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EJA-D-19-00766

Eur J Anaesthesiol 2020; 37:1–12

REVIEW ARTICLE

The impact of peri-operative intravenous lidocaine on

postoperative outcome after elective colorectal surgery
A meta-analysis of randomised controlled trials
Katie E. Rollins, Hannah Javanmard-Emamghissi, Michael J. Scott and Dileep N. Lobo
Downloaded from https://journals.lww.com/ejanaesthesiology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3yRlXg5VZA8vvJz0Tn6A01Owa1fcsDe5qEwPBWMiIeDs= on 03/10/2020

BACKGROUND There has recently been increasing interest
in the use of peri-operative intravenous lidocaine (IVL) due to
its analgesic, anti-inflammatory and opioid-sparing effects.
However, these potential benefits are not well established in
elective colorectal surgery.
OBJECTIVES To examine the effect of peri-operative IVL
infusion on postoperative outcome in patients undergoing
elective colorectal surgery.
DESIGN A meta-analysis of randomised controlled trials
(RCTs) comparing peri-operative IVL with placebo infusion
in elective colorectal surgery. The primary outcome measure
was postoperative pain scores up to 48 h. The secondary
outcome measures included time to return of gastrointestinal
function, postoperative morphine requirement, anastomotic
leak, local anaesthetic toxicity and hospital length of stay.
emergency procedures, non-RCT methodology or lack of
relevant outcome measures.
RESULTS A total of 10 studies were included (n ¼ 508
patients; 265 who had undergone IVL infusion, 243 who
had undergone placebo infusion). IVL infusion was associ-
ated with a significant reduction in time to defecation (mean
difference 12.06 h, 95% CI 17.83 to 6.29, I2 ¼ 93%,
P ¼ 0.0001), hospital length of stay (mean difference 0.76
days, 95% CI 1.32 to 0.19, I2 ¼ 45%, P ¼ 0.009) and
postoperative pain scores at early time points, although this
difference does not meet the threshold for a clinically relevant
difference. There was no difference in time to pass flatus
(mean difference 5.33 h, 95% CI 11.53 to 0.88,
I2 ¼ 90%, P ¼ 0.09), nor in rates of surgical site infection
or anastomotic leakage.

DATA SOURCES PubMed, Scopus and the Cochrane
Library databases were searched on 5 November 2018.
ELIGIBILITY CRITERIA Studies were included if they were
RCTs evaluating the role of peri-operative IVL vs. placebo in
adult patients undergoing elective colorectal surgery. Exclu-
sion criteria were paediatric patients, noncolorectal or
CONCLUSION This meta-analysis provides some support
for the administration of peri-operative IVL infusion in elective
colorectal surgery. However, further evidence is necessary to
fully elucidate its potential benefits in light of the high levels of
study heterogeneity and mixed quality of methodology.
Published online xx month 2020

Introduction
There has been significant interest in the potential for peri-
operative intravenous lidocaine (IVL) infusion in patients
undergoing abdominal surgery,1 with increasing evidence
in a range of surgical specialties, including colorectal sur-
gery,2 hepatobiliary surgery,3 obstetrics4 and gynaecology.5
Studies have suggested that IVL conveys a postoperative
benefit in terms of its analgesic, anti-inflammatory and
opioid-sparing effects, resulting in reduced postoperative
pain, reduced time to return of gastrointestinal function,
and reduced nausea and vomiting.6 In addition, there is

From Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham
University Hospitals and University of Nottingham, Queen’s Medical Centre, Nottingham, UK (KER, HJE, DNL), Department of Anesthesiology, Virginia Commonwealth
University Health System, Richmond, Virginia and Department of Anesthesiology and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania,
Philadelphia, USA (MJS), MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen’s Medical Centre,
Nottingham, UK (DNL)
Correspondence to Professor Dileep N. Lobo, Department of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, National Institute for Health Research
Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, Nottingham NG7 2UH, UK
Tel: +44 115 8231149; e-mail: dileep.lobo@nottingham.ac.uk
0265-0215 Copyright ß 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology.
DOI:10.1097/EJA.0000000000001165
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
CE: Swati; EJA/EJA-D-19-00766; Total nos of Pages: 12;
EJA-D-19-00766
2 Rollins et al.
some evidence for a beneficial effect on intra-operative
parameters, including a reduction in anaesthetic require-
ment7,8 and improved recovery from general anaesthesia.9
A Cochrane review1 compared IVL infusion with placebo or
thoracic epidural analgesia for postoperative pain and recov-
ery in a total of 68 randomised controlled trials (RCTs) across
a range of surgical specialties, including general, spinal,
endocrine and cardiothoracic surgery, and gynaecology.This
demonstrated an unclear effect of IVL vs. placebo on pain
scores, recovery of gastrointestinal function, postoperative
nausea and overall opioid requirement, and highlighted poor
quality evidence. This review1 did not seek to differentiate
the benefits in individual surgical specialities such as colo-
rectal alone, although a comparison was made between
open and laparoscopic abdominal surgery. This included a
range of nongastrointestinal procedures so is not directly
comparable to the aims of the current meta-analysis.
Specific to the field of colorectal surgery, a recently pub-
lished systematic review10 examined the role of IVL in the
setting of elective colorectal surgery and concluded that
this provided limited benefit in the reduction of early
postoperative pain and morphine requirement when com-
pared with placebo, and a variable degree of improvement
when compared with epidural analgesia. This has been
followed by a meta-analysis within colorectal surgery,
which found improved time to recovery of gastrointestinal
function as well as reduced hospital length of stay.11
The recently published Enhanced Recovery After Surgery
(ERAS) Society Recommendations for peri-operative care
in elective colorectal surgery12 have concluded that
although ‘the use of lidocaine infusions to reduce opioid
use and nausea in colorectal surgery is now well established’,
the benefit in terms of reduction of postoperative ileus is
unclear. Despite this, no meta-analysis has been conducted
to date to assess the role of combined intra-operative and
postoperative IVL in colorectal surgery specifically. In
addition, substantial additional evidence has been pub-
lished2,13,14 since the previous systematic review.10
The aims of this meta-analysis were to examine the effect
of peri-operative IVL on postoperative outcome in
patients undergoing elective colorectal surgery, including
postoperative pain, morphine consumption, time to
return of gastrointestinal function, hospital length of stay
and complications; to study the role of peri-operative
lidocaine infusion in laparoscopic vs. open elective colo-
rectal surgical procedures; to identify the optimal dosing
and infusion regimen as well as duration of infusion; and
to determine the incidence of local anaesthetic toxicity.
Materials and methods
Search strategy
A search of PubMed, Scopus and the Cochrane Library
databases was conducted up to 5 November 2018 in order
to identify full-text studies examining the impact of peri-
operative IVL in elective colorectal surgery. The
Eur J Anaesthesiol 2020; 37:1–12
electronic search terms adopted were (intravenous OR
infusion) AND (lidocaine OR lignocaine) AND (colon
OR rectal OR colorectal OR proctectomy OR colonic),
with no limitation placed on data or language for inclusion.
The bibliographies of all studies that met the inclusion
criteria were hand-searched for any additional suitable
articles and relevant conference abstracts to ensure study
inclusion was as complete as possible, and this accounts for
the additional 39 manuscripts identified from other
sources. The meta-analysis was conducted according to
the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) statement.15
Selection of articles
Following the exclusion of initial studies on the basis of
article title and abstract by two independent researchers
(KR and HJE), the remaining full-text articles were
screened in detail for inclusion. Studies were included if
they were RCTs that evaluated the role of peri-operative
intravenous IVL infusion vs. placebo in adult patients
undergoing elective colorectal surgery. Exclusion criteria
comprised paediatric patients, noncolorectal or emergency
procedures, non-RCT methodology or lack of any relevant
clinical outcome measures. Studies that included more
than two study arms, but had IVL and placebo groups, were
included and only those groups pertinent to this meta-
analysis were considered. No consideration was given to
how long the lidocaine infusion was continued after sur-
gery, but to be eligible for inclusion, the infusion had to
commence before the surgical incision.
Data extraction
Study data were extracted from the included RCTs by one
author (KER) and checked by another (HJE). The primary
outcome measure was postoperative pain scores up to 48 h
[at rest and movement scored on the visual analogue scale
(VAS)]. In line with the previous Cochrane meta-analysis1
and reflecting the International Association for the Study of
Pain (IASP) recommendations, we have considered a 1-cm
difference in VAS (on a 0 to 10 cm scale) as a clinically,
rather than just statistically, significant difference. Second-
ary outcome measures included time to return of gastroin-
testinal function, both in terms of flatus and defecation,
postoperative morphine requirement, incidence of pro-
longed ileus, surgical site infection, anastomotic leak, signs
of local anaesthetic toxicity and overall hospital length of
stay. In addition, data were collated on patient baseline
demographics[(age, sex, American Society of Anesthesiol-
ogists’ (ASA) physical status], operative variables (operat-
ing time, estimated blood loss, nature of colorectal
resection and indication for surgery) and details of the
lidocaine infusion (dose, starting point, duration postoper-
atively and any bolus dose administered) as well as the
details of the placebo administered. The studies included
were stratified according to whether the patients under-
went open or laparoscopic resection. If the data necessary
for meta-analysis of continuous variables were not
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EJA-D-19-00766

