+
MODEL
Journal of Plastic, Reconstructive & Aesthetic Surgery (2016) xx, 1e10
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 Veräjänkorva a
a
b
Department of Plastic and General Surgery, Turku University Hospital, Turku, Finland
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, administration 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 haematomas 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 Elsevier 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], [email protected] (S. Giordano).
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.
Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A metaanalysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/
j.bjps.2016.11.028
+
MODEL
2
S. Giordano et al.
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Data extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Outcome measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Statistical analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
00
00
00
00
00
00
00
00
00
00
00
00
00
Introduction
Search strategy
Face lift procedures may cause several complications such
as haematoma, ecchymosis, oedema, seroma, skin necrosis, wound dehiscence, nerve injury and wound infection.
Among them, haematoma is one of the most common, with
a rate of 1.1%e9% and representing 62% of all complications.1,2 Haematoma may compromise the skin flap’s
vascularity, thus delaying post-operative recovery because
of possible ecchymosis, oedema and seroma. Nonetheless,
the long-term course may lead to local unwanted effects
such as hyperpigmentation and contour changes due to
possible sub-cutaneous scarring. Therefore, any strategy to
decrease all these complications is attractive.
Fibrin-based tissue adhesives have gained popularity
among plastic surgeons for different procedures,3 particularly facial plastic surgery.4 Different fibrin sealant products are available in the market, and previous studies
suggest 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 powered
to demonstrate the effectiveness of tissue sealants in facelifts. A previous meta-analysis on this topic failed to show
significant benefits; however, it reported a trend towards
diminished post-operative drainage and ecchymosis using
data from three studies.9 Furthermore, the use of fibrinbased tissue adhesives has been recently investigated by
several studies, which were not included in the abovementioned meta-analysis.7,8,10 Thus, we performed a
meta-analysis of comparative studies to evaluate the outcomes, hypothesising that tissue sealants may provide significant benefits in preventing not only haematoma rates
but also complications in face-lifts.
All authors individually performed a full systematic literature search of all records through Medline, Cochrane Library, Embase, Scopus, Google Scholar and Research Gate
for any study on tissue sealants use in human subjects for
face-lift/rhytidectomy procedures.
The terms employed in the search were ‘fibrin tissue
adhesive’, ‘tissue sealant’ and ‘platelet rich plasma’ combined with ‘face-lift’, ‘rhytidoplasty’, ‘rhytidectomy’ and
‘facial plastic surgery’, and they were combined using
Boolean operators. In addition, the reference lists of all
relevant articles were scrutinised. Each author’s search results were merged and duplicate citations were discarded.
The search was performed from inception to 29 June
2016, aiming at those studies that compared the outcomes
of tissue sealant use in face-lifts with internal or external
control in both randomised and non-randomised fashion. No
language restrictions were applied.
Materials and methods
The present systematic review and meta-analysis followed
the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement,
and the relevant checklist was completed.11
Study selection
We searched for and assessed studies that compared the
use of any fibrin sealant with any control in face-lift procedures. Studies included in this review had to match predetermined criteria according to the PICOS (patients,
intervention, comparator, outcomes and study design)
approach. Criteria for inclusion and exclusion are specified
in Table 1. No limitations were applied on ethnicity, age of
patients or type of fibrin sealant used.
Two authors (SG and EV) independently reviewed the
abstracts and articles. In addition, the reference lists of all
relevant articles were scrutinised. For the purpose of this
analysis, studies reporting on quantitative outcomes after
fibrin sealant use compared with control in face-lift procedures were considered eligible.
Each study was independently evaluated by two coauthors (SG and EV) for inclusion or exclusion from this
analysis (Table 1). To be included, studies had to provide
details on baseline characteristics, type of face-lift procedure, type of fibrin sealant, and outcomes of post-
Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A metaanalysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/
j.bjps.2016.11.028
+
MODEL
Tissue sealants may reduce haematoma in face lifts
Table 1
3
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 or
other types of facial procedures.
Intervention
Local application of any type of fibrin sealant,
including autologous plated-rich plasma.
Any type of control, internal (face side) or external.
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 hypertrophic
scarring at follow-up.
Randomized controlled trials; non-randomized
observational trials; retrospective, prospective,
or concurrent cohort studies.
At least 1-month follow-up.
Comparator
Outcomes
Study design
operative complications compared with control patients or
side in the same patient (internal control).
