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Review Tissue sealants may reduce haematoma and complications in face-lifts: A meta-analysis of comparative studies Salvatore Giordano a,b, *, Ilkka Koskivuo a , Erkki Suominen a , Esko Vera ¨ja ¨nkorva a a Department of Plastic and General Surgery, Turku University Hospital, Turku, Finland b Department of Surgery, Welfare District of Forssa, Forssa, Finland Received 18 July 2016; accepted 30 November 2016 KEYWORDS Face-lift; Rhytidoplasty; Rhytidectomy; Tissue sealant; Haematoma; Platelet-rich plasma Summary The use of tissue sealants has increased among different surgical specialities. Face-lift and rhytidoplasty may cause several complications such as haematoma, ecchymosis, oedema, seroma, skin necrosis, wound dehiscence and wound infection. However, administra- tion of tissue sealants may prevent the occurrence of some complications. We performed a meta-analysis of studies that compared tissue sealant use with controls to evaluate the outcomes. A systematic literature search was performed. The primary outcome was the incidence of haematoma. Secondary outcomes were wound drainage amount, oedema, ecchymosis, seroma, skin necrosis and hypertrophic scarring. Thirteen studies involving 2434 patients were retrieved and included in the present analysis. A statistically significantly decrease in post-operative haematoma [risk ratio (RR), 0.37; 95% CI, 0.18e0.74; p Z 0.005] and wound drainage (MD, 16.90, 95% CI Z 25.71, 8.08, p < 0.001) was observed with tissue sealant use. A significant decrease in oedema was detected (RR, 0.30; 95% CI, 0.11e0.85, p Z 0.02) but not in ecchymosis, seroma, skin necrosis, and hypertrophic scarring with tissue sealant use. The use of tissue sealants prevents post-operative haemato- mas and reduces wound drainage. Previous studies have shown a similar trend, but the power of this meta-analysis could verify this perception. Level of Evidence: III. ª 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Else- vier Ltd. All rights reserved. * Corresponding author. Department of Plastic and General Surgery, Turku University Hospital, OS 299, PL 52, 20521, Turku, Finland. Fax: þ358 02 3132284. E-mail addresses: [email protected], salvatore.giordano@tyks.fi (S. Giordano). + MODEL Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A meta- analysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/ j.bjps.2016.11.028 http://dx.doi.org/10.1016/j.bjps.2016.11.028 1748-6815/ª 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. Journal of Plastic, Reconstructive & Aesthetic Surgery (2016) xx,1e10
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Page 1: Tissue sealants may reduce haematoma and complications in ... · evaluate the outcomes. A systematic literature search was performed. The primary outcome was the incidence of haematoma.

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Journal of Plastic, Reconstructive & Aesthetic Surgery (2016) xx, 1e10

Review

Tissue sealants may reduce haematoma andcomplications in face-lifts: A meta-analysisof comparative studies

Salvatore Giordano a,b,*, Ilkka Koskivuo a, Erkki Suominen a,Esko Verajankorva a

a Department of Plastic and General Surgery, Turku University Hospital, Turku, Finlandb Department of Surgery, Welfare District of Forssa, Forssa, Finland

Received 18 July 2016; accepted 30 November 2016

KEYWORDSFace-lift;Rhytidoplasty;Rhytidectomy;Tissue sealant;Haematoma;Platelet-rich plasma

* Corresponding author. DepartmenFax: þ358 02 3132284.

E-mail addresses: salvatore.giorda

Please cite this article in press as: Ganalysis of comparative studies,j.bjps.2016.11.028

http://dx.doi.org/10.1016/j.bjps.2016.11748-6815/ª 2016 British Association of P

Summary The use of tissue sealants has increased among different surgical specialities.Face-lift and rhytidoplasty may cause several complications such as haematoma, ecchymosis,oedema, seroma, skin necrosis, wound dehiscence and wound infection. However, administra-tion of tissue sealants may prevent the occurrence of some complications.

We performed a meta-analysis of studies that compared tissue sealant use with controls toevaluate the outcomes. A systematic literature search was performed. The primary outcomewas the incidence of haematoma. Secondary outcomes were wound drainage amount,oedema, ecchymosis, seroma, skin necrosis and hypertrophic scarring.

