effect on the reduction of vomiting over
24 h, OR (95% CI) of 0.32 (0.018.24).
The combined effect of three studies
69 71
performed by
the author Yoshitaka Fujii that would meet inclusion criteria
in the current meta-analysis did not show a significant bene-
ficial effect of 10 mg i.v. metoclopramide compared with
placebo on the incidence of 24 h vomiting, OR (95% CI) of
0.77 (0.381.56).
Early (16 h) vomiting
The overall combined effect of 12 studies (14 compari-
sons)
40 42 44 48 52 59 61 65 68
evaluating the effect of 10
mg i.v. metoclopramide on the incidence of early vomiting
compared with placebo favoured metoclopramide, OR (95%
CI) of 0.44 (0.290.65), NNT¼ 10.5 (Fig. 7). Heterogeneity
was low (I
2
¼ 5). The analysis was limited by the presence
of an asymmetric funnel plot (P¼ 0.03), suggesting the pres-
ence of publication bias. Sixty-three missing studies would be
required to change the analysis.
The combined effect of two studies
40 44
evaluating meto-
clopramide as part of a combination regimen did not show a
significant benefit compared with control, OR (95% CI) of
0.72 (0.134.03).
Postoperative need for rescue anti-emetics in 24 h
The aggregate effect of three studies
46 49 51
examining 10
mg i.v. metoclopramide on the need of rescue anti-emetics
over 24 h demonstrated a beneficial effect of
Study name Comparison Outcome Statistics for each study Events/Total Odds ratio and 95% Cl
Odds
ratio
Lower
limit
Upper
limit Z-value P-value Metoclopramide Control
Entezariasl
Entezariasl 2
Nasek-adam 2004
Huang
Wilson
Helmy
Paxton
Joshi
Madej Out Gyne
Handley
Nasek-adam 2
Nasek-adam
Rauers
Bilgin
Meto-saline Early vomiting
Early vomiting
Early vomiting
Early vomiting
Early vomiting
Early vomiting
Early vomiting
Early vomiting
Early vomiting
Early vomiting
Early vomiting
Early vomiting
Early vomiting
Early vomiting
0.167
0.320
0.123
1.137
0.673
1.000
0.624
0.525
0.323
0.145
0.764
0.130
0.298
0.229
0.441
0.018
0.012
0.025
0.457
0.194
0.134
0.160
0.169
0.121
0.017
0.204
0.025
0.076
0.036
0.298
1.546
8.245
0.593
2.828
2.333
7.470
2.436
1.626
0.866
1.268
2.860
0.680
1.174
1.445
0.652
0.115
0.492
0.009
0.782
0.533
1.000
0.497
0.265
0.025
0.081
0.689
0.016
0.083
0.117
0.000
1 / 25
0 / 25
2 / 40
12 / 59
5 / 40
2 / 40
4 / 35
6 / 38
6 / 72
1 / 40
5 / 29
2 / 25
3 / 50
2 / 26
51 / 544
5 / 25
1 / 25
12 / 40
11 / 60
7 / 40
2 / 40
6 / 35
10 / 38
18 / 82
6 / 40
6 / 28
10 / 25
9 / 51
4 / 15
107 / 544
–1.577
–0.687
–2.611
–0.277
–0.624
0.000
–0.679
–1.116
–2.245
–1.745
–0.400
–2.417
–1.731
–1.568
–4.109
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
0.01 0.1
Metoclopramide Control
1 10 100
Fig 7 Pooled data evaluating the effect of systemic metoclopramide on the early incidence of vomiting compared with control. Data were
evaluated by calculating OR. The point estimate (95% CI) for the overall effect was 0.44 (0.29 0.65). OR for individual studies represented
by square on the Forrest plot with 95% CI of the difference shown as solid line. Larger sized squares denote larger sample size. The
diamond represents the pooled estimate and uncertainty for the combined effect.
