Anaesthesia 2014, 69, 11381150 doi:10.1111/anae.

12713

Review Article
A comparison of total intravenous anaesthesia using propofol with
sevoflurane or desflurane in ambulatory surgery: systematic
review and meta-analysis
G. Kumar,1,2 C. Stendall,1 R. Mistry,2 K. Gurusamy3 and D. Walker4

1 Speciality Registrar, 4 Consultant, Department of Anaesthesia and Intensive Care, University College London
Hospitals NHS Foundation Trust, London, UK
2 Research Fellow, Department of Peri-operative Medicine, 3 Lecturer, Division of Surgery, University College London,
London, UK

Summary
With the popularity of ambulatory surgery ever increasing, we carried out a systematic review and meta-analysis to
determine whether the type of anaesthesia used had any bearing on patient outcomes. Total intravenous propofol
anaesthesia was compared with two of the newer inhalational agents, sevourane and desurane. In total, 18 trials
were identied; only trials where nitrous oxide was administered to, or omitted from, both groups were included. A
total of 1621 patients were randomly assigned to either propofol (685 patients) or inhalational anaesthesia
(936 patients). If surgical causes of unplanned admissions were excluded, there was no difference in unplanned
admission to hospital between propofol and inhalational anaesthesia (1.0% vs 2.9%, respectively; p = 0.13). The inci-
dence of postoperative nausea and vomiting was lower with propofol than with inhalational agents (13.8% vs 29.2%,
respectively; p < 0.001). However, no difference was noted in post-discharge nausea and vomiting (23.9% vs 20.8%,
respectively; p = 0.26). Length of hospital stay was shorter with propofol, but the difference was only 14 min on
average. The use of propofol was also more expensive, with a mean (95% CI) difference of 6.72 (5.138.31 (8.16
(6.23 10.09); $11.29 ($8.62$13.96))) per patient-anaesthetic episode (p < 0.001). Therefore, based on the published
evidence to date, maintenance of anaesthesia using propofol appeared to have no bearing on the incidence of unplanned
admission to hospital and was more expensive, but was associated with a decreased incidence of early postoperative
nausea and vomiting compared with sevourane or desurane in patients undergoing ambulatory surgery.
.................................................................................................................................................................
Correspondence to: G. Kumar
Email: gautamkumar@doctors.org.uk
Accepted: 7 April 2014

Introduction is related primarily to cost savings and enhanced con-

The incidence and popularity of ambulatory surgery
(also known as day-case or outpatient surgery) have
increased rapidly over the last two decades, from over
500 000 cases annually in the UK in the 1990s to over
700 000 in 2005, and are continuing to rise [1]. This
venience for patients [2, 3]. This proliferation has in
part been made possible by the development of both
intravenous and inhalational anaesthetic agents with
improved pharmacokinetic proles, favouring early
recovery and reduced side-effects. So-called total