Peri-operative lidocaine in elective colorectal surgery 3

available, the corresponding author was approached to
provide the raw data, and if a response was not received,
the technique described by Hozo et al.16 was employed to
estimate the mean and standard deviation from the median
and interquartile range [IQR].
Where results were available only in graphical format and the
authors did not respond to the request for raw data, data were
extracted in either direct or indirect form using plotdigitizer
(www.plotdigitizer.sourceforge.net). Where opioid drugs
other than morphine were provided by the study, previously
described conversion methods were used to standardise all
opiates to an equivalent morphine dose.17 Risk of bias was
assessed using the Cochrane Collaboration tool,18 which
focuses upon random sequence generation (selection bias),
allocation concealment (selection bias), blinding of partici-
pants and personnel (performance bias), blinding of out-
come assessment (detection bias), incomplete outcome data
(attrition bias) and selective reporting (reporting bias).
Statistical analysis
Statistical analysis was performed using RevMan 5.318
(Cochrane, London, UK). Dichotomous variables were
Fig. 1
analysed using the Mantel–Haenszel random effects
model and quoted as a risk ratio with 95% CIs. Continuous
variables were analysed using the inverse-variance random
effects model and quoted as a mean difference with 95%
CI. Data were used to construct forest plots, with a P value
less than 0.05 on two-tailed testing indicating a statistically
significant difference. Study heterogeneity and inconsis-
tency were assessed using the I2 statistic,19 with 25% or less
representing low heterogeneity, 25 to 50% as moderate and
more than 50% high heterogeneity.
Protocol registration
The protocol for this meta-analysis was registered with
the PROSPERO database (www.crd.york.ac.uk/pros-
pero) - registration no. CRD42018115916.
Results
The initial literature search identified a total of 489
potentially eligible full-text articles, of which a total of
10 studies were included in the meta-analysis2,13,20–27
(Fig. 1). Two studies initially identified as potentially
eligible were excluded subsequently because the

Records identified through database Additional records identified through

Identification

searching other sources

(n = 489) (n = 39)

Duplication (n = 121)
Records after duplicates and retractions removed
(n = 407)
Screening

Abstracts excluded (n = 385)

Not colorectal surgery (n = 104)

Not ReT (n = 62)
Animal studies (n = 76)
Records screened Systematic review or meta-analysis
(n = 22) (n = 49)
letter, editorial, review (n = 33)
No relevant clinical outcomes (n = 37)
Eligibility

Paediatric cases (n = 24)

Full text assessed for eligibility

(n = 22)
Full texts excluded (n = 12)

Infusion commenced postoperatively

(n = 2)
Included

No control group (n = 2)
Included emergency cases (n = 3)
No relevant clinical outcomes (n = 5)
Studies included in quantitative
evidence synthesis
(n = 10)

PRISMA diagram of studies considered for inclusion from the initial literature search.

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4 Rollins et al.

Fig. 2 studies2,23,24,27 included study groups such as neuraxial

techniques and continuous wound infusions, which did
– High risk of bias not fall within the remit of the meta-analysis, and these
groups were excluded. Therefore, a total of 265 partici-
? Uncertain risk of bias
pants received a peri-operative IVL infusion and 243

Blinding of participants and personnel (performance bias)

received a placebo infusion. In six studies, the surgery
+ Low risk of bias
was performed laparoscopically,2,20–22,24,26 and in four via
an open technique.13,23,25,27 Baseline patient demo-

Blinding of outcome assessment (detection bias)

graphics are shown in Supplementary Digital Content
Random sequence generation (selection bias)

Table 1, http://links.lww.com/EJA/A277 and details of

the interventions are given in Supplementary Digital

Incomplete outcome data (attrition bias)

Allocation concealment (selection bias)

Content Table 2, http://links.lww.com/EJA/A277.

Selective reporting (reporting bias)

Although postoperative pain scores at rest were signifi-
cantly lower in the IVL group, there were no differences
in pain scores on coughing when the IVL and placebo
groups were compared. However, when the clinically
relevant difference in VAS-rated pain scores as employed
by the previous Cochrane meta-analysis and reflecting
the IASP threshold were used, there were no clinically
Other bias