Study name Comparison Outcome Statistics for each study Events/Total Odds ratio and 95% Cl
Odds
ratio
Lower
limit
Upper
limit Z-value P-value Metoclopramide Control
Entezariasl
Entezariasl 2
Nasek-adam 2004
Rusch 1999
Huang
Rusch
Helmy
Morris
Ascaso
Paxton
Rust
Meto-saline Vomiting 24 h
Vomiting 24 h
Vomiting 24 h
Vomiting 24 h
Vomiting 24 h
Vomiting 24 h
Vomiting 24 h
Vomiting 24 h
Vomiting 24 h
Vomiting 24 h
Vomiting 24 h
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
Meto-saline
0.167
0.320
0.698
0.543
0.655
0.292
0.321
0.551
0.229
0.814
0.588
0.516
0.018
0.012
0.214
0.202
0.229
0.103
0.122
0.348
0.064
0.286
0.371
0.402
1.546
8.245
2.275
1.465
1.868
0.822
0.844
0.872
0.822
2.322
0.931
0.664
0.115
0.492
0.551
0.228
0.428
0.020
0.021
0.011
0.024
0.701
0.024
0.000
–1.577
–0.687
–0.596
–1.205
–0.792
–2.330
–2.303
–2.543
–2.260
–0.384
–2.262
–5.165
1 / 25
0 / 25
6 / 35
10 / 33
8 / 38
9 / 33
9 / 40
289 / 462
3 / 51
12 / 29
296 / 462
643 / 1233
5 / 25
1 / 25
8 / 35
16 / 36
11 / 38
18 / 32
19 / 40
88 / 117
18 / 84
13 / 28
88 / 117
285 / 1577
0.01 0.1
Metoclopramide Control
1 10 100
Fig 6 Pooled data evaluating the effect of systemic metoclopramide on the 24 h incidence of vomiting compared with control. Data were
evaluated by calculating OR. The point estimate (95% CI) for the overall effect was 0.51 (0.40 0.66). OR for individual studies represented
by the square on the Forrest plot with 95% CI of the difference shown as a solid line. Larger sized squares denote larger sample size. The
diamond represents the pooled estimate and uncertainty for the combined effect.
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metoclopramide compared with placebo, OR (95% CI) of 0.41
(0.190.92), NNT¼ 6.0. Heterogeneity was low (I
2
¼ 0). The
funnel plot was not asymmetric (P¼ 0.31). All three studies
evaluated metoclopramide as a single agent for PONV
prophylaxis.
Safety analysis
Extrapyramidal symptoms
Two studies reported the presence of extrapyramidal symp-
toms.
65 66
The combined effect did not show a significant
effect of metoclopramide, OR (95% CI) of 1.0 (0.23.7). Het-
erogeneity was low (I
2
¼ 0).
Dizziness
The combined effect of five studies
39 41 44 45 53
did not reveal
a significant effect of metoclopramide on the incidence of
postoperative dizziness, OR (95% CI) of 1.3 (0.53.5). Hetero-
geneity was low (I
2
¼ 0).
Headache
The overall effect of six studies on the incidence of post-
operative headache
39 41 44 45 53 56
did not reveal a significant
effect of metoclopramide over placebo, OR (95% CI) of 0.7
(0.41.4). Heterogeneity was low (I
2
¼ 0).
Sedation
The aggregated effect of eight studies
39 41 44 45 50 62 65 66
examining the effect of metoclopramide on postoperative
sedation did not show a significant effect of metoclopramide,
OR (95% CI) of 1.0 (0.6 1.5). Heterogeneity was low (I
2
¼ 0).
Discussion
The most important finding of the current investigation is the
detection of an effect of systemic metoclopramide in the pre-
vention of PONV. Metoclopramide was also effective in redu-
cing the incidence of nausea and vomiting when these
outcomes were examined separately. Systemic metoclopra-
mide can also be a viable alternative to prevent PONV
in countries where other anti-emetic agents are cost
prohibitive.
72
Our findings have important clinical implications because
a previous systematic review examining the effect of meto-
clopramide did not find a clinically significant effect in the re-
duction in PONV.
5
It is important to note that the previous
systematic review included multiple trials with questioned
validity performed by the author Yoshitaka Fujii.
78
This
trials were performed to compare ‘newer’ anti-emetic
agents with saline and metoclopramide and did not demon-
strate a benefit of metoclopramide compared with saline, as
demonstrated in our post hoc analysis. Expert reviews and
the current Society of Ambulatory Anaesthesia guidelines
do not recommend systemic metoclopramide to prevent
PONV.
67374
Our results suggest that metoclopramide is a
reasonable alternative to other commonly used anti-emetic.
It remains to be determined if the 10 mg i.v. metoclopra-
mide offers benefit when used as a second anti-emetic as
part of a multimodal therapy. Our analysis was very limited
by the low number of studies providing that comparison.
Wallenborn and colleagues
36
have performed a large rando-
mized controlled trial where they found a benefit of greater
doses of metoclopramide (25 and 50 mg) but not 10 mg
i.v. in combination with dexamethasone to prevent PONV.