Thirteen studies involving 2434 patients were retrieved and included in the present analysis.A statistically significantly decrease in post-operative haematoma [risk ratio (RR), 0.37; 95% CI,0.18e0.74; p Z 0.005] and wound drainage (MD, �16.90, 95% CI Z �25.71, �8.08, p < 0.001)was observed with tissue sealant use. A significant decrease in oedema was detected (RR, 0.30;95% CI, 0.11e0.85, p Z 0.02) but not in ecchymosis, seroma, skin necrosis, and hypertrophicscarring with tissue sealant use. The use of tissue sealants prevents post-operative haemato-mas and reduces wound drainage. Previous studies have shown a similar trend, but the powerof this meta-analysis could verify this perception.

Level of Evidence: III.ª 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Else-vier Ltd. All rights reserved.

t of Plastic and General Surgery, Turku University Hospital, OS 299, PL 52, 20521, Turku, Finland.

[email protected], [email protected] (S. Giordano).

iordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A meta-Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/

1.028lastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

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Contents

Pleasanalyj.bjp

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

Search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00Data extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00Outcome measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00Statistical analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00

Introduction

Face lift procedures may cause several complications suchas haematoma, ecchymosis, oedema, seroma, skin necro-sis, wound dehiscence, nerve injury and wound infection.Among them, haematoma is one of the most common, witha rate of 1.1%e9% and representing 62% of all complica-tions.1,2 Haematoma may compromise the skin flap’svascularity, thus delaying post-operative recovery becauseof possible ecchymosis, oedema and seroma. Nonetheless,the long-term course may lead to local unwanted effectssuch as hyperpigmentation and contour changes due topossible sub-cutaneous scarring. Therefore, any strategy todecrease all these complications is attractive.

Fibrin-based tissue adhesives have gained popularityamong plastic surgeons for different procedures,3 particu-larly facial plastic surgery.4 Different fibrin sealant prod-ucts are available in the market, and previous studiessuggest that these sealants have numerous proven benefits,including the reduction of wound drainage, oedema,ecchymosis and comfort in addition to haematoma.5e8

However, none of these studies were sufficiently poweredto demonstrate the effectiveness of tissue sealants in face-lifts. A previous meta-analysis on this topic failed to showsignificant benefits; however, it reported a trend towardsdiminished post-operative drainage and ecchymosis usingdata from three studies.9 Furthermore, the use of fibrin-based tissue adhesives has been recently investigated byseveral studies, which were not included in the above-mentioned meta-analysis.7,8,10 Thus, we performed ameta-analysis of comparative studies to evaluate the out-comes, hypothesising that tissue sealants may provide sig-nificant benefits in preventing not only haematoma ratesbut also complications in face-lifts.

Materials and methods

The present systematic review and meta-analysis followedthe guidelines of the Preferred Reporting Items for Sys-tematic Reviews and Meta-Analyses (PRISMA) statement,and the relevant checklist was completed.11

e cite this article in press as: Giordano S, et al., Tissue sealantssis of comparative studies, Journal of Plastic, Reconstrucs.2016.11.028

Search strategy

All authors individually performed a full systematic litera-ture search of all records through Medline, Cochrane Li-brary, Embase, Scopus, Google Scholar and Research Gatefor any study on tissue sealants use in human subjects forface-lift/rhytidectomy procedures.

The terms employed in the search were ‘fibrin tissueadhesive’, ‘tissue sealant’ and ‘platelet rich plasma’ com-bined with ‘face-lift’, ‘rhytidoplasty’, ‘rhytidectomy’ and‘facial plastic surgery’, and they were combined usingBoolean operators. In addition, the reference lists of allrelevant articles were scrutinised. Each author’s search re-sults were merged and duplicate citations were discarded.

The search was performed from inception to 29 June2016, aiming at those studies that compared the outcomesof tissue sealant use in face-lifts with internal or externalcontrol in both randomised and non-randomised fashion. Nolanguage restrictions were applied.

Study selection

We searched for and assessed studies that compared theuse of any fibrin sealant with any control in face-lift pro-cedures. Studies included in this review had to match pre-determined criteria according to the PICOS (patients,intervention, comparator, outcomes and study design)approach. Criteria for inclusion and exclusion are specifiedin Table 1. No limitations were applied on ethnicity, age ofpatients or type of fibrin sealant used.

