Journal of Clinical Anesthesia 51 (2018) 20–31

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Journal of Clinical Anesthesia

journal homepage: www.elsevier.com/locate/jclinane

Original Contribution

Comparison of the postoperative effect between epidural anesthesia and T

continuous wound infiltration on patients with open surgeries: A meta-
analysis
⁎
Haifang Lia,1, Rui Chenb, Zaiqi Yangc, Cuifang Nied, Shengqiang Yangc,
a
Anesthesiology Department, the Third People's Hospital of Qingdao, Qingdao City, ShanDong Province 266041, China
b
Anesthesiology Department, the Second People's Hospital of Xintai, Xintai City, ShanDong Province 271219, China
c
Anesthesiology Department, Taian City Central Hospital, Tai'an City, ShanDong Province 271000, China
d
Infectious Diseases Department, Taian City Central Hospital, Tai'an City, ShanDong Province 271000, China

A R T I C LE I N FO A B S T R A C T

Keywords: Purpose: The study aimed to compare the effect of epidural anesthesia (EA) and continuous wound infiltration
Surgery (CWI) on surgical patients.
Epidural anesthesia Methods: The literature retrieval was conducted in relevant databases from their inception to June 2018 with the
Continuous wound infiltration predefined searching strategy and selection criteria. Then, the Cochrane Collaboration's tool was used to assess
Complication
the quality of included studies. In addition, odds ratio (OR) and standardized mean difference (SMD) with its
Pain score
corresponding 95% confidence interval (CI) were used as a measure of effect size for evaluating outcomes
Meta-analysis
indicators.
Results: Totally, sixteen RCTs were included. The incidence of hypotension in EA group was significantly higher
than CWI group (OR = 3.7398; 95% CI: 1.0632 to 13.1555). In addition, EA provided better pain relief than CWI
on rest at 72 h (SMD = −0.6037; 95% CI: −1.0767 to −0.1308) after surgery. Additionally, there were no
significant differences in pain score on rest and mobilization at 2 h, 12 h, 24 h and 48 h. Moreover, the subgroup
analysis showed that pain scores in EA group was significantly reduced at 2 h on rest and 12 h on mobilization
than CWI group after liver resection surgery, as well as at 72 h on rest after colorectal surgery.
Conclusion: CWI is superior to EA with a lower incidence of complications for use in surgery, and EA may
provide better pain control than CWI on pain relief after surgery.

1. Introduction shorten hospital length of stay [3, 4].

According to Practice Guidelines developed by the American Society
of Anesthesiologists (ASA), procedure-related complications and acute
pain are accompanied with various surgical operations, and appropriate
analgesia is important for humanitarian reasons, early movement and
rehabilitation [1]. In order to reduce or eliminate postoperative pain as
much as possible for patients before discharge, pain management be-
comes an important course [2]. Newer methods of patient-controlled
analgesia and regional analgesia have been developed, and an effective
analgesia may not only enhance the postoperative satisfaction of pa-
tients, but also reduce the incidence of complications, relieve pain and
In recent years, epidural analgesia (EA) has been widely used for
varied surgical operation, such as abdominal surgery, thoracotomy, and
cesarean section [5, 6], since EA has advantages of decreasing the in-
cidence of complications and reducing pain after many surgeries [7–9].
However, some studies have indicated that EA has adverse effects such
as urinary retention, hypotension, nausea and vomiting, pruritus, in-
complete block and delay mobilization [10–12]. On the other hand,
continuous wound infiltration (CWI) acts as an alternative technique
that may offer satisfying analgesic effectiveness, and reduce morphine
consumption and pain intensity, which allow earlier mobilization for
patients [13, 14]. Thus, it is meaningful to compare the efficacy of EA

Abbreviations: EA, epidural anesthesia; CWI, continuous wound infiltration; OR, odds ratio; SMD, standardized mean difference; CI, confidence interval; ASA,
American Society of Anesthesiologists; RCTs, randomized controlled trials; BMI, body mass index; OR, odds ratio; CI, confidence interval
⁎
Corresponding author at: Anesthesiology Department, Tai'an City Central Hospital, No.29 Longtan Rd, Taishan District, Tai'an City, ShanDong Province 271000,
China.
E-mail address: yaq8080808@hotmail.com (S. Yang).
1
First author.

