British Journal of Anaesthesia, 118 (1): 839 (2017)

doi: 10.1093/bja/aew375
Clinical Practice

Chewing gum for the treatment of postoperative

nausea and vomiting: a pilot randomized

Downloaded from http://bja.oxfordjournals.org/ at University of California, San Diego on December 30, 2016
controlled trial
J. N. Darvall1,2,3,*, M. Handscombe1 and K. Leslie1,3,4,5
1
Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne, Victoria, Australia,
2
Royal Melbourne Hospital Clinical School, Faculty of Medicine, Dentistry and Health Sciences, University of
Melbourne, Melbourne, Victoria, Australia, 3Anaesthesia, Perioperative and Pain Medicine Unit, University of
Melbourne, Melbourne, Victoria, Australia, 4Department of Pharmacology and Therapeutics, University of
Melbourne, Melbourne, Victoria, Australia and 5Department of Epidemiology and Preventive Medicine,
Monash University, Melbourne, Victoria, Australia

*Corresponding author. E-mail: jai.darvall@mh.org.au

Abstract
Background. A novel treatment, chewing gum, may be non-inferior to ondansetron in inhibiting postoperative nausea and
vomiting (PONV) in female patients after laparoscopic or breast surgery. In this pilot study, we tested the feasibility of a large
randomized controlled trial.
Methods. We randomized 94 female patients undergoing laparoscopic or breast surgery to ondansetron 4 mg i.v. or chewing
gum if PONV was experienced in the postanaesthesia care unit (PACU). The primary outcome was full resolution of PONV,
with non-inferiority defined as a difference between groups of <15% in a per protocol analysis. Secondary outcomes were
PACU stay duration, anti-emetic rescue use, and acceptability of anti-emetic treatment. The feasibility of implementing the
protocol in a larger trial was assessed.
Results. Postoperative nausea and vomiting in the PACU occurred in 13 (28%) ondansetron patients and 15 (31%) chewing
gum patients (P0.75). Three chewing gum patients could not chew gum when they developed PONV. On a per protocol
basis, full resolution of PONV occurred in five of 13 (39%) ondansetron vs nine of 12 (75%) chewing gum patients [risk differ-
ence 37% (6.367%), P0.07]. There was no difference in secondary outcomes between groups. Recruitment was satisfactory,
the protocol was acceptable to anaesthetists and nurses, and data collection was complete.
Conclusions. In this pilot trial, chewing gum was not inferior to ondansetron for treatment of PONV after general anaesthe-
sia for laparoscopic or breast surgery in female patients. Our findings demonstrate the feasibility of a larger, multicentred
randomized controlled trial to investigate this novel therapy.
Clinical trial registration. Australian New Zealand Clinical Trials Registry: ACTRN12615001327572.

Key words: chewing gum; ondansetron; postanaesthesia nursing; postoperative nausea and vomiting

Postoperative nausea and vomiting (PONV) affects one-third of cause of admission after planned ambulatory surgery and may
untreated patients after general anaesthesia.1 2 It is a leading lead to dehydration, bleeding, surgical wound complications, and