Two authors (SG and EV) independently reviewed theabstracts and articles. In addition, the reference lists of allrelevant articles were scrutinised. For the purpose of thisanalysis, studies reporting on quantitative outcomes afterfibrin sealant use compared with control in face-lift pro-cedures were considered eligible.

Each study was independently evaluated by two co-authors (SG and EV) for inclusion or exclusion from thisanalysis (Table 1). To be included, studies had to providedetails on baseline characteristics, type of face-lift pro-cedure, type of fibrin sealant, and outcomes of post-

may reduce haematoma and complications in face-lifts: A meta-tive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/

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Table 1 PICOS criteria for inclusion and exclusion of studies.

Parameter Inclusion criteria Exclusion criteria

Patients Patients of any age undergoing face-lift surgery. Patients underwent mini-invasive rejuvenation orother types of facial procedures.

Intervention Local application of any type of fibrin sealant,including autologous plated-rich plasma.

Comparator Any type of control, internal (face side) or external. Studies comparing different types of fibrin sealants.Outcomes Primary outcome measure: haematoma occurrence

requiring re-operation. Secondary outcome measures:drainage amount from the wound bed after 24 h;post-operative ecchymosis; oedema when reported;and seroma, skin necrosis and hypertrophicscarring at follow-up.

Study design Randomized controlled trials; non-randomizedobservational trials; retrospective, prospective,or concurrent cohort studies.At least 1-month follow-up.

Reviews, expert opinion, comments,letter to editor, case reports, studies on animals,conference reports. Shorter follow-up,<1 month. Studies with no outcomes reported.

Tissue sealants may reduce haematoma in face lifts 3

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operative complications compared with control patients orside in the same patient (internal control).

Data extraction

Data were independently collected by two investigators (SGand EV) and checked by a third investigator (IK) only fromthe retrieved articles. Disagreement on collected data wassettled by consensus between these investigators. Noattempt was made to obtain specific or missing data fromthe authors. The following data were extracted: firstauthor, year of publication, study design, number of pa-tients, type of procedure, and primary and secondarymeasures.

The quality of the included studies was independentlyassessed by three investigators (SG, EV and IK) using theCochrane Collaboration’s risk of bias assessment tool forrandomized controlled trials (RCT)12 while using the New-castleeOttawa scale to evaluate individual non-randomisedstudies.13 The research team convened to resolve anydisagreement on the assessment and reach consensus.

Outcome measures

The primary outcome measure was haematoma occurrencerequiring re-operation. The secondary outcome measureswere the drainage amount from the wound bed after 24 h,post-operative ecchymosis, oedema at 7e8 days or, whenreported, seroma, skin necrosis and hypertrophic scarringat follow-up. We assumed that drainages were not placed instudies not reporting outcomes on drainage amount. Defi-nitions for these endpoints were those adopted by the in-vestigators of the included studies. However, minorhaematoma, reported in two studies, was considered asecchymosis,5,14 whereas prolonged oedema with ecchy-mosis, described in one study,5 and haematoma/seroma notrequiring surgical intervention, stated in one study,15 wereconsidered as seroma. Missing data were dealt according topreviously validated estimations.16

The patient’s contralateral side was used as control insome of the included studies, represented by the

Please cite this article in press as: Giordano S, et al., Tissue sealantsanalysis of comparative studies, Journal of Plastic, Reconstrucj.bjps.2016.11.028

contralateral face side, whereas in the other studies, pa-tients were allocated into different groups according towhether fibrin sealants were used or not. Therefore, theoutcome occurrence pooled in the analysis was the one byface side when studies with internal and external controlwere pooled together.17

Statistical analysis

Statistical analysis was performed using Review Manager5.3 software (Copenhagen: The Nordic Cochrane Centre,The Cochrane Collaboration, 2014).18 Differences incontinuous variables were expressed as mean differ-ence (MD) with 95% confidence interval (CI). Differences indichotomous variables and outcome endpoints were re-ported as risk ratio (RR) with 95% CI. Heterogeneity wasassessed by I2 statistic, which describes the percentage oftotal variation across the studies, which is due to hetero-geneity rather than chance.19 I2 values were evaluated aslow, moderate or high at 25%, 50% or 75%, respectively. Inalmost all the cases, we performed random-effect analysis,which considers both within- and between-study varia-tions,20,21 because of the observational nature of somestudies included in this analysis. However, in one pooledanalysis including only RCTs (Figure 3A), a fixed effect wasused. A p < 0.05 was considered statistically significant.

