Tissue adhesives for closure of surgical incisions

  • Review
  • Intervention

Authors


Abstract

Background

Sutures, staples and adhesive tapes are the traditional methods of wound closure, whilst tissue adhesives have entered clinical practice more recently. Closure of wounds with sutures enables meticulous closure, but they may show tissue reactivity and can require removal. Tissue adhesives offer the advantages of no risk of needlestick injury and no requirement to remove sutures later. Tissue adhesives have been used primarily in emergency rooms but this review looks at the use of tissue adhesives in the operating room where surgeons are increasingly using these for the closure of surgical skin incisions.

Objectives

To determine the relative effects of various tissue adhesives and conventional skin closure techniques on the healing of surgical wounds.

Search methods

For this update we searched the Cochrane Wounds Group Specialised Register (Searched 17/11/09); The Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library Issue 4 2009; Ovid MEDLINE  - 1950 to November Week 1 2009; Ovid EMBASE - 1980 to 2009 Week 46; EBSCO CINAHL - 1982 to 17 November 20098. No date or language restrictions were applied.

Selection criteria

Only randomised controlled clinical trials were eligible for inclusion.

Data collection and analysis

Screening of eligible studies and data extraction were conducted independently and in triplicate whilst assessment of the methodological quality of the trials was conducted independently and in duplicate. Results were expressed as random effects models using mean difference for continuous outcomes and relative risks with 95% confidence intervals for dichotomous outcomes. Heterogeneity was investigated including both clinical and methodological factors.

Main results

This update identified an additional six trials resulting in a total of fourteen RCTs (1152 patients) which met the inclusion criteria. Sutures were significantly better than tissue adhesives for minimising dehiscence (10 trials). Sutures were also found to be significantly faster to use. For all other analyses of infection, patient and operator satisfaction and cost there was no significant difference between sutures and tissue adhesives. No differences were found between tissue adhesives and tapes (2 trials) for minimising dehiscence, infection, patients assessment of cosmetic appearance, patient satisfaction or surgeon satisfaction. However a statistically significant difference in favour of using tape was found for surgeons' assessment of cosmetic appearance (mean difference 13, 95% CI 5 to 21). Tapes were also demonstrated to be significantly faster to use than tissue adhesives as were staples (1 trial). No other outcome measures were analysed in this group. 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. In this same trial tissue adhesives were significantly less time consuming to use. For the remaining outcomes of dehiscence and infection no difference was observed between groups. This trial also compared high viscosity with low viscosity adhesives and found that high viscosity adhesives were less time consuming to use than low viscosity tissue adhesives. For all other outcomes of dehiscence, infection, patient satisfaction and operator satisfaction there was no statistically significant difference between high and low viscosity adhesives.

Authors' conclusions

Sutures were significantly better than tissue adhesives for minimising dehiscence and were found to be significantly faster to use. Although surgeons may consider the use of tissue adhesives as an alternative to other methods of surgical site closure in the operating theatre they must be aware that adhesives may take more time to apply and that if higher tension is needed upon an incision, sutures may minimise dehiscence. There is a need for more well designed randomised controlled trials comparing tissue adhesives and alternative methods of closure. These trials should include people whose health may interfere with wound healing and surgical sites of high tension.

Résumé

Colles tissulaires pour la fermeture des incisions chirurgicales

Contexte

Les sutures, les agrafes et les rubans adhésifs sont les méthodes traditionnelles pour la fermeture de plaies, alors que les colles tissulaires sont apparues plus récemment dans la pratique clinique. Les points de suture permettent une fermeture méticuleuse de la plaie, mais ils peuvent donner lieu à une réaction des tissus et devoir être enlevés. Les colles tissulaires offrent le double avantage de ne pas comporter de risque de blessure par piqûre d'aiguille et de ne pas nécessiter le retrait ultérieur de points de suture. Les colles tissulaires ont été utilisées principalement en salle d'urgence, mais cette revue se penche sur l'utilisation des colles tissulaires en salle d'opération où elles sont de plus en plus employées par les chirurgiens pour la fermeture des incisions chirurgicales cutanées.

Objectifs

Déterminer les effets relatifs de différentes colles tissulaires et techniques conventionnelles de fermeture de la peau sur la cicatrisation des plaies chirurgicales.

Stratégie de recherche documentaire

Pour cette mise à jour nous avons effectué des recherches dans le registre spécialisé du groupe Cochrane sur les plaies et les contusions (le 17/11/09), le registre Cochrane des essais contrôlés (CENTRAL) (The Cochrane Library, numéro 4, 2009), Ovid MEDLINE (de 1950 à la 1ère semaine de novembre 2009), Ovid EMBASE (de 1980 à la 46ème semaine de 2009) et EBSCO CINAHL (de 1982 au 17 novembre 2009).

Critères de sélection

Seuls les essais cliniques contrôlés randomisés étaient éligibles à l'inclusion.

Recueil et analyse des données

Le tri des études éligibles et l'extraction des données ont été réalisées en triple de manière indépendante, tandis que l'évaluation de la qualité méthodologique des essais a été conduite en double de manière indépendante. Les résultats étaient exprimés sous forme de modèles à effets aléatoires au moyen de la différence moyenne pour les résultats continus et du risque relatif avec intervalle de confiance à 95 % pour les résultats dichotomiques. L'hétérogénéité a fait l'objet d'études, notamment les facteurs cliniques et méthodologiques.

Résultats Principaux

Cette mise à jour a identifié six essais supplémentaires, résultant en un total de quatorze ECR (1152 patients) qui répondaient aux critères d'inclusion. Afin de minimiser la déhiscence les sutures étaient significativement supérieures aux colles tissulaires (10 essais ). Les sutures s'étaient également révélées être d'utilisation beaucoup plus rapide. Pour toutes les autres analyses de l'infection, de la satisfaction du patient et de l'opérateur et du coût, il n'y avait pas de différence significative entre les sutures et les colles tissulaires. Aucune différence n'avait été constatée entre les colles tissulaires et les rubans adhésifs (2 essais) pour la minimisation de la déhiscence, l'infection, l'évaluation de l'aspect esthétique par les patients, la satisfaction du patient ou la satisfaction du chirurgien. Une différence statistiquement significative en faveur des rubans adhésifs a toutefois été constatée pour ce qui concerne l'évaluation de l'aspect esthétique par les chirurgiens (différence moyenne 13, IC 95% 5 à 21). Les rubans, comme les agrafes, se sont également avérés être beaucoup plus rapides à utiliser que les colles tissulaires (1 essai). Aucune autre mesure de résultat n'avait été analysée dans ce groupe. Un essai avait comparé les colles tissulaires à une variété de méthodes de fermeture de plaie et avait trouvé que tant les patients que les cliniciens étaient significativement plus satisfaits avec les méthodes alternatives de fermeture qu'avec les colles. Dans ce même essai, l'emploi de colles tissulaires prenait significativement moins de temps. Pour les autres critères de déhiscence et d'infection aucune différence entre les groupes n'avait été observée. Cet essai avait également comparé des colles à viscosité élevée et à faible viscosité et avait constaté que l'utilisation de colles à viscosité élevée prenait moins de temps que celle des colles tissulaires à faible viscosité. Pour tous les autres critères de déhiscence, d'infection, de satisfaction du patient et de satisfaction de l'opérateur, il n'y avait pas de différence significative entre les colles à viscosité élevée ou faible.

Conclusions des auteurs

Les sutures avaient été significativement supérieures aux colles tissulaires pour minimiser la déhiscence et s'étaient avérées être beaucoup plus rapides à utiliser. Même si les chirurgiens peuvent considérer les colles tissulaires comme une alternative à d'autres méthodes de fermeture du site chirurgical en salle d'opération, ils doivent être conscients que l'application de colles tissulaires peut prendre plus de temps et que si une plus forte tension est nécessaire sur l'incision, les sutures sont susceptibles de réduire la déhiscence. Il y a un besoin d'essais contrôlés randomisés supplémentaires et bien conçus, comparant les colles tissulaires à d'autres méthodes de fermeture. Ces essais devraient inclure des personnes dont l'état de santé est susceptible d'interférer avec la cicatrisation de la plaie, ainsi que des sites chirurgicaux à forte tension.

Plain language summary

Tissue adhesives for closure of surgical skin incisions

Tissue adhesives or glues are increasingly used in place of sutures (stitches) or staples to close wounds and it has been suggested that they may be quicker and easier to use than sutures for closing surgical wounds. Adhesives carry no risk of sharps injury and are thought to provide a barrier to infection that also promotes healing as well as do away with the need for suture removal.

Fourteen studies were included and for most outcomes assessed there was no difference between tissue adhesives and the alternatives. However fewer wounds broke down when stitches were used and tissue adhesives were more time consuming to use than other methods. Some surgeons and patients preferred the alternatives to tissue adhesives.

Résumé simplifié

Colles tissulaires pour la fermeture des incisions chirurgicales

Colles tissulaires pour la fermeture des incisions chirurgicales

Les colles tissulaires sont de plus en plus utilisées à la place des points de suture ou des agrafes pour fermer les plaies, et il a été suggéré qu'elles pourraient être plus rapides et plus aisées à utiliser que les sutures pour fermer les plaies chirurgicales. Les colles ne comportent aucun risque de blessure aigue et sont considérées former une barrière contre les infections, qui favorise aussi la cicatrisation et élimine la procédure de retrait des sutures.

Quatorze études ont été incluses et pour la plupart des critères de résultat évalués il n'y avait aucune différence entre les colles tissulaires et les autres méthodes. Toutefois, moins de plaies s'étaient ouvertes lors de l'emploi de points de suture et l'utilisation de colles tissulaires prenait plus de temps que celle d'autres méthodes. Certains chirurgiens et patients préféraient les méthodes alternatives aux colles tissulaires.