1138 2014 The Association of Anaesthetists of Great Britain and Ireland

Kumar et al. | Systematic review of maintenance anaesthesia in day surgery
intravenous anaesthesia (TIVA), with modern drugs
like propofol administered by continuous infusion, is
now commonplace in ambulatory surgical settings.
However, the proposed advantages and propagation of
the relatively new and less-soluble inhaled anaesthetics,
sevourane and desurane, have added a new dimen-
sion to patient care by rivalling propofol in ambula-
tory surgery. In theory, they allow faster recovery and
earlier discharge home than the more traditional
inhalational anaesthetic agents [4, 5].
A number of anaesthetic issues may delay discharge
from hospital, including: cognitive recovery; cardiovas-
cular recovery; pain; return to normal activity; and
postoperative nausea and vomiting (PONV) [6]. Postop-
erative nausea and vomiting can be particularly prob-
lematic in ambulatory surgery as it may lead to delay in
discharge or unscheduled admission to hospital [7].
Additionally, it has been reported as the anaesthetic
complication that is of most concern to patients [8].
Multiple factors, including the anaesthetic agent deliv-
ered, are associated with an increased incidence of
PONV and the optimal strategy for preventing PONV
continues to be debated. Postoperative pain is also prob-
lematic, with over 30% of patients reporting moderate to
severe pain following ambulatory surgery [9, 10].
We undertook a systematic review and meta-
analysis to assess whether the maintenance of anaes-
thesia using propofol TIVA is associated with fewer
unplanned hospital admissions than maintenance with
the inhalational agents sevourane or desurane.
Methods
The systematic review was conducted following the Pre-
ferred Reporting Items for Systematic Reviews and
Meta-analyses (PRISMA) guidelines [11]. We designed
a PICOS framework (Population, Intervention, Control,
Outcome, Study design) to identify controlled studies,
and used its elements as our primary selection criteria
[12]. Articles were regarded as potentially eligible if they
met all of the criteria depicted in Table 1. Also shown
are the studys primary and secondary endpoints.
Only studies where the use of nitrous oxide was
matched (i.e. present or absent in both study groups)
were included, as this was deemed a signicant con-
founder having both analgesic properties and a higher
incidence of PONV [1315]. All studies were included
2014 The Association of Anaesthetists of Great Britain and Ireland
Anaesthesia 2014, 69, 11381150
Table 1 Inclusion criteria according to the PICOS
framework [12].
Population Adult (16 years or over), elective
ambulatory surgery, undergoing general
anaesthesia, non-sedation procedures
Interventions Maintenance anaesthesia with propofol
(total intravenous anaesthesia)
Controls Maintenance with desflurane and/or
(intervention) sevoflurane (inhalational anaesthesia)
Outcomes Primary: unplanned admission after
planned day surgery
Secondary: serious adverse events;
postoperative and post-discharge nausea
and vomiting; postoperative pain (48 h
postoperatively); length of hospital stay;
cost analysis; quality of life
Study design Randomised controlled studies in any
language
PICOS, Population, Intervention, Control, Outcome, Study
design.
irrespective of the method of induction of anaesthesia
(intravenous or inhalational), and whether an anti-
emetic was used intra-operatively (provided that it was
used in both groups).
We searched MEDLINE, EMBASE, the Cochrane
Central Register of Controlled Trials (CENTRAL) in the
COCHRANE Library, Science Citation Index Expanded
and the meta-register of controlled trials were until
November 2013 through a formal search strategy. The
medical subject headings (MeSH) terms anaesthesia,
inhalational, anaesthesia, intravenous or TIVA, and
ambulatory or day-case surgery were used along with
equivalent free-text search terms as part of the search
strategy. Additional studies were identied by review of
the reference sections of all eligible studies.
The decision to include a study was based on an
independent review of each of the identied manu-
scripts by two study investigators (GK and CS) Poten-
tially eligible studies (as determined by either reviewer)
underwent review of the full-text manuscript by both
reviewers working independently, who subsequently
compared their judgements. Disagreements were har-
monised by consensus and if necessary by arbitration
by the senior researcher. Data extraction tables and an
extraction form, including a set of parameters for
relevant information on pre-operative testing, were
created.
1139
Anaesthesia 2014, 69, 11381150 Kumar et al. | Systematic review of maintenance anaesthesia in day surgery
The risk of bias was assessed according to the
guidelines of the Cochrane Collaboration [16, 17],
since there is a risk of overestimation of benecial
treatment effects in randomised clinical trials with a
high risk of bias [18, 19]. The assessment of risk of
bias was based on: sequence generation; allocation
concealment; blinding (of patients, anaesthetists and
outcome assessors); incomplete outcome data; selective
outcome reporting; and source of funding [20].
Considering that follow-up was generally short
(< 24 h after discharge), and the incidence of compli-
cations relatively low, trials that did not report the
outcomes of all randomly assigned patients were
considered to suffer from bias owing to incomplete out-
come data. Exploration of bias using a funnel plot was
performed when assessing PONV and length of stay in
all trials, but was not possible for other outcomes
because of the small number of trials included [21].
The software package RevMan 5 [22], provided by
the Cochrane Collaboration, was used for analysis. For
dichotomous data, the relative risk (RR) with the cor-
responding 95% condence intervals (CI) was calcu-
lated for each study, and the results were pooled
together using the MantelHaenszel method for com-
bining trials. For continuous data, the mean difference
and its corresponding 95% CI were calculated using
the inverse variance method for meta-analysis. The
individual effect sizes were weighted according to the
reciprocal of their variance. If the standard deviation
was not available for continuous outcomes, it was
calculated according to the guidelines of the Cochrane
Collaboration [20].
The outcomes from both xed- and random-effects
models were obtained in the meta-analysis; the model
used did not inuence the interpretation of effectiveness
and the random-effects model is presented in the
Results section as we included different types of ambu-
latory procedures. Heterogeneity (across-study inconsis-
tency) was quantied using the I2 statistic, which
estimates the percentage of variability across studies not
due to chance [23, 24]. Values of I2 < 40% might not be
important, 3060% may represent moderate heteroge-
neity, 5090% may represent high heterogeneity and
values > 75% considerable heterogeneity.
Subgroup analysis was performed where possible
for each outcome to explore heterogeneity between
1140
propofol vs sevourane and propofol vs desurane.
Chi-squared tests for heterogeneity were performed to
identify the differences between subgroups. A planned
subgroup analysis of ASA status was not possible due
to the relatively low anaesthetic risk of included
patients, and a planned subgroup analysis comparing
different types of surgery was also not possible due to
there being too few trials in each category.
Sensitivity analysis was performed excluding all
trials where nitrous oxide was used. The impact of this
on the primary outcome and PONV is presented in
the results. Too few studies existed to perform it on
other outcomes. All evidence were graded as low- or
moderate-quality as per the GRADE approach [20],
due to the limitations in trial design and implementa-
tion and/or the imprecision of the results due to small
sample sizes.
Results
After removing duplicates a, total of 347 references
were identied from medical journal databases and the
World Health Organization International Clinical Tri-
als Registry Platform. One additional trial was identi-
ed by searching through references (Fig. 1). In total,
18 publications describing 18 completed randomised
trials fullled the inclusion criteria. A total of 1621
patients were randomly assigned to either TIVA (685
patients) or inhalational anaesthesia (936 patients). All
trials included adult patients (age 16 or above) who
underwent ambulatory surgery and compared TIVA vs
sevourane (1052 patients; 10 trials) and TIVA vs des-
urane (569 patients; eight trials) (Table 2). Five trials
included patients who did not receive nitrous oxide
[27, 35, 3941]. No serious adverse incidents attribut-
able to any of the anaesthetic agents were reported.
The majority of trials had a high risk of bias.
Blinding was achieved in only one trial [38] as to
whether TIVA or inhalational anaesthesia was used,
and in most trials, details of the randomisation proce-
dure or whether blinding of the outcome assessors
took place was unclear (Table 3). Dropouts after ran-
domisation were reported in only three studies [29, 37,
42]. Only 10 out of the 18 trials reported the primary
outcome, thus raising the possibility of selective out-
come reporting. It was unclear whether any trial was
free from funding bias.
2014 The Association of Anaesthetists of Great Britain and Ireland
Kumar et al. | Systematic review of maintenance anaesthesia in day surgery Anaesthesia 2014, 69, 11381150