We excluded that trial from our analysis because the anaes-
thetic care was not standardized and some subjects received
regional anaesthesia. Recently, Mishriky and Habib
75
found a
benefit of 10 mg i.v. metoclopramide to prevent PONV in
patients undergoing Caesarean delivery under regional an-
aesthesia, but their analysis did not include subgroup com-
parisons testing the efficacy of 10 mg i.v. metoclopramide
given as part of a combination regimen.
PONV has been mentioned as a frequent reason to
prolong hospital discharge.
76
In the current investigation,
we were able to demonstrate a clinically significant effect
of 10 mg i.v. metoclopramide in early PONV (NNT¼ 7.6). The
clinical effect seems to be more pronounced against
nausea (NNT¼ 5.9) than against vomiting (NNT¼ 10.5). It is
plausible that the addition of a drug with reported greater
anti-vomiting effects than anti-nausea effects such as
ondansetron may provide additional benefits on early symp-
toms of PONV and expedite hospital discharge.
77
Future
studies to examine the effect of metoclopramide on time
to hospital discharge are required.
Our systematic review did not detect an increase in com-
monly reported side-effects such as headache, dizziness, or
sedation because of the use of systemic 10 mg i.v. metoclopra-
mide. Only two studies reported on the incidence of extrapyr-
amidal symptoms, but the combined effect did not suggest an
increase in those side-effects compared with saline (OR¼ 1.0).
Wallenborn and colleagues
36
found that greater doses of
metoclopramide caused more tachycardia and a small risk of
extrapyramidal symptoms. The 10 mg i.v. metoclopramide is
clinically effective to reduce PONV and does not seem to
have the side-effects reported by greater dosage regimens.
It seems that the clinical effect of metoclopramide when
used as a single regimen has similar efficacy as commonly
used anti-emetic agents, specifically when examining the
previously reported efficacy of those agents. Henzi and col-
leagues
78
evaluating the effect of 810 mg dexamethasone
in a systematic review reported that the NNT (95% CI) to
prevent early and late vomiting compared with placebo in
adults was 7.1 (95% CI 4.518). With regard to ondansetron,
the NNT was found to be 6 for the prevention of vomiting and
7 for the prevention of nausea.
6
Nevertheless, only a direct
comparison will be able to exclude potential benefits of other
agents compared with metoclopramide in PONV prophylaxis.
We assessed the risk of bias in the individual studies using
the Jadad scale. The use of rating scales is controversial in
systematic reviews due to large interobserver variation
detected in the utilization of those scales. We attempted to
minimize the effect of interobserver variation by having
two investigators rate the studies and a third investigator
BJA De Oliveira Jr et al.
694
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in cases of a dispute. In addition, we did not exclude studies
based on rating and did not perform a weighted analysis
based on the study quality. It is also important to note
that the use of scale does not exclude the possibility of
bias in the individual studies.
Our analysis is only valid if interpreted within the context
of its limitations. In order to obtain generalizable results, we
have included a large number of different surgical procedures
which can be criticized when performing quantitative sys-
tematic reviews. Nevertheless, the measured heterogeneity
in all analysis was very low which in fact suggests the gener-
alizability of our findings. Some of our secondary analysis
was limited by the presence of an asymmetric funnel plot
and the possibility of publication bias; therefore, those ana-
lyses need to be interpreted with caution. It is possible that
the detection of studies that were file drawered because of
negative results could possibly overestimate the ORs deter-
mined in some of those analyses.
79
In summary, we demonstrated that 10 mg i.v. metoclo-
pramide is effective to prevent PONV in patients having sur-
gical procedures under general anaesthesia. In times of drug
shortages and in circumstances where other anti-emetic are
cost prohibitive, metoclopramide seems to be a reasonable
alternative to prevent PONV.
Supplementary material
Supplementary material is available at British Journal of
Anaesthesia online.
Declaration of interest
None declared.
Funding
This study was funded by the Department of Anesthesiology,
Northwestern University Feinberg School of Medicine.