Editorial decision October 7, 2016; Accepted: October 7, 2016

C The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
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83
 84 | Darvall et al.
Editors key points
Chewing gum may be as effective as ondansetron in in-
hibiting postoperative nausea and vomiting (PONV).
Either ondansetron 4 mg or chewing gum was randomly
provided to female patients who had PONV after laparo-
scopic or breast surgery, to test the feasibility of a large
randomized controlled trial.
A large randomized controlled trial would be feasible,
because recruitment was satisfactory, the protocol was
acceptable to anaesthetists and nurses, and data collec-
tion was complete.
aspiration of gastric contents.3 4 Well-established guidelines for
the pharmacological prophylaxis and treatment of PONV exist;
however, medications such as the 5-hydroxytryptamine type 3 (5-
HT) receptor antagonists are only partly effective and have side-
effects.5 More recently, interest has emerged in non-
pharmacological therapies, such as P6 stimulation with acupunc-
ture modalities6 and ginger,7 which have advantages including
low cost, favourable side-effect profile, and patient acceptability.
Chewing gum has been prospectively evaluated as a therapy
to reduce postoperative paralytic ileus after gastrointestinal sur-
gery. Postulated mechanisms of its effect surround the principle
of sham feeding, with chewing resulting in increased gastro-
intestinal activity via cephalic vagal stimulation.8 Recent meta-
analyses (the largest involving 272 patients across seven
randomized controlled trials) have demonstrated a reduced
time to first flatus and bowel motion, and a non-significant
trend towards earlier hospital discharge.911 To date, however,
no study has examined the effect of gum chewing on PONV.
We previously conducted a prospective cohort study to as-
sess the safety and acceptability of chewing gum in the postan-
aesthesia care unit (PACU), enrolling 41 patients undergoing
ambulatory gynaecological laparoscopy.12 Thirty-one patients
(76%) were awake enough to chew gum. Chewing gum was ac-
ceptable to patients and PACU nurses, with no identified safety
concerns. Chewing gum has also been linked to lowered cortisol
concentrations, improved stress and anxiety, and more positive
mood in the research setting.13 14
We therefore conducted a pilot randomized controlled non-
inferiority trial to test the hypothesis that chewing gum in the
PACU would prove to be non-inferior to ondansetron for the
treatment of PONV in female patients after laparoscopic or
breast surgery and to test the feasibility of a large multicentre
randomized controlled trial using this protocol. The primary
outcome was full resolution of PONV after either ondansetron
or chewing gum. Secondary outcomes were the duration of
PACU stay, anti-emetic rescue use in the PACU, and patient ac-
ceptability of anti-emetic treatment. Feasibility outcomes were
recruitment rate, protocol compliance, incidence of PONV, abil-
ity to chew gum, and the primary outcome.
Methods
This pilot randomized controlled non-inferiority trial was con-
ducted in the Department of Anaesthesia and Pain
Management, Royal Melbourne Hospital. Approval was gained
from the hospital Human Research and Ethics Committee (21
December 2015, HREC number 2015.230), and the trial was regis-
tered with the Australian New Zealand Clinical Trials Registry
(ACTRN12615001327572; 3 December 2015).
Female patients aged 18 yr and of ASA physical status IIII
undergoing laparoscopic or breast surgery were enrolled be-
tween January and June 2016, after being advised that the prin-
cipal purpose of the study was to assess the feasibility of a
larger randomized controlled trial and after written informed
consent had been obtained. Patients were excluded if they had
inadequate English comprehension, significant cardiorespira-
tory impairment, impaired pharyngeal or oesophageal function,
phenylketonuria (contraindication to the sweetener aspartame
in chewing gum), a full upper or lower denture (not feasible to
chew gum), or a contraindication to any of the protocolized
anti-emetic drugs. Patients were randomized to either chewing
gum or ondansetron after written informed consent had been
obtained and before surgery. The randomization schedule was
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created via a computerized random number generator, with se-
quentially numbered envelopes used for allocation concealment
until PONV developed in the PACU. Patients, anaesthetists,
PACU nurses, and observers therefore were blind to group allo-
cation until PONV developed in the PACU.
Procedure
Induction of general anaesthesia was accomplished with either
fentanyl or alfentanil, propofol, and a non-depolarizing neuromus-
cular blocker if indicated. Midazolam premedication was permitted
at the discretion of the attending anaesthetist. Anaesthesia was
maintained with sevoflurane without nitrous oxide. Patient moni-
toring was established in accordance with the standards published
by the Australian and New Zealand College of Anaesthetists. At
the conclusion of anaesthesia, antagonism of neuromuscular block
was accomplished with neostigmine and glycopyrrolate, or if the
train of four count was zero with sugammadex 200 mg. Non-opioid
analgesics and additional fentanyl or morphine were given at the
discretion of the attending anaesthetist.
Anti-emetic prophylaxis
Intraoperative anti-emetic prophylaxis was protocolized accord-
ing to simplified Apfel risk factors, commensurate with the
Consensus Guidelines for the Management of Postoperative
Nausea and Vomiting published by the Society for Ambulatory
Anesthesia.5 Risk factors were female gender, non-smoking sta-
tus, past history of PONV or motion sickness, or anticipated re-
quirement for postoperative opioids (defined as estimated
requirement of at least 20 mg oral oxycodone equivalent in the
first 24 h after surgery, consistent with the initial validation tri-
als of the Apfel scoring system).15 Patients with one risk factor
(low risk) received no prophylaxis; patients with two or three
risk factors (medium risk) received dexamethasone 4 mg i.v.;
and patients with four risk factors (high risk) received dexa-
methasone 4 mg i.v. and droperidol 0.625 mg.
Treatment of postoperative nausea and vomiting
Patients randomized to chewing gum and experiencing PONV in
the PACU, with an Observers Assessment of Alertness/Sedation
(OAA/S) rating scale of 516 (responding readily to name spoken
in normal tone) and with the PACU nurse satisfied that the pa-
tient was not sleeping between observations, commenced gum
R
chewing (Wrigleys Extra Sugarfree GumV, peppermint flavour),
aiming for a period of 15 min. Patients randomized to ondanse-
tron, or those randomized to chewing gum who either refused it
or were too drowsy, received ondansetron 4 mg i.v. in the event
of PONV. The feasibility of chewing gum was recorded (able; un-
able because of refusal; unable because of drowsiness). Rescue

