Tissue Adhesives For Closure of Surgical Incisions

Tissue adhesives for closure of surgical incisions (Review)
Dumville JC, Coulthard P, Worthington HV, Riley P, Patel N, Darcey J, Esposito M, van der
Elst M, van Waes OJF
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2014, Issue 11
http://www.thecochranelibrary.com

Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . . 3
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
ADDITIONAL SUMMARY OF FINDINGS . . . . . . . . . . . . . . . . . . . . . . . . . . 20
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Analysis 1.1. Comparison 1 Adhesive versus suture, Outcome 1 Dehiscence: all studies. . . . . . . . . . . 97
Analysis 1.2. Comparison 1 Adhesive versus suture, Outcome 2 Dehiscence: sensitivity analysis. . . . . . . . . 99
Analysis 1.3. Comparison 1 Adhesive versus suture, Outcome 3 Infection: all studies. . . . . . . . . . . . 100
Analysis 1.4. Comparison 1 Adhesive versus suture, Outcome 4 Infection: sensitivity analysis. . . . . . . . . 101
Analysis 1.5. Comparison 1 Adhesive versus suture, Outcome 5 Cosmetic appearance rated by patient. . . . . . 102
Analysis 1.6. Comparison 1 Adhesive versus suture, Outcome 6 Cosmetic appearance rated by surgeon. . . . . . 102
Analysis 1.7. Comparison 1 Adhesive versus suture, Outcome 7 Patient/parent satisfaction (% satisfied). . . . . . 103
Analysis 1.8. Comparison 1 Adhesive versus suture, Outcome 8 Patient/parent satisfaction (VAS Scale 0 to 100). . . 103
Analysis 1.9. Comparison 1 Adhesive versus suture, Outcome 9 Surgeon satisfaction (% satisfied). . . . . . . . 104
Analysis 1.10. Comparison 1 Adhesive versus suture, Outcome 10 Time taken for wound closure. . . . . . . . 105
Analysis 2.1. Comparison 2 Adhesive versus adhesive tape, Outcome 1 Dehiscence. . . . . . . . . . . . . 106
Analysis 2.2. Comparison 2 Adhesive versus adhesive tape, Outcome 2 Infection. . . . . . . . . . . . . . 106
Analysis 2.3. Comparison 2 Adhesive versus adhesive tape, Outcome 3 Cosmetic appearance rated by patient (VAS). 107
Analysis 2.4. Comparison 2 Adhesive versus adhesive tape, Outcome 4 Cosmetic appearance rated by patient (%
satisfied). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Analysis 2.5. Comparison 2 Adhesive versus adhesive tape, Outcome 5 Cosmetic appearance rated by surgeon (VAS). 108
Analysis 2.6. Comparison 2 Adhesive versus adhesive tape, Outcome 6 Patient satisfaction. . . . . . . . . . 109
Analysis 2.7. Comparison 2 Adhesive versus adhesive tape, Outcome 7 Surgeon satisfaction. . . . . . . . . . 109
Analysis 2.8. Comparison 2 Adhesive versus adhesive tape, Outcome 8 Time taken for wound closure. . . . . . 110
Analysis 3.1. Comparison 3 Adhesive versus staples, Outcome 1 Dehiscence. . . . . . . . . . . . . . . 110
Analysis 3.2. Comparison 3 Adhesive versus staples, Outcome 2 Infection. . . . . . . . . . . . . . . . 111
Analysis 3.3. Comparison 3 Adhesive versus staples, Outcome 3 Cosmetic appearance rated by patient (scar scale). . 111
Analysis 3.4. Comparison 3 Adhesive versus staples, Outcome 4 Cosmetic appearance by plastic surgeons (VAS). . . 112
Analysis 3.5. Comparison 3 Adhesive versus staples, Outcome 5 Patient satisfaction. . . . . . . . . . . . . 113
Analysis 3.6. Comparison 3 Adhesive versus staples, Outcome 6 Time taken for wound closure. . . . . . . . . 113
Analysis 4.1. Comparison 4 Adhesive versus other method, Outcome 1 Dehiscence. . . . . . . . . . . . . 114
Analysis 4.2. Comparison 4 Adhesive versus other method, Outcome 2 Infection. . . . . . . . . . . . . 114
Analysis 4.3. Comparison 4 Adhesive versus other method, Outcome 3 Patient satisfaction. . . . . . . . . . 115
Analysis 4.4. Comparison 4 Adhesive versus other method, Outcome 4 Clinician satisfaction. . . . . . . . . 116
Analysis 4.5. Comparison 4 Adhesive versus other method, Outcome 5 Time taken for wound closure. . . . . . 116
Analysis 5.1. Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 1 Dehiscence. . 117
Analysis 5.2. Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 2 Infection. . . 117
Analysis 5.3. Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 3 Patient satisfaction. 118
Tissue adhesives for closure of surgical incisions (Review) i
Analysis 5.4. Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 4 Clinician
satisfaction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
Analysis 5.5. Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 5 Time taken for wound
closure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Analysis 6.1. Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 1
Dehiscence. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Analysis 6.2. Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 2
Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Analysis 6.3. Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 3 Cosmetic
assessment rated by patient (VAS). . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Analysis 6.4. Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 4 Cosmetic
assessment rated by surgeon (VAS). . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Analysis 6.5. Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 5 Surgeon
satisfaction (with device). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
Analysis 6.6. Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 6 Surgeon
satisfaction (with closure). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122
Analysis 6.7. Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate, Outcome 7 Time taken
for wound closure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 135
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Tissue adhesives for closure of surgical incisions (Review) ii

[Intervention Review]
Tissue adhesives for closure of surgical incisions
Jo C Dumville1 , Paul Coulthard2 , Helen V Worthington3 , Philip Riley3 , Neil Patel4 , James Darcey2 , Marco Esposito3 , Maarten van
der Elst5 , Oscar J F van Waes5
1 School of Nursing, Midwifery and Social Work, University of Manchester, Manchester, UK. 2 Department of Oral and Maxillofacial
Surgery, School of Dentistry, The University of Manchester, Manchester, UK. 3 Cochrane Oral Health Group, School of Dentistry, The
University of Manchester, Manchester, UK. 4 Oral Surgery, University Dental Hospital of Manchester, Manchester, UK. 5 Department
of Surgery, Reinier de Graaf Groep, Delft, Netherlands
Contact address: Jo C Dumville, School of Nursing, Midwifery and Social Work, University of Manchester, Manchester, M13 9PL,
UK. jo.dumville@manchester.ac.uk.
Editorial group: Cochrane Wounds Group.

Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 11, 2014.
Review content assessed as up-to-date: 12 March 2014.
Citation: Dumville JC, Coulthard P, Worthington HV, Riley P, Patel N, Darcey J, Esposito M, van der Elst M, van Waes OJF.
Tissue adhesives for closure of surgical incisions. Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD004287. DOI:
10.1002/14651858.CD004287.pub4.
ABSTRACT
Background
Sutures (stitches), staples and adhesive tapes have been used for many years as methods of wound closure, but tissue adhesives have
entered clinical practice more recently. Closure of wounds with sutures enables the closure to be meticulous, but the sutures may
show tissue reactivity and can require removal. Tissue adhesives offer the advantages of an absence of risk of needlestick injury and no
requirement to remove sutures later. Initially, tissue adhesives were used primarily in emergency room settings, but this review looks
at the use of tissue adhesives in the operating room/theatre where surgeons are using them increasingly for the closure of surgical skin
incisions.
Objectives
To determine the effects of various tissue adhesives compared with conventional skin closure techniques for the closure of surgical
wounds.
Search methods
In March 2014 for this second update we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register
of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed
Citations); Ovid EMBASE and EBSCO CINAHL. We did not restrict the search and study selection with respect to language, date of
publication or study setting.
Selection criteria
Only randomised controlled trials were eligible for inclusion.
Data collection and analysis
We conducted screening of eligible studies, data extraction and risk of bias assessment independently and in duplicate. We expressed
results as random-effects models using mean difference for continuous outcomes and risk ratios (RR) with 95% confidence intervals
(CI) for dichotomous outcomes. We investigated heterogeneity, including both clinical and methodological factors.
Tissue adhesives for closure of surgical incisions (Review) 1
Main results
This second update of the review identified 19 additional eligible trials resulting in a total of 33 studies (2793 participants) that met
the inclusion criteria. There was low quality evidence that sutures were significantly better than tissue adhesives for reducing the risk of
wound breakdown (dehiscence; RR 3.35; 95% CI 1.53 to 7.33; 10 trials, 736 participants that contributed data to the meta-analysis).
The number needed to treat for an additional harmful outcome was calculated as 43. For all other outcomes - infection, patient and
operator satisfaction and cost - there was no evidence of a difference for either sutures or tissue adhesives. No evidence of differences was
found between tissue adhesives and tapes for minimising dehiscence, infection, patients’ assessment of cosmetic appearance, patient
satisfaction or surgeon satisfaction. However there was evidence in favour of using tape for surgeons’ assessment of cosmetic appearance
(mean difference (VAS 0 to 100) 9.56 (95% CI 4.74 to 14.37; 2 trials, 139 participants). One trial compared tissue adhesives with
a variety of methods of wound closure and found both patients and clinicians were significantly more satisfied with the alternative
closure methods than the adhesives. There appeared to be little difference in outcome for different types of tissue adhesives. One study
that compared high viscosity with low viscosity adhesives found that high viscosity adhesives were less time-consuming to use than low
viscosity tissue adhesives, but the time difference was small.
Authors’ conclusions
Sutures are significantly better than tissue adhesives for minimising dehiscence. In some cases tissue adhesives may be quicker to apply
than sutures. Although surgeons may consider the use of tissue adhesives as an alternative to other methods of surgical site closure in
the operating theatre, they need to be aware that sutures minimise dehiscence. There is a need for more well designed randomised
controlled trials comparing tissue adhesives with alternative methods of closure. These trials should include people whose health may
interfere with wound healing and surgical sites of high tension.
PLAIN LANGUAGE SUMMARY

Tissue adhesives for closure of surgical skin incisions
Tissue adhesives or glues are increasingly used in place of stitches (sutures) or staples to close wounds. It has been suggested that tissue
adhesives may be quicker and easier to use than sutures for closing surgical wounds. Tissue adhesives carry no risk of sharps injury
- unlike needles that are used for sutures - and are thought to provide a barrier to infection. This may mean that they also promote
healing, and the need for removal of sutures is avoided.
The researchers searched the medical literature up to March 2014, and identified 33 medical studies that investigated the use of tissue
adhesives for closure of wounds. They compared tissue adhesive with another method of closure such as sutures, staples, tape, or another
type of tissue adhesive. The main outcomes of interest were whether wounds stayed closed - and did not break down - and whether
they became infected. The results of the review showed clearly that fewer wounds broke down when sutures were used. Studies also
reported that some types of tissue adhesives might be slightly quicker to use than other types. There was no clear difference between
tissue adhesives and the alternative closure methods for cosmetic results or costs. Results regarding surgeons’ and patients’ preferred
skin closure method were mixed.

Tissue adhesives for closure of surgical incisions (Review) S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation]
Tissue adhesive compared to sutures for surgical incisions
Patient or population: People with surgical incisions

Settings:
Intervention: Tissue adhesive
Comparison: Sutures
Outcomes Illustrative comparative risks*4 (95% CI) Relative effect No of participants Quality of the evidence Comments
(95% CI) (studies) (GRADE)
Assumed risk Corresponding risk
Sutures Tissue adhesive
Wound dehiscence Study population RR 3.35 736 ⊕⊕

(1.53 to 7.32) (10 studies) low1,2
13 per 1000 45 per 1000
(21 to 99)
Moderate
Wound infection Study population RR 1.72 744 ⊕

(0.92 to 3.16) 10 studies very low2,3
38 per 1000 76 per 1000
(14 to 397)
Moderate
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the
assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
CI: Confidence interval; RR: Risk ratio
3
GRADE Working Group grades of evidence

High quality: further research is very unlikely to change our confidence in the estimate of effect
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low quality: we are very uncertain about the estimate
1 Possible unit of analyses issues. A sensitivity analysis changes a statistically significant difference to a non-statistically significant
difference
2
Study 95% CIs are wide
3 Possible unit of analysis issues
4 Median control (suture) group risk across studies
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4
BACKGROUND Why it is important to do this review
It is important that clinical decision-makers are able to make evi-
dence-informed decisions regarding the use of tissue adhesives to
Description of the condition close surgical incisions. This review was first published in 2004.
As tissue adhesives become more widely used, more randomised
Millions of surgical procedures are conducted around the world
controlled trials are conducted, and this update is required to in-
each year. The majority of procedures result in surgical wounds
corporate this new evidence.
that will heal by primary intention - this is where wound edges are
brought together (re-approximated) and held together, e.g. with
sutures, to facilitate tissue healing.
OBJECTIVES
Description of the intervention To determine the effects of various tissue adhesives compared with
In the past the options for wound closure have been limited largely conventional skin closure techniques for the closure of surgical
to sutures (needle and thread) with other alternatives such as sta- wounds.
ples, adhesive tapes and tissue adhesives entering clinical practice
more recently. Closure of wounds with sutures enables meticulous
closure, but skin may react to sutures and they usually require METHODS
removal. Tissue adhesives (glues) offer the advantages that suture
removal is not required at a later date and there is no risk of needle-
stick injury to the surgeon or assistant. Criteria for considering studies for this review
Tissue adhesives have been used in various forms for many years
since the first cyanoacrylate adhesives were synthesised (Coover
1959). The early adhesives were appropriate for small superficial Types of studies
lacerations and incisions, but their limited physical properties pre-
Randomised controlled trials (RCTs).
vented use in the management of other wounds. There were also
reports of acute and chronic inflammatory reactions (Houston
1969). Further development led to the introduction of the n-2- Types of participants
butylcyanoacrlyates that were purer and stronger, but did not re-
People of any age and in any setting requiring closure of a surgical
ceive widespread acceptance because their clinical performance
skin incision of any length.
was limited by their low tensile strength and brittleness (Bruns
1996; Quinn 1993). More recently stronger tissue adhesives have
been developed by combining plasticisers and stabilisers to increase Types of interventions
flexibility and reduce toxicity (Quinn 1997). Surgical skin incision closure with tissue adhesive compared with
Tissue adhesives have been used primarily in emergency rooms and another tissue adhesive or any alternative conventional closure
there is increasing support in the literature for their effectiveness in device such as sutures, staples or adhesive tapes (e.g. Steri-Strips/
the closure of various traumatic lacerations (Farion 2001; Osmond butterfly stitches).
1999; Perron 2000; Quinn 1997). Surgeons now also use tissue
adhesives in the operating room for the closure of surgical skin
incisions. Types of outcome measures
Primary outcomes
How the intervention might work
• Proportion of wounds that break down (wound
The introduction of tissue adhesives was received enthusiastically dehiscence).
as they may produce equivalent tensile strength, improved cos-
metic appearance of the scar and a lower infection rate when com-
pared with sutures, staples and adhesive tapes, while avoiding many Secondary outcomes
of the risks and disadvantages of alternative methods (Osmond • Proportion of infected wounds (using the study
1999). As with standard adhesives, tissue adhesives are applied to investigator’s diagnosis of infection).
the wound in a liquid form - following application they undergo • Cosmetic appearance at or after three months where the
polymerisation and bonding and setting occurs. investigator has used a validated measure.

• Patient (or in the case of studies performed with #13 MeSH descriptor: [Acrylates] explode all trees 1757
participants under the age of 16 years, parents’) general #14 acrylate* 254
satisfaction with skin incision closure technique (this is more #15 MeSH descriptor: [Bucrylate] explode all trees 0
than cosmetic appearance as other factors such as suture removal #16 bucrylate* 6
experience may have an input). #17 #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #
• Surgeon satisfaction with skin incision closure technique 13 or #14 or #15 or #16 2397
(this may take into account the time for surgeon to close skin #18 #3 and #17 225
incision amongst other factors). The search strategies for Ovid MEDLINE, Ovid EMBASE and
• Relative cost of materials required for the skin incision Ovid CINAHL can be found in Appendix 3, Appendix 4 and
closure techniques being compared (this will be reported in a Appendix 5 respectively. The Ovid MEDLINE search was com-
narrative form). bined with the Cochrane Highly Sensitive Search Strategy for
• Time taken to wound closure (at end of surgery) has been identifying randomised trials in MEDLINE: sensitivity- and pre-
added to the review as a post hoc outcome measure. The review cision-maximizing version (2008 revision); (Lefebvre 2011). We
authors believe this to be a contributory factor towards both combined the EMBASE search with the Ovid EMBASE filter de-
cost-effectiveness and satisfaction. veloped by the UK Cochrane Centre (Lefebvre 2011). We com-
bined the CINAHL searches with the trial filters developed by the
Scottish Intercollegiate Guidelines Network (SIGN 2011).
Search methods for identification of studies
For an outline of the search methods used in the original version Searching other resources
of this review see Appendix 1 The reviewers checked the bibliographies of new studies included
For an outline of the search methods used in the first update of in this updated review for potentially eligible references that had
this review see Appendix 2. not been identified in the electronic searches outlined above.
Electronic searches
For this second update in March 2014 we searched the following Data collection and analysis
electronic databases:
• Cochrane Wounds Group Specialised Register (searched 13
Selection of studies
March 2014);
• The Cochrane Central Register of Controlled Trials Two review authors independently examined the titles and ab-
(CENTRAL; The Cochrane Library 2014 Issue 1); stracts of all the articles identified by the search to identify poten-
• Ovid MEDLINE (1946 to March Week 1 2014); tially relevant trials and then assessed the full text of these arti-
• Ovid MEDLINE (In-Process & Other Non-Indexed cles independently using a standardised form to check for eligibil-
Citations, 12 March 2014); ity in the review. Disagreements about inclusion were resolved by
• Ovid EMBASE (1974 to 12 March 2014); consensus or a further review author where necessary. Two review
• EBSCO CINAHL (1982 to 13 March 2014). authors performed validity assessment and data extraction on all
studies meeting the inclusion criteria. Studies rejected at this stage
The following strategy was used to search the Cochrane Central were recorded in a table of excluded studies and reasons for exclu-
Register of Controlled Trials (CENTRAL): sion recorded.
#1 MeSH descriptor: [Wounds and Injuries] explode all trees
15958
#2 surgical next wound* 3679 Data extraction and management
#3 #1 or #2 19357 Data were extracted by at least two review authors independently
#4 MeSH descriptor: [Tissue Adhesives] explode all trees 387 using specially designed data extraction forms. The data extraction
#5 MeSH descriptor: [Fibrin Tissue Adhesive] explode all trees forms were piloted on several papers and modified as required
329 before use. Any disagreements were resolved by discussion and
#6 tissue next adhesive* 655 third review author consulted where necessary. All study authors
#7 MeSH descriptor: [Cyanoacrylates] explode all trees 154 were contacted for clarification, or to request missing information
#8 octylcyanoacrylate* 52 where necessary. Data were excluded if further clarification could
#9 Dermabond 44 not be obtained.
#10 MeSH descriptor: [Enbucrilate] explode all trees 42 For each trial the following data were recorded:
#11 enbucrilate 62 • year of publication, country of origin and source of study
#12 butylcyanoacrylate* 7 funding;

• details of the participants including demographic The reviewers intended to meta-analyse the results of trials with
characteristics and criteria for inclusion; a split wound (different parts of the same wound randomised to
• details of the type of intervention (adhesive, suture, staples alternate treatments), and split body designs (different wounds on
or adhesive tape) and type of adhesive (butylcyanoacrylate or the same participant randomised to alternative treatments) using
octylcyanoacrylate); the inverse variance method for paired data if appropriate data
• details of the outcomes reported, including method of were available.
assessment and time intervals. Cosmetic appearance was included
if the authors stated that was measured on a validated scale.
’Summary of findings’ tables
Assessment of risk of bias in included studies In this second update we also present the main results of the review
Two review authors independently assessed each eligible study for in ’Summary of findings’ tables. These tables present key informa-
risk of bias using the Cochrane ‘Risk of bias assessment tool’. The tion concerning the quality of the evidence, the magnitude of the
tool addresses six specific domains (see Appendix 6), namely se- effects of the interventions examined, and the sum of the available
quence generation, allocation concealment, blinding, incomplete data for the main outcomes (Schunemann 2011a). The ’Summary
outcome data, selective outcome reporting and other issues that of findings’ tables also include an overall grading of the evidence
may potentially bias the study (Higgins 2011). They completed a related to each of the main outcomes using the GRADE (Grades
‘Risk of bias’ table for each eligible study, and a separate assessment of Recommendation, Assessment, Development and Evaluation)
of blinding and completeness of outcome data for each outcome. approach. The GRADE approach defines the quality of a body of
Discrepancies between review authors were resolved through dis- evidence as the extent to which one can be confident that an esti-
cussion. Findings are presented using the ‘Risk of bias’ summary mate of effect or association is close to the true quantity of specific
figure, which presents all of the judgements in a cross-tabulation interest. The quality of a body of evidence involves consideration
of study by risk of bias domain. of within-trial risk of bias (methodological quality), directness of
evidence, heterogeneity, precision of effect estimates and risk of
publication bias (Schunemann 2011b). We present the following
Assessment of heterogeneity outcomes in the ’Summary of findings’ tables:
This assessment of clinical and methodological heterogeneity will • wound dehiscence;
be supplemented by information regarding statistical heterogene- • wound infection.
ity - assessed using the Chi² test (a significance level of P less than
0.10 will be considered to indicate statistically significant hetero-
geneity in conjunction with I² measure; Higgins 2003). I² exam- Subgroup analysis and investigation of heterogeneity
ines the percentage of total variation across RCTs that is due to The reviewers intended to undertake a subgroup analysis of age
heterogeneity rather than chance. In general I² values of 25%, or (under 18 years and 18 years or older), location of incision on
less, may mean a low level of heterogeneity, and values of 75%, or body (face and body), length of incision (less than 4 cm and 4 cm
more, indicate very high heterogeneity (Deeks 2011). or greater), and patient characteristics such as diabetes and source
of trial funding (commercially or independently funded), however
Data synthesis there were insufficient studies reporting these data to undertake
these analyses.
For dichotomous outcomes, the reviewers used risk ratios (RR) to
express estimates of effect of an intervention, together with 95%
confidence intervals (CI). For continuous outcomes, the reviewers
Sensitivity analysis
used mean differences and standard deviations to summarize the
data for each group. Where there were studies of similar compar- Where possible we planned to undertake a sensitivity analysis to
isons reporting the same outcome measures, we attempted a meta- examine the effect of randomisation, allocation concealment and
analysis. Risk ratios were combined for dichotomous data, and blinded outcome assessment on the overall estimates of effect. In
weighted mean differences (WMD) for continuous data, using a addition, we also planned a sensitivity analysis to examine the
random-effects model (indicated as RE in the results section) as effect of including unpublished literature on the review’s findings.
some heterogeneity between studies was anticipated. We planned In this second update of the review we conducted a post-hoc sen-
to analyse time taken to close wound (after surgery) as survival sitivity analysis where we removed studies from key analyses where
(time-to-event) data, using the appropriate analytical method (as we had concerns about possible unit of analysis issues (i.e. where
per the Cochrane Reviewers’ Handbook guidance Deeks 2011), dehiscence and infection had been recorded over multiple time
or as a continuous outcome, if data from all participants were periods and it was not clear from the analyses whether some par-
available. ticipants had more than one event).

RESULTS UK (Dowson 2006; Jallali 2004; Keng 1989; Kent 2014;
Krishnamoorthy 2009; Livesey 2009; Ridgway 2007; Sinha
2001), USA (Brown 2009; Eggers 2011; Greene 1999; Kouba
Description of studies 2011; Maloney 2013; Sebesta 2004; Sniezek 2007; Switzer 2003;
Tierny 2009; Toriumi 1998), and one was multicentre and inter-
See Characteristics of included studies; Characteristics of excluded national (Blondeel 2004). All studies included adults, except for
studies and Characteristics of studies awaiting classification . six that included children (Brown 2009; Cheng 1997; Ong 2002;
Romero 2011; Toriumi 1998; van den Ende 2004). All trials were
Characteristics of the trial setting and investigators of parallel group design except for two that had a split body design
(different wounds on same participant randomised; Greene 1999;
In the original review, of the 22 potentially eligible studies of
Kouba 2011), and two that had a split wound design (different
which eight were excluded (Alhopuro 1976; Gorozpe-Calvillo
portions of the same wound randomised; Sniezek 2007; Tierny
1999; Jaibaji 2000; Kuo 2006; Orozco-Razon 2002; Singer 2002;
2009). Kent 2014 randomised participants with multiple wounds
Silvestri 2006; Steiner 2000) and 14 were included (Blondeel
(port sites) to treatments - with all wounds on the participant re-
2004; Cheng 1997; Dowson 2006; Greene 1999; Keng 1989;
ceiving the same intervention. Some outcome data were presented
Maartense 2002; Ong 2002; Ozturan 2001; Ridgway 2007;
by wound rather than at the participant level, thus potentially fail-
Shamiyeh 2001; Sinha 2001; Sniezek 2007; Switzer 2003; Toriumi
ing to account for clustering.
1998). We excluded one study because no data were presented and
Five included trials had more than two arms: Eggers 2011 had four
none were received after we sent a written request to the authors
arms and compared two tissue adhesives, staples and sutures for
(Alhopuro 1976). Another study was excluded as we could not
skin closure; Khan 2006 had three arms comparing tissue adhe-
use the data for incision closure because they were combined with
sive, sutures and staples; Maartense 2002 and Shamiyeh 2001 had
data for laceration closure (Singer 2002); we wrote to the authors
three arms comparing tissue adhesive, sutures and adhesive tape,
to request data separated by group, but received no reply. The
and Blondeel 2004 compared two types of tissue adhesive with
third study was excluded because after full translation we discov-
each other and also other non-tissue adhesive closure techniques
ered not to be a randomised trial (Gorozpe-Calvillo 1999). We
(a mixed comparison group). These studies are thus included in
excluded two papers because their methodology was flawed. The
multiple comparisons.
first of these was excluded because the intervention group had a
subcuticular suture in place that was thought to bias the outcome
in favour of the intervention (Jaibaji 2000). The second was ex- Characteristics of interventions
cluded because all participants had a subcuticular suture placed In total 24 of the 33 included studies compared tissue adhe-
and the review authors thought this adjunct method of closure sive with sutures for incision closure (Avsar 2009; Brown 2009;
would invalidate an independent assessment of the primary inter- Cheng 1997; Dowson 2006; Eggers 2011; Greene 1999; Jallali
ventions (Kuo 2006). Three further studies were excluded, as two 2004; Keng 1989; Khan 2006; Kouba 2011; Krishnamoorthy
were not randomised (Silvestri 2006; Steiner 2000), and the third 2009; Maartense 2002; Millan 2011; Mota 2009; Ong 2002;
did not appear to be randomised, and although we sought clarifi- Ozturan 2001; Sebesta 2004; Shamiyeh 2001; Sinha 2001;
cation from the trial authors, no reply was received (Orozco-Razon Sniezek 2007, Switzer 2003; Tierny 2009; Toriumi 1998; van
2002). In the current update of this review we obtained full text den Ende 2004). Three trials compared tissue adhesive with ad-
for a total of 36 potentially eligible new studies. Twelve of these hesive tape (Maartense 2002; Romero 2011; Shamiyeh 2001).
were excluded: three because they did not assess a relevant wound One of these studies also compared tissue adhesive with su-
type - e.g. lacerations (Ak 2012; Quinn 1998; Wong 2011); three tures (Maartense 2002). Six trials compared adhesives with sta-
because the studies did not report relevant outcomes (Chen 2010; ples (Amin 2009; Eggers 2011; Khan 2006; Livesey 2009; Pronio
Chow 2010; Sun 2005); five were not considered to be RCTs (Giri 2011; Ridgway 2007). Three trials compared one type of tissue
2004; Matin 2003; Maw 1997; Spencker 2011; Sajid 2009), and adhesive with another type (Blondeel 2004; Kent 2014; Maloney
one study because the closure approach was not the only system- 2013). Chibbaro 2009 compared a tissue adhesive with a compar-
atic difference between groups (Ong 2010). We included 19 new ison arm where staples or sutures were used and Blondeel 2004
studies in this update, which led to a total of 33 included studies. compared tissue adhesives with any other skin closure techniques.
Five additional studies are awaiting assessment. These comparisons are summarised in Table 1.
The 33 included studies were conducted in Austria (Shamiyeh
2001), Hong Kong (Cheng 1997), the Netherlands (Maartense
2002; van den Ende 2004), Turkey (Avsar 2009; Ozturan Comparison 1: Tissue adhesive compared with sutures
2001), Ireland (Amin 2009), Italy (Chibbaro 2009; Pronio
2011), Austalia (Khan 2006), Mexico (Millan 2011), Portugal
Butylcyanoacrylate versus sutures
(Mota 2009), Germany (Romero 2011), China (Ong 2002);

Seven studies investigated the use of butylcyanoacrylate compared • Jallali 2004 compared octylcyanoacrylate tissue adhesive
with sutures (Cheng 1997; Dowson 2006; Eggers 2011; Keng with absorbable sutures in people undergoing laparoscopic
1989; Ozturan 2001; Sinha 2001; van den Ende 2004). cholecystectomy.
• Cheng 1997 compared butylcyanoacrylate tissue adhesive • Khan 2006 compared octylcyanoacrylate tissue adhesive
with 4.0 catgut suture in boys under 12 years of age requiring with Monocryl sutures in people undergoing either a total knee
elective circumcision. arthroplasty or a total hip arthroplasty.
• Dowson 2006 compared butylcyanoacrylate tissue adhesive • Krishnamoorthy 2009 compared octylcyanoacrylate tissue
with interruptible, non-absorbable suture after laparoscopic adhesive with absorbable sutures in people undergoing
procedures. saphenous vein harvesting.
• Eggers 2011 was a four-arm trial in participants undergoing • Maartense 2002 compared octylcyanoacrylate tissue
total knee arthroplasty, with one arm receiving adhesive with intracutaneous poliglecaprone interrupted sutures
butylcyanoacrylate tissue adhesive and one receiving Monocryl in people requiring elective laparoscopic procedures.
sutures. • Millan 2011 compared cyanoacrylate tissue adhesive (no
• Keng 1989 investigated butylcyanoacrylate in patients further details available) compared with monofilament sutures in
requiring groin incisions. Skin incisions were closed with either people undergoing skin biopsies.
butylcyanoacrylate tissue adhesive or Dexon subcuticular • Mota 2009 compared octylcyanoacrylate tissue adhesive
sutures. Three of the 43 patients had bilateral operations when with rapidly absorbably polyglactin sutures in women
the left side was closed with adhesive (butylcyanoacrylate) and undergoing mediolateral episiotomy after a vaginal delivery.
the right with sutures. • Sebesta 2004 compared octylcyanoacrylate with
• Ozturan 2001) compared butylcyanoacrylate tissue subcuticular suture in people who had undergone laparoscopic
adhesive with 6.0 polypropylene sutures for columellar skin surgery.
closure after the majority of the tension had been taken up using • Shamiyeh 2001 compared octylcyanoacrylate tissue
5.0 chromic catgut. adhesive with 5.0 monofilament sutures in patients requiring
• Sinha 2001 compared butylcyanoacrylate tissue adhesive mini-phlebectomy with the Muller technique. This study also
with 4.0 monofilament suture in adult patients requiring hand compared tissue adhesive with adhesive tape.
or wrist surgery. • Switzer 2003 compared octylcyanoacrylate tissue adhesive
• van den Ende 2004 compared butylcyanoacrylate tissue with a subcuticular Monocryl suture for the elective repair of
adhesive with polyglactin 5-0 (Vicryl) suture in children inguinal hernias. Ong 2002 also compared octylcyanoacrylate
undergoing inguinal hernia repair. with a Monocryl subcuticular suture, but in children requiring
herniotomies.
Octylcyanoacrylate versus sutures • Sniezek 2007 followed a split wound design comparing
octylcyanoacrylate with a cuticular polypropylene suture on head
Eighteen studies investigated the use of octylcyanoacrylate tis-
and neck surgical sites following the removal of carcinomas using
sue adhesives versus sutures (Avsar 2009; Brown 2009; Eggers
the Mohs technique.
2011; Greene 1999; Jallali 2004; Khan 2006; Kouba 2011;
• Tierny 2009 compared octylcyanoacrylate tissue adhesive
Krishnamoorthy 2009; Maartense 2002; Millan 2011; Mota
with rapid absorbing gut sutures in people undergoing surgery
2009; Ong 2002; Sebesta 2004; Shamiyeh 2001; Sniezek 2007;
for non-melanomas skin cancer.
Switzer 2003; Tierny 2009; Toriumi 1998).
• Toriumi 1998 investigated incisions with and without
• Avsar 2009 compared high viscosity octylcyanoacrylate
subcutaneous sutures and then randomised for closure with
tissue adhesive with polypropylene sutures in women undergoing
octylcyanoacrylate tissue adhesive or 5.0 or 6.0 nylon suture in
the Pfannenstiel incision in the abdomen.
people over one year of age and over requiring elective surgery
• Brown 2009 compared octylcyanoacrylate tissue adhesive
for benign skin lesions predominantly in the face and neck.
with Monocryl sutures in children undergoing inguinal
herniorrhaphy.
• Eggers 2011 compared octylcyanoacrylate tissue adhesive Comparison 2: Tissue adhesives compared with adhesive
with monocryl sutures in people undergoing total knee tape
arthroplasty.
• Greene 1999 and Kouba 2011 randomised participants
requiring bilateral blepharoplasty. This model with two identical
skin sites on the same patient allowed a split-body study design Octylcyanoacrylate versus adhesive tape
and each participant to act as his or her own control. The left or Three studies compared octylcyanoacrylate tissue adhesive with
right upper eye lid was closed with octylcyanoacrylate and the adhesive tapes.
other eyelid closed with 6.0 suture.