References
1 Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six inter-
ventions for the prevention of postoperative nausea and vomit-
ing. N Engl J Med 2004; 350: 244151
2 Le TP, Gan TJ. Update on the management of postoperative
nausea and vomiting and postdischarge nausea and vomiting
in ambulatory surgery. Anesthesiol Clin 2010; 28: 22549
3 Myles PS, Wengritzky R. Simplified postoperative nausea and
vomiting impact scale for audit and post-discharge review. Br J
Anaesth 2012; 108: 4239
4 De Oliveira GS Jr, Theilken LS, McCarthy RJ. Shortage of periopera-
tive drugs: implications for anesthesia practice and patient
safety. Anesth Analg 2011; 113: 1429 35
5 Henzi I, Walder B, Trame
`
r MR. Metoclopramide in the prevention
of postoperative nausea and vomiting: a quantitative systematic
review of randomized, placebo-controlled studies. Br J Anaesth
1999; 83: 76171
6 Gan TJ, Meyer TA, Apfel CC, et al.; Society for Ambulatory Anesthe-
sia. Society for Ambulatory Anesthesia guidelines for the
management of postoperative nausea and vomiting. Anesth
Analg 2007; 105: 161528
7 Carlisle JB. The analysis of 169 randomised controlled trials to
test data integrity. Anaesthesia 2012; 67: 521 37
8 Pandit JJ. On statistical methods to test if sampling in trials is
genuinely random. Anesthesia 2012; 67: 456 62
9 Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for
reporting systematic reviews and meta-analyses of studies that
evaluate health care interventions: explanation and elaboration.
J Clin Epidemiol 2009; 62:e134
10 Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of
reports of randomized clinical trials: is blinding necessary?
Control Clin Trials 1996; 17:112
11 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin
Trials 1986; 7: 17788
12 Egger M, Davey Smith G, Schneider M, Minder C. Bias in
meta-analysis detected by a simple, graphical test. Br Med J
1997; 315: 62934
13 Rosenthal R. The file drawer problem and tolerance for null
results. Psychol Bull 1979; 86: 63841
14 Krobbuaban B, Pitakpol S, Diregpoke S. Ondansetron vs. metoclo-
pramide for the prevention of nausea and vomiting after gyneco-
logic surgery. J Med Assoc Thai 2008; 91: 66974
15 Sandhu T, Tanvatcharaphan P, Cheunjongkolkul V. Ondansetron
versus metoclopramide in prophylaxis of nausea and vomiting
for
laparoscopic cholecystectomy: a prospective double-blind
randomized study. Asian J Surg 2008; 31:504
16 Leksowski K, Peryga P, Szyca R. Ondansetron, metoclopramid,
dexamethason, and their combinations compared for the preven-
tion of postoperative nausea and vomiting in patients undergo-
ing laparoscopic cholecystectomy: a prospective randomized
study. Surg Endosc 2006; 20: 87882
17 Maddali MM, Mathew J, Fahr J, Zarroug AW. Postoperative nausea
and vomiting in diagnostic gynaecological laparoscopic proce-
dures: comparison of the efficacy of the combination of dexa-
methasone and metoclopramide with that of dexamethasone
and ondansetron. J Postgrad Med 2003; 49: 302 6
18 Quaynor H, Raeder JC. Incidence and severity of postoperative
nausea and vomiting are similar after metoclopramide 20 mg
and ondansetron 8 mg given by the end of laparoscopic chole-
cystectomies. Acta Anaesthesiol Scand 2002; 46: 10913
19 Dabbous A, Khoury SJ, Chehab IR, Bartelmaos T, Khoury G.
Ondansetron versus dehydrobenzoperidol and metoclopramide
for management of postoperative nausea in laparoscopic
surgery patients. J Soc Laproendosc Surg 2001; 5: 13942
20 Steinbrook RA, Gosnell JL, Freiberger D. Prophylactic antiemetics
for laparoscopic cholecystectomy: a comparison of perphenazine,
droperidol plus ondansetron, and droperidol plus metoclopra-
mide. J Clin Anesth 1998; 10: 494 8
21 Pugh SC, Jones NC, Barsoum LZ. A comparison of prophylactic
ondansetron and metoclopramide administration in patients
undergoing major neurosurgical procedures. Anaesthesia 1996;
51: 11624
22 Watts SA. A randomized double-blinded comparison of metoclo-
pramide, ondansetron and cyclizine in day-case laparoscopy.