relevant differences in pain scores between patients

receiving peri-operative IVL or placebo.
Pain scores at rest were analysed at 4, 12, 24 and 48 h
postoperatively. A total of eight studies2,13,20,22–25,27 con-
Ahn 2015 + ? + + – ? +
sidered VAS pain scores at 4 h postoperatively, four in the
Dewinter 2018 + ? + + + + + laparoscopic group2,20,22,24 and four in the open
group.13,23,25,27 Overall, IVL was associated with a signif-
Elhafz 2012 ? ? ? ? – ? + icantly lower VAS pain score at rest (0.62, 95% CI 1.14
to 0.10, P ¼ 0.02, I2 ¼ 91%; Fig. 3), and in those under-
Herroeder 2007 + ? + ? + ? + going open surgery (0.75, 95% CI 1.04 to 0.45,
Ho 2018 P < 0.00001, I2 ¼ 14%). However, no significant differ-
+ + + + + + +
ence was seen in patients undergoing laparoscopic sur-
Kaba 2007 + ? + + + ? + gery (0.67, 95% CI 1.63 to 0.30, P ¼ 0.17, I2 ¼ 95%).
Kim 2014 + ? ? + + + + Pain at 12 h postoperatively was considered in six stud-
ies,13,20,22 –24,27 including 265 patients, with three studies
Kuo 2006 + + + + + ? + in patients undergoing laparoscopic surgery20,22,24 and
three studies in those undergoing open surgery.13,23,27
Staikou 2014 ? ? + + + ? ? IVL was associated with a significant reduction in pain
Tikuisis 2014
scores at rest in the overall group (mean difference 0.58,
+ ? + + + ? +
95% CI 0.82 to 0.33, P < 0.00001, I2 ¼ 64%; Fig. 3), as
well as the laparoscopic group (mean difference 0.80,
Risk of bias assessment of the included studies. 95% CI 1.16 to 0.44, P < 0.0001, I2 ¼ 66%) and open
group (mean difference 0.32, 95% CI 0.63 to 0.01,
P ¼ 0.04, I2 ¼ 21%).
lidocaine infusion was not commenced until after the Pain scores at rest at 24 h postoperatively were considered
completion of surgery.14,28 Overall, the risk of bias within by all studies included within the meta-analysis.2,13,20–27
the included studies was moderate and the quality of the IVL was again associated with a significant reduction in
studies was similarly moderate (Fig. 2). In the assessment pain scores in the overall (mean difference 0.49, 95% CI
of publication bias, markers of imprecision and inconsis- 0.81 to 0.18, P ¼ 0.002, I2 ¼ 65%; Fig. 3), laparoscopic
tency (as estimated from the sample size and CI of the (mean difference 0.62, 95% CI 1.14 to 0.10, P ¼ 0.02,
effect sizes), and the quality of evidence was low to I2 ¼ 76%) and open surgical groups (mean difference
moderate, in keeping with the recent Cochrane meta- 0.35, 95% CI 0.61 to 0.08, P ¼ 0.01, I2 ¼ 10%).
analysis1 on a similar topic.
A total of nine studies2,13,20,22 –27 considered the impact of
There was a total of 610 participants in the 10 RCTs IVL on pain scores at rest at 48 h postoperatively in 448
included within the meta-analysis. However, several patients. There were no significant differences in pain

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Peri-operative lidocaine in elective colorectal surgery 5

Fig. 3

IVL Placebo Mean difference Mean difference

4h Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Ahn 2015 2.67 0.18 25 4.05 0. 18 25 17.0% –1.38 (–1.48, –1.28)
Dewinter 2018 1.68 1.27 50 1.04 1.14 25 14.2% 0.64 (0.07, 1.2 1)
Elhafz 2012 3.1 1.3 9 4.9 2.5 9 5.4% –1.80 (– 3.64, 0.04)
Ti kuisis 2014 5.2 0.81 30 5.8 0.76 30 15.5% –0.60 (–1.00, –0.20)
Subtotal (95% CI) 114 89 52.1% –0.67 (–1.63, 0.30)
2 2 2
Heterogeneity: Tau = 0.81; Chi = 59.17, df = 3 (P < 0.00001); I = 95%
Test for overall effect: Z = 1.36 (P = 0.17)

Open surgery
Herroede r 2007 3.88 2.05 31 4.16 1.79 29 10.7% –0.28 (–1.25, 0.69)
Ho 2018 4 2.96 28 4 3.7 29 5.9% 0.00 (–1.74, 1.74)
Kuo 2006 2.7 0.47 20 3.35 0.67 20 15.8% –0.65 (– 1.01, –0.29)
Staikou 2014 0.2 0.4 20 1.2 0.8 20 15.6% –1.00 (– 1.39, – 0.61)
Subtotal (95% CI) 2 2
99 2
98 47.9% –0.75 (–1.04, –0.45)
Heterogeneity: Tau = 0.01; Chi = 3.47, df = 3 (P < 0.32); I = 14%
Test for overall effect: Z = 5.00 (P = 0.00001)

Total (95% CI) 213 187 100.0% –0.62 (–1.14, –0.10)

2 2 2
Heterogeneity: Tau = 0.41; Chi = 77.06, df = 7 (P < 0.00001); I = 91%
Test for overall effect: Z = 2.35 (P = 0.02) –4 –2 0 2 4
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 0.02, df = 1 (P = 0.88), I = 0%

IVL Placebo Mean difference Mean difference

12h Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Ahn 2015 2.42 0.14 25 3.04 0.13 25 34.7% –0.62 (–0.69, –0.55)
Elhafz 2012 2.9 1.8 9 4.7 2.8 9 1.2% –1.80 (–3.97, 0.37)
Ti kuisis 2014 2.8 0.66 30 3.8 0.66 30 21.5% –1.00 (–1.33, –0.67)
Subtotal (95% CI) 64 64 57.4% –0.80 (–1.16, –0.44)
2 2 2
Heterogeneity: Tau = 0.06; Chi = 5.83, df = 2 (P < 0.05); I = 56%
Test for overall effect: Z = 4.35 (P = 0.0001)

Open surgery
Ho 2018 3.5 2.22 28 4 3.7 29 2.3% –0.50 (– 2.08, 1.08)
Kuo 2006 2.65 0.49 20 3.1 0.31 20 25.8% –0.45 (– 0.70, – 0.20)
Staikou 2014 0.6 0.8 20 0.6 0.8 20 14.5% 0.00 (–0.50, 0.50)
Subtotal (95% CI) 68 69 42.6% –0.32 (–0.63, –0.01)
2 2 2
Heterogeneity: Tau = 0.02; Chi = 2.54, df = 2 (P < 0.28); I = 21%
Test for overall effect: Z = 2.05 (P = 0.04)

Total (95% CI) 132 133 100.0% –0.58 (–0.82, –0.33)

2 2 2
Heterogeneity: Tau = 0.04; Chi = 13.81, df = 5 (P < 0.02); I = 64%
Test for overall effect: Z = 4.64 (P = 0.00001) –4 –2 0 2 4
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 3.95, df = 1 (P = 0.05), I = 74.7%

IVL Placebo Mean difference Mean difference

24h Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Ahn 2015 2.41 0.7 25 2.752 0.55 25 15.0% –0.34 (–0.69, 0.01)
Dewinter 2018 1.88 1.33 50 1.88 1.42 25 10.1% 0.00 (–0.67, 0.67)
Elhafz 2012 2. 7 1.6 9 4.1 1.2 9 4.4% –1.40 (–2 .71, –0.09)
Kaba 2007 0.41 1.15 20 1.335 1.442 20 8.3% –0.93 (–1.73, –0.12)
Kim 2014 5.5 1.48 32 5.5 1.3 36 10.1% 0.00 (–0.67, 0.67)
Tikuisis 2014 2.6 0.67 30 4 1.2 30 12.7% –1.40 (–1.89, –0.91)
Subtotal (95% CI) 166 145 60.7% –0.62 (–1.14, –0.10)
2 2 2
Heterogeneity: Tau = 0.29; Chi = 20.49, df = 5 (P < 0.001); I = 76%
Test for overall effect: Z = 2.35 (P = 0.02)

Open surgery
Herroeder 2007 3.1 1.87 31 3.2 1.98 29 6.7% –0.10 (–1.08, 0.88)
Ho 2018 3 2.22 28 4 2.96 29 4.2% –1.00 (–2.36, 0.36)
Kuo 2006 2.45 0.51 20 2.9 0.31 20 16.4% –0.45 (–0. 71, –0.19)
Staikou 2014 1 1 20 1 0.7 20 12.0% 0.00 (–0.53, 0.53)
Subtotal (95% CI) 99 98 39.3% –0.35 (–0.61, –0.08)
2 2 2
Heterogeneity: Tau = 0.01; Chi = 3.32, df = 3 (P < 0.34); I = 10%
Test for overall effect: Z = 2.53 (P = 0.01)

Total (95% CI) 265 243 100.0% –0.49 (–0.81, –0.18)