https://doi.org/10.1016/j.jclinane.2018.07.008
Received 4 April 2018; Received in revised form 2 July 2018; Accepted 24 July 2018
0952-8180/ © 2018 Elsevier Inc. All rights reserved.
H. Li et al.
Fig. 1. Flow chart showing selection of the included studies.
with CWI, and select a better analgesic therapy for further clinical
guidance.
Previously, a study of meta-analysis focused on the postoperative
pain comparison between CWI and EA, was performed by Ventham N
et al. [15]. In their work, complications and pain score were also chosen
as outcomes to assess the effect of EA and CWI on analgesia. However,
they only evaluated the pain score at rest and movement after surgery
24 and 48 h, while the effects comparison on other time points was not
performed. Moreover, their sample size was small. Therefore, we car-
ried out this update meta-analysis, and evaluated pain score on rest and
mobilization at postoperative 2 h, 6 h, 12 h, 24 h, 48 h, 72 h, respec-
tively, to provide a comprehensive and precise evaluation of EA and
CWI.
2. Methods
2.1. Data resources
Studies were retrieved in electronic databases such as PubMed
electronic database (http://www.ncbi.nlm.nih.gov/pubmed), Cochrane
library (http://www.cochranelibrary.com/) and Embase database
(http://www.embase. com) up to June 2018. The key searching terms
were (“epidural anesthesia” OR “EA” OR “epidural analgesia” OR
“caudalanaesthesia” OR “epidural infusion”) AND (“wound” AND “ca-
theters” OR “infusion” OR “infiltration”) AND (surgery OR surgical OR
operation) AND ("humans"[MeSHTerms] AND English[lang]).
2.2. Inclusion and exclusion criteria
The inclusion criteria were as follows: (1) the studies were English
publications; (2) the studies were concerning the analgesia effect of EA
and CWI on surgical patients; (3) the studies were randomized con-
trolled trials (RCTs); (4) the complications or pain score between both
groups were evaluated in the study.
Exclusion criteria were: (1) the study was a letter, review or report;
(2) the study was a non-RCT.
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Journal of Clinical Anesthesia 51 (2018) 20–31
2.3. Data extraction and quality assessment
Study retrieval and inclusion, data extraction and quality assess-
ment was undertaken by two investigators (HFL and RC) in-
dependently. In our analysis, the patients underwent CWI during
postoperative analgesia was designated as control group, while patients
underwent EA during postoperative analgesia was designated as ex-
periment group. After selecting eligible studies, they independently
extracted the required information, including first author name, pub-
lication time, research region, research time, intervention manner, the
case numbers in each group, duration of surgery, demographic char-
acteristic of the cases such as age, sex, body mass index (BMI) and ASA
classification, level of placement of the wound catheter, level of pla-
cement of the epidural catheter, the numbers and types of complica-
tions, static and dynamic pain score after surgery.
Following the data extraction, literature quality assessment was
performed by using Cochrane Collaboration's tool to assess risk of bias
according to Cochrane Collaboration recommendations [16]. Finally,
the two investigators exchanged the information and inconsistent
places were marked. Disagreements were resolved by discussion with a
third assessor (SQY) during the course of study inclusion, data extrac-
tion and literature quality assessment.
2.4. Statistical analysis
The R 3.13 software (R Foundation for Statistical Computing, Beijing1,
China, meta package) was utilized to perform this meta-analysis. The odds
ratio (OR) with its corresponding 95% confidence interval (CI) was used to
measure the effect size of the dichotomous data, and the standardized mean
difference (SMD) with its corresponding 95% CI acted as a measure of effect
size for calculating continuous data. In addition, heterogeneity was ex-
amined by chi-square test based on Q statistic and I2 test [17]. A random
effects model was chosen to calculate the pooled effect size if there was a
significant heterogeneity between the included studies (P < 0.05 or
I2 > 50%), otherwise, a fixed effects model was used [18]. Publication bias
was evaluated by the method of Egger's test according to Cochrane's sug-
gestion [19]. Subgroup analyses were also performed stratified by different
surgeries (Colorectal surgery and Liver resection surgery).
 H. Li et al.

Table 1
Characteristics of the included studies.
Author Public Year Location Study Year Group Surgical type N Age (years) Sex(M) BMI (kg/m2)/Weight, Duration of surgery ASA grade (I/ Complication Postoperative Pain
kg (min) II/III) Scores