Finally, we conducted sensitivity analyses omitting eachstudy in turn using the ‘leave one out’ methodology todetermine whether the results were excessively influencedby a single study. Publication bias was assessed using thefunnel plot for primary outcomes.

Results

Literature search yielded 4912 articles, of which135e8,10,12,22e27 were pertinent to the present meta-analysis and had sufficient sources of information on out-comes using fibrin sealants for face-lifts to be included inthe meta-analysis (Table 2), involving a total of 2434 pa-tients. The literature search flowchart is shown in Figure 1.All the studies showed different approaches and different

may reduce haematoma and complications in face-lifts: A meta-tive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/

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Table 2 Retrieved studies included in the analysis.

Author Study type Total numberof patients

Control Sides offaces

Mean age(years)

Procedure Sealant Volume Outcome measuresextracted

Marchac, 19945 Retrospectivenon-randomized

200 100 200 vs 200 39e73 SMAS plicationand liposuction

Tissucol R 0.5e1 ml Haematoma, Ecchymosis,Oedema, Hypertrophicscar, Skin necrosis

Oliver, 20016 RCT 20 Self 20 vs 20 44e70 Sub-cutaneous,SMAS plication

Beriplast P 1 ml Drainage at 24 h

Powell, 200122 RCT 8 Self 8 vs 8 N/A Deep-plane face-lift Platelet-richPlasma

7e8 ml Ecchymosis, Oedema

Fezza, 200223 Retrospectivenon-randomized

24 24 48 vs 48 48e87 Strip SMAS andliposuction

HaemaseelAPR

1 ml Haematoma

Marchac &Greensmith, 200524

RCT 30 Self 30 vs 30 42e72 Vertical U incision,SMAS plication

Tisseel N/A Drainage at 24 h,Ecchymosis, Oedema

Brown, 200525 Prospectivenon-randomised

33 14 38 vs 28 55e56 SMAS plication Platelet-richPlasma

7 ml Drainage at 8e24 h,Haematoma, Seroma,Skin necrosis

Kamer, 200726 Retrospectivenon-randomized

100 100 200 vs 200 45e81 Deep-plane face-lift Tisseel 1 ml Haematoma, Ecchymosis,Seroma

Zoumalan, 200814 Retrospectivenon-randomized

605 146 918 vs 292 37e79 Deep-plane face-lift,lateral SMASectomy

Tisseel N/A Haematoma (major,minor)

Lee, 200915 Retrospectivenon-randomized

9 Self 9 vs 9 N/A Deep-plane face-lift Crosseal 2 ml Ecchymosis, Oedema

Hester & Gerut, 20137 RCT 45 Self 45 vs 45 18e75 Sub-cutaneous, SMASplication or elevation,liposuction

Artiss 0.02e0.04 ml Haematoma, Drainageat 24 h, Seroma

Hester & Shire, 20138 RCT 71 Self 71 vs 71 18e75 Sub-cutaneous, SMASplication or elevation,liposuction

Artiss 0.02e0.04 ml Haematoma, Drainageat 24 h, Seroma

Costa, 201527 Retrospectivenon-randomized

1089 502 1174 vs 1004 35e89 SMASectomy orSMAS stacking

Platelet-richPlasma

8 ml Haematoma

Berry, 201510 Retrospectivenon-randomized

200 100 200 vs 200 35e81 SMAS dissection,plication, SMAS flap,e-SMAS

Tisseel 1 ml Haematoma, Hypertrophicscar, Skin necrosis

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Figure 1 Flow chart summarizing the literature search results.

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harvesting planes (Table 2). Of them, five were RCT6e8,22,24

and the others were comparative studies. Six studiesinvolved self/internal control where tissue sealant wasapplied on one side.6e8,13,22,24 Details on the quality of theincluded study are summarized in Table S1 (available assupplemental file). In the RCT studies, the risk of bias wasmostly either low or unclear using the Cochrane Collabo-ration’s tool for assessing risk of bias.12 Non-RCTs wereassessed with NewcastleeOttawa scale for risk of bias,which resulted in 0e4 stars per category, indicating a highto low bias.13

Figure 2 Forest plot showing the significantly reduced haematomcontrol group.

