8
FIBRIN SEALANT DECREASES POSTOPERATIVE DRAINAGE IN IMMEDIATE BREAST RECONSTRUCTION BY DEEP INFERIOR EPIGASTRIC PERFORATOR FLAP AFTER MASTECTOMY WITH AXILLARY DISSECTION MIKAE ¨ L HIVELIN, M.D., 1,2 * JEAN LAURENT HEUSSE, M.D., 3 * NADIA MATAR, M.D., 1,2 CHRISTOPHE LEPAGE, M.D., 1,2 and LAURENT LANTIERI, M.D. 1,2 Background: Serosanguinous drainage after breast reconstruction by deep inferior epigastric perforator flap (DIEP) can limit patient’s discharge. We introduced fibrin sealant in immediate breast reconstruction by DIEP flap to reduce drainage after mastectomy with axillary dissection. Materials and methods: We performed an open study on 30 consecutive female aged from 28 to 63 years old. All underwent immediate breast reconstructions by DIEP flaps after mastectomy and axillary dissection for cancer. Patients were divided in group 1 (N 5 15) without fibrin sealant and group 2 (N 5 15) where the flap, thoracic, and axillary areas were sprayed with 5 mL of liquid fibrin sealant before drains insertion. There was no difference in the patient’s BMI, height, weight or age between both the groups. Blake suction drains were placed under the flap and in the axillary area. Results: No adverse effects were reported, after a 20-month median follow-up. Drain- age volumes or durations were not correlated to the patient’s BMI, nor the height, weight or age. Thoracic drainage duration was longer than abdominal drainage in both the groups. Average drained volumes from the thoracic area were lower (427 vs. 552 mL; P 5 0.015) and thoracic drains were removed earlier (5.47 vs. 6.33 days P 5 0.022), in group 2 than in group 1. The length of stay was also reduced after the use of fibrin sealant (5.53 vs. 6.33 days; P 5 0.032). Conclusion: This study introduce the interest of fibrin sealant to significantly decrease the postoperative drainage volume and duration in the thoracic area after immediate breast reconstruction by DIEP flap. V V C 2010 Wiley-Liss, Inc. Microsurgery 31:18–25, 2011. Deep inferior epigastric perforator (DIEP) flap is a refer- ence technique for breast reconstruction by autologous tis- sue, with total failure rates ranging from 0.5 to 10%. 1–3 Failure rates have been more reported and studied than minor complications such as hematoma or seroma, which can alter the cosmetic result or delay adjuvant therapies. Patient’s discharge after drain removal is still per- formed in the great majority of surgery departments in France, where the hospitalization cost is in its majority defrayed by the public health insurance and the few rest by patient’s own health insurance. Discharge with drains in situ is sometime considered as increasing risk of infec- tions. 4 Early drain removal by an increase in patients freedom of movement (real or felt) also motivate them to move earlier and walk, contributing to reduce thrombo- embolic risks, and improving their satisfaction; but adverse effects make early drain removal after modified radical mastectomy being still controversial. 5,6 Fibrin sealant has been approved by the Food and Drug Administration in 1998 to promote hemostasis in coronary artery bypass surgery and splenic injury when uncontrolled by standard suturing techniques. 7 Fibrin sealant has been shown to be effective and to be safe in animal models of microvascular anastomosis repair 8,9 and has been used suc- cessfully to prevent hemorrhage and seroma. Its adhesive qualities have been reported in visceral surgery for pancre- atic wounds, 10 in neurosurgery on cerebrospinal leaks 11 or in reconstructive surgery in the prevention or treatment of seromas. 12,13 Fibrin sealant has been successfully used in visceral surgery, on splenic wounds origin, 14 and in cardio- vascular surgery 15 for an hemostatic purpose. In esthetic surgery, some authors have reported a reduction in severe hematoma in face and neck lifts. 16,17 We designed a clinical research protocol to assess the efficacy of fibrin sealant (Tissucol 1 , Baxter, France) in reducing the postoperative drainage in breast reconstruc- tion by DIEP free flap. This study is the first clinical one to evaluate the effi- ciency of fibrin sealant spray on free flap to decrease the postoperative drainage and patient’s hospital stay. MATERIALS AND METHODS We compared two groups of patients operated on, with and without the application of fibrin sealant. The protocol was designed as an open study. All procedures were in accord with the Standards of the Committee on Human Experimentation of the institution in which the experiments were done or in accord with the Helsinki Declaration of 1975. 18 The final research protocol was approved by our hospital committee. Mikae ¨l Hivelin and Laurent Heusse contributed equally to this work and considered as coauthors. 1 Plastic Surgery Department, Henri Mondor Hospital, Creteil, France 2 Faculte ´ de Me ´ decine, Universite Paris, 12-PRES Paris Est, France 3 Plastic Surgery Department, Ho ˆ pital Sud-Rennes-Rennes University, France *Correspondence to: Mikae ¨l Hivelin, M.D., Plastic Surgery Department, Henri Mondor Hospital, Creteil, France UMR 7054 CNRS and Faculte ´ de Me ´decine, Universite Paris, 12-PRES Paris Est, France. E-mail: [email protected] Received 24 January 2010; Accepted 24 May 2010 Published online 27 September 2010 in Wiley Online Library (wileyonlinelibrary. com). DOI 10.1002/micr.20812 V V C 2010 Wiley-Liss, Inc.