Anaesth Intensive Care 1996; 24: 54651
23 Chen PP, Chui PT, Gin T. Comparison of ondansetron and metoclo-
pramide for the prevention of post-operative nausea and vomit-
ing after major gynaecological surgery. Eur J Anaesthesiol 1996;
13: 48591
24 Raphael JH, Norton AC. Antiemetic efficacy of prophylactic
ondansetron in laparoscopic surgery: randomized, double-blind
Metoclopramide and PONV BJA
695
by guest on December 27, 2015http://bja.oxfordjournals.org/Downloaded from
Page 8
comparison with metoclopramide. Br J Anaesth 1993; 71:
845 8
25 Alon E, Himmelseher S. Ondansetron in the treatment of post-
operative vomiting: a randomized, double-blind comparison
with droperidol and metoclopramide. Anesth Analg 1992; 75:
561 5
26 Vollmer-Larsen B, Sonne N. The effect of metoclopramide on
postoperative nausea and vomiting. Ugeskr Laeger 1988; 150:
154 5
27 Pandit SK, Kothary SP, Pandit UA, Mirakhur RK. Premedication with
cimetidine and metoclopramide. Effect on the risk factors of acid
aspiration. Anaesthesia 1986; 41: 48692
28 Kauste A, Tuominen M, Heikkinen H, Gordin A, Korttila K. Droper-
idol, alizapride and metoclopramide in the prevention and treat-
ment of post-operative emetic sequelae. Eur J Anaesthesiol 1986;
3:19
29 Guldager H, Jensen FM, Andersen KH, Arnfred I. Domperidone
and metoclopramide in the prevention of postoperative nausea
and vomiting. Ugeskr Laeger 1983; 145: 1777 9
30 Jensen NH, Termansen K. Metoclopramide in the prevention of
postoperative nausea and vomiting. Ugeskr Laeger 1983; 145:
230 2
31 Talesh KT, Motamedi MH, Kahnamouii S. Comparison of ondanse-
tron and metoclopramide antiemetic prophylaxis in maxillofacial
surgery patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
2011; 111: 2757
32 Ebrahim Soltani A, Mohammadinasab H, Goudarzi M, et al. Acu-
pressure using ondansetron versus metoclopramide on reduction
of postoperative nausea and vomiting after strabismus surgery.
Arch Iran Med 2010; 13: 28893
33 Unal Y, Ozsoylar O, Arslan M, Sarigu
¨
ney D, Akc¸abay M. Compari-
son of the efficacy of propofol and metoclopramide in preventing
postoperative nausea and vomiting after middle ear surgery.
Saudi Med J 2009; 30: 77882
34 Karlidag
˘
T, Kaygusuz I, Bestas¸ A, Keles¸ E, Demirbag
˘
E, Yalc¸in S.
The efficacy of droperidol, metoclopramide, propofol, and
ondansetron for the prevention of nausea and vomiting follow-
ing middle ear surgery. Kulak Burun Bogaz Ihtis Derg 2002; 9:
331 6
35 Eberhart LH, Seeling W, Ulrich B, Morin AM, Georgieff M. Dimenhy-
drinate and metoclopramide for prevention of nausea and vomit-
ing following septorhinoplasties in women. Anasthesiol
Intensivmed Notfallmed Schmerzther 1999; 34: 4804
36 Wallenborn J, Gelbrich G, Bulst D, et al. Prevention of post-
operative nausea and vomiting by metoclopramide combined
with dexamethasone: randomised double blind multicentre
trial.
Br Med J 2006; 333:
324
37 Tzeng JI, Hsing CH, Chu CC, Chen YH, Wang JJ. Low-dose dexa-
methasone reduces nausea and vomiting after epidural mor-
phine: a comparison of metoclopramide with saline. J Clin
Anesth 2002; 14:1923
38 Treen DC Jr, Downes TW III, Hayes DH, McKinnon WM. Outpatient
cholecystectomy simulated in an inpatient population. Am Surg
1991; 57:3945
39 Ekinci O, Malat I, Is¸ıtmangil G, Aydın N. A randomized comparison
of droperidol, metoclopramide, tropisetron, and ondansetron for
the prevention of postoperative nausea and vomiting. Gynecol
Obstet Invest 2011; 71:5965
40 Entezariasl M, Khoshbaten M, Isazadehfar K, Akhavanakbari G. Ef-
ficacy of metoclopramide and dexamethasone for postoperative
nausea and vomiting: a double-blind clinical trial. East Mediterr
Health J 2010; 16: 300 3
41 Bilgin TE, Birbicer H, Ozer Z, Doruk N, Tok E, Oral U. A comparative
study of the antiemetic efficacy of dexamethasone, ondansetron,
and metoclopramide in patients undergoing gynecological
surgery. Med Sci Monit 2010; 16: CR33641
42 Rauers NI, Stu
¨
ber F, Lee EH, et al. Antagonistic effects of ondan-