Data extraction
Data were independently collected by two investigators (SG
and EV) and checked by a third investigator (IK) only from
the retrieved articles. Disagreement on collected data was
settled by consensus between these investigators. No
attempt was made to obtain specific or missing data from
the authors. The following data were extracted: first
author, year of publication, study design, number of patients, type of procedure, and primary and secondary
measures.
The quality of the included studies was independently
assessed by three investigators (SG, EV and IK) using the
Cochrane Collaboration’s risk of bias assessment tool for
randomized controlled trials (RCT)12 while using the NewcastleeOttawa scale to evaluate individual non-randomised
studies.13 The research team convened to resolve any
disagreement on the assessment and reach consensus.
Outcome measures
The primary outcome measure was haematoma occurrence
requiring re-operation. The secondary outcome measures
were the drainage amount from the wound bed after 24 h,
post-operative ecchymosis, oedema at 7e8 days or, when
reported, seroma, skin necrosis and hypertrophic scarring
at follow-up. We assumed that drainages were not placed in
studies not reporting outcomes on drainage amount. Definitions for these endpoints were those adopted by the investigators of the included studies. However, minor
haematoma, reported in two studies, was considered as
ecchymosis,5,14 whereas prolonged oedema with ecchymosis, described in one study,5 and haematoma/seroma not
requiring surgical intervention, stated in one study,15 were
considered as seroma. Missing data were dealt according to
previously validated estimations.16
The patient’s contralateral side was used as control in
some of the included studies, represented by the
Studies comparing different types of fibrin sealants.
Reviews, expert opinion, comments,
letter to editor, case reports, studies on animals,
conference reports. Shorter follow-up,
<1 month. Studies with no outcomes reported.
contralateral face side, whereas in the other studies, patients were allocated into different groups according to
whether fibrin sealants were used or not. Therefore, the
outcome occurrence pooled in the analysis was the one by
face side when studies with internal and external control
were pooled together.17
Statistical analysis
Statistical analysis was performed using Review Manager
5.3 software (Copenhagen: The Nordic Cochrane Centre,
The Cochrane Collaboration, 2014).18 Differences in
continuous variables were expressed as mean difference (MD) with 95% confidence interval (CI). Differences in
dichotomous variables and outcome endpoints were reported as risk ratio (RR) with 95% CI. Heterogeneity was
assessed by I2 statistic, which describes the percentage of
total variation across the studies, which is due to heterogeneity rather than chance.19 I2 values were evaluated as
low, moderate or high at 25%, 50% or 75%, respectively. In
almost all the cases, we performed random-effect analysis,
which considers both within- and between-study variations,20,21 because of the observational nature of some
studies included in this analysis. However, in one pooled
analysis including only RCTs (Figure 3A), a fixed effect was
used. A p < 0.05 was considered statistically significant.
Finally, we conducted sensitivity analyses omitting each
study in turn using the ‘leave one out’ methodology to
determine whether the results were excessively influenced
by a single study. Publication bias was assessed using the
funnel plot for primary outcomes.
Results
Literature search yielded 4912 articles, of which
135e8,10,12,22e27 were pertinent to the present metaanalysis and had sufficient sources of information on outcomes using fibrin sealants for face-lifts to be included in
the meta-analysis (Table 2), involving a total of 2434 patients. The literature search flowchart is shown in Figure 1.
All the studies showed different approaches and different
Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A metaanalysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/
j.bjps.2016.11.028
4
Retrieved studies included in the analysis.