• Shamiyeh 2001 compared octylcyanoacrylate tissue Butylcyanoacrylate versus mixture of other closure approaches
adhesive with tape in adults requiring mini-phlebectomy with • Chibbaro 2009 compared a group allocated to
the Muller technique. butylcyanoacrylate tissue adhesive with a group allocated to
• Maartense 2002 compared octylcyanoacrylate tissue receive either sutures or staples for skin closure - based on
adhesive to 76 mm x 6 mm adhesive paper (Steri-Strips) in clinician choice - in people undergoing elective cranial
people undergoing elective laparoscopic surgery. supratentorial surgery.
• Romero 2011 compared octylcyanoacrylate tissue adhesive
with standard adhesive strips (strips applied in star-shaped
manner) in children undergoing laparoscopic appendectomy. Comparison 5: Tissue adhesive compared with tissue
adhesive
Comparison 3: Tissue adhesives compared with staples
High versus low viscosity adhesives

Butylcyanoacrylate versus staples
• Blondeel 2004 compared high and low viscosity adhesive in
Two studies compared butylcyanoacrylate tissue adhesive with sta- the trial described above.
ples.
• Livesey 2009 compared butylcyanoacrylate tissue adhesive
with staples in people undergoing a total hip replacement. Octylcyanoacrylate versus butylcyanoacrylate
• Eggers 2011 compared butylcyanoacrylate tissue adhesive
Three studies compared octylcyanoacrylate tissue adhesive with
with staples in people undergoing total knee arthroplasty.
butylcyanoacrylate tissue adhesive for skin closure.
• Eggers 2011 compared these tissue adhesives in people
Octylcyanoacrylate versus staples undergoing total knee arthroplasty.
Five studies compared octylcyanoacrylate tissue adhesives with sta- • Kent 2014 compared these tissue adhesives in people
ples. undergoing a range of laparoscopic procedures.
• Ridgway 2007 compared octylcyanoacrylate tissue adhesives • Maloney 2013 compared these tissue adhesives in people
with staples in people requiring thyroid and parathyroid surgery. undergoing a skin incision to remove skin cancer.
• Eggers 2011 compared octylcyanoacrylate tissue adhesives
with staples in participants undergoing total knee arthroplasty.
• Amin 2009 compared octylcyanoacrylate tissue adhesives Characteristics of outcome measures
with staples in people undergoing minimally invasive
thyroidectomy.
• Khan 2006 compared octylcyanoacrylate tissue adhesives Wound dehiscence
with staples in people undergoing either a total knee arthroplasty
Twenty-three studies reported wound dehiscence. The time of
or a total hip arthroplasty.
post-operative wound examination for dehiscence varied between
• Pronio 2011 compared octylcyanoacrylate tissue adhesives
studies. Cheng 1997 reported dehiscence at days 1, 2, 3, 7 and 30;
with staples in people undergoing thyroid surgery.
Toriumi 1998 reported dehiscence at 5 to 7 days; Chibbaro 2009,
Ozturan 2001, Pronio 2011, Sniezek 2007 and Tierny 2009 at 7
Comparison 4: Tissue adhesives compared with other days; Shamiyeh 2001 and van den Ende 2004 at 10 days; Greene
techniques 1999 at weeks 1, 2 and 4; and Sinha 2001 at 10 days, 2 weeks
and 6 weeks. Ong 2002 assessed dehiscence at 2 to 3 weeks; Keng
1989 and Sebesta 2004 at 2 weeks; Dowson 2006 at day 1, 2 and
Octylcyanoacrylate versus mixture of other closure at 4 to 6 weeks; Switzer 2003 at 2 and 4 weeks; Blondeel 2004 at
approaches day 10; Brown 2009 at 6 weeks; Eggers 2011 at 24 hours, 3 weeks
• Blondeel 2004 was the only study that investigated the use and 6 weeks; Maloney 2013 at 2 weeks and 3 months; Mota 2009
of tissue adhesives in incisions of 4 cm or longer. High viscosity from 42 hours to 68 hours; Romero 2011 at day 10 and day 90;
octylcyanoacrylate tissue adhesive was compared with any other and Millan 2011 on days 5, 7, 10 and 14.
commercially available device such as sutures, staples or tapes We felt there were potential unit of analysis issues in four studies
and also compared with low viscosity octylcyanoacrylate. The where it was not clear whether one person had more than one
high viscosity formulation is six-times more viscous than the episode of dehiscence over multiple time periods (Cheng 1997;
normal adhesive and designed to reduce run-off of pre- Eggers 2011; Millan 2011; Sinha 2001). We acknowledged this in
polymerised adhesive from the application site. the ’Risk of bias’ assessment and sensitivity analysis we conducted.

Wound infection tionnaire. Surgical residents who were blinded to the wound clo-
In total 25 studies measured wound infection. One study noted sure method also scored the cosmetic appearance with a VAS and
infection, defined as wound discharge with positive bacterial cul- the Hollander Wound Evaluation Score (Hollander 1995). These
ture, at days 1, 2, 3, 7 and 30 (Cheng 1997). A second study de- assessments were undertaken at two weeks and three months (with
fined infection as the presence of pus (Keng 1989), and examined three month data presented). Ozturan 2001 reported cosmetic ap-
wounds at 1 and 4 weeks postoperatively. A third study defined pearance at 3 months by blinded assessment of photographs using
infection as an abscess that required drainage (Ozturan 2001), and VAS, with best possible scar rated as 100 and worst possible scar
examined wounds at 1 week. A fourth study defined infection as as 0 (Quinn 1995), and the Hollander Scale. A third study also
a spontaneous drainage of purulent fluid (Maartense 2002), and reported surgeon-assessed cosmetic appearance at three months
noted this at 2 weeks and 3 months. Blondeel 2004 defined in- using a modified Hollander Wound Evaluation scale - this was
fection as redness more than 3 mm to 5 mm from the wound a blinded assessment (Kent 2014). Livesey 2009, Maloney 2013
margin, swelling, purulent discharge, pain, increased skin tem- and Romero 2011 reported surgeon-assessed cosmetic appearance
perature, fever or other signs of infection and assessed this at day at three months using a 100 mm VAS, where 0 represented the
10. Switzer 2003 described an infection as a draining sinus. Avsar worst outcome and 100 the best outcome - in all cases the sur-
2009 assessed infection at 2, 7 and 40 days postoperatively using geon-assessed outcome was blinded. Livesey 2009 and Maloney
a definition of infection that was thought to be purulence and ac- 2013 also used the same VAS scale to assess participant data on
companying erythema, but the translation we used was not com- cosmetic appearance, but it was unclear whether these assessments
pletely clear about this definition. Livesey 2009 defined wound were blinded.
infection as a participant requiring antibiotics specifically for sus- Pronio 2011 asked participants to assess cosmetic appearance us-
pected wound infection, this was assessed at 24 hours, 3 weeks ing the Stony Brook scar evaluation scale composed of five di-
and 6 weeks postoperatively. Khan 2006 classed follow-up as early, chotomous, evenly weighted categories. Mean data presented here
which seemed to be the first 3 days after surgery, and then late, were calculated by the review authors from data included in the
which was between 8 weeks and 12 weeks postoperatively; where study report. Kouba 2011 reported surgeon-assessed cosmetic ap-
cultures were positive or there was clinical evidence of cellulitis, the pearance at one month and three months (we report three month
participants were treated with a course of antibiotics and recorded data). The cosmetic presence of the wound was scored on a scale
as having an ‘infection’. Romero 2011 assessed wounds at the 10th of 1 (excellent wound healing, scar matches surrounding skin) to
and 90th days postoperatively and defined infection as an abscess 5 (poor scar wound healing, does not match surrounding skin);
or redness more than 3 mm perpendicular to the wound. One this was a blinded assessment.
study simply referred to wound complications (Dowson 2006). A A number of studies reported data that could not be used further.
further 14 studies reported upon infection, but did not describe Toriumi 1998 assessed cosmetic appearance at three months and
how infection would be defined for diagnosis and reporting in the one year using a modified Hollander scale at three months and
study (Chibbaro 2009; Eggers 2011; Greene 1999; Kent 2014; a VAS of photographs at one year using two surgeons blinded to
Ong 2002; Maloney 2013; Pronio 2011; Sebesta 2004; Shamiyeh treatment group. However, we could not use the data from this
2001; Sinha 2001; Sniezek 2007; Tierny 2009; Toriumi 1998; van study at three months as the standard deviation was not reported
den Ende 2004). and one participant dropped out from an unspecified group. Data
We felt there were potential unit of analysis issues in two stud- at one year could not be used, as the group(s) from which 11
ies where it was not clear whether one person had more than participants had dropped out was not clear. Ong 2002 evaluated
one episode of infection over multiple time periods (Eggers 2011; cosmesis using a VAS and the Hollander Scale at three weeks and
Khan 2006). While we have reported the total number of infec- three months, but the first data could not be used as it was too
tions reported by group it was not clear whether some participants early, and the data at three months could not be used due to large
reported more than one infection, as the number of infections was and unspecified loss to follow-up. Dowson 2006 assessed cosmetic
reported rather than number of people having at least one infec- outcome using the Hollander scale at six weeks and three months.
tion. We have acknowledged this in the ’Risk of bias’ assessment The six-week data were not included as it was too early and the
and sensitivity analysis we conducted. three-month data did not report mean and standard deviation
statistics; we contacted the authors but they did not respond, there-
fore the data could not be included. Sniezek 2007 also assessed
Cosmetic appearance cosmesis at three months using a VAS, but there were insufficient
data for inclusion. Amin 2009, Chibbaro 2009 and Tierny 2009
Eleven studies reported cosmetic appearance with data that could
also reported cosmetic appearance at three months, but the data
be used for further analyses. One study asked participants to score
were not clear and were also not used.
their own cosmetic result using a validated visual analogue scale
Several studies evaluated cosmetic appearance less than three
(VAS; Maartense 2002). Participants in the Dunker 1998 trial were
months after surgery (Avsar 2009; Blondeel 2004; Brown 2009;
also asked to complete the cosmetic scale of the Body Image Ques-

Cheng 1997;Eggers 2011; Greene 1999; Keng 1989; Khan 2006; reported surgeon satisfaction immediately after closure, when the
Krishnamoorthy 2009; Ong 2002; Ridgway 2007; Sebesta 2004; surgeon was asked to give his or her opinion on the time needed
Sinha 2001; Switzer 2003). for wound closure and the practicality of the materials used by an-
swering multiple choice questions (potential responses included:
’far too long’, ’a little too long’, ’not too long’, ’not practical’,
Patient/parent satisfaction
’not very practical’ and ’very practical’; Maartense 2002). Due to
Thirteen studies reported satisfaction outcomes. Patient satisfac- differences in methods used to measure this outcome, these stud-
tion interviews in one study included questions about comfort, ies were not included in the meta-analysis. One study did report
presence of a pulling sensation and appreciation of lack of suture surgeon satisfaction via a questionnaire that included ratings for
removal at weeks one, two and four (Greene 1999). Wound com- wound cosmetic appearance, safety, effectiveness, applicability for
fort at one and four weeks was assessed in another study (Keng a wide range of incisions, perceived patient satisfaction and overall
1989). A third study assessed participants at one year using a scale satisfaction (Blondeel 2004). Kent 2014 assessed surgeons’ satis-
of satisfaction with scar (Shamiyeh 2001). One study assessed pa- faction with wound (considering expression, application, delivery
tient satisfaction by using a questionnaire that included ratings for and ease of use for product); the options were ’satisfied’ or ’dis-
cosmetic appearance, overall comfort, ability to shower, dressing satisfied’. Maloney 2013 assessed surgeon satisfaction (at time of
changes, tension at the wound, hygienic problems or allergic reac- wound closure) using 100 mm VAS scales for: ease of use (0 ’im-
tion and overall satisfaction (Blondeel 2004). Amin 2009 assessed possible’ to 10 ’very easy to use’) and satisfaction with device and
patient satisfaction at three months using a self-completed 10 cm the closure achieved (0 ’completely dissatisfied’ to 10 ’completely
VAS line where 0 was poor and 10 was excellent. Avsar 2009 as- satisfied’).
sessed patient satisfaction at day 40 when participants were asked
how satisfied they were with their skin closure and could choose
from the following responses: very bad, poor, average, good, very Relative cost of materials
good. Ong 2002 and Khan 2006 assessed participant/parent satis- Costs of closure devices were reported in five studies (Brown 2009;
faction using a VAS scale that ran from 0 to 100, where 100 repre- Eggers 2011; Maartense 2002, Sebesta 2004; Shamiyeh 2001).
sented maximal satisfaction. Data for Khan 2006 were presented
as median values, and separately for different types of arthroplasty,
and are not reported further in this review. Dowson 2006 and Time for wound closure following surgery
Romero 2011 reported patient satisfaction as a simple ’satisfied’ Time for closure was reported in 24 studies (Avsar 2009; Brown
or ’not satisfied’, but gave little information about the criteria 2009; Blondeel 2004; Cheng 1997; Chibbaro 2009; Dowson
used. Likewise, Kent 2014 report participants’ satisfaction with 2006; Eggers 2011; Greene 1999; Jallali 2004; Keng 1989;
incisional wound closure - options were ’satisfied’ or ’dissatisfied’. Kent 2014; Khan 2006; Krishnamoorthy 2009; Livesey 2009;
Pronio 2011 assessed participants’ satisfaction with wound man- Maartense 2002; Maloney 2013; Ong 2002; Ozturan 2001;
agement at a seven-day follow-up when participants were asked Ridgway 2007; Sebesta 2004; Shamiyeh 2001; Switzer 2003;
to rate their level of satisfaction with the early postoperative man- Toriumi 1998; van den Ende 2004). The data from 15 of these
agement of the wound (regarding the requirement of a return visit studies were excluded as they were insufficient (Avsar 2009; Cheng
for medications, the possibility of washing oneself, and suture re- 1997; Chibbaro 2009; Dowson 2006; Eggers 2011; Greene 1999;
moval) using a numerical scale ranging from 0 to 10. Data were Jallali 2004; Keng 1989; Khan 2006; Krishnamoorthy 2009;
reported in merged categories (e.g. percentage of participants re- Livesey 2009; Maartense 2002; Switzer 2003; Toriumi 1998; van
porting a score of 10 to 9, 8 to 7 etc.), which limited further use of den Ende 2004). Data from the remaining nine studies were el-
these data. One paper reported upon participant satisfaction as an igible for inclusion (Blondeel 2004; Brown 2009; Kent 2014;
outcome measure in the text (Sniezek 2007), but no results were Maloney 2013; Ong 2002; Ozturan 2001; Ridgway 2007; Sebesta
reported in the analyses. We attempted to contact the authors, but 2004; Shamiyeh 2001). The time was recorded as a continuous
received no reply. variable in seconds or minutes elapsed from beginning of wound
closure to completion of wound closure. Mean time to closure
times were only used in the review if this was measured on all
Surgeon satisfaction
participants, thereby avoiding concerns about time to event data
In one study (Greene 1999), surgeon satisfaction included quality being analysed incorrectly.
of wound closure by assessment of eversion, regularity, approxi-
mation and any difficulties in attaining approximation. This was
reported at weeks one, two and four. Another study reported sur-
geon satisfaction at 10 days using a scale of satisfaction with the
Risk of bias in included studies
scar on a five-point score (where 1 was a ’perfect cosmetic re- The results of the quality assessment for included trials is shown
sult’ to 5 ’unsatisfactory result’; Shamiyeh 2001). A third study in Figure 1 and Figure 2.

Figure 1. Risk of bias summary: review authors’ judgements about each risk of bias item for each included
study

Figure 2. Risk of bias graph: review authors’ judgements about each risk of bias item presented as
percentages across all included studies
Random sequence generation

were opened shortly before the intervention was given. Livesey
Random sequence generation was performed adequately in twelve 2009 did not indicate that numbered envelopes were used, but
studies (Amin 2009; Blondeel 2004; Eggers 2011; Khan 2006; stated that envelopes were opened by independent personnel. All
Krishnamoorthy 2009; Maartense 2002; Mota 2009; Ong 2002; remaining studies were deemed to be at unclear risk of bias for
Romero 2011; Shamiyeh 2001; Sniezek 2007; Switzer 2003). All allocation concealment. Some studies gave evidence that they used
studies used a random sequences generated by computerised ran- envelopes that were sealed and opaque, but lacked sufficient ev-
domisation programmes except for Sniezek 2007, which used coin idence that they were sequentially numbered or that the process
tossing. was undertaken by an independent person. Many other studies
In the remaining 20 studies, the risk of bias in the random sequence provided no information on allocation of the randomisation se-
generation was unclear. This was largely because, although there quence at all.
was mention of the participants being randomised into different
intervention arms, there was no mention of the methods used to
achieve this (Brown 2009; Cheng 1997; Chibbaro 2009; Dowson Blinding of participants and personnel
2006; Greene 1999; Jallali 2004; Keng 1989; Kent 2014; Kouba The risk of bias for blinding of participants and personnel was
2011; Livesey 2009; Maloney 2013; Millan 2011; Ozturan 2001; judged to be unclear in all studies. It was difficult to see how the
Pronio 2011; Ridgway 2007; Sebesta 2004; Sinha 2001; Tierny operating surgeon could be completely blinded to an intervention
2009; Toriumi 1998). The partial translation of Avsar 2009 was he/she was supposed to undertake. Only Dowson 2006 and Mota
such that no conclusion could be derived about whether there was 2009 suggest that participants remained blinded to the interven-
adequate evidence of random sequence generation, therefore the tion they received. Given the difficulties faced in blinding partic-
judgement remained unclear. ipants (in most cases) and personnel to the intervention, we felt it
reasonable to judge all of the included studies as being at unclear
risk of bias, as it is uncertain how this influenced the performance
Allocation concealment of the personnel.
Four studies were judged to be at low risk of bias for the domain
of allocation concealment: Amin 2009, Dowson 2006, and Ong
Blinding of outcome assessment
2002 reported that they used sealed, sequential envelopes, that
Risk of bias for blinding of outcome assessment was undertaken whether dehiscence or other data, or both, were reported per per-
for each relevant outcome, and thus was often characterised as son, or if the same wounds had more than one infection during the
being at both unclear and high risk of bias within the same study. period of the trial (Cheng 1997; Eggers 2011; Jallali 2004; Kent
This was often because numbers of wounds breaking down and 2014; van den Ende 2004). Avsar 2009 and Millan 2011 were
wound infection were assessed in a way that was not obviously classed as being at unclear risk of bias for this domain, as we could
blinded, but cosmesis was deemed to be blinded. Such examples of not make a judgement using the translations that we had. The
studies where blinding of dehiscence was unclear and blinding of remaining 25 studies were deemed not to offer any other sources
cosmesis was adequate were: Blondeel 2004, Dowson 2006, Kent of bias.
2014, Livesey 2009, Maloney 2013, Ong 2002, Ozturan 2001,
Romero 2011, Shamiyeh 2001, and Toriumi 1998. Effects of interventions
There were studies that did give enough evidence for us to in-
fer a low risk of detection bias. These were Amin 2009, Brown See: Summary of findings for the main comparison Tissue
2009, and Maartense 2002, all of which revealed adequate blind- adhesive compared to sutures for surgical incisions; Summary
ing of outcome assessment for all measures extracted for this re- of findings 2 Tissue adhesive compared to adhesive tape for
view. In one study, there was evidence to suggest a high risk of bias surgical incisions; Summary of findings 3 Tissue adhesive
(Mota 2009), as the study report indicated that those assessing the compared to staples for surgical incisions; Summary of findings 4
wounds were the authors of the paper. Tissue adhesive compared to other methods for surgical incisions;
The remaining studies did not provide evidence of adequate blind- Summary of findings 5 High viscosity tissue adhesive compared
ing of outcome assessments at any stage and were classed as being to low viscosity tissue adhesive for surgical incisions; Summary
at unclear risk of bias for this domain. of findings 6 Octylcyanoacrylate compared to butylcyanoacrylate
for surgical incisions
Incomplete outcome data

Comparison 1. Tissue adhesives compared with
Four studies were classed as having a high risk of attrition bias
sutures
(Dowson 2006; Kent 2014; Ong 2002; Sinha 2001). This was
often due to high proportional rates of drop out, or unclear reasons
for large numbers of drop outs, or both.
Primary outcome
Eleven studies were judged as being at unclear risk of bias for this
domain, as reasons for drop out were not clear, or the extent to Data from 17 trials compared the use of tissue adhesive with su-
which the drop-out rates affected the results were unclear (Amin tures for dehiscence, however as seven trials had no cases of dehis-
2009; Avsar 2009; Eggers 2011; Kouba 2011; Krishnamoorthy cence, only data from the remaining ten trials contributed to the
2009; Livesey 2009; Millan 2011; Mota 2009; Ridgway 2007; meta-analysis (Cheng 1997; Dowson 2006; Eggers 2011; Millan
Romero 2011; Toriumi 1998). 2011; Mota 2009; Sebesta 2004; Shamiyeh 2001; Sinha 2001;
The remaining 18 studies suffered fewer losses to follow-up and, Switzer 2003; van den Ende 2004). Overall a significant difference
where these did occur they were fully explained in the literature, so was detected between the proportion of wounds with dehiscence
these studies were judged to be at low risk of bias for this domain. (RR 3.35, 95% CI 1.53 to 7.33; Analysis 1.1), that favoured clo-
sure by suture with no evidence of heterogeneity (I2 = 0). Taking
an assumed control risk of 0.01 (10 per 1000) this returns a num-
Selective outcome data ber needed to harm of 43. Only one study was deemed to be at
Amin 2009, Kouba 2011, Livesey 2009 and Ozturan 2001 were low risk of bias for blinded outcome assessment for this outcome
reported to be at high risk of bias due to possible selective reporting (Sinha 2001; Figure 1; Figure 2). Dowson 2006, Mota 2009 and
of outcomes.Twenty-seven studies were deemed to have a low risk Sinha 2001 had one domain at high risk of bias. The remaining
of reporting bias as they reported on all the outcomes that were studies had domains classed at low or unclear risk of bias.
outlined in the methodology, We also conducted a sensitivity analysis in which we removed
Two studies were judged as unclear, either due to an unclear En- studies that were at unclear risk of bias for this outcome due to
glish translation (Avsar 2009), or because outcomes that were out- possible unit of analysis issues: these studies were Cheng 1997,
lined as being assessed were not clearly reported (Sebesta 2004). Millan 2011, and Sinha 2001 (these authors were contacted where
possible to request clarification regarding their data) and also van
den Ende 2004, as we were not clear whether this trial reported
Other sources of bias data at the participant level. When this analysis was undertaken a
Eight studies were classed as being at unclear risk of bias for this similar effect size was found, however, there was reduced precision
domain, including six studies where it was it was not possible to and the findings were no longer statistically significant (RR 2.70,
exclude unit of analysis issues, for example, we could not establish 95% CI 0.95 to 7.68; P value 0.06; Analysis 1.2).

Secondary outcomes package of poliglecaprone suture (used together with a dressing
at EUR 0.42 each) and EUR 1.15 per package of adhesive paper
tape (Maartense 2002). Eggers 2011 reported that the total cost
Infection associated with surgery for each of the closure groups (including all
Eighteen trials that compared the use of tissue adhesives with su- aspects of surgery associated with materials, labour, and operating
tures reported wound infection data, however, as eight of these room expenses) was USD 993.20 for octylcyanoacrylate; USD
had no cases of infection, only data from the remaining ten studies 878.27 for butylcyanoacrylate and USD 1056.32 for staples. No
contributed to the meta-analysis (Avsar 2009; Cheng 1997; Eggers measures of variation were presented. Sebesta 2004 reported that
2011; Khan 2006; Maartense 2002; Ozturan 2001; Sebesta 2004; the mean tissue adhesive cost per patient was USD 65.10 (range
Shamiyeh 2001; Switzer 2003; van den Ende 2004). There was USD 40.60 to USD 101.5; standard deviation (SD) USD 13.70)
no evidence of a difference in the proportion of participants de- whilst the total cost for surgery in the octylcyanoacrylate group
veloping infection in the individual trials, or when data from the (i.e. cost for operating room time, cost and cost of suture material)
trials were pooled (RR 1.72, 95% CI 0.94 to 3.16; Analysis 1.3); was USD 193.32 (range USD 130 to USD 365; SD USD 49.40).
again there was no evidence of heterogeneity (I2 = 0). For the suture group the mean suture cost per patient was USD
Three studies were considered to have the potential for unit of 7.74 (range USD 3.60 to USD 10.80; SD USD 2.05) and the
analysis issues for this outcome (Eggers 2011; Khan 2006; van den total mean cost was USD 497 (range USD 295 to USD 835; SD
Ende 2004). We conducted a sensitivity analysis removing these USD 139.70).
studies from the meta-analysis. Again there was no evidence of a
difference in the proportion of participants developing infection Time for wound closure following surgery
between groups (RR 2.03, 95% CI 0.80 to 5.12; Analysis 1.4).
Five studies reported the time taken for closure (Brown 2009;
Ong 2002; Ozturan 2001; Sebesta 2004; Shamiyeh 2001). Pooling
Cosmetic appearance these trials was not appropriate due to massive heterogeneity (I2
= 100%; Analysis 1.10). Two of the trials suggested that adhesive
There was no evidence of a difference in the participants’ assess- took longer to apply than sutures, and in one of these trials the
ment of cosmetic appearance (MD -2.12, 95% CI -7.20 to 2.95; difference was statistically significant (Shamiyeh 2001), although
Analysis 1.5). Likewise there was no evidence of a difference for the the units for this were unclear - if measured in seconds then the
surgeons’ assessment of cosmetic appearance based on a 0 to 100 difference, although significant, could be small in terms of total
VAS (MD 3.00, 95% CI -3.30 to 9.30), or a scar assessment scale time saved with one method compared to the other. In remaining
(MD -0.26, 95% CI -0.58 to 0.06; Analysis 1.6; Kouba 2011). three trials, suturing took significantly more time than adhesive (
Brown 2009; Ozturan 2001; Sebesta 2004). Sebesta 2004 reported
that application of adhesive took on average 3.7 minutes compared
Patient/surgeon satisfaction
with 14 minutes on average in the suture group. Ong 2002 and
There was no evidence of a difference in patient, surgeon or pa- Ozturan 2001 were both deemed to be at high risk of bias for one
tient/parent satisfaction with treatment (Analysis 1.7; Analysis domain (Figure 1; Figure 2).
1.8; Analysis 1.9; Dowson 2006; Maartense 2002; Ong 2002;
Shamiyeh 2001). In one further study 13/20 participants stated
that they preferred the tissue adhesive while the remaining seven Summary: tissue adhesives compared with sutures
preferred the sutures (Greene 1999). Avsar 2009 reported that 6/ There was an overall difference favouring sutures over tissue ad-
20 participants in the adhesive group reported average satisfac- hesives in that sutures led to a reduced risk of dehiscence, though
tion; 5/20 good and 9/20 very good. This was compared to 13/ several studies that contributed data to this analysis had at least one
20 recording good and 7/20 very good in the suture arm. risk of bias domain that was classed as being at high risk. Removal
of studies with a possible unit of analysis issue reduced the preci-
sion and the results then lay just outside the standard definition of
Costs statistical significance.There was no evidence of a difference in the
Four studies reported costs. Shamiyeh 2001 reported that one tube risk of developing a wound infection in trial groups - although the
of tissue adhesive at USD 11.00 could be used to close 3.5 incisions comparison is underpowered and confidence intervals are wide.
of 5 mm mean length, while one suture at USD 1.10 could be used One study was at both low and unclear risk of bias across domains:
to close five incisions, and one package of tape (six pieces) at USD its results were statistically significant and suggested that using
0.24 could be used to close three incisions - this calculation assumes sutures for closure was slightly faster than using tissue adhesives.
multiple incisions on the same patient. A second study reported However, a second study had opposite findings, which were also
that for closure of laparoscopic trocar wounds the costs were EUR statistically significant, suggesting that closure with tissue adhesive
13.90 for one ampoule of octylcyanoacrylate, EUR 2.47 for one was significantly faster than sutures by over 10 minutes on average.