Fibrin sealant decreases postoperative drainage in immediate breast reconstruction by deep inferior epigastric perforator flap after mastectomy with axillary dissection

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FIBRIN SEALANT DECREASES POSTOPERATIVE DRAINAGE INIMMEDIATE BREAST RECONSTRUCTION BY DEEP INFERIOREPIGASTRIC PERFORATOR FLAP AFTER MASTECTOMY WITHAXILLARY DISSECTION

MIKAEL HIVELIN, M.D.,1,2* JEAN LAURENT HEUSSE, M.D.,3* NADIA MATAR, M.D.,1,2 CHRISTOPHE LEPAGE, M.D.,1,2

and LAURENT LANTIERI, M.D.1,2

Background: Serosanguinous drainage after breast reconstruction by deep inferior epigastric perforator flap (DIEP) can limit patient’sdischarge. We introduced fibrin sealant in immediate breast reconstruction by DIEP flap to reduce drainage after mastectomy with axillarydissection. Materials and methods: We performed an open study on 30 consecutive female aged from 28 to 63 years old. All underwentimmediate breast reconstructions by DIEP flaps after mastectomy and axillary dissection for cancer. Patients were divided in group 1 (N 515) without fibrin sealant and group 2 (N 5 15) where the flap, thoracic, and axillary areas were sprayed with 5 mL of liquid fibrin sealantbefore drains insertion. There was no difference in the patient’s BMI, height, weight or age between both the groups. Blake suction drainswere placed under the flap and in the axillary area. Results: No adverse effects were reported, after a 20-month median follow-up. Drain-age volumes or durations were not correlated to the patient’s BMI, nor the height, weight or age. Thoracic drainage duration was longerthan abdominal drainage in both the groups. Average drained volumes from the thoracic area were lower (427 vs. 552 mL; P 5 0.015)and thoracic drains were removed earlier (5.47 vs. 6.33 days P 5 0.022), in group 2 than in group 1. The length of stay was also reducedafter the use of fibrin sealant (5.53 vs. 6.33 days; P 5 0.032). Conclusion: This study introduce the interest of fibrin sealant to significantlydecrease the postoperative drainage volume and duration in the thoracic area after immediate breast reconstruction by DIEP flap.VVC 2010 Wiley-Liss, Inc. Microsurgery 31:18–25, 2011.

Deep inferior epigastric perforator (DIEP) flap is a refer-

ence technique for breast reconstruction by autologous tis-

sue, with total failure rates ranging from 0.5 to 10%.1–3

Failure rates have been more reported and studied than

minor complications such as hematoma or seroma, which

can alter the cosmetic result or delay adjuvant therapies.