Author
Study type
Total number Control Sides of
of patients
faces
Mean age Procedure
(years)
Sealant
Volume
Outcome measures
extracted
Marchac, 19945
Retrospective
200
non-randomized
100
200 vs 200
39e73
SMAS plication
and liposuction
Tissucol R
0.5e1 ml
Self
20 vs 20
44e70
Beriplast P
1 ml
Self
8 vs 8
N/A
Sub-cutaneous,
SMAS plication
Deep-plane face-lift
Haematoma, Ecchymosis,
Oedema, Hypertrophic
scar, Skin necrosis
Drainage at 24 h
Oliver, 20016
RCT
20
Powell, 200122
RCT
8
Fezza, 200223
Retrospective
24
non-randomized
RCT
30
24
48 vs 48
48e87
Marchac &
Greensmith, 200524
Prospective
33
Brown, 200525
non-randomised
Self
30 vs 30
42e72
14
38 vs 28
55e56
Strip SMAS and
liposuction
Vertical U incision,
SMAS plication
SMAS plication
Kamer, 200726
100
100
200 vs 200
45e81
Deep-plane face-lift
Tisseel
1 ml
605
146
918 vs 292
37e79
Deep-plane face-lift,
lateral SMASectomy
Deep-plane face-lift
Tisseel
N/A
Crosseal
2 ml
Artiss
0.02e0.04 ml Haematoma, Drainage
at 24 h, Seroma
Artiss
0.02e0.04 ml Haematoma, Drainage
at 24 h, Seroma
9 vs 9
N/A
45
Self
45 vs 45
18e75
Hester & Shire, 20138
RCT
71
Self
71 vs 71
18e75
Costa, 201527
Retrospective
1089
non-randomized
Retrospective
200
non-randomized
502
1174 vs 1004 35e89
100
200 vs 200
Lee, 200915
Berry, 201510
35e81
Sub-cutaneous, SMAS
plication or elevation,
liposuction
Sub-cutaneous, SMAS
plication or elevation,
liposuction
SMASectomy or
SMAS stacking
SMAS dissection,
plication, SMAS flap,
e-SMAS
Platelet-rich 8 ml
Plasma
Tisseel
1 ml
Haematoma
Drainage at 24 h,
Ecchymosis, Oedema
Drainage at 8e24 h,
Haematoma, Seroma,
Skin necrosis
Haematoma, Ecchymosis,
Seroma
Haematoma (major,
minor)
Ecchymosis, Oedema
Haematoma
Haematoma, Hypertrophic
scar, Skin necrosis
S. Giordano et al.
Self
Zoumalan, 200814
Platelet-rich 7 ml
Plasma
Ecchymosis, Oedema
MODEL
9
Hester & Gerut, 20137
Retrospective
non-randomized
Retrospective
non-randomized
Retrospective
non-randomized
RCT
Platelet-rich 7e8 ml
Plasma
Haemaseel
1 ml
APR
Tisseel
N/A
+
Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A metaanalysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/
j.bjps.2016.11.028
Table 2
+
MODEL
Tissue sealants may reduce haematoma in face lifts
Figure 1
5
Flow chart summarizing the literature search results.
harvesting planes (Table 2). Of them, five were RCT6e8,22,24
and the others were comparative studies. Six studies
involved self/internal control where tissue sealant was
applied on one side.6e8,13,22,24 Details on the quality of the
included study are summarized in Table S1 (available as
supplemental file). In the RCT studies, the risk of bias was
mostly either low or unclear using the Cochrane Collaboration’s tool for assessing risk of bias.12 Non-RCTs were
assessed with NewcastleeOttawa scale for risk of bias,
which resulted in 0e4 stars per category, indicating a high
to low bias.13
All but one study,5e10,12,22e27 involving a total of 2425
patients, reported the incidence of post-operative haematoma, and pooled analysis showed significant difference
that favoured tissue sealants (RR, 0.37; 95% CI, 0.18e0.74;
p Z 0.005; Figure 2). Sub-group analysis for the assessment
of overall haematoma among only RCTs (RR, 0.26; 95% CI,
0.08e0.83; p Z 0.02, Figure 3A) and among only comparative 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 used
sealants showed significant outcomes only for Artiss (RR,
Figure 2 Forest plot showing the significantly reduced haematoma occurrence in fibrin sealant patient group compared with the
control group.
Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A metaanalysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/
j.bjps.2016.11.028
+
MODEL
6
S. Giordano et al.
Figure 3 AeB. Forest plots assessing overall haematoma occurrence in RCTs (A) and retrospective studies (B), favouring the fibrin
sealant patient group.
0.13; 95% CI, 0.03e0.86; p Z 0.03; Figure 4C), although a
trend towards benefit was noted (Figure 4AeB). When subgroup analysis was performed on the basis of dissection
plane, tissue sealants were significantly beneficial for subcutaneous 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 a
significantly reduced post-operative wound drainage using
tissue sealants (MD, 16.90, 95% CI Z 25.71, 8.08,
p < 0.001; Figure 6). Pooled analysis comparing haematoma
rates in patients where tissue sealants were used without
drains (8/2748) with those in patients where tissue sealants
were used with drains (2/204) did not show significant difference (RR, 3.37; 95% CI, 0.72e15.75; p Z 0.14).
