Meta-analysis

Meta-analysis of the effect of warm humidified insufflation

on pain after laparoscopy
T. Sammour1 , A. Kahokehr1 and A. G. Hill2
Department of Surgery, South Auckland Clinical School, 1 University of Auckland and 2 Middlemore Hospital, Auckland, New Zealand
Correspondence to: Dr T. Sammour, Department of Surgery, University of Auckland, Middlemore Hospital, Private Bag 93311, Otahuhu, Auckland 1640,
New Zealand (e-mail: tsammour@middlemore.co.nz)

Background: Studies on the use of warmed and humidified insufflation (WHI) in laparoscopic abdominal

procedures to reduce pain have been inconclusive owing to small sample sizes.
Methods: An electronic database search identified all randomized controlled trials (RCTs) on adults
undergoing elective laparoscopic abdominal surgery under general anaesthesia in which the exposure
group had WHI and the control group had standard cold and dry carbon dioxide. The outcome measure
was pain by visual analogue score or morphine usage.
Results: Seven RCTs were included. Patients in the WHI group experienced a significant reduction in
pain score at 6 h (P = 0006), 1 day (P = 0010) and 3 days (P < 0001) after operation, and in morphine
usage on day 2 (P = 0040).
Conclusion: WHI reduces pain after laparoscopy.
Paper accepted 18 April 2008
Published online in Wiley InterScience (www.bjs.co.uk). DOI: 10.1002/bjs.6304

Introduction

Working space in laparoscopic surgery is created by

using pneumoperitoneum to lift the abdominal wall.
The gas used is typically carbon dioxide at 21 C with
0 per cent relative humidity. The effect of this dry, cool
gas on the peritoneal environment has probably been
underestimated. Carbon dioxide is a peritoneal irritant
that, when dry, also has a desiccating effect. The result
is structural, morphological and biochemical changes in
the peritoneal mesothelial surface layer1 5 . Some studies
in awake laparoscopy have shown that this translates
into a conscious sensation of pain, but results have been
conicting6 8 .
Warming and humidication of the carbon dioxide is
relatively easily achieved by incorporating a commercially
available humidier into the tubing of the insufation
apparatus. Several randomized controlled trials (RCTs)
have been published evaluating the use of warming
and humidication in laparoscopic cholecystectomy,
gastric bypass, gastric fundoplication and gynaecological
procedures. The European Association for Endoscopic
Surgery clinical practice guideline on the establishment
of pneumoperitoneum suggests that data on the inuence
Copyright 2008 British Journal of Surgery Society Ltd
Published by John Wiley & Sons Ltd

of warming and humidication on postoperative pain are

contradictory. It also states that, because most studies
have small sample sizes with possible type II error,
no rm conclusions can be drawn9 . There is also the
question of whether the benecial effects noted by some
authors are due to prevention of hypothermia alone (this
is easily achieved by using an external warming device
such as a forced-air warming blanket) and other simple
measures9 .
The aim of this meta-analysis is to evaluate the effect on
postoperative pain of warming and humidifying the carbon
dioxide insufation in laparoscopic abdominal procedures
in adults.

Methods

The principal question is whether or not, in patients

aged more than 15 years undergoing elective laparoscopic
abdominal surgery under general anaesthesia, humidication and warming of the insufated carbon dioxide (HWI)
reduces postoperative pain. Pain may be measured by
visual analogue scale (VAS) score and/or morphine usage10
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Pain after laparoscopy

951

for up to 72 h after surgery. The group for comparison is patients receiving standard cold and dry carbon
dioxide, with or without the use of an external warming
device.

Search strategy
Relevant primary studies were identied from the
Cochrane Central Register of Controlled Trials
(CENTRAL/CCTR), the Cochrane Library, Medline
including in-process and non-indexed citations (from January 1966 to January 2008), PubMed (from 1950 to January
2008) and Embase (from 1947 to January 2008). The
search terms are outlined in Appendix 1 (available online as
supplementary material at www.bjs.co.uk).