Patient’s discharge after drain removal is still per-

formed in the great majority of surgery departments in

France, where the hospitalization cost is in its majority

defrayed by the public health insurance and the few rest

by patient’s own health insurance. Discharge with drains

in situ is sometime considered as increasing risk of infec-

tions.4 Early drain removal by an increase in patients

freedom of movement (real or felt) also motivate them to

move earlier and walk, contributing to reduce thrombo-

embolic risks, and improving their satisfaction; but

adverse effects make early drain removal after modified

radical mastectomy being still controversial.5,6

Fibrin sealant has been approved by the Food and Drug

Administration in 1998 to promote hemostasis in coronary

artery bypass surgery and splenic injury when uncontrolled

by standard suturing techniques.7 Fibrin sealant has been

shown to be effective and to be safe in animal models of

microvascular anastomosis repair8,9 and has been used suc-

cessfully to prevent hemorrhage and seroma. Its adhesive

qualities have been reported in visceral surgery for pancre-

atic wounds,10 in neurosurgery on cerebrospinal leaks11 or

in reconstructive surgery in the prevention or treatment of

seromas.12,13 Fibrin sealant has been successfully used in

visceral surgery, on splenic wounds origin,14 and in cardio-

vascular surgery15 for an hemostatic purpose. In esthetic

surgery, some authors have reported a reduction in severe

hematoma in face and neck lifts.16,17

We designed a clinical research protocol to assess the

efficacy of fibrin sealant (Tissucol1, Baxter, France) in

reducing the postoperative drainage in breast reconstruc-

tion by DIEP free flap.

This study is the first clinical one to evaluate the effi-

ciency of fibrin sealant spray on free flap to decrease the

postoperative drainage and patient’s hospital stay.

MATERIALS AND METHODS

We compared two groups of patients operated on,

with and without the application of fibrin sealant. The

protocol was designed as an open study. All procedures

were in accord with the Standards of the Committee on

Human Experimentation of the institution in which the

experiments were done or in accord with the Helsinki

Declaration of 1975.18 The final research protocol was

approved by our hospital committee.

Mikael Hivelin and Laurent Heusse contributed equally to this work andconsidered as coauthors.

1Plastic Surgery Department, Henri Mondor Hospital, Creteil, France2Faculte de Medecine, Universite Paris, 12-PRES Paris Est, France3Plastic Surgery Department, Hopital Sud-Rennes-Rennes University, France

*Correspondence to: Mikael Hivelin, M.D., Plastic Surgery Department, HenriMondor Hospital, Creteil, France UMR 7054 CNRS and Faculte de Medecine,Universite Paris, 12-PRES Paris Est, France. E-mail: [email protected]

Received 24 January 2010; Accepted 24 May 2010

Published online 27 September 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/micr.20812

VVC 2010 Wiley-Liss, Inc.

Patients and Study Design

From September 2003 to September 2008, 158 patients

underwent breast reconstructions by DIEP free flap in our

department. Fifty-three underwent immediate breast recon-

struction after mastectomy. Patients sustaining a mastec-

tomy for extended ductal carcinoma in situ with sentinels

lymph node dissection and six patients who underwent

bilateral reconstruction for prophylactic mastectomy were

excluded from this survey. Bilateral breast reconstructions

were also excluded as loss of fluid could hardly be com-

pared with those from two flaps added together. Moreover,

an increased time of the procedure and different hemody-

namic conditions could have influenced the postoperative

drainage. Thirty-two consecutive patients who underwent

an immediate breast reconstruction with DIEP flap after

mastectomy with axillary dissection (modified radical mas-

tectomy) were included. Two patients presented flap fail-

ures due to arterial thrombosis and were excluded. One had

received fibrin sealant while the other had not. The experi-

mental design was an open study on these 30 consecutive

subjects assigned chronologically into both experimental

groups. The first 15 patients were assigned in the first group

and the last 15 in the second one. Patients from group 1

were operated from January 2007 to February 2008 and

patients from group 2 were operated from February 2008 to

February 2009. All women included in the study were

more than 18 years old and were operated by the senior

author (L.L.) to prevent any bias imputable to a learning

curve. The durations of the full procedures were recorded.

They included the modified radical mastectomy, the imme-

diate breast reconstruction by DIEP flap, and a chemother-

apy port inset when indicated. Delayed wound healing,

postoperative abdominal hernia or late seromas, were not

considered as exclusion criteria.