Among the secondary endpoints, no significant difference was detected in ecchymosis (RR, 0.58; 95% CI,
0.21e1.62; p Z 0.30; Figure 7), but oedema occurrence
was significantly lower (RR, 0.30; 95% CI, 0.11e0.85;
p Z 0.02; Figure 8). We did not find a significant difference
between the two treatment groups with regard to seroma
occurrence (RR, 0.41; 95% CI, 0.15e1.11; p Z 0.08), skin
necrosis (RR, 0.49; 95% CI, 0.11e2.26; p Z 0.36) and hypertrophic scarring (RR, 0.19; 95% CI, 0.03e1.12; p Z 0.07).
Although not statistically significant, these pooled results
showed a certain trend towards the reduction of skin necrosis and hypertrophic scarring; however, these results
were obtained from only two studies.5,10
Finally, the exclusion of any study from the analysis did
not materially change the summary estimates, and absence
of significant asymmetry in the funnel plot for haematoma
was observed (Figure 9A). However, wound drainage funnel
plot showed some asymmetry because of the high heterogeneity (Figures 7 and 9B).
Discussion
The present meta-analysis including 13 studies and 2434
patients provides compelling evidence that tissue sealants
are effective in preventing haematoma occurrence and
reducing post-operative drainage amount in patients undergoing face-lift independent of the technique used
(Figure 2 and 3). Haematoma rates were similar using
fibrin sealants with or without drains. In addition, it was
also observed that the occurrence of oedema was significantly reduced (Figure 6). However, the use of tissue
sealant did not significantly prevent the incidence of
ecchymosis, seroma, skin necrosis or hypertrophic
scarring.
Haematoma is one of the most common complications
in face-lift, with incidences up to 9%, that can require
surgical evacuation.1,28e30 Previous studies showed that
possible risk factors are high BMI, hypertension, perioperative nausea/vomiting and heparin prophylaxis.1,29
Interestingly, male patients experience this complication
almost three times more than female patients.1 This fact
may be due to hormonal factors, facial follicle differences, and thicker and more vascularized facial flaps,
which are prominent in males.1,30 In this analysis, we
included only haematoma requiring re-operation,
excluding the minor non-expanding ones. In fact, data
concerning patients’ baseline risk factors were not elucidated in the included studies.
Reducing the wound drainage amount and oedema are
important to improve patients’ comfort and reduce possible
infection, the second most common complication in facelifts, occurring in 0.3% of cases.1 Infection was not considered an endpoint in this pooled analysis, and it was not
mentioned in most studies on this topic.
Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A metaanalysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/
j.bjps.2016.11.028
+
Tissue sealants may reduce haematoma in face lifts
MODEL
7
Figure 4 AeC. Forest plots for haematoma occurrence using Tisseel (A), Platelet-rich plasma (B), or Artissª (C), favouring the
fibrin sealant patient group only for Artissª (C).
Figure 5 AeB. Forest plots for haematoma occurrence in sub-cutaneous face-lifts (A) and deep-plane face-lifts (B), favouring the
fibrin sealant patient group only for sub-cutaneous face-lifts (A).
Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A metaanalysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/
j.bjps.2016.11.028
+
MODEL
8
S. Giordano et al.
Figure 6 Forest plot showing the significantly reduced wound drainage amount in the fibrin sealant patient group compared with
the control group.
Figure 7
Forest plot showing ecchymosis occurrence in the fibrin sealant patient group compared with the control group.
Figure 8 Forest plot showing the significantly reduced oedema occurrence in the fibrin sealant patient group compared with the
control group.
Figure 9
AeB. Funnel plots for bias assessment in haematoma occurrence (A) and wound drainage amount (B).