Notes de traduction

Traduit par: French Cochrane Centre 15th April, 2013
Traduction financée par: Pour la France : Minist�re de la Sant�. Pour le Canada : Instituts de recherche en sant� du Canada, minist�re de la Sant� du Qu�bec, Fonds de recherche de Qu�bec-Sant� et Institut national d'excellence en sant� et en services sociaux.

Background

In the past the options for wound closure have been limited largely to sutures (needle and thread) with other alternatives such as staples, adhesive tapes and tissue adhesives entering clinical practice more recently. Closure of wounds with sutures enables meticulous closure, but sutures may induce reactivity and they usually require removal. Tissue adhesives (glues) offer the advantages that the patient does not require suture removal at a later date and there is no risk of needlestick injury to the surgeon or assistant. The introduction of tissue adhesives has been received enthusiastically since they may result in equivalent tensile strength, improved cosmetic appearance of the scar and lower infection rate when compared with sutures, staples and adhesive tapes, and they are without many of the risks and disadvantages of alternative methods (Osmond 1999).

Tissue adhesives have been used in various forms for more than 35 years since the first cyanoacrylate adhesives were synthesised in 1949 (Coover 1959). The early adhesives were appropriate for small superficial lacerations and incisions but their limited physical properties prevented their 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-butylcyanoacrlyates that were purer and stronger. However, these adhesives did not receive widespread acceptance because their clinical performance 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 flexibility and reduce toxicity when applied topically for skin closure (Quinn 1997).

Tissue adhesives have been used primarily in emergency rooms and there is increasing support in the literature for their effectiveness in the closure of various traumatic lacerations (Farion 2001; Osmond 1999; Perron 2000; Quinn 1997). Surgeons have begun to use tissue adhesives in the operating room for the closure of surgical skin incisions although there are fewer clinical trials to support this indication. This review looks at the use of tissue adhesives 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.

Methods

Criteria for considering studies for this review

Types of studies

Randomised controlled trials.

Types of participants

All patients of any age and in any setting requiring closure of a surgical skin incision of any length.

Types of interventions

Surgical skin incision closure with tissue adhesive compared with another tissue adhesive or any alternative conventional closure device such as sutures, staples or adhesive tapes.

Types of outcome measures

Primary outcomes
  • Proportion of wounds breaking down (wound dehiscence).

Secondary outcomes
  • Proportion of wounds becoming infected where the investigator has used a valid method of ascertaining infection.

  • Cosmetic appearance at or after three months where the investigator has used a validated measure.

  • Patient (or in the case of studies performed with participants under the age of 16 years, parents') general satisfaction with skin incision closure technique (this is more than cosmetic appearance as other factors such as suture removal experience may have an input).

  • Surgeon satisfaction with skin incision closure technique (this may take into account the time for surgeon to close skin incision amongst other factors).

  • Relative cost of materials required for skin incision closure techniques being compared (this will be reported in a narrative form).

  • Time to closure as an outcome measure has been added to the review post hoc. The review authors believe this to be a contributory factor towards both cost-effectiveness and satisfaction.

Search methods for identification of studies

Electronic searches

For an outline of the search methods used in the original version of this review see Appendix 1.

For this first update we searched the following electronic databases:

  • Cochrane Wounds Group Specialised Register (Searched 17/11/09)

  • The Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library Issue 4 2009

  • Ovid MEDLINE  - 1950 to November Week 1 2009

  • Ovid EMBASE - 1980 to 2009 Week 46

  • EBSCO CINAHL - 1982 to 17 November 2009

The following strategy was used to search 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)

There was no restriction by language or date of publication.

The search strategies for Ovid MEDLINE, Ovid EMBASE and Ovid CINAHL can be found in Appendix 2, Appendix 3 and Appendix 4 respectively. The Ovid MEDLINE search was combined with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity- and precision-maximizing version (2008 revision); Ovid format (Lefebvre 2008). The EMBASE and CINAHL searches were combined with the trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN) (SIGN 2009).

Searching other resources

The bibliographies of new studies included in this updated review were checked for potentially eligible references not identified in the electronic searches outlined above.

Data collection and analysis

Selection of studies

Four review authors (JD, PC, OvW, ME) independently examined the titles and abstracts of all the articles identified by the search to identify potentially relevant trials. The full text of these articles were then independently assessed (JD, PC, OvW, ME) using a standardised form to check for eligibility in the review. Disagreements about inclusion were resolved by consensus or a fifth review author (HW) where necessary. All studies meeting the inclusion criteria underwent validity assessment and data extraction. Studies rejected at this stage were recorded in a table of excluded studies and reasons for exclusion recorded.

Data extraction and management

Data were extracted by three review authors independently (three of: JD, PC, OvW, HW) using specially designed data extraction forms. The data extraction forms were piloted on several papers and modified as required before use. Any disagreements were resolved by discussion and a fourth review author consulted where necessary. All study authors were contacted for clarification or missing information requested where necessary. Data were excluded if further clarification could not be obtained.

For each trial the following data were recorded;

  1. Year of publication, country of origin and source of study funding.

  2. Details of the participants including demographic characteristics and criteria for inclusion.

  3. Details of the type of intervention (adhesive, suture, staples or adhesive tape) and type of adhesive (butylcyanoacrylate or octylcyanoacrylate).

  4. Details of the outcomes reported, including method of assessment and time intervals. Cosmetic appearance was included if the authors stated that is was measured on a validated scale.

Assessment of risk of bias in included studies

The quality assessment of the included trials was undertaken independently and in duplicate by two of the four review authors (JD, PC, OvW, ME) as part of the data extraction process. Three main quality criteria were examined; methods of randomisation and allocation concealment (recorded as adequate, unclear, inadequate and not used); blind outcome assessment (recorded as yes, no, unclear and not possible); and completeness of follow-up (recorded as whether or not there was a clear explanation for withdrawals and drop-outs in each treatment group). The quality assessment criteria were pilot tested using several articles and the agreement between the assessors for the quality assessments was measured using the kappa statistic. We also noted whether or not a priori calculation had been undertaken for sample size. Further quality assessment was carried out to assess the comparability of control and treatment groups at entry. The quality assessment criteria are presented in a table of quality assessment. Consideration was given to all the quality items and studies were categorised according to low, medium or high risk of bias according to the Cochrane Handbook 5 after the receipt of any clarification from the authors (see additional table on quality assessment: Table 1).

Table 1. Quality assessment of trials
  1. A = Adequate; B = Unclear; C = Inadequate.

StudyConcealed allocationOutcome
blinded
Explanation drop outRisk of biasWithdrawals %
Sniezek 2007AYesYesModerate (No evidence of appropriateness of sample size)0
Ong 2002AYesNoHigh85
Dowson 2006ANoYesModerate8
Ridgway 2007APrimary outcome no, secondary outcome yesYesModerate3
Switzer 2003BYesNoModerateUnclear
Blondeel 2004AYesYesLow5
Cheng 1997BUnclearYesModerate0
Greene 1999CYesYesModerate0
Keng 1989CUnclearNoHighunclear
Maartense 2002BYesNoHighunclear
Ozturan 2001CYesNoHighunclear
Shamiyeh 2001AYesYesLow4
Sinha 2001BYesYesLow0
Toriumi 1998BYesYesLow0
  1. Low: low risk of bias (plausible bias unlikely to seriously alter the results) if all criteria were met.

  2. Moderate: moderate risk of bias (plausible bias that raises some doubts about the results) if one or more criteria are partly met (for example when authors respond that they had made some attempts to conceal the allocation of patients, or to give an explanation of withdrawals but these attempts were not judged to be ideal, these criteria will be categorised as "partly").

  3. High: high risk of bias (plausible bias that seriously weakens confidence in the results) if one or fewer criteria are met.

Assessment of heterogeneity

The significance of any discrepancies in the estimates of the treatment effects from the different trials was assessed by means of Cochran's test for heterogeneity.

Data synthesis

For dichotomous outcomes, the estimates of effect of an intervention were expressed as relative risks (RR) together with 95% confidence intervals (CI). For continuous outcomes, mean differences and standard deviations were used to summarise the data for each group. Where there were studies of similar comparisons reporting the same outcome measures a meta-analysis was attempted. Relative risks were combined for dichotomous data, and weighted mean differences (WMD) for continuous data, using a random effects model (indicated as RE in the results section) as some heterogeneity between studies is anticipated. We planned to analyse time to wound healing/closure as survival (time to event) data, using the appropriate analytical method (as per the Cochrane Reviewers' Handbook version 5), or as a continuous outcome if data from all participants were available.

It was intended to meta analyse the results of trials with a split wound, and split body design using the inverse variance method for paired data however these studies did not include any events and were therefore not included in any meta analysis.

Subgroup analysis and investigation of heterogeneity

It was intended that a subgroup analysis would be undertaken with regard to age (less than 18 years and 18 years or older), location of incision on body (face and body), length of incision (less than 4 cm and 4 cm or greater), and patient characteristics such as diabetes and source of funding (commercially or independently funded), however there were insufficient studies reporting this data to undertake this.

Sensitivity analysis

It was intended that a sensitivity analysis would be undertaken to examine the effect of randomisation, allocation concealment and blind outcome assessment on the overall estimates of effect. In addition, a sensitivity analysis to examine the effect of including unpublished literature on the review's findings was examined. In the event these analyses were not undertaken.

Results

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

See Characteristics of included studies; Characteristics of excluded studies.