Demographic and Morphologic Characteristic

for the Two Groups

The first group included 15 patients aged from 32 to

60 years (average: 43.6 6 7.1 years) with the body

mass index ranging from 22.2 to 29.8 (average: 25.8 62.47). The second group included 15 patients aged from

28 to 63 years (average: 46.3 6 9.9 years) with the

body mass index ranging from 22.15 to 29.75 (average:

26.7 6 4.7). We did not observe any significant differ-

ence between the two groups in terms of age, weight,

height, and body mass index (Table 1).

Fibrin Sealant

Fibrin sealant Tissucol1 (Baxter, Maurepas, France)

was used in this study. The kit for this fibrin sealant

was delivered in three different packs (1, 2, and 5 mL)

including four vials. The first contained: human fibrino-

gen, factor XIII, fibronectin, and plasminogen; the three

Table

1.DatasIssuedforGroups1and2andResults

ofStatisticalComparisons

Groups

Patients

Age(years)

Weight(kg)

Height(m

)BMI

Procedure

duration

(hh:m

m)

Thoracic

volume

(mL)

Abdominal

volume

(mL)

Thoracic

drain

remova

l

(POD)

Abdominal

drain

remova

l

(POD)

Discharge

(POD)

Maximal

follow-up

(months)

Group1:

DIEP

without

fibrin

sealant

Mean

6SD

43.676

7.13

69.876

9.21

1.646

0.06

25.816

2.47

7:446

0:49

552.006

129.80

325.336

80.03

6.336

1.05

4.406

1.12

6.336

1.05

26.976

4.09

Group2:

DIEP

withfibrin

sealant

Mean

6SD

46.336

8.21

72.4067.67

1.646

0.04

26.726

2.11

8:016

0:46

427.676

105.52

338.006

75.02

5.476

0.92

4.336

0.82

5.536

0.92

13.576

3.67

Pva

lue

between

group

1and2

P5

0.124a

P5

0.40a

P5

0.96a

P5

0.19a

P5

0.85a

P5

0.015a

P5

0.158a

P5

0.022b

P5

0.76b

P5

0.032b

aWilcoxontestfordemographic

data

orvo

lumes.

bLogranktests

onKaplan-M

eiercurvesfordrainagedurations.

Fibrin Sealant in Immediate Breast Reconstruction 19

Microsurgery DOI 10.1002/micr

others: aprotinin, thrombin, and calcium chloride, respec-

tively. The aprotinin solution was added in the powder

vial. Then the calcium chloride was mixed with the

thrombin. The two solutions previously obtained were

warmed up to 378C for around 6 min, and then taken in

two separate syringes attached to a connector with a Y

nozzle (Duploject1, Baxter, Maurepas, France).

Surgical Technique

All patients underwent a modified radical mastectomy,

with an immediate reconstruction by a DIEP flap. As all

patients had an axillary dissection, we performed the mi-

crovascular anastomosis on the circumflex scapular ves-

sels, as described.19 The flap was then inset and modeled

on the mastectomy area.

The first group included patients operated without the

use of fibrin sealant. In second group, since the flap was

modeled, we applied 5 mL of Tissucol1 on its raw sur-

face and edges and in thoracic and axillary undermining

(Figs. 1a and 1b). The 5 mL of fibrin sealant were

sprayed with a pressure of 1.5–2 bars through a syringe-

holder (Duploject1) linked to a compressed gas regulator

(Tissomat1, Baxter, Maurepas, France). With this tech-

nique, 250 cm2 could be covered with 5 mL of fibrin

sealant. Fibrin sealant was sprayed in a thin layer, far

from the vascular anastomosis.

Considering our previous experience in immediate

breast reconstruction by DIEP flap, we noticed thoracic

drains produce more drainage than abdominal ones due to

the mastectomy with axillary dissection. Thus we decided

not to apply fibrin sealant on the abdominal undermining as

it might not influence the patient discharge.

Drains were inset in a same fashion for both groups

with two suction drains in the axillary and pectoral area

and two Blake drains in the donor site, linked to separate

collectors. Fibrin sealant was always sprayed before the

inset of the suction drains to prevent their obstruction by

fluid glue. Two Blake suction drains were inserted under

the abdominal flap. The volume for the abdominal area

was the sum of the drainage from both drains.