195 results were entered into a unied database, after

which duplicate results were removed. The titles and
abstracts of the studies were scrutinized, and reference
lists were searched manually to identify further relevant
articles. Relevant scientic meeting abstracts were also
searched manually. A total of 28 potentially relevant
publications were identied and reviewed by two authors
(T.S., A.K.) independently. Papers that met the inclusion
criteria as posed by the research question were selected. Any
disagreement was resolved by consensus, with consultation
with the third author (A.G.H.) if consensus could not
be reached. Nine RCTs comparing HWI with standard
carbon dioxide were identied11 19 . Two trials, however,
had insufcient data and were excluded from the nal
analysis11,18 (Fig. 1).

Validity assessment
Study selection
The search was run independently by two of the authors
(T.S., A.K.), with no restrictions on language. A total of

Assessment of the RCTs was performed by one author

(T.S.) who was blinded to the journal title, article title and
authors of the publications. Methodological quality was

Potentially relevant studies identified and

screened for retrieval
n = 28
Studies excluded n = 7
Not RCT n = 7

RCTs excluded n = 12
Animal study n = 5
Thoracoscopy study n = 1
Awake laparoscopy n = 2
Warmed but not humidified n = 1
Humidified versus heated n = 1
Duplicate n = 2

RCTs retrieved for more detailed evaluation

n = 21

Potentially appropriate RCTs to be included

in meta-analysis
n=9

RCTs excluded from meta-analysis n = 2

Not enough data provided n = 2
RCTs included in meta-analysis
n=7

RCTs withdrawn, by outcome n = 0

RCTs with usable information, by outcome

n=7
Fig. 1

QUOROM diagram showing study selection. RCT, randomized controlled trial

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952

Table 1

T. Sammour, A. Kahokehr and A. G. Hill

Summary characteristics and quality assessment of included studies according to Jadad et al.19
Champion
et al.12
(USA)

Humidified
Control
Withdrawals
External
warming
device
Indication
Mean age
(years)
Operating
time (min)
Double
blinding
Randomized

Adequate
control
Jadad score
Outcome
reported

Farley
et al.10
(USA)

Hamza
et al.13
(USA)

Mouton
et al.14
(Australia)

Nguyen
et al.15
(USA)

Savel
et al.17
(USA)

Ott et al.16
(USA)

25
25
NS
No

49
52
16
Anaesthetists
discretion

23
21
6

16
16
8
NS

10
10
NS

25
25
NS
No

15
15
NS
Anaesthetists
discretion

Gastric
bypass
43

LC

LC

Gastric bypass

NS

Nissen
fundoplication
44

Gynaecological

52

Gastric
bypass
44

NS

40

62

91

114

NS

108

NS

89

Yes (method
inadequate)
Yes (method
inadequate)

Yes (method
adequate)
Yes (method
adequate)

Yes

No

No

No

Yes

Yes

Yes

Yes

Yes (method
inadequately
described)
Yes

Yes (method
inadequately
described)
Yes

Yes (method
inadequately
described)
Yes

Yes (method
inadequate)
Yes (method
inadequately
described)
Yes

0
Pain score

5
Morphine
equivalent

5
Pain score
and
morphine
equivalent

2
Pain score

1
Pain score and
morphine
equivalent

1
Pain score

1
Pain score and
morphine
equivalent

NS, not stated; LC, laparoscopic cholecystectomy.

determined using the Jadad scale19 . This scale depends on

three items: random allocation, masking of patients, and
dropouts and withdrawals. The scale ranges from 0 to 5
points, with 2 or less indicating low quality and 3 or more
indicating high quality. The results of this assessment and
a summary of the characteristics of each study are shown
in Table 1.

Data abstraction

measured pain scores at slightly different intervals, values

for VAS pain scores were collated and grouped into the
following postoperative time intervals: up to 6 h, on day
1, on day 2 and on day 3. When pain was measured more
than once within a particular time interval (for example,
pain at 2 h and at 4 h for the 6-h interval), a mean value
was calculated and used as the value for the relevant time
period. Morphine usage was similarly grouped into usage
up to 6 h, on day 1 and on day 2.