Characteristics of the trial setting and investigators

Of the 22 potentially eligible studies (Alhopuro 1976; Blondeel 2004; Cheng 1997; Dowson 2006; Gorozpe-Calvillo 99; Greene 1999; Jaibaji 2000; Keng 1989; Kuo 2006; Maartense 2002; Ong 2002; Orozco-Razon 2002; Ozturan 2001; Ridgway 2007; Shamiyeh 2001; Silvestri 2006; Singer 2002; Sinha 2001; Sniezek 2007; Steiner 2000; Switzer 2003; Toriumi 1998), eight were excluded (Alhopuro 1976; Gorozpe-Calvillo 99; Jaibaji 2000; Kuo 2006; Orozco-Razon 2002; Singer 2002; Silvestri 2006; Steiner 2000). One study (Alhopuro 1976) was excluded because there were no data presented and none was received following a written request to the authors. Another study (Singer 2002) was excluded as the data for incision closure could not be used because it was combined with data for laceration closure. We wrote to the authors to request separate data by group but received no reply. The third study (Gorozpe-Calvillo 99) was excluded because after full translation it was found not to be a randomised trial. Two papers were excluded because their methodology was flawed. The first of these (Jaibaji 2000) was excluded because the intervention group had a subcuticular suture in place which was thought to bias the outcome in favour of the intervention. The second (Kuo 2006) was excluded because all patients had a subcuticular suture placed and the review authors thought this adjunct method of closure would invalidate an independent assessment of the primary interventions. Three further studies were excluded as two were not randomised (Silvestri 2006; Steiner 2000) and the third (Orozco-Razon 2002) did not appear to be randomised and though clarification was sought from the trial authors no reply was received.

The fourteen included studies were conducted in Austria (Shamiyeh 2001), Hong Kong (Cheng 1997), The Netherlands (Maartense 2002), Turkey (Ozturan 2001), China (Ong 2002) UK (Dowson 2006; Keng 1989; Ridgway 2007; Sinha 2001), USA (Greene 1999; Sniezek 2007; Switzer 2003; Toriumi 1998), and one was multicentre and international (Blondeel 2004). Four of the included eligible studies had industrial sponsorship (Blondeel 2004; Dowson 2006; Sniezek 2007; Toriumi 1998), four were independent (Greene 1999; Ozturan 2001; Shamiyeh 2001; Sinha 2001) and in 6, funding was unclear (Cheng 1997; Keng 1989; Maartense 2002; Ong 2002; Ridgway 2007; Switzer 2003). All studies included adults except for three (Cheng 1997; Ong 2002; Toriumi 1998) that included children. All were of parallel group design except two, one of which was a split body design (Greene 1999) and one was a split wound design (Sniezek 2007). All studies excluded patients who had poor general health with the potential to impair wound healing and surgical procedures on high tension sites such as the elbow and knee. In total 1152 patients were included in the trials.

Characteristics of interventions

Eleven of the fourteen included studies compared tissue adhesive with suture for incision closure (Cheng 1997; Dowson 2006; Greene 1999; Keng 1989; Ong 2002; Ozturan 2001; Shamiyeh 2001; Sinha 2001; Sniezek 2007, Switzer 2003; Toriumi 1998). Two trials (Maartense 2002; Shamiyeh 2001) compared tissue adhesive with adhesive tape. One of these studies also compared tissue adhesive with suture. One trial ( Ridgway 2007) compared adhesives with staples. One trial (Blondeel 2004) compared tissue adhesives with any other skin closure technique and this same trial also compared one tissue adhesive with another tissue adhesive.

Adhesive compared with suture
Butylcyanoacrylate

Five studies investigated the use of butylcyanoacrylate. One study compared the use of butylcyanoacrylate (Histoacryl) with 4.0 catgut suture in patients under twelve years of age requiring elective circumcision (Cheng 1997). A second study investigated butylcyanoacrylate (Histoacryl) in patients requiring groin incisions for inguinal hernia, femoral hernia, sapheno ligations, testicular operations or lymph node biopsies (Keng 1989). Skin incisions were closed with either butylcyanoacrylate tissue adhesive or dexon subcuticular sutures. Three of the 43 patients had bilateral operations when the left side was closed with adhesive (butylcyanoacrylate) and the right with sutures.

A further study (Sinha 2001) compared n-butyl-2-cyanoacrylate adhesive (Indermil) with 4.0 monofilament suture in adult patients requiring hand or wrist surgery (carpal tunnel syndrome, trigger finger, De Quervain's tenosynovitis, ganglions of the wrist and hand and cysts of the fingers). Skin incisions were approximated with skin hooks and all cases has local anaesthetic infiltration with or without general anaesthesia. A fourth study (Ozturan 2001) compared butylcyanoacrylate (Liquiband) tissue adhesive with 6.0 polypropylene sutures for columellar skin closure after the majority of the tension had been taken up using 5.0 chromic catgut. A fifth study (Dowson 2006) also compared butylcyanoacrylate (Liquiband) with interruptible, non-absorbable suture after laparoscopic procedures.

Octylcyanoacrylate

Seven studies investigated the use of octylcyanoacrylate tissue adhesive. One study investigated incisions with and without subcutaneous sutures and then randomised for closure with octyl-2-cyanoacrylate or 5.0 or 6.0 nylon suture in patients one year of age and over requiring elective surgery for benign skin lesions predominantly in face and neck (Toriumi 1998). Another study investigated patients requiring bilateral blepharoplasty for functional or aesthetic indications (Greene 1999). This model with two identical skin sites on the same patient allowed a split-body study design and each patient to act as his or her own control. The left or right upper eye lid was closed with octyl-2-cyanoacrylate (Dermabond®, Ethicon Inc, a Johnson & Johnson company, Somerville, New Jersey, USA) and the other eyelid closed with 6.0 suture (10 fast-absorbing gut or 10 polypropylene, Prolene, Ethicon Inc). Blepharoplasties were closed on the tissue adhesive side by using Castroviejo forceps to approximate the skin edges in 15 patients and by using 3 to 4 sutures as handles to facilitate apposition and eversion of edges in 5 patients. 20 patients undergoing blepharoplasty (40 eyelids were treated). A third study compared octylcyanoacrylate tissue adhesive with 5.0 monofilament suture or with tape in adult patients requiring miniphlebectomy with the Muller technique (Shamiyeh 2001). Wounds were created that were of 5 mm average wound length. After phlebectomy and 5 minutes compression of the leg, incisions were closed with the tissue adhesive or suture or tape. Tape was placed crosswise. A small plaster was placed over each wound. The study was undertaken at the Ludwig Boltzmann Institute for Surgical Laparoscopy, Linz, Austria. This study also compared tissue adhesive with adhesive tape. The fourth study compared octylcyanoacrylate (Dermabond) tissue adhesive with intracutaneous poliglecaprone interrupted sutures in adult patients requiring elective laparoscopic procedures (Maartense 2002). This study also compared tissue adhesive with tape

The fifth study in this group (Switzer 2003) compared octylcyanoacrylate (Dermabond) with a subcuticular monocryl suture for the elective repair of inguinal hernias. Another study (Ong 2002) also compared octylcyanoacrylate with a monocryl subcuticular suture for patient requiring herniotomies. These patients were children. The final study included in this group (Sniezek 2007) followed a split wound design comparing octylcyanoacrylate with a cuticular polypropylene suture on head and neck surgical sites following the removal of carcinomas using the Mohs technique.

Adhesive compared with adhesive tape
Octylcyanoacrylate

Two studies compared octylcyanoacrylate with adhesive tapes. One study compared octylcyanoacrylate tissue adhesive with 5.0 monofilament suture or with tape in adult patients requiring miniphlebectomy with the Muller technique (Shamiyeh 2001). Wounds were created that were of 5mm average wound length. After phlebectomy and 5 minutes compression of the leg, incisions were closed with the tissue adhesive or suture or tape. Tape was placed cross-wise. A small plaster was placed over each wound. The second study investigated tissue adhesive compared with adhesive paper tape and compared with intracutaneous sutures in adult patients requiring elective laparoscopic surgery (Maartense 2002). Octylcyanoacrylate (Dermabond) tissue adhesive was compared with 76mm X 6mm adhesive paper (SteriStrip).

Adhesive compared with staples
Octylcyanoacrylate

Only one study (Ridgway 2007) compared adhesive (octylcyanoacrylate, Dermabond) and staples (Vivistat) and undertook this comparison in patients requiring thyroid and parathyroid surgery.

Adhesive compared with other techniques
Octylcyanoacrylate

One study (Blondeel 2004) investigated the use of tissue adhesives in incisions of 4 cm or greater in length. High viscosity 2-octylcyanoacrylate (High Viscosity Dermabond) tissue adhesive was compared with any other commercially available device such as sutures, staples or tapes and also compared with low viscosity 2-octylcyanoacrylate. The high viscosity formulation is six-times more viscous than the normal adhesive and designed to reduce run-off of pre polymerised adhesive from the application site.

Adhesive (high viscosity) compared with adhesive (low viscosity)

Blondeel 2004 also compared high and low viscosity adhesive in the trial described above.

Characteristics of outcome measures

Wound dehiscence

Eleven studies reported dehiscence. The time of wound examination for dehiscence varies between studies. Cheng 1997 reported dehiscence at day 1, 2, 3, 7 and 30. Toriumi 1998 reported dehiscence at 5 to 7 days, Ozturan 2001 at 7 days, Shamiyeh 2001 at 10 days, Greene 1999 at week 1, 2 and 4 and Sinha 2001 at 10 days, 2 weeks and 6 weeks. Sniezek 2007 assessed dehiscence at 7 days, Ong 2002 at 2 to 3 weeks, Dowson 2006 at day 1, 2 and at 4 to 6 weeks, Switzer 2003 at 2 and 4 weeks and Blondeel 2004 at day 10.