All drains used in both groups of this study were Blake

silicone suction drains (Round BLAKE Hubless Silicone

Drains-Full Fluted, Ethicon, Johnson and Johnson medical

limited, Livingston, UK) systematically collected in Drain-

obag1 Lock (B Braun, Melsungen, Germany) bottles.

These 600-mL collectors performed a 800-millibars con-

stant depression and were exchanged immediately when

they were full or when they lost their depression.

As the axillary area and the area under the DIEP flap

were not separated compartments, it was not relevant to

distinguish their respective drains.

The flap donor site closure and the flap modeling

were performed as described previously.20 We performed

abdominal padding closure for the abdominal area.

Postoperative Care

All patients were monitored for 24 hours in the recov-

ery room. Drained volumes were recorded by nurses ev-

ery 6 hours and recorded in a patients database (Acti-

pidos1, Stylus SA-Ares, France). Each Blake suction

drains was removed when its drained volume was under

30 mL/day. This 30-mL limit has already been described

in the literature for drainage after breast surgery.21

All patients were discharged after the removal of the

last suction drain.

Assessment and Data Collection

Clinical follow-up were performed for all the patients

three times a day during their hospitalization, then sys-

tematically at 1 week, 2 weeks, 1 month, and 3 months

and after these protocol exams as long as patients came

to the clinic for long term follow-up.

Figure 1. Fibrin sealant (Tissucol1) sprayed through a nozzle

(Duploject1) to cover the de-epidermized part of the DIEP flap and

the thoracic undermining (1a). Fibrin sealant sprayed to cover the

edges and the posterior part of the DIEP flap and the axillary

undermining before the drain inset and the closure (1b).

20 Hivelin et al.

Microsurgery DOI 10.1002/micr

Data were collected prospectively for each groups for:

age, height, and weight, drained volumes in the abdomi-

nal and thoracic areas, postoperative day (POD) for drain

removal and day of discharge. Abdominal and thoracic

drain bottles were distinguished. Results were compared

between the two groups, for the total drainage volume in

the thoracic area, abdominal area, the date for drain re-

moval in these areas, and the day of discharge, using

JMP 5.1.21 software (SAS Institute, Cary). The search

for correlation between the volume and duration of tho-

racic drainage and patients BMI were performed with

nonparametric Spearman rank tests. Wilcoxon tests were

used to compare the total drained volumes in the thoracic

area or abdominal area between the two groups. For the

duration of drainage and length of stay, log-rank test

were performed on Kaplan–Meier models.

RESULTS

Patients Outcomes

All patients included in the study underwent an

uneventful procedure with a termino-terminal anastomosis

on axillar circumflex vessels. The procedure duration for

both groups ranged from 7 hours and 15 minutes to 9 hours

and 45 minutes, with a global average of 8 hours and 34

minutes. There was no difference between group 1 and 2

considering the procedure duration (Table 1). The average

maximal follow-up was 26.97 6 4.09 for group 1 and 13.57

6 3.67 months for group 2. No patients were lost to follow-

up in both groups as the 3-months postoperative clinical

exam. No immediate or late adverse effect at the maximal

follow-up were reported for both groups. There were no al-

lergic reaction nor fever and we did not noticed any sero-

conversion or abscess. No major side effect was reported,

nor drain obstruction, specially in the second group. We

didnot reported blood, platelets or coagulating factors trans-

fusion in both groups, as patients were selected for the ab-

sence of secondary emergency procedure (revision for

hemostasis and/or anastomosis failure). We noticed two

seromas occurring at day 10 on the abdominal area in group

2 and at day 12 on the axillary area in group 1. These sero-

mas did not required evacuative puncture. Two other

patients presented limited fat necrosis with delayed wound

healing. Seromas and fat necrosis did not threatened the

cosmetic result at the final follow-up, nor delayed the adju-

vant chemotherapy that was initiated in the 6 weeks postop-

eratively.