Comparison 2. Tissue adhesives compared with Summary: tissue adhesive compared with adhesive tape
adhesive tape There were limited data for wound dehiscence and wound infec-
Three trials provided data comparing tissue adhesives with adhe- tion for the comparison of tissue adhesive against adhesive tape.
sive tape (Maartense 2002; Romero 2011; Shamiyeh 2001). These Only one trial reported dehiscence as an outcome, and this was
trials were rated as being at low or unclear risk of bias for domains underpowered. Three trials reported wound infection as an out-
(Figure 1; Figure 2). come, and these were also underpowered. Based on these small
studies there is currently no evidence of a difference in the inci-
dence of dehiscence or wound infection when wounds are closed
Primary outcome with tissue adhesive or tape. Surgeons’ assessment (blinded) of the
cosmetic outcome was better in the tape group. One study re-
There was no significant difference between closure techniques in
ported a significant difference in time taken for closure and this
the single trial that contributed data to this comparison for dehis-
favoured adhesive tape (time units not clear).
cence (RR 0.96, 95% CI 0.06 to 14.55; Analysis 2.1; Shamiyeh
2001): this comparison was underpowered, as only one partici-
pant experienced dehiscence in each group. Comparison 3. Tissue adhesives compared with
staples
Six studies compared a tissue adhesive with staples for wound
Secondary outcomes
closure (Amin 2009; Eggers 2011; Khan 2006; Livesey 2009;
Pronio 2011; Ridgway 2007).
Infection
Primary outcome
All three trials reported wound infection, but there was no evidence
of a difference between the groups in the proportion of participants Two trials that compared the use of tissue adhesives with staples
with infection (RR 1.37 95% CI 0.39 to 4.81; Analysis 2.2). Again presented data for dehiscence (Eggers 2011; Pronio 2011). As there
this comparison was underpowered, with only 10 infection events were no cases of dehiscence in one trial, only one trial contributed
in total. data to the comparison (Eggers 2011). There was no statistically
significant difference in the proportion of wounds that dehisced
in the tissue adhesive group compared to the staples group (RR
Cosmetic appearance 0.53, 95% CI 0.05 to 5.33; Analysis 3.1).
Maartense 2002 and Romero 2011 found no statistically signif-

icant difference for participants’ assessment of cosmetic appear- Secondary outcomes
ance (Analysis 2.3; Analysis 2.4), however both studies reported
evidence of a difference for the surgeons’ blinded assessment using
a VAS favouring closure by adhesive tape (pooled estimate MD
Infection
9.56, 95% CI: 4.74 to 14.37; I2 = 14%; Analysis 2.5).
Four trials that compared the use of tissue adhesive with staples
presented data on wound infection (Eggers 2011; Khan 2006;
Patient/surgeon satisfaction Livesey 2009; Pronio 2011), however as there were no cases of
wound infection in one trial, data from three trials contribute
Shamiyeh 2001 found no difference between the groups for pa-
data to the comparison (Eggers 2011; Khan 2006; Livesey 2009).
tient satisfaction (Analysis 2.6). Similarly, Maartense 2002 and
There was no evidence of a difference in the proportion of wounds
Shamiyeh 2001 found no evidence of a difference between the that became infected in the tissue adhesive group compared to the
groups with respect to surgeons’ satisfaction (Analysis 2.7). staples group (RR 1.39, 95% CI 0.30 to 6.54; Analysis 3.2).
Time to wound closure following surgery Cosmetic appearance

Shamiyeh 2001 presented data for time to closure and demon- Pronio 2011 found no evidence of a difference between the groups
strated that tapes were significantly faster to use than adhesives for patient-assessed cosmetic outcome (Analysis 3.3). Similarly
(MD 0.56, 95% CI 0.42 to 0.70; Analysis 2.8). (Review authors’ Livesey 2009 found there was no evidence for a difference between
note: units not reported in trial, we assumed that units are min- the groups with respect to the cosmetic appearance by surgeons
utes). (Analysis 3.4).

Patient/surgeon satisfaction Secondary outcomes
Amin 2009 found a statistically significant difference between the
groups for patient satisfaction in favour of tissue adhesive (MD
1.10; 95% CI 0.41 to 1.79; Analysis 3.5). Infection
Blondeel 2004 found no significant difference between the groups
Costs for infection (RR 0.41, 95% CI 0.11 to 1.60; Analysis 4.2).
Eggers 2011 reported that the total cost associated with surgery Chibbaro 2009 reported wound infection, but there were no events
for each of the closure groups (including all aspects of surgery in either group.
associated with materials, labour, and operating room expenses)
was USD 993.20 for octylcyanoacrylate; USD 878.27 for butyl-
cyanoacrylate and USD 802.79 for staples. Patient/surgeon satisfaction
Blondeel 2004 reported statistically significant differences in
favour of the group treated with other devices such as sutures,
Time to wound closure following surgery
staples and tapes for both patient satisfaction (MD 0.40, 95% CI
Ridgway 2007 reported the time to closure and found a statisti- 0.10 to 0.70; Analysis 4.3) and clinician satisfaction (MD 0.53,
cally significant difference favouring the use of staples (MD 67.0 95% CI 0.29 to 0.77; Analysis 4.4).
seconds, 95% CI 39.3 to 94.7; Analysis 3.6). The study had risk
of bias domains classified as both low and unclear.
Time for closure
Summary: tissue adhesive compared with staples Blondeel 2004 reported that closure took significantly less time
There was no evidence of a difference in wound dehiscence, wound with tissue adhesive (MD -1.05 minutes, 95% CI -1.79 to -0.31;
infection, or cosmetic appearance between use of tissue adhesives Analysis 4.5). Data reported for this outcome by Chibbaro 2009
or staples for wound closure. There was a significant difference in were unclear.
patient satisfaction in favour of tissue adhesives. There was also
a significant difference in time taken for closure that favoured
staples, however, the difference between groups was only just over Summary: tissue adhesive compared with other techniques
60 seconds, so whilst the result was statistically significant, it was When tissue adhesives were compared with other techniques there
not significant from a clinical point of view. was no evidence of a difference in wound dehiscence or wound
infection between groups. When assessing surgeon and patient
Comparison 4. Tissue adhesives compared with other satisfaction there was a statistical difference favouring the control
techniques group (other techniques) over tissue adhesives. In this same analysis
there was a statistically significant difference favouring the tissue
Blondeel 2004 compared high viscosity adhesive with any other
adhesive for time taken to closure - the mean time saving was one
commercially available devices such as sutures, staples, tapes or
minute.
low viscosity adhesive. We requested further information from the
authors, specifically data regarding high and low viscosity adhe-
sives compared with the remaining commercially available devices
Comparison 5. Adhesives compared with adhesives
and data for the comparison of high viscosity with low viscosity
adhesives for the outcomes of interest to this review. This compar-
ison of data was not reported within the published paper, but the
author made the data available to the review team. This paper was Comparison 5.1. High versus low viscosity adhesives
designated as being at low risk of bias. Chibbaro 2009 compared
The data for this comparison were provided by the authors as an
tissue adhesive with a comparison group that received sutures or
additional analysis to that found in the paper.
staples.
Primary outcome Primary outcome

Blondeel 2004 found no significant difference between the groups Blondeel 2004 found no significant difference between the high
for dehiscence (RR 0.55, 95% CI 0.13 to 2.38; Analysis 4.1). viscosity and low viscosity adhesive intervention groups for dehis-
Chibbaro 2009 reported dehiscence, but there were no events in cence (RR 3.74, 95% CI 0.21 to 67.93; Analysis 5.1). This paper
either group. was designated as being at unclear risk of bias.

Secondary outcomes 95% CI 0.21 to 1.88; Analysis 6.2). Maloney 2013 reported no
events for either trial arm for infection.
Infection
No statistically significant differences were found between inter- Cosmetic appearance
vention groups for infection (Analysis 5.2).
Maloney 2013 reported no evidence of a difference in participant-
assessed cosmetic outcome between study groups. Likewise there
was no evidence of a difference in blinded surgeon-assessed cos-
Patient/surgeon satisfaction metic appearance (Analysis 6.3; Analysis 6.4).
No statistically significant differences were found between inter-
vention groups for patient or surgeon satisfaction (Analysis 5.3;
Analysis 5.4).
Patient/surgeon satisfaction
Surgeons’ satisfaction with skin incision closure technique, in
Time for closure terms of ease of use and satisfaction with closure, was assessed us-
For time to closure, there was a significant difference favouring ing a VAS. There was no evidence of a difference between groups
low viscosity adhesive (MD 0.54 minutes, 95% CI 0.03 to 1.05; for these measures (Analysis 6.5; Analysis 6.6.).
Analysis 5.5).
Comparison 5.2. Octylcyanoacrylate vs butylcyanoacrylate

Costs
Three trials compared octylcyanoacrylate tissue adhesive with
butylcyanoacrylate tissue adhesive (Eggers 2011; Kent 2014; Eggers 2011 reported that the total cost associated with surgery
Maloney 2013). We assessed Maloney 2013 as being at low or for each of the closure groups (including all aspects of surgery as-
unclear risk of bias for domains. Eggers 2011 was assessed as being sociated with materials, labour, and operating room expenses) was
at unclear risk of bias for incomplete outcome data and Kent 2014 USD 993.20 for octylcyanoacrylate and USD 878.27 for butyl-
for randomising at the participant level, but presenting unadjusted cyanoacrylate.
data at the wound level. We were unable to re-analyse the Kent
2014 data correctly here, as we had planned to report data at the
participant level only, but did not do this because of the amount
of missing data. Time for wound closure following surgery
Maloney 2013 reported a significant difference in time for wound
Primary outcome closure favouring octylcyanoacrylate (MD -25.50, 95% CI -39.79
Eggers 2011 reported no statistically significant difference in to -11.21; Analysis 6.7). It is important to note that the units
wound dehiscence between groups (RR: 0.95, 95% CI 0.06 to for this assessment were seconds - so whilst there is a statistically
14.04; Analysis 6.1). Likewise Maloney 2013 did not report a significant difference it is one of, on average, about 26 seconds
statistically significant difference in wound dehiscence between between treatment arms, which probably does not translate to a
groups (RR: 2.63, 95% CI 0.11 to 61.05; Analysis 6.1). These significant clinical difference.
data were pooled and returned a result that showed there could
be an effect in either direction, or none (RR 1.46, 95% CI 0.19
to 11.30; Analysis 6.1; very low precision due to the small sample Summary: tissue adhesive compared with other tissue
size). adhesive
There was no evidence of a difference in any outcome assessed
Secondary outcomes when different types of tissue adhesives were compared, except for
high viscosity compared with low viscosity adhesives where there
was a statistical difference favouring the low viscosity adhesive for
time taken for closure (mean difference approximately 1 minute).
Infection Likewise, one study reported a significant difference in time taken
Eggers 2011 report no statistically significant different between for wound closure favouring octylcyanoacrylate but the size of the
different tissue adhesives in terms of wound infection (RR 0.63, difference was small.

Overall summary of results by outcome Time to wound closure (following surgery)
One study suggested that, on average, it took 10 minutes longer

Dehiscence to close a wound with sutures than with tissue adhesives, but this
was not borne out in all the studies and may depend on factors
When tissue adhesives were compared with sutures, pooled data
such as wound type. There was a statistically significant difference
from 17 studies (with 10 contributing data towards the analysis)
in time taken for closure between tissue adhesives and tape-closed
showed a statistically significant difference favouring sutures, as
wounds, that favoured the tape group. There was also a signifi-
they reduced the risk of dehiscence. It is possible this result may
cant difference in time taken for closure between tissue adhesives
have been influenced by unit of analysis issues, as it was not clear
compared with staples that favoured the staples group, however,
whether more than one dehiscence event per participant had been
the difference between groups was only just over 60 seconds, so
recorded in studies with multiple follow-up points. No other com-
whilst it was statistically significant it was not clinically significant.
parison of tissue adhesives with other closure methods showed a
Another study that compared tissue adhesive with a mixed control
statistically significant difference in the risk of wound dehiscence.
group (i.e. staples, sutures and tape) found a statistically signif-
icant difference in time to closure that favoured tissue adhesive,
Wound infection although the mean difference between groups was again approx-
imately one minute. Finally, one study reported that there was a
There was no evidence of a difference in the risk of wound infection
small, but statistically significant difference in time to closure that
between wounds closed with tissue adhesives and wounds closed
favoured low viscosity adhesive over high viscosity adhesive, and
using other methods reported here.
favoured octylcyanoacrylate tissue adhesive over butylcyanoacry-
late tissue adhesive.
Cosmetic appearance
Two studies with blinded outcome assessment reported a statis-
tically significant difference in surgeon-assessed appearance score
that favoured the tape group over tissue adhesives. ’Summary of findings’ table
We present ’Summary of findings’ tables for the dehiscence and

Patient/surgeon satisfaction infection outcomes. These tables confirm our conclusion that the
When tissue adhesives were compared with a mixed control group available evidence is generally underpowered and is limited in some
(i.e. sutures, staples and tape), one study reported a statistically cases by a lack of reported methodological information that would
significant difference in patient and surgeon satisfaction scores permit full analysis of the data. (Summary of findings for the
that favoured the mixed control group, while another study that main comparison; Summary of findings 2; Summary of findings
compared tissue adhesive with staples found a significant difference 3; Summary of findings 4; Summary of findings 5; Summary of
in patient satisfaction that favoured the tissue adhesive. findings 6)

Tissue adhesives for closure of surgical incisions (Review) A D D I T I O N A L S U M M A R Y O F F I N D I N G S [Explanation]
Tissue adhesive compared to adhesive tape for surgical incisions
Patient or population: people with surgical incisions

Settings:
Intervention: tissue adhesive
Comparison: adhesive tape
Adhesive tape Tissue adhesive

(0.06 to 14.55) (1 study) low1
42 per 1000 40 per 1000
(2 to 606)
Moderate
Wound infection Study population RR 1.37 190 ⊕⊕

(0.39 to 4.81) (3 studies) low1,2
43 per 1000 60 per 1000
(17 to 209)
Moderate
21

1 Study 95% CIs are very wide
2 Evidence of inconsistency in point estimates. With the point estimate from one study lying outside the 95% CIs of another
3
Control (tape) group risk in included study
22
Tissue adhesive compared to staples for surgical incisions

Settings:
Comparison: staples
Staples Tissue adhesive

(0.05 to 5.33) (1 study) low1
105 per 1000 56 per 1000
(5 to 561)
Moderate

(0.3 to 6.54) (3 studies) very low1,2
71 per 1000 99 per 1000
(21 to 463)
Moderate
assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;
23

High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.
1 Study 95% CIs are very wide.
2 Evidence of point estimates lying in opposite directions with the estimate for one study lying outside the 95% CI of another.
3
Control (staples ) group risk for included study.
24
Tissue adhesive compared to other methods for surgical incisions

Settings:
Comparison: other methods
Outcomes Illustrative comparative risks* (95% CI) Relative effect No of participants Quality of the evidence Comments
Other methods Tissue adhesive

(0.13 to 2.38) (1 study) low1,2
49 per 1000 27 per 1000
(6 to 117)
Moderate

(0.11 to 1.6) (1 study) low1,2
66 per 1000 27 per 1000
(7 to 105)
Moderate
25

2 Single study with low event rate
26
High viscosity tissue adhesive compared to low viscosity tissue adhesive for surgical incisions

Settings:
Intervention: high viscosity tissue adhesive
Comparison: low viscosity tissue adhesive
Outcomes Illustrative comparative risks* (95% CI) Relative effect No of participants Quality of the evidence Comments
Low viscosity tissue ad- High viscosity tissue ad-

hesive hesive
Wound dehiscence Study population RR 3.74 148 ⊕

(0.21 to 67.93) (1 study) very low1,2
Could not be calculated Could not be calculated

(0.16 to 4.31) (1 study) very low1,2
47 per 1000 38 per 1000
(7 to 200)
Moderate
27

2 Single study with low event rate
28
Octylcyanoacrylate compared to butylcyanoacrylate for surgical incisions

Settings:
Intervention: octylcyanoacrylate
Comparison: butylcyanoacrylate
Butylcyanoacrylate Octylcyanoacrylate
Wound dehiscence 26 per 1000 38 per 1000 RR 1.46 80 ⊕⊕

(5 to 297) (0.19 to 11) (2 studies) low1

(0.21 to 1.88) (1 study) low1
333 per 1000 210 per 1000
(70 to 627)
Moderate

1 The 95% CI estimate around the RR of 1.46 is very wide
29
2 Median control group risk across studies
30
DISCUSSION metic appearance at one year (Quinn 1998), the same investiga-
tion reported that early outcome, such as at five or 10 days, is
poorly predictive of the three month appearance. This can present
Summary of main results a problem for trials, as attrition bias may influence the results. The
only difference identified in cosmetic appearance was for the com-
Traditional methods of surgical incision closure have been used
parison of tissue adhesive with adhesive tape - this was a blinded
for many years. However, these techniques are not without some
assessment by surgeons that favoured tape. Assessments for this
problems and it is therefore important to consider new develop-
comparison were limited, so there was a great deal of uncertainty
ments - such as tissue adhesives - which may offer some advan-
regarding the comparative risk of wound dehiscence and infection
tages for patients. This review included a total of 33 studies: 23
when tape was compared with tissue adhesive.
studies compared tissue adhesives with sutures; three studies com-
Patient satisfaction is also important when comparing alternative
pared tissue adhesives with adhesive tape, which is often used for
incision closure devices providing that the primary efficacy vari-
smaller incisions; six studies compared adhesives with staples; two
ables of dehiscence, infection and cosmetic appearance are satisfac-
studies compared tissue adhesives with mixed control groups; and
tory. Patient satisfaction may include ratings for cosmesis, overall
two studies compared different types of tissue adhesives. A no-
comfort, ability to shower, dressing changes, tension on wounds,
table finding in this review was that, when data from ten studies
hygiene problems, allergic reactions and overall satisfaction. An-
that compared tissue adhesives with sutures were pooled, a sig-
other important benefit of tissue adhesives is that they do not need
nificant difference in risk of wound dehiscence became apparent,
to be removed. One small study suggested that patients had a pref-
with a higher risk of dehiscence associated with tissue adhesives.
erence for adhesive rather than sutures (Greene 1999), although it
No other comparison showed evidence for a difference in risk of
was not clear what dimensions it measured. A further small study
wound dehiscence for alternative treatments. It is important to
also suggested that patients were had higher satisfaction with tis-
note the often unclear and sometime high risk of bias of included
sue adhesive than staples. Conversly, one study that compared tra-
studies. Many studies were also underpowered, and the primary
ditional closure methods to tissue adhesives demonstrated a sig-
outcome here - dehiscence - was not used as a basis for sample size
nificant patient preference for the alternatives to tissue adhesives
calculation. The surgical procedures described by the studies were
(Blondeel 2004): this was the largest of the studies to assess patient
diverse and included blepharoplasty, circumcision, and excision of
satisfaction. It would be helpful if validated questionnaires were
benign skin lesions. Incision in areas of high tension and in those
available to use in studies.
patients whose medical health may have reduced their ability to
Surgeon satisfaction assessments typically sought ratings for
heal were excluded and so tissue adhesives have not been evaluated
wound cosmesis or ease of use for the technique. Certainly there is
in this population.
no risk of needle-stick injury to the surgeon whilst using adhesive
Postoperative site infection is a common problem and has a sig-
rather than sutures, and this may be a factor in favour of adhesives,
nificant impact on patients and healthcare systems. More than
though none of the studies in this review considered this. In one
70% of surgical procedures are now performed on a outpatient
study physicians completed a questionnaire that measured satis-
basis, which poses major problems for surveillance of surgical site
faction with the ease of use of a device, wound cosmesis, safety,
infections (Emori 1993). In one study of 2345 patients under-
effectiveness, applicability to a wide range of incisions, perceived
going surgery, the overall incidence of surgical site infection was
patient satisfaction and overall satisfaction (Blondeel 2004). This
8.5% (Malone 2002). One might anticipate that a tissue adhe-
study showed that clinicians significantly preferred the alternative
sive offers a barrier to micro-organisms at the site of the healing
to tissue adhesive, but when comparing high viscosity adhesives
incision and may therefore contribute towards reducing wound
to other adhesives, operators showed no difference in preference.
infection. However, the studies identified for this review did not
We included time to closure as an outcome measure in the re-
demonstrate any significant difference in the proportion of infec-
view post hoc, as the review authors believe this to be a contribu-
tions in incisions closed with tissue adhesives compared with other
tory factor towards both cost-effectiveness and satisfaction. Stud-
conventional techniques. No study reported an a priori calcula-
ies suggested that tissue adhesives might be significantly quicker
tion for the sample size, and this may be relevant. Even the largest
than suturing for some wounds, although there was heterogeneity
of the studies would have been unlikely to have been adequately
around this that might be related to the type and size of wound
powered to show any significant difference given the relatively low
being assessed, and suturing was reported to be the faster method
incidence of wound infections following many types of surgery.
in other studies. In other comparisons closure with tape and sta-
Cosmetic outcome is an important long-term outcome of wound
ples was found to be faster than with tissue adhesives - but the
repair for the patient and we considered appearance at or beyond
differences in time, whilst statistically significant, were generally
three months after surgery to be meaningful. Some studies re-
only small periods of difference - for example 60 seconds.
ported cosmetic outcome earlier than this three month time point
Whilst time taken is an attractive aspect for surgeons, it should be
(Blondeel 2004). Whilst is has been reported that an individual
noted that although there maybe a significant difference in time
patient’s cosmetic outcome at three months is predictive of cos-

taken for closure, the overall time taken was still relatively small Implications for practice
in both groups with even the longest closure times rarely exceed-
Thirty-three studies, including 2793 participants, compared tis-
ing two minutes. In clinical practice the reduction of wound clo-
sue adhesives with alternative methods of surgical wound closure.
sure time through using the quickest method may be insufficient
These provided no evidence of a difference in rates of wound in-
to increase the number of operations in a given operating room
fection after surgical incision closure with tissues adhesives, su-
schedule. However, a faster wound closure technique may increase
tures, tapes, staples or amongst different tissue adhesives. When
surgeon satisfaction and may also be attractive to patients when
adhesive was compared with suture there was evidence of a benefit
surgery is undertaken using only local anaesthetic. Alternatively,
for using sutures for minimising dehiscence.
patients may be happy with a lengthier closure time for a tech-
nique that achieves better outcomes. Although there was some evidence that surgeons and patients may
Generally, tissue adhesives cost more than the alternatives. An prefer alternative methods to tissue adhesives, there was also ev-
ampoule of tissue adhesive may be three times or more the cost of idence that patient satisfaction with tissue adhesives was higher
the suture required to close the same length of incision. However, than for staples. Although some analyses demonstrated that alter-
a dressing is not required over the tissue adhesive, but is routinely natives to tissue adhesives were less time consuming to use, this
used with alternatives. Also, when taking into account the overall does not contraindicate their use, and this conclusion was refuted
cost of the surgical procedure, this small difference may be of by the results of other studies. However, these trials did not con-
less significance. It may be considered important to use a specific sider incisions in areas of high tension, such as the elbow and knee,
closure device, even if the cost is greater, if significant superiority is which therefore have not been evaluated with tissue adhesives.
demonstrated for wound healing, including cosmetic outcome and Similarly, trials excluded patients whose general health may have
patient satisfaction. Thus the length of time for closure and cost had the potential to impair wound healing, so tissue adhesives
may be important only after other outcomes such as dehiscence, have not been evaluated in these populations.
cosmesis and infection have been considered.
In summary, there is some evidence that dehiscence rates may be
Implications for research
higher in wounds closed with tissue adhesives than with sutures.
This finding agrees with a review published in 2010 that includes Further adequately powered trials should be undertaken to investi-
similar wound dehiscence data to this review (Chow 2010), al- gate the effects of tissue adhesives in clinical situations commonly
though the authors did not perform a sensitivity analysis based on excluded in trials, specifically, wound closure in areas of high ten-
possible unit of analysis issues, as we have here. sion and in patients with general health that could potentially im-
There was no evidence of any difference between sutures and tis- pair wound healing. Trials should be sufficiently powered to de-
sue adhesive for outcomes such as cosmetic appearance and satis- tect any differences in the rate of wound infection or dehiscence
faction. The relative time taken using sutures for wound closure as statistically significant when comparing different incision clo-
rather than tissue adhesives seems to vary, with one study showing sure devices. As any future trial would need to be large, it would
use of adhesive to be significantly faster than sutures and another probably be multicentred. It would require methodological rigour
study showing suturing to be significantly faster than tissue ad- to address the outstanding uncertainties in this area appropriately.
hesive. Other studies reported that tissue adhesive took longer to Development and validation of patient satisfaction and surgeon
apply than staples and tape. Generally, there was limited compar- satisfaction questionnaires would be helpful.
ative evidence to determine whether tissue adhesives led to lower
or higher levels of dehiscence, infection, satisfaction with cosmetic
outcome, or patient or surgeon general satisfaction. Surgeons and
patients were significantly more satisfied with the alternatives to
adhesives in one analysis, but this finding was not replicated in
ACKNOWLEDGEMENTS
other studies. There was no evidence of a difference in outcomes
between tissue adhesive types except that high viscosity adhesives We wish to thank Sally Bell-Syer and Ruth Foxlee (Cochrane
took significantly more time for skin closure, adding a minute on Wounds Group) for their assistance with literature searching the
average to the procedure. preparation of this review. We would also like to thank the fol-
lowing referees: Nicky Cullum, David Margolis, Michelle Briggs,
Seokyung Hahn, James V Quinn, Ken Farion and Jac Dinnes.
We also thank Matthew Fortnam who extracted data and checked
AUTHORS’ CONCLUSIONS quality of data extraction for this second review update.