Wound infection

One study (Cheng 1997) noted infection at day 1, 2, 3, 7 and 30. Infection was defined as wound discharge with positive bacterial culture. A second study defined infection as the presence of pus (Keng 1989) and examined wounds at 1 and 4 weeks post operatively. A third study defined infection as an abscess that required drainage (Ozturan 2001) and examined wounds at 1 week. A fourth study defined infection as a spontaneous drainage of purulent fluid (Maartense 2002) and noted this at two weeks and 3 months. Blondeel 2004 defined infection as redness >3 to 5 mm from the wound margin, swelling, purulent discharge, pain, increased skin temperature, fever or other signs of infection and assessed this at day 10. One study (Switzer 2003) described an infection as a draining sinus. One study (Dowson 2006) simply refers to wound complications. A further 6 studies reported upon infection but did not describe how infection would be defined for diagnosis and reporting in the study (Greene 1999; Ong 2002; Shamiyeh 2001; Sinha 2001; Sniezek 2007; Toriumi 1998).

Cosmetic appearance

Thirteen studies reported cosmetic appearance as an outcome. In one study (Maartense 2002) patients were asked to score their own cosmetic result using a validated visual analogue scale. Patients were also asked to complete the cosmetic scale of the Body Image Questionnaire (BIQ) (Dunker 1998). Surgical residents who were blind to the wound closure method also scored the cosmetic appearance with a visual analogue scale and the Hollander Wound Evaluation Score (Hollander 1995). These assessments were undertaken at 2 weeks and 3 months. A second study (Ozturan 2001) reported cosmetic appearance at 3 months by blinded assessment of photographs using VAS with best possible scar as 100 and worst possible scar as 0 (Quinn 1995) and the Hollander Scale. A third study (Toriumi 1998) assessed at 3 months and one year using a modified Hollander scale at 3 months and a VAS of photographs at one year using 2 surgeons blind to the group. However we could not use the data from this study at three months as the standard deviation was not reported and one patient dropped out from an unspecified group. Data at one year could not be used as it was unclear from which group the 11 patients had dropped out.

Ong 2002 evaluated cosmesis using a VAS and the Hollander Scale at 3 weeks and 3 months but the first data could not be used as it was too early and the data at 3 months could not be used due to large and unspecified loss to follow-up. Dowson 2006 assessed cosmetic outcome using the Hollander scale at 6 weeks and 3 months. The 6 week data was not included as it was too early and the 3 month data did not report mean and standard deviation statistics, the authors were contacted but did not respond therefore the data could not be included. Sniezek 2007 also assessed cosmesis at 3 months using a visual analogue scale but there was insufficient data for inclusion. The authors were contacted for the mean difference and the standard deviation of the mean difference between cosmetic scores but no reply was received.

Cosmetic appearance was evaluated at a time point of less than 3 months following surgery for several studies (Blondeel 2004; Cheng 1997; Greene 1999; Keng 1989; Ong 2002; Ridgway 2007; Sinha 2001; Switzer 2003)

Patient/parent satisfaction

Patient satisfaction interviews in one study (Greene 1999) included questions about comfort, presence of a pulling sensation and appreciation of lack of suture removal at week 1, 2 and 4. Wound comfort at 1 and 4 weeks was assessed in another study (Keng 1989). A third study assessed patients at one year using a scale of satisfaction with scar (Shamiyeh 2001). One study (Blondeel 2004) assessed patient satisfaction by using a questionnaire including ratings for cosmetic appearance, overall comfort, ability to shower, dressing changes, tension at the wound, hygienic problems or allergic reaction and overall satisfaction. One paper (Sniezek 2007) reported upon patient satisfaction as an outcome measure in the text but no results were reported in the analyses. The authors were contacted but no reply was received. One study (Dowson 2006) reported patient satisfaction as a simple satisfied or not satisfied though gave little information on the criteria used.

Surgeon satisfaction

Surgeon satisfaction in one study (Greene 1999) included quality of wound closure by assessment of eversion, regularity, approximation and any difficulties in attaining approximation. This was reported at week 1, 2 and 4. Another study (Shamiyeh 2001) reported surgeon satisfaction at 10 days using a scale of satisfaction with the scar on a five point score (1=perfect cosmetic result to 5=unsatisfactory result). A third study (Maartense 2002) reported surgeon satisfaction immediately after closure, when the surgeon was asked to give his or her opinion on the time needed for wound closure and the practicality of the materials used by answering multiple choice questions (far too long, a little too long, not too long and not practical, not very practical and very practical). Due to differences in the outcome measured these studies were not included in the meta analysis. One study (Blondeel 2004) did report surgeon satisfaction. A surgeon satisfaction questionnaire included ratings for wound cosmetic appearance, safety, effectiveness, applicability for a wide range of incisions, perceived patient satisfaction and overall satisfaction.

Relative cost of materials

Costs of closure devices were reported in two studies (Maartense 2002, Shamiyeh 2001).

Time for closure

Time for closure was reported in twelve studies (Blondeel 2004; Dowson 2006; Cheng 1997; Greene 1999; Keng 1989; Maartense 2002; Ong 2002; Ozturan 2001; Ridgway 2007; Shamiyeh 2001; Switzer 2003; Toriumi 1998). The data from seven of these studies (Cheng 1997; Dowson 2006; Greene 1999; Keng 1989; Maartense 2002; Switzer 2003; Toriumi 1998) were excluded as there was insufficient data and on writing to the authors no reply was received. Data from the remaining five studies were eligible for inclusion (Blondeel 2004; Ong 2002; Ozturan 2001; Ridgway 2007; Shamiyeh 2001). The time was recorded as a continuous variable in seconds or as 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 patients thereby avoiding concerns about time to event data being analysed incorrectly.

Risk of bias in included studies

The results of the quality assessment for included trials is shown in Table 1.

Randomisation and allocation concealment

The method of randomisation and allocation concealment was inadequate in three studies (Greene 1999; Keng 1989; Ozturan 2001). It was unclear in four studies despite writing to the authors for clarification (Cheng 1997; Sinha 2001; Switzer 2003; Toriumi 1998), and adequate in seven studies (Blondeel 2004; Dowson 2006; Maartense 2002; Ong 2002; Ridgway 2007; Shamiyeh 2001; Sniezek 2007).

Blinding

It is not possible to blind early outcome assessment in the case of the patient or investigator as the difference in appearance of tissue adhesive and suture is obvious. However, it is possible to blind later outcomes and the involvement of an independent outcome assessor would facilitate this. There was an attempt at blinding in eight studies ( Maartense 2002; Ong 2002; Ozturan 2001; Shamiyeh 2001; Sinha 2001; Sniezek 2007; Switzer 2003; Toriumi 1998). In one study (Greene 1999), photographs were assessed by observers blind to the treatment group to report cosmetic appearance at 4 weeks. Blinding was unclear in the other three studies (Cheng 1997; Dowson 2006; Keng 1989). In one study (Ridgway 2007) there was no blinding for the primary outcome but all secondary outcomes were blinded. In one study (Blondeel 2004) an independent observer, blind to the groups, carried out the 30 day assessment of cosmetic appearance but this data was not used as it was deemed too early to assess cosmesis.

Completeness of follow-up

There were no withdrawals in four studies (Greene 1999; Maartense 2002; Ozturan 2001; Sniezek 2007). Three studies (Blondeel 2004; Dowson 2006; Ridgway 2007) had withdrawals and these were accounted for. The number of withdrawals was unclear in five of the included studies (Cheng 1997; Keng 1989; Sinha 2001; Switzer 2003; Toriumi 1998) and remained so after writing to the authors. In one study (Shamiyeh 2001) the withdrawals were accounted for after writing to the authors. One study (Ong 2002) had explicit withdrawal data but gave no explanation of this.

Sample size

One study (Blondeel 2004) reported that they had undertaken a priori calculation for the sample size. Three studies (Dowson 2006; Ong 2002; Ridgway 2007) reported an a priori sample size calculation to assess the group size required but in all three studies it was based solely upon the time taken to closure.

Baseline comparability between treatment groups

Only 2 studies provided information about baseline comparability (Blondeel 2004; Shamiyeh 2001) and the latter provided information about age, gender and Body Mass Index. In this study (Shamiyeh 2001) the groups were well balanced for all factors except gender, with 15% men in one study group and 43% in another. Two studies (Greene 1999; Sniezek 2007) was performed as a split wound/body trial to improve baseline comparability. Two studies were matched for age and sex (Dowson 2006; Ong 2002).

Agreement of quality assessment

The percentage agreement and kappa scores between the two raters for the nine included studies was: 88% (kappa 0.80) for allocation concealment, 88% (kappa 0.60) for outcome assessor blinding, and 88% (kappa 0.60) for reporting of attrition. Percentage agreement was not calculated for the update of this review.

Effects of interventions

Adhesive compared with suture

Primary outcome

There were data from ten trials comparing the use of tissue adhesive with sutures for dehiscence, however as there were no cases of dehiscence in five trials, data from only five trials contributed data to the meta-analysis (Cheng 1997; Dowson 2006; Shamiyeh 2001; Sinha 2001; Switzer 2003). There was an overall significant difference detected between the proportion of wounds with dehiscence, RR 4.29 95%CI 1.45 to 12.73 (Analysis 1.1), favouring closure by suture with no evidence of heterogeneity (I2= 0). Three of these trials were regarded as having a medium risk of bias and two as having a low risk of bias.

Secondary outcomes
Infection

For infection, data from five out of ten trials were included in the meta-analysis (Cheng 1997; Maartense 2002; Ozturan 2001; Shamiyeh 2001; Switzer 2003). There was no statistically significant difference in the proportion of patients developing infection in any of the trials individually nor when data from the trials were pooled; RR 1.66, 95%CI 0.59 to 4.64 (Analysis 1.2). Again there was no evidence of heterogeneity (I2= 0).