2 2 2
Heterogeneity: Tau = 0.14; Chi = 25.36, df = 9 (P < 0.003); I = 65%
Test for overall effect: Z = 3.05 (P = 0.002) –4 –2 0 2 4
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 0.85, df = 1 (P = 0.36), I = 0%

IVL Placebo Mean difference Mean difference

48h Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Ahn 2015 2.07 0.9 25 2.34 0.615 25 14.8% –0.27 (–0.70, 0. 16)
Dewinter 2018 1.76 1.51 50 1.28 1.65 25 11.3% 0.48 (–0.29, 1.25)
Elhafz 2012 1.9 1.4 9 3.5 2.7 9 3.9% –1.60 (–3.59, 0.39)
Kaba 2007 0.67 1.035 20 1.535 1.72 20 10.3% –0.86 (–1.74, 0.01)
Kim 2014 5 1.48 32 4 1.48 36 12.0% 1.00 (0.30, 1.70)
Subtotal (95% CI) 136 115 52.3% – 0.06 (– 0.79, 0.66)
2 2 2
Heterogeneity: Tau = 0.47; Chi = 16.95, df = 4 (P < 0.002); I = 76%
Test for overall effect: Z = 0.16 (P = 0.87)

Open surgery
Herroeder 2007 2.2 1.98 31 2.2 1.32 29 10.6% 0.00 (–0.85, 0.85)
Ho 2018 3 2.96 28 2 2.22 29 6.6% 1.00 (–0.36. 2.36)
Kuo 2006 1.95 0.39 20 2.6 0.5 20 16.1% –0.65 (–0.93, –0.37)
5taikou 2014 1.2 0.8 20 1 0.7 20 14.4% 0.20 (–0. 27, 0.67)
Subtotal (95% (I) 99 98 47.7% –0.02 (– 0.67,0.63)
2 2 2
Heterogeneity: Tau = 0.30; Chi = 14.26, df = 3 (P < 0.003); I = 79%
Test for overall effect: Z = 0.06 (P = 0.95)

Total (95% CI) 235 213 100.0% –0.03 (–0.47,0.42)

2 2 2
Heterogeneity: Tau = 0.30; Chi = 34.28, df = 8 (P < 0.0001); I = 77%
Test for overall effect: Z = 0.12 (P = 0.91) –10 –5 0 5 10
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 0.01, df = 1 (P = 0.93), I = 0%

Pain at rest

Forest plot comparing visual analogue scale pain scores at rest at 4, 12, 24 and 48 h postoperatively for patients receiving intravenous lidocaine vs.
placebo, for both laparoscopic and open surgery.

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6 Rollins et al.
scores between the IVL and placebo groups in any
analysis (Fig. 3).
A total of six studies considered VAS pain score on
coughing at 4 h postoperatively,2,22–25,27 three including
patients undergoing laparoscopic surgery2,22,24 and three
with patients undergoing open surgery.23,25,27 There was
no significant difference in the VAS pain score on cough-
ing between those receiving IVL and placebo, either
overall (mean difference 0.50, 95% CI 1.02 to 0.03,
P ¼ 0.07, I2 ¼ 72%) or in those undergoing open (mean
difference 0.89, 95% CI 1.85 to 0.07, P ¼ 0.07,
I2 ¼ 75%) or laparoscopic procedures (mean difference
0.21, 95% CI 1.02 to 0.60, P ¼ 0.61, I2 ¼ 72%; Fig. 4).
In terms of VAS on coughing at 12 h postoperatively, four
studies included data on this variable including 158
patients,22–24,27 of which two were in open23,27and two
in laparoscopic22,24 studies (Fig. 4). Overall, IVL was
associated with a significant reduction in postoperative
pain on coughing at 12 h vs. placebo (mean difference
0.69, 95% CI 0.97 to 0.41, P < 0.00001, I2 ¼ 0%).
This was mirrored when only laparoscopic (mean differ-
ence 0.93, 95% CI 1.39 to 0.46, P ¼ 0.0001, I2 ¼ 0%)
and open studies (mean difference 0.55, 95% CI 0.90
to 0.20, P ¼ 0.002, I2 ¼ 0%) were included.
Seven studies (333 patients)2,22–27 included data on VAS
pain score on coughing at 24 h postoperatively, of which
four studies2,22,24,26 were conducted in laparoscopic sur-
gery and three studies in open surgery.23,25,27 IVL was
associated with no significant difference in pain on cough-
ing at 24 h postoperatively vs. placebo, both overall and in
either open or laparoscopic groups (Fig. 4).
VAS score on coughing at 48 h postoperatively was con-
sidered in six studies,2,23–27 three in laparoscopic sur-
gery2,24,26 and three in open procedures.23,25,27 At 48 h
postoperatively, IVL did not significantly affect VAS-
rated pain on coughing in any of the groups (Fig. 4).
The time to passage of flatus was considered in eight
studies2,13,21,23–27 including a total of 398 patients. Overall,
IVL infusion was not associated with a significant differ-
ence in the time to passage of flatus (mean difference
5.33 h, 95% CI 11.53 to 0.88, P ¼ 0.09, I2 ¼ 90%; Fig. 5).
When the four studies in laparoscopic surgery were con-
sidered, an IVL infusion (n ¼ 201) was not associated with
any difference in the time to passage of flatus (mean
difference 3.78 h, 95% CI 12.88 to 5.32, P ¼ 0.42,
I2 ¼ 87%). However, in patients undergoing open surgery
(four studies; n ¼ 197), IVL was associated with a signifi-
cant reduction in the time to passage of flatus of 8.4 h (95%
CI 13.7 to 3.1, P ¼ 0.002, I2 ¼ 31%).
Time to defecation was examined in seven studies
including a total of 378 patients. Overall, the use of
IVL was associated with a significant reduction in time
to defecation (mean difference 12.06 h, 95% CI 17.83
to 6.29, P ¼ 0.0001, I2 ¼ 93%; Fig. 5). When the five
Eur J Anaesthesiol 2020; 37:1–12
studies involving laparoscopic surgery were considered
(n ¼ 261), IVL was associated with a significant reduction
in the time to defecation (mean difference 12.33 h, 95%
CI 18.63 to 6.03, P ¼ 0.0001, I2 ¼ 96%). However, no
difference was seen in patients undergoing open surgery
(mean difference 11.04 h, 95% CI 23.56 to 1.48,
P ¼ 0.08, I2 ¼ 0%), although this was based upon data
from two studies alone including a total of 107 patients.
The incidence of prolonged postoperative ileus was
considered in four studies,2,21,22,25 of which three were
conducted in patients undergoing laparoscopic sur-
gery2,21,22 and one in open surgery.25 Overall, the use
of IVL was not associated with any difference in the
incidence of prolonged postoperative ileus in either
group (Fig. 5).
A total of five studies considered the time to tolerance of
oral intake,2,20–22,25 of which four studies were conducted
in laparoscopic surgery (253 patients) and one in open
procedures (60 patients) (Fig. 6). Overall, the use of IVL
was not associated with a significant difference in time to
tolerance of enteral intake (mean difference 3.02 h, 95%
CI 6.06 to 0.01, P ¼ 0.05), and in just those undergoing
laparoscopy (mean difference 1.96 h, 95% CI 4.97 to
1.04, P ¼ 0.20). No meta-analysis was conducted on those
undergoing open surgery, as this only considered data
from a single study.
The most common variable considered was the overall
postoperative morphine requirement, which was consid-
ered in a total of seven studies,13,20,21,23,25–27 three of which
were conducted in laparoscopic surgery20,21,26 and four in
open surgery.13,23,25,27 Overall, there was no difference in
the postoperative morphine requirement between those
receiving IVL and placebo (mean difference 8.86 mg,
95% CI 21.87 to 4.15, P ¼ 0.18, I2 ¼ 97%; Fig. 6), nor in
those undergoing laparoscopic (mean difference
3.31 mg, 95% CI 15.01 to 8.39, P ¼ 0.58, I2 ¼ 76%) or
open surgery alone (mean difference 13.79 mg, 95% CI
35.75 to 8.18, P ¼ 0.22, I2 ¼ 98%).
Hospital LOS was reported in eight studies included
within the meta-analysis,2,13,20–22,25–27 including 450
patients, of whom 293 underwent laparoscopic surgery
(five RCTs) and 157 underwent open surgery (three
RCTs). Overall, the use of IVL was associated with a
significantly shorter hospital LOS (mean difference
0.76 days, 95% CI 1.32 to 0.19, P ¼ 0.009,
I2 ¼ 45%; Fig. 6), as well as when analysis was undertaken
of those undergoing laparoscopic surgery (mean difference
0.83 days, 95% CI 1.58 to 0.09, P ¼ 0.03, I2 ¼ 32%).
However, no significant difference was seen when those
undergoing open surgery were considered (mean differ-
ence 0.73, 95% CI 1.65 to 0.18, P ¼ 0.12, I2 ¼ 52%).
Only two studies21,22 included data on the incidence of
surgical site infection (n ¼ 128). IVL was not associated
with any difference in the incidence of surgical site
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Peri-operative lidocaine in elective colorectal surgery 7