Records idenfied through Addional records idenfied

database searching through other sources

Idenficaon
n = 547 n=1

Records aer duplicates removed

n = 348
Screening

Records screened
n = 348
Records excluded
based on abstract
screening
n = 311
Eligibility

Full text arcles

screened for eligibility
n = 37
Full text arcles
excluded
n = 19

Studies included in
qualitave synthesis
n = 18
Included

Studies Included in
quantave synthesis
n = 18

Figure 1 PRISMA ow-diagram.

In total, 10 trials reported unplanned admission to
hospital following ambulatory surgery. Four out of
them detailed no admissions [25, 30, 34, 35], and one
trial excluded inpatient admissions after randomisation
[27]. The incidence of unplanned admission was lower
with propofol compared with inhalational agents (1.3%
vs 4.4%, respectively, RR 0.35 (95% CI 0.140.91),
p = 0.03, Fig. 2). However, if surgical causes of admis-
sion were excluded and only anaesthetic reasons for
admission included (pain, PONV, respiratory depres-
sion), there was no difference between propofol and
inhalational anaesthesia (1.0% vs 2.9%, respectively,
RR 0.44 (95% CI 0.151.27), p = 0.13; Fig. 3). No het-
erogeneity was noted (I2 = 0%). Sensitivity analysis
excluding all trials involving nitrous oxide showed no
difference in unplanned admission between the two
anaesthetic techniques.
All trials reported pre-discharge PONV. The
incidence of PONV with propofol was lower compared
with inhalational anaesthesia (13.8% vs 29.2%, respec-
tively, RR 0.50 (95% CI 0.350.71, p < 0.001; Fig. 4).
Similarly, PONV was lower comparing propofol with
sevourane (15.1% vs 26.7%, respectively, RR 0.56
(95% CI 0.340.90); p = 0.02), and propofol with des-
urane (10.9% vs 33.3%, respectively, RR 0.41 (95% CI
0.240.70); p = 0.001). There was moderate to high
heterogeneity in these results (I2 = 52%). Sensitivity
analysis excluding all trials involving nitrous oxide
showed no difference in PONV (17% vs 20%, respec-
tively, RR 0.87 (95% CI 0.511.47); p = 0.60).
Seven trials reported PONV up to 24 h after dis-
charge (Fig. 5). There was no difference between prop-
ofol and inhalational anaesthesia (23.9% vs 20.8%,
respectively, RR 1.17 (95% CI 0.891.55; p = 0.26).
Analogous results were seen when comparing propofol
with sevourane (27.7% vs 23.6%, respectively, RR
1.22 (95% CI 0.891.67; p = 0.22) [27, 33, 34, 42], and
propofol with desurane (15.8% vs 15.0%; respectively,

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Anaesthesia 2014, 69, 11381150 Kumar et al. | Systematic review of maintenance anaesthesia in day surgery

Table 2 Studies included in the meta-analysis and their characteristics.

Total Documented
number Was pre- or
Type of of Mean N2O Induction of intra-operative
Study Comparison surgery patients age; years used? anaesthesia anti-emetic
Ashworth and Propofol vs Body surface 60 44 Yes Propofol No
Smith [25] desflurane
Chen et al. [26] Propofol vs Gynaecology 80 29 Yes Propofol No
sevoflurane
Fish et al. [27] Propofol vs Urology 71 63 No Propofol or No
sevoflurane sevoflurane
Fredman et al. [28] Propofol vs Mixed 146 35 Yes Propofol or No
sevoflurane sevoflurane
van Hemelrijk et al. [29] Propofol vs Gynaecology 90 30 Yes Propofol or No
desflurane desflurane
Jakobsson et al. [30] Propofol vs Orthopaedic 80 35 Yes Propofol No
desflurane
Kurpiers et al. [31] Propofol vs Not stated 53 40 Yes Propofol No
desflurane
Lebenbom-Mansour Propofol vs Orthopaedic 60 29 Yes Propofol or No
et al. [32] desflurane desflurane
Nathan et al. [33] Propofol vs Gynaecology 52 ? Yes Propofol or No
sevoflurane sevoflurane
Raeder et al. [34] Propofol vs Orthopaedic 169 33 Yes Propofol No
sevoflurane
Raeder et al. [35] Propofol vs General 60 ? No Propofol Ondansetron
desflurane surgery or droperidol
Rapp et al. [36] Propofol vs Orthopaedic 91 34 Yes Propofol or No
desflurane desflurane
Smith et al. [37] Propofol vs Mixed 211 39 Yes Propofol or No
sevoflurane sevoflurane
Smith and Propofol vs Mixed 61 38 Yes Propofol or No
Thwaites [38] sevoflurane sevoflurane
Stevanovic et al. [39] Propofol vs General 60 48 No Propofol Metoclopramide
sevoflurane surgery
Tan et al. [40] Propofol vs Gynaecology 80 34 No Propofol or Dexamethasone
sevoflurane sevoflurane
Tang et al. [41] Propofol vs Mixed 75 55 Yes Propofol Metoclopramide,
desflurane ondansetron,
droperidol
White et al. [42] Propofol vs Gynaecology 122 38 No Propofol Dolasteron
sevoflurane