Effect of Fibrin Sealant on Total Volumes Drained

in the Thoracic and Abdominal Areas

In group 1, thoracic drained volumes ranged from 330

to 740 mL (average of 552 6 129 mL), while total thoracic

drained volume in group 2 ranged from 290 to 685 mL (av-

erage: 427 6 143 mL) (Table 1). There was a significant

decrease in the volumes collected from the thoracic area in

the group treated with fibrin sealant (P 5 0.015). In group

1, abdominal drained volumes ranged from 210 to 520 (av-

erage: 325 6 80 mL) and in group 2 from 285 to 470 (aver-

age: 338 6 86 mL) (Table 1) with no significant difference

between both the groups (P 5 0.158).

With or without fibrin sealant, drained volumes for

the axillary and thoracic area were higher than the ab-

dominal ones.

The daily drainage might appear to be more accurate

to compare both groups (as we choose an arbitrary limit

of 30 mL/day for the drain removal). The average daily

drained volumes for the thoracic area were compared.

The fibrin sealant group had lower average daily drained

volumes for the thoracic area than the group without

sealant (P 5 0.0343).

In our study, when the increase in abdominal22 and axil-

lary23 drained volumes has been described to be related to

an increase in BMI, only the average daily abdominal vol-

ume was correlated with the BMI in the fibrin sealant group

(second group) (P 5 0.03) (Fig. 2). All other Spearman cor-

relation test between BMI and total volume of drainage or

drainage duration were not significant.

Nevertheless we compared the ratio of these average

drained volumes on the BMI by using the average daily vol-

ume/BMI ratio (Fig. 3) to assess and rule out any bias related

to patients BMI. The average daily volume/BMI ratio was

still significantly lower in the fibrin sealant group for the tho-

racic drainage (P 5 0.0152) (Fig. 3a), while there was no

difference for the abdominal one (P5 0.589) (Fig. 3b).

We have also analyzed the relation between the pro-

cedure duration and the abdominal and axillary drained

volumes and we could not find a correlation.

Figure 2. Linear fit (interrupted line for the 95% confidence interval)

of daily average abdominal volume by BMI in the fibrin sealant

group. A Spearman test (P 5 0.0308) illustrated the correlation

between the daily average abdominal volume and the BMI in the

fibrin sealant group.

Fibrin Sealant in Immediate Breast Reconstruction 21

Microsurgery DOI 10.1002/micr

Effect of Fibrin Sealant on Postoperative Delay

Before Drain Removal and Patient Discharge

The duration of thoracic drainage was significantly

longer than the abdominal one in both the groups. Indeed,

only one patient from group 2 had longer abdominal

drainage than the thoracic one. (confirmed by a Wilcoxon

signed rank test on a matched pair analysis).

The mean time to thoracic drain removal in control group

1 was 6.33 days while group 2 women treated with fibrin

sealant were drained during 5.47 days (Table 1). This differ-

ence was statistically significant (P5 0.022) (Fig. 4a). There

was no significant difference considering the duration of ab-

dominal drainage between both the groups (Fig. 4b).

Group 1 patients were discharged at a mean of 6.33

days versus 5.47 days for group 2 (Table 1). This earlier

discharge in the fibrin sealant group was also significant

(P 5 0.032) (Fig. 4c).

Figure 3. Comparison of both groups for the thoracic and abdomi-

nal drainage using the daily average drained volume/BMI ratio. As

for the comparison using gross drained volumes, daily average tho-

racic volume/BMI was lower in group 2 (P 5 0.0152) (3a) and there

was no significant difference between groups 1 and 2 for abdominal

(P 5 0.589) (3b).

Figure 4. Comparison between groups 1 and 2 for thoracic drain

removal (4a), abdominal drain removal (4b), and discharge (4c).

(Log-rank tests performed on Kaplan–Meier curves).The duration

for thoracic drainage was shorter in group 2 (fibrin sealant) than in

group 1 (P 5 0.022), so as the length of stay (P 5 0.032), while

there was no statistical difference between both groups for the

abdominal drainage duration (P 5 0.76).