Please cite this article in press as: Giordano S, et al., Tissue sealantsanalysis of comparative studies, Journal of Plastic, Reconstrucj.bjps.2016.11.028

All but one study,5e10,12,22e27 involving a total of 2425patients, reported the incidence of post-operative haema-toma, and pooled analysis showed significant differencethat favoured tissue sealants (RR, 0.37; 95% CI, 0.18e0.74;p Z 0.005; Figure 2). Sub-group analysis for the assessmentof overall haematoma among only RCTs (RR, 0.26; 95% CI,0.08e0.83; p Z 0.02, Figure 3A) and among only compar-ative studies (RR, 0.39; 95% CI, 0.17e0.88; p Z 0.02,Figure 3B) confirmed these outcomes.

Sub-group analysis for haematoma among the most usedsealants showed significant outcomes only for Artiss� (RR,

a occurrence in fibrin sealant patient group compared with the

may reduce haematoma and complications in face-lifts: A meta-tive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/

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Figure 3 AeB. Forest plots assessing overall haematoma occurrence in RCTs (A) and retrospective studies (B), favouring the fibrinsealant patient group.

6 S. Giordano et al.

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0.13; 95% CI, 0.03e0.86; p Z 0.03; Figure 4C), although atrend towards benefit was noted (Figure 4AeB). When sub-group analysis was performed on the basis of dissectionplane, tissue sealants were significantly beneficial for sub-cutaneous face-lifts (RR, 0.27; 95% CI, 0.10e0.73;p Z 0.01, Figure 5A), but not for deep-plane face-lifts(Figure 5B).

Similarly, analysis of five studies6e8,24,25 reported asignificantly reduced post-operative wound drainage usingtissue sealants (MD, �16.90, 95% CI Z �25.71, �8.08,p < 0.001; Figure 6). Pooled analysis comparing haematomarates in patients where tissue sealants were used withoutdrains (8/2748) with those in patients where tissue sealantswere used with drains (2/204) did not show significant dif-ference (RR, 3.37; 95% CI, 0.72e15.75; p Z 0.14).

Among the secondary endpoints, no significant differ-ence was detected in ecchymosis (RR, 0.58; 95% CI,0.21e1.62; p Z 0.30; Figure 7), but oedema occurrencewas significantly lower (RR, 0.30; 95% CI, 0.11e0.85;p Z 0.02; Figure 8). We did not find a significant differencebetween the two treatment groups with regard to seromaoccurrence (RR, 0.41; 95% CI, 0.15e1.11; p Z 0.08), skinnecrosis (RR, 0.49; 95% CI, 0.11e2.26; p Z 0.36) and hy-pertrophic scarring (RR, 0.19; 95% CI, 0.03e1.12; pZ 0.07).Although not statistically significant, these pooled resultsshowed a certain trend towards the reduction of skin ne-crosis and hypertrophic scarring; however, these resultswere obtained from only two studies.5,10

Finally, the exclusion of any study from the analysis didnot materially change the summary estimates, and absenceof significant asymmetry in the funnel plot for haematomawas observed (Figure 9A). However, wound drainage funnelplot showed some asymmetry because of the high hetero-geneity (Figures 7 and 9B).

Please cite this article in press as: Giordano S, et al., Tissue sealantsanalysis of comparative studies, Journal of Plastic, Reconstrucj.bjps.2016.11.028

Discussion

The present meta-analysis including 13 studies and 2434patients provides compelling evidence that tissue sealantsare effective in preventing haematoma occurrence andreducing post-operative drainage amount in patients un-dergoing face-lift independent of the technique used(Figure 2 and 3). Haematoma rates were similar usingfibrin sealants with or without drains. In addition, it wasalso observed that the occurrence of oedema was signifi-cantly reduced (Figure 6). However, the use of tissuesealant did not significantly prevent the incidence ofecchymosis, seroma, skin necrosis or hypertrophicscarring.

Haematoma is one of the most common complicationsin face-lift, with incidences up to 9%, that can requiresurgical evacuation.1,28e30 Previous studies showed thatpossible risk factors are high BMI, hypertension, periop-erative nausea/vomiting and heparin prophylaxis.1,29

Interestingly, male patients experience this complicationalmost three times more than female patients.1 This factmay be due to hormonal factors, facial follicle differ-ences, and thicker and more vascularized facial flaps,which are prominent in males.1,30 In this analysis, weincluded only haematoma requiring re-operation,excluding the minor non-expanding ones. In fact, dataconcerning patients’ baseline risk factors were not eluci-dated in the included studies.