The safest plane dissection for face-lift remains
controversial because it is mostly personal and related to
the patient. Some authors prefer limited incision techniques to reduce haematoma,28,29 while others propose a
relatively aggressive technique to obtain more sustained
results in term of rejuvenation.30 According to our study,
fibrin sealants seem beneficial independent of the dissection amount and plane used. Moreover, for deeper
plane techniques, fibrin sealants may improve superficial muscular aponeurotic system (SMAS) fixation after
Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A metaanalysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/
j.bjps.2016.11.028
+
MODEL
Tissue sealants may reduce haematoma in face lifts
repositioning with sutures, thus reducing their tension
because of adhesion properties (gluing together of structures).31 Particularly, Tissucol seems to have better gluing
effects than Quixil.32,33
A previous meta-analysis on this topic including only
prospective randomised studies failed to show significant
benefits, but it reported a trend towards diminished postoperative drainage and ecchymosis using data from three
studies.9 More recently, another meta-analysis including
seven trials demonstrated a significant reduction of haematoma incidence; however, their pooled analysis on 24-h postoperative wound drainage was based on only two studies.34
To evaluate the efficiency of any tissue sealant, it is of
great importance to conduct research in a double-blinded
and controlled setting to eliminate any confounding elements such as patients’ age, the plane of dissection, the
type of sealant used, and control treatment. Hence, it can
be concluded that the current scientific evidence on the
benefit of tissue sealants is still limited and inconsistent
and bias effect should be considered. Thirteen studies were
used for this pooled analysis, and only five of them were
RCTs6e8,22,24 with self-control, represented by the contralateral face side. When pooling data of studies with internal
and external controls, we considered face sides to reduce
overestimation bias,14 and to further clarify this, we performed a sub-group analysis using only RCTs with hemi-face
self-control (Figure 3A) and retrospective studies using
different groups (Figure 3B). However, four studies6e8,24 of
the 13 received financial support from industrial sources,
which may cause bias.
Tissue sealants comprise two natural materials,
thrombin and fibrinogen, forming the final common
pathway of the coagulation cascade. However, as several
products are available in the market, a major limitation of
this analysis is due to the heterogeneity and plurality of the
tissue sealants used. In general, tissue sealants can be
divided into several sub-groups: fibrin glue products
(Artiss; Tisseel, Evicel, Beriplast P), thrombin and
gelatin matrix compounds (Floseal, Surgiflo), bovine
serum albumin and glutaraldehyde mixes (BSAG, BioGlue),
polyethylene glycol hydrogels (DuraSeal) and even starch
powder (4DryField, Perclot). However, the products
used in the included articles were Tisseel in four
studies10,12,13,23 and ARTISS in two studies.7,8
Because fibrin sealants are derived from human or animal source, they can potentially cause an allergic reaction
and have the theoretical possibility of transmitting infectious disease in homologous-derived forms.34,35 From this
perspective, the use of autologous platelet gel could be
beneficial22,25,27; only two fatal adverse reactions have
been reported during neurosurgical procedures, which may
be due to the co-ingredient tranexamic acid.36 Platelet-rich
plasma is well known for its haemostatic, adhesive and
healing properties because of the multiple growth factors
released from the platelets.22,25,27
The cost of tissue sealants varies between different
products: fibrin products cost approximately 250 US$ per
unit, gelatin products costs varies from 1300 to 2700 US$,
BSAG products cost approximately 300 US$ per unit and
DuraSeal costs approximately 100 US$ per unit. However,
according to literature, only fibrin products have been
specifically used in rhytidoplasty.
9
As demonstrated in this meta-analysis, tissue sealants
reduce the risk for haematoma, which also correlates to the
finding that these patients have less post-operative
drainage. Haematomas may range in severity from minor
bruising requiring only conservative management to large
expanding collections that demand aggressive surgical
measures. Therefore, the application of fibrin sealants
would be cost-effective if their use prevents one haematoma evacuation in every 25 patients (i.e. 4%). As the rate
of haematoma after rhytidectomy ranges from 0.2% to 8%
and its incidence ranges from 3% to 4%,1,2,28,29 fibrin tissue
sealants appear to be beneficial in economic terms. This
evaluation obviously covers the cost of not only reoperations but also minor bruising due to extra load in
outpatient clinic, inducing additional time and costs.
Nonetheless, the linked trend in reducing skin necrosis
and hypertrophic scarring can be cost beneficial as well,
although we did not find it statistically significant in our
pooled analysis.
We had to exclude some interesting studies37e39
reporting outcomes on fibrin sealants because they did
not provide sufficient data for the meta-analysis.
Our analysis has several limitations. As discussed
above, only comparative studies were included in this
meta-analysis, thus excluding the one-arm cohorts. The
quality of the included studies was heterogeneous as five
of them were RCTs6e8,22,24 and the others were comparative studies. Nevertheless, six studies involved self/internal control, i.e. tissue sealant was applied in one
side,6e8,13,22,24 whereas in other studies, patients were
allocated into groups where tissue sealants were either
used or not used (Table 1). All these issues certainly
confer further bias and might affect the outcomes.