Fig. 4

IVL Placebo Mean difference Mean difference

4h Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Dewinter 2018 2.94 1.63 50 24 1.53 25 17.4% 0.54 (–0.2 1, 1.29)
El hafz 2012 4.3 1.7 9 5.8 1.2 9 9.7% –1.50 (– 2.86, – 0.14)
Tiku is is 2014 6.4 0.5 30 6.6 0.81 30 24.2% –0.20 (–0.54, 0.14)
Subtotal (95% CI) 89 64 51.2% –0.21 (–1.02, 0.60)
2 2 2
Heterogeneity: Tau = 0.35; Chi = 7.11, df = 2 (P < 0.03); I = 72%
Test for overall effect: Z = 0.51 (P = 0.61)

Open surgery
Herroeder 2007 6.18 1.9 31 6.77 1.64 29 15.1% –0.59 (–1.4 9, 0.31)
Kuo 2006 4.95 0.76 20 5.25 0.64 20 22.7% –0.30 (–0.74, 0.14)
Staikou 2014 1.2 0.8 20 3.4 2.7 20 10.9% –2.20 (– 3.43, – 0.97)
Subtotal (95% CI) 71 69 48.8% –0.89 (–1.85, 0.07)
2 2 2
Heterogeneity: Tau = 0.53; Chi = 8.12, df = 2 (P < 0.02); I = 75%
Test for overall effect: Z = 1.81 (P = 0.07)

Total (95% CI) 160 133 100.0% –0.50 (–1.02, 0.03)

2 2 2
Heterogeneity: Tau = 0.27; Chi = 17.64, df = 5 (P < 0.003); I = 72%
Test for overall effect: Z = 1.84 (P = 0.07) –4 –2 0 2 4
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 1.11, df = 1 (P = 0.29), I = 10.0%

IVL Placebo Mean difference Mean difference

12h Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Elhafz 2012 3.7 2.6 9 5.4 2.9 9 1.2% –1. 70 (–4.24, 0.84)
Kaba 2007 1.935 2.22 20 0 0 20 Not estimable
Tik uisis 2014 2.8 0.48 30 3.7 1.24 30 34.7% –0.90 (–1.38, –0.42)
Subtotal (95% CI) 39 39 35.9% –0.93 (–1.39, –0.46)
2 2 2
Heterogeneity: Tau = 0.00; Chi = 0.37, df = 1 (P < 0.54); I = 0%
Test for overall effect: Z = 3.88 (P = 0.0001)

Open surgery
Kuo 2006 4.3 0.57 20 4.8 0.62 20 57.6% –0.50 1–0.87, –0.13)
Staikou 2014 1.8 1 20 2.8 2.3 20 6.5% –1.00 (–2.10, 0.10)
Subtotal (95% CI) 40 40 64.1% – 0.55 (– 0.90, – 0.20)
2 2 2
Heterogeneity: Tau = 0.00; Chi = 0.71, df = 1 (P < 0.40); I = 0%
Test for overall effect: Z = 3.08 (P = 0.002)

Total (95% CI) 79 79 100.0% –0.69 (–0.97, –0.41)

2 2 2
Heterogeneity: Tau = 0.00; Chi = 2.68, df = 3 (P < 0.44); I = 0%
Test for overall effect: Z = 4.80 (P = 0.00001) –4 –2 0 2 4
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 1.59, df = 1 (P = 0.21), I = 37.3%

IVL Placebo Mean difference Mean difference

24h Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Dewi nter 2018 4.82 1.87 50 3.88 1.83 25 15.6% 0.94 (0.05, 1.83)
Elhafz 2012 3.5 2.3 9 5.2 2.7 9 7.0% – 1.70 (–4.02, 0.62)
Kaba 2007 2.99 3.37 20 4.5 1.84 20 10.1% –1.51 (–3.19, 0.17)
Tikuisis 20 14 3.1 0.8 30 4.8 1.13 30 18.2% –1.70 (–2.20, –1.20)
Subtotal (95% CI) 109 84 50.9% – 0.91 (– 2.53, 0.70)
2 2 2
Heterogeneity: Tau = 2.21; Chi = 26.52, df = 3 (P < 0.00001); I = 89%
Test for overall effect: Z = 1.11 (P = 0.27)

Open surgery
Herroeder 2007 5.9 2.32 31 5.87 2.43 29 13.2% 0.03 (–1.17, 1.23)
Kuo 2006 3.85 0.81 20 4.45 0.69 20 18.4% –0.60 (–1.07, –0.13)
Staikou 2014 2 0.7 20 2 1.2 20 17.5% 0.00 (–0.61,0.61)
Subtotal (95% CI) 71 69 49.1% –0.30 (–0.75, 0.14)
2 2 2
Heterogeneity: Tau = 0.04; Chi = 2.75, df = 2 (P < 0.25); I = 27%
Test for overall effect: Z = 1.33 (P = 0.18)

Total (95% CI) 180 153 100.0% –0.54 (–1.31,0.22)

2 2 2
Heterogeneity: Tau = 0.77; Chi = 37.07, df = 6 (P < 0.00001); I = 84%
Test for overall effect: Z = 1.39 (P = 0.17) –4 –2 0 2 4
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 0.51, df = 1 (P = 0.48), I = 0%

IVL Placebo Mean difference Mean difference

48h Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Dewinter 2018 4.14 1.55 50 3.88 2.01 25 17.8% 0.26 (–0.64, 1.16)
Elhafz 2012 2.5 1.8 9 3.8 2.1 9 8.6% –1.30 (–3.11, 0.51)
Kaba 2007 1.45 1.84 20 2.83 1.93 20 14.3% –1.38 (–2.55, –0.21)
Subtotal (95% CI) 79 54 40.7% –0.69 (–1.90, 0.51)
2 2 2
Heterogeneity: Tau = 0.72; Chi = 5.68, df = 2 (P < 0.06); I = 65%
Test for overall effect: Z = 1.13 (P = 0.26)