Cosmetic appearance

There were no statistically significant differences detected for either the patients' (MD -2.12, 95%CI -7.20 to 2.95 Analysis 1.3), or surgeons' assessment of cosmetic appearance (MD 10.25, 95%CI -3.96 to 24.46 Analysis 1.4). Both papers presenting information upon cosmesis (Maartense 2002; Ozturan 2001) were rated as having a high risk of bias.

Patient / surgeon satisfaction

There were no statistically significant differences detected for the patient, surgeon or patient/parent satisfaction with treatment (Analysis 1.5; Analysis 1.6; Analysis 1.7) (Dowson 2006; Maartense 2002; Ong 2002; Shamiyeh 2001). In one further study (Greene 1999) 13/20 patients stated that they preferred the glue and seven the sutures.

Costs

Two studies reported costs. Shamiyeh 2001 reported that for closure of incisions of 5 mm mean length one tube of tissue adhesive at $11.00 can be used to close 3.5 incisions, 1 suture at $1.10 can be used to close 5 incisions, and one package of tape (six pieces) at $0.24 can be used to close 3 incisions. This assumes that there are multiple incisions on the same patient. A second study reported that for closure of laparoscopic trocar wounds: Euro 13.90 for one ampoule of octylcyanoacrylate, Euro 2.47 for one package of poliglecaprone suture (used together with a dressing at Euro 0.42 each) and Euro1.15 per package of adhesive paper tape (Maartense 2002).

Time to closure

Three studies reported the time taken for closure (Ong 2002; Ozturan 2001; Shamiyeh 2001). Pooling these trials was not appropriate due to massive heterogeneity (I2 = 100%) (Analysis 1.8). Two of the trials suggested that adhesive took longer to apply than sutures and in one of these trials the difference was statistically significant (Shamiyeh 2001). In the third trial, suturing took significantly more time than adhesive (Ozturan 2001). Two of these trials were at high risk of bias (Ong 2002; Ozturan 2001).

Adhesive compared with adhesive tape

Two trials (Maartense 2002; Shamiyeh 2001) provided data comparing tissue adhesive with adhesive tape, although most outcomes had data from only one trial. One of these trials (Shamiyeh 2001) was rated as a low risk of bias and the other (Maartense 2002) as a high risk of bias.

Primary outcome

There was no significant difference in the single trial (Shamiyeh 2001) comparing tissue adhesive with adhesive tape for dehiscence, with RR 0.96, 95%CI 0.06 to 14.55 (Analysis 2.1) however this comparison is underpowered as only one participant experienced the event in each group.

Secondary outcomes
Infection

Both trials reported wound infection but there was no significant difference between the groups in the proportion of patients with infection (RR 1.77 95%CI 0.45 to 6.99) (Analysis 2.2). Again this comparison is underpowered as there were only 9 infections in total.

Cosmetic appearance

Maartense 2002 found no statistically significant difference for patients' assessment of cosmetic appearance (Analysis 2.3), however there was a statistically significant difference for the surgeons' assessment using a visual analogue scale favouring closure by adhesive tape (MD 13, 95%CI: 5 to 21)(Analysis 2.4).

Patient / surgeon satisfaction

Shamiyeh 2001 found no difference between the groups for patient satisfaction (Analysis 2.5). Similarly both trials found there was no difference between the groups with respect to the satisfaction of the surgeons (Analysis 2.6).

Time to closure

Shamiyeh 2001 presented data for time to closure and demonstrated that tapes were significantly faster to use than adhesives (MD 0.56, 95% CI 0.42 to 0.70)(Analysis 2.7). (Review authors note: units not reported in trial, assumption that units are minutes).

Adhesive compared with staples

Primary outcome

Ridgway 2007 did not report data on dehiscence.

Secondary outcomes
Time to closure

Ridgway 2007 reported the time to closure and found a statistically significant difference favouring the use of staples for this outcome with MD 67.0 seconds, 95% CI 39.3 to 94.7 (Analysis 3.1). This study was designated at medium risk of bias.

Cosmetic appearance

This paper also presented data for cosmesis but this was not included as it was measured at an inappropriately early time.

Adhesive compared with other techniques

Blondeel 2004 compared high viscosity adhesive with any other commercially available devices such as sutures, staples, tapes or low viscosity adhesive. We requested further information from the authors, specifically data regarding high and low viscosity adhesives compared with the remaining commercially available devices and data for the comparison of high viscosity with low viscosity adhesives for the outcomes of our interest. This comparison of data is not reported within the published paper but the author made the data available to the review team. This paper was designated as at low risk of bias.

Primary outcome

Blondeel 2004 found no significant difference between the groups for dehiscence RR 0.55, 95% CI 0.13 to 2.38 (Analysis 4.1).

Secondary outcomes
Infection

Blondeel 2004 found no significant difference between the groups for infection RR 0.41, 95% CI 0.11 to 1.60 (Analysis 4.2).

Patient / surgeon satisfaction

There were statistically significant differences in favour of the group treated with other devices such as sutures, staples and tapes for both patient (MD 0.40, 95%CI 0.10 to 0.70 Analysis 4.3) and clinician (MD 0.53, 95%CI 0.29 to 0.77 Analysis 4.4).

Time to closure

Closure took significantly less time with high viscosity tissue adhesive (MD -1.05 mins, 95%CI -1.79 to -0.31 Analysis 4.5).

Adhesive (high viscosity) compared with adhesive (low viscosity)

The data for this comparison was provided by the authors as an additional analysis to that found in the paper.

Primary outcome

Blondeel 2004 found no significant difference between the intervention groups for dehiscence (RR 3.74, 95%CI 0.21 to 67.93)(Analysis 5.1). This paper was designated as at low risk of bias.

Secondary outcomes
Infection

No statistically significant differences were found this outcome (Analysis 5.2).

Patient / surgeon satisfaction

No statistically significant differences were found this outcome (Analysis 5.3; Analysis 5.4).

Time to closure

For the outcome time to closure, there was a significant difference favouring low viscosity adhesive (MD 0.54 mins, 95%CI 0.03 to 1.05)(Analysis 5.5).

To summarise:

  • For adhesive compared with sutures, there was an overall difference favouring sutures for dehiscence. Sutures were significantly faster to use than tissue adhesives.

  • For adhesives compared with tapes, there was a significant difference in time taken for closure and this favoured the control, tapes. Surgeons opinion of the cosmetic outcome was better in the tape group.

  • For adhesives compared with staples, there was a significant difference in time taken for closure and this favoured the staples.

  • For adhesives compared with other techniques, when assessing operator and patient satisfaction there was a statistical difference favouring the control group over adhesives. In this same analysis there was a statistical difference favouring the adhesive for time taken to closure.

  • For high viscosity compared with low viscosity, there was a statistical difference favouring the low viscosity adhesive for time taken for closure.

For all other analyses there was insufficient evidence either to support or refute the idea that using the tissue adhesive led to lower or higher levels of dehiscence, satisfaction with cosmetic appearance when assessed by patients or surgeons, patients' and surgeons' general satisfaction, or infection, when used in comparison with sutures, adhesive tape, staples or an adhesive with a lower viscosity.

There was evidence of heterogeneity between the studies. Four of the studies were commercially sponsored, four were independently sponsored and for the remaining 6 studies, funding was unclear.

Discussion

Traditional methods of surgical incision closure have been used for many years. However, these techniques are not without some problems and it is therefore important to consider new developments that may offer some advantages for the patient. The most common device for incision closure is the suture. Thirteen of the 14 studies included compared tissue adhesives with sutures. Two studies compared tissue adhesives with tapes which are traditionally used for smaller incisions. One study compared adhesives with staples and found that though offering good, speedy closure with low dehiscence rates staples can compromise post operative cosmesis. The most significant outcome of effectiveness of incision closure is dehiscence. Thirteen studies reported this outcome but a paucity of data reduced the inclusive studies to 8 for meta-analysis. There was a significant difference in dehiscence demonstrated between sutures and adhesives, favouring the sutures. No other intervention showed a statistical difference between intervention and adhesive. It should also be noted that one study (Blondeel 2004) compared adhesive to all other methods of skin closure and this included sutures. Nor was there any difference apparent between low viscosity and high viscosity adhesives in respect to dehiscence. However, the validity of these studies must also be taken into account including the poor quality of some studies and the poorly powered sample sizes of these studies. Dehiscence rates were used in no studies as a basis for sample size calculation. This data would indicate that although sutures maybe a better choice to minimise dehiscence over a tissue adhesive, tissue adhesives remain an option for surgical wound closure. Surgical procedures that were described by the studies were diverse and included blepharoplasty, circumcision, and excision of benign skin lesions yet exclusion criteria were applied. Incision in areas of high tension and in those patient's whose medical health may have reduced their ability to heal were excluded and so tissue adhesives have not been evaluated in this population.

Post operative site infection is a common problem and has a significant impact on patients and healthcare systems. More than 70% of surgical procedures are now performed on a outpatient basis, which poses major problems for surveillance of surgical site infections (Emori 1993). In one study of 2,345 patients undergoing surgery, the overall incidence of surgical site infection was 8.5% (Malone 2002). One may anticipate that a tissue adhesive offers a barrier to micro-organisms at the site of the healing incision and may therefore have some success towards reducing wound infection. However, the studies identified for this review did not demonstrate any significant difference in the proportion of wounds with infections when incisions were closed with tissue adhesives or other conventional techniques. No study reported an a priori calculation for the sample size and this may be relevant. Even the largest of the studies would have been unlikely to have been adequately powered to show any significant difference given the uncommon nature of wound infection. The diagnosis of infection maybe made on clinical examination or by positive bacterial culture. There may be variations between surgeons in making the diagnosis and it is not routine in clinical practice to undertake a confirmatory microbiological culture. For the outcome of surgical site infection in this review we required that the investigator used a valid method of ascertaining infection. Typically an infection was considered present if any of the following were observed: redness, swelling, purulent discharge, pain, increased skin temperature, fever or other systemic signs of infection. Whilst a confirmatory culture was not required one study (Cheng 1997) did undertake this. Six of the included studies did not reference how their diagnosis of infection was made.