RR 1.03 (95% CI 0.561.87); p = 0.93) [25, 35, 41].
Overall, heterogeneity was high (I2 = 76%).
In total, nine trials reported postoperative pain; in
all these trials, there was no difference between propo-
fol and inhalational anaesthesia. Eleven trials reported
either the total hospital stay or t-for-discharge time
(Fig. 6). These times were shorter in patients receiving
propofol compared with those receiving inhalational
anaesthesia; mean (95% CI) difference was 14 ( 21
to 8) min, p < 0.001. Hospital stay was also shorter
comparing propofol with sevourane ( 14 ( 21 to
6) min, p < 0.001), but not when comparing propo-
fol with desurane ( 15 ( 30 to 1) min, p = 0.06).
The chi-squared test for subgroup differences was not
signicant (p = 0.92), and heterogeneity was moderate.
Five trials reported a cost analysis (Fig. 7). Three
included the cost of maintenance anaesthesia only (i.e.
the cost of the propofol or desurane/sevourane
used) [30, 38, 39], and two included the cost of all
ancillary drugs (induction agents, neuromuscular
blockers, analgesics and anti-emetics) [31, 37]. Total
costs were signicantly higher with propofol compared
with inhalational anaesthesia in each individual trial
and in the meta-analysis. The mean (95% CI) differ-
ence was 6.72 (5.138.31 (8.16 (6.23 10.09);
$11.29 ($8.62 $13.96))) per patient anaesthetic

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Table 3 Risk of bias (?, unclear risk of bias; , high risk of bias; +, low risk of bias).

Incomplete Free Free from

Blinding of outcome from source of
Sequence Allocation outcome Blinding of data academic funding
Study generation concealment assessors anaesthetists addressed bias bias
Ashworth and Smith [25] ? ? + + + ?
Chen et al. [26] + + + ?
Fish et al. [27] ? + + + ?
Fredman et al. [28] ? ? ? + ?
van Hemelrijk et al. [29] ? ? + ?
Jakobsson et al. [30] ? ? ? + + ?
Kurpiers et al. [31] ? ? + ?
Lebenbom- ? ? + + ?
Mansour et al. [32]
Nathan et al. [33] ? + ? + + ?
Raeder et al. [34] ? ? ? + + ?
Raeder et al. [35] ? ? ? + + ?
Rapp et al. [36] ? ? ? + + ?
Smith et al. [37] + + ? + + ?
Smith and Thwaites [38] ? ? + + + ?
Stevanovic et al. [39] + ? ? + ?
Tan et al. [40] + + + + + ?
Tang et al. [41] + ? ? + ?
White et al. [42] + + ? + + ?

Propofol Desflurane/Sevoflurane Odds ratio Odds ratio

Study or subgroup Events Total Events Total Weight M-H, Random, 95% Cl M-H, Random, 95% Cl
Ashworth 1998 0 30 0 30 Not estimable
Jakobssen 1997 0 40 0 40 Not estimable
Nathan 1998 1 26 6 26 18.8% 0.13 [0.01, 1.20]
Raeder 1997 0 85 0 84 Not estimable
Raeder 1998 0 30 0 30 Not estimable
Rapp 1992 0 23 4 68 10.3% 0.30 [0.02, 5.88]
Smith 1999 0 72 1 139 8.8% 0.64 [0.03, 15.83]
Tan 2010 1 40 4 40 18.1% 0.23 [0.02, 2.16]
White 2007 3 55 6 67 44.0% 0.59 [0.14, 2.46]

Total (95% Cl) 401 524 100.0% 0.35 [0.14, 0.91]

Total events 5 21
Heterogeneity: Tau2 = 0.00; Chi2 = 1.53, df = 4 (p = 0.82); I2 = 0%
Test for overall effect: Z = 2.14 (P = 0.03) 0.01 0.1 1 10 100
Favours propofol Favours inhalational

Figure 2 Unplanned admissions comparing propofol vs inhalational anaesthesia; all causes.