REFERENCES
References to studies included in this review incisions. Journal of Laparoendoscopic and Advanced Surgical
Techniques 2004 Aug;14(4):209–11.
Amin 2009 {published data only}
Amin M, Glynn F, Timon C. Randomised trial of tissue Keng 1989 {published data only}
adhesive vs staples in thyroidectomy integrating patient Keng TM, Bucknall TE. A clinical trial of tissue adhesive
satisfaction and Manchester score. Otolaryngology - Head (histoacryl) in skin closure of groin wounds. Medical Journal
and Neck Surgery 2009;140(5):703–8. of Malaysia 1989;44(2):122–8.
Avsar 2009 {published data only} Kent 2014 {published data only}
∗
Avsar A, Ustunnner I, Keskin L, Ozturk O, Tas E. 2- Kent A, Liversedge N, Dobbins B, McWhinnie D,
octylcyanoacrylate tissue adhesive versus polypropylene Haider J. A prospective randomised controlled double-
suture for skin closure of Pfannenestiel incision. Trk masked multi-center clinical trial of medical adhesives for
the closure of laparoscopic incisions. Journal of Minimally
Jinekoloji ve Obstetrik Derne i Dergisi 2009;6:117–22. Invasive Gynecology 2014;21:252–8.
Blondeel 2004 {published data only} Khan 2006 {published data only}
Blondeel P, Murphy J, Debrosse D, Nix, J, Puls LE, Khan RJK, Fick D, Yao F, Tang K, Hurworth M, Nivbrant
Theodore N, et al.Closure of long surgical incisions with B, et al.A comparison of three methods of wound closure
a new formulation of 2-octylcyanoacrylate tissue adhesive following arthroplasty: a prospective randomised controlled
versus commercially available methods. American Journal of trial. The Journal of Bone and Joint Surgery 2006;88:238–42.
Surgery 2004;188:307–13.
Kouba 2011 {published data only}
Brown 2009 {published data only} Kouba DJ, Tierney E, Mahmoud BH, Woo D. Optimizing
Brown JK, Campbell BT, Drongowski RA, Alderman AK, closure materials for upperlid blepharoplasty: a randomized,
Geiger JD, Teitelbaum DH, et al.A prospective, randomized controlled trial. Dermatologic Surgery 2011;37(1):19–30.
comparison of skin adhesive and subcuticular suture for
closure of pediatric hernia incisions: cost and cosmetic Krishnamoorthy 2009 {published data only}
considerations. Journal of Paediatric Surgery 2009;44(7): Krishnamoorthy B, Najam O, Khan UA, Waterworth
1418–22. P, Fildes JE, Yonan N. Randomized prospective study
Cheng 1997 {published data only} comparing conventional subcuticular skin closure with
Cheng W, Saing H. A prospective randomised study of Dermabond skin glue after saphenous vein harvesting. The
wound approximation with tissue glue in circumcision in Annals of Thoracic Surgery 2009;88(5):1445–9.
children. Journal of Paediatric Child Health 1997;33:515–6. Livesey 2009 {published data only}
Chibbaro 2009 {published data only} Livesey C, Wylde V, Descamps S, Estela CM, Bannister
Chibbaro S, Tacconi L. Use of skin glue versus traditional GC, Learmonth ID, et al.Skin closure after total hip
wound closure methods in brain surgery: a prospective, replacement: a randomised controlled trial of skin adhesive
randomized, controlled study. Journal of Clinical versus surgical staples. Journal of Bone and Joint Surgery
Neuroscience 2009;16(4):535–9. 2009;91(6):725–9.
Dowson 2006 {published data only} Maartense 2002 {published data only}
Dowson C, Gilliam A, Speake W, Lobo D, Beckingham. A Maartense S, Bemelman WA, Dunker MS, de Lint C,
prospective, randomised controlled trial comparing n-butyl Pierik EGJM, Busch ORC, et al.Randomised study of the
cyanoacrylate tissue adhesive (Liquiband) with sutures for effectiveness of closing laparoscopic trocar wounds with
skin closure after laparoscopic general surgical procedures. octylcyanoacrylate, adhesive papertape or poliglecaprone.
Surgical Laparoscopy, Endoscopy and Percutaneous Techniques British Journal of Surgery 2002;89:1370–5.
2006;16(3):146–50. Maloney 2013 {published data only}
Eggers 2011 {published data only} Maloney J, Rogers GS, Kapadia M. Surgical corner: a
Eggers MD, Fang L, Lionberger DR. A comparison of prospective randomized evaluation of cyanoacrylate glue
wound closure techniques for total knee arthroplasty. devices in the closure of surgical wounds. The Journal of
Journal of Arthroplasty 2011;26(8):1251–8. Drugs in Dermatology 2013;12(7):810–4.
Greene 1999 {published data only} Millan 2011 {published data only}
Greene D, Kock RJ, Goode RL. Efficacy of octyl-2- Millan P, Olivera R, Sanchez A. Efficacy and safety of 2-
cyanoacrylate tissue glue in blepharoplasty. Archives of Facial octylcyanoacrylate versus simple suture in surgical wound
Plastic Surgery 1999;1:292–6. closure of chronic skin inflammation. Dermatologia Revista
Jallali 2004 {published data only} Mexicana 2011;55(4):185–7.
∗
Jallali N, Haji A, Watson CJ. A prospective randomized Mota 2009 {published data only}
trial comparing 2-octylcyanoacrylate to conventional Mota R, Costa F, Amaral A, Oliveira F, Santos CC, Ayres-
suturing in closure of laparoscopic cholecystectomy De-Campos D. Skin adhesive versus subcuticular suture
for perineal skin repair after episiotomy - a randomized Switzer 2003 {published data only}
controlled trial. Acta Obstetricia et Gynecologica Scandinavica Swtizer E, Dinsmore R, North J. Subcuticular closure versus
2009;88(6):660–6. dermabond: a prospective randomised trial. The American
Surgeon 2003;69:434–6.
Ong 2002 {published data only}
Ong C, Jacobsen A, Joseph V. Comparing wound closure Tierny 2009 {published data only}
using tissue glue versus subcuticular suture for paediatric Tierney EP, Moy RL, Kouba DJ. Rapid absorbing gut
surgical incisions: a prospective, randomised trial. Paediatric suture versus 2-octylethylcyanoacrylate tissue adhesive in
Surgery International 2002;18:553–5. the epidermal closure of linear repairs. Journal of Drugs in
Dermatology 2009;8(2):115–9.
Ozturan 2001 {published data only}
Ozturan O, Miman MC, Aktas D, Oncel S. Toriumi 1998 {published data only}
Butylcyanoacrylate tissue adhesive for columellar incision Toriumi DM, O’Grady K, Desai D, Bagal AB. Use of octyl-
closure. The Journal of Laryngology and Otology 2001;115: 2-cyanoacrylate for skin closure in facial plastic surgery.
535–40. Plastic and Reconstructive Surgery 1998;102(6):2209–19.
Pronio 2011 {published data only} van den Ende 2004 {published data only}
Pronio A, Di Fillippo A, Narillii P, Caporilli D, Vestri A, van den Ende ED, Vriens PWHE, Allema JH, Breslau
Ciamberlaon B, et al.Closure of cutaneous incision after PJ. Adhesive bonds or percutaneous absorbable suture
thyroid surgery: a comparison between metal clips and for closure of surgical wounds in children. Results of a
cutaneous octyl-2-cyanoacrylate adhesive. A prospective prospective randomized trial. Journal of Pediatric Surgery
randomized clinical trial. European Journal of Plastic Surgery 2004;39:1249–51.
2011;34:103–10.
References to studies excluded from this review
Ridgway 2007 {published data only}
Ridgway D, Mahmood F, Moore L, Bramley D, Moore P. A Ak 2012 {published data only}
blinded, randomised, controlled trial of stapled versus tissue Ak G, Alpk l ç Bak rt E, Kürklü E, Koray M, Tanyeri
glue closure of neck surgery incisions. Annals of the Royal H, Zülfikar B. The evaluation of fibrin sealants and tissue
College of Surgeons of England 2007;89(3):242–6. adhesives in oral surgery among patients with bleeding
Romero 2011 {published data only} disorders. Turkish Journal of Hematology 2012;29(1):40–7.
Romero P, Frongia G, Wingerter S, Holland-Cunz S. Alhopuro 1976 {published data only}
Prospective, randomized,controlled trial comparing a tissue Alhopuro S, Rintala A, Salo H, Ritsila V. Tissue adhesive
adhesive (Dermabond™) with adhesive strips (Steri- versus sutures in closure of incision wounds. A comparative
Strips™) for the closure of laparoscopic trocar wounds in study in human skin. Annales Chirurgiae et Gynaecologiae
children. European Journal of Pediatric Surgery 2011;21(3): 1976;65:308–12.
159–62. Chen 2010 {published data only}
Sebesta 2004 {published data only} Chen K, Klapper AS, Voige H, Del Priore G. A randomized,
Sebesta MJ, Bishoff JT. Octylcyanoacrylate skin closure controlled study comparing two standardized closure
in laparoscopy. Journal of the Society of Laparoendoscopic methods of laparoscopic port sites. Journal of the Society of
Surgery 2004;8(1):9–14. Laparoendoscopic Surgery 2010;14(3):391–4.
Shamiyeh 2001 {published data only} Chow 2010 {published data only}
Shamiyeh A, Schrenk P, Stelzer T, Wayand WU. Prospective Chow A, Marshall H, Zacharakis E, Paraskeva P, Purkayastha
randomised blind controlled trial comparing sutures, tape, S. Use of tissue glue for surgical incision closure: a systematic
and octylcyanoacrylate tissue adhesive for skin closure after review and meta-analysis of randomized controlled trials.
phlebectomy. Dermatologic Surgery 2001;27(10):877–80. Journal of the American College of Surgery 2010;211:115–25.
Sinha 2001 {published data only} Giri 2004 {published data only}
Sinha S, Naik M, Wright V, Timmons J, Campbell AC. A Giri P, Das MK, Majumdar Giri A. Management of
single blind, prospective, randomised trial comparing n- different types of wound by cyanoacrylate glue fixation: a
butyl 2-cyanoacrylate tissue adhesive (Indermil) and sutures random study of 213 patients. Journal of the Indian Medical
for skin closure in hand surgery. Journal of Hand Surgery Association 2004;102(11):624, 626.
2001;26B(3):264–5. Gorozpe-Calvillo 1999 {published data only}
Sniezek 2007 {published data only} Gorozpe-Calvillo JI, Gonzalez-Villamil J, Santoya-Haro
Sniezek P, Walling H, DeBloom III J, Messingham M, S. Closure of the skin with cyanoacrylate in caesarian
VanBeek M, Kreiter C, et al.A randomised controlled surgery [Cierre de la piel con cianoacrilato en las cesareas].
trial of high-viscosity 2-octyl cyanoacrylate tissue adhesive Ginecologia y Obstetricia de Mexico 1999;67:491–5.
versus sutures in repairing facial wounds following Mohs Jaibaji 2000 {published data only}
micrographic surgery. Dermatological Surgery 2007;33(8): Jaibaji M, Liddington M, Geary P, Darcy C, Batchelor A,
966–71. Roberts A. Evaluation of the long term outcome of wounds
closed with “Indermil” adhesive. European Journal of Plastic European Journal of Pacing, Arrhythmias and Cardiac
Surgery 2000;23:330–2. Electrophysiology 2011;13(3):416–20.
Kuo 2006 {published data only} Steiner 2000 {published data only}
Kuo F, Lee D, Rodgers G. Prospective, randomised, blinded Steiner Z, Mogilner J. Histoacryl vs Dermabond
study of a new wound closure film versus cutaneous suture cyanoacrylate glue for closing small operative wounds.
for surgical wound closure. Dermatological Surgery 2006; Harefuah 2000;139(11-12):409-11, 496.
32:676–81. Sun 2005 {published data only}
Matin 2003 {published data only} Sun J, Chen Q-M, Zhang M, Shi C. Octylcyanoacrylate
Matin SF. Prospective randomized trial of skin adhesive versus absorbable suture in the repair of skin wounds in
versus sutures for closure of 217 laparoscopic port-site children. Zhongguo Linchuang Kangfu 2005;9(19):186–7.
incisions. Journal of the America College of Surgeons 2003;
Wong 2011 {published data only}
196(6):845–53.
Wong EM, Rainer TH, Ng YC, Chan MS, Lopez V. Cost-
Maw 1997 {published data only} effectiveness of Dermabond versus sutures for lacerated
Maw JL, Quinn JV, Wells GA, Ducic Y, Odell PF, Lamothe wound closure: a randomised controlled trial. Hong Kong
A, et al.A prospective comparison of octylcyanoacrylate Medical Journal 2011;17 Suppl 6:4–8.
tissue adhesive and suture for the closure of head and neck
incisions. Journal of Otolaryngology 1997;26(1):26–30. References to studies awaiting assessment
Ong 2010 {published data only}
Gennari 2004 {published data only}
Ong J, Ho KS, Chew MH, Eu KW. Prospective randomised
study to evaluate the use of DERMABOND ProPen (2- Handschel 2006 {published data only}
octylcyanoacrylate) in the closure of abdominal wounds Jan 2013 {published data only}
versus closure with skin staples in patients undergoing
Nipshagen 2008 {published data only}
elective colectomy. International Journal of Colorectal Disease
2010;25(7):899–905. Yoon 2006 {published data only}
Orozco-Razon 2002 {published data only} Additional references
Orozco-Razon LF, Millan-Guerrero RO, Vera-Rodriguez
SE. Butylcyanoacrylate tissue adhesive for columellar Bruns 1996
incision closure [Cyanoacrylate compared with traditional Bruns TB, Simon HK, McLario DJ. Laceration repair using
surgery in tension–free incision closure [Spanish]]. Gaceta a tissue adhesive in a children’s emergency department.
Medica de Mexico 2002;138(6):505–9. Pediatrics 1996;98:673–5.
Quinn 1998 {published data only} Coover 1959
Quinn J, Wells G, Sutcliffe T, Jarmuske M, Maw J, Stiell I, Coover HN, Joyner FB, Sheere NH. Chemistry and
et al.Tissue adhesive versus suture wound repair at 1 year: performance of cyanoacrylate adhesive. Journal of the Society
randomized clinical trial correlating early, 3-month, and 1- of Plastic Surgery of England 1959;1:5–6.
year cosmetic outcome. Annals of Emergency Medicine 1998; Deeks 2011
32(6):645–9. Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9:
Sajid 2009 {published data only} Analysing data and undertaking meta-analyses. In: Higgins
Sajid MS, Siddiqui MR, Khan MA, Baig MK. Meta-analysis JPT, Green S (editors). Cochrane Handbook for Systematic
of skin adhesives versus sutures in closure of laparoscopic Reviews of Interventions. Version 5.1.0 (updated March
port-site wounds. Surgical Endoscopy 2009;23(6):1191–7. 2011). The Cochrane Collaboration, 2011. available from
Silvestri 2006 {published data only} www.cochrane-handbook.org.
Silvestri A, Brandi C, Grimaldi L, Nisi G, Brafa A, Calabro Dunker 1998
M, et al.Octyl-2-cyanoacrylate adhesive for skin closure and Dunker MS, Stiggelbout AM, van Hogezand RA, Ringers
prevention of infection in plastic surgery. Aesthetic Plastic J, Griffioen G, Bemelman WA. Cosmesis and body image
Surgery 2006;30:695–9. after laparoscopic assisted and ileocolic resection for Crohn’s
disease. Surgical Endoscopy 1998;12:1334–40.
Singer 2002 {published data only}
Singer AJ, Quinn JV, Clarke RE, Hollander JE. Closure Emori 1993
of lacerations and incisions with octylcyanoacrylate: a Emori TG, Gaynes RP. An overview of nosocomial
multicentre randomised controlled trial. Surgery 2002;131: infections, including the role of the microbiological
270–6. laboratory. Clinical Microbiology 1993;6:428–42.
Spencker 2011 {published data only} Farion 2001
Spencker S, Coban N, Koch L, Schirdewan A, Mueller D. Farion KJ, Russell KF, Osmond MH, Hartling L,
Comparison of skin adhesive and absorbable intracutaneous Klassen TP, Durec T, et al.Tissue adhesives for traumatic
suture for the implantation of cardiac rhythm devices. lacerations in children and adults. Cochrane Database

of Systematic Reviews 2001, Issue 4. [DOI: 10.1002/ of lacerations during competitive athletics. American Journal
14651858.CD003326] of Emergency Medicine 2000;18:261–3.
Higgins 2003
Quinn 1993
Higgins JPT, Thompson SG, Deeks JJ, Altman DG.
Quinn JV, Drzewiecki A, Li MM, Stiell IG, Sutcliffe T,
Measuring inconsistency in meta-analyses. BMJ 2003;327
Elmslie TJ, et al.A randomised, controlled trial comparing a
(7414):557–60.
tissue adhesive with suturing in the repair of paediatric facial
Higgins 2011 lacerations. Annals of Emergency Medicine 1993;22:1130–5.
Higgins JPT, Altman DG, Sterne JAC (editors). Chapter
8: Assessing risk of bias in included studies. In: Higgins Quinn 1995
JPT, Green S (editors). Cochrane Handbook for Systematic Quinn JV, Drzewiecki AE, Stiell IG, Elmslie TJ. Appearance
Reviews of Interventions. Version 5.1.0 (updated March scales to measure cosmetic outcomes of healed lacerations.
2011). The Cochrane Collaboration, 2011. Available from American Journal of Emergency Medicine 1995;13:229–31.
www.cochrane-handbook.org.
Quinn 1997
Hollander 1995 Quinn J, Wells G, Sutcliffe T. A randomized trial comparing
Hollander JE, Singer AJ, Valentine S, Henry MC. Wound octylcyanoacrylate tissue adhesive and sutures in the
registry: development and validation. Annals of Emergency management of lacerations. JAMA 1997;277(19):1527–30.
Medicine 1995;25:675–85.
Schunemann 2011a
Houston 1969
Schünemann HJ, Oxman AD, Higgins JPT, Vist GE,
Houston S, Hodge JW Jr, Ousterhout DK, Leonard F. The
Glasziou P, Guyatt GH. Chapter 11: Presenting results
effect of alpha-cyanoacrylates on wound healing. Journal of
and ’Summary of findings’ tables. In: Higgins JPT,
Biomedical Materials Research 1969;3(2):281–9.
Green S (editors). Cochrane Handbook for Systematic
Lefebvre 2011 Reviews of Interventions Version 5.1.0 (updated March
Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching 2011). The Cochrane Collaboration, 2011. Available from
for studies. In: Higgins JPT, Green S (editors). Cochrane www.cochrane-handbook.org.
Handbook for Systematic Reviews of Interventions. Version
5.1.0 (updated March 2011). The Cochrane Collaboration, Schunemann 2011b
2011. Available from www.cochrane-handbook.org 2011. Schünemann HJ, Oxman AD, Higgins JPT, Deeks JJ,
Malone 2002 Glasziou P, Guyatt GH. Chapter 12: Interpreting results
Malone DL, Genuit T, Tracy JK. Surgical site infections: and drawing conclusions. In: Higgins JPT, Green S
reanalysis of risk factors. Journal of Surgical Research 2002; (editors). Cochrane Handbook for Systematic Reviews
103:89–95. of Interventions Version 5.1.0 (updated March 2011).
The Cochrane Collaboration, 2011. Available from
Osmond 1999
www.cochrane-handbook.org.
Osmond MH. Pediatric wound management: the role of
tissue adhesives. Pediatric Emergency Care 1999;15(2): SIGN 2011
137–40. Scottish Intercollegiate Guidelines Network (SIGN). Search
Perron 2000 filters. http://www.sign.ac.uk/methodology/filters.html#
Perron AD, Garcia JA, Hays EP. The efficacy of random 2011.
∗
cyanoacrylate-derived surgical adhesive for use in the repair Indicates the major publication for the study

CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Amin 2009
Methods RCT with 3 months follow-up. 72 participants randomised, but only 60 had 3-month
outcome data collected and reported
Participants 72 participants receiving minimally invasive thyroidectomy using either video-assisted

thyroidectomy or minimal incision thyroidectomy
Surgery performed in 1 centre in Ireland. All cases were performed by the senior surgeon
Exclusion criteria: autoimmune thyroiditis, diabetes mellitus and/or poor general health
Trial conducted in Dublin, Ireland
Interventions Group 1 (n = 38; results reported for 33): 2-octylcyanoacrylate (Dermabond®) tissue
adhesive (Ethicon Inc, a Johnson & Johnson company, Somerville, New Jersey, USA)
Group 2 (n = 34; results reported for 27): staples
Outcomes Cosmetic appearance by participant and by surgeon (at 3 months) using the Manchester
scar scale
Patient satisfaction (self assessed at 3 months): collected using a 10 cm VAS line where
0 was poor and 10 was excellent. Data for overall patient satisfaction score (n = 60) was
calculated by the review authors using summary data presented in the study report. The
patient satisfaction assessment form also measured: cosmesis; ability to shower same day
(as operation); need to visit GP for wound; pain on removing clips; pain/tightness of
wound; overall wound comfort and allergic reactions. Only ability to shower data was
reported in addition to overall satisfaction score - ability to shower data are not presented
here
Notes Cosmetic appearance outcome data not clearly presented for participants or surgeons.
Authors contacted
Study also reports pain at 1 and 10 days after surgery - not reported here
Cost of tissue adhesive reported as EUR22 - no corresponding data for staples
Risk of bias
Bias Authors’ judgement Support for judgement
Random sequence generation (selection Low risk Quote: “Randomization was performed prior
bias) to commencement of the study as follows:
Opaque envelopes were numbered sequen-
tially from 1 to 75. A table of random num-
bers was generated by a computer program
and used for group assignment; if the last digit
of the random number was from 0 to 4, the
assignment was to Group A (tissue adhesive)
, and if the last digit was from 5 to 9, the
assignment was to Group B (staples).”
Comment: adequate method of random se-

Amin 2009 (Continued)
quence generation
Allocation concealment (selection bias) Low risk Quote: “The assignments were then placed
into the opaque envelopes and the envelopes
sealed. As eligible participants were entered
into the trial, these envelopes were opened in
sequential order to give each patient his or
her random group assignment. The envelopes
were opened by the operating surgeon follow-
ing patient consent and just prior to the sur-
gical procedure.”
Comment: use of sealed, numbered opaque
envelopes considered robust
Blinding of participants and personnel Unclear risk Quote: “Blinding was not feasible at the time
(performance bias) of skin closure, nor was it of any benefit at the
All outcomes two-week postoperative visit, as wound cosme-
sis at this stage is not considered predictive of
the long-term cosmetic outcome.”
Comment: understandably difficult to
blind operating surgeon and participants
to the intervention.Staff would have been
aware of allocation on wound closure and
during short-term post-operative assess-
ment - however none of these outcomes
are reported here. Participants were not
blinded. Unclear whether this would have
led to bias in the study in terms of satisfac-
tion in favour of 1 treatment
Blinding of outcome assessment (detection Low risk Quote: “Blinding was achieved during eval-
bias) uation of the surgical wound at or after three
All outcomes months postoperatively as surgeons were un-
aware of the wound closure method used. A
three-month appointment was arranged for
each participant for wound evaluation by a
surgeon who was not involved in the patient
management.”
Comment: blinded outcome assessment
undertaken at 3 months for surgeon cos-
metic outcome data although we were un-
able to extract these data for the review. Par-
ticipant assessment not blinded (as noted
above)
Incomplete outcome data (attrition bias) Unclear risk Quote: “Sixty out of the 72 patients agreed
All outcomes to come back for the three-month postopera-
tive evaluation. The remainder did not at-
tend do to the long travelling [sic]/commuting

Amin 2009 (Continued)
distance to the tertiary service”

Comment: data from only 60 of the 72
participants randomised were available at 3
months. Also possible differential attrition
(adhesive 13%, staples 21%). Deemed to
be at unclear risk of bias
Selective reporting (reporting bias) High risk Comment: multiple dimensions of patient
satisfaction assessed with ability to shower
selectively reported - data not presented
here. Study protocol not sought
Other bias Low risk None noted
Avsar 2009
Methods RCT with 40 participants with 40 days follow-up
Participants 40 women undergoing the Pfannenstiel incision

Exclusion criteria: known allergy to trial products
Conducted in Turkey
Interventions Group 1 (n = 20): high viscosity 2-octylcyanoacrylate (High Viscocity Dermabond®;

Ethicon Inc, a Johnson & Johnson company, Somerville, New Jersey, USA) tissue adhe-
sive
Group 2 (n = 20): polypropylene sutures
All participants had skin cleansed with povidone iodine and 1 g antibiotic prophylaxis
Outcomes Wound infection (at 2, 7 and 40 days after surgery: 7-day data used for analyses, as these
data were most clear from the translation)
Time for skin closure
Participant satisfaction at day 40. Participants were asked how satisfied they were with
their skin closure they could select from the following responses: very bad, poor, average,
good, very good
Notes Data extraction based on English language abstract and partial translation of report text
that was published in Turkish
The study reports an outcome - wound disruption - as yet we have been unable to
translate whether this can be interpreted as wound dehiscence
Cometic appearance not used in this review as assessed at less than 3 months
Risk of bias
Random sequence generation (selection Unclear risk Comment: unable to gauge from transla-
bias) tion

Avsar 2009 (Continued)
Allocation concealment (selection bias) Unclear risk Comment: unable to gauge from transla-
tion
Blinding of participants and personnel Unclear risk Comment: unable to gauge from transla-
(performance bias) tion
All outcomes
Blinding of outcome assessment (detection Unclear risk Comment: unable to gauge from transla-
bias) tion
All outcomes
Incomplete outcome data (attrition bias) Unclear risk Comment: unable to gauge from trans-
All outcomes lation. We acknowledge risk of selection
bias from reporting infection outcome data
from the time point where statistical signif-
icance was observed
Selective reporting (reporting bias) Unclear risk Comment: unable to gauge from transla-
tion
Other bias Unclear risk Comment: unable to gauge from transla-

tion
Blondeel 2004
Methods RCT with 1-month follow-up
Participants 217 adults requiring any skin incision closure 4 cm or greater in length. Multicentre study
conducted at: Department of Plastic Surgery, University Hospital Gent, Gent, Belgium;
Intitute Mutualiste Montsouris, Paris, France; Crestwood Hospital, Huntsville, AL, USA;
Gynecologic Oncology Research and Development, LLC, Greenville, SC, USA; Naval
Medical Centre, San Diego, CA, USA; University Dental Hospital, Manchester, UK
Exclusion criteria: a history of peripheral vascular disease; insulin-dependent diabetes; a
blood-clotting disorder or taking anticoagulants within 7 days of surgery; concurrent use
of steroids; or a personal or family history of keloid formation or hypertrophy; impaired
wound healing; or a known allergy to cyanoacrylate or formaldehyde

sive
Group 2 (n = 103): any other commercially available device such as sutures, staples,
or tapes or compared with low viscosity 2-octylcyanoacrylate (n = 42; Dermabond®,
Ethicon Inc, a Johnson & Johnson company, Somerville, New Jersey, USA)
Outcomes Wound dehiscence, infection, patient satisfaction and surgeon satisfaction at 10 days
Notes Cosmetic appearance data not used as measured at less than 3 months

Blondeel 2004 (Continued)
Risk of bias
Random sequence generation (selection Low risk Quote: ” . . . patients at each study site were randomised
bias) by computer generated code in a 1:1 ratio to epidermal
incision closure with high viscosity 2-octylcyanoacrlate or
a commercially available device“
Comment: use of computer generated code constitutes
low risk
Allocation concealment (selection bias) Unclear risk Quote: ”Sealed envelopes containing the concealed treat-
ment allocations were opened in the operating room im-
mediately before epidermal closure.“
Comment: judgement of unclear risk of bias made as
not clear whether envelopes were sequentially num-
bered and opaque. Not clear who was responsible for
allocation
Blinding of participants and personnel Unclear risk Quote: ”Blinding to type of treatment was not feasible“,
(performance bias) due to the nature of the personnel-led intervention
All outcomes Comment: understandably difficult to fully blind par-
ticipants and personnel to intervention
Blinding of outcome assessment (detection Unclear risk Quote: ”On day 10, wounds were assessed for adequate
bias) progress in healing, wound-related infection, and indica-
All outcomes tors of an acute inflammatory reaction.“ Similarly, ” . .
. on day 10, physicians completed a questionnaire that
measured satisfaction with each use of a device.“, also, “a
counterpart questionnaire [given to patients] for patient
satisfaction for cosmesis, overall comfort, ability to shower,
dressing changes, tension at the wound, hygienic problem,
allergic reaction, and overall satisfaction”
Comment: there is no mention that the wound was
assessed by a blinded assessor. Such assessment would
be difficult for satisfaction scores - as noted above
Incomplete outcome data (attrition bias) Low risk Quote: “The study was not completed by 4 patients as-
All outcomes signed to high viscosity group 2 octylcyanoacrylate because
of voluntary withdrawal (n=2), or loss to follow up (n=
2) and by 6 patients to the control devices because of vol-
untary withdrawal (n=2), loss to the follow up (n=3), or
death (n=1) [attributed to Burkitt’s Lymphoma]”.
Comment: the numbers were fairly small and were
fairly evenly distributed between the treatment arms.
Therefore we do not believe this represented a signifi-
cant risk of bias

Blondeel 2004 (Continued)
Selective reporting (reporting bias) Low risk No direct quotations, but all the variables outlined in
the methodology were accounted for in the results
Comment: judged as low risk. Study protocol not
sought
Other bias Low risk No other sources of bias were detected
Brown 2009
Methods Parallel RCT with 6 weeks follow-up. No withdrawals reported
Participants 134 children undergoing inguinal herniorrhaphy (ages ranged from 1 month to 12 years)
All operations performed by 1 of 4 paediatric surgeons
No other inclusion or exclusion data reported
Undertaken in 1 centre in the USA
Interventions Group 1 (n = 64): 2-octylcyanoacrylate (Dermabond®) tissue adhesive (Ethicon Inc, a

Johnson & Johnson company, Somerville, New Jersey, USA)
Group 2 (n = 70): sutures (5.0 Monocryl)
Group numbers calculated from data in paper as not reported directly
Outcomes Wound dehiscence (6 weeks)

Time for skin closure
Relative costs of materials required for skin closure
Notes Surgeon cosmetic appearance data not used as measured at < 3 months
Risk of bias
Random sequence generation (selection Unclear risk Quote: “Just before wound closure, a sealed
bias) envelope indicating randomization to skin
adhesive or suture closure was revealed.”
Comment: no information about how the
randomisation sequence was generated
Allocation concealment (selection bias) Unclear risk Quote: “Just before wound closure, a sealed
envelope indicating randomization to skin
adhesive or suture closure was revealed.”
Comment: no information about whether
envelopes were opaque and sequential and
who prepared or opened these
Blinding of participants and personnel Unclear risk Quote: “Masking as to skin adhesive vs su-
(performance bias) ture closure was not possible for the operating
All outcomes surgeon because of the nature of the interven-
tion.”
Brown 2009 (Continued)

blind operating surgeon and participants
to the intervention. Staff would have been
aware of allocation on wound closure
Blinding of outcome assessment (detection Low risk Quote: “However, subsequent interviewers
bias) were masked as to group during assessment of
All outcomes cosmetic outcome measures, as well as those
related to efficiency, cost, and complications of
wound closure.”
Comment: deemed at low risk of bias for
debridement and costs outcomes
Incomplete outcome data (attrition bias) Low risk No report of any loss to follow-up
All outcomes Comment: judged as low risk
Selective reporting (reporting bias) Low risk No direct quotations, but all the vari-
ables outlined in the methodology were ac-
counted for in the results
Comment: judged as low risk. Study pro-
tocol not sought
Cheng 1997
Methods RCT with 1-month follow-up
Participants 86 healthy male patients under the age of 12 years requiring elective circumcision. Study
conducted at Duchess of Kent Hospital, Hong Kong. No specific exclusion criteria were
described
Interventions Group 1 (n =40): butylcyanoacrylate (Histoacryl®) tissue adhesive

Group 2 (n = 46): 4.0 catgut sutures
Outcomes Dehiscence and infection at days 1, 2, 3, 7 and 30. Cosmetic appearance, bleeding
and wound inflammation were also assessed at these time points. Bleeding and wound
inflammation were not of interest to this review
Notes Cosmetic appearance data were not used as measured at < 3 months
Risk of bias
Random sequence generation (selection Unclear risk Quote: “ . . . [patients were] randomised into two groups”
bias) Comment: no method of random sequence generation
was actively discussed; therefore the risk of bias for this

Cheng 1997 (Continued)
domain is unclear
Allocation concealment (selection bias) Unclear risk Quote: Patients were “ . . . randomised into two groups”
as previously mentioned
Comment: no method of allocation concealment was
made clear. Therefore, the risk of bias is again unclear
Blinding of participants and personnel Unclear risk Not reported whether the participants or personnel
(performance bias) were blinded to the intervention
All outcomes Comment: as the participants were under the age of
12 and under general anaesthesia, it is reasonable to as-
sume that they were blinded to the intervention. How-
ever, the personnel were probably not blinded as they
carried out the intervention
Blinding of outcome assessment (detection Unclear risk Quote: “The wounds of all the patients were then assessed
bias) on day 1, day 2 and day 3, 1 week and 1 month after the
All outcomes operation. Wound inflammation, infection, bleeding, cos-
metic result and dehiscence were assessed. A questionnaire
was completed”
Comment: no mention of whether the assessors of the
wound and the cosmetic results were blinded to the
intervention. It is not clear if the questionnaire was
filled out by parents of the children, who may have
been blinded to the intervention, or the assessors, who
were likely to know which intervention was given. The
judgement for this domain is therefore unclear
Incomplete outcome data (attrition bias) Low risk No direct quotations, but no losses to follow-up were
All outcomes reported
Comment: therefore judged as low risk
Selective reporting (reporting bias) Low risk No direct quotations, but the results account for the all
the assessment methods identified to qualify the success
of the intervention
Comment: no evidence of reporting bias, therefore
judged as low risk
Other bias Unclear risk Possible unit of analysis issue for dehiscence outcome
Chibbaro 2009
Methods RCT with up to 12 months follow-up, with assessment at 1, 3, 5-7 and 14 days, then 1,
3, 6 and 12 months
Participants 40 participants undergoing elective cranial supratentorial surgery

Exclusion criteria: undergoing a procedure for infective pathology; head trauma; admis-
sion to the intensive care unit; a dermatologic disease; previous cranial radiotherapy;
diabetes mellitus; known blood-clotting disorders; and allergy to cyanoacrylate products
Chibbaro 2009 (Continued)
Undertaken in 1 centre in Italy
Interventions Group 1 (n = 20): n-butyl-cyanoacrylate (Liquiband®; MedLogic Global Ltd, Plymouth,

Devon, UK) tissue adhesive
Group 2 (n = 20): sutures (Monosof 2/0, Tyco United States Surgical, Norwalk, CT,
USA) or staples (Auto Suture Appose ULC 35, Tyco United States Surgical)
All participants received the same antibiotic prophylaxis (1 dose of 3rd-generation
cephalosporin 20 min prior to surgical incision)
Wound dressings were not used for those allocated to tissue adhesive because this formed
its own waterproof and antimicrobial wound dressing
Participants in the tissue adhesive group (Group 1) were permitted to shower from
the day after the surgical procedure, while those participants allocated to sutures were
instructed to keep their wounds clean and dry until the removal of the sutures
Outcomes Wound dehiscence (collected to 7th day postoperatively)

Wound infection (collected to 7th day postoperatively; infection not defined)
Cosmetic appearance (nurse-blinded) using modified Hollander Wound Score scale (up
to 12 months)
Skin closure time
Notes Cosmetic appearance (patient and surgeon) using a VAS of 1 to 10 where a score of 10
reflected optimal cosmetic outcome. It is not clear at what time points these data were
collected. Authors were contacted
Supplmentary material referenced in the main paper also checked
Risk of bias
Random sequence generation (selection Unclear risk Quote:”At the moment of skin closure, they
bias) [the patients] were randomly allocated into
one of two groups (A or B) of 20 patients each.
“
Comment: no reporting on how the pa-
tients were randomly allocated or the
method used
Allocation concealment (selection bias) Unclear risk Quote: ”The randomization sequence was
arranged on the same day as surgery; each pa-
tient’s name was randomly assigned to one of
40 envelopes (20 marked as LiquiBand, 10
as TTS and 10 as SC).“
Comment: no indication that the alloca-
tion was concealed
Blinding of participants and personnel Unclear risk No direct quotations. Did not report that
(performance bias) the participants or personnel were blinded
All outcomes to the intervention

Chibbaro 2009 (Continued)
blind the operating surgeon to the inter-

vention
Blinding of outcome assessment (detection Unclear risk Quote: ”All of the patients were followed up
bias) post-operatively on days 1, 3, 5-7 by the same
All outcomes ward nurse who initially recorded details re-
garding their wound aspects“
”After discharge, a second nurse (not from
the neurosurgical department), using the same
scale, continued the follow-up, initially at 2
weeks, and then at 1, 3, 6 and 12 months
post-operatively”. Noted in abstract that this
second nurse was blinded
Comment: although the study intimates
that the nurse was not from the department
and the second nurse was blinded it is not
clear that the first nurse was blinded
Incomplete outcome data (attrition bias) Low risk Quote: “Only 39 patients (19 in group
All outcomes A and 20 in group B) were available at
the 12 month follow up, as one patient in
group A developed a post-operative intracra-
nial haematoma. This required an emergency
evacuation procedure and the wound was sub-
sequently closed with stitched”
Comment: given that 39/40 participants
had 12-month data available, we made an
overall judgment of low risk of attrition bias
tocol not sought
Other bias Low risk No other sources of bias detected
Dowson 2006
Methods Parallel group RCT with 3-month follow-up
Participants 168 patients recruited for laparoscopic procedures at Queen’s Medical Centre, Notting-
ham. 154 participants included in the final analysis. Withdrawals were accounted for.
Exclusion criteria included insulin dependant diabetes, prolonged corticosteroid use;
known keloid scarring; wounds greater than 5cm in length without deep layer sutures;
those undergoing emergency surgery; patients unable to give informed consent

Dowson 2006 (Continued)
Interventions Group 1 (n = 76): n-butyl-cyanoacrylate (Liquiband®; MedLogic Global Ltd, Plymouth,

Group 2 (n = 78): interrupted, non-absorbable suture
Outcomes Time to closure, dehiscence, satisfaction, cosmesis and infection (we used 24 to 48 h
figures to avoid unit of analysis issues for dehiscence and infection)
Notes Unclear reference to subcutaneous layers being dealt with. Authors contacted for mean
and standard deviations of time to closure and cosmesis, but as we received no reply, this
information was not included
Risk of bias
Random sequence generation (selection Unclear risk Quote: “Randomisation was performed using
bias) consecutively numbered, sealed envelopes by a
person not involved with the study”
Comment: although allocation was con-
cealed, there was no specific mention of
how the sequence was randomly generated
Allocation concealment (selection bias) Low risk Quote: “Randomisation was performed using
consecutively numbered, sealed envelopes by a
person not involved with the study”
Comment: allocation was concealed ade-
quately
Blinding of participants and personnel Unclear risk Quote: “Participants in the trial were not in-
(performance bias) formed of the wound closure method they had
All outcomes been allocated to until they had undergone
surgery. The investigators were not blinded”
Comment: the risk of performance bias was
unclear as it was not possible to blind the in-
vestigators to the procedure they were car-
rying out
Blinding of outcome assessment (detection Unclear risk Quote: “Patients were followed up at 24 to
bias) 48 hours, 4 to 6 weeks and 3 months postoper-
All outcomes atively by C.C.D, A.D.G., or W.J.S. At these
times it was documented if wounds showed
any of the following characteristics; erythema,
oedema, tenderness, inflammation, drainage/
discharge and/or malodorous smell.”
Concurrently, at the 3 month cosmetic
evaluation, “a blinded assessment by a quali-
fied nurse or surgical registrar not involved in
the study also being made at 3 months”