Cosmetic outcome is an important long-term outcome of wound repair for the patient and we considered appearance at or after three months to be meaningful. Some studies reported cosmetic outcome earlier than three months (Blondeel 2004). Whilst is has been reported that an individual patient's cosmetic outcome at 3 months is predictive of cosmetic appearance at 1 year (Quinn 1998), the same investigation reported that early outcome, such as at 5 or 10 days, is poorly predictive of the 3 month appearance. This can present a problem for clinical trials though as drop-out bias may influence the results. Eight studies presented data for cosmesis at less than 3 months and this data was not included. One study (Ong 2002) had such large loss to follow-up that the data could not be used. The investigator was required to have used a validated measure, for example, the Modified Hollander Instrument (Hollander 1995). Using this scale, an incision is given a score of 0 or 1 for the respective presence or absence of each of the following: step-off borders, contour irregularities, wound margin separation, edge inversion, excessive inflammation, and poor overall appearance. The 6 category scores are summated to calculate an overall cosmesis score. Generally studies did use validated methods of assessment yet these were diverse and it would have been useful if a standard outcome measurement scale had been used. Three studies did use validated techniques but the data presented was insufficient to analyse and though the authors were contacted, none replied. Study bias may be reduced by blinding outcome assessors. Whilst the difference between incisions closed with either an adhesive or an alternative is obvious, blinding at time points required for observation of cosmetic outcome is possible. Only one study (Maartense 2002) showed significantly better cosmetic appearance as assessed by the surgeon blinded to the study group, for incisions closed with tissue adhesives when compared with adhesive tape.

Patient satisfaction is also important when comparing alternative incision closure devices providing that the primary efficacy variables of dehiscence, infection and cosmetic appearance are satisfactory. Patient satisfaction may include ratings for cosmesis, overall comfort, ability to shower, dressing changes, tension on wounds, hygiene problems, allergic reactions and overall satisfaction. A further important factor that might be expected to be in favour of tissue adhesives is the lack of requirement for removal. All these factors were used by the studies that assessed patient/parent satisfaction. In one small study (Greene 1999) there was a preference for the adhesive rather than sutures. In other studies (Dowson 2006; Ong 2002; Shamiyeh 2001) no difference was demonstrated. One study (Blondeel 2004) did demonstrate a significant preference in patients for the alternatives to tissue adhesives. This was the largest of the studies to assess patient satisfaction and also had a low risk of bias. It would be helpful to have available some validated questionnaires that could be used in studies.

Surgeon satisfaction typically sought ratings for wound cosmesis or ease of use for the technique. Certainly there is no risk of needle stick injury to the surgeon whilst using adhesive rather than sutures and this may be a factor though none of the studies in this review considered this. In one study (Blondeel 2004) physicians completed a questionnaire that measured satisfaction with the ease of use of a device, wound cosmesis, safety, effectiveness, applicability to a wide range of incisions, perceived patient satisfaction and overall satisfaction. This study showed that clinicians significantly preferred the alternative to tissue adhesive but when comparing high viscosity adhesives to other adhesives operators showed no difference in preference.

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. Many of the studies report that using tissue adhesive requires less time for skin closure than alternative techniques such as suturing. Howevere, four studies (Ong 2002; Ozturan 2001; Ridgway 2007; Shamiyeh 2001) demonstrated that tissue adhesives are more time consuming to use. One good quality study (Blondeel 2004), found that tissue adhesives were less time consuming than all comparable alternatives. Time taken is an attractive aspect for surgeons yet it should be noted that although there maybe a significant difference in time taken for closure the overall time taken was still relatively small in both groups with even the longest closure times rarely exceeding 2 minutes. In clinical practice the reduction of wound closure time by using the quickest method may be insufficient to increase the number of operations in a given operating room schedule. However a faster wound closure technique may increase surgeon satisfaction and may also be attractive to patients when surgery is undertaken using only local anaesthetic. Alternatively, patients may be happy with a lengthier closure time for a technique which achieves better outcomes.

Generally, tissue adhesives cost more than alternatives. An ampoule of tissue adhesive may be three times or more the cost of a suture required to close the same incision length. However, a dressing is not required over the tissue adhesive as is the usual with alternatives. Also, when taking into the account the overall cost of the surgical procedure then this small difference may be of less significance. It may be considered important to use a specific closure device even if the cost is greater than another if significant superiority is demonstrated for wound healing, including cosmetic outcome and patient satisfaction. Thus the length of time for closure and cost may be important only after other outcomes such as dehiscence, cosmesis and infection are clear.

In summary there is evidence to show that dehiscence rates may be higher in wounds closed with tissue adhesives when compared with sutures. There is also some evidence that the time taken to close the wound closure may be longer when using tissue adhesives than sutures, tapes or staples. Despite surgeons and patients being significantly more satisfied with the alternatives to adhesives in one analysis this is not supported in other analyses. There is insufficient evidence that using tissue adhesives leads to lower or higher levels of dehiscence, infection, satisfaction with cosmetic outcome, patient or surgeon general satisfaction in all other analyses. When comparing different adhesives, high viscosity adhesives were significantly more time consuming to use but for all other outcomes of dehiscence, infection and patient and surgeon satisfaction there was no evidence of any differences.

Authors' conclusions

Implications for practice

Adhesives have been compared with alternative methods of surgical wound closure in 14 studies including 931 patients with outcome data in total. There is no evidence of a difference in rates of wound infection after surgical incision closure with tissues adhesives, sutures, tapes staples or amongst different tissue adhesives. For all comparisons except sutures there was no difference in dehiscence rates between adhesive and the comparator. However in the comparison of adhesive with suture there was a significant difference favouring suture for minimising dehiscence. However no studies calculated the power of their sample size based upon dehiscence rates and therefore these figures may be under powered.

Although there maybe some evidence to demonstrate surgeons and patients may prefer the alternatives to tissue adhesives they may still consider the use of tissue adhesives for closing surgical incisions in the operating theatre. Although four analyses demonstrated the alternative to tissue adhesives being less time consuming, this is not a contraindication to their use and this conclusion was refuted by the results of one large good quality study. However, incisions in areas of high tension such as the elbow and knee were not considered by these trials and therefore as yet have not been evaluated in these situations. Similarly, patients whose general health may have had the potential to impair wound healing were excluded, similarly tissue adhesives have not been evaluated in these circumstances.

Implications for research

Further trials should be undertaken to investigate the effects of tissue adhesives in clinical situations commonly excluded in trials. For example wound closure in areas of high tension and in patients with general health that could potentially impair wound healing. Trials should be sufficiently powered to detect any differences in the rate of wound infection or dehiscence as statistically significant when comparing different incision closure devices. Development and validation of patient satisfaction and surgeon satisfaction questionnaires would be helpful.

Acknowledgements

We wish to thank Sally Bell-Syer and Ruth Foxlee (Cochrane Wounds Group) for their assistance with literature searching the preparation of this review. We would like to thank Sally Stapley of the Cochrane Wounds Group, for her help in the updating process. We would also like to thank the following referees: Nicky Cullum, David Margolis, Michelle Briggs, Seokyung Hahn, James V Quinn, Ken Farion and Jac Dinnes.

Data and analyses

Download statistical data

Comparison 1. adhesive versus suture
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 dehiscence10721Risk Ratio (M-H, Fixed, 95% CI)4.29 [1.45, 12.73]
2 infection12862Risk Ratio (M-H, Random, 95% CI)1.66 [0.59, 4.64]
3 cosmetic appearance by patient (VAS 0-100))2199Mean Difference (IV, Random, 95% CI)-2.12 [-7.20, 2.95]
4 cosmetic appearance by surgeon (VAS)2209Mean Difference (IV, Random, 95% CI)10.25 [-3.96, 24.46]
5 patient/parent satisfaction2206Risk Ratio (M-H, Random, 95% CI)1.01 [0.96, 1.07]
6 surgeon satisfaction2150Risk Ratio (M-H, Random, 95% CI)1.12 [0.58, 2.19]
7 patient/parent satisfaction159Mean Difference (IV, Fixed, 95% CI)-3.0 [-11.92, 5.92]
8 time taken for closure3 Mean Difference (IV, Fixed, 95% CI)Totals not selected
Analysis 1.1.

Comparison 1 adhesive versus suture, Outcome 1 dehiscence.

Analysis 1.2.

Comparison 1 adhesive versus suture, Outcome 2 infection.

Analysis 1.3.

Comparison 1 adhesive versus suture, Outcome 3 cosmetic appearance by patient (VAS 0-100)).

Analysis 1.4.

Comparison 1 adhesive versus suture, Outcome 4 cosmetic appearance by surgeon (VAS).

Analysis 1.5.

Comparison 1 adhesive versus suture, Outcome 5 patient/parent satisfaction.

Analysis 1.6.

Comparison 1 adhesive versus suture, Outcome 6 surgeon satisfaction.

Analysis 1.7.

Comparison 1 adhesive versus suture, Outcome 7 patient/parent satisfaction.

Analysis 1.8.

Comparison 1 adhesive versus suture, Outcome 8 time taken for closure.