The corresponding author for each publication was

contacted to obtain as much raw data as possible. As
noted above, two RCTs were excluded from the analysis.
The rst reported pain outcome as the presence or absence
of pain, with no data on analogue score or analgesia use18 .
The second had no measure of data distribution, standard
deviation or statistical signicance11 .
Data on VAS pain scores and morphine usage from
the seven remaining RCTs were gathered and the results
of each trial summarized on an intention-to-treat basis
in 2 2 tables for each outcome. As different studies

Statistical analysis

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Analysis of combined data was performed using RevMan

version 4.2 (The Nordic Cochrane Centre, Rigshospitalet,
Copenhagen, Denmark). Standard deviation of the
outcome data was used if provided by the authors, or
calculated from P values, condence intervals (c.i.) or
data ranges if not. Results of the meta-analysis were
assessed by graphical presentations of mean difference with
95 per cent c.i. on forest plots using the xed-effects model;
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Pain after laparoscopy

953

P < 0050 was considered statistically signicant. A 2 test

for heterogeneity was also performed, in which P < 0100
was regarded as signicant. Subset analyses based on the
use of an external warming device and on only gastric
bypass studies were performed.

Reference

SMD

Hamza et al.13
Savel et al.17
Champion et al.12
Mouton et al.14
Ott et al.16

000 (059, 059)

057 (017, 130)
054 (003, 110)
133 (270, 005)
056 (113, 001)
003 (027, 032)
4

Results

Of the seven studies included in the analysis, three

described gastric bypass12,13,17 , two laparoscopic cholecystectomy10,14 , one Nissen fundoplication15 and one
gynaecological procedures16 . Six RCTs came from the
USA and one from Australia, and were published
between 1999 and 2006. A total of 327 patients were
included, with 163 in the HWI group and 164 in the
control group. A summary of the results is presented in
Appendix 2 (available online as supplementary material at
www.bjs.co.uk).

060 (120, 001)

025 (047, 097)
017 (073, 038)
085 (158, 012)
056 (113, 001)

2
Favours
control

Forest plot for pain by visual analogue scale on day 2 after

surgery. Values in parentheses are 95 per cent condence
intervals. SMD, standardized mean difference

Reference

SMD
126 (191, 061)
496 (1187, 195)
056 (113, 001)

13

Hamza et al.
Mouton et al.14
Ott et al.16

088 (130, 045)

SMD

Hamza et al.13
Savel et al.17
Champion et al.12
Mouton et al.14
Ott et al.16

Fig. 4

4
Reference

2
Favours
treatment

2
Favours
treatment

2
Favours
control

Forest plot for pain by visual analogue scale on day 3 after

surgery. Values in parentheses are 95 per cent condence
intervals. SMD, standardized mean difference

Fig. 5

039 (067, 011)

Pain by visual analogue score

4

2
Favours
treatment

2
Favours
control

Forest plot for pain by visual analogue scale up to 6 h after

surgery. Values in parentheses are 95 per cent condence
intervals. SMD, standardized mean difference

Fig. 2

Reference

SMD

Hamza et al.13
Savel et al.17
Champion et al.12
Mouton et al.14
Nguyen et al.15
Ott et al.16

000 (059, 059)

129 (208, 049)
030 (026, 086)
086 (166, 007)
038 (127, 050)
056 (112, 001)
034 (061, 007)
4

2
Favours
treatment

2
Favours
control

There was a statistically signicant reduction in VAS pain

scores in the HWI group within 6 h (P = 0006), on
day 1 (P = 0010) and on day 3 (P < 0001) (Figs 25).
The reduction on day 1 is less certain as there was
signicant heterogeneity between studies in these data
(P = 0020). Subset analysis was repeated, including only
the studies where an external warming device had been
used; this demonstrated signicantly lower scores on day
1 (P = 0003) in the HWI group, with no signicant
heterogeneity in the data. It was not possible to perform
this analysis at other intervals as there were not enough
studies to combine. With no external warming device,
there was a signicant reduction in pain in the HWI group
within 6 h (P = 0001) and on day 3 (P < 0001), with no
signicant heterogeneity.

Forest plot for pain by visual analogue scale on day 1 after

surgery. Values in parentheses are 95 per cent condence
intervals. SMD, standardized mean difference

Fig. 3

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Morphine usage
A statistically signicant reduction in morphine usage10 was
noted on day 2 (P = 0040) in the HWI group (Figs 68).
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T. Sammour, A. Kahokehr and A. G. Hill

Subset analysis of studies that used an external warming

device did not show any signicant difference between the
two groups. Analysis of morphine usage on day 2 without
external warming was not performed as this would have
included only one study13 .
Subset analysis of the three gastric bypass studies was
also performed for both pain and morphine usage. No
statistically signicant difference was detected for either
pain measure between the HWI group and controls (data
not shown).