Hughes MJ 2015 UK 2012.12–2014.8 EA Liver resection surgery 44 62.6 ± 11.1 29 27.7 ± 4.2 158.77 ± 58.74 3/32/9 31 VAS
CWI 49 62.8 ± 12.1 28 28.5 ± 5.0 161.13 ± 50.34 3/39/7 25
Jouve P 2013 France 2009.10–2012.4 EA Colorectal surgery 24 63 ± 12 13 73 ± 17 NA 5/15/4 2 VNS
CWI 26 68 ± 9 13 68 ± 12 NA 2/18/6 4
Kilic M 2014 Turkey NA EA Hysterectomy 23 53.8 ± 5.5 NA 70.3 ± 12.1 143.5 ± 26.4 NA 13* NRS
CWI 24 51.4 ± 5.3 NA 65.7 ± 10.5 132.2 ± 24.8 NA 8*
Pandazi A 2013 Greece 2008.7–2009.12 EA Total hip arthroplasty 21 NA NA NA NA NA NA VAS
CWI 21 NA NA NA NA NA NA
Revie EJ 2012 UK 2009.8–2010.7 EA Liver resection surgery 31 60 (23–85) 19 24 (18–33) 190 (90–540) 5/20/6 18 MPS
CWI 33 60 (39–84) 17 25 (19–36) 265 (50–550) 2/20/11 16
Zheng X 2016 China 2012.1–2014.3 EA Open gastrectomy 25 62.40 ± 9.69 14 22.90 ± 3.46 268.40 ± 66.67 6/14/5 NA VAS
CWI surgery 25 61.96 ± 12.72 16 22.60 ± 2.27 251.20 ± 63.02 4/18/3 NA
Bertoglio S 2012 Italy 2010.3–2011.8 EA Colorectal surgery 53 64.51 ± 6.66 27 70.62 ± 8.54 158.77 ± 58.74 14/39/0 16 VAS
CWI 53 65.70 ± 7.82 28 73.02 ± 10.65 161.13 ± 50.34 12/41/0 8
Boulind CE 2012 UK 2010.4–2.11.3 EA Colorectal surgery 14 74 ± 8 8 27.9 ± 5.2 NA 12(> I) 3 MPAS
CWI 17 68 ± 12 11 27.1 ± 3.7 NA 11(> I) 3

22
de Almeida MCS 2011 Brazil NA EA Abdominal surgery 19 55.7 ± 10.7 10 NA NA 77(I and II)/ 16 VAS
12
CWI 19 49.9 ± 13 8 NA NA 17(I and II)/2 6
Fant F 2011 Sweden 2007.3–2009.12 EA Radical retropubic 25 63.1(53–71) NA 80.6 ± 11.1 123 ± 33 NA 10 NRS
CWI prostatectomy 25 63.5(54–73) NA 83.7 ± 8.9 113 ± 22 NA 11
O'Neill P 2012 Portugal NA EA Cesarean Delivery 29 NA NA NA NA NA 11 VRS
CWI 29 NA NA NA NA NA 0
Renghi A 2013 Italy 2005.2–2006.2 EA Abdominal Aortic 29 72.2 ± 9.6 26 68.9 ± 10 151.7 ± 43.7 3/15/11 1 VAS
CWI Surgery 30 68.9 ± 10 28 25.2 ± 2.9 164.9 ± 53.3 4/23/3 1
Ranta PO 2006 Sweden NA EA Liver resection surgery 20 28 ± 5 NA 30 ± 3 54 ± 12 I and II 1 NRS
CWI 20 29 ± 6 NA 29 ± 5 53 ± 26 I and II 2
Stefancic L 2013 Croatia 2012–2013 EA Liver resection surgery 14 NA NA NA NA I and II 3 NRS
CWI 15 NA NA NA NA I and II 3
Wong-Lun-Hing 2014 UK 2004.7–2.11.7 EA Liver resection surgery 69 63 (29–84) 42 24.0(20.0–33.5) 260 (150–475) 2/51/13 27 NA
EM CWI 429 63 (21–86) 269 26.0(16.0–44.0) 260 (28–480) 10/320/87 112
Mouawad NJ 2017 USA NA EA Colorectal surgery 44 60.8 ± 12.6 23 29.6 ± 5.9 NA NA NA NPS
CWI 46 59.4 ± 12.2 28 29.1 ± 6.6 NA NA NA

EA: Epidural analgesia; CWI: continuous wound infiltration; VNS: Visual numerical rating scale; NRS: numerical rating scale; ASA grade: American Society of Anesthesiologists;
VAS: visual analog score; *: Number of patients with postoperative nausea; **: Number of patients with postoperative nausea/vomiting; MPS: Mean pain scores; VRS: verbal rating score; MPAS: Memorial Pain Assessment
Card; M: Male; BMI: Body mass index.
Journal of Clinical Anesthesia 51 (2018) 20–31
 H. Li et al.