episode, and heterogeneity was high (I2 = 86%). No Discussion

trial looked at long-term outcome or quality-adjusted
life years.
Bias exploration suggested that publication bias
among the data (PONV and duration of hospital stay)
was unlikely (Fig. 8). For PONV, Eggers bias was
0.5 (95% CI 2.9 to 1.9, p = 0.67), and for duration
of hospital stay it was 2.4 (95% CI 10.9 to 6.1,
p = 0.54). It was not possible to assess publication bias
for other outcomes because of the small number of
trials included.
We have shown that unplanned admission to hospital
is less frequent when TIVA is used compared with
inhalational anaesthesia, but importantly, this was not
statistically signicant when surgery-related complica-
tions were excluded from the analysis. Surgical compli-
cations such as bowel perforation and traumatic
haemorrhage were unlikely to be related to the
intervention and hence the interpretation is that there
is no evidence to support a difference in unplanned
admission between TIVA and inhalational anaesthesia.

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Propofol Desflurane/Sevoflurane Odds ratio Odds ratio

Study or subgroup Events Total Events Total Weight M-H, Random, 95% Cl M-H, Random, 95% Cl
Ashworth 1998 0 30 0 30 Not estimable
Jakobssen 1997 0 40 0 40 Not estimable
Nathan 1998 0 26 0 26 Not estimable
Raeder 1997 0 85 0 84 Not estimable
Raeder 1998 0 30 0 30 Not estimable
Rapp 1992 0 23 4 68 12.7% 0.30 [0.02, 5.88]
Smith 1999 0 72 1 139 10.8% 0.64 [0.03, 15.83]
Tan 2010 1 40 4 40 22.3% 0.23 [0.02, 2.16]
White 2007 3 55 6 67 54.2% 0.59 [0.14, 2.46]

Total (95% Cl) 401 524 100.0% 0.44 [0.15, 1.27]

Total events 4 15
Heterogeneity: Tau2 = 0.00; Chi2 = 1.59, df = 3 (p = 0.90); I2 = 0%
Test for overall effect: Z = 1.51 (p = 0.13) 0.01 0.1 1 10 100
Favours propofol Favours inhalational

Figure 3 Unplanned hospital admissions comparing propofol vs inhalational anaesthesia; anaesthetic causes.

Propofol Inhalational Risk ratio Risk ratio

Study or subgroup Events Total Events Total Weight M-H, Random, 95% Cl M-H, Random, 95% Cl
10.1.1 Propofol vs Sevoflurane
Chen 2006 2 40 10 40 4.2% 0.20 [0.05, 0.86]
Fish 1999 1 36 1 25 1.6% 0.97 [0.06, 14.94]
Fredman 1995 14 50 41 96 10.7% 0.66 [0.40, 1.08]
Nathan 1998 6 26 18 26 8.6% 0.33 [0.16, 0.70]
Raeder 1997 15 85 16 84 9.5% 0.93 [0.49, 1.75]
Smith & Thwaites 1999 4 72 30 139 6.6% 0.26 [0.09, 0.70]
Smith 1999 1 30 14 31 2.7% 0.07 [0.01, 0.53]
Stevanovic 2008 2 30 4 30 3.6% 0.50 [0.10, 2.53]
Tan 2010 7 40 7 40 7.0% 1.00 [0.39, 2.59]
White 2007 18 55 16 67 10.1% 1.37 [0.77, 2.43]
Subtotal (95% CI) 464 588 64.7% 0.56 [0.34, 0.90]
Total events 70 157
Heterogeneity: Tau2 = 0.31;Chi2 = 23.29, df = 9 (p = 0.006); I2 = 61%
Test for overall effect: Z = 2.41 (p = 0.02)

10.1.2 Propofol vs Desflurane

Ashworth 1998 3 30 0 30 1.4% 7.00 [0.38, 129.93]
Hemelrijk 1991 9 23 42 67 10.4% 0.62 [0.36, 1.07]
Jakobssen 1997 2 40 7 40 4.0% 0.29 [0.06, 1.29]
Kurpiers 1996 3 26 11 27 5.7% 0.28 [0.09, 0.90]
Lebenbom-Mansour 1993 0 14 13 46 1.5% 0.12 [0.01, 1.84]
Raeder 1998 5 30 12 30 7.3% 0.42 [0.17, 1.04]
Rapp 1992 1 23 27 68 2.8% 0.11 [0.02, 0.76]
Tang 2001 1 35 4 40 2.4% 0.29 [0.03, 2.44]
Subtotal (95% CI) 221 348 35.3% 0.41 [0.24, 0.70]
Total events 24 116
Heterogeneity: Tau2 = 0.14; Chi2 = 9.40, df = 7 (p = 0.23); I2 = 25%
Test for overall effect: Z = 3.28 (p = 0.001)

Total (95% Cl) 685 936 100.0% 0.50 [0.35,0.71]

Total events 94 273
Heterogeneity: Tau2 = 0.25; Chi2 = 35.20, df = 17 (p = 0.006); I2 = 52%
Test for overall effect: Z = 3.79 (p = 0.0001) 0.01 0.1 1 10 100
Test for subgroup differences: Chi2 = 0.73, df = 1 (p = 0.39), I2 = 0% Favours propofol Favours inhalational

Figure 4 Postoperative nausea and vomiting in propofol vs inhalational anaesthesia.