anti-emetics if the first-line therapy was not fully successful
consisted of the following: first line, ondansetron 4 mg i.v. (if not
already administered); second line, droperidol 0.625 mg i.v.;
third line, promethazine 6.25 mg i.v.; fourth line, dexametha-
sone 4 mg i.v.; fifth line, prochlorperazine 12.5 mg i.v.; and sixth
line, propofol 20 mg i.v. bolus. Observers recorded the number of
episodes of nausea, retching, and vomiting and the time when
each one occurred. Relief of PONV was graded on a four-point
verbal descriptive scale: worse, no change, partial resolution, or
full resolution. At readiness for discharge from the PACU, pa-
tients graded their acceptability of both anti-emetic treatment
and anaesthetic care using a five-point Likert scale ranging
from completely unacceptable to completely acceptable. Anti-
emetic and analgesic requirements for the first 24 h after sur-
gery were recorded.
Sample size calculation
The primary outcome was full resolution of PONV after the
randomized treatment. The target sample size for a definitive
non-inferiority randomized controlled trial was computed. A
non-inferiority trial using a hypothesized difference for equiva-
lence of 15% (i.e. effective treatment of PONV in 6075% of chew-
ing gum-treated patients considered equivalent to ondansetron
treatment) at a power of 80% and a0.05 would require 204 pa-
tients, 102 in each group. This clinically relevant margin for
equivalence was chosen as, if achieved, it was considered likely
to result in acceptance and potentially practice change by an-
aesthetists. In our previous cohort study,12 85% of patients
Enrolment Assessed for eligibility (n = 155)
Consented (n = 102)
Randomized (n = 94)
Allocated to chewing gum (n =48)
Received allocated intervention (n =12)
Did not receive allocated intervention (n =36)
No PONV (n = 33)
Too sleepy to chew (n = 2)
Refused gum (n = 1)
Lost to follow-up (n = 0)
Discontinued intervention (n = 0)
Analysed for primary outcome (n =12)
Excluded from analysis (n = 0)
Fig 1 CONSORT diagram. PONV, postoperative nausea and vomiting.
Chewing gum and PONV | 85
achieved an OAA/S score of 5 and were thus deemed sufficiently
awake to chew gum, and 40% of patients experienced PONV des-
pite appropriate prophylaxis. On the assumption that 40% of
randomized patients would experience PONV, of whom 85%
would be sufficiently awake to chew gum, a total of 600 patients
would be required, 300 in each group. To guide a future large
randomized controlled trial, we conducted an initial pilot trial
on a targeted convenience sample of 100 patients.
The feasibility objectives for this pilot trial were as follows:
(i) to refine and test the trial protocol for a large multicentre
study; (ii) to assess acceptability of the trial protocol to our pa-
tients and anaesthetic and nursing staff, because a high recruit-
ment and participation rate will be required for a viable
definitive study; (iii) to confirm the high rates of PONV despite
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prophylaxis seen in our previous study, to inform sample size
estimates for a definitive trial; (iv) to assess the proportion of
patients meeting criteria for chewing gum in the PACU, to guide
the external validity of this trial; and (v) to assess the event rates
using the protocol developed.
Feasibility outcomes were recruitment rate, protocol compli-
ance, incidence of PONV, ability to chew gum, and the primary
outcome.
Statistical analysis
Continuous data were tested for normality. Normally distrib-
uted data were summarized using the mean (SD) and compared
using Students unpaired two-tailed t-tests. Skewed data were
summarized using the median (interquartile range) and
Excluded (n =53)
Patient declined (n= 25)
Anaesthetist declined (n= 7)
Direct to theatre from radiology (n= 6)
Other reasons (n=15)
Excluded (n= 8)
Anaesthetist declined (n= 5)
Other reasons (n= 3)
Allocation Allocated to ondansetron (n= 46)
Received allocated intervention (n= 13)
Did not receive allocated intervention (n=33)
No PONV (n= 33)
Follow-up Lost to follow-up (n= 0)
Discontinued intervention (n= 0)
Analysis Analysed for primary outcome (n=13)
Excluded from analysis (n = 0)
 86 | Darvall et al.