setron and tramadol? A randomized placebo and active drug con-
trolled study. J Pain 2010; 11: 127481
43 Kaki AM, Abd El-Hakeem EE. Prophylaxis of postoperative nausea
and vomiting with ondansetron, metoclopramide, or placebo in
total intravenous anesthesia patients undergoing laparoscopic
cholecystectomy. Saudi Med J 2008; 29: 1408 13
44 Nesek-Adam V, Grizelj-Stojcic
´
E, Rasic
´
Z, Cala Z, Mrsic
´
V,
Smiljanic
´
A. Comparison of dexamethasone, metoclopramide,
and their combination in the prevention of postoperative
nausea and vomiting after laparoscopic cholecystectomy. Surg
Endosc 2007; 21: 60712
45 Nesek-Adam V, Grizelj-Stojcic
´
E, Mrsic
´
V, Smiljanic
´
A, Rasic
´
Z,
Cala Z. Prophylactic antiemetics for laparoscopic cholecystec-
tomy: droperidol, metoclopramide, and droperidol plus metoclo-
pramide. J Laparoendosc Adv Surg Tech A
46 Ru
¨
sch D, Palm S, Sauerwald M, Ro
¨
mer T, Wulf H. Prophylaxis of
postoperative nausea and vomiting following gynaecological
laparoscopy. Anasthesiol Intensivmed Notfallmed Schmerzther
2002; 37:1623
47 Huang JC, Shieh JP, Tang CS, Tzeng JI, Chu KS, Wang JJ. Low-dose
dexamethasone effectively prevents postoperative nausea and
vomiting after ambulatory laparoscopic surgery. Can J Anaesth
2001; 48: 9737
48 Wilson EB, Bass CS, Abrameit W, Roberson R, Smith RW. Metoclo-
pramide versus ondansetron in prophylaxis of nausea and vomit-
ing for laparoscopic cholecystectomy. Am J Surg 2001; 181:
138 41
49 Muhammad SR, Abbas SZ, Abbas SQ. Randomised, prospective,
controlled trial comparing tropisetron with metoclopramide and
placebo in controlling postoperative nausea and vomiting. JPak
Med Assoc 2000; 50: 386 8
50 Sharma S, Abdullah N. A comparison of commonly used
anti-emetics for the prevention of emetic sequelae after a
major gynaecological surgery. Singapore Med J 2000; 41: 14750
51 Ru
¨
sch D, Bernhardt J, Wulf H. Prophylaxis of nausea and vomiting
after pelviscopy. Dolasetron or MCP in comparison with placebo.
Anaesthesist 1999; 48: 70512
52 Helmy SA. Prophylactic anti-emetic efficacy of ondansetron
in laparoscopic cholecystectomy under total intravenous
anaesthesia. A randomised, double-blind comparison with
droperidol, metoclopramide and placebo. Anaesthesia 1999; 54:
266 71
53 Morris RW, Aune H, Feiss P, et al. International, multicentre,
placebo-controlled study to evaluate the effectiveness of ondan-
setron vs. metoclopramide in the prevention of post-operative
nausea and vomiting. Eur J Anaesthesiol 1998; 15:6979
54 Loo CC, Thomas E, Tan HM, Sia TH. A comparison of
antiemetic efficacy of droperidol alone and in combination with
metoclopramide in day surgery anaesthesia. Med J Malaysia
1997; 52: 2648
55 Ascaso FJ, Ayala I, Carbonell P, Castro FJ, Palomar A. Prophylactic
intravenous ondansetron in patients undergoing cataract extrac-
tion under general anesthesia. Ophthalmologica 1997; 211: 2925
56 Pertusa V, Bellver J, Marque
´
sA,et al. Antiemetic prophylaxis after
laparoscopic cholecystectomy: comparative study of dehydro-
benzperidol, metoclopramide, ondansetron and placebo. Rev
Esp Anestesiol Reanim 1996; 43: 23942
BJA De Oliveira Jr et al.
696
by guest on December 27, 2015http://bja.oxfordjournals.org/Downloaded from
Page 9
57 Naguib M, el Bakry AK, Khoshim MH, et al. Prophylactic antiemetic
therapy with ondansetron, tropisetron, granisetron and metoclo-
pramide in patients undergoing laparoscopic cholecystectomy: a
randomized, double-blind comparison with placebo. Can J
Anaesth 1996; 43: 22631
58 Desilva PH, Darvish AH, McDonald SM, Cronin MK, Clark K. The
efficacy of prophylactic ondansetron, droperidol, perphenazine,
and metoclopramide in the prevention of nausea and vomiting
after major gynecologic surgery. Anesth Analg 1995; 81: 13943
59 Paxton LD, McKay AC, Mirakhur RK. Prevention of nausea and
vomiting after day case gynaecological laparoscopy. A compari-
son of ondansetron, droperidol, metoclopramide and placebo.