Open surgery
Herroeder 2007 4.71 2.33 31 5.14 2.16 29 14.7% –0.43 (–1.57, 0.71)
Kuo 2006 3.1 0.31 20 3.45 0.51 20 26.4% –0.35 (–0.61, –0.09)
Staikou 2014 2.5 1.3 20 1.4 1.5 20 18.2% 1.10 (0.23, 1.97)
Subtotal (95% CI) 71 69 59.3% 0.09 (–0.86, 1.04)
2 2 2
Heterogeneity: Tau = 0.54; Chi = 9.90, df = 2 (P < 0.007); I = 80%
Test for overall effect: Z = 0.18 (P = 0.86)

Total (95% CI) 150 123 100.0% –0.22 (–0.85, 0.42)

2 2 2
Heterogeneity: Tau = 0.38; Chi = 16.02, df = 5 (P < 0.007); I = 69%
Test for overall effect: Z = 0.67 (P = 0.50) –4 –2 0 2 4
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 0.99, df = 1 (P = 0.32), I = 0%

Pain on coughing

Forest plot comparing visual analogue scale pain scores on coughing at 4, 12, 24 and 48 h postoperatively for patients receiving intravenous
lidocaine vs. placebo, for both laparoscopic and open surgery.

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EJA-D-19-00766

8 Rollins et al.

Fig. 5

IVL Placebo Risk ratio Risk ratio

Study or subgroup Events Total Events Total Weight M–H, Random, 95% CI M–H, Random, 95% CI
Laparoscopic surgery
Dewinter 2018 2 50 0 25 8.2% 2.55 (0.13, 51.17)
Kim 2014 1 32 4 36 16.1% 0.28 (0.03, 2.39)
Tikuisis 2014 3 30 5 30 41.2% 0.60 (0.16, 2.29)
Subtotal (95% CI) 112 91 65,6% 0.60 (0.21, 1.72)
Total events 6 9
2 2 2
Heterogeneity: Tau = 0.00; Chi = 1.38, df = 2 (P < 0.50); I = 0%
PONV Test for overall effect: Z = 0.95 (P = 0.34)

Open surgery
Herroeder 2007 2 31 8 29 34.4% 0.23 (0.05, 1.01)
Subtotal (95% CI) 30 29 34.4% 0.23 (0.0 5, 1.01)
Total events 2 8
Heterogeneity: Not applicable
Test for overall effect: Z = 1.94 (P = 0.05)

Total (95% CI) 143 120 100.0% 0.43 (0.18, 1.02)

Total events 8 17
2 2 2
Heterogeneity: Tau = 0.00; Chi = 2.41, df = 3 (P < 0.49); I = 0%
Test for overall effect: Z = 1.91 (P = 0.06) –0.05 –0.2 1 5 20
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 1.03, df = 1 (P = 0.31), I = 3.0%

IVL Placebo Mean difference Mean difference

Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Dewinter 2018 1.88 1.26 50 1.76 1.09 25 17.5% 0.12 (–0.43, 0.67)
Elhafz 2012 39.6 12.7 9 51.4 14.2 9 10.3% –11.80 (– 24.25, 0.65)
Kaba 2007 17.95 9.09 20 31.25 11.48 20 14.8% –13.30 (–19.72, –6.88)
Kim 20 14 58 18.37 32 48 27.78 36 11 .2% 10.00 (–l.08, 21.08)
Time to pass flatus

Subtotal (95% CI) 111 90 53.8% –3.78 (–12.88, 5.32)

2 2 2
Heterogeneity: Tau = 68.40; Chi = 23.25, df = 3 (P < 0.0001); I = 87%
Test for overall effect: Z = 0.81 (P = 0.42)

Open surgery
Herroeder 2007 51.6 20.2 31 59.9 28.5 29 10.2% –8.30 (–20.88, 4.28)
Ho 2018 64.7 38.5 28 70 31.2 29 7.0% –5.30 (–23.53, 12.93)
Kuo 2006 60.15 5.84 20 71.7 4.7 20 16.7% – 11.55 (–14.84, –8.26)
Staikou 2014 72.4 6.54 20 73.6 21 20 12 .3% –1.20 (–10.84, 8.44)
Subtotal (95% CI) 99 98 46.2% –8.40 (– 13.70, –3.10)
2 2 2
Heterogeneity: Tau = 10.09; Chi = 4.36, df = 3 (P < 0.22); I = 31%
Test for overall effect: Z = 3.10 (P = 0.002)

Total (95% CI) 210 188 100.0% –5.33 (–11.53, 0.88)

2 2 2
Heterogeneity: Tau = 57.15; Chi = 71.50, df = 7 (P < 0.00001); I = 90%
Test for overall effect: Z = 1.68 (P = 0.09) –20 –10 0 10 20
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 74, df = 1 (P = 0.05), I = 0%

IVL Placebo Mean difference Mean difference

Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Dewinter 2018 76.8 2.75 50 91.2 2.74 25 24.0% – 14.40 (– 15.72, –13.08)
Elhafz 2012 61.4 9.5 9 82.3 10.1 9 15.2% –20.90 (–29.96, –11.84)
Kaba 2007 31.85 12.83 20 51.4 17.55 20 14.6% – 19.55 (–29.08, –10.02)
Kim 2014 78 25.56 32 73.5 44 .07 36 7.9% 4.50 (–12.40, 21.40)
Time to defecation

Tikuisis 2014 26.97 2.3 30 32.93 2.86 30 24.0% –5 .96 (–7.27, – 4.65)
Subtotal (95% CI) 141 120 85.6% – 12.33 (– 18.63, – 6.03)
2 2 2
Heterogeneity: Tau = 36.67; Chi = 91.00, df = 4 (P < 0.00001); I = 96%
Test for overall effect: Z = 3.83 (P = 0.0001)

Open surgery
Herroeder 2007 66.6 26.4 31 82.1 33.8 29 8.9% –15.50 (–30.92, –0.08)
Ho 2018 80.1 42 .2 28 82.5 40.4 29 5.6% –2.40 (–23 .86, 19.06)
Subtotal (95% CI) 59 58 14.4% –11.04 (–23.56, 1.48)
2 2 2
Heterogeneity: Tau = 0.00; Chi = 0.94, df = 1 (P < 0.33); I = 0%
Test for overall effect: Z = 1.73 (P = 0.08)

Total (95% CI) 200 178 100.0% –12.06 (–17.83, –6.29)

2 2 2
Heterogeneity: Tau = 35.69; Chi = 91.96, df = 6 (P < 0.00001); I = 93%
Test for overall effect: Z = 4.10 (P = 0.0001) –20 –10 0 10 20
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 0.03, df = 1 (P = 0.86), I = 0%

IVL Placebo Risk ratio Risk ratio

Study or subgroup Events Total Events Total Weight M–H, Random, 95% CI M–H, Random, 95% CI
Laparoscopic surgery
Dewi nter 2018 2 50 0 25 8.2% 2.55 (0.13, 51.17)
Kim 2014 1 32 4 36 16. 1% 0.28 (0.03, 2.39)
Tikuisis 2014 3 30 5 30 41.2% 0.60 (0.16, 2.29)
Postoperative ileus

Subtotal (9 5% CI) 112 91 65.6% 0.60 (0.21, 1.72)

Total events 6 9
2 2 2
Heterogeneity: Tau = 0.00; Chi = 1.38, df = 2 (P < 0.50); I = 0%
Test for overall effect: Z = 0.95 (P = 0.34)

Open surgery
Herroeder 2007 2 31 8 29 34.4% 0.23 (0.05, 1.01)
Subtotal (95% CI) 31 29 34.4% 0.23 (0.05, 1.01)
Total events 2 8
Heterogeneity: Not applicable
Test for overall effect: Z = 1.94 (P = 0.05)

Total (95% CI) 143 120 100.0% 0.43 (0.18, 1.02)

Total events 8 17
2 2 2
Heterogeneity: Tau = 0.00; Chi = 2.41, df = 3 (P < 0.49); I = 0%
Test for overall effect: Z = 1.91 (P = 0.06) 0.05 0.2 1 5 20
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 1.03, df = 1 (P = 0.31), I = 3.0%

Forest plot comparing incidence of postoperative nausea and vomiting, time to pass flatus (h), time to defaecation (h) and incidence of postoperative
ileus for patients receiving intravenous lidocaine vs. placebo, for both laparoscopic and open surgery.