Table 2
The detailed information of included studies.
Author Surgical type Level of placement of the wound catheter Level of placement of the epidural catheter Type of complications

Bertoglio S colorectal cancer surgery preperitoneal space intervertebral hypotension, surgical wound infection, surgical wound hematoma, and cutaneous
space (from T8 to L1) layer dehiscence
Boulind CE laparoscopic colorectal preperitoneal space preperitoneal space T9–10 or T10–11 anastomotic leak, necrotizing fasciitis and multiple organ failure, postoperative ileus and
resection rectal bleeding
Almeida MCSD elective laparotomy aponeurosis and the deepest portion of the 4 cm below the end of the incision nausea, vomiting, hypotension, pruritus and urinary retention
subcutaneous tissue
Fant F radical retropubic intra-abdominal Th9–12 inter-space infection, nausea or vomiting and hypopnoea
prostatectomy
Hughes MJ open liver resection musculofascial layers T8–T9 bleeding, wound dehiscence, wound infection, hypotension, lower respiratory, tract
infection
urinary retention, ileus, acute kidney injury and arrhythmia
Jouve P open colorectal surgery preperitoneal T9–11 left-sided resection or T8–10 right- anastomotic leakage, wound abscess, intra-abdominal abscess, urinary tract infection and

23
sided resection venous thromboembolism
Kilic M hysterectomy subfascial L2–3 interspace nausea and vomiting
O'Neill P cesarean delivery no detailed information no detailed information nausea/vomiting, Pruritus,
urinary retention
Pandazi A total hip arthroplasty fascia lata, gluteus maximus 27-G pencilpoint spinal needle at L2–L3 or no detailed information
L3–L4 interspaces
Ranta PO cesarean delivery subfascial wound catheters L1–2 interspace nausea and pruritus
Renghi A Fast-Track Abdominal Aortic subfascial and subcutaneous placement T6-T7 hypotension and lipothymia
Surgery
Revie EJ liver resection surgery deep muscle layers T7–8 grade of complications: I, II, IIIa, IIIb, Iva, IVb, V
Stefancic L liver resection in carcinoma fascia epidural space of all patients at the T8–T11 nausea and vomiting
level
Wong-Lun-Hing EM major hepatectomy upper abdominal wall horacic T5–T12 urinary retention, pruritus, hallucinations, dizziness, hypotension requiring treatment,
region acute confused episode, wound infection and urinary retention
Xing Z gastrectomy deep fascia T7–8 no detailed information
Mouawad NJ colorectal cancer surgery preperitoneal space T6-T12 ureteral injury, intra-abdominal hemorrhage, deep venous thrombosis, small bowel injure
Journal of Clinical Anesthesia 51 (2018) 20–31
H. Li et al. Journal of Clinical Anesthesia 51 (2018) 20–31

Fig. 2. Quality assessments of the included studies. A: Bias risk of the identified studies; B: Sensitivity and specificity of the 18 included studies. “+” indicates Low
risk of bias; “?” represents unclear risk of bias; “–”represents high risk of bias.

2.5. Sensitivity analysis 3.2. Quality assessment of the selected studies

In order to evaluate the influence of each included study on the
value of pooled OR or SMD, a sensitivity analysis was performed
through removing one study at one time [20]. If the results were not
obviously reversed, it indicated that the meta-analysis had a good re-
liability.
According to the Cochrane Collaboration's tool, most of the studies
had a low risk of publication bias, except five studies [26, 28, 32–34].
Meanwhile, five studies had a relatively low risk of publication bias at
all items (Fig. 2). Totally, the quality of the articles in the present study
was moderate.