Dowson 2006 (Continued)
Comment: adequate blinding of assess-

ment at 3 months. Potential for high risk of
detection bias for outcomes reported prior
to this
Incomplete outcome data (attrition bias) High risk Flow chart suggests no loss to follow-up
All outcomes in first 48 h postoperatively. At 4-6 weeks
20 participants were lost to follow-up in
the suture arm and 15 in the adhesive arm.
There was further loss to follow-up at 3
months: the suture arm suffered a total loss
of 14 (with 7 missing both the 4-6 week and
the 3-month follow-up), while the adhesive
group had 8 missing the 3-month follow-
up (with 6 missing both follow-ups)
Comment: relative high attrition of data
from study for outcomes collected at later
time points
tocol not sought
Other bias Low risk No other sources of bias identified
Eggers 2011
Methods 4-arm parallel RCT with 90 participants with 6 weeks of follow-up (assessment at 24 h,
3 and 6 weeks). Only data on 75 of participants were reported
Participants Participants undergoing total knee arthroplasty

Exclusion criteria: medical conditions or personal circumstances that would prevent par-
ticipation and completion of physical therapy and follow-up visits; current participation
in another clinical trial; preoperative systemic infections; uncontrolled diabetes; diseases
or conditions known to effect the wound healing process; known hypersensitivity to
cyanoacrylate, formaldehyde, or the dye D&C Violet #2 (Aesculap, Inc, Center Valley,
PA); prior knee hardware fixation devices; prior knee incisions greater than 9 cm, and
arthrofibrosis as evidence by limited ROM of 80° or higher
Study performed in 1 centre in the USA
Interventions Group 1 (n = 19): subcutaneous closure method: sutures at 1.5/cm; skin closure method:
2-octylcyanoacrylate (Dermabond®) tissue adhesive (Ethicon Inc, a Johnson & Johnson
company, Somerville, New Jersey, USA)
Group 2 (n = 18): subcutaneous closure method: sutures at 1.5/cm; skin closure method:
butylcyanoacrylate tissue adhesive (Histoacryl Blue tissue adhesive B Braun Corp)
staples (Visistat 35W Stapler (Teleflex Corp)
Eggers 2011 (Continued)
Monocryl suture (poliglecaprone 25; Ethicon)
Data on 15 participants were excluded from analysis data: it was not reported which trial
groups these participants were from.
We note there were slight difference to the procedures in each group for the method of
closure of the sub-cutaneous layer. Details for (1) sub-cutaneous closure methods and
(2) skin closure method are provided above
Outcomes Wound dehiscence (24 h, 3 weeks, and 6 weeks postoperatively)

Wound infection (24 h, 3 weeks, and 6 weeks postoperatively; infection not defined. We
have taken the total number of infections reported over the 6-week period, however, it
is not clear whether some participants reported more than 1 infection as the number of
infections was reported rather than number of people having an infection
Relative costs of materials required for skin closure
Skin closure time
Notes Surgeon cosmetic appearance data not used as measured at < 3 months
Risk of bias
Random sequence generation (selection Low risk Quote: “ . . . the eligible subjects were
bias) randomly categorized (via a pseudo-random
number generator algorithm) into 1 of 4 co-
horts”
Comment: adequate random sequence
generation
Allocation concealment (selection bias) Unclear risk Quote: “ . . . the eligible subjects were
randomly categorized (via a pseudo-random
number generator algorithm) into 1 of 4 co-
horts”. The study also states, “The surgeon
was blinded to the closure technique before
and during the operation until subcutaneous
closure”
Comment: although sequence generation
was adequate and there is evidence to sug-
gest that allocation was concealed, there is
not enough evidence to suggest how this
was done and how allocation was concealed
to the personnel
Blinding of participants and personnel Unclear risk Quote: “The surgeon was blinded to the clo-
(performance bias) sure technique and during the operation until
All outcomes subcutaneous closure”
Comment: although attempts were made
to conceal the allocated treatment, it would
be difficult to blind the operating surgeon

Eggers 2011 (Continued)
to the intended intervention, therefore our

judgement is unclear. No information was
provided about the extent to which partic-
ipants were blinded
Blinding of outcome assessment (detection Unclear risk Quote: “At each visit, a physical exami-
bias) nation was conducted; and adverse events
All outcomes were recorded. The physical examinations af-
ter TKA included evaluation of peripheral
edema, infection, and dehiscence as well as
pain level (0-10 scale) and cosmesis (100-
mm visual analogue scale (VAS)) evaluation
by patient. General health and wellness were
further evaluated by an SF-12v2 survey”
Comment: the extent to which the par-
ticipants were blinded to the intervention
is unclear; it is also unclear whether those
conducting the examinations were aware
of the treatment given. The outcome of
cosmesis was evaluated before the our spec-
ified time-frame for the purposes of our re-
view. The judgement remains unclear in
this case
Incomplete outcome data (attrition bias) Unclear risk Quote:“Of the 90 subjects recruited, 15 were
All outcomes excluded because of screen failure; 6 were di-
agnosed with arthrofibrosis after surgery, 4
failed to follow preferred physical therapy, and
5 sustained unrelated co-morbidities prevent-
ing study completion.”
“Consequently, a total of 75 subjects, 19 per
cohort with the exception of 18 for the n-
butyl-2 adhesive cohort, completed the study;
and their data are presented in the following
section.”
Comment: it seems that these participants
were excluded post-randomisation
tocol not sought
Other bias Unclear risk Possible issues with clustering for infection
outcome data

Greene 1999
Methods Randomised split-body design study with 1-month follow-up. No participants lost to
follow-up
Participants 20 adults requiring bilateral blepharoplasty for functional or aesthetic indications (40
eyelids were treated). Procedure conducted at: Division of Otolaryngology - Head and
Neck Surgery, Plastic and Reconstructive Surgery, Standford University Medical Centre
and Palo Alto Veterans Healthcare System, Palo Alto, California, and Department of
Otolayngology - Head and Neck Surgery, Cleveland Clinic Florida, Naples, USA. Used
a blepharoplasty model with identical skin sites on the same participant and each par-
ticipant acted as his or her own control. No specific exclusion criteria were described
Interventions Group 1 (n = 20): left or right upper eye lid incision closed with 2-octylcyanoacrylate
(Dermabond®, Ethicon Inc, a Johnson & Johnson company, Somerville, New Jersey,
USA)
Group 2 (n = 20): other eyelid incision closed with 6.0 suture (10 fast-absorbing gut
or 10 polypropylene, Prolene, Ethicon Inc, a Johnson & Johnson company, Somerville,
New Jersey, USA)
Blepharoplasties were closed on the tissue adhesive side by using Castroviejo forceps to
approximate the skin edges in 15 participants and by using 3-4 sutures as handles to
facilitate apposition and eversion of edges in 5 participants
Outcomes Dehiscence, infection, patient satisfaction, and surgeon satisfaction at 1, 2, and 4 weeks.
Time for closure at end of procedure
Notes Cosmetic appearance data could not be used as measured at < 3 months
Risk of bias
Random sequence generation (selection Unclear risk Quote: ”Each patient had been randomised
bias) to have either the right or left upper eyelid
serve as the experimental closure [with adhe-
sive] . . . and the opposite eyelid as the control
with sutures“
Comment: despite stating that each patient
was randomised to treatment group, there
was no specific description of how the ran-
domisation process was done or achieved
Allocation concealment (selection bias) Unclear risk Quote: ”Each patient had been randomised
...“
Comment: no description of how alloca-
tion was undertaken and whether it was
concealed
Blinding of participants and personnel Unclear risk Not reported whether participants or per-
(performance bias) sonnel were blinded to the intervention
All outcomes Comment: understandably difficult to

Greene 1999 (Continued)
blind surgeon to the intervention
Blinding of outcome assessment (detection Unclear risk Quote: ”The photographs were shown to 5
bias) observers blinded to the technique of closure“
All outcomes to evaluate wound quality post operatively.”
Comment: blinding of outcome assess-
ment achieved for cosmetic appearance,
which was not included in this review. Not
clear whether blinded assessment was un-
dertaken for other outcomes
Incomplete outcome data (attrition bias) Low risk Quote: “The 5 blinded observers using the
All outcomes visual analogue scale to rate the 40 treated
eyelids did not find any statistically significant
difference between the wound quality . . .”
Comment: suggested that all participants
were accounted for, as the study had 20
participants (40 eyelids)
tocol not sought
Jallali 2004
Methods RCT in which participants (with multiple port wounds) were randomised. Follow-up
was for between 6 and 8 weeks. No withdrawals reported
Participants Participants undergoing laparoscopic cholecystectomy

No other inclusion or exclusion information
Undertaken in 1 UK centre
Interventions Group 1 (12 participants; 48 wounds): 2-octylcyanoacrylate

Group 2 (13 participants; 51 wounds): absorbable sutures
Participants in the suture arms had a dressing placed over the wound. Those in the tissue
adhesive arm did not require a dressing
Outcomes Skin closure time (not clear if these data were collected for multiple wounds on the same
person)
Notes Outcome reporting was unclear, so not sure if results were reported for a reference wound
for each participant or if outcome data from multiple wounds were collected
Cosmetic appearance data could not be used in the review as measured at < 3 months
Wound complications reported as an outcome - but nature of the complications was not

Jallali 2004 (Continued)
clear
Risk of bias
Random sequence generation (selection Unclear risk Quote: “Randomization was performed by
bias) asking the patient to select an envelope out of
a hat”
Comment: although it seems efforts were in
place to randomise patients, it is not wholly
clear that a truly randomised sequence was
generated
Allocation concealment (selection bias) Unclear risk Quote:“Randomization was performed by

asking the patient to select an envelope out of
a hat”
Comment: there was no mention of
whether allocation was concealed to the in-
vestigators
Blinding of participants and personnel Unclear risk No direct quotations about whether the
(performance bias) participants or personnel were blinded in
All outcomes this study. It would be difficult to blind per-
sonnel in a surgical procedure
Blinding of outcome assessment (detection Unclear risk No direct quotations about whether the
bias) participants or personnel were blinded in
All outcomes this study. It would be difficult to blind
personnel in a surgical procedure. The only
outcome reported here relevant to the re-
view was time to skin closure. It is not clear
if this was assessed by a blinded assessor
Incomplete outcome data (attrition bias) Low risk Quote: “All patients were followed up. In the
All outcomes suture group one patient refused to have a
photograph taken”
Comment: adequate outcome data gath-
ered
tocol not sought
Other bias Unclear risk Based on information collected it is not

clear whether data were presented for an
incorrectly analysed cluster trial

Keng 1989
Methods RCT with 7-month follow-up. 3 participants lost to follow-up: 1 from the suture group
and 2 from the tissue adhesive group
Participants 43 people requiring groin incisions (for: inguinal hernia, femoral hernia, sapheno liga-
tions, testicular operations and lymph node biopsies). Skin incisions were closed with
either butylcyanoacrylate (Histoacryl) tissue adhesive or Dexon subcuticular suture. In
bilateral operations the left side was closed with Histoacryl and the left with Dexon.
Conducted at Burton General Hospital, Burton-on-Trent, UK
Interventions Group 1: butylcyanoacrylate (Histoacryl) tissue adhesive

Group 2: Dexon suture on straight needle using anchoring knot both ends or opposing
the wound with forceps
Outcomes Infection, inflammation, cosmetic appearance, wound closing time, wound comfort and
haematoma
Notes Exclusion criteria were not stated. Cosmetic appearance data not used in the review, as
measured at < 3 months
Risk of bias
Random sequence generation (selection Unclear risk Quote:“The patients were randomised just
bias) prior to skin closure into two groups. Even
numbers were closed with Dexon subcuticu-
lar suture (Dexon group) and odd numbers
were closed with Histoacryl-Blue tissue adhe-
sive (Histoacryl)”
Comment: whilst use of odd and even
numbers is detailed in terms of how the
randomisation was implemented there was
no detail about how the sequence was gen-
erated
Allocation concealment (selection bias) Unclear risk Quote:“Even numbers were closed with
Dexon subcuticular suture (Dexon group)
and odd numbers were closed with Histoacryl-
Blue tissue adhesive (Histoacryl)”
Comment: no indication mention that this
sequence was concealed from surgeons
Blinding of participants and personnel Unclear risk No direct quotation. Not reported whether
(performance bias) participants or personnel were blinded to
All outcomes the intervention. It is possible that par-
ticipants may have been aware of 2 dif-
ferent methods of closure. “When the pa-
tients had bilateral operations, the left side

Keng 1989 (Continued)
was closed with Histoacryl and the right side

with Dexon”.
blind operating surgeon to intervention
Blinding of outcome assessment (detection Unclear risk Quote: “Cosmesis was assessed by an indepen-
bias) dent observer (the experienced clinic sister) on
All outcomes a scale of one to five . . . ”
“The patients and wounds were assessed at one
week and one month postoperatively in the
surgical outpatients clinic. A simple scheme
was used to assess the wound . . .”
Comment: blinding of outcome assess-
ment achieved for wound appearance, but
this was not used in this review. Blinding
not clear with regard to the other outcomes
Incomplete outcome data (attrition bias) Low risk Comment: 3/43 participants were lost to
All outcomes follow-up. Considered low risk of bias
Selective reporting (reporting bias) Low risk All the variables outlined in the methodol-
ogy were accounted for in the results
tocol not sought
Kent 2014
Methods Parallel RCT in 433 participants with 3 months follow-up
Participants 433 participants undergoing a range of laparoscopic procedures

Exclusion criteria: known sensitivity to cyanoacrylates; pregnancy or breastfeeding; or
conditions known to interfere with wound healing (no further information provided)
4 UK centres
Interventions Group 1 (216 participants; 636 treated wounds): high viscosity 2-octylcyanoacrylate
(High Viscocity Dermabond®; Ethicon Inc, a Johnson & Johnson company, Somerville,
New Jersey, USA) tissue adhesive
Group 2 (217 participants; 618 treated wounds): n-butyl-cyanoacrylate (Liquiband®)
tissue adhesive (LiquiBand. MedLogic Global Ltd, Plymouth, Devon, UK)
Outcomes Wound dehiscence (evaluated at 14 days and 3 months postoperatively)

Wound infection (evaluated at 14 days and 3 months postoperatively; infection not
defined)
Cosmetic appearance by surgeon (at 3 months) using a modified Hollander Wound
Evaluation scale
Participants’ satisfaction with incisional wound closure - options were ’satisfied’ or ’dis-

Kent 2014 (Continued)
satisfied’
Sugeons’ satisfaction with wound (considering expression, application, delivery and ease
of use for product): options were ’satisfied’ or ’dissatisfied’
Skin closure time
Notes Unit of randomisation was person with some data reported per wound (with multiple
port incisions on each participant)
Cosmetic appearance by participants and surgeon (at 3 months). Participants and sur-
geons were asked to assess whether they were ’satisfied’ or ’dissatisfied’ with the overall
appearance of the wound. Whilst this was referred to as satisfaction in the study we
deemed it to be an unvalidated measure of cosmetic appearance
Risk of bias
Random sequence generation (selection Unclear risk Quote: ”Subjects were randomised into 1 of
bias) 2 treatment groups: LB or DB. Although the
adhesive user was not masked, both the study
subject and evaluators were blinded to the
randomised study treatment assignment“
Comment. it is unclear how the randomisa-
tion sequence was achieved. Judged as un-
clear
Allocation concealment (selection bias) Unclear risk Quote:”Subjects were randomised into 1 of
2 treatment groups: LB or DB. Although the
adhesive user was not masked, both the study
subject and evaluators were blinded to the
randomised study treatment assignment“
Comment: no method of allocation con-
cealment described, therefore judged as un-
clear
Blinding of participants and personnel Unclear risk Quote: ”The adhesive user was not masked,
(performance bias) both the study subject and evaluators were
All outcomes blinded to the randomised study treatment as-
signment“
Comment: this indicates that personnel
were not blinded to the procedure, whilst
participants were blinded. Given that this
was a study investigating two adhesives,
blinding might have been possible. The
judgement is unclear
Blinding of outcome assessment (detection Unclear risk Quote: ”Wound cosmesis was evaluated by a
bias) masked panel at the 3-month visit. Cosme-
All outcomes sis was measured using a modified 6-point
Hollander Wound Evaluation Scale (HWES)

Kent 2014 (Continued)
score.“
Comment: adequate blinding of outcome
assessment
Quote: Satisfaction measures were obtained
from different study participants throughout
the course of this trial. First, the surgical user
was asked to indicate his/her satisfaction with
the expression, application, delivery as ease
of use of products. The user marked on a
sheet that he/she was either ”satisfied“ or ”dis-
satisfied“. At the 3-month follow up visit,
the masked evaluators were requested to state
whether they were satisfied with the healing
and the overall appearance of the incisions”
Comment: satisfaction outcome blinded
adequately
Not clear if wound dehiscence and infec-
tion were blinded
Incomplete outcome data (attrition bias) High risk Quote:“A total of 76 subjects withdrew from
All outcomes the study, primarily because they were lost to
follow up, resulting in a loss to follow up rate
of 17.6%. Final data analysis was performed
on 373 subjects and a total of 1089 incisions”
Comment: high number of missing data at
the participant level
tocol not sought
Other bias Unclear risk Data presented and analysed as an individ-

ual trial, but this is a cluster trial (wounds
clustered per person)
Khan 2006
Methods 3-arm parallel trial with 187 participants. No withdrawals reported

Follow-up was classed as ’early’, which seems to have been the first 3 days after surgery,
and then ’late’ which was between 8 and 12 weeks after surgery
Participants 187 participants undergoing either a total knee arthroplasty or a total hip arthroplasty
Exclusion criteria: having a revision or with a previous incision in the operative field; a
history of keloid formation; allergy to superglue; regular anticoagulation therapy; or an
underlying malignancy
The study was performed in 1 centre in Australia

Khan 2006 (Continued)

Group 2 (n = 64): continuous 3.0 subarticular absorbable poliglecaprone suture
(Monocryl, Johnson and Johnson)
Group 3 (n = 63): skin staples
Outcomes Wound infection: (report states that“where cultures were positive or there was clinical
evidence of cellulitis, the patients were treated with a course of antibiotics and recorded as
having an ‘infection”) data collected at 2 time points - early and late
Patient satisfaction with the techniques of skin closure was assessed with a VAS between
0 and 100, where 100 represented maximal satisfaction
Skin closure time
Notes Cosmetic appearance data (surgeon) could not be used in this review as measured at < 3
months
Risk of bias
Random sequence generation (selection Low risk Quote: “The patients were randomised using
bias) a computer-generated method . . . ”
Comment: Adequate random sequence
generation method utilised
Allocation concealment (selection bias) Unclear risk Quote: “The patients were randomised using
a computer-generated method stored in sealed
identical opaque envelopes. Allocation took
place in the operating theatre after closure of
the deep layers. Enrolment, generation of the
allocation sequence and assignment of the pa-
tients was performed by the lead author.”
Comment: not clear if envelopes were
numbered or otherwise labelled or stored
so that allocation was concealed
Blinding of participants and personnel Unclear risk Quote: “The patients and assessors remained
(performance bias) blinded to the treatment allocated until the
All outcomes dressings were changed, prior to discharge. At
follow-up, the assessors were not informed of
the technique of closure.”
Comment: no mention of whether the per-
sonnel were blinded to the procedure, al-
though this would be understandably dif-
ficult for a surgical procedure
Blinding of outcome assessment (detection Unclear risk Quote: “The patients and assessors remained
bias) blinded to the treatment allocated until the
All outcomes dressings were changed, prior to discharge. At

Khan 2006 (Continued)
follow-up, the assessors were not informed of

the technique of closure.”
Incomplete outcome data (attrition bias) Low risk No direct quotation, but no account of a
All outcomes loss to follow-up, therefore judged as low
risk
Selective reporting (reporting bias) Low risk No direct quotation, but no outcomes se-
lectively reported, therefore judged as ade-
quate
Other bias Unclear risk Possible issues with clustering for infection
outcome data
Kouba 2011
Methods Split-body design RCT with 12 weeks of follow-up. Data missing for 1 participant
Participants Adults undergoing upper lid blepharoplasty who had not previously undergone this
procedure
Participants were recruited from a singe site, Henry Ford Health System, USA
1 cosmetic surgeon performed whole procedure
Exclusion criteria: taking salicylates and/or anticoagulants; taking oral retinoids in the
last 3 months; an unexplained history of excessive bleeding; a history of acute glaucoma
or Sjogren’s syndrome; having resurfacing or laser techniques for the eyelid
Interventions Group 1 (24 participants; 24 eyes): 2-octylcyanoacrylate (Dermabond®) tissue adhesive

(Ethicon Inc, a Johnson & Johnson company, Somerville, New Jersey, USA)
Group 2 (24 participants; 24 eyes): standard monofilament suture (6-0 fast-absorbing
gut or polypropylene)
The study authors randomised each participant to have either (1) one eye treated with
adhesive and the other with gut sutures; or (2) one eye treated with adhesive and the
other with polypropylene sutures; or (3) one eye treated with gut sutures and the other
treated with polypropylene sutures. For this review the adhesive data and the suture data
from the two separate ’sub-studies’ involving adhesives have been pooled together and
treated as one study
Outcomes Wound dehiscence: assessed at 1 week

Cosmetic appearance (surgeon-rated): assessed at 1 month and 3 months (we report 3-
month data). Scoring performed using a scale of 1 (excellent wound healing, scar matches
surrounding skin) to 5 (poor scar wound healing, does not match surrounding skin).
This was a blinded assessment. The data presented here were calculated by the review
authors from raw data presented in the study report
Notes The following outcome was reported, but was not thought to be a validated measure
for cosmetic appearance, “Participant cosmetic evaluation: (thickness, width, texture, color
change, overall cosmetic outcome) was assessed at 3 months. A composite score was calculated
as the sum of the scores for thickness, width, texture, and color change.”

Kouba 2011 (Continued)
No clear information was reported on wound dehiscence

No comparative baseline data reported
Funding source not reported
Risk of bias
Random sequence generation (selection Unclear risk Quote:“They [the patients] were randomised
bias) for treatment in three subgroups in which each
eyelid was repaired with a different material”
Comment: no indication that there was
randomised sequence generation
Allocation concealment (selection bias) Unclear risk Quote: “They [the patients] were randomised
for treatment in three subgroups in which each
eyelid was repaired with a different material”
Comment: no indication allocation was
concealed to the personnel
Blinding of participants and personnel Unclear risk No direct quotation, but no indication that
(performance bias) there was blinding of the participant or the
All outcomes personnel during the procedure. However,
there are obvious difficulties in blinding the
operating surgeon to the procedure
Blinding of outcome assessment (detection Unclear risk Quote: “Incidence of wound dehiscence and
bias) side effects of itching, bleeding, and pain were
All outcomes assessed at 1 week”
Comment: no indication that this wound
evaluation was undertaken by a blinded as-
sessor
Quote. [At 3 months] “A blinded physician
assessed cosmetic outcome of wound closure
technique using standardized photographs”
Comment: adequate blinding of this out-
come assessment
Incomplete outcome data (attrition bias) Unclear risk No direct information regarding drop out
All outcomes rates, however different numbers used in
total participants at 1 month to those at
3 months. Therefore the judgement is un-
clear
Selective reporting (reporting bias) High risk Quote: “Incidence of wound dehiscence and
side effects of itching, bleeding, and pain were
assessed at 1 week”
Comment: incidence of wound dehiscence
not clearly reported in the results

Kouba 2011 (Continued)
Other bias Low risk None reported
Krishnamoorthy 2009
Methods A parallel RCT with follow-up at 7 days and 6 weeks postoperatively. No missing data
reported, but the number included in analysis was not clear
Participants 106 participants undergoing saphenous vein harvesting (for coronary artery bypass graft-
ing). Participants were recruited from a single UK site
Excluded patients with high risk of vein harvest failure (defined as those with varicose
veins, those with small or thin legs and those who required emergency or repeat proce-
dures)

Group 2 (n = 53): sutures (monofilament synthetic absorbable Biosyn 3-0; Covidien
PLC, Dublin, Ireland)
In the suture group the wound was dressed with Mepore dressing (Mölnlycke Health
Care, Manchester, United Kingdom),and a pressure bandage was applied for 48 h
In the adhesive group a pressure bandage and Steri-Strips (3M, St Paul,MN) were applied
to hold the edges together for 24 h
Outcomes Skin closure time
Notes Cosmetic appearance (surgeon-reported) data not used in this review as measured at <
3 months
An outcome that study authors referred to as a ’patient satisfaction score’ was also mea-
sured, however, this seemed to focus on satisfaction of cosmetic appearance so was deemed
a cosmetic evaluation; as it was collected at 6 weeks after surgery it is not reported here
Risk of bias
Random sequence generation (selection Low risk Quote: “A computerized randomization sys-
bias) tem was used to place patients into two groups
of 53 each.”
Comment: judged as adequate evidence of
sequence randomisation
Allocation concealment (selection bias) Unclear risk Quote: “A computerized randomization sys-
tem was used to place patients into two groups
of 53 each.”
Comment: no indication that allocation
was concealed from personnel

Krishnamoorthy 2009 (Continued)
Blinding of participants and personnel Unclear risk No direct quotation or indication that ei-
(performance bias) ther participants or personnel were blinded
All outcomes from the study. However it is understand-
ably difficult for personnel to be blinded in
this case as it is a surgical procedure
Blinding of outcome assessment (detection Unclear risk Quote:“Two surgeons independent of the
bias) study who were blinded to the type of skin clo-
All outcomes sure rated photographs at the same time points
using a visual analogue scale evaluating cos-
metic appearance and the previously validated
Hollander wound evaluation scale.”
Comment: although this would correlate
to a perceived low risk of bias, the cosmesis
outcome should be excluded at less than 3
months as per the systematic review proto-
col. No direct quotation available regarding
blinding related to the time to skin closure
study outcome
Incomplete outcome data (attrition bias) Unclear risk Quote “We identified and excluded as addi-
All outcomes tional 12 patients . . . ”
Comment: this quote is presented in the
results. It is not clear if these were post-
randomisation exclusions
tocol not sought
Other bias Low risk None detected
Livesey 2009
Methods RCT with a 3-month follow-up period. In total 13 participants did not contribute data
at 3 months
Participants 90 people having a total hip replacement

Exclusion criteria: revision total hip replacement; a previous incision in the operative field,
local skin conditions such as psoriasis, eczema or dermatitis; history of keloid formation;
underlying malignancy; peripheral vascular disease; insulin-dependant diabetes; allergy
to skin adhesive or metal staples
Undertaken in 1 UK centre
Interventions Group 1 (n = 45): butylcyanoacrylate (LiquiBand®. MedLogic Global Ltd, Plymouth,

Devon, UK)
Group 2 (n = 45): staples (appose UCL 35W, Tyco, Norfolk, Connecticut)

Livesey 2009 (Continued)
Data at 3 months only available for 38 in Group 1 and 39 in Group 2 thanks to missing
data
Outcomes Wound infection: defined as participant requiring antibiotics specifically for suspected
wound infection
Cosmetic appearance (participant-rated) at 3 months: used a 100 mm VAS where 0 =
worst outcome and 100 = best outcome. Median rather than mean data presented for
this outcome
Cosemtic appearance (surgeon-rated) at 3 months: used a 100 mm VAS where 0 = worst
outcome and 100 = best outcome
Notes Data on participant satisfaction with scar and appearance of the wound in relation
to expected appearance were also collected using a VAS scale (as above). Reviewers
considered this to be a variation of cosmetic appearance and so it is not reported in the
review
Surgeons also reported cosmetic appearance using modified version of the Hollander
wound evaluation score and modified Vancover scar score. The modified versions were
deemed to be not validated (they only included 3 items)
Time to wound closure data and ease of wound closure were collected on a sub-set of 10
participants in each trial arm. There was no information about how these sub-sets were
selected, so these data could not be considered as data from an RCT per se and have not
been presented here
Follow-up appointments took place a mean of 14.4 weeks after surgery (no evidence of
significant difference between groups)
Risk of bias
Random sequence generation (selection Unclear risk Quote:“Randomisation was performed, us-
bias) ing the sealed envelope method, which in-
volved identical sealed envelopes containing
a card stating either ’skin adhesive’ or ’staple’
being opened by an independent researcher on
the day of surgery”
Comment: no indication that adequate
randomised sequence generation was per-
formed
Allocation concealment (selection bias) Low risk Quote: “Randomisation was performed, us-
ing the sealed envelope method, which in-
volved identical sealed envelopes containing
a card stating either ’skin adhesive’ or ’staple’
being opened by an independent researcher on
the day of surgery. The operating surgeon was
blinded to the skin closure method until the
patient was in theatre”
Comment: although it was not indicated
that the envelopes were numbered sequen-

tially, there is reasonable evidence here to

describe the allocation concealment as ade-
quate, and as it was undertaken by an inde-
pendent researcher it has been judged ac-
cordingly
Blinding of participants and personnel Unclear risk Quote: “All patients had the same post-oper-
(performance bias) ative care pathways and were blinded to the
All outcomes method of skin closure until the dressings were
changed post-operatively”
Comment: adequate blinding of partic-
ipants, however study design unable to
blind personnel effectively, as a surgical in-
tervention required
Blinding of outcome assessment (detection Unclear risk Quote: “A researcher collected information
bias) on the presence of oozing and wound infec-
All outcomes tion, which was defined as the patient requir-
ing antibiotics specifically for suspected wound
infection. Patients whose wound was closed
with staples had these removed between ten
and 14 days post-operatively”
Comment: indication that those evaluating
the wounds were not blinded to the proce-
dure, however this is not explicit, therefore
the judgment remains unclear
Quote: “An orthopaedic surgeon (AWB) also
evaluated the scars using the VAS for cosmetic
appearance. Both the plastic and orthopaedic
surgeon were blinded to which method of skin
closure had been used to each patient, and to
each others’ scores”
Comment: adequate blinding of cosmesis
outcome
Incomplete outcome data (attrition bias) Unclear risk Quote: “In all, 12 patients (of 90) were
All outcomes lost to follow-up because of non-attendance
or cancellation of the three-month outpatient
appointment. These patients have been seen
subsequently with no reported adverse occur-
rences, but were not included in the final anal-
ysis as the time point for the last follow-up in
the study was three months”
Comment: impact of these missing data
unclear
Selective reporting (reporting bias) High risk Quote: “Evaluation of the cosmetic appear-
ance of the scars was completed by a plastic
surgeon (CME) using a modified version of

the Hollander wound evaluation score and

the Vancouver scar score, a Likert Scale and
a VAS”. .
Comment: The results section reports only
the Vancouver scar score, the Likert Scale
and the VAS . The Hollander wound eval-
uation score has been omitted the judge-
ment here is of high risk of bias
Other bias Low risk None reported
Maartense 2002
Methods Randomised parallel group study with 16-month follow-up. There were no withdrawals,
however 7 patients treated with paper tape and 3 with tissue adhesive were converted to
the suture group
Participants 140 adults requiring elective laparoscopic surgery. Patients were excluded if they had
undergone previous laparotomy or were pregnant. The study was undertaken at 2 centres,
Department of Surgery, Academic Medical Centre, Amsterdam; and The Netherlands
and Department of Surgery, Isala Clinics, Zwolle, the Netherlands
Interventions Group 1 (n = 48): octylcyanoacrylate (Dermabond®, Johnson & Johnson, Amersfoot,

the Netherlands) tissue adhesive
Group 2 (n = 42): 76 mm x 6 mm adhesive paper tape (SteriStrip® Bioplasty/Uroplasty,
Geleen, the Netherlands)
Group 3 (n = 50): intracutaneous poliglecaprone (Monocryl®) 4/0, Johnson & Johnson)
interrupted sutures
Outcomes Infection, cosmetic appearance, and surgeon satisfaction at 2 weeks and 3 months, and
costs
Notes We wrote to the authors who confirmed that there were no withdrawals
Risk of bias
Random sequence generation (selection Low risk Quote: “Patients were allocated to one of the
bias) three groups using a computer randomization”
Comment: random sequence generation
undertaken by computer
Allocation concealment (selection bias) Unclear risk Quote: “Patients were allocated to one of the
three groups using a computer randomization”
Comment: not reported whether this al-
location was concealed from the operating
surgeon

Maartense 2002 (Continued)
vention
Blinding of outcome assessment (detection Low risk Quote: “At follow up [at 10-14 days and
bias) 3 months], the incidence of wound infection
All outcomes and cosmesis were scored. Patients were also
asked to score their own cosmetic results. Sur-
gical residents scored wound infection and cos-
metic results, they were blinded to the method
used for wound closure”
Comment: this infers a low risk of detection
bias at both intervals for outcomes assessed
by surgeons
Incomplete outcome data (attrition bias) Low risk No direct relevant quotations, although
All outcomes some patients who underwent closure with
adhesive tape or adhesive liquid had to be
converted intra-operatively to suture clo-
sure. These seem to be analysed in the
groups to which they were randomised (in-
tention-to-treat analysis)
Comment: judgement of low risk of attri-
tion bias
Selective reporting (reporting bias) Low risk No direct relevant quotations, but all vari-
ables listed in the methods section are listed
in the tables in the Results section
Comment: a low risk of reporting bias is
inferred
Maloney 2013
Methods Parallel RCT in 43 participants. Follow-up was for 3 months (assessment at 2 weeks and
3 months after surgery). No withdrawals noted
Participants 43 participants undergoing a skin incision to remove skin cancer

Exclusion criteria: known sensitivity to cyanoacrylates; wounds under high tension forces;
wounds < 2 cm or > 5 cm in length; or participant pregnant or breastfeeding
Study undertaken in USA, number of centres involved was unclear

sive

Maloney 2013 (Continued)
Group 2 (n = 20): n-butyl-cyanoacrylate (Liquiband®) tissue adhesive (LiquiBand.