22 Hivelin et al.

Microsurgery DOI 10.1002/micr

DISCUSSION

Fibrin sealant reproduces the fibrino-formation or final

stage of coagulation, when fibrinogen is converted into

fibrin under the effect of calcic thrombin and factor XIII. It

includes six components: fibrinogen, factor XIII, calcium

thrombin, fibronectin, aprotinin, and plasminogen. Fibrino-

gen is an adhesive that is activated by thrombin to form

monomers of fibrin. The factor XIII is a catalyst, activated

by calcium thrombin, responsible for the polymerization of

the fibrin monomers. Calcium thrombin concentration influ-

ence the kinetic of adhesion and the fibrin network density.

Fibronectin act as an inductor of healing and aprotinin and

plasminogen are both inhibitors of fibrinolysis.

This fibrin sealant (Tissucol1) was extracted from

human plasma, processed to ensure its safety and trace-

ability (selection of donors, quarantining of plasma, test-

ing for viral contamination by Polymerase Chain Reac-

tion, viral inactivation processes, measures with regard to

bovine spongiform encephalopathy, specially for aprotinin

from bovine origin). Before any processing, donors were

screened during the plasma harvesting and 3 months after

for human immunodeficiency virus, Epstein-Barr virus,

cytomegalovirus, and hepatitis A, B, and C.24

Two factors influence the formation of seromas: lym-

phatic vessels disruption and the creation of a cavity

caused by the removal of tissue. Fibrin sealant’s hemo-

static and adhesive properties can both prevent seromas

by sealing open tissue channels and coapting the elevated

skin flap to underlying tissues to eliminate surgically cre-

ated dead space.25

The results of fibrin sealant usage to prevent lymphor-

rhea after mastectomy and axillary node dissection can

seem controversial.26–29 Low amounts of sprayed fibrin

sealant (2–5 mL) had already been studied in breast sur-

gery.21 Same results on the decrease on the total drained

volume, with fibrin sealant use, have been described after

total or modified radical mastectomy.

We acknowledge the limits and bias of our study con-

sidering the negative controls. It was not possible to use

fibrin sealant with one component missing as suggested as

any of the seven components have an influence on coagula-

tion. The aim of such a sham sealant would have been a

double blindness study, which has an importance if the sur-

geon could modify the procedure in a way influencing the

outcome. However, fibrin sealant was not compared or

associated to a surgical technique to reduce the drainage

(such as padding suture for instance). Moreover, a sham

sealant would have a limited influence on the assessment of

the amount of fluids by nurses. The last one were not aware

whether the patient had received fibrin sealant or not.

We choose a data collection and an assessment in a

prospective fashion to reduce the bias. We arbitrarily

choose the first group of patients to be operated without

fibrin sealant while the fibrin sealant has been used in

our department for this indication for more than 5 years.

We could also have alternated the patients between both

the groups. As surgical procedures were performed by

the senior author, who have performed more than 450

DIEP flaps, and fibrin sealant used for more than 5 years,

we limited the effects imputable to a learning curve.

Arterial and venous anastomosis had to be avoided

when using the spray, as intravascular application of

fibrin sealant could result in life-threatening thromboem-

bolic events.7 In two studies on the use of fibrin sealant

to complete vascular anastomosis,30 or to prevent any

kinking on the anastomosis,31 fibrin sealant was not

sprayed under pressure.

We didnot noticed any drain obstruction after fibrin

sealant use. Drain obstruction with underestimation of the

drained volume has been cited32 but never well docu-

mented. To prevent any drain obstruction, we always

sprayed the sealant before their inset.

A correlation between the BMI and the exposed sur-

gical area has already been described by some authors in

studies on the efficiency of fibrin sealant to decrease

seroma after radical mastectomy.33 In our study, we did

not find any correlation between the BMI and the drained

volume nor the duration of drainage, in the thoracic or

abdominal areas, with or without fibrin sealant except for

the average daily abdominal volume in the second group

(Spearman test; P 5 0.0496). The main interest of fibrin

sealant in this series might be mainly explained because

of its efficiency on the axillary drainage after lymph node

dissection.

We focused on patients undergoing immediate breast

reconstruction as the thoracic drainage seemed a real lim-

iting factor for their discharge from the hospital. Suction

drain removal is known to be limiting factor for dis-

charge after mastectomy with axillary dissection and a

prolonged drainage seems not to prevent late seroma for-

mation.34 The removal of abdominal drains was statisti-

cally earlier than the thoracic one. A potential decrease

in the abdominal drainage duration would not improve

the delay before discharge without drain after immediate

breast reconstruction.