Anaesthesia 1995; 50: 4036
60 Rust M. Intravenous administration of ondansetron vs. metoclo-
pramide for the prophylaxis of postoperative nausea and vomit-
ing. Anaesthesist 1995; 44: 28890
61 Joshi R, Sivaganesanathan A. Tiapride versus metoclopramide:
comparison after minor gynaecological surgery. Eur J Anaesthe-
siol 1993; 10: 10912
62 Lim KS, Lim BL, Tee CS, Vengadasalam D. Nausea and vomiting
after termination of pregnancy as day surgery cases: comparison
of 3 different doses of droperidol and metoclopramide as
anti-emetic prophylaxis. Singapore Med J 1991; 32: 3423
63 Dimich I, Katende R, Singh PP, Mikula S, Sonnenklar N. The effects
of intravenous cimetidine and metoclopramide on gastric pH and
volume in outpatients. J Clin Anesth 1991; 3:404
64 Bone ME, Wilkinson DJ, Young JR, McNeil J, Charlton S. Ginger
root—a new antiemetic. The effect of ginger root on post-
operative nausea and vomiting after major gynaecological
surgery. Anaesthesia 1990; 45: 66971
65 Madej TH, Simpson KH. Comparison of the use of domperidone,
droperidol and metoclopramide in the prevention of nausea
and vomiting following gynaecological surgery in day cases. Br
J Anaesth 1986; 58: 87983
66 Madej TH, Simpson KH. Comparison of the use of domperidone,
droperidol and metoclopramide in the prevention of nausea
and vomiting following major gynaecological surgery. Br J
Anaesth 1986; 58: 8847
67 Waldmann CS, Verghese C, Short SM, Goldhill DR, Evans SJ.
The evaluation of domperidone and metoclopramide as
antiemetics in day care abortion patients. Br J Clin Pharmacol
1985; 19: 30710
68 Handley AJ. Metoclopramide in the prevention of
post-operative nausea and vomiting. Br J Clin Pract 1967; 21:
460 2
69 Fujii Y, Tanaka H, Toyooka H. Prevention of nausea and vomiting in
female patients undergoing breast surgery: a comparison with
granisetron, droperidol, metoclopramide and placebo. Acta
Anaesthesiol Scand 1998; 42: 2204
70 Fujii Y, Toyooka H, Tanaka H. Prevention of PONV with granisetron,
droperidol and metoclopramide in female patients with history of
motion sickness. Can J Anaesth 1997; 44: 8204
71 Fujii Y, Saitoh Y, Tanaka H, Toyooka H. Anti-emetic efficacy of
prophylactic granisetron, droperidol and metoclopramide in the
prevention of nausea and vomiting after laparoscopic cholecyst-
ectomy: a randomized, double-blind, placebo-controlled trial. Eu
r
J Anaesthesiol 1998; 15: 16671
72 Diemunsch P, Diemunsch AM. Economics of antiemetics. Curr
Opin Anaesthesiol 2002; 15: 2337
73 Kolodzie K, Apfel CC. Nausea and vomiting after office-based an-
esthesia. Curr Opin Anaesthesiol 2009; 22: 5328
74 Kranke P, Eberhart LH. Possibilities and limitations in the pharma-
cological management of postoperative nausea and vomiting.
Eur J Anaesthesiol 2011; 28: 75865
75 Mishriky BM, Habib AS. Metoclopramide for nausea and vomit-
ing prophylaxis during and after Caesarean delivery: a system-
atic review and meta-analysis. Br J Anaesth 2012; 108:
37483
76 Awad IT, Chung F. Factors affecting recovery and
discharge following ambulatory surgery. Can J Anaesth 2006;