MedLogic Global Ltd, Plymouth, Devon, UK)
Outcomes Wound dehiscence (2 weeks and 3 months after surgery - no events reported at 3 months
and 1 event only at 2 weeks, no unit of analysis issue)
Wound infection (not defined)
Cosmetic appearance at 3 months (blinded evaluators - panel of 6 doctors) using 100
mm VAS scale where 0 = worst scar and 10 = best scar
Cosmetic appearance at 3 months (participant-reported) using VAS scale on worst scar
(0) to best scar (10)
Surgeon satisfaction (at time of wound closure) assessed using 100 mm VAS scales for:
ease of use (0 = impossible; 10 = very easy to use) and satisfaction with device and the
closure achieved (0 = completely dissatisfied; 10 = completely satisfied)
Notes Wound infection listed as outcome, but not clearly reported

Cosmetic appearance assessed by blinded evaluator was also measured using Modifed
Hollander Wound Evaluation Scale (modified to measure 5 not 6 items). This was not
deemed to be validated, and so reviewers did not present the data
Risk of bias
Random sequence generation (selection Unclear risk Quote: “Subjects were randomly assigned to
bias) receive either LB or DB for wound closure.
Randomization occurred immediately follow-
ing placement of the subcuticular sutures”
Comment: unclear how the randomised se-
quence was generated
Allocation concealment (selection bias) Unclear risk Quote: “Randomization occurred immedi-
ately following placement of the subcuticular
sutures. Due to the fact that the devices are
packaged differently, it was not possible for the
surgeon to be masked from the knowledge of
the randomised treatment assignments”
Comment: no evidence of adequate con-
cealment of allocation
Blinding of participants and personnel Unclear risk Quote: “Due to the fact that devices are pack-
(performance bias) aged differently, it was not possible for the sur-
All outcomes geon to be masked from the knowledge of the
randomised treatment assignments, however,
the study subjects and the follow up assess-
ments were masked to the device being used”
Comment: adequate evidence that partici-
pants were blinded to the intervention, but
personnel were not blinded. This is under-
standable due to the nature of the interven-

Maloney 2013 (Continued)
tion
Blinding of outcome assessment (detection Unclear risk Quote: “ . . . subjects were asked to return at
bias) two weeks and three months post surgery at
All outcomes which time any applicable wound complica-
tions (erythema, pain, infection, and dehis-
cence) were captured along with any reported
adverse events”
Comment: no indication that the 2 week
assessment was undertaken by a blinded as-
sessor
Quote “ . . . the photos were independently
evaluated by a masked panel for cosmesis using
the same 100mm VAS as well as a modified
Hollander Wound Evaluation Scale (HWES)
.” “The masked panel consisted of 6 physi-
cians: 2 general dermatologists, 1 dermato-
logic surgeon, 1 oculoplastic surgeon, 1 facial
plastic surgeon, and 1 plastic surgeon.”
Comment: adequate blinding of assess-
ment outcome of cosmetic appearance at 3
months
Incomplete outcome data (attrition bias) Low risk Quote: “A total of 43 subjects participated in
All outcomes this trial completing all study visits including
2-week and 3-month follow up”
Comment: adequate evidence that no loss
to follow-up occurred
tocol not sought
Millan 2011
Methods RCT with 60 participants and 14 days of follow-up
Participants 60 people undergoing a skin biopsy with chronically inflamed skin

Exclusion criteria: infection at location where biopsy was planned and known hypersen-
sitivity to cyanoacrylate or other tissue adhesive
Surgery was undertaken in 1 centre in Mexico
Interventions Group 1 (n = 30): 2-octylcyanoacrylate tissue adhesive (no further details)

Group 2 (n = 30): monofilament suture (no further details)

Millan 2011 (Continued)
Outcomes Wound dehiscence (on days 5, 7, 10 and 14 after surgery)

Skin closure time
Notes Data extraction based on English language abstract and partial translation of report text
which was published in Spanish
Risk of bias
Random sequence generation (selection Unclear risk Comment: study described as randomised.
bias) No further detail
Allocation concealment (selection bias) Unclear risk Comment: no detail reported
Blinding of participants and personnel Unclear risk Comment: no detail reported

(performance bias)
All outcomes
Blinding of outcome assessment (detection Unclear risk Comment: no detail reported

bias)
All outcomes
Incomplete outcome data (attrition bias) Unclear risk Comment: no detail reported
All outcomes
Selective reporting (reporting bias) Low risk Comment: wound dehiscence was the only
outcome listed in the methods and reported
Other bias Unclear risk Comment: not noted from the translation
available
Mota 2009
Methods Parallel RCT with 100 women and 30-day follow-up

Data on the primary outcome was not available for 2 participants in the adhesive arm
and 1 participant in the suture arm
Participants 100 women undergoing mediolateral episiotomy after a vaginal delivery in the absence
of any other perianal or vaginal lesions
Exclusion criteria: existing local infections or lesions; body mass index 35 (kg/m2 ); severe
pulmonary disease; collagen disease; known immunodeficiency; diabetes mellitus; or
currently receiving immunosuppressive treatment
The study was conducted in 1 hospital centre in Portugal

Group 2 (n = 47): continuous subcuticular suture (rapidly absorbable polyglactin 910)

Mota 2009 (Continued)
Outcomes Wound dehiscence (42 h-68 h post-partum)
Notes The main outcome measure for the paper was self-assessed perineal pain during the first
30 days after delivery. This was not deemed to be an outcome relevant to the review
given the outcomes listed
Skin closure time not reported - only time for whole procedure
Risk of bias
Random sequence generation (selection Low risk Quote: “Allocation was decided by opening a
bias) previously prepared, opaque, sealed envelope
containing a 1:1 computer-generated random
number, assigning the patient to one of the
two arms”
Comment: use of computer-generated ran-
domisation adequate
Allocation concealment (selection bias) Unclear risk Quote: “Allocation was decided by opening a
previously prepared, opaque, sealed envelope
containing a 1:1 computer-generated random
number, assigning the patient to one of the
two arms”
Comment: use of opaque, sealed envelopes
but not noted whether numbered in such
a way as to ensure maintenance of robust
allocation concealment. Not clear if per-
son who opened the envelopes was inde-
pendent
Blinding of participants and personnel Unclear risk Quote: “Women were not informed of the
(performance bias) technique that was used to close the perineal
All outcomes skin throughout the study period.” “As both
groups required stitching of other layers, it is
believed that they were not able to see or feel
the difference between the two types of perineal
skin closure, at the time of repair or thereafter.
”
Comment: participants were blinded. Un-
derstandably difficult to blind the operat-
ing surgeon to the intervention
Blinding of outcome assessment (detection High risk Quote: “Other outcomes evaluated were .
bias) . . duration of surgical repair and perineal
All outcomes wound complications observed at hospital dis-
charge, 42-68 hours post -partum. This ob-
servation was carried out in all cases by one

Mota 2009 (Continued)
of two authors (RM, FC)”

Comment: as the authors were aware of the
intervention undertaken, the judgement is
that this potentially carries a high risk of
bias
Incomplete outcome data (attrition bias) Unclear risk Quote: “Intra-operative data was available
All outcomes for all participants. Data from 42-68 hours
post-op was missing for 2 participants in the
adhesive arm and one in the suture arm.”
Quote: “Eighty-six women returned the ques-
tionnaires, 49 (92%) from the skin adhesive
arm and 37 (79%) from the subcuticular su-
ture arm. This difference was very close to
achieving statistical difference p= 0.05 . . .”.
The results also indicated that the reason
for loss of follow up was the participants
“did not return questionnaire”, rather than
“discontinued intervention”
Comment: unclear risk of bias
Selective reporting (reporting bias) Low risk Quote: No direct quotations, but all vari-
ables listed in methods section were listed
in the tables in the results section
inferred
Ong 2002
Methods RCT with 3-month follow-up. 50 withdrawals at 3-month follow-up
Participants 59 patients requiring unilateral or bi-lateral herniotomies at KK Womens’ and Childrens’

Hospital, Singapore

Group 2 (n = 33): subcuticular polyglecaprone (Monocryl®) suture
Outcomes Infection, dehiscence, parent satisfaction and time for closure
Notes Cosmesis scores at 3 weeks not usable as too early and those at 3-months not usable due
to large loss to follow-up. Viewed as a high risk of bias with 50 participants dropping
out
Risk of bias

Ong 2002 (Continued)
Random sequence generation (selection Low risk Quote: “All enrolled patients were allocated
bias) to glue or suture by opening serial sealed en-
velopes prepared with computerised randomi-
sation”
Comment: computerised randomisation
probably represents randomised sequence
generation
Allocation concealment (selection bias) Low risk Quote: “All enrolled patients were allocated
to glue or suture by opening serial sealed en-
velopes prepared with computerised randomi-
sation”
Comment: the use of sequential sealed en-
velopes would reduce risk of selection bias.
We have taken serial to mean that envelopes
were kept in a pre-arranged and transparent
fixed order and therefore judged this study
to be at low risk of bias for this domain
Blinding of participants and personnel Unclear risk Not reported whether the patients or per-
blind the operating surgeon to the proce-
dure
Blinding of outcome assessment (detection Unclear risk Quote: “ . . . assessment was done by an in-
bias) dependent, blinded observer (staff nurse) us-
All outcomes ing a previously validated score [The Hollan-
der score] . . . Parent satisfaction with wound
cosmesis was recorded at the same time on a
100mm visual analogue scale (VAS)”
Comment: reasonable to deduce that this
represents a low risk of detection bias for
nurse-assessed cosmetic outcome, but not
necessarily participant-assessed outcomes.
Not clear if other outcomes such as wound
infection or dehiscence were collected via
blinded assessment
Incomplete outcome data (attrition bias) High risk Quote: “We were unable to do a 3-month
All outcomes wound assessment on most of the patients, as
only 9 returned for late follow up”
Comment: it is difficult to draw any con-
clusions from the results of the long-term
outcomes due to high rates of losses to fol-
low-up. This leads to a high risk of attrition
bias

Ong 2002 (Continued)
Selective reporting (reporting bias) Low risk No direct quotations, but all variables listed
in the methods are listed in the tables in the
results section
inferred
Ozturan 2001
Methods RCT with 3-month follow-up. There were no withdrawals
Participants 101 people requiring rhinoplasty or septorhinoplasty entered the study

Exclusion criteria: a history of peripheral vascular disease; diabetes mellitus; a clotting
disorder; keloid or hypertrophic scarring; or an allergy to cyanoacrylate or formaldehyde
Conducted at Inonu University Hospital, Turkey
Interventions Group 1 (n = 34): butylcyanoacrylate (LiquiBand®. MedLogic Global Ltd, Plymouth,

Group 2 (n = 67): 6.0 polypropylene sutures for columellar skin closure after the majority
of the tension had been taken up using 5.0 chromic catgut
Outcomes Dehiscence and infection at 1 week

Cosmesis at 3 months by blinded assessment of photographs using VAS and Hollander
scale
Time required for skin closure
Notes We wrote to the authors to clarify the numbers in each group randomised by coin toss
and received confirmation that the numbers were correct. We also received clarification
that the standard deviations were presented after the means in the results section of the
paper
Risk of bias
Random sequence generation (selection Unclear risk Quote: “Patients were randomly allocated by
bias) coin toss”
Comment: random sequence generated
Allocation concealment (selection bias) Unclear risk Quote: “Patients were randomly allocated by
coin toss”
Comment: no mention of allocation con-
cealment from personnel
Blinding of participants and personnel Unclear risk No mention of blinding of participants or

(performance bias) personnel
Ozturan 2001 (Continued)

dure
Blinding of outcome assessment (detection Unclear risk Quote: “All patients were examined once ev-
bias) ery week in the first post-operative month, and
All outcomes once a month for the second and third months.
Columellar wounds were examined for infec-
tion, inflammation, dehiscence and scarring
in addition to cosmetic and functional nasal
evaluations”.
“The three month basal view photograph of
each subject were given to two otolaryngologic
surgeons who were blinded to the method of
repair of the columellar incision”
Comment: 3-month cosmetic assessment
blinded. Unclear whether assessments at
prior time points were blinded
Incomplete outcome data (attrition bias) Low risk Quote: “One hundred and one patients .
All outcomes . . were eligible for inclusion”; this figure
corresponds with the 101 participants ac-
counted for in the results table
Comment: no evidence of loss to follow-
up
Selective reporting (reporting bias) High risk No direct quotations, but all variables listed
in methods are listed in the tables in the
results section
inferred
Other bias Low risk No other sources of bias were identified
Pronio 2011
Methods RCT with follow up at 7 days, 15 days, 1 month, 3 months, 6 months and 12 months.
There were no withdrawals
Participants 70 people who underwent thyroid surgery from November 2005 to May 2007
No inclusion/exclusion criteria were stated
In all cases, participants underwent thyroidectomy following a cervical incision
The study took place in Italy, although no further information is given regarding the
exact location of the trial
Interventions Group 1 (n = 32): 2-octylcyanoacrylate (Dermabond, Ethicon Inc)

Group 2 (n = 38): skin staples (Proximate, Ethicon Inc)
Prophylactic antibiotics in the form of ceftriaxone were administered to both groups

Pronio 2011 (Continued)
Outcomes Wound dehiscence (7days)

Wound infection (7 days; not defined)
Cosmetic appearance (assessments by participants at 3, 6 and 12 months relevant here)
. Data were recorded using the Stony Brook scar evaluation scale composed of 5 di-
chotomous, evenly weighted categories. Scars are assigned 0-1 point for the presence or
absence of a width greater than 2 mm at any point of the scar, a raised (or depressed)
scar, a darker coloration than surrounding skin, any hatch or staples marks, an overall
poor appearance, the total score ranging from 0 (worst) to 5 (best)
Patient’s satisfaction with wound management (7 days). Participants were asked to rate
their level of satisfaction with the early postoperative management of the wound (regard-
ing the requirement of a return visit for medications, the possibility of washing oneself,
the suture removal) using a numerical scale ranging from 0-10
Notes Study records how many closures were considered rapid (between 30 and 60 seconds).
These data were not extracted as it was felt that they reported skin closure time in a way
that could not be summarised meaningfully
Participants were also asked to provide a score using a verbal rating response regarding
their scar (at 7 days, 15 days and 3, 6, 9 and 12 months after surgery). Scores could range
from 0 to 10: 0-4, poor; 5-6, mild; 7-8, good; and 9-10, excellent. These data were only
presented categorically and are not extracted - instead the scar evaluation scale data are
presented
Risk of bias
Random sequence generation (selection Unclear risk Quote: “Only when the surgical proce-
bias) dure was completed, after the closure of the
platysma, each patient was randomly assigned
to the two treatment groups”
Comment: no indication that there was ev-
idence of randomised sequence allocation
Allocation concealment (selection bias) Unclear risk Quote: “Only when the surgical proce-
dure was completed, after the closure of the
platysma, each patient was randomly assigned
to the two treatment groups”
Comment: no indication of allocation con-
cealment from personnel
Blinding of participants and personnel Unclear risk No direct quotations, but no indication
(performance bias) that the participants or the personnel were
All outcomes blinded to treatment. It is understandably
difficult to blind personnel to the interven-
tion arm given during an operation

Pronio 2011 (Continued)
Blinding of outcome assessment (detection Unclear risk Quote: “In the follow-up over 7 and 15
bias) days, 1-month, 3, 6 and 12-months peri-
All outcomes ods wound-healing process was monitored by
clinical assessment and documented by digital
photographs.”
Comment: there was no indication that
the clinical assessments were made by peo-
ple who were blinded to the intervention.
Therefore the risk of bias here is unclear
Incomplete outcome data (attrition bias) Low risk No direct quotations, but no losses to fol-
All outcomes low-up encountered
Selective reporting (reporting bias) Low risk No direct quotations, although all meth-
ods of evaluating the interventions were ac-
Comment: adequate outcome reporting
Ridgway 2007
Methods RCT with 6-week follow-up. 1 withdrawal but no explanation
Participants 30 participants recruited for cervicotomy for thyroid and para thyroid surgery at Scun-
thorpe General Hospital, North Lincs, UK. 29 successfully randomised. No reference
to inclusion/exclusion criteria

Group 2 (n = 15): staples (Vivistat®)
Outcomes Time to closure, neck mobility, cosmesis and adverse events
Notes Cosmesis results could not be included as they were measured too early to be usable. No
explanation of what characterised an adverse event or the occurrence of such outcomes
was provided
Risk of bias
Random sequence generation (selection Unclear risk Quote: “Randomisation to glue or stapled
bias) closure was performed following induction of
general anaesthesia by random envelope allo-
cation”
Comment: method of random sequence al-
location not stated
Ridgway 2007 (Continued)
Allocation concealment (selection bias) Unclear risk Quote: “Randomisation to glue or stapled
closure was performed following induction of
general anaesthesia by random envelope allo-
cation”
Comment: It is not clear whether the enve-
lope was sealed or ordered and marked to
be sequential, therefore without further in-
formation, the judgement is of an unclear
risk of selection bias
Blinding of participants and personnel Unclear risk No statement made about whether the per-
(performance bias) sonnel were blinded to the procedure
vention
Blinding of outcome assessment (detection Unclear risk Quote: “Scar cosmesis assessment by both pa-
bias) tient, surgeon and independent blinded asses-
All outcomes sor at 6 weeks.”
Comment: this assessment was not in-
cluded in the review (as conducted at less
than 3 months) no other information about
blinded assessment of other outcomes pro-
vided
Incomplete outcome data (attrition bias) Unclear risk No direct quotations, although no losses
All outcomes to follow-up were reported, and all partic-
ipants accounted for in results
Comment: judged as low risk
Selective reporting (reporting bias) Low risk No direct quotations although all meth-
Romero 2011
Methods RCT with 90 days of follow-up (assessment at 10 and 90 days postoperatively). Assumed
all participants’ wounds assessed at day 10. There were 6 withdrawals from 90 day follow-
up (2 from adhesives and 4 from strips)
Participants 49 children undergoing laparoscopic appendectomy

Exclusion criteria: presence of concomitant chronic diseases; immunosuppression; ma-
lignancies; and conversion to laparotomy or intraoperative enlargement of incisions for
intact specimen extractions
Conducted in 1 centre in Germany

Romero 2011 (Continued)
Interventions Group 1 (n = 23): 2-octylcyanoacrylate (Dermabond®) tissue adhesive (Dermabond,

Ethicon, Sommerville, NJ)
Group 2 (n = 24): standard adhesive strips ( strips applied in star-shaped manner)
Postoperative antibiotic therapy with cefotaxime and metronidazole was administered
intravenously
Outcomes Wound dehiscence (assessment at 10 and 90 days after surgery)

Wound infection (defined as abscess or redness > 3 mm perpendicular to incision)
Cosmetic appearance (surgeon-rated; at day 10 and day 90 - day 90 data reported here)
using a 100 mm VAS where 0 = best scar and 100 = worse scar and assessed by 2 blinded
surgeons using macrophotos of each scar (3 photos per participant). Mean value of the
2 assessments has been taken
Cosmetic appearance (participant-rated; at day 10 and day 90 - day 90 data reported
here) assessed using a dichotomous question (wording of question not clear but results
were reported as % expressing dissatisfaction with cosmetic result)
Notes
Risk of bias
Random sequence generation (selection Low risk Quote: “For randomization, a computer-
bias) generated randomization pattern was imple-
mented and patients were intraoperatively as-
signed to a procedure by means of a blind en-
velope system”
Comment: adequate random sequence
generation
Allocation concealment (selection bias) Unclear risk Quote: “For randomization, a computer-
generated randomization pattern was imple-
mented and patients were intraoperatively as-
signed to a procedure by means of a blind en-
velope system”
Comment: although attempts made to
conceal allocation of the intervention, it
was not stated whether the envelopes
were sealed sequentially, whether they were
sealed, or whether they were opaque, there-
fore the judgement remains unclear
Blinding of participants and personnel Unclear risk No direct quotations, however it is under-
(performance bias) standably difficult to blind the operating
All outcomes surgeon from the intervention, therefore
the judgement is unclear

Romero 2011 (Continued)
Blinding of outcome assessment (detection Unclear risk Quote: “Follow up examinations were car-
bias) ried out on the 10th and 90th postoperative
All outcomes day . . . Follow-up included clinical investiga-
tion and a questionnaire to assess satisfaction
with the cosmetic results, postoperative pain
at port sites, wound infections, wound dehis-
cence, and any other adverse events associated
with the wound”
Comment: no indication that the follow-
up examination on the 10th postoperative
day was undertaken by a blinded assessor
Quote: [At 90 days] “This assessment was
completed by 2 pediatric surgeons blinded to
the method of wound repair”
Comment: adequate blinding of cosmesis
outcome at 3 months
Incomplete outcome data (attrition bias) Unclear risk Quote: “A total of 49 patients (24 Der-
All outcomes mabondT M , 25 Steri-StripT M) were enrolled
between August 2007 and August 2008”.
“Photographs were taken from 21 patients in
the Steri-StripT M Group and from 22 pa-
tients in the DermabondT M Group”
Comment: there is a discrepancy concern-
ing 6 participants that were unaccounted
for the in the final outcome assessment
without clear reporting of why they were
not included in the results. Therefore there
is a risk of attrition bias, leaving the judge-
ment unclear
Selective reporting (reporting bias) Low risk No direct quotations, although all meth-
Sebesta 2004
Methods RCT with 2-week follow-up. No participants were lost to follow-up
Participants 59 participants were enrolled, in whom 228 trocar sites were closed following undergoing
laparoscopic surgery performed by one surgeon in the department of Urology, Wilford
Hall Medical Center, Texas, USA
No inclusion/exclusion criteria were stated

Sebesta 2004 (Continued)
Interventions Group 1 (30 participants; 118 incisions): 2-octylcyanoacrylate (Dermabond, Ethicon,

Sommerville, NJ)
Group 2 (29 participants; 110 incisions): subcuticular suture (4-0 absorbable sutures,
either Vicryl or Monocryl)
Data presented at participant, not wound, level
The fascia of all sites > 1 cm were closed with absorbable suture. Wounds in both groups
that did not closely approximate to 1 cm received interrupted, subcutaneous sutures
Those who received subcuticular sutures had their wounds dressed with steri-strips, a 2
x 2xm gauze pad, and tape or a Tegaderm dressing
No dressings were applied to the octylcyanoacrylate-closed wounds
Outcomes Wound dehiscence (2 weeks after surgery)

Wound infection (2 weeks after surgery; not defined)
Mean closure time
Cost per patient
Notes Cosmetic appearance measured at < 3 months so not included
Risk of bias
Random sequence generation (selection Unclear risk Quote: “All patients undergoing laparoscopic
bias) surgery by one surgeon (JTB) were ran-
domised to receive skin closure with either sub-
cuticular suture of octylcyanoacrylate”
Comment: no further information given
regarding how the randomised sequence
was generated, and therefore the judgement
is unclear
Allocation concealment (selection bias) Unclear risk Quote: “All patients undergoing laparoscopic
surgery by one surgeon (JTB) were ran-
domised to receive skin closure with either sub-
cuticular suture of octylcyanoacrylate”
Comment: no further information given
regarding how the allocation was concealed
to the operating surgeon (if at all), there-
fore the judgement remains unclear
Blinding of participants and personnel Unclear risk No direct quotations, but no information
(performance bias) given regarding blinding of participants or
All outcomes personnel in this study. It is understandably
difficult to blind the operating surgeon to
the intervention. Therefore the judgement
here is unclear

Sebesta 2004 (Continued)
Blinding of outcome assessment (detection Unclear risk Quote: “Patients were evaluated 2 weeks post-
bias) operatively for evidence of infection, dehis-
All outcomes cence, seroma, and general cosmetic appear-
ance.”
Comment: unclear whether this evaluation
was undertaken by a blinded assessor
Incomplete outcome data (attrition bias) Low risk No direct quotations, but no reported loss
All outcomes to follow-up, therefore judgment of low
risk
Selective reporting (reporting bias) Unclear risk Quote: “Postoperative wound complications
were similar for both groups. Five patients
in the octylcyanoacrylate group had wound
complications in 9 incisions. Two patients
experienced skin separation in 5 incisions.
One patient had a minor wound infection
at one incision site treated with oral antibi-
otics. Two patients experienced small seromas
at 2 incision sites, requiring incision open-
ing and healing by secondary intention. We
noted small seromas in 2 patients receiving
suture closure. These healed by secondary in-
tention after skin opening and drainage. Ta-
ble 4 presents a summary of the results.”
Comment: however the table shown does
not compare rates of wound complication
and the reporting of the outcomes is un-
clear, it is this author’s judgement therefore
that the risk of bias here is unclear
Shamiyeh 2001
Methods RCT with 9-month follow-up. 2 participants were lost to follow-up from the suture
group due to failure to attend and could not be traced by mail or phone
Participants 79 adults requiring varicose vein surgery on the leg. Trial conducted at Ludwick Boltz-
mann Institure, Linz, Austria
Exclusion criteria: a history of chronic venous insufficiency with dermatosclerosis; pre-
vious phlebectomies; or allergy to plaster or octylcyanoacrylate
Interventions Mullerian phlebectomy performed creating an average wound length of 5 mm. Used 5
min wound compression followed by skin closure with:
Group 1 (n = 26): octylcyanoacrylate tissue adhesive
Group 2 (n = 28): 5.0 monofilament suture
Group 3 (n = 25): tape

Shamiyeh 2001 (Continued)
A small plaster was placed over each wound
Outcomes Wound dehiscence, infection at 10 days, and patient and surgeon satisfaction, and cos-
metic appearance at 1 year and costs. Time required for incision closure was also recorded
Notes
Risk of bias
Random sequence generation (selection Low risk Quote:“Randomisation was done by a com-
bias) puter [during] the morning of the operation
day”
Comment: this was judged to be an ade-
quate method of generating the randomi-
sation sequence i.e. ‘by computer’
Allocation concealment (selection bias) Unclear risk Quote:“Randomisation was done by a com-
puter [during] the morning of the operation
day”.
Comment: there is no mention of the
method used to conceal allocation

dure
Blinding of outcome assessment (detection Unclear risk Quote: “The follow up by the operating sur-
bias) geon was performed [at] 10 days and 6 weeks
All outcomes after the operation” and, “Eight to 14 months
after the operation all patients had been inves-
tigated by one senior dermatologist who was
blinded to the method of skin closure, the scars
were examined for color, width, and cosmetic
appearance . . .”
Comment: blinded outcome assessment
achieved for outcomes collected after 8
months. Not clear if blinding was imple-
mented for earlier follow-up times when
wound dehiscence and infection were as-
sessed
Incomplete outcome data (attrition bias) Low risk Quote:“Only 2 of 79 patients were lost to fol-
All outcomes low-up, resulting in 77 patients with postop-
erative control”
Comment: no reasons reported for those

Shamiyeh 2001 (Continued)
lost to follow-up, but as they only repre-

sented a small percentage of the total par-
ticipants, this was judged overall to be at
low risk of attrition bias
results section
inferred
Sinha 2001
Methods RCT with 6-month follow-up. 6 participants were lost to follow-up: 5 in tissue adhesive
and 1 in suture group
Participants 50 adults requiring hand or wrist surgery (carpal tunnel syndrome, trigger finger, De
Quervain’s tenosynovitis, ganglions of wrist and hand, and cysts of fingers)
Exclusion criteria: requiring surgery for Dupuytren’s contracture; repeat surgery; a history
of skin allergy or keloid formation; diabetes; or corticosteroid use
Trial conducted at Monklands Hospital, Airdre, UK
Interventions Skin approximated with skin hooks then:

Group 1 (n = 20): application of butylcyanoacrylate adhesive (Indermil), or
Group 2 (n = 24): suturing with 4.0 monofilament
All cases had local anaesthetic infiltration with or without general anaesthesia
Outcomes Dehiscence, infection, cosmetic appearance at 10 days, 2 weeks and 6 weeks
Notes Cosmetic appearance data not used as assessed at < 3 months
Risk of bias
Random sequence generation (selection Unclear risk Quote: “Patients were randomised to wound
bias) adhesive or suture on the basis of 50 previously
prepared and sealed envelopes (25 of each)”
Comment: whilst the trial was reported
as randomised there was no information
about how the sequence was generated
Allocation concealment (selection bias) Unclear risk Quote: “Patients were randomised to wound
adhesive or suture on the basis of 50 previously
prepared and sealed envelopes (25 of each)”
Comment: judgement of unclear risk of

Sinha 2001 (Continued)
bias, as not clear if envelopes were sequen-

tially numbered and opaque. Not clear who
was responsible for allocation
Blinding of participants and personnel Unclear risk No information provided about blinding
(performance bias) of participants or surgeons
All outcomes Comment: it would be difficult to blind the
operating surgeon
Blinding of outcome assessment (detection Low risk Quote: “Patients were subsequently assessed
bias) at 2 and 6 weeks post-surgery by a designated
All outcomes tissue viability nurse who was blinded to the
method of closure”
Comment: outcome assessment blinded
Incomplete outcome data (attrition bias) High risk Quote: “Of the study 50 participants, six were
All outcomes lost to follow up (five in the adhesive group
and one in the suture group)”
Comment: the sample size of the study is
small, 6 participants lost represents over
20% of the total sample. No information
reported on reasons for withdrawal
results section
inferred
Sniezek 2007
Methods RCT with 3-month follow-up. No reference to withdrawals
Participants 14 participants recruited for removal of basal cell carcinoma or squamous cell carcinoma
of the head and neck using the Mohs technique at the Department of Dermatology at
University Hospital Iowa
Interventions Split wound design, so both methods of closure were used for part of each wound
Intervention 1: 2-octylcyanoacrylate (Dermabond®; Ethicon Inc, a Johnson & Johnson
company, Somerville, New Jersey, USA)
Intervention 2: polypropylene cuticular suture
Outcomes Dehiscence, infection and cosmesis
Notes As a split wound design the data were paired. The authors were contacted for the mean
difference and the standard deviation of the cosmetic scores on a participant basis. No
reply was received, therefore this information was not included in the review
Sniezek 2007 (Continued)
Risk of bias
Random sequence generation (selection Low risk Quote: “Half of the surgical wound was ran-
bias) domly selected (by coin toss) for epidermal ap-
proximation . . .”
Comment: use of coin toss judged to con-
stitute adequate random sequence genera-
tion
Allocation concealment (selection bias) Unclear risk Quote: “Half of the surgical wound was ran-
domly selected (by coin toss) for epidermal ap-
proximation . . .”
Comment: no information given about
whether the personnel were concealed to
the allocation
Blinding of participants and personnel Unclear risk No reporting of either participants or per-
(performance bias) sonnel being blinded to the intervention
All outcomes Comment: as the nature of the interven-
tion was that the two methods of closure
were placed together to close the same in-
cision, there is potential that participants
may have understood the method of clo-
sure. Similarly it is understandably difficult
to blind the operating surgeon to the in-
tervention. The judgement is therefore un-
clear
Blinding of outcome assessment (detection Unclear risk Quote: “Patients returned in 7 days for suture
bias) removal and were evaluated for early compli-
All outcomes cations such as wound separation, or dehis-
cence, inflammation or infection. High res-
olution photographs were obtained immedi-
ately post-operatively and 3 months postop-
eratively” and, “The primary outcome mea-
sure was scar cosmesis, evaluated by compar-
ing both halves of the scar from the 3 month
photographs by five blinded dermatologists”
Comment: unclear whether assessment at
day 7 was blinded. 3-month assessment of
cosmesis was blinded
Incomplete outcome data (attrition bias) Low risk Quote: “All 14 patients completed all study
All outcomes end points”
Comment: judged as low risk.