compared using ranksum tests. Categorical data were summar-
ized using the number (%) and compared using the v2 test or
Fishers exact test where applicable. Survival data were sum-
marized using the median (interquartile range) and compared
using log-rank tests. Statistical analyses were performed using
Stata 14.1 (Stata Corporation, College Station, TX, USA). A value
of P <0.05 was considered statistically significant.
Table 1 Baseline characteristics of patients. Values are ex-
pressed as the mean (SD), median (interquartile range), or n (%).
PONV, postoperative nausea and vomiting; postoperative opi-
oid requirement is defined as at least 20 mg oral oxycodone
equivalent requirement in first 24 h after surgery
We used a per protocol analysis for the primary outcome, be-
cause intention-to-treat analyses, with usually smaller differ-
ences in efficacy between treatments than per protocol
analyses, make it easier to establish non-inferiority by rejecting
the null hypothesis of no difference between treatments.17 Risk
differences with 90% confidence intervals (CIs) were calcu-
lated.17 We also conducted intention-to-treat and per treatment
analyses, because expert guidance suggests performing these
analyses, with equivalence or non-inferiority established when
both intention-to-treat and per protocol analyses agree.17
Results

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A total of 155 patients were screened for inclusion in this pilot
Variable Control group Chewing gum trial. After exclusions, 94 patients were enrolled and followed to
(n46) group (n48) the final analysis, 46 randomized to ondansetron and 48 to
chewing gum (Fig. 1) between 5 February 2016 and 23 June 2016.
Age (yr) 46 (14) 46 (16)
There were no protocol violations. The two groups were similar
BMI (kg m2) 29 (2436) 25 (2230)
in terms of patient characteristics, PONV risk factors, and sur-
ASA physical status
I 15 (33) 19 (40)
gery and anaesthesia details (Tables 1 and 2).
II 29 (63) 24 (50)
III 2 (4) 5 (10)
Non-smoker 41 (89) 41 (85) Table 3 Postoperative characteristics (intention to treat). Values
are expressed as the mean (SD), median (interquartile range), or
PONV/motion sickness 21 (46) 29 (60)
n (%). OAA/S, Observers Assessment of Alertness/Sedation
Postoperative opioid 2 (4) 3 (6)
Score; PACU, postanaesthesia care unit; PONV, postoperative
Apfel score nausea and vomiting
1 2 (4) 2 (4)
2 25 (54) 19 (40)
Variable Ondansetron Chewing P-value
3 18 (39) 27 (56)
group gum group
4 1 (2) 0 (0)
(n46) (n48)
Type of surgery
Laparoscopic 21 (46) 27 (56) Duration of PACU stay (min) 42 (3063) 46.5 (3468.5) 0.22
Breast surgery 25 (54) 21 (44) PACU opioid 25 (54) 28 (58) 0.70
Morphine equivalents (mg) 6.7 (5.09.3) 6.7 (4.08.9) 0.94
PACU nausea
First event 12 (26) 15 (31) 0.58
Second event 2 (4) 4 (8) 0.43
Third event 1 (2) 0 (0) 0.30
PACU vomiting
First event 3 (7) 3 (6) 0.96
Table 2 Intraoperative characteristics (intention to treat). Second event 1 (2) 3 (6) 0.33
Values are expressed as the mean (SD), median (interquartile
Third event 0 (0) 1 (2) 0.33
range), or n (%)
PACU PONV 13 (28) 15 (31) 0.75
PACU PONV initial
Variable Ondansetron Chewing gum P-value
treatment
group (n46) group (n48)
Ondansetron 13 (100) 3 (20)
Midazolam 13 (28) 12 (25) 0.72 Chewing gum 0 (0) 12 (80) <0.001
Dose (mg) 2.0 (0.6) 1.8 (0.2) 0.47 Full resolution after initial 5 (38) 9 (60) 0.26
Morphine equivalents 13 (1020) 13 (717) 0.83 treatment
(mg) Time to full resolution (min) 7 (47) 10 (715) 0.08
Propofol (mg) 184 (40) 177 (40) 0.38 PACU PONV subsequent 4 (9) 7 (15) 0.52
Neuromuscular block 23 (50) 28 (58) 0.42 treatment
Neostigmine 14 (30) 23 (48) 0.08 Acceptability (PONV treatment)
Sugammadex 9 (20) 5 (10) 0.21 Neither acceptable nor 1 (8) 0 (0)
Sevoflurane 2.0 (1.82.2) 2.0 (1.82.2) 0.50 unacceptable
(% end-tidal) Mildly acceptable 3 (23) 7 (47)
I.V. fluid 45 (98) 47 (98) 0.98 Completely acceptable 9 (69) 8 (53) 0.32
Dose (litres) 0.6 (0.41.0) 0.7 (0.51.0) 0.43 Ward treatment of PONV
Anti-emetic 44 (96) 47 (98) 0.53 patients
Dexamethasone 44 (96) 47 (98) 0.53 Anti-emetic 8 (62) 7 (47) 0.43
Droperidol 1 (2) 0 (0) 0.49 Opioid 9 (69) 12 (80) 0.43
Duration of anaesthesia 57 (3175) 62 (3491) 0.39 Morphine 10 (7.712.7) 7.7 (5.040.5) 0.62
(min) equivalents (mg)
 Chewing gum and PONV | 87