53: 85872
77 White PF, Watcha MF. Has the use of meta-analysis enhanced our
understanding of therapies for postoperative nausea and vomit-
ing? Anesth Analg 1999; 88: 12002
78 Henzi I, Walder B, Trame
`
r MR. Dexamethasone for the prevention
of postoperative nausea and vomiting: a quantitative systematic
review. Anesth Analg 2000; 90: 18694
79 De Oliveira GS Jr, Chang R, Kendall MC, Fitzgerald PC, McCarthy RJ.
Publication bias in the anesthesiology literature. Anesth Analg
2012; 114: 10428
Metoclopramide and PONV BJA
697
by guest on December 27, 2015http://bja.oxfordjournals.org/Downloaded from
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    • "Similarly, other researchers declared early feeding after cesarean leads to earlier establishment of intestinal motility, but sometimes, it was accompanied by vomiting [33]. The considerable point in our method is the fact that metoclopramide in addition to decreasing ileus has other advantages like prevention of nausea , vomiting, and esophageal reflux [34, 35]. At the end, we declare that this study has had some limitations in point of blindness. "
    [Show abstract] [Hide abstract] ABSTRACT: Ileus is a common event following cesarean section. Early post-cesarean recovery is very important not only for the mother but also for the baby who is dependent on breastfeeding. This article aims to demonstrate the efficacy of metoclopramide for the prevention of ileus after cesarean. In this randomized controlled trial, 696 women scheduled for cesarean were randomized in two groups. Three hundred fifty-three persons settled in control group and 343 were assigned in intervention group who received an injection of 10-mg intramuscular metoclopramide prior to operation. After cesarean, the participants recorded the first flatus, defecation, feeling of hunger, feeding and ambulation in a questionnaire, and also their sense of bloating in a visual analog scale under supervision of a research assistant. The data was analyzed by SPSS 17, t test, and chi-square, while p < 0.05 was considered significant. The interval between cesarean and the first flatus (p < 0.0001), defecation (p < 0.0001), feeling of hunger (p < 0.0001), feeding (p = 0.007), and ambulation (p < 0.0001) were significantly shorter in the metoclopramide group. In addition, polytomous logistic regression analysis showed the metoclopramide group had less bloating with significant difference (OR = 2.83 and CI 1.91-4.21). Our study proved the functionality of metoclopramide in preventing ileus. As this drug is safe, tolerable, harmless, inexpensive and available, and also no definite method has been developed to prevent ileus after cesarean; yet, metoclopramide could be considered as a suitable option. Certainly with regard to some limitations in our study, further comprehensive studies are still required to ensure validity of the obtained results.
    Full-text · Article · Apr 2015 · European Journal of Clinical Pharmacology
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    • "There are several classical receptor antagonists apart from the 5-HT-3 blockers that have effect on PONV and systematic review around antiemetics and drug combination have recently been published [71e73] . A meta-analysis by DeOliviera et al. published late 2012 [74] showed that the old and wellestablished metoclopramide 10 is effective for prevention of PONV. Likewise the antiemetic effects of low <1 mg droperidol has been documented in a meta analysis by Shaub et al. [75]. "
    [Show abstract] [Hide abstract] ABSTRACT: Postoperative nausea and vomiting “the little big problem” after surgery/anaesthesia is still a common side-effect compromising quality of care, delaying discharge and resumption of activities of daily living. A huge number of studies have been conducted in order to identify risk factors, preventive and therapeutic strategies. The Apfel risk score and a risk based multi-modal PONV prophylaxis is advocated by evidence based guidelines as standards of care but is not always followed. Tailored anaesthesia and pain management avoiding too liberal dosing of anaesthetics and opioid analgesics is also essential in order to reduce risk. Thus multi-modal opioid sparing analgesia and a risk based PONV prophylaxis should be provided in order to minimise the occurrence. There is however still no way to guarantee an individual patient that he or she should not experience any PONV. Further studies are needed trying to identify risk factors and ways to tailor the individual patient prevention/therapy are warranted.
    Full-text · Article · Jan 2015 · International Journal of Surgery
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    • "A dose of 10 mg of metoclopramide is commonly administered, and a recent meta-analysis showed that there were no side effects of metoclopramide, such as extrapyramidal symptoms, dizziness, headache, and sedation, at doses up to this level [21]. "
    [Show abstract] [Hide abstract] ABSTRACT: Postoperative nausea and vomiting (PONV) is a long-standing issue, not a new concept in anesthesiology. Despite many studies over the last several decades, PONV remains a significant problem due to its complex mechanism. This review presents a summary of the mechanism underlying the pathogenesis of PONV, focusing on preventive treatment, particularly the use of new drugs. In addition, we discuss the latest meta-analysis results regarding correct clinical use of classic drugs. I also summarize the latest trends of postdischarge nausea and vomiting and the pharmacogenetics, which is attracting a great deal of attention from other medical fields in PONV-related studies. Finally, we discuss the drawbacks of existing studies on PONV and suggest a focus for future investigations.
    Full-text · Article · Sep 2014 · Korean journal of anesthesiology
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