Comparison 2. adhesive versus adhesive tape
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 dehiscence151Risk Ratio (M-H, Random, 95% CI)0.96 [0.06, 14.55]
2 infection2141Risk Ratio (M-H, Random, 95% CI)1.77 [0.45, 6.99]
3 cosmetic appearance by patient (VAS)190Mean Difference (IV, Random, 95% CI)-3.0 [-12.09, 6.09]
4 cosmetic appearance by surgeon (VAS)190Mean Difference (IV, Random, 95% CI)13.0 [5.15, 20.85]
5 patient satisfaction151Risk Ratio (M-H, Random, 95% CI)1.09 [0.93, 1.29]
6 surgeon satisfaction2141Risk Ratio (M-H, Random, 95% CI)0.87 [0.63, 1.19]
7 time taken for closure151Mean Difference (IV, Fixed, 95% CI)0.56 [0.42, 0.70]
Analysis 2.1.

Comparison 2 adhesive versus adhesive tape, Outcome 1 dehiscence.

Analysis 2.2.

Comparison 2 adhesive versus adhesive tape, Outcome 2 infection.

Analysis 2.3.

Comparison 2 adhesive versus adhesive tape, Outcome 3 cosmetic appearance by patient (VAS).

Analysis 2.4.

Comparison 2 adhesive versus adhesive tape, Outcome 4 cosmetic appearance by surgeon (VAS).

Analysis 2.5.

Comparison 2 adhesive versus adhesive tape, Outcome 5 patient satisfaction.

Analysis 2.6.

Comparison 2 adhesive versus adhesive tape, Outcome 6 surgeon satisfaction.

Analysis 2.7.

Comparison 2 adhesive versus adhesive tape, Outcome 7 time taken for closure.

Comparison 3. adhesive versus staples
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 time taken for closure129Mean Difference (IV, Fixed, 95% CI)67.0 [39.30, 94.70]
Analysis 3.1.

Comparison 3 adhesive versus staples, Outcome 1 time taken for closure.

Comparison 4. adhesive versus other method
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 dehiscence1209Risk Ratio (M-H, Random, 95% CI)0.55 [0.13, 2.38]
2 infection1209Risk Ratio (M-H, Random, 95% CI)0.41 [0.11, 1.60]
3 patient satisfaction1187Mean Difference (IV, Fixed, 95% CI)0.40 [0.10, 0.70]
4 clinician satisfaction1209Mean Difference (IV, Fixed, 95% CI)0.53 [0.29, 0.77]
5 time taken for closure1209Mean Difference (IV, Fixed, 95% CI)-1.05 [-1.79, -0.31]
Analysis 4.1.

Comparison 4 adhesive versus other method, Outcome 1 dehiscence.

Analysis 4.2.

Comparison 4 adhesive versus other method, Outcome 2 infection.

Analysis 4.3.

Comparison 4 adhesive versus other method, Outcome 3 patient satisfaction.

Analysis 4.4.

Comparison 4 adhesive versus other method, Outcome 4 clinician satisfaction.

Analysis 4.5.

Comparison 4 adhesive versus other method, Outcome 5 time taken for closure.

Comparison 5. adhesive (high viscosity) versus adhesive (low viscosity)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 dehiscence1148Risk Ratio (M-H, Random, 95% CI)3.74 [0.21, 67.93]
2 infection1148Risk Ratio (M-H, Random, 95% CI)0.82 [0.16, 4.31]
3 patient satisfaction1133Mean Difference (IV, Fixed, 95% CI)-0.05 [-0.28, 0.18]
4 clinician satisfaction1148Mean Difference (IV, Fixed, 95% CI)-0.02 [-0.23, 0.19]
5 time taken for closure1148Mean Difference (IV, Fixed, 95% CI)0.54 [0.03, 1.05]
Analysis 5.1.

Comparison 5 adhesive (high viscosity) versus adhesive (low viscosity), Outcome 1 dehiscence.

Analysis 5.2.

Comparison 5 adhesive (high viscosity) versus adhesive (low viscosity), Outcome 2 infection.

Analysis 5.3.

Comparison 5 adhesive (high viscosity) versus adhesive (low viscosity), Outcome 3 patient satisfaction.

Analysis 5.4.

Comparison 5 adhesive (high viscosity) versus adhesive (low viscosity), Outcome 4 clinician satisfaction.

Analysis 5.5.

Comparison 5 adhesive (high viscosity) versus adhesive (low viscosity), Outcome 5 time taken for closure.

Appendices

Appendix 1. Search strategy - Original version

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 MEDLINE, 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 5c 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 proceedings and abstracts. A list of journals currently being handsearched by the group may be found at http:/www.cochranewounds.org.

Appendix 2. Ovid MEDLINE search strategy

1     exp "Wounds and Injuries"/
2     (surgical adj wound$).mp.
3     or/1-2
4     exp Tissue Adhesives/
5     exp Fibrin Tissue Adhesive/
6     tissue adhesive$.mp.
7     exp Cyanoacrylates/
8     octylcyanoacrylate$.mp.
9     Dermabond.mp.
10     exp Enbucrilate/
11     enbucrilate.mp.
12     butylcyanoacrylate$.mp.
13     exp Acrylates/
14     acrylate$.mp.
15     exp Bucrylate/
16     bucrylate$.mp.
17     or/4-16
18     3 and 17

Appendix 3. Ovid EMBASE search strategy

1     exp Surgical Wound/
2     (surgical adj wound$).mp.
3     or/1-2
4     exp Tissue Adhesive/
5     exp Fibrin Glue/
6     (tissue adj adhesive$).mp.
7     exp Cyanoacrylate Derivative/
8     exp Cyanoacrylic Acid Octyl Ester/
9     octylcyanoacrylate$.mp.
10     Dermabond.mp.
11     exp ENBUCRILATE/
12     enbucrilate.mp.
13     butylcyanoacrylate$.mp.
14     exp Acrylic Acid/
15     acrylate$.mp.
16     exp Bucrilate/
17     bucrylate$.mp.
18     or/4-17

Appendix 4. EBSCO CINAHL search strategy

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")

What's new

DateEventDescription
3 August 2010AmendedContact details updated.

History

Protocol first published: Issue 3, 2003
Review first published: Issue 2, 2004

DateEventDescription
23 November 2009New citation required and conclusions have changedTime 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 update.
23 November 2009New search has been performedNew 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 assessment.
16 May 2002New citation required and conclusions have changedSubstantive amendment

Contributions of authors

Paul Coulthard: conceived, designed and co-ordinated the 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.
Marco Esposito: developed the search strategy, undertook the searches for the original review and advised on the review.
Helen V Worthington: 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 advised on the review and the review update.
Maarten van der Elst Provided general advice on the review and undertook previous work that was the foundation of the current review.
Oscar J F van Waes: screened search results against the inclusion criteria and retrieved papers, appraised quality and extracted data, wrote to trial authors for additional information. 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 updated review, managed data for the review and entered data into RevMan. Analysed and interpreted data and wrote the 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: coordinated the editorial process. Advised on methodology, interpretation and content. Edited and copy edited the review and the updated review.
Ruth Foxlee: designed the search strategy, ran the searches and edited the search methods section for the update.

Declarations of interest

One of the authors (Paul Coulthard) was a co-author in the Blondeel 2004 study. This study was also commercially supported by Ethicon.

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.

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.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Blondeel 2004

MethodsOne-month follow-up randomised parallel group study.
Participants217 adult patients requiring any skin incision closure 4 cm or greater in length. Multicentre study: 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. Patients were excluded if they had a history of peripheral vascular disease, insulin-dependent diabetes, a blood-clotting disorder or in receipt of anticoagulants within 7 days of surgery, concurrent use of steroids, or a personal or family history of keloid formation or hypertrophy, impaired wound healing, and a known allergy to cyanoacrylate or formaldehyde.
InterventionsHigh viscosity 2-octylcyanoacrylate (High Viscocity Dermabond®, Ethicon Inc, a Johnson & Johnson company, Somerville, New Jersey, USA) tissue adhesive compared with any other commercially available device such as sutures, staples, or tapes or compared with low viscosity 2-octylcyanoacrylate (Dermabond®, Ethicon Inc, a Johnson & Johnson company, Somerville, New Jersey, USA). 106 patients were in the high viscosity tissue adhesive group and 103 patients were in the any other device group including 42 who received low viscosity tissue adhesive.
OutcomesDehiscence, infection, patient satisfaction and surgeon satisfaction at 10 days and cosmetic appearance at 30 days. Time required for incision closure was also recorded although this outcome was not of interest to this review.
NotesCosmetic appearance data not used as less than 3 months.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesAdequate

Cheng 1997

MethodsOne-month follow-up randomised parallel group study. The number of withdrawals was not clear and there was no reply following writing to the authors.
Participants86 male patients under the age of 12 years requiring elective circumcision were entered into the study. Duchess of Kent Hospital, Hong Kong. Patients were healthy. No specific exclusion criteria were described.
InterventionsCyanoacrlyate (Histoacryl®) tissue adhesive compared with 4.0 catgut sutures. 40 patients were in the adhesive group and 46 patients were in the suture group.
OutcomesDehiscence and infection at day 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.
NotesCosmetic appearance data not used as less than 3 months.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearUnclear

Dowson 2006

MethodsThree-month follow-up randomised parallel group study.
Participants168 patients recruited for laparoscopic procedures at Queen's Medical Centre, Nottingham. 154 patients included in the final analysis. Withdrawals were accounted for. Extensive exclusion criteria.
InterventionsN-butyl-cyanoacrylate (Liquiband®) tissue adhesive compared with interrupted, non-absorbable suture. 76 assigned to the adhesive group and 78 to the suture group.
OutcomesTime to closure, dehiscence, satisfaction, cosmesis and infection.
NotesUnlcear reference to subcutaneous layers being dealt with. Authors contacted for mean and standard deviations of time to closure and cosmesis but no reply, therefore this information was not included.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesAdequate

Greene 1999

MethodsOne-month follow-up randomised split-body design study . No patients lost to follow-up.
Participants20 adult patients requiring bilateral blepharoplasty for functional or aesthetic indications. 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. A blepharoplasty model with identical skin sites on the same patient and each patient acting as his or her own control. No specific exclusion criteria are described.
InterventionsLeft or right upper eye lid with octyl-2-cyanoacrylate (Dermabond®, Ethicon Inc, a Johnson & Johnson company, Somerville, New Jersey, USA) and other eyelid 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 patients and by using 3 - 4 sutures as handles to facilitate apposition and eversion of edges in 5 patients. 20 patients undergoing blepharoplasty (40 eyelids were treated).
OutcomesDehiscence, infection, patient satisfaction, surgeon satisfaction and cosmetic appearance at 1, 2, and 4 weeks. Time required for incision closure and allergic reaction were also recorded although these outcomes were not of interest to this review.
NotesCosmetic appearance data could not be used as only up to 4 weeks.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoInadequate

Keng 1989

MethodsSeven-month follow-up randomised parallel group study. Three patients lost follow-up: 1 from the suture group and 2 from the tissue adhesive group.
Participants43 patients requiring groin incisions (inguinal hernia, femoral hernia, sapheno ligations, testicular operations and lymph node biopsies). Skin incisions were closed with either Histoacryl tissue adhesive or dexon subcuticular suture . In bilateral operations the left side was closed with Histoacrly and the left with dexon. Burton General Hospital, Burton-on-Trent, UK.
InterventionsDexon suture on straight needle using anchoring knot both ends or opposing the wound with forceps and Histoacryl.
OutcomesInfection, inflammation, Cosmetic appearance, wound closing time, wound comfort and haematoma.
NotesExclusion criteria were not stated. Cosmetic appearance not used as only evaluated up to 4 weeks.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoInadequate

Maartense 2002

MethodsSixteen-month follow-up randomised parallel group study. There were no withdrawals, however 7 patients treated with paper tape and 3 with tissue adhesive were converted to the suture group.
Participants140 adults patients requiring elective laparoscopic surgery. Patients were excluded if they had undergone previous laparotomy or were pregnant. The study was undertaken at two centres, Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands and Department of Surgery, Isala Clinics, Zwolle, The Netherlands.
InterventionsOctylcyanoacrylate (Dermabond®, Johnson & Johnson, Amersfoot, The Netherlands) tissue adhesive compared with 76 mm X 6 mm adhesive paper tape (SteriStrip® Bioplasty/Uroplasty, Geleen, The Netherlands) compared with intracutaneous poliglecaprone (Monocryl®) 4/0, Johnson & Johnson) interrupted sutures. 48 patients were in the adhesive group, 42 were in the tape group and 50 were in the suture group.
OutcomesInfection, cosmetic appearance, and surgeon satisfaction at 2 weeks and 3 months, and costs. Time required for incision closure was also recorded although this outcome was not of interest to this review.
NotesWe wrote to the authors who confirmed that there were no withdrawals.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearUnclear

Ong 2002

MethodsThree-month follow-up randomised, parallel group study. 50 withdrawals at 3-month follow-up.
Participants59 patients requiring unilateral or bi-lateral herniotomies at KK Womens' and Childrens' Hospital, Singapore.
Interventions2-Octylcyanoacrylate (Dermabond®) tissue adhesive compared with subcuticular polyglecaprone (Monocryl®) suture. 26 patients assigned to the adhesive group and 33 to the control group.
OutcomesInfection, dehiscence, parent satisfaction and time for closure.
NotesCosmesis 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 patients dropping out.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesAdequate

Ozturan 2001

MethodsThree-month follow-up randomised, parallel group study. There were no withdrawals.
Participants101 patients requiring rhinoplasty or septorhinoplasty were entered to the study. Patients were excluded if they had a history of peripheral vascular disease, diabetes mellitus, clotting disorder, keloid or hypertrophy, or allergy to cyanoacrylate or formaldehyde. Inonu University Hospital, Turkey.
InterventionsButylcyanoacrylate (LiquiBand. MedLogic Global Ltd, Plymouth, Devon, UK) tissue adhesive compared with 6.0 polypropylene sutures for columellar skin closure after the majority of the tension had been taken up using 5.0 chromic catgut. 34 patients were in the adhesive group and 67 patients were in the suture group.
OutcomesDehiscence and infection at one week. Cosmesis at three months by blinded assessment of photographs using VAS and Hollander scale. Time required for skin closure was also measured although this was not an outcome of interest for this review.
NotesWe 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
ItemAuthors' judgementDescription
Allocation concealment?NoInadequate

Ridgway 2007

MethodsSix-week follow-up, randomised, parallel group study. One withdrawal but no explanation.
Participants30 patients recruited for cervicotomy for thyroid and para thyroid surgery at Scunthorpe General Hospital, North Lincs. 29 successfully randomised. No reference to inclusion/exclusion criteria.
Interventions2-Octylcyanoacrylate (Dermabond®) tissue adhesive compared with staples (Vivistat®). 14 patients assigned to intervention and 15 to control groups.
OutcomesTime to closure, neck mobility, cosmesis and adverse events.
NotesCosmesis results could not be included as measured too early to be usable. No explanation of what characterised an adverse event or the occurrence of such outcomes.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesAdequate

Shamiyeh 2001

MethodsNine-month follow-up randomised, parallel group study. 2 patients were lost to follow-up from the suture group due to failure to attend and could not be traced by mail or phone.
Participants79 adult patients requiring varicose vein surgery on the leg. Ludwick Boltzmann Institure, Linz, Austria. Patients were excluded if they had a history of chronic venous insufficiency with dermatosclerosis, previous phlebectomies, or allergy to plaster or octylcyanoacrylate.
InterventionsMullerian phlebectomy creating average wound length of 5 mm. Used 5 min wound compression followed by skin closure with octylcyanoacrylate tissue adhesive or 5.0 monofilament suture or tape. A small plaster was placed over each wound. 26 patients were in the tissue adhesive group, 28 in the suture group, and 25 in the tape group.
OutcomesWound dehiscence, infection, at 10 days and patient and surgeon satisfaction, and cosmetic appearance at 1 year and costs. Time required for incision closure was also recorded although this outcome was not of interest to this review.
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesAdequate

Sinha 2001

MethodsSix-month follow-up randomised, parallel group study. Six patients were lost to follow-up: 5 in tissue adhesive and 1 in suture group.
Participants50 adult patients requiring hand or wrist surgery (carpal tunnel syndrome, trigger finger, De Quervain's tenosynovitis, ganglions of wrist and hand, and cysts of fingers). Patients were excluded if they required surgery for Dupuytren's contracture, repeat surgery or had a history of skin allergy, keloid formation, diabetes, or corticosteroid use. Monklands Hospital, Airdre, UK.
InterventionsSkin approximating with skin hooks and applying n-butyl 2-cyanoacrylate adhesive (Indermil) or suturing with 4.0 monofilament. All cases has local anaesthetic infiltration with or without general anaesthesia. 20 patients were in the tissue adhesive group and 24 were in the suture group.
OutcomesDehiscence, infection, pain on movement, cosmetic appearance at 10 days, 2 weeks and 6 weeks. Pain on movement was not of interest to this review.
NotesCosmetic appearance data not used as less than 3 months.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearUnclear

Sniezek 2007

MethodsThree-month follow-up, randomised, parallel group study. No reference to withdrawals.
Participants14 patients 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.
Interventions2-Octylcyanoacrylate (Dermabond®) compared with a cuticular polypropylene cuticular suture. Split wound design.
OutcomesDehiscence, infection and cosmetics.
NotesAs split wound design the data is paired. The authors were contacted for the mean difference and the standard deviation of the cosmetic scores on a patient basis. No reply was received therefore this information was not included.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesAdequate

Switzer 2003

MethodsFour-week follow-up, randomised, parallel group study. 2 withdrawals accounted for.
Participants45 patients recruited for elective repair of inguinal hernias at the Eisenhower Army Medical Centre, Fort Gordon, Georgia. No reference to inclusion/exclusion criteria.
Interventions2-Octylcyanoacrylate (Dermabond®) tissue adhesive compared with subcuticular polyglecaprone (Monocryl®) suture. 24 patients enrolled in the adhesive group and 22 assigned to the control.
OutcomesDehiscence, infection, cosmetics and time taken to closure.
NotesThe cosmetic data was not included as the data was taken at less than 3 months. The authors were contacted for the mean and standard deviations for the time to closure but no response has been received therefore this was not included.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearUnclear

Toriumi 1998

MethodsOne-year follow-up randomised, parallel group study. 11 patients were lost to follow-up: not stated as to which groups
Participants1 years of age and over requiring elective surgery for benign skin lesions predominantly in face and neck. Patients were excluded if there was a history of significant trauma, peripheral vascular disease, diabetes mellitus, blood clotting disorder, keloid or hypertrophy, known allergy to cyanoacrylate or formaldehyde. University of Illinois, Chicago, USA.
InterventionsIncisions with and without subcutaneous sutures and then randomised for closure with octyl-2-cyanoacrylate or 5.0 or 6.0 nylon suture.
OutcomesDehiscence, infection, cosmesis and closure time.
NotesPatients lost to follow up were not reported by group.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearUnclear

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Alhopuro 1976No data given in the paper. We have contacted authors but did not receive a reply.
Gorozpe-Calvillo 99After full translation, found not to be a randomised controlled trial.
Jaibaji 2000All patients 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 2006All patients 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 an adjunct.
Orozco-Razon 2002There is no reference to randomisation. The authors have been contacted but we have received no reply.
Silvestri 2006Not a randomised controlled trial.
Singer 2002Data could not be used because combined with data for lacerations. We have written to the authors requesting data by group but did not receive a reply.
Steiner 2000Not a randomised controlled trial.

Ancillary