Reducing the wound drainage amount and oedema areimportant to improve patients’ comfort and reduce possibleinfection, the second most common complication in face-lifts, occurring in 0.3% of cases.1 Infection was not consid-ered an endpoint in this pooled analysis, and it was notmentioned in most studies on this topic.

may reduce haematoma and complications in face-lifts: A meta-tive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/

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Figure 5 AeB. Forest plots for haematoma occurrence in sub-cutaneous face-lifts (A) and deep-plane face-lifts (B), favouring thefibrin sealant patient group only for sub-cutaneous face-lifts (A).

Figure 4 AeC. Forest plots for haematoma occurrence using Tisseel (A), Platelet-rich plasma (B), or Artissª (C), favouring thefibrin sealant patient group only for Artissª (C).

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Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A meta-analysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/j.bjps.2016.11.028

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Figure 8 Forest plot showing the significantly reduced oedema occurrence in the fibrin sealant patient group compared with thecontrol group.

Figure 9 AeB. Funnel plots for bias assessment in haematoma occurrence (A) and wound drainage amount (B).

Figure 6 Forest plot showing the significantly reduced wound drainage amount in the fibrin sealant patient group compared withthe control group.

Figure 7 Forest plot showing ecchymosis occurrence in the fibrin sealant patient group compared with the control group.

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The safest plane dissection for face-lift remainscontroversial because it is mostly personal and related tothe patient. Some authors prefer limited incision tech-niques to reduce haematoma,28,29 while others propose arelatively aggressive technique to obtain more sustained

Please cite this article in press as: Giordano S, et al., Tissue sealantsanalysis of comparative studies, Journal of Plastic, Reconstrucj.bjps.2016.11.028

results in term of rejuvenation.30 According to our study,fibrin sealants seem beneficial independent of the dissec-tion amount and plane used. Moreover, for deeperplane techniques, fibrin sealants may improve superfi-cial muscular aponeurotic system (SMAS) fixation after

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repositioning with sutures, thus reducing their tensionbecause of adhesion properties (gluing together of struc-tures).31 Particularly, Tissucol seems to have better gluingeffects than Quixil.32,33

A previous meta-analysis on this topic including onlyprospective randomised studies failed to show significantbenefits, but it reported a trend towards diminished post-operative drainage and ecchymosis using data from threestudies.9 More recently, another meta-analysis includingseven trials demonstrated a significant reduction of haema-toma incidence; however, their pooled analysis on 24-h post-operative wound drainage was based on only two studies.34

To evaluate the efficiency of any tissue sealant, it is ofgreat importance to conduct research in a double-blindedand controlled setting to eliminate any confounding ele-ments such as patients’ age, the plane of dissection, thetype of sealant used, and control treatment. Hence, it canbe concluded that the current scientific evidence on thebenefit of tissue sealants is still limited and inconsistentand bias effect should be considered. Thirteen studies wereused for this pooled analysis, and only five of them wereRCTs6e8,22,24 with self-control, represented by the contra-lateral face side. When pooling data of studies with internaland external controls, we considered face sides to reduceoverestimation bias,14 and to further clarify this, we per-formed a sub-group analysis using only RCTs with hemi-faceself-control (Figure 3A) and retrospective studies usingdifferent groups (Figure 3B). However, four studies6e8,24 ofthe 13 received financial support from industrial sources,which may cause bias.

Tissue sealants comprise two natural materials,thrombin and fibrinogen, forming the final commonpathway of the coagulation cascade. However, as severalproducts are available in the market, a major limitation ofthis analysis is due to the heterogeneity and plurality of thetissue sealants used. In general, tissue sealants can bedivided into several sub-groups: fibrin glue products(Artiss�; Tisseel�, Evicel�, Beriplast P�), thrombin andgelatin matrix compounds (Floseal�, Surgiflo�), bovineserum albumin and glutaraldehyde mixes (BSAG, BioGlue�),polyethylene glycol hydrogels (DuraSeal�) and even starchpowder (4DryField�, Perclot�). However, the productsused in the included articles were Tisseel in fourstudies10,12,13,23 and ARTISS in two studies.7,8