Another major weakness of this meta-analysis is due to
the methodological heterogeneity in the surgical technique used and the amount of undermining performed,
which might affect the incidence of complications. In
particular, only five studies6e8,24,25 reported outcomes on
post-operative wound drainage, while the others did not
provide sufficient data regarding this.
However, we found a benefit in all the studies independent of the product used. Interestingly, the haematoma
rates were considerably high in many studies, which may
not reflect the typical practice scenarios, adding further
possible bias. Nevertheless, patients’ comorbidities and
medicaments among the included studies were not taken
into account, and this may also affect the outcomes.
Additional studies are needed to validate this promising
treatment modality for these complications, particularly in
patients with high risks, such as those who are obese,
smokers, and using anti-coagulants or corticosteroids.
Conclusions
Fibrin sealants prevent haematoma occurrence and reduce
the amount of wound drainage in face-lifts. Thus, we
recommend their use, especially in the case of more
extensive dissection techniques, to reduce complications.
However, these sealants cannot be considered a replacement for meticulous haemostasis but an adjunct to improve
outcomes.
Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A metaanalysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/
j.bjps.2016.11.028
+
MODEL
10
Conflicts of interest
The authors have no financial interest to declare in relation
to the content of this article.
Appendix A. Supplementary data
Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.bjps.2016.11.028.
References
1. Gupta V, Winocour J, Shi H, Shack RB, Grotting JC, Higdon KK.
Preoperative risk factors and complication rates in facelift:
analysis of 11,300 patients. Aesthet Surg J 2016;36:1e13.
2. Beer GM, Goldscheider E, Weber A, Lehmann K. Prevention of
acute hematoma after face-lifts. Aesthetic Plast Surg 2010;34:
502e7.
3. Mooney E, Loh C, Pu LL, ASPS/PSEF Technology Assessment
Committee. The use of fibrin glue in plastic surgery. Plast
Reconstr Surg 2009;124:989e92.
4. Kleinberger AJ, Spiegel JH. What is the best method for minimizing the risk of hematoma formation after rhytidectomy?
Laryngoscope 2015;125:534e6.
5. Marchac D, Sándor G. Face lifts and sprayed fibrin glue: an
outcome analysis of 200 patients. Br J Plast Surg 1994;47:
306e9.
6. Oliver DW, Hamilton SA, Figle AA, Wood SH, Lamberty BG. A
prospective, randomized, double-blind trial of the use of fibrin
sealant for face lifts. Plast Reconstr Surg 2001;108:2101e5.
7. Hester Jr TR, Gerut ZE, Shire JR, et al. Exploratory, randomized, controlled, phase 2 study to evaluate the safety and efficacy of adjuvant fibrin sealant VH S/D 4 S-Apr (ARTISS) in
patients undergoing rhytidectomy. Aesthet Surg J 2013;33:
323e33.
8. Hester Jr TR, Shire JR, Nguyen DB, et al. Randomized,
controlled, phase 3 study to evaluate the safety and efficacy of
fibrin sealant VH S/D 4 s-apr (Artiss) to improve tissue adherence in subjects undergoing rhytidectomy. Aesthet Surg J
2013;33:487e96.
9. Por YC, Shi L, Samuel M, Song C, Yeow VK. Use of tissue sealants in face-lifts: a metaanalysis. Aesthetic Plast Surg 2009;33:
336e9.
10. Berry MG, Stanek JJ. Fibrin tissue adhesive for face- and
necklift. J Plast Reconstr Aesthet Surg 2015;68:1325e31.
11. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting
items for systematic reviews and meta-analyses: the PRISMA
statement. Int J Surg 2010;8:336e41.
12. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.
BMJ 2011;343:d5928.
13. Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa
Scale for assessing the quality of nonrandomised studies in
meta-analyses. 2014. Available at: http://www.ohri.ca/
programs/clinical_epidemiology/oxford.asp [Accessed 28
June 2016].
14. Zoumalan R, Rizk SS. Hematoma rates in drainless deep-plane
face-lift surgery with and without the use of fibrin glue. Arch
Facial Plast Surg 2008;10:103e7.
15. Lee S, Pham AM, Pryor SG, Tollefson T, Sykes JM. Efficacy of
Crosseal fibrin sealant (human) in rhytidectomy. Arch Facial
Plast Surg 2009;11:29e33.
16. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and
standard deviation from the sample size, median, range and/or
interquartile range. BMC Med Res Methodol 2014;14:135.