Sniezek 2007 (Continued)
results section
inferred
Switzer 2003
Methods RCT with 4-week follow-up. 2 withdrawals accounted for
Participants 45 participants recruited for elective repair of inguinal hernias at the Eisenhower Army
Medical Centre, Fort Gordon, Georgia, USA
Inclusion/exclusion criteria not reported

Group 2 (n = 22): subcuticular polyglecaprone (Monocryl®) suture
Outcomes Dehiscence, infection, cosmesis and time taken to closure
Notes The cosmetic data were not included as the data were taken at < 3 months. The authors
were contacted for the mean and standard deviations for the time to closure, but since
no response has been received these data were not included
Risk of bias
Random sequence generation (selection Low risk Quote: “ . . . patients were then randomised
bias) with the use of a computerized random
number generator to receive either 2-octyl-
cyanoacrylate tissue adhesive or subcuticular
running 4-0 poliglecaprone 25 (Monocryl,
Ethicon, Inc) skin closure”
Comment: judgement of a low risk of se-
lection bias due to use of computer to gen-
erate random number sequence
Allocation concealment (selection bias) Unclear risk Quote: “ . . . patients were then randomised
with the use of a computerized random
number generator to receive either 2-octyl-
cyanoacrylate tissue adhesive or subcuticular
running 4-0 poliglecaprone 25 (Monocryl,
Ethicon, Inc) skin closure”
Comment: No specific mention of how se-
quence was allocated.

Switzer 2003 (Continued)
blind operating surgeon to intervention
Blinding of outcome assessment (detection Unclear risk Quote: “Patients were monitored postopera-
bias) tively for complications of their closures, and
All outcomes all patients were scheduled for post-operative
visits at 2 weeks and at 4 weeks”
Comment: it is not reported whether those
monitoring for post-operative complica-
tions were blinded to the intervention.
Cosmesis assessment was blinded, but these
data were not extracted here as taken at < 3
months after surgery
Incomplete outcome data (attrition bias) Low risk Not directly stated, but no participants
All outcomes were reported to have been lost to follow-
up and all were accounted for in results
Comment: judged as low risk of attrition
bias
results section
inferred
Tierny 2009
Methods Split body design RCT with 3 months follow-up
Participants 8 participants undergoing surgery for non-melanomas skin cancer

Exclusion criteria: on immuno-suppressive medication and/or recipients of organ trans-
plants
Undertaken in 1 centre in the USA
Interventions 8 participants, each having half of incisional wound randomised to each intervention
Intervention 1 (8 half wounds): 2-octylcyanoacrylate (Dermabond®) tissue adhesive
(Ethicon Inc, a Johnson & Johnson company, Somerville, New Jersey, USA)
Intervention 2 (8 half wounds): rapid absorbing gut suture
Outcomes Wound dehiscence (1 week postoperatively)

Wound infection (1 week postoperatively - no definition provided)

Tierny 2009 (Continued)
Notes Cosmetic appearance (surgeon) at 3 months and cosmetic appearance (participant) at

3 months were collected but the data are not clear and not presented here. The report
suggests that outcome data were reported on a 1 to 4 point scale but some data are > 4
so this is unclear. Also unclear what the scale measured
Patient reference data not extracted
Risk of bias
Random sequence generation (selection Unclear risk Quote: “Patients were randomised for epi-
bias) dermal closure with one half of the wounds
(chest (n=6) and upper extremities n=2))
with rapid absorbing gut structure and on the
other half with 2-octylethylcyanoacrylate tis-
sue adhesive”
Comment: no information given about the
method of randomisation
Allocation concealment (selection bias) Unclear risk Quote: “Patients were randomised for epi-
dermal closure with one half of the wounds
(chest (n=6) and upper extremities n=2))
with rapid absorbing gut structure and on the
other half with 2-octylethylcyanoacrylate tis-
sue adhesive”
whether allocation was concealed from the
participants
Blinding of participants and personnel Unclear risk Quote: “All wounds were closed by a single
(performance bias) surgeon (DJK) using a linear, bilayered clo-
All outcomes sure method . . .”
whether the participants or the personnel
were blinded to the intervention. However,
it would be difficult to blind personnel to
a surgical intervention
Blinding of outcome assessment (detection Unclear risk Quote: “Patients were seen for evaluation
bias) at postoperative visits at both 1 week and
All outcomes 3 months after the procedure. Incidence of
wound dehiscence and side effects of itching,
bleeding, and pain were assessed at 1 week”
Comment: unclear whether those evaluat-
ing the wounds at 1 week were blinded to
the intervention

Tierny 2009 (Continued)
Incomplete outcome data (attrition bias) Low risk No direct quotations, although there was
All outcomes no loss to follow-up reported within the
study
results section
inferred
Toriumi 1998
Methods RCT with 1-year follow-up. 11 participants were lost to follow-up, but the groups from
which they came were not specified
Participants People over 1 year of age requiring elective surgery for benign skin lesions predominantly
in face and neck
Exclusion criteria: a history of significant trauma; peripheral vascular disease; diabetes
mellitus; blood clotting disorder; keloid or hypertrophy scarring; known allergy to
cyanoacrylate or formaldehyde
Trial conducted at University of Illinois, Chicago, USA
Interventions Incisions with and without subcutaneous sutures were randomised for closure with:
Group 1: 2-octylcyanoacrylate, or
Group 2: 5.0 or 6.0 nylon suture
Outcomes Dehiscence, infection, cosmesis and closure time
Notes Participants lost to follow up were not reported by group
Risk of bias
Random sequence generation (selection Unclear risk Quote: ”Using clinical indications as evalu-
bias) ated by the surgeon, patients were assigned to
one of the two treatment groups“. Later trial
report mentions ”Patients were randomised
. . .“
Comment: no method of randomised se-
quence generation stated. The initial quo-
tation suggests clinicians had some auton-
omy in deciding which participants were
to receive which treatment, which in turn
represents a high risk of bias, but this is un-
clear

Toriumi 1998 (Continued)
Allocation concealment (selection bias) Unclear risk Quote: ”Using clinical indications as evalu-
ated by the surgeon, patients were assigned to
one of the two treatment groups“
Comment: no mention of allocation con-
cealment and possible evidence that sur-
geon was aware of allocation

All outcomes Comment: due to the nature of the surgical
procedure, it would be difficult to blind
either the operating surgeon or participants
Blinding of outcome assessment (detection Unclear risk Quote: ”At each postoperative visit, wounds
bias) were examined for infection, inflammation,
All outcomes wound dehiscence or separation, and scarring.
“ and, ”At the 90 day follow up visit, the
wounds were graded for cosmesis using the
modified Hollander wound evaluation scale”,
and, at one year, the patients were assessed
by way of a standardised method of pho-
tography of the wound, “The photographs
were then given to two facial plastic surgeons
that were unfamiliar with the study design,
the purpose or the site of the surgical incision,
or the type of treatment received”
Comment: no indication of blinded out-
come assessment for outcomes assessed
prior to one year. Blinded outcome assess-
ment of wound appearance at 12 month
follow-up
Incomplete outcome data (attrition bias) Unclear risk No direct quotations given, but results
All outcomes show that of the 100/111 (90%) patients
enrolled in the study for their long term 1-
year follow-up wound evaluation
Comment: 10% loss of follow-up data at
12 months
results section
inferred

van den Ende 2004
Methods 2-arm RCT with 6 week follow-up
Participants 100 children undergoing correction of hernia inguinalis

No inclusion or exclusion criteria stated
Interventions Group 1 (n = 50): butylcyanoacrylate (Indermil) tissue adhesive

Group 2 (n = 50): polyglactin 5-0 (Vicryl) sutures
Outcomes Wound dehiscence (10 days after surgery)

Wound infection (not defined; 10 days after surgery)
Mean closure time
Notes It is noted that 100 participants were randomised and that some had surgery on both sides
of the abdomen. It was not clear from the study results whether outcomes were presented
at the participant level. In one instance where % data are presented the denominator
used was 50 for each group suggesting that there is no unit of analysis issue but this is
not clear
Wound cosmesis assessed at 6 weeks - not presented here
Risk of bias
Random sequence generation (selection Unclear risk Quote: “Patients were selected randomly to receive
bias) wound adhesive or suture on the basis of 100 previ-
ously prepared and sealed envelopes containing slips
for either suture closure or the use of Indermil (50 of
each)”
Comment: use of opaque, sealed envelopes, but
not noted whether numbered in such a way as to
ensure robust allocation concealment maintained.
Not clear if person who opened envelopes was
independent
Allocation concealment (selection bias) Unclear risk Not reported
Blinding of participants and personnel Unclear risk No mention of blinding of participants or person-
(performance bias) nel
All outcomes Comment: due to the nature of the surgical pro-
cedure, it would be difficult to blind either the
operating surgeon
Blinding of outcome assessment (detection Unclear risk No mention of blinded outcome assessment
bias)
All outcomes
Incomplete outcome data (attrition bias) Low risk No mention of loss to follow-up
All outcomes

van den Ende 2004 (Continued)
Selective reporting (reporting bias) Low risk No direct quotations, but all variables listed in
methods are listed in the tables in the results sec-
tion
Comment: a low risk of reporting bias is inferred
Other bias Unclear risk Comment: it is noted that 100 participants were
randomised and that some had surgery on both
sides of the abdomen. It is not clear from the study
results if outcomes are presented at the participant
level. Where % data is presented in one case the
denominator used was 50 for each group suggest-
ing that there is no unit of analysis issue but this
is not clear
Abbreviations
h = hour(s)
min = minute(s)
RCT = randomised controlled trial
ROM = range of motion
VAS = visual analogue scale
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Ak 2012 Not relevant wound type (not surgical wound)
Alhopuro 1976 No data given in the paper. We have contacted authors but did not receive a reply
Chen 2010 Does not include any outcome relevant to this review
Chow 2010 Does not include any outcome relevant to this review
Giri 2004 Not an RCT
Gorozpe-Calvillo 1999 After full translation, found not to be an RCT
Jaibaji 2000 All participants in the intervention group had a precautionary subcuticular suture placed. The reviewers
viewed this as an inherent bias to the outcome of this group and thus the study was excluded
Kuo 2006 All participants had a subcuticular suture placed and described the intervention as a method of “superficial”
closure. The reviewers viewed this as unnecessary and counter-intuitive as the aim of the study is to assess
the adhesive as an alternative to other methods of closure of incisions, not as an adjunct

(Continued)
Matin 2003 Not an RCT - see quotation below - considered alternation

Quote: “Randomization was performed weekly. Each odd numbered week of the study (first week, third week,
etc. was randomized to either OCA or suturing by a biostatistician, and then the subsequent even numbered week
(second week, fourth week, etc) received the opposite treatment.”
Maw 1997 Not considered an RCT
Ong 2010 Skin closure method was not the only systematic difference between groups
Orozco-Razon 2002 There was no reference to randomisation. The authors have been contacted but we have received no reply
Quinn 1998 Not relevant wound type (not surgical wound)
Sajid 2009 Not an RCT
Silvestri 2006 Not an RCT
Singer 2002 Data could not be used because combined with data for lacerations. We wrote to the authors requesting
data by group but did not receive a reply
Spencker 2011 Not an RCT
Steiner 2000 Not an RCT
Sun 2005 No relevant outcomes (based on translation)
Wong 2011 Not relevant wound type (not surgical wounds)
Abbreviation
RCT = randomised controlled trial
Characteristics of studies awaiting assessment [ordered by study ID]
Gennari 2004
Methods
Participants
Interventions
Outcomes
Notes Citation retrieved through handsearching awaiting full text retrieval

Handschel 2006
Methods
Participants
Interventions
Outcomes
Jan 2013
Methods
Participants
Interventions
Outcomes
Notes Conference abstract with limited data - contacting authors to find out if there is a pending publication or if further
information available
Nipshagen 2008
Methods
Participants
Interventions
Outcomes
Yoon 2006
Methods Requires translation
Participants
Interventions
Outcomes
Notes

DATA AND ANALYSES
Comparison 1. Adhesive versus suture
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Dehiscence: all studies 17 1225 Risk Ratio (M-H, Random, 95% CI) 3.35 [1.53, 7.33]
2 Dehiscence: sensitivity analysis 13 935 Risk Ratio (M-H, Random, 95% CI) 2.70 [0.95, 7.68]
3 Infection: all studies 18 1239 Risk Ratio (M-H, Random, 95% CI) 1.72 [0.94, 3.16]
4 Infection: sensitivity analysis 15 977 Risk Ratio (M-H, Random, 95% CI) 2.03 [0.80, 5.12]
5 Cosmetic appearance rated by 2 199 Mean Difference (IV, Random, 95% CI) -2.12 [-7.20, 2.95]
patient
5.1 VAS 0 to 100 2 199 Mean Difference (IV, Random, 95% CI) -2.12 [-7.20, 2.95]
6 Cosmetic appearance rated by 2 Mean Difference (IV, Fixed, 95% CI) Totals not selected
surgeon
6.1 VAS scale 0 to 100 1 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
6.2 Scar assessment (0 to 5 1 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
scale)
7 Patient/parent satisfaction (% 2 206 Risk Ratio (M-H, Random, 95% CI) 1.01 [0.96, 1.07]
satisfied)
8 Patient/parent satisfaction (VAS 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only
Scale 0 to 100)
9 Surgeon satisfaction (% satisfied) 2 150 Risk Ratio (M-H, Random, 95% CI) 1.12 [0.58, 2.19]
10 Time taken for wound closure 5 Mean Difference (IV, Random, 95% CI) Subtotals only
Comparison 2. Adhesive versus adhesive tape
No. of No. of
1 Dehiscence 2 Risk Ratio (M-H, Random, 95% CI) Subtotals only

2 Infection 3 190 Risk Ratio (M-H, Random, 95% CI) 1.37 [0.39, 4.81]
3 Cosmetic appearance rated by 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only
patient (VAS)
4 Cosmetic appearance rated by 1 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only
patient (% satisfied)
5 Cosmetic appearance rated by 2 139 Mean Difference (IV, Random, 95% CI) 9.56 [4.74, 14.37]
surgeon (VAS)
6 Patient satisfaction 1 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only
7 Surgeon satisfaction 2 141 Risk Ratio (M-H, Random, 95% CI) 0.87 [0.63, 1.19]
8 Time taken for wound closure 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only

Comparison 3. Adhesive versus staples
No. of No. of
1 Dehiscence 2 107 Risk Ratio (M-H, Random, 95% CI) 0.53 [0.05, 5.33]
3 Cosmetic appearance rated by 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only
patient (scar scale)
4 Cosmetic appearance by plastic 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only
surgeons (VAS)
5 Patient satisfaction 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only
Comparison 4. Adhesive versus other method
No. of No. of
3 Patient satisfaction 1 187 Mean Difference (IV, Fixed, 95% CI) 0.40 [0.10, 0.70]
4 Clinician satisfaction 1 209 Mean Difference (IV, Fixed, 95% CI) 0.53 [0.29, 0.77]
5 Time taken for wound closure 1 209 Mean Difference (IV, Fixed, 95% CI) -1.05 [-1.79, -0.31]
Comparison 5. Adhesive versus adhesive: High viscosity versus low viscosity
No. of No. of
1 Dehiscence 1 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only

2 Infection 1 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only
3 Patient satisfaction 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only
4 Clinician satisfaction 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only

Comparison 6. Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate
No. of No. of
2 Infection 2 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only
3 Cosmetic assessment rated by 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only
patient (VAS)
4 Cosmetic assessment rated by 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only
surgeon (VAS)
5 Surgeon satisfaction (with 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only
device)
6 Surgeon satisfaction (with 1 Mean Difference (IV, Fixed, 95% CI) Subtotals only
closure)
Analysis 1.1. Comparison 1 Adhesive versus suture, Outcome 1 Dehiscence: all studies.
Review: Tissue adhesives for closure of surgical incisions
Comparison: 1 Adhesive versus suture
Outcome: 1 Dehiscence: all studies
Study or subgroup Adhesive Suture Risk Ratio Weight Risk Ratio

M- M-
H,Random,95% H,Random,95%
n/N n/N CI CI
Brown 2009 0/64 0/70 Not estimable
Cheng 1997 2/40 0/46 6.8 % 5.73 [ 0.28, 115.97 ]
Dowson 2006 4/76 0/78 7.3 % 9.23 [ 0.51, 168.63 ]
Eggers 2011 1/19 1/19 8.5 % 1.00 [ 0.07, 14.85 ]
Greene 1999 0/20 0/20 Not estimable
Millan 2011 3/30 0/30 7.2 % 7.00 [ 0.38, 129.93 ]
Mota 2009 3/51 2/46 20.2 % 1.35 [ 0.24, 7.74 ]
Ong 2002 0/26 0/33 Not estimable
Ozturan 2001 0/34 0/67 Not estimable
Sebesta 2004 2/29 0/30 6.9 % 5.17 [ 0.26, 103.21 ]
Shamiyeh 2001 1/26 0/26 6.2 % 3.00 [ 0.13, 70.42 ]
0.002 0.1 1 10 500

Favours adhesive Favours suture
(Continued . . . )

(. . .Continued)
M- M-
n/N n/N CI CI
Sinha 2001 3/20 2/24 21.6 % 1.80 [ 0.33, 9.73 ]
Sniezek 2007 0/14 0/14 Not estimable
Switzer 2003 4/24 0/22 7.5 % 8.28 [ 0.47, 145.50 ]
Tierny 2009 0/8 0/8 Not estimable
Toriumi 1998 0/54 0/57 Not estimable
van den Ende 2004 13/50 0/50 7.9 % 27.00 [ 1.65, 442.17 ]
Total (95% CI) 585 640 100.0 % 3.35 [ 1.53, 7.33 ]

Total events: 36 (Adhesive), 5 (Suture)
Heterogeneity: Tau2 = 0.0; Chi2 = 6.52, df = 9 (P = 0.69); I2 =0.0%
Test for overall effect: Z = 3.02 (P = 0.0025)
Test for subgroup differences: Not applicable
0.002 0.1 1 10 500


Analysis 1.2. Comparison 1 Adhesive versus suture, Outcome 2 Dehiscence: sensitivity analysis.
Outcome: 2 Dehiscence: sensitivity analysis

M- M-
n/N n/N CI CI
Brown 2009 0/64 0/70 Not estimable
Dowson 2006 4/76 0/78 12.9 % 9.23 [ 0.51, 168.63 ]
Eggers 2011 1/19 1/19 15.0 % 1.00 [ 0.07, 14.85 ]
Mota 2009 3/51 2/46 35.8 % 1.35 [ 0.24, 7.74 ]
Ozturan 2001 0/34 0/67 Not estimable
Sebesta 2004 2/29 0/30 12.1 % 5.17 [ 0.26, 103.21 ]
Shamiyeh 2001 1/26 0/26 10.9 % 3.00 [ 0.13, 70.42 ]
Switzer 2003 4/24 0/22 13.3 % 8.28 [ 0.47, 145.50 ]
Total (95% CI) 445 490 100.0 % 2.70 [ 0.95, 7.68 ]

0.01 0.1 1 10 100

Favours adhesive Favours sutures

Analysis 1.3. Comparison 1 Adhesive versus suture, Outcome 3 Infection: all studies.
Outcome: 3 Infection: all studies

M- M-
n/N n/N CI CI
Avsar 2009 3/20 0/20 4.4 % 7.00 [ 0.38, 127.32 ]
Cheng 1997 1/40 0/46 3.7 % 3.44 [ 0.14, 82.13 ]
Dowson 2006 0/76 0/78 Not estimable
Eggers 2011 4/19 5/19 27.8 % 0.80 [ 0.25, 2.53 ]
Keng 1989 0/21 0/22 Not estimable
Khan 2006 7/60 2/64 15.7 % 3.73 [ 0.81, 17.27 ]
Maartense 2002 5/48 3/50 19.5 % 1.74 [ 0.44, 6.87 ]
Ozturan 2001 0/34 3/67 4.3 % 0.28 [ 0.01, 5.22 ]
Sebesta 2004 1/29 0/30 3.7 % 3.10 [ 0.13, 73.14 ]
Shamiyeh 2001 1/26 0/26 3.7 % 3.00 [ 0.13, 70.42 ]
Sinha 2001 0/20 0/24 Not estimable
Switzer 2003 1/24 0/22 3.7 % 2.76 [ 0.12, 64.41 ]
van den Ende 2004 4/50 2/50 13.5 % 2.00 [ 0.38, 10.43 ]
Total (95% CI) 589 650 100.0 % 1.72 [ 0.94, 3.16 ]

0.002 0.1 1 10 500


Analysis 1.4. Comparison 1 Adhesive versus suture, Outcome 4 Infection: sensitivity analysis.
Outcome: 4 Infection: sensitivity analysis

M- M-
n/N n/N CI CI
Avsar 2009 3/20 0/20 10.2 % 7.00 [ 0.38, 127.32 ]
Cheng 1997 1/40 0/46 8.5 % 3.44 [ 0.14, 82.13 ]
Dowson 2006 0/76 0/78 Not estimable
Keng 1989 0/21 0/22 Not estimable
Maartense 2002 5/48 3/50 45.4 % 1.74 [ 0.44, 6.87 ]
Ozturan 2001 0/34 3/67 10.0 % 0.28 [ 0.01, 5.22 ]
Sebesta 2004 1/29 0/30 8.6 % 3.10 [ 0.13, 73.14 ]
Shamiyeh 2001 1/26 0/26 8.6 % 3.00 [ 0.13, 70.42 ]
Sinha 2001 0/20 0/24 Not estimable
Switzer 2003 1/24 0/22 8.7 % 2.76 [ 0.12, 64.41 ]
Total (95% CI) 460 517 100.0 % 2.03 [ 0.80, 5.12 ]

0.01 0.1 1 10 100

Favours adhesive Favours sutures

Analysis 1.5. Comparison 1 Adhesive versus suture, Outcome 5 Cosmetic appearance rated by patient.
Outcome: 5 Cosmetic appearance rated by patient
Mean Mean
Study or subgroup Adhesive Suture Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
1 VAS 0 to 100
Maartense 2002 48 76 (24) 50 78 (17) 37.7 % -2.00 [ -10.26, 6.26 ]
Ozturan 2001 34 70.3 (14.9) 67 72.5 (16.8) 62.3 % -2.20 [ -8.62, 4.22 ]
Total (95% CI) 82 117 100.0 % -2.12 [ -7.20, 2.95 ]

-20 -10 0 10 20
Favours suture Favours adhesive
Analysis 1.6. Comparison 1 Adhesive versus suture, Outcome 6 Cosmetic appearance rated by surgeon.
Outcome: 6 Cosmetic appearance rated by surgeon
Mean Mean
Study or subgroup Adhesive Suture Difference Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
1 VAS scale 0 to 100

Maartense 2002 48 82 (20) 50 79 (10) 3.00 [ -3.30, 9.30 ]
2 Scar assessment (0 to 5 scale)

Kouba 2011 24 1.26 (0.45) 24 1.52 (0.67) -0.26 [ -0.58, 0.06 ]
-10 -5 0 5 10

Analysis 1.7. Comparison 1 Adhesive versus suture, Outcome 7 Patient/parent satisfaction (% satisfied).
Outcome: 7 Patient/parent satisfaction (% satisfied)

M- M-
n/N n/N CI CI
Dowson 2006 76/76 76/78 76.6 % 1.03 [ 0.98, 1.07 ]
Shamiyeh 2001 25/26 26/26 23.4 % 0.96 [ 0.87, 1.07 ]
Total (95% CI) 102 104 100.0 % 1.01 [ 0.96, 1.07 ]

Heterogeneity: Tau2 = 0.00; Chi2 = 1.33, df = 1 (P = 0.25); I2 =25%
0.5 0.7 1 1.5 2

Favours sutures Favours adhesive
Analysis 1.8. Comparison 1 Adhesive versus suture, Outcome 8 Patient/parent satisfaction (VAS Scale 0 to
100).
Outcome: 8 Patient/parent satisfaction (VAS Scale 0 to 100)
Mean Mean
Ong 2002 26 78 (19) 33 81 (15) -3.00 [ -11.92, 5.92 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

Heterogeneity: not applicable
Test for overall effect: Z = 0.0 (P < 0.00001)
-100 -50 0 50 100


Analysis 1.9. Comparison 1 Adhesive versus suture, Outcome 9 Surgeon satisfaction (% satisfied).
Outcome: 9 Surgeon satisfaction (% satisfied)

M- M-
n/N n/N CI CI
Maartense 2002 20/48 13/50 45.7 % 1.60 [ 0.90, 2.85 ]
Shamiyeh 2001 15/26 18/26 54.3 % 0.83 [ 0.55, 1.26 ]
Total (95% CI) 74 76 100.0 % 1.12 [ 0.58, 2.19 ]

0.01 0.1 1 10 100


Analysis 1.10. Comparison 1 Adhesive versus suture, Outcome 10 Time taken for wound closure.
Outcome: 10 Time taken for wound closure
Mean Mean
Sebesta 2004 29 222 (67.8) 30 845 (360) -623.00 [ -754.16, -491.84 ]
Ozturan 2001 34 55 (10) 67 155 (25) -100.00 [ -106.87, -93.13 ]
Brown 2009 64 1.4 (0.8) 70 2.4 (1.1) -1.00 [ -1.32, -0.68 ]
Shamiyeh 2001 26 1.14 (0.24) 28 0.64 (0.23) 0.50 [ 0.37, 0.63 ]
Ong 2002 26 181 (61) 33 161 (45) 20.00 [ -8.03, 48.03 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

Heterogeneity: Tau2 = 0.0; Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
-100 -50 0 50 100


Analysis 2.1. Comparison 2 Adhesive versus adhesive tape, Outcome 1 Dehiscence.
Comparison: 2 Adhesive versus adhesive tape
Outcome: 1 Dehiscence
Study or subgroup Adhesive Tape Risk Ratio Weight Risk Ratio

M- M-
n/N n/N CI CI
Romero 2011 0/24 0/25 Not estimable
Shamiyeh 2001 1/26 1/25 0.96 [ 0.06, 14.55 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

Total events: 1 (Adhesive), 1 (Tape)
0.001 0.01 0.1 1 10 100 1000

Favours adhesive Favours tape
Analysis 2.2. Comparison 2 Adhesive versus adhesive tape, Outcome 2 Infection.
Outcome: 2 Infection

M- M-
n/N n/N CI CI
Maartense 2002 5/48 2/42 62.7 % 2.19 [ 0.45, 10.69 ]
Romero 2011 0/24 1/25 15.9 % 0.35 [ 0.01, 8.12 ]
Shamiyeh 2001 1/26 1/25 21.4 % 0.96 [ 0.06, 14.55 ]
Total (95% CI) 98 92 100.0 % 1.37 [ 0.39, 4.81 ]

0.005 0.1 1 10 200


Analysis 2.3. Comparison 2 Adhesive versus adhesive tape, Outcome 3 Cosmetic appearance rated by
patient (VAS).
Outcome: 3 Cosmetic appearance rated by patient (VAS)
Mean Mean
Study or subgroup Adhesive Tape Difference Weight Difference
Maartense 2002 48 76 (24) 42 79 (20) -3.00 [ -12.09, 6.09 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-50 -25 0 25 50
Favours tape Favours adhesive

patient (% satisfied).
Outcome: 4 Cosmetic appearance rated by patient (% satisfied)

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Romero 2011 19/22 19/20 0.91 [ 0.75, 1.10 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

0.01 0.1 1 10 100

surgeon (VAS).
Outcome: 5 Cosmetic appearance rated by surgeon (VAS)
Mean Mean
Maartense 2002 48 82 (20) 42 69 (18) 33.8 % 13.00 [ 5.15, 20.85 ]
Romero 2011 24 28.9 (10.4) 25 21.1 (8.3) 66.2 % 7.80 [ 2.52, 13.08 ]
Total (95% CI) 72 67 100.0 % 9.56 [ 4.74, 14.37 ]

-50 -25 0 25 50

Analysis 2.6. Comparison 2 Adhesive versus adhesive tape, Outcome 6 Patient satisfaction.
Outcome: 6 Patient satisfaction

Shamiyeh 2001 25/26 22/25 1.09 [ 0.93, 1.29 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

0.5 0.7 1 1.5 2

Analysis 2.7. Comparison 2 Adhesive versus adhesive tape, Outcome 7 Surgeon satisfaction.
Outcome: 7 Surgeon satisfaction

M- M-
n/N n/N CI CI
Maartense 2002 20/48 21/42 48.9 % 0.83 [ 0.53, 1.31 ]
Shamiyeh 2001 15/26 16/25 51.1 % 0.90 [ 0.58, 1.40 ]
Total (95% CI) 74 67 100.0 % 0.87 [ 0.63, 1.19 ]

0.05 0.2 1 5 20

Analysis 2.8. Comparison 2 Adhesive versus adhesive tape, Outcome 8 Time taken for wound closure.
Mean Mean
Shamiyeh 2001 26 1.14 (0.24) 25 0.58 (0.27) 0.56 [ 0.42, 0.70 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-2 -1 0 1 2
Analysis 3.1. Comparison 3 Adhesive versus staples, Outcome 1 Dehiscence.
Comparison: 3 Adhesive versus staples
Study or subgroup Adhesive Staples Risk Ratio Weight Risk Ratio

M- M-
n/N n/N CI CI
Eggers 2011 1/18 2/19 100.0 % 0.53 [ 0.05, 5.33 ]
Pronio 2011 0/32 0/38 Not estimable
Total (95% CI) 50 57 100.0 % 0.53 [ 0.05, 5.33 ]