Because fibrin sealants are derived from human or ani-mal source, they can potentially cause an allergic reactionand have the theoretical possibility of transmitting infec-tious disease in homologous-derived forms.34,35 From thisperspective, the use of autologous platelet gel could bebeneficial22,25,27; only two fatal adverse reactions havebeen reported during neurosurgical procedures, which maybe due to the co-ingredient tranexamic acid.36 Platelet-richplasma is well known for its haemostatic, adhesive andhealing properties because of the multiple growth factorsreleased from the platelets.22,25,27

The cost of tissue sealants varies between differentproducts: fibrin products cost approximately 250 US$ perunit, gelatin products costs varies from 1300 to 2700 US$,BSAG products cost approximately 300 US$ per unit andDuraSeal costs approximately 100 US$ per unit. However,according to literature, only fibrin products have beenspecifically used in rhytidoplasty.

Please cite this article in press as: Giordano S, et al., Tissue sealantsanalysis of comparative studies, Journal of Plastic, Reconstrucj.bjps.2016.11.028

As demonstrated in this meta-analysis, tissue sealantsreduce the risk for haematoma, which also correlates to thefinding that these patients have less post-operativedrainage. Haematomas may range in severity from minorbruising requiring only conservative management to largeexpanding collections that demand aggressive surgicalmeasures. Therefore, the application of fibrin sealantswould be cost-effective if their use prevents one haema-toma evacuation in every 25 patients (i.e. 4%). As the rateof haematoma after rhytidectomy ranges from 0.2% to 8%and its incidence ranges from 3% to 4%,1,2,28,29 fibrin tissuesealants appear to be beneficial in economic terms. Thisevaluation obviously covers the cost of not only re-operations but also minor bruising due to extra load inoutpatient clinic, inducing additional time and costs.

Nonetheless, the linked trend in reducing skin necrosisand hypertrophic scarring can be cost beneficial as well,although we did not find it statistically significant in ourpooled analysis.

We had to exclude some interesting studies37e39

reporting outcomes on fibrin sealants because they didnot provide sufficient data for the meta-analysis.

Our analysis has several limitations. As discussedabove, only comparative studies were included in thismeta-analysis, thus excluding the one-arm cohorts. Thequality of the included studies was heterogeneous as fiveof them were RCTs6e8,22,24 and the others were compar-ative studies. Nevertheless, six studies involved self/in-ternal control, i.e. tissue sealant was applied in oneside,6e8,13,22,24 whereas in other studies, patients wereallocated into groups where tissue sealants were eitherused or not used (Table 1). All these issues certainlyconfer further bias and might affect the outcomes.Another major weakness of this meta-analysis is due tothe methodological heterogeneity in the surgical tech-nique used and the amount of undermining performed,which might affect the incidence of complications. Inparticular, only five studies6e8,24,25 reported outcomes onpost-operative wound drainage, while the others did notprovide sufficient data regarding this.

However, we found a benefit in all the studies inde-pendent of the product used. Interestingly, the haematomarates were considerably high in many studies, which maynot reflect the typical practice scenarios, adding furtherpossible bias. Nevertheless, patients’ comorbidities andmedicaments among the included studies were not takeninto account, and this may also affect the outcomes.

Additional studies are needed to validate this promisingtreatment modality for these complications, particularly inpatients with high risks, such as those who are obese,smokers, and using anti-coagulants or corticosteroids.

Conclusions

Fibrin sealants prevent haematoma occurrence and reducethe amount of wound drainage in face-lifts. Thus, werecommend their use, especially in the case of moreextensive dissection techniques, to reduce complications.However, these sealants cannot be considered a replace-ment for meticulous haemostasis but an adjunct to improveoutcomes.

may reduce haematoma and complications in face-lifts: A meta-tive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/

Page 10: Tissue sealants may reduce haematoma and complications in ... · evaluate the outcomes. A systematic literature search was performed. The primary outcome was the incidence of haematoma.

10 S. Giordano et al.

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Conflicts of interest

The authors have no financial interest to declare in relationto the content of this article.

Appendix A. Supplementary data

Supplementary data related to this article can be found athttp://dx.doi.org/10.1016/j.bjps.2016.11.028.

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