Postoperative nausea and vomiting in the PACU occurred in
13 (28%) of the ondansetron group patients and 15 (31%) of the
chewing gum group patients (P0.75; Table 3 and Fig. 2). Three
patients randomized to chewing gum did not proceed with gum
chewing (two patients were too drowsy; one refused) and
received ondansetron instead. Therefore, 13 ondansetron group
patients and 12 chewing gum group patients were included in
the per protocol analysis (the primary analysis), 13 ondansetron
group patients and 15 chewing gum group patients were
included in the intention-to-treat analysis, and 16 ondansetron
group patients and 12 chewing gum group patients were
included in the per treatment analysis (Fig. 3).
The median (interquartile range) time for which the gum
was chewed was 31.5 (1736) min. Full resolution of PONV was
PACU stay, and requirement for ward anti-emetic treatment did
not differ between groups (Table 3). All sticks of chewing gum
were retrieved from patients, with no safety concerns identified.
No differences in acceptability of PONV treatment were found,
with all patients finding chewing gum either completely or
mildly acceptable.
Discussion
In this randomized controlled pilot trial, we demonstrated the
feasibility of conducting a large randomized controlled trial. We
showed that chewing gum was not inferior to ondansetron in
the treatment of PONV in the PACU in female patients after lap-

seen in five of 13 (39%) ondansetron group patients and nine of
12 (75%) chewing gum group patients [per protocol risk differ-
ence (90% CI): 37% (6.367%), P0.07; confirming non-inferiority].
Both intention-to-treat risk difference (90% CI) of 22% (8.9 to
52.0%), P0.22 and per treatment risk difference (90% CI) of 44%
(15.771.8%), P0.02 confirmed non-inferiority (Fig. 3). There
was no difference in the time to full resolution of PONV between
groups (Table 3).
Recurrence of PONV in the PACU after full resolution was
seen in one ondansetron-treated patient (39 min after initial full
resolution, requiring droperidol rescue) and two chewing gum-
treated patients (one patient 24 min after initial full resolution,
resolving completely with further chewing gum requested by
the patient, and one patient 34 min after full resolution, requir-
ing ondansetron rescue). Rescue PONV treatment, duration of
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aroscopic or breast surgery. The incidence of PONV, acceptabil-
ity of chewing gum, and effect size for full resolution recorded
in this study will be valuable in planning the definitive study.
This is the first randomized controlled trial assessing this
novel treatment for PONV. Strengths of our study include a high
recruitment rate, complete protocol adherence, and complete
data collection, including follow-up of anti-emetic and opioid
requirements for 24 h after surgery. Our study has several limi-
tations. This study was planned as a pilot rather than a defini-
tive randomized controlled trial, using a sample based on
convenience rather than a sample size calculation. We did not
measure nausea severity, merely recorded it as present or ab-
sent. We therefore cannot report whether the severity of nausea
was similar in the two groups. Twenty per cent of the chewing
gum group patients were unable to chew gum because of either