3.3. Outcomes
3. Results
3.3.1. Postoperative complications
3.1. Eligible studies and the characteristics
A total of 14 studies that included 1350 patients (438 in EA group
and 814 in CWI group) had involved the assessment of complications of
Based on the aforementioned strategies, a total of 942 studies were
abscess, bleeding/hematoma, hypotension, ileus, nausea or vomiting,
retrieved after the preliminary selection from PubMed and Embase
pruritus, urinary retention, urinary tract infection, would dehiscence
databases. Then, by scanning titles and reading abstracts, 310 dupli-
and wound infection [21–28, 30–34, 36]. The results of heterogeneity
cates and 483 articles irrelevant with the inclusion criteria were
test showed that there was significant heterogeneity between included
eliminated, and 149 studies were remained. Following further selec-
studies involving nausea or vomiting (I2 = 55%, P = 0.07) and pruritus
tion, another 133 articles (including 9 letters, 19 case reports or series,
(I2 = 83%, P < 0.01). Thus, a random effects model was chosen to
25 literature reviews, 44 animal studies and 31 descriptive researches)
calculate the pooled results. Whereas no notable heterogeneity was
were eliminated. Finally, 16 RCTs were included in the present meta-
found between included studies involving other complications, thus the
analysis [21–36] (Fig. 1).
fixed effects model was used to merge the data. As a result, the in-
As shown in Table 1, all the included articles were published from
cidence of hypotension in EA group was significantly higher than CWI
2006 to 2017, and the articles were come from several countries such as
group (OR = 3.7398; 95% CI: 1.0632 to 13.1555) (Fig. 3), but the in-
UK, France, Turkey, Egypt, Greece and China. Additionally, there were
cidence of abscess, bleeding/hematoma, ileus, nausea or vomiting,
no significant differences on demographic characteristics (such as age,
pruritus, urinary retention, urinary tract infection, would dehiscence
sex and BMI) and duration of surgeries between EA and CWI groups.
and wound infection were not statistically significant in both group.
Moreover, the two groups had no differences according to ASA grade.
In addition, as shown in Table 2, among the included studies, the
placements of wound catheters were mainly inserted into preperitoneal 3.3.2. Postoperative pain score
space, subfascial and subcutaneous placement, deep muscle layers, and The meta-analysis evaluated the pain scores on rest and mobiliza-
deep fascia. The levels of placement of the epidural catheter were tion at 2 h, 6 h, 12 h, 24 h, 48 h and 72 h after surgery, and striking
mainly at the region of T8–12 and L1–4. heterogeneity was detected between studies at 2 h, 6 h, 12 h, 24 h, 48 h

24
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(caption on next page)

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H. Li et al. Journal of Clinical Anesthesia 51 (2018) 20–31

Fig. 3. Forest plot of the postoperative complications in EA and CWI groups. Squares denote the study-specific outcome estimates, and the size of the square
represents the study-specific weight. Horizontal lines and figures in parentheses represent the 95% CI. Diamonds indicate the pooled effect size with the corre-
sponding 95% CI. EA: epidural analgesia; CWI: continuous wound infiltration.

Fig. 4. Forest plot of pain scores on rest and mobilization at 2 h and 6 h after surgery in EA and CWI groups. A: Forest plot of pain score at postoperative 2 h. B: Forest
plot of pain score at postoperative 6 h. EA: epidural analgesia; CWI: continuous wound infiltration. Squares denote the study-specific outcome estimates, and the size
of the square represents the study-specific weight. Horizontal lines and figures in parentheses represent the 95% CI. Diamonds indicate the pooled effect size with the
corresponding 95% CI.

and 72 h after surgery at rest and on mobilization (I2 > 50% and
P < 0.05). Thus, a random effects model was used to calculate pooled
effect size.
There were six studies recorded the pain scores on rest [21, 25–27,
32] and five studies recorded the pain scores on mobilization [21,
25–27, 30, 32] at postoperative 2 h. In addition, a total of eight studies
comprising 480 patients (236 in EA group and 244 in CWI group) [21,
23, 25, 27, 29, 30, 32, 35] and six studies [21, 25, 27, 29, 32, 35]
assessed pain scores on rest and mobilization at postoperative 6 h and
12 h, respectively. Moreover, eleven RCTs and thirteen RCTs involved
postoperative pain at 24 h on mobilization [21, 23–31, 35] and rest
[21–32, 35], respectively. Meanwhile, a total of eight studies examined
the pain scores at postoperative 48 h on mobilization [21, 24–28, 30,
35], and nine studies assessed the scores on rest [21, 22, 24–28, 30, 35].
The results revealed that no remarkable differences in pain scores were
detected between EA and CWI groups on rest and mobilization at
postoperative 2 h (Fig. 4A), 6 h (Fig. 4B), 12 h (Fig. 5A), 24 h (Fig. 5B)
and 48 h (Fig. 6A) (Table 3). Furthermore, four RCTs recorded the pain
scores on rest and mobilization at 72 h postoperatively [21, 25, 26, 30].
Notably, pain scores in EA group was significantly reduced with better
pain relief on rest (SMD = −0.6037; 95% CI: −1.0767 to −0.1308)
than CWI group, while CWI showed no better pain control on mobili-
zation than EA group (Fig. 6B).
3.4. Subgroup analysis
Considering that different surgeries were crucial variables for the
effect evaluation and most included studies were related to liver

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H. Li et al. Journal of Clinical Anesthesia 51 (2018) 20–31