Total events: 1 (Adhesive), 2 (Staples)
0.01 0.1 1 10 100

Favours staples Favours adhesive

Analysis 3.2. Comparison 3 Adhesive versus staples, Outcome 2 Infection.
Study or subgroup Adhesive Staples Risk Ratio Weight Risk Ratio

M- M-
n/N n/N CI CI
Eggers 2011 6/18 1/19 31.0 % 6.33 [ 0.84, 47.57 ]
Khan 2006 4/60 7/63 47.5 % 0.60 [ 0.19, 1.95 ]
Livesey 2009 1/45 1/45 21.5 % 1.00 [ 0.06, 15.50 ]
Pronio 2011 0/32 0/38 Not estimable
Total (95% CI) 155 165 100.0 % 1.39 [ 0.30, 6.54 ]

Total events: 11 (Adhesive), 9 (Staples)
0.01 0.1 1 10 100

Favours adhesive Favours staples
Analysis 3.3. Comparison 3 Adhesive versus staples, Outcome 3 Cosmetic appearance rated by patient
(scar scale).
Outcome: 3 Cosmetic appearance rated by patient (scar scale)
Mean Mean
Study or subgroup Adhesive Staples Difference Weight Difference
Pronio 2011 32 4.94 (0.25) 38 4.86 (0.36) 0.08 [ -0.06, 0.22 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-1 -0.5 0 0.5 1
Favours adhesive Favours staples

Analysis 3.4. Comparison 3 Adhesive versus staples, Outcome 4 Cosmetic appearance by plastic surgeons
(VAS).
Outcome: 4 Cosmetic appearance by plastic surgeons (VAS)
Mean Mean
Livesey 2009 45 78.2 (10.9) 45 81.1 (7.4) -2.90 [ -6.75, 0.95 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-20 -10 0 10 20

Analysis 3.5. Comparison 3 Adhesive versus staples, Outcome 5 Patient satisfaction.
Mean Mean
Amin 2009 33 9.1 (1.3) 27 8 (1.4) 1.10 [ 0.41, 1.79 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-4 -2 0 2 4
Analysis 3.6. Comparison 3 Adhesive versus staples, Outcome 6 Time taken for wound closure.
Mean Mean
Ridgway 2007 14 95 (52) 15 28 (10) 67.00 [ 39.30, 94.70 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-200 -100 0 100 200

Favours adhesive Favours staple

Analysis 4.1. Comparison 4 Adhesive versus other method, Outcome 1 Dehiscence.
Comparison: 4 Adhesive versus other method
Study or subgroup HV adhesive Other Risk Ratio Weight Risk Ratio

M- M-
n/N n/N CI CI
Blondeel 2004 4/148 3/61 100.0 % 0.55 [ 0.13, 2.38 ]
Chibbaro 2009 0/20 0/20 Not estimable
Total (95% CI) 168 81 100.0 % 0.55 [ 0.13, 2.38 ]

Total events: 4 (HV adhesive), 3 (Other)
0.002 0.1 1 10 500

Favours HV adhesive Favours other
Analysis 4.2. Comparison 4 Adhesive versus other method, Outcome 2 Infection.
Study or subgroup HV adhesive Other Risk Ratio Weight Risk Ratio

M- M-
n/N n/N CI CI
Blondeel 2004 4/148 4/61 100.0 % 0.41 [ 0.11, 1.60 ]
Chibbaro 2009 0/20 0/20 Not estimable
Total (95% CI) 168 81 100.0 % 0.41 [ 0.11, 1.60 ]

Total events: 4 (HV adhesive), 4 (Other)
0.001 0.01 0.1 1 10 100 1000


Analysis 4.3. Comparison 4 Adhesive versus other method, Outcome 3 Patient satisfaction.
Mean Mean
Study or subgroup HV adhesive Other Difference Weight Difference
Blondeel 2004 133 4.51 (0.66) 54 4.11 (1.06) 100.0 % 0.40 [ 0.10, 0.70 ]
Total (95% CI) 133 54 100.0 % 0.40 [ 0.10, 0.70 ]

-2 -1 0 1 2

Analysis 4.4. Comparison 4 Adhesive versus other method, Outcome 4 Clinician satisfaction.
Outcome: 4 Clinician satisfaction
Mean Mean
Blondeel 2004 148 4.53 (0.6) 61 4 (0.89) 100.0 % 0.53 [ 0.29, 0.77 ]
Total (95% CI) 148 61 100.0 % 0.53 [ 0.29, 0.77 ]

-1 -0.5 0 0.5 1
Analysis 4.5. Comparison 4 Adhesive versus other method, Outcome 5 Time taken for wound closure.
Mean Mean
Blondeel 2004 148 1.96 (1.67) 61 3.01 (2.76) 100.0 % -1.05 [ -1.79, -0.31 ]
Total (95% CI) 148 61 100.0 % -1.05 [ -1.79, -0.31 ]

-2 -1 0 1 2

Analysis 5.1. Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 1
Dehiscence.
Comparison: 5 Adhesive versus adhesive: High viscosity versus low viscosity

Study or subgroup HV adhesive LV adhesive Risk Ratio Weight Risk Ratio

Blondeel 2004 4/105 0/43 3.74 [ 0.21, 67.93 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

Total events: 4 (HV adhesive), 0 (LV adhesive)
0.01 0.1 1 10 100

Favours HV adhesive Favours LV adhesive
Infection.

Study or subgroup HV adhesive LV adhesive Risk Ratio Weight Risk Ratio

Blondeel 2004 4/105 2/43 0.82 [ 0.16, 4.31 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

Total events: 4 (HV adhesive), 2 (LV adhesive)
0.005 0.1 1 10 200


Patient satisfaction.

Mean Mean
Study or subgroup HV adhesive LV adhesive Difference Weight Difference
Blondeel 2004 95 4.5 (0.68) 38 4.55 (0.6) -0.05 [ -0.28, 0.18 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-0.5 -0.25 0 0.25 0.5

Clinician satisfaction.

Outcome: 4 Clinician satisfaction
Mean Mean
Blondeel 2004 105 4.52 (0.61) 43 4.54 (0.59) -0.02 [ -0.23, 0.19 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-1 -0.5 0 0.5 1

Analysis 5.5. Comparison 5 Adhesive versus adhesive: High viscosity versus low viscosity, Outcome 5 Time
taken for wound closure.

Mean Mean
Blondeel 2004 105 2.12 (1.79) 43 1.58 (1.26) 0.54 [ 0.03, 1.05 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-2 -1 0 1 2
Analysis 6.1. Comparison 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate,

Outcome 1 Dehiscence.
Comparison: 6 Adhesive versus adhesive: octylcyanoacrylate versus butylcyanoacrylate

Study or subgroup Octylcyanoacrylate Butylcyanoacrylate Risk Ratio Weight Risk Ratio

M- M-
n/N n/N CI CI
Eggers 2011 1/19 1/18 57.7 % 0.95 [ 0.06, 14.04 ]
Maloney 2013 1/23 0/20 42.3 % 2.63 [ 0.11, 61.05 ]
Total (95% CI) 42 38 100.0 % 1.46 [ 0.19, 11.30 ]

Total events: 2 (Octylcyanoacrylate), 1 (Butylcyanoacrylate)
0.01 0.1 1 10 100

Favours octyl’ Favours butyl’

Outcome 2 Infection.

Study or subgroup Octylcyanoacrylate Butylcyanoacrylate Risk Ratio Weight Risk Ratio

Eggers 2011 4/19 6/18 0.63 [ 0.21, 1.88 ]
Maloney 2013 0/23 0/20 Not estimable
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

Total events: 4 (Octylcyanoacrylate), 6 (Butylcyanoacrylate)
0.01 0.1 1 10 100


Outcome 3 Cosmetic assessment rated by patient (VAS).

Outcome: 3 Cosmetic assessment rated by patient (VAS)
Mean Mean
Study or subgroup Octylcyanoacrylate Butylcyanoacrylate Difference Weight Difference
Maloney 2013 23 9 (1.2) 20 8.4 (2.1) 0.60 [ -0.44, 1.64 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-10 -5 0 5 10

Outcome 4 Cosmetic assessment rated by surgeon (VAS).

Outcome: 4 Cosmetic assessment rated by surgeon (VAS)
Mean Mean
Maloney 2013 23 6.8 (1.7) 20 7.2 (1.6) -0.40 [ -1.39, 0.59 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-10 -5 0 5 10

Outcome 5 Surgeon satisfaction (with device).

Outcome: 5 Surgeon satisfaction (with device)
Mean Mean
Maloney 2013 23 8.8 (0.7) 20 9 (1) -0.20 [ -0.72, 0.32 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-4 -2 0 2 4

Outcome 6 Surgeon satisfaction (with closure).

Outcome: 6 Surgeon satisfaction (with closure)
Mean Mean
Maloney 2013 23 8.3 (1) 20 8.4 (1.2) -0.10 [ -0.77, 0.57 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-4 -2 0 2 4

Outcome 7 Time taken for wound closure.

Mean Mean
Maloney 2013 23 54.5 (25.6) 20 80 (22.2) -25.50 [ -39.79, -11.21 ]
Subtotal (95% CI) 0 0 0.0 [ 0.0, 0.0 ]

-100 -50 0 50 100

ADDITIONAL TABLES
Table 1. Summary of study comparisons
Tis- 2- 2- 2- Trial 2- Su- Sta- Ad- All

sue Mixed Butyl- octyl octyl Butyl- octyl ID octyl Butyl- tures ples he- Mixed non- Other
adhe- con- 2- 2- 2- sive su- tissue vis-
sive trol cyanoacry-
cyanoacry- cyanoacry- cyanoacry- tape/ tures adhe- cos-
vs tis- late
cyanoacrylate late
cyanoacrylate cyanoacry- strips and sive ity 2-
sue (Comp late vs vs late vs su- late sta- clo- octyl
adhe- 4) vs sta- tape vs sutures ples sure
sive staples tures meth- cyanoacry-
ples (Comp (Comp1) ods late
(Comp (Comp 2) (Comp
5) (Comp 3) 1)
3)
√ √
3 Amin
2009
√ √
1 Avsar
2009
√ √ √
5 4 Blon-
deel
2004

Table 1. Summary of study comparisons (Continued)
√ √
1
Brown
2009
√ √
1
Cheng
1997
√ √
4 Chib-
baro
2009
√ √
1 Dow-
son
2006
√ √ √ √
5 3 3 1 1 Eg-
gers
2011
√ √
1
Greene
1999
√ √
1 Jallali
2004
√ √
1 Keng
1989
√ √
5 Kent
2014
√ √ √
3 1 Khan
2006
√ √
1
Kouba
2011
√ √
1 Kr-
ish-
namoor-
thy
2009
√ √
3
Livesey
2009
√ √ √
2 1
Maartense
2002

√ √
5 Mal-
oney
2013
√ √
1 Mil-
lan
2011
√ √
1 Mota
2009
√ √
1 Ong
2002
√ √
1 Oztu-
ran
2001
√ √
3 Pro-
nio
2011
√ √
3 Ridg-
way
2007
√ √
1
Sebesta
2004
√ √ √
2 1
Shamiyeh
2001
√ √
1 Sinha
2001
√ √
1
Sniezek
2007
√ √
1
Switzer
2003
√ √
1
Tierny
2009
√ √
1 Tori-
umi
1998

√ √
2
Romero
2011
√ √
1 van
den
Ende
2004
Abbreviation
Comp = comparison
APPENDICES
Appendix 1. Search strategy used in the original version of this review - 2007
In order to identify studies to be considered for this review the following databases were searched:
Cochrane Wounds Group Trials Register - November 2007
The Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library Issue 2, November 2007
MEDLINE 1966 - November 2007
EMBASE 1980 - November 2007
The Cochrane Wounds Group Trials Register has been compiled through searching of the major health databases including MED-
LINE, Cinahl and EMBASE and is regularly updated through searching of the Cochrane Central Register of Controlled Trials,
handsearching of wound care journals and relevant conference proceedings. See: Collaborative review group search strategy (http:/
www.cochranewounds.org).
The following search strategy was used for searching the Cochrane Wounds Group Trials Register and CENTRAL:
1 WOUNDS-AND-INJURIES*:ME
2 INCISION*
3 WOUND*
4 (SURGICAL and WOUND*)
5 (((#1 or #2) or #3) or #4)
6 TISSUE-ADHESIVES*:ME
7 ADHESIVES*:ME
8 ACRYLATES*:ME
9 (TISSUE* and ADHESIVE*)
10 ACRYLATE*
11 CYANOACRYLATE*
12 (GLU or GLUES)
13 (GLUE or GLUES)
14 FIBRIN-TISSUE-ADHESIVE*:ME
15 BUCRYLATE*:ME
16 BUCRYLATE*
17 SUTURES*:ME
18 SUTUR*
19 SURGICAL-STAPLING*:ME
20 STAPLE*
21 TAPE*
22 (((((((((((((((#6 or #7) or #8) or #9) or #10) or #11) or #12) or #13) or #14) or #15) or #16) or #17) or #18) or #19) or #20) or #
21)
23 (#5 and #22)
Search strategies were developed for Medline and Embase and these search strategies combined a sensitive search strategy for RCTs
revised from phases 1 and 2 of the Cochrane Sensitive Search Strategy for RCTs (as published in Appendix 6c in the Cochrane
Handbook). The subject search used a combination of controlled vocabulary and free text terms based on the search strategy for
searching the Cochrane Wounds Group Trial Register.
LANGUAGE
There were no language restrictions.
UNPUBLISHED STUDIES
Authors of the identified RCTs were written to in order to obtain further information about the trial and to attempt to identify
unpublished or ongoing studies. In addition, wound care product manufacturers were contacted.
HANDSEARCHING
Trials for Wounds Group Trials Register are identified by systematically handsearching specialised journals, relevant conference pro-
ceedings and abstracts. A list of journals currently being handsearched by the group may be found at http:/www.cochranewounds.org.
Appendix 2. Search strategy for the first update of this review - 2009
In order to identify studies to be considered for this review the following databases were searched:
Cochrane Wounds Group Specialised Register (November 2009;);
The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4);
Ovid MEDLINE (1996 to November week 1 2009);
Ovid MEDLINE (In-Process & Other Non-Indexed Citations, November 16 2009);
Ovid EMBASE (1996 to 2009 week 46);
EBSCO CINAHL (1982 to 11 November 2009)
The Cochrane Wounds Group Trials Register has been compiled through searching of the major health databases including MED-
LINE, Cinahl and EMBASE and is regularly updated through searching of the Cochrane Central Register of Controlled Trials,
handsearching of wound care journals and relevant conference proceedings. See: Collaborative review group search strategy (http:/
www.cochranewounds.org).
The following search strategy was used for searching the Cochrane Central Register of Controlled Trials (CENTRAL):
#1 MeSH descriptor Wounds and Injuries explode all trees
#2 surgical next wound*
#3 (#1 OR #2)
#4 MeSH descriptor Tissue Adhesives explode all trees
#5 MeSH descriptor Fibrin Tissue Adhesive explode all trees
#6 tissue next adhesive*
#7 MeSH descriptor Cyanoacrylates explode all trees
#8 octylcyanoacrylate*
#9 Dermabond
#10 MeSH descriptor Enbucrilate explode all trees
#11 enbucrilate
#12 butylcyanoacrylate*
#13 MeSH descriptor Acrylates explode all trees
#14 acrylate*
#15 MeSH descriptor Bucrylate explode all trees
#16 bucrylate*
#17 (#4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16)
#18 (#3 AND #17) with New in Record Status

Appendix 3. Ovid MEDLINE search strategy
Undertaken for second update in 2014
1 exp “Wounds and Injuries”/ (691113)
2 (surgical adj wound$).mp. (35309)
3 or/1-2 (721540)
4 exp Tissue Adhesives/ (12636)
5 exp Fibrin Tissue Adhesive/ (3859)
6 tissue adhesive$.mp. (8303)
7 exp Cyanoacrylates/ (3816)
8 octylcyanoacrylate$.mp. (103)
9 Dermabond.mp. (114)
10 exp Enbucrilate/ (1496)
11 enbucrilate.mp. (1236)
12 butylcyanoacrylate$.mp. (119)
13 exp Acrylates/ (41800)
14 acrylate$.mp. (8636)
15 exp Bucrylate/ (280)
16 bucrylate$.mp. (309)
17 or/4-16 (51986)
18 3 and 17 (3841)
19 randomized controlled trial.pt. (366703)
20 controlled clinical trial.pt. (87802)
21 randomi?ed.ab. (318385)
22 placebo.ab. (143748)
23 clinical trials as topic.sh. (168638)
24 randomly.ab. (189528)
25 trial.ti. (114737)
26 or/19-25 (860509)
27 exp animals/ not humans.sh. (3901060)
28 26 not 27 (791299)
29 18 and 28 (276)
Appendix 4. Ovid EMBASE search strategy

1 exp Surgical Wound/ (3914)
2 (surgical adj wound$).mp. (8021)
3 or/1-2 (8021)
4 exp Tissue Adhesive/ (13492)
5 exp Fibrin Glue/ (6712)
6 (tissue adj adhesive$).mp. (5179)
7 exp Cyanoacrylate Derivative/ (1595)
8 exp Cyanoacrylic Acid Octyl Ester/ (340)
9 octylcyanoacrylate$.mp. (130)
10 Dermabond.mp. (343)
11 exp ENBUCRILATE/ (2847)
12 enbucrilate.mp. (2852)
13 butylcyanoacrylate$.mp. (190)
14 exp Acrylic Acid/ (3718)
15 acrylate$.mp. (6120)
16 exp Bucrilate/ (623)
17 bucrylate$.mp. (138)
18 or/4-17 (23772)
19 3 and 18 (181)
20 Randomized controlled trials/ (47799)
21 Single-Blind Method/ (17933)
22 Double-Blind Method/ (114456)
23 Crossover Procedure/ (38119)
24 (random$ or factorial$ or crossover$ or cross over$ or cross-over$ or placebo$ or assign$ or allocat$ or volunteer$).ti,ab. (1300258)
25 (doubl$ adj blind$).ti,ab. (143978)
26 (singl$ adj blind$).ti,ab. (14109)
27 or/20-26 (1365111)
28 exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/ (19982416)
29 human/ or human cell/ (14519180)
30 and/28-29 (14472519)
31 28 not 30 (5509897)
32 27 not 31 (1177074)
33 19 and 32 (35)
Appendix 5. EBSCO CINAHL search strategy

S29 S16 AND S28
S28 S17 or S18 or S19 or S20 or S21 or S22 or S23 or S24 or S25 or S26 or S27
S27 TX allocat* random*
S26 (MH “Quantitative Studies”)
S25 (MH “Placebos”)
S24 TX placebo*
S23 TX random* allocat*
S22 (MH “Random Assignment”)
S21 TX randomi* control* trial*
S20 TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or
(tripl* n1 mask*) ) or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) )
S19 TX clinic* n1 trial*
S18 PT Clinical trial
S17 (MH “Clinical Trials+”)
S16 S5 and S15
S15 S6 or S7 or S8 or S9 or S10 or S11 or S12 or S13 or S14
S14 TI Dermabond or AB Dermabond
S13 TI enbucrilate or AB enbucrilate
S12 TI bucrylate* or AB bucrylate*
S11 TI acrylate* or AB acrylate*
S10 TI butylcyanoacrylate* or AB butylcyanoacrylate*
S9 TI octylcyanoacrylate* or AB octylcyanoacrylate*
S8 TI cyanoacrylate* or AB cyanoacrylate*
S7 TI tissue adhesive* or AB tissue adhesive*
S6 (MH “Fibrin Tissue Adhesive”)
S5 S1 or S2 or S3 or S4
S4 TI surgical wound* or AB surgical wound*
S3 (MH “Surgical Wound Care”)
S2 (MH “Surgical Wound”)
S1 (MH “Tears and Lacerations”)

Appendix 6. Risk of bias assessment
1. Was the allocation sequence randomly generated?
Low risk of bias

The investigators describe a random component in the sequence generation process such as: referring to a random number table; using
a computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots.
High risk of bias

The investigators describe a non-random component in the sequence generation process. Usually, the description would involve some
systematic, non-random approach, for example: sequence generated by odd or even date of birth; sequence generated by some rule
based on date (or day) of admission; sequence generated by some rule based on hospital or clinic record number.
Unclear
Insufficient information about the sequence generation process provided to permit a judgement of low or high risk of bias.
2. Was the treatment allocation adequately concealed?
Low risk of bias

Participants and investigators enrolling participants could not foresee assignment because one of the following, or an equivalent
method, was used to conceal allocation: central allocation (including telephone, web-based and pharmacy-controlled randomisation);
sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes.
High risk of bias

Participants or investigators enrolling participants could possibly foresee assignments and thus introduce selection bias, such as allocation
based on: using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate
safeguards (e.g. if envelopes were unsealed or non opaque or not sequentially numbered); alternation or rotation; date of birth; case
record number; any other explicitly unconcealed procedure.
Unclear
Insufficient information provided to permit a judgement of low or high risk of bias. This is usually the case if the method of concealment
is not described or not described in sufficient detail to allow a definite judgement, for example if the use of assignment envelopes is
described, but it remains unclear whether envelopes were sequentially numbered, opaque and sealed.
3. Blinding - was knowledge of the allocated interventions adequately prevented during the study?
Low risk of bias

Any one of the following.
• No blinding, but the review authors judge that the outcome and the outcome measurement are not likely to be influenced by
lack of blinding.
• Blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
• Either participants or some key study personnel were not blinded, but outcome assessment was blinded and the non-blinding of
others unlikely to introduce bias.

High risk of bias
• No blinding or incomplete blinding, and the outcome or outcome measurement is likely to be influenced by lack of blinding.
• Blinding of key study participants and personnel attempted, but likely that the blinding could have been broken.
• Either participants or some key study personnel were not blinded, and the non-blinding of others was likely to introduce bias.
Unclear
• Insufficient information provided to permit a judgement of low or high risk of bias.
• The study did not address this outcome.
4. Were incomplete outcome data adequately addressed?
Low risk of bias

• No missing outcome data.
• Reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing
bias).
• Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
• For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a
clinically relevant impact on the intervention effect estimate.
• For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing
outcomes not enough to have a clinically relevant impact on observed effect size.
• Missing data have been imputed using appropriate methods.
High risk of bias

• Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing
data across intervention groups.
• For dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce
clinically relevant bias in intervention effect estimate.
• For continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing
outcomes enough to induce clinically relevant bias in observed effect size.
• ‘As-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation.
• Potentially inappropriate application of simple imputation.
Unclear
Either of the following.
• Insufficient reporting of attrition/exclusions to permit judgement of low or high risk of bias (e.g. number randomised not stated,
no reasons for missing data provided).
• The study did not address this outcome.
5. Are reports of the study free of suggestion of selective outcome reporting?
Low risk of bias

Either of the following.
• The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the
review have been reported in the pre-specified way.
• The study protocol is not available but it is clear that the published reports include all expected outcomes, including those that
were pre-specified (convincing text of this nature may be uncommon).
High risk of bias

• Not all of the study’s pre-specified primary outcomes have been reported.
• One or more primary outcomes are reported using measurements, analysis methods or subsets of the data (e.g. subscales) that
were not pre-specified.
• One or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as
an unexpected adverse effect).
• One or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis.
• The study report fails to include results for a key outcome that would be expected to have been reported for such a study.
Unclear:
Insufficient information to permit judgement of low or high risk of bias. It is likely that the majority of studies will fall into this category.
6. Other sources of potential bias
Low risk of bias

The study appears to be free of other sources of bias.
High risk of bias

There is at least one important risk of bias. For example, the study:
• had a potential source of bias related to the specific study design used; or
• has been claimed to have been fraudulent; or
• had some other problem.
Unclear
There may be a risk of bias, but there is either:
• insufficient information to assess whether an important risk of bias exists; or
• insufficient rationale or evidence that an identified problem will introduce bias.
WHAT’S NEW
Last assessed as up-to-date: 12 March 2014.

Date Event Description
1 August 2014 New citation required but conclusions have not changed New search, risk of bias updated for all studies into cur-
rent format, revisions to text, no change to conclusions
1 August 2014 New search has been performed Second update: 19 new studies added: Amin 2009;
Avsar 2009; Brown 2009; Chibbaro 2009; Eggers
2011; Jallali 2004; Kent 2014; Khan 2006; Kouba
2011; Krishnamoorthy 2009; Livesey 2009; Maloney
2013; Millan 2011; Mota 2009; Pronio 2011; Romero
2011; Sebesta 2004; Tierny 2009; van den Ende 2004.
Five studies are awaiting assessment: Gennari 2004;
Handschel 2006; Jan 2013; Nipshagen 2008; Yoon 2006
HISTORY
Protocol first published: Issue 3, 2003
Review first published: Issue 2, 2004
Date Event Description
3 August 2010 Amended Contact details updated.
23 November 2009 New search has been performed New search and an additional 6 studies included in
the review (Blondeel 2004; Dowson 2006; Ong 2002;
Ridgway 2007; Sniezek 2007; Switzer 2003). Three
studies were excluded (Jaibaji 2000; Orozco-Razon
2002; Steiner 2000) and 7 studies are awaiting assess-
ment.
23 November 2009 New citation required and conclusions have changed Time to closure as an outcome measure was included
in the review at the time of this update (post hoc).
The review authors believe this to be a contributory
factor towards both cost-effectiveness and satisfaction.
An additional review author has joined the review team
for this first update
16 May 2002 New citation required and conclusions have changed Substantive amendment

CONTRIBUTIONS OF AUTHORS
Jo Dumville: coordinated the second review update. Extracted data and checked quality of data extraction. Undertook and checked
quality assessment. Analysed and interpreted data. Performed statistical analysis and checked quality of statistical analysis. Performed
part of writing and editing the review. Approved final review update prior to submission. Secured funding. Is the guarantor of the
review.
Paul Coulthard: conceived, designed and co-ordinated the initial review. Undertook the searches for the original review and screened
search results. Appraised quality and extracted data, wrote to trial authors for additional information. Managed data for the review and
entered data into RevMan. Analysed and interpreted data and wrote the review. Undertook previous work that was the foundation of
the current review. Approved final review update prior to submission.
Philip Riley: analysed and interpreted data for the second review update. Performed statistical analysis and checked quality of statistical
analysis. Performed part of writing and editing the review. Approved final review update prior to submission.
Helen Worthington: analysed and interpreted data for all versions of the review. Performed statistical analysis and checked quality
of statistical analysis. Performed part of writing and editing the review. screened search output for the second update. Approved final
review update prior to submission
Neil Patel: undertook quality assessment and checked quality assessment for the first update. Performed part of writing and editing
the review. Approved final review update prior to submission.
Marco Esposito: developed the search strategy, undertook the searches for the original review and advised on the review and commented
on all updates of the review.
Maarten van der Elst: Provided general advice on the original version of the review and undertook previous work that was the
foundation of the current review.
Oscar JF van Waes: screened search results against the inclusion criteria and retrieved papers, appraised quality and extracted data,
wrote to trial authors for additional information for the original version of the review. Undertook previous work that was the foundation
of the current review.
James Darcey: screened search results against the inclusion criteria, retrieved papers, appraised quality and extracted data, wrote to
trial authors for additional information for the for the first review update, managed data for the first review update and entered data
into RevMan. Analysed and interpreted data and wrote the first review update.
Contributions of editorial base

Nicky Cullum: edited the review, advised on methodology, interpretation and review content. Approved the final review and review
update prior to submission.
Sally Bell-Syer: co-ordinated the editorial process. Advised on methodology, interpretation and content. Edited and copy edited the
review and the updated review.
Amanda Briant: ran the searches and edited the search methods section for the update.
DECLARATIONS OF INTEREST
Jo C Dumville: None known
Paul Coulthard: was a co-author in the Blondeel 2004 study. This study was also commercially supported by Ethicon.
Philip Riley: None known
Helen V Worthington: None known
Neil Patel: None known
Marco Esposito: None known
Maarten van der Elst: None known
Oscar J F van Waes: None known
James Darcey: None known
SOURCES OF SUPPORT
Internal sources
• The University of Manchester, UK.
• Renier de Graaf Hospital, Netherlands.
• The Sahlgrenska Academy at Goteborg University, Sweden.
External sources
• Swedish Medical Research Council (9495), Sweden.
• The Hjalmar Svensson Research Fund, Sweden.
• The National Institute for Health Research (NIHR) is the sole funder of the Cochrane Wounds Group, UK.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

Time to closure as an outcome measure was included in the review post hoc as the review authors believe this to be a contributory
factor towards both cost-effectiveness and satisfaction.
INDEX TERMS
Medical Subject Headings (MeSH)

∗ Surgical
Procedures, Operative; ∗ Sutures; ∗ Tissue Adhesives; ∗ Wound Healing; Bandages; Cyanoacrylates; Enbucrilate; Randomized
Controlled Trials as Topic; Surgical Wound Dehiscence [∗ prevention & control]; Surgical Wound Infection [diagnosis]
MeSH check words

Humans


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Tissue adhesives for closure of surgical incisions (Review)

Tissue adhesives for closure of surgical incisions (Review)

Tissue adhesives for closure of surgical incisions (Review) ii

Tissue adhesives for closure of surgical incisions

Editorial group: Cochrane Wounds Group.

PLAIN LANGUAGE SUMMARY

Tissue adhesives for closure of surgical incisions (Review) 2

Tissue adhesive compared to sutures for surgical incisions

Patient or population: People with surgical incisions

Assumed risk Corresponding risk

Sutures Tissue adhesive

Wound dehiscence Study population RR 3.35 736 ⊕⊕

Wound infection Study population RR 1.72 744 ⊕

GRADE Working Group grades of evidence

Tissue adhesives for closure of surgical incisions (Review) 5

Tissue adhesives for closure of surgical incisions (Review) 6

Tissue adhesives for closure of surgical incisions (Review) 7

Tissue adhesives for closure of surgical incisions (Review) 8

Tissue adhesives for closure of surgical incisions (Review) 9

Comparison 3: Tissue adhesives compared with staples

High versus low viscosity adhesives

Tissue adhesives for closure of surgical incisions (Review) 10

Tissue adhesives for closure of surgical incisions (Review) 11

Tissue adhesives for closure of surgical incisions (Review) 12

Tissue adhesives for closure of surgical incisions (Review) 13

Random sequence generation

Incomplete outcome data

Tissue adhesives for closure of surgical incisions (Review) 15

Tissue adhesives for closure of surgical incisions (Review) 16

Maartense 2002 and Romero 2011 found no statistically signif-

Time to wound closure following surgery Cosmetic appearance

Tissue adhesives for closure of surgical incisions (Review) 17

Primary outcome Primary outcome

Tissue adhesives for closure of surgical incisions (Review) 18

Comparison 5.2. Octylcyanoacrylate vs butylcyanoacrylate

Tissue adhesives for closure of surgical incisions (Review) 19

One study suggested that, on average, it took 10 minutes longer

We present ’Summary of findings’ tables for the dehiscence and

Tissue adhesives for closure of surgical incisions (Review) 20

Tissue adhesive compared to adhesive tape for surgical incisions

Patient or population: people with surgical incisions

Assumed risk Corresponding risk

Adhesive tape Tissue adhesive

Wound dehiscence Study population RR 0.96 50 ⊕⊕

Wound infection Study population RR 1.37 190 ⊕⊕

GRADE Working Group grades of evidence

Tissue adhesive compared to staples for surgical incisions

Patient or population: people with surgical incisions

Assumed risk Corresponding risk

Staples Tissue adhesive

Wound dehiscence Study population RR 0.53 37 ⊕⊕

Wound infection Study population RR 1.39 250 ⊕

GRADE Working Group grades of evidence

Tissue adhesive compared to other methods for surgical incisions

Patient or population: people with surgical incisions

Assumed risk Corresponding risk

Other methods Tissue adhesive

Wound dehiscence Study population RR 0.55 209 ⊕⊕