Ondansetron Chewing gum

group group
PONV = 13 PONV = 15

3 received
13 received ondansetron
12 received gum
ondansetron (2 too drowsy,
1 refused gum)

7 partially 3 partially 9 fully 3 partially

5 fully resolved 1 no change
resolved resolved resolved resolved

1 recurrent
2 recurrent
event (fully 3 received 3 received 3 received
PONV episodes
resolved after droperidol droperidol ondansetron
(1 fully resolved
droperidol rescue rescue rescue
after 2nd gum)
rescue)
(1 fully resolved
after
ondansetron
1 received rescue) 1 received
further further
promethazine droperidol
rescue rescue

Fig 2 Flowchart of patients with postoperative nausea and vomiting (PONV) in the postanaesthesia care unit (PACU).
 88 | Darvall et al.

Intention-to-treat
21.5% (90% CI: 9 52%); P= 0.22
Ondansetron = 13; success = 5 (38.5%)
Chewing gum = 15; success = 9 (60.0%)

Per protocol
36.5% (90% CI: 6 67%); P=0.07
Ondansetron = 13; success = 5 (38.5%)
Chewing gum = 12; success = 9 (75.0%)

Per treatment
44% (90% CI: 16 72%); P=0.02

Downloaded from http://bja.oxfordjournals.org/ at University of California, San Diego on December 30, 2016
Ondansetron = 16; success = 5 (31.3%)
Chewing gum = 12; success = 9 (75.0%)

15 0 15 30 45 60 75
Risk difference (%)

Fig 3 Difference between percentage full resolution of postoperative nausea and vomiting (PONV) in chewing gum group vs ondansetron group via intention-to-
treat, per protocol and as-treated analyses. CI, confidence interval.

drowsiness or a preference to avoid it. The treatment is there- may also benefit from randomization of patients when experi-
fore not universally applicable to postoperative patients. encing PONV, making analysis of end points simpler.
Although chewing gum represented a potential PONV treatment
for patients in this trial, whether it would be suitable for pa-
tients undergoing more major surgery, with higher opioid re-
Conclusion
quirements and potentially longer emergence times, requires In summary, chewing gum was not inferior to ondansetron for
further research. We used a flavoured (peppermint) gum, which the treatment of PONV in this pilot, randomized controlled trial
may have confounded the association between chewing and of female patients undergoing general anaesthesia for laparo-
PONV treatment. Peppermint has been shown to have effects on scopic or breast surgery. Our findings demonstrate the feasibil-
gastric emptying, although literature is conflicting (evidence of ity of a larger, multicentred randomized controlled trial to
both increasing and decreasing gastric motility).18 19 Some evi- investigate this novel therapy.
dence also exists for aromatherapy as a treatment for PONV,
with blends including ginger found to be efficacious.20 A recent
Cochrane review, however, suggests no benefit from pepper-
Authors contributions
mint aromatherapy for PONV.21 Finally, PONV beyond the PACU Study conception: J.N.D.
was not measured in our study, although anti-emetic require- Study design, study coordination data analysis, manuscript
ments were used as a surrogate marker for its incidence. preparation: J.N.D., K.L.
This pilot study has potentially important implications for Patient recruitment: M.H.
practice, if the results are confirmed in a definitive trial. Data collection: J.N.D., M.H.
Chewing gum is a readily accessible therapy, of negligible cost Data analysis: J.N.D., K.L.
and without storage considerations. It is also familiar to pa- Manuscript review: M.H.
tients and can be self-administered. In contrast, the require-
ment for equipment and training in some non-pharmacological
techniques (e.g. acupressure or transcutaneous electrical nerve
Declaration of interest
stimulation) limits applicability for the majority of anaesthe- None declared.
tists. Chewing gum has been acceptable to patients and PACU
staff in two studies by this group at different sites, which lends
support to the external validity of our findings. Funding
Our protocol was simple to implement and acceptable to an- Australian and New Zealand College of Anaesthetists (project
aesthetists and nurses, and would be generalizable to a multi- grant 16/040).
centred study. The non-inferiority margin remains appropriate,
but the sample size calculation for the main study might need
to be modified in light of the lower than expected incidence of References
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Handling editor: T. Asai