Fig. 5. Forest plot of pain scores on rest and mobilization at 12 h and 24 h after surgery in EA and CWI groups. A: Forest plot of pain score at postoperative 12 h. B:
Forest plot of pain score at postoperative 24 h. EA: epidural analgesia; CWI: continuous wound infiltration. Squares denote the study-specific outcome estimates, and
the size of the square represents the study-specific weight. Horizontal lines and figures in parentheses represent the 95% CI. Diamonds indicate the pooled effect size
with the corresponding 95% CI.

resection and colorectal surgery, thus, subgroup analysis was performed
stratified by above two kind surgeries. As a result, it showed pain scores
in EA group was significantly reduced at 2 h on rest (SMD = −0.9548;
95% CI: −1.8780 to −0.0315) and 12 h on mobilization
(SMD = −0.5879; 95% CI: −0.9091 to −0.2667) than CWI group
after liver resection surgery, while no remarkable differences of pain
scores were found between the two groups after liver resection surgery
at other time on rest or mobilization. Additionally, the pain scores in EA
group were significantly lower in EA group compared to CWI group at
72 h on rest after colorectal surgery (SMD = −0.7720; 95% CI:
−1.4333 to −0.1107), while no notably difference was observed be-
tween the two groups after colorectal surgery at other time on rest or
mobilization (Table 4).
3.5. Sensitive analysis
The sensitive analysis were conducted by eliminating one included study
each time, which reported pain scores on rest and mobilization at post-
operative 2 h, 6 h, 12 h, 24 h, 48 h and 72 h. As a result, the sensitive analysis
showed that the pooled outcomes on rest and mobilization at postoperative
2 h and on rest at postoperative 6 h and 12 h, were altered after omitting
Kilic M's study. In addition, the pooled outcomes on mobilization at post-
operative 6 h were also altered after omitting Kilic M, Almeida MCS and
Bertoglio S's studies. Whereas, the pooled outcomes on rest at postoperative
72 h were reversed while omitted Jouve P, Bertoglio S and Ranta PO ‘s
studies. It indicated that the results at postoperative 2 h, 6 h,12 h and 72 h
were unstable, which might lead by small number of included studies.

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Fig. 6. Forest plot of pain scores on rest and mobilization at 48 h and 72 h after surgery in EA and CWI groups. A: Forest plot of pain score at postoperative 48 h. B:
Forest plot of pain score at postoperative 72 h. EA: epidural analgesia; CWI: continuous wound infiltration. Squares denote the study-specific outcome estimates, and
the size of the square represents the study-specific weight. Horizontal lines and figures in parentheses represent the 95% CI. Diamonds indicate the pooled effect size
with the corresponding 95% CI.

Table 3
The result of meta-analysis.
Time Item Total people Test of association Model Test of heterogeneitya,b Egger's test for publication biasc

EA CWI SMD(95%CI) Z P Q P I2 (%) t P value

2h Mobilization 175 185 −0.2829 [−0.6749; 0.1091] 1.41 0.1572 Random 43.73 0.0098 70.0 0.4845 0.6612
Rest 195 205 −0.6005 [−1.2244; 0.0233] 1.89 0.0592 Random 43.33 < 0.0001 88.6 1.7046 0.1635
6h Mobilization 236 244 −0.3029 [−0.6740; 0.0681] 1.60 0.1096 Random 27.52 < 0.0001 74.6 0.1167 0.9109
Rest 236 244 −0.3155 [−0.7848; 0.1538] 1.32 0.1876 Random 43.27 < 0.0001 83.8 0.5411 0.6079
12 h Mobilization 197 205 −0.1577 [−0.5306; 0.2153] 0.83 0.4073 Random 70.4 0.0047 16.88 0.6667 0.6650
Rest 197 205 −0.3934 [−1.0809; 0.2942] 1.12 0.2621 Random 53.71 < 0.0001 90.7 0.7558 0.4918
24 h Mobilization 312 321 −0.1042 [−0.4993; 0.2909] 0.52 0.6053 Random 58.99 < 0.0001 83 0.1549 0.8803
Rest 357 370 −0.1975 [−0.5303; 0.1354] 1.16 0.2449 Random 57.98 < 0.0001 79.3 0.81823 0.4306
48 h Mobilization 243 251 −0.2998 [−0.9113; 0.3116] 0.96 0.3365 Random 73.91 < 0.0001 90.5 1.5768 0.1659
Rest 257 267 −0.3113 [−0.8631; 0.2406] 1.11 0.2690 Random 72.71 < 0.0001 89 1.1733 0.279
72 h Mobilization 141 148 0.4786 [−0.0685; 1.0257] 1.71 0.0864 Random 14.75 0.0020 79.7 0.6833 0.565
Rest 141 148 −0.6037 [−1.0767; −0.1308] 2.50 0.0124 Random 10.93 0.0121 72.6 1.9787 0.1864

a
Random-effects model was used when the P for heterogeneity test < 0.05, otherwise the fixed-effect model was used.
b
P < 0.05 is considered statistically significant for Q statistics. MD: Mean difference; CI: confidence interval; EA, Epidural analgesia; CWI, continuous wound
infiltration.
c
Egger's test to evaluate publication bias, P-value < 0.05 is considered statistically significant.