A total overall unplanned admission rate of 2.1% was from 0.5% to 10% [43, 44], with an ideal standard of
identied in this review, which is comparable with sev- under 2% [45]. We have also shown that the incidence
eral clinical studies that have reported rates ranging of PONV was lower when propofol was used

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Kumar et al. | Systematic review of maintenance anaesthesia in day surgery Anaesthesia 2014, 69, 11381150

Propofol Inhalational Risk ratio Risk ratio

Study or subgroup Events Total Events Total Weight M-H, Random, 95% Cl M-H, Random, 95% Cl
10.2.1 Propofol vs Sevoflurane
Fish 1999 1 36 0 35 4.5% 2.92 [0.12, 69.32]
Nathan 1998 6 26 18 26 19.5% 0.33 [0.16, 0.70]
Raeder 1997 15 85 16 84 20.6% 0.93 [0.49, 1.75]
White 2007 34 55 16 67 22.1% 2.59[1.61, 4.16]
Subtotal (95% CI) 202 212 66.8% 1.05 [0.36, 3.13]
Total events 56 50
Heterogeneity: Tau2 = 0.91; Chi2 = 22.22, df = 3 (p < 0.0001); I2 = 87%
Test for overall effect: Z = 0.09 (p = 0.92)

10.2.2 Propofol vs Desflurane

Ashworth 1998 1 30 0 30 4.5% 3.00 [0.13, 70.83]
Raeder 1998 13 30 10 30 20.5% 1.30 [0.68, 2.49]
Tang 2001 1 35 5 40 8.3% 0.23 [0.03, 1.86]
Subtotal (95% CI) 95 100 33.2% 0.97 [0.31, 3.06]
Total events 15 15
Heterogeneity: Tau2 = 0.40; Chi2 = 2.92, df = 2 (p = 0.23); I2 = 31%
Test for overall effect: Z = 0.04 (p = 0.96)

Total (95% CI) 297 312 100.0% 1.01 [0.48, 2.12]

Total events 71 65
Heterogeneity: Tau2 = 0.59; Chi2 = 25.16, df = 6 (p = 0.0003); I2 = 76%
0.02 0.1 1 10 50
Test for overall effect: Z = 0.02 (p = 0.98)
Favours propofol Favours inhalational
Test for subgroup differences: Chi2 = 0.01, df = 1 (p = 0.92); I2 = 0%

Figure 5 Post-discharge nausea and vomiting in propofol vs inhalational anaesthesia.

Propofol Inhalational Mean Difference Mean Difference

Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% Cl IV, Random, 95% Cl
10.3.1 Propofol versus Sevoflurane
Fredman 1995 183 82 50 196 75 96 5.1% 13.00 [40.23,14.23]
Raeder 1997 143 11 85 155 12 84 29.2% 12.00 [15.47, 8.53]
Smith 1999 195 145 72 189 133 139 2.5% 6.00 [34.13, 46.13]
Tan 2010 235 10 40 255 9 40 28.2% 20.00 [24.17, 15.83]
White 2007 202 116 55 179 109 67 2.5% 23.00 [17.26, 63.26]
Subtotal (95% CI) 302 426 67.6% 13.64 [21.36, 5.91]
Heterogeneity: Tau2 = 32.21; Chi2 = 12.89, df = 4 (p = 0.01); I2 = 69%
Test for overall effect: Z = 3.46 (p = 0.0005)
10.3.2 Propofol versus Desflurane
Ashworth 1998 156 49 30 166 50 30 5.8% 10.00 [35.05, 15.05]
Jakobssen 1997 254 79 40 255 60 40 4.1% 1.00 [31.74, 29.74]
Kurpiers 1996 176 0 26 184 0 27 Not estimable
Lebenbom-Mansour 1993 110 22 14 147 59 46 7.9% 37.00 [57.58, 16.42]
Raeder 1998 287 63 30 278 54 30 4.4% 9.00 [20.69 ,38.69]
Rapp 1992 130 26 23 150 57 68 10.2% 20.00 [37.22, 2.78]
Subtotal (95% CI) 163 241 32.4% 14.56 [29.65, 0.53]
Heterogeneity: Tau2 = 145.33; Chi2 = 8.03, df = 4 (p = 0.09); I2 = 50%
Test for overall effect: Z = 1.89 (p = 0.06)
Total (95% Cl) 465 667 100.0% 14.27 [20.95, 7.59]
Heterogeneity: Tau2 = 36.63; Chi2 = 21.05, df = 9 (p = 0.01); I2 = 57%
50 25 0 25 50
Test for overall effect: Z = 4.19 (p < 0.0001)
Favours propofol Favours inhalational
Test for subgroup differences: Chi2 = 0.01, df = 1 (p = 0.92), I2 = 0%

Figure 6 Length of hospital stay in propofol vs inhalational anaesthesia.

compared with inhalational anaesthesia, but no differ- shorter with propofol but it is arguable whether the
ence was noted in the incidence of nausea and vomit- small difference found is likely to be clinically relevant.
ing after discharge. Length of hospital stay also was Additionally, no difference was noted in the incidence