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Peri-operative lidocaine in elective colorectal surgery 9

Fig. 6

Time to tolerance of diet

IVL Placebo Mean difference Mean difference
Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Ahn 2015 4 1.11 25 4 0.74 25 28.6% 0.00 (–0.52, 0.52)
Dewinter 2018 1.62 1.81 50 1.4 0.71 25 28.6% 0.22 (–0.35, 0.79)
Kim 2014 70 18.15 32 72.5 14.07 36 10.0% –2.50 (–10.29, 5.29)
Tikuisis 2014 30.97 1.83 30 36.97 1.75 30 28.1% –6.00 (–6.91, – 5.09)
Subtotal (95% CI) 137 116 95.3% –1.96 (–4.97, 1.04)
2 2 2
Heterogeneity: Tau = 0.01; Chi = 147.78, df = 3 (P < 0.00001); I = 98%
Test for overall effect: Z = 1.28 (P = 0.20)

Open surgery
Herroeder 2007 74.3 23.2 31 98.7 27.1 29 4.7% –24.40 (–37.21, –11.59)
Subtotal (95% CI) 31 29 4.7% –24.40 (–37.21, –11.59)
Heterogeneity: Not applicable
Test for overall effect: Z = 3.73 (P = 0.0002)

Total (95% CI) 168 145 100.0% –3.02 (–6.06,0.01)

2 2 2
Heterogeneity: Tau = 8.33; Chi = 160.78, df = 4 (P < 0.00001); I = 98%
–20 –10 0 10 20
Test for overall effect: Z = 1.95 (P = 0.05)
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 11.18, df = 1 (P = 0.0008), I = 91.1%

Postoperative morphine requirement

IVL Placebo Mean difference Mean difference
Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Ahn 2015 89.07 100 25 102.06 115.9 25 3.9% –12.99 (–73.00, 47.02)
Kaba 2007 5.28 6.35 20 14.52 10.75 20 21.1% –9.24 (–14.71, – 3. 77)
Kim 2014 9.375 16.875 32 5.63 11.25 36 20.6% 3.75 (–3.16, 10.65)
Subtotal (95% CI) 77 81 45.6% –3.31 (–15.01, 8.39)
2 2 2
Heterogeneity: Tau = 63.87; Chi = 8.42, df = 2 (P < 0.01); I = 76%
Test for overall effect: Z = 0.55 (P = 0.58)

Open surgery
Herroeder 2007 69.5 67.25 31 70.22 53.1 29 9.9% –0.72 (–31.28, 29.84)
Ho 2018 157.2 205.6 28 271.6 260.2 29 1.1% –114.40 (–235.92, 7.12)
Kuo 2006 55 5.3 20 81.6 6.5 20 21.5% –26.60 (–30.28, –2 2. 92)
Staikou 2014 2.72 1.01 20 3.36 0.96 20 21.9% –0.64 (–1.25, –0.03)
Subtotal (95% CI) 99 98 54.4% –13.79 (–35.75, 8.18)
2 2 2
Heterogeneity: Tau = 332.44; Chi = 189.80, df = 3 (P < 0.00001); I = 98%
Test for overall effect: Z = 1.23 (P = 0.22)

Total (95% CI) 176 179 100.0% –8.86 (–21.87, 4.15)

2 2 2
Heterogeneity: Tau = 201.11; Chi = 200.00, df = 6 (P < 0.00001); I = 97%
–200 –100 0 100 200
Test for overall effect: Z = 1.34 (P = 0.18)
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 0.68, df = 1 (P = 0.41), I = 0%

Length of stay
IVL Placebo Mean difference Mean difference
Study or subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
Laparoscopic surgery
Ahn 2015 12 6.3 25 13 5.93 25 2.5% –1.00 (–4.39, 2.39)
Dewinter 2018 5.56 4.36 50 5.48 4.58 25 5.6% 0.08 (– 2.08, 2.24)
Kaba 2007 2.45 0.51 20 3.75 1.77 20 19.7% –1.30 (–2.11, –0.49)
Kim 2014 9 4.81 32 8 2.96 36 6.8% 1.00 (–0.93, 2.93)
Tikuisis 2014 4.7 1.29 30 5.9 1.97 30 19.0% –1.20 (–2 .04, –0.36)
Subtotal (95% CI) 157 136 53.7% 0.83 (–1.58, –0.09)

2 2 2
Heterogeneity: Tau = 0.21; Chi = 5.84, df = 4 (P < 0.21); I = 32%
Test for overall effect: Z = 2.20 (P = 0.03)

Open surgery
Herroeder 2007 7 1.48 31 8 2.96 29 13.3% –1.00 (–2.20, 0.20)
Ho 2018 9 4.44 28 11 2.96 29 6.6% –2.00 (–3.97, –0.03)
Kuo 2006 6.9 0.8 20 7.1 0.8 20 26.4% –0.20 (–0.70, 0.30)
Subtotal (95% CI) 79 78 46.3% –0.73 (–1.65, 0.18)
2 2 2
Heterogeneity: Tau = 0.34; Chi = 4.13, df = 2 (P < 0.13); I = 52%
Test for overall effect: Z = 1.57 (P = 0.12)

Total (95% CI) 236 214 100.0% –0.76 (–1.32, –0.19)

2 2 2
Heterogeneity: Tau = 0.25; Chi = 12.73, df = 7 (P < 0.08); I = 45%
–4 –2 0 2 4
Test for overall effect: Z = 2.63 (P = 0.009)
2 2 Favours IVL Favours Placebo
Test for subgroup differences: Chi = 0.03, df = 1 (P = 0.87), I = 0%

Forest plot comparing comparing time to tolerance of diet, overall postoperative morphine requirement and hospital length of stay in patients
receiving intravenous lidocaine vs. placebo, for both laparoscopic and open surgery.