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Table 4
The results of subgroup analysis.
Time Item Group K Test of association Model Test of heterogeneitya,b

SMD(95%CI) Q P I2 (%)

2h Mobilization Colorectal surgery 2 −0.2977 [−0.7993;0.2039] Random 2.22 0.14 54.9

Liver resection 2 −0.5291 [−1.3198;0.2617] Random 5.76 0.02 82.6
Rest Colorectal surgery 2 −0.6480 [−1.9626;0.6665] Random 13.11 < 0.01 92.4
Liver resection surgery 3 −0.9548 [−1.8780;−0.0315] Random 17.29 < 0.01 88.4
6h Mobilization Colorectal surgery 1 −0.0992 [−0.4801;0.2818] – 0 – –
Liver resection 2 −0.9419 [−2.0548;0.1711] Random 10.25 < 0.01 90.2
Rest Colorectal surgery 1 0.0000 [−0.3807;0.3807] – 0 – –
Liver resection surgery 2 −0.8264 [−2.1401;0.4874] Random 14.4 < 0.01 93.1
12 h Mobilization Colorectal surgery 1 0.0000 [−0.3807;0.3807] – 0 – –
Liver resection 2 −0.5879 [−0.9091;−0.2667] Fixed 1.76 0.18 43.2
Rest Colorectal surgery 1 0.0000 [−0.3807;0.3807] – 0 – –
Liver resection surgery 2 −0.6929 [−2.0756;0.6899] Random 16.29 < 0.01 93.9
24 h Mobilization Colorectal surgery 2 0.0876 [−0.2271;0.4024] Fixed 1.29 0.26 22.3
Liver resection 2 −0.0961 [−0.7751;0.5829] Random 3.35 0.07 70.2
Rest Colorectal surgery 3 −0.1189 [−0.6582;0.4203] Random 5.88 0.05 66.0
Liver resection surgery 3 −0.1162 [−0.7553;0.5229] Random 9.46 < 0.01 78.9
48 h Mobilization Colorectal surgery 2 −1.1609 [−4.4881;2.1664] Random 55.14 < 0.01 98.2
Liver resection 2 −0.2485 [−0.5907;0.0937] Fixed 0.89 0.35 0.0
Rest Colorectal surgery 3 −0.9108 [−2.6692;0.8476] Random 46.54 < 0.01 95.7
Liver resection surgery 2 −0.2393 [−0.5816;0.1029] Fixed 0.91 0.34 0.0
72 h Mobilization Colorectal surgery 2 0.9200 [−0.1082;1.9481] Random 7.76 0.4811 87.1
Liver resection 2 0.0756 [−0.2648;0.4160] Fixed 0.08 0 0.0
Rest Colorectal surgery 2 −0.7720 [−1.4333;−0.1107] Random 3.46 0.1643 71.1
Liver resection 2 −0.4524 [−1.3171;0.4123] Random 5.05 0.3147 80.2

a
Random-effects model was used when the P for heterogeneity test < 0.05, otherwise the fixed-effect model was used.
b
P < 0.05 is considered statistically significant for Q statistics. MD: Mean difference; CI: confidence interval; EA, Epidural analgesia; CWI, continuous wound
infiltration.