2014 The Association of Anaesthetists of Great Britain and Ireland 1145

Anaesthesia 2014, 69, 11381150 Kumar et al. | Systematic review of maintenance anaesthesia in day surgery

Propofol Inhalational Mean difference Mean difference

Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% Cl IV, Random, 95% Cl
10.4.1 Propofol vs Sevoflurane
Smith & Thwaites 1999 8.84 4.49 30 5.91 1.5 31 20.8% 2.93 [1.24, 4.62]
Smith 1999 19.52 4.67 72 11.81 4.51 139 23.0% 7.71 [6.40, 9.02]
Stevanovic 2008 12.56 1.32 30 5.56 0.87 30 26.3% 7.00 [6.43, 7.57]
Subtotal (95% Cl) 132 200 70.1% 5.99 [3.76, 8.21]
Heterogeneity: Tau2 = 3.47; Chi2 = 22.40, df = 2 (p < 0.0001); I2 = 91%
Test for overall effect: Z = 5.27 (p < 0.00001)

10.4.2 Propofol vs Desflurane

Jakobssen 1997 10.72 3.2 40 3.81 1.69 40 24.0% 6.91 [5.79, 8.03]
Kurpiers 1996 35.47 12.37 26 21.33 8.65 27 5.9% 14.14 [8.37, 19.91]
Subtotal (95% Cl) 66 67 29.9% 9.95 [2.95, 16.94]
Heterogeneity: Tau2 = 21.64; Chi2 = 5.82, df = 1 (p = 0.02); I2 = 83%
Test for overall effect: Z = 2.79 (p = 0.005)
Total (95% Cl) 198 267 100.0% 6.72 [5.13, 8.31]
Heterogeneity: Tau2 = 2.42; Chi2 = 28.69, df = 4 (p < 0.00001); I2 = 86%
Test for overall effect: Z = 8.28 (p < 0.00001) 20 10 0 10 20
Test for subgroup difference: Chi2 = 1.12, df = 1 (p = 0.29), l2 = 10.7% Favours propofol Favours inhalational

Figure 7 Cost analysis of propofol vs inhalational anaesthesia.

SE(log[RRI) SE(MD)
0
0 (a) (b)

10

0.5

20

30

1.5
40

RR MD
2 50
0.01 0.1 1 10 100 50 25 0 25 50

Figure 8 Funnel plot for propofol vs inhalational anaesthesia, for (a) postoperative nausea and vomiting and (b)
length of hospital stay. The vertical axis shows the precision of the estimate of the treatment effect (the smaller the
condence interval, the more precise the study, and the further up the study is placed). The horizontal axis measures
the treatment effect (relative risk or mean difference.) The data points are from each study and the vertical line
shows where the pooled estimate from the meta-analysis lies.

of postoperative pain but maintenance anaesthesia
with propofol was more expensive than with sevoura-
ne or desurane.
No serious anaesthetic adverse events were
reported in any of the selected studies, and this was as
expected, since major morbidity and mortality directly
attributed to anaesthesia now occur extremely rarely
[46]. Likewise, no studies reported quality of life, and
this was expected due to the nature of surgery, with
no difference in quality of life resulting from different