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EJA-D-19-00766
10 Rollins et al.
infection vs. placebo (risk ratio 1.06, 95% CI 0.11 to 10.19,
P ¼ 0.96, I2 ¼ 2%). Four studies considered the incidence
of anastomotic leakage,2,21,22,25 three in patients under-
going laparoscopic surgery2,21,22 and just one in open
surgery.25 Both overall and in those undergoing laparo-
scopic surgery, the use of IVL was not associated with any
difference in the incidence of anastomotic leak. Due to a
lack of data, no meta-analysis was performed in those
undergoing open surgery.
Six studies examined the incidence of local anaesthetic
toxicity in IVL vs. placebo including 300
patients,2,13,20,22,24,27 with four studies2,20,22,24 conducted
on patients undergoing laparoscopic surgery and two in
those undergoing open procedures.13,27 Only one study2
had any incidence of local anaesthetic toxicity, with all
other studies reporting no events, hence a meta-analysis
was not conducted on this outcome. There was only one
case of local anaesthetic toxicity, which was mild in
nature, with a metallic taste and tinnitus.
Discussion
This meta-analysis of 10 RCTs examining the impact of
IVL vs. placebo in elective colorectal surgery has dem-
onstrated that IVL is associated with a statistically signif-
icant reduction in VAS pain scores at rest at early time
points (4, 12 and 24 h) and pain scores on coughing at 12 h
only. However, when these are interpreted in light of the
IASP threshold for a clinically significant difference in
VAS-rated pain scales, these cannot be interpreted as
clinically significant results. In addition, there was a
significant reduction in time to defecation and hospital
LOS in those who underwent IVL infusion vs. placebo.
No difference was seen in the time to passage of flatus,
pain at rest at 48 h postoperatively, pain on coughing at 4,
24 and 48 h postoperatively, overall morphine consump-
tion or complication rates (Supplementary Digital Con-
tent Table 3, http://links.lww.com/EJA/A277). However,
the results should be interpreted with some caution in
respect of the time to first flatus and hospital length of
stay, as these differences are almost entirely the result of
one or two studies (Kuo et al.27 for the time to first flatus
and Kaba et al.26 and Tikuisis et al.22 for the hospital
LOS). This renders the conclusion potentially weaker
and further evidence is needed to provide a more defini-
tive answer. When studies in laparoscopic surgery were
analysed, the benefits of peri-operative IVL were more
pronounced. IVL was associated with a significant reduc-
tion in time to defecation, pain at rest, and at 12 and 24 h,
pain on coughing at 12 h and overall hospital LOS, but no
difference in pain scores at any other time point, time to
return of flatus, morphine requirement or surgical com-
plications. However, again, the differences in pain score
cannot be considered clinically significant. When open
surgery studies were considered, IVL was associated with
a significant reduction in time to flatus but not faeces,
pain at rest at early time points (4, 12 and 24 h) and on
Eur J Anaesthesiol 2020; 37:1–12
coughing at 12 h only, but there was no difference in the
hospital LOS or morphine requirement.
The details of the lidocaine infusion differed greatly
between studies included within this meta-analysis. In
terms of commencement of the IVL infusion, one study
commenced 30 min before the start of surgery,27 five
studies commenced before induction of anaesthe-
sia,20,22,23,25,26 one started at the time of induction2 and
three commenced after induction or at the time of skin
incision.13,21,24 In addition, there was a degree of vari-
ability in the dosage of lidocaine. In terms of the lidocaine
bolus, all but one study24 administered a bolus before
commencing the infusion, with the most common dosage
being 1.5 mg kg1, which was used in seven stud-
ies,2,13,20,22,23,25,26 with one study27 administering
2 mg kg1, and one21 1 mg kg1. This was also reflected
in differing doses for the IVL infusion, with the most
common rate of 2 mg kg1 h1 being administered in four
studies,20,22,23,25 followed by 1 mg kg1 h1 in two stud-
ies,13,21 3 mg kg1 h1 in one study27 and 1.5 mg kg1 h1
in one study.2 One study administered a weight-depen-
dent rate of infusion,24 and one study reduced the infu-
sion rate between intra-operative and postoperative
stages.26
There was also variability in the infusion duration; three
studies administered the infusion only intra-opera-
tively,20,23,27 and three commenced intra-operatively
and continued for 24 h.21,22,26 Two studies discontinued
the infusion at 4 h postoperatively,2,25 one after 48 h13 and
one24 on return of gastrointestinal function or at day 5,
whichever was sooner. The level of heterogeneity
between different infusions is a potentially significant
source of bias. There are insufficient data for the indi-
vidual regimens to separately analyse these and draw
meaningful conclusions. There were significant levels of
heterogeneity observed in the meta-analyses. Overall, 10
of the 14 analyses demonstrated high levels of heteroge-
neity, with a similar level in the analyses concerning
laparoscopic surgery (n ¼ 10/15). This was lower when
studies of open surgery alone were analysed (n ¼ 5/12),
but this remains a significant confounder.
One previous systematic review10 has examined the
impact of IVL in elective colorectal surgery, which
included five RCTs comparing IVL and placebo. That
demonstrated that IVL provided limited benefit in the
reduction of early postoperative pain and morphine con-
sumption. No meta-analysis of the available data was
conducted, and since its publication, two further
RCTs2,13 have been published that are included in the
current meta-analysis. In addition, a meta-analysis of nine
RCTs11 has recently been published focusing on the time
to return of gastrointestinal function following IVL in
patients undergoing colorectal surgery. That meta-anal-
ysis did not include two RCTs,2,20 which were potentially
eligible, and also included one RCT which administered
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EJA-D-19-00766
the lidocaine in the postoperative setting only,28 which
the current meta-analysis excluded due to the potential
heterogeneity that this causes. The findings of the
current meta-analysis mirror these previous studies in
their observation of a statistically significant improve-
ment in early postoperative pain and time to return of
gastrointestinal function in those receiving IVL. How-
ever, the current meta-analysis did not find any differ-
ence in morphine consumption rates, contrary to the
previous systematic review. In addition, no conclusions
were drawn regarding the relative effectiveness of
IVL in open vs. laparoscopic surgery by the previous
systematic review.
A recently updated meta-analysis1,29 examined the role of
IVL in all branches of surgery which included a total of 68
RCTs, finding IVL to be associated with a statistically
significant benefit in terms of pain scores. However, this
did not meet the threshold for a clinically relevant
difference. A significant difference was also seen in
gastrointestinal recovery, hospital length of stay and
opioid requirement. This Cochrane review1 and a
recently published commentary article30 make note of
the significant level of heterogeneity introduced by
including studies conducted in a range of surgical spe-
cialties, which is avoided in the current meta-analysis.
There is also significant variability in the details of the
IVL infusion, which are also relevant to the current meta-
analysis and are due to a lack of standardisation in
the literature.
Conclusion
This meta-analysis provides support for the administra-
tion of peri-operative IVL in elective colorectal surgery,
in terms of earlier return of gastrointestinal function and
reduced hospital LOS, with no difference in complication
rates or apparent issues surrounding local anaesthetic
toxicity. The pain scores at early time points were sig-
nificantly lower in those receiving the IVL infusion,
although this did not meet the threshold for a clinically
relevant difference. This meta-analysis supports the use
of peri-operative IVL infusion as a good choice for
analgesia, particularly in laparoscopic colorectal surgery,
with benefits most pronounced in the first 24 h following
surgery, which may help promote early mobilisation and
nutrition, key components of enhanced recovery path-
ways. There remains the option to give regular multi-
modal analgesia alongside IVL in the postoperative
setting, thus reserving opioid analgesia for breakthrough
pain alone. Further research is needed to explore whether
the anti-inflammatory and natural killer cell effects result
in improved oncological outcomes. In addition, further
evidence would be beneficial in light of the high levels of
study heterogeneity as well as to understand the optimal
dosage and timing of the IVL infusion in order to
standardise further studies and maximise the potential
benefits of its administration.
Peri-operative lidocaine in elective colorectal surgery 11
Acknowledgements relating to this article
Assistance with the study: none
Funding: this work was supported by the Medical Research Council
(grant number MR/K00414X/1), Arthritis Research UK (grant num-
ber 19891) and Royal College of Surgeons of England Systematic
Review Grant.
Conflict of Interest: none.
Presentation: data from this study were presented to the 7th ERAS
World Congress, Liverpool in May 2019. It has been published in
abstract form - Clin Nutr ESPEN 2019; 31:104–105.
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