S. Giordano et al.
17. Hunter JE, Jensen JL, Rodgers R. The control group and metaanalysis. J Methods Meas Soc Sci 2014;5:3e21.
18. Review Manager (RevMan) computer program. Version 5.3.
Copenhagen: The Nordic Cochrane Centre, The Cochrane
Collaboration; 2014.
19. Mantel N, Haenszel W. Statistical aspects of the analysis of
data from retrospective studies of disease. J Natl Cancer Inst
1959;22:719e48.
20. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring
inconsistency in meta-analyses. BMJ 2003;327:557e60.
21. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control
Clin Trials 1986;7:177e88.
22. Powell DM, Chang E, Farrior EH. Recovery from deep-plane
rhytidectomy following unilateral wound treatment with
autologous platelet gel: a pilot study. Arch Facial Plast Surg
2001;3:245e50.
23. Fezza JP, Cartwright M, Mack W, Flaharty P. The use of aerosolized fibrin glue in face-lift surgery. Plast Reconstr Surg 2002;
110:658e64.
24. Marchac D, Greensmith AL. Early postoperative efficacy of
fibrin glue in face lifts: a prospective randomized trial. Plast
Reconstr Surg 2005;115:911e6.
25. Brown SA, Appelt EA, Lipschitz A, Sorokin ES, Rohrich RJ.
Platelet gel sealant use in rhytidectomy. Plast Reconstr Surg
2006;118:1019e25.
26. Kamer FM, Nguyen DB. Experience with fibrin glue in rhytidectomy. Plast Reconstr Surg 2007;120:1045e51.
27. Costa CR, Ramanadham SR, O’Reilly E, Coleman JE, Rohrich RJ.
The role of the superwet technique in face lift: an analysis of
1089 patients over 23 years. Plast Reconstr Surg 2015;135:
1566e72.
28. Mustoe TA, Park E. Evidence-based medicine: face lift. Plast
Reconstr Surg 2014;133:1206e13.
29. Wan D, Small KH, Barton FE. Face lift. Plast Reconstr Surg
2015;136:676ee89e.
30. Baker DC, Stefani WA, Chiu ES. Reducing the incidence of hematoma requiring surgical evacuation following male rhytidectomy: a 30-year review of 985 cases. Plast Reconstr Surg
2005;116:1973e85.
31. Botti C, Botti G. Facelift 2015. Facial Plast Surg 2015;31:
491e503.
32. Spotnitz WD. Fibrin sealant: the only approved hemostat,
sealant, and adhesive-a laboratory and clinical perspective.
ISRN Surg 2014;2014:203943.
33. Botti G, Pascali M, Botti C, Bodog F, Gentile P, Cervelli V.
Comparison of commercial fibrin sealants in facelift surgery: a
prospective study. Clin Cosmet Investig Dermatol 2013;6:
273e80.
34. Killion EA, Hyman CH, Hatef DA, Hollier Jr LH, Reisman NR. A
systematic examination of the effect of tissue glues on rhytidectomy complications. Aesthet Surg J 2015;35:229e34.
35. Kanazawa R, Sato S, Iwamoto N, Teramoto A. Allergic reaction
following arachnoid plasty with a fibrin sealant. Neurol Med
Chir 2010;50:608e10.
36. Kober BJ, Scheule AM, Voth V, Deschner N, Schmid E, Ziemer G.
Anaphylactic reaction after systemic application of aprotinin
triggered by aprotinin-containing fibrin sealant. Anesth Analg
2008;107:406e9.
37. Grossman JA, Capraro PA, Atagi T. A prospective, randomized,
double-blind trial of the use of fibrin sealant for face lifts.
Plast Reconstr Surg 2002;110:1371e2.
38. Jones BM, Grover R. Avoiding hematoma in cervicofacial rhytidectomy: a personal 8-year quest. Reviewing 910 patients.
Plast Reconstr Surg 2004;113:381e7.
39. Jones BM, Grover R. Early postoperative efficacy of fibrin glue
in face lifts: a prospective randomized trial. Plast Reconstr
Surg 2007;119:433e4.
Please cite this article in press as: Giordano S, et al., Tissue sealants may reduce haematoma and complications in face-lifts: A metaanalysis of comparative studies, Journal of Plastic, Reconstructive & Aesthetic Surgery (2016), http://dx.doi.org/10.1016/
j.bjps.2016.11.028