4. Discussion
In this meta-analysis, total 16 RCTs were included to compare the
effect of EA and CWI on patients after surgery. As a result, it demon-
strated that the incidence of complications of patients treated with CWI
in surgery was much lower than EA, but there was no statistically sig-
nificant except for the significant increased risk of hypotension in EA
group. In addition, the pain score was significantly reduced in EA group
than CWI group on rest at postoperative 72 h. Notably, EA showed a
better pain controls than CWI with lower pain score at 2, 12, 24 and 48
postoperative hours on rest and mobilization, but without significant
difference. The subgroup analysis showed that pain scores in EA group
was significantly reduced at 2 h on rest and 12 h on mobilization than
CWI group after liver resection surgery, as well as at 72 h on rest after
colorectal surgery.
Our results demonstrated that hypotension rate reported in EA
group was higher than this observed in CWI group. Marret et al. have
demonstrated EA leads to a significant increase of the incidence of
complications, such as arterial hypotension, urinary retention and
pruritus, compared to parenteral opioid analgesia after colorectal sur-
gery [37]. It also has been reported that hypotensive episodes is an
unexpected complication of EA after major abdominal and thoracic
surgery, which is associated with the application of epidural local an-
esthetics [38]. The high incidence of hypotension in EA than CWI may
be explained by their different anesthesia types. EA is a method that
achieves anesthetic effect via sympathetic nerves block, but it also can
lead to reduced venous return and further blood pressure fall. Whereas,
CWI is a local wound infiltration for nerve endings block. Although in
this study, no significant difference of complications including vo-
miting, nausea, urinary retention, pruritus, urinary tract infection,
would dehiscence and wound infection were found between EA and
CWI groups, the incidence of those complications were all higher in EA
group than in CWI group. Similarly, Ventham et al. have proved that EA
is related to a higher incidence of urinary retention than local anes-
thetic infiltration [15]. O'Neill et al. also find that the incidence of
complications such as vomiting, nausea, urinary retention and pruritus
is significantly higher in EA group than CWI group after cesarean de-
livery [28]. Integrally, our results showed that the incidence of com-
plications of patients treated with CWI after open surgical operations
was much lower than EA.
CWI has been previously proved to be almost equivalent efficacy
with EA for pain management [39]. However, it has been reported that
EA remains the gold standard for abdominal and thoracic surgery [38].
Meanwhile, Ventham et al. have demonstrated that EA has lower pain
scores than CWI on movement at 24 and 48 h, but there was no sta-
tistical significance [15]. Similarly, in the present study, it was shown
that there were no significant differences in pain scores on movement at
24 and 48 h, and on rest 48 h after surgery between the CWI and EA
group. However, the superiority of the EA seemed to provide better
pain relief after surgery on rest at 72 h after surgery in our study. Re-
portedly, the mean pain scores in EA group was statistically lower than
in local anesthetic infiltrating catheter group on the day of hepatic
resection and postoperative day 1 [40]. Similarly, our result of sub-
group analysis showed that EA had better pain relief on postoperative
2 h on rest and 12 h on mobilization than CWI after liver resection
surgery. In addition, EA is superior to intravenous opioid in relieving
postoperative pain for up to 72 h in patients after intra-abdominal
surgery [41]. Moreover, EA can provide significantly better post-
operative analgesia than parenteral opioid analgesia [42]. Furthermore,
Pandazi et al. have proved that pain scores evaluated by visual analog
scale in EA group was significantly lower on mobilization at first 6 h
postoperatively than patient-controlled analgesia group with morphine
[29]. Combined our results of comparison the pain score between EA
and CWI as noted above, EA might provide a better pain control than
CWI after abdominal surgeries. However, which type of anesthesia
technique was taken into account by practitioners evaluating the type
of surgeries and other factors.
There existed significant heterogeneity between the included stu-
dies regarding to pain scores (I2 > 50%), and this may be associated
with different types of surgery, and the utilization of different types or
dose regimens of analgesia. In our work, several different surgeries
were involved such as colorectal cancer surgery [21], laparoscopic

29
H. Li et al.
colorectal resection [22], open liver resection [25] and hysterectomy
[27]. Although postoperative pain is inevitable for each surgery, the
pain intensity is varied based on different surgical procedures and in-
cision sizes [43]. It was complex to compare the pooled effects within
different trials, since the types and dose regimens of analgesia were not
all unified, even types and dose regimens of in both groups for same
surgery were not same in different articles. Thus, different types and
doses of anesthetics were crucial variables for the effect evaluation.
In addition to the significant heterogeneity, our study had some
limitations. Firstly, due to few related information of dose regimens of
analgesics in the included studies was not reported and anesthetics used
varied by different surgeries, subgroup analysis stratified by different
types and dose regimens of analgesics was not incorporated, which
might figure out potential sources of heterogeneity. Secondly, the
sample size was still small. Thirdly, although all the included studies
were RCTs, quality of some was moderate, which might influence the
pooled result to some extent.
In summary, CWI was superior to EA in reducing the risk of com-
plications following surgery. In aspect of pain scores, EA techniques had
better pain relief than CWI techniques on rest at 72 h after surgery.
Those two methods all had their advantages and disadvantages.
Therefore, the current evidence was insufficient to draw systematic
comparisons about the overall effect on postoperative complications
and pain relief of the two methods, and future comparisons should take
place within more high-quality RCTs with large samples.
Acknowledgement
None.
Funding
None.
Conflict of interest
All authors declare that they have no conflicts of interest.
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