1146 2014 The Association of Anaesthetists of Great Britain and Ireland

Kumar et al. | Systematic review of maintenance anaesthesia in day surgery
methods of anaesthesia anticipated several days follow-
ing discharge. Considering that mortality and quality
of life contribute to the quality-adjusted life year,
which is the main measure used to assess benets in
cost-effectiveness analyses, the choice of anaesthetic
agent will depend on re-admission to hospital, costs,
PONV and pain.
We have shown that PONV was less common
when TIVA was used this correlates with extensive
evidence that propofol is the best anaesthetic agent for
preventing PONV [4749], and is of particular impor-
tance since it is the postoperative anaesthetic complica-
tion that is of most concern to patients [8]. It is also
signicant because of the potential association with
delayed discharge and unplanned admissions, and
related cost implications [6, 50]. This may be sup-
ported by the fact that hospital admission was lower
with TIVA in all the selected studies, although this did
not reach statistical signicance. The distinction
between pre- and post-discharge nausea and vomiting
has not been well investigated [42]. After discharge,
PONV has been reported to have an incidence of 30
50%, and we have reported an incidence of 22% in this
meta-analysis. Many patients experience PONV for the
rst time only after leaving hospital [50, 51]. Interest-
ingly, despite propofols being associated with signi-
cantly less in-hospital PONV, our analysis shows it
provides no benet in the rst 24 h after discharge.
This may be explained by propofols pharmacokinetic
prole. A minimum plasma concentration of propofol
(mean 343 ng.ml 1 [52]) is necessary to produce an
anti-emetic effect; this is lower than that required to
produce an anaesthetic effect (approximately
500 ng.l 1), and since it has a short half-life, therapeu-
tic anti-emetic plasma levels are unlikely to persist
after several hours [53]. Propofol may provide prophy-
laxis against early PONV only, and suitable strategies
should be planned for patients after discharge.
Although not having a direct cost implication to the
hospital, preventing PONV once the patient has
returned home is still important as it may delay
resumption of normal activities and readiness for
work, and negatively impact on patient experience.
The reduction in the incidence of PONV may be
the reason why our analysis demonstrated that propo-
fol was associated with earlier readiness for discharge
2014 The Association of Anaesthetists of Great Britain and Ireland
Anaesthesia 2014, 69, 11381150
home compared with inhalational anaesthesia, sup-
ported by a previous study that concluded that nausea
was the single most important factor which affected
discharge following ambulatory surgery [7]. However,
although statistically signicantly different, the clinical
signicance of the difference in hospital readiness is
very minimal, as the average difference was only about
1015 min between the two techniques.
None of the trials reported any signicant differ-
ence in postoperative pain or opioid use. This may be
because the analgesic properties of propofol have been
well reported, and so this was not investigated [54
56]. Alternatively, it may be that there was no
signicant difference in pain between TIVA and inha-
latational anaesthesia because of the nature of the pro-
cedures carried out.
In interpreting differences in actual discharge and
t-for-discharge times, it is critical to understand that
other co-factors inuencing the interpretation of each
outcome may be relevant. Being ready for discharge is
usually assessed using standardised recovery protocols,
whereas discharge time is the actual time when the
patient leaves hospital. The latter is affected by many
factors such as local guidelines, delay in transport, or
needing to pass urine, although type of anaesthetic
should not affect this. Unfortunately, many authors
have not made a distinction between these variables.
In our study, the cost of propofol as a mainte-
nance anaesthetic was signicantly higher than that of
desurane or sevourane. No trials calculated the total
cost including ancillary equipment or wastage. It has
been recommended that drug wastage should be
included in the total cost [57]. If this was the case,
propofol may cost even more, in part, because it is
packaged as a preservative-free, single-patient-use
agent [58]. Therefore, any opened propofol remaining
at the end of surgery would have been wasted.
Although the saving per patient was small, the poten-
tial for savings over the course of a year would be
large. Whether this saving would be negated by the
potential extra need for anti-emetics with inhalational
anaesthesia, or the need for different equipment such
as infusion pumps [59], has not been analysed.
There are a number of limitations to our meta-
analysis. Although we conducted a thorough review of
work published in all languages, one trial was
1147
Anaesthesia 2014, 69, 11381150 Kumar et al. | Systematic review of maintenance anaesthesia in day surgery
excluded due to being untraceable [60]. Many authors
did not differentiate between nausea and vomiting or
did not state whether it was counted twice as two
pathologies. We included patients who were adminis-
tered nitrous oxide; although it is less commonly used
in the UK [6163], it may be used in other countries.
However, our sensitivity analysis showed nitrous oxide
had no impact on hospital admission, but may have
affected PONV. Patients undergoing inducution of
anaesthesia with inhalational agents were included,
and this could affect the primary endpoints since in a
few patients, induction was with desurane, an airway
irritant and hence potentially emetogenic [64, 65].
This could have decreased the effect of propofol on
PONV. However, we have presented the results from
pragmatic trials that reect real-life situations and the
inuence of the induction method on the ability of
propofol to reduce PONV should be further investi-
gated. Perhaps the biggest limitation is the fact that
only three of the included trials were conducted
within the past 10 years, with the majority in the
1990s. These older trials may have more inuence on
outcomes since they were conducted at a time when
sevourane, desurane and TIVA were relatively new
and thus less rened, potentially producing more
adverse outcomes than may be expected in the mod-
ern era. However, it was necessary to include all these
trials due to their abundance and large trial numbers,
increasing the likelihood of producing signicant
results.
There was no evidence of heterogeneity in the pri-
mary outcome of unplanned hospital admission, but for
all other outcomes signicant heterogeneity was
detected, with poor overlapping of condence intervals
even within the subgroups, decreasing condence in the
effect estimate. A potential reason could be the type of
surgery, but there were not enough trials to investigate
the inuence of each surgical specialty on the effective-
ness of TIVA. There was no evidence of publication bias
for the two outcomes where we could explore them.
The majority of trials in this analysis are relatively
small. A power calculation has identied that a large,
double-blinded randomised controlled trial of at least
820 participants in each of the TIVA and inhalational
groups would be needed to corroborate the results
found here with a condence of 95%. This is the rst
1148
meta-analysis of this nature and the results are compa-
rable with a previous systematic review that included
seven of the trials we analysed and included compari-
son with isourane, but did not differentiate use of
nitrous oxide [4].
Although the evidence was of low quality overall,
based on the literature, TIVA appears to be preferable to
inhalational anaesthesia in patients undergoing ambula-
tory surgery with regards to preventing PONV, but no
other major advantages were discovered. When hospital
admissions due to surgical causes were excluded, there
was no evidence of a difference in hospital admission
between TIVA and inhalational anaesthesia. However,
given that there was an almost threefold difference in
unplanned hospital admissions between TIVA and inha-
lational anaesthesia (1.0% vs 2.9%, respectively) further
robust randomised controlled trials are needed to iden-
tify whether a truly signicant difference exists.
Competing interests
No competing interests declared.
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