Reference

SMD

Farley et al.10
Hamza et al.13
Savel et al.17

019 (020, 059)

060 (120, 001)
022 (094, 050)
007 (037, 023)
4
2
Favours
treatment

2
Favours
control

Forest plot for morphine usage up to 6 h after surgery.

Values in parentheses are 95 per cent condence intervals. SMD,
standardized mean difference

Fig. 6

Reference

SMD
051 (112, 009)
043 (116, 029)
020 (068, 108)

Hamza et al.13
Savel et al.17
Nguyen et al.15

033 (074, 008)

4

2
Favours
treatment

2
Favours
control

Forest plot for morphine usage on day 1 after surgery.

Values in parentheses are 95 per cent condence intervals. SMD,
standardized mean difference

Fig. 7

Reference

SMD
078 (139, 016)
007 (079, 064)

Hamza et al.13
Savel et al.17

048 (095, 0011)

4

2
Favours
treatment

2
Favours
control

Forest plot for morphine usage on day 2 after surgery.

Values in parentheses are 95 per cent condence intervals. SMD,
standardized mean difference

Fig. 8

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Discussion

This meta-analysis demonstrates a reduction in postoperative pain with HWI in major laparoscopic surgery; this
appears to be consistent at different intervals in the postoperative period, whether measured by VAS score or analgesic
requirement. There are two ways in which preconditioning insufation gases might exert a benecial effect.
The rst is by counteracting a reduction in the patients
core temperature, thereby preventing hypothermia. The
second is through a direct effect on the peritoneum in
which desiccation and local temperature reduction are
prevented.
Insufation of cold, dry gas during laparoscopy causes
hypothermia; it is the humidity rather than the temperature
of the gas that is largely to blame20 22 . The adverse effects
of hypothermia are well established, but its relationship
to postoperative pain and fatigue less so23,24 . Given that
prevention of hypothermia can be achieved successfully
with the use of warming blankets, forced-air warming
devices and warmed uids25 , it has been argued that the
role for warming and humidication of insufation gases
is diminished11,14 .
Subset analysis of only those studies that employed
an external warmer showed a statistically signicant
reduction in pain scores on day 1 when the insufate
was warmed and humidied compared with when it was
not. This is important. If hypothermia is adequately
prevented in the control group by external warming,
the benecial effects of warming and humidifying the
insufation gases will be greater than those of hypothermia
prevention alone. Damage to the peritoneum has been
demonstrated microscopically when dry and cold carbon
dioxide is used1 5 . It may be that a reduction in
peritoneal desiccation plays an important role in reducing
pain, or that local peritoneal hypothermia contributes
to pain sensation independently from overall core body
temperature.
The conclusions to be drawn from this meta-analysis are
limited by the quality of the included studies. Five of the
seven RCTs were methodologically poor, as assessed by the
Jadad scale. Furthermore, variation between the studies in
terms of surgical indication and reported outcome variables
weakens the analysis. Ideally, further high-quality trials
should be done, particularly for procedures that have not
previously been investigated in a RCT, such as laparoscopic
colorectal surgery (research in this area is limited to a
small prospective case-matched study26 ). For this particular
indication, as well as for other prolonged laparoscopies,
the effect of peritoneal desiccation and hypothermia may
be more pronounced. It should also be recognized that
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British Journal of Surgery 2008; 95: 950956

Pain after laparoscopy

the effects of WHI on postoperative recovery and fatigue

have not yet been determined. Measurement of peritoneal
inammation may also prove to be a useful area for
research. A costbenet analysis for WHI may also be
warranted.
Acknowledgements

There is no conict of interest pertaining to this publication

from the point of view of the authors or the institution.
There is no nancial relationship between the authors and
the company that manufactures the devices in the study.
No external source of funding was required or used for the
purposes of this study.
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British Journal of Surgery 2008; 95: 950956