Some authors have assessed the cost-effectiveness of

fibrin sealant versus drain placement in breast surgery.29

In the French public health system, one day in a surgical

unit costs about 1,504 euros, while a 5-mL fibrin sealant

dose cost about 306 euros. As it shortened the length of

hospital stay, the application of fibrin sealant is cost

effective. The potential reduction in seroma formation

and in early surgical revisions seemed particularly inter-

esting on this patient subset, prompt to receive chemo-

therapy in the postoperative period.

Axillary drainage persisted but was significantly

reduced by fibrin sealant. A prospective comparison

between fibrin sealant only versus drain only, focusing on

Fibrin Sealant in Immediate Breast Reconstruction 23

Microsurgery DOI 10.1002/micr

the occurrence of late seroma requiring puncture, would

be interesting.

As we performed abdominal padding closure for the

abdominal area, this could explain our lower amount and

duration for the abdominal drainage when compared with

the thoracic one in group 1. Axillary padding was not an

option in our study, considering the risk of constricting

the pedicle. The absence of drainage after axillary dissec-

tion, increasing the risks of infections,35 seems dangerous

for an immediate breast reconstruction on a women who

can underwent chemotherapy. This additional morbidity

might delay the inset of chemotherapy in this immediate

breast reconstruction subset,36,37 even if this point

remains controversial.38

Internal mammary vessels are a gold standard for DIEP

flap inset39,40 but it puts away one possibility of coronary

bypass and add some morbidity.41 However when a modi-

fied radical mastectomy is performed, the use of the thor-

aco-dorsal vessels seems appropriate as they are already

exposed.42 Circumflex scapular vessels have the advantage

of being dissected in immediate reconstruction after axil-

lary lymph node dissection and does not jeopardize the vas-

cularization of the latissimus dorsi. In secondary recon-

struction, the dissection can be difficult because of fibrosis

caused by radiotherapy and previous procedure.19

Tissucol1 is extracted from pooled human plasmas

and processed to ensure its safety and traceability but

parvovirus infections have been reported,43 thus autolo-

gous fibrin sealant such as Vivostat1, (Alleroed, Den-

mark)44 or Magellan1 (Medtronic, Minneapolis) might

seem interesting.

A recent study on sealant use45 concluded on the ab-

sence of efficacy and the induction of an important

inflammation. The glues studied were not fibrin sealants

but synthetic polyethylene glycol hydrogel (COSEAL1,

Baxter, Maurepas, France) designed for an external use,

or a bovine albumin and glutaraldehyde solution (Bio-

Glue1, Cryolife Europa, Guildford, United Kingdom)

designed for liver and vascular surgery. These composi-

tions might explain the important foreign body reaction

described, which we didnot faced with fibrin sealant.

The use of fibrin sealant on the abdominal area would

not improve the delay before discharge as the abdominal

drainage was statistically shorter than the thoracic one in

both groups. Fibrin sealant seems to have an interest in

immediate breast reconstruction by DIEP flap after mas-

tectomy with axillary dissection, to decrease drained

volumes in the thoracic area and the length of stay. The

absence of axillary dissection in secondary breast recon-

struction by DIEP flap might explain the higher abdomi-

nal drained volumes when compared with the thoracic

ones. In secondary breast reconstruction by DIEP flap, it

might be more efficient to spray the fibrin sealant on the

abdominal undermining only.

CONCLUSION

This study introduce the interest of fibrin sealant to

decrease the postoperative drainage immediate breast

reconstructions by DIEP flaps. Fibrin sealant use was

safe, with a 20-month median follow-up. Fibrin sealant

has significantly decreased the total volume and duration

of postoperative drainage in the thoracic area, compared

to controls. In both the groups, the duration of thoracic

drainage was longer than the abdominal drainage. These

drainages were generally not correlated to the patient’s

BMI, nor the height, weight or age in our series. The

length of stay was significantly reduced after the use of

fibrin sealant when compared with controls.

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