"1,il:::J"J`,,:).:.r)n:1ffi .::::::.::::,*1

1503
frel
C O I , Y R I C H To 2 O O I B Y T H I
'OURNAL oF BoNE AND IoINT SURGERY,INCoRPORATED
LJspoF FrsRrNSEnTANTTo
RpoucE BrooDy DnnTNAGEAND
HEvrocLoBrNLoss AFTER
Torer KxEE AnruRopLASTy
,"1,il:::J"J',,:).:.r)n:1ffi
.::::::.::::,*1:
M.A. MON'I, IVlD,S.G. BURKS,I]SN, S.L. MAYERS,
PHD, AND
W.D. SPOTNITZ,
MT)
Investigation
perfornrcJtr (Jnivt.r:ityoJ'\tirginhFlealth Systenr,
Charlottesville,
Virginia;GoodSamantanHospital,Boltitrtore,
Maryland; Huglston Sports|v,tcdicineCIinic,Columbus,Georgia;
and Midiest Orthopaedics,Chicago,IIIinois
Background:A phase-llltrial that includedfifty-threepatients
undergoingunilateralprlmarytotal knee arthroplastywith cementwas conductedto investigate
the hemostaticefficacyof fibrinsealant.
Methods:Following
cementingof the joint, 10 mL of fibrinsealantwas sprayedonto
the woundbeforetourniquer
deflationand woundclosure.No placebowas used in the controlgroup.
All patientsreceiveddrains.
Results:within twelve-.hours
after the surgery,the amountof bloodydrainagewas 1g4.5
t 2g.g mL (meanand
standarderror)in the fibrin-sealant
group(information
availablefor twenty-three
patients)and 40g.3 + 54.6 mL in
the controlgroup(information
availablefor twenty-three
patients)(p = O.OO2,
after adjustmentfor variancein the
time that the drainagewas measured).on the hrst postoperaiive
day,the hemoglotinlevel had decreasedby
20'1+ 2'L g/L in the fibrin-sealant
group(information
availablefortwentytwopatients)and by 27.3+ 2.r
{Lin
the controlgroup (informationavailablefor twenty{ourpatients).
nfter iolustment foi baselinevalues,the decreasein the hemoglobinlevelwas 283% less in the fibrin-seaiant
groupthan in the controlgroup(p = o.oo5,
95%confidence
limits=L0.2,43.7). Therewereno seroconversilns
in the fibrin-sealantgroup.
conclusion:Theseresultssuggestthat fibrinsealant.an
suret/ieducebloodydrainagefollowingtotal knee arthroplastywhilemaintaininghigherhemoglobinlevets.
ubstantially decreasingpostoperativebloody drainage
following total knee arthroplasty n.rayreduce patient
morbidity, the length of the stay in the hospital, and
costsby eliminating the needfor transfusionsand, potentially,
fbr drains.Furthermore,the useof effectiveintraoperativehe_
mostaticagentsmay facilitatethe earlieradministrationof anticoagulantsas prophylaxis againstdeep_veinthrombosis,
a
measurerecommended in a recent large_scale
study,. Since
1972,fibrin sealantshavebeenincreasinglyusedashemostatic
and sealingagentsin a variety of surgicalspecialties,.,,
includ_
ing,
total
knee
replacement5.
Thus,
it
was
hypothe_
_recently,
sized that fibrin sealantcould improve hemostasisfoilowing
kneearthroplastv.
Materials and Methods
multicenter, randomized,controlled phase_
g_rospective,
,{A \III (expandedclinical) trial was performed, with
the in_
vestigatorsblinded until the applicationof fibrin sealantjust
prior to wound closure.After giving their informed written
consentto,a protocol previouslyapprovedby institutional re_
view boardsand the Food and Drug Administration, patients
with osteoarthritisunderwent primary un-ilateraltotal knee
arthroplastywith cement,under tourniquet control, with
he_
mostasisachievedwith use of cauterizationand diathermv.
(Neither hemodilution nor hypotensiveanesthesia*u,
u..d.)
Patientswith a baselinehemoglobinlevelof <l l0 g/L and evi_
dence of a-bleeding or metabolic-basedhen-rolyiicdisorder
wereexcludedfrom the study.In the fibrin-sealantgroup, fol_
lowing cementingof the joint and beforetourniquei defiation
and wound closure,l0 mL of an investigational,virally inacti_
vated fibrin sealant(euixil; Omrix Biopharmaceuticals
SA,
Brussels,Belgium) was sprayedonto the raw surfacesof the
exposedbone and soft tissueat a distanceof approximately
l5
cm with use of a dual-syringe spray device-(International
Patent Application Number pCT/Ep96103975).No placebo
was used in the control group. AII patientshad placement
of
drainsaccordingto standardpractice,and all receiveda 30_mg
dose of enoxaparinsodium (Lovenox) subcutaneously
everv
r504
.
l'l{E JoultN-AL otj lloNE & JOIN'I SURGERY IB,S.OII.G
V()r.uML[13-A' NuruBEu l0 . Oc'foBER 2001
'l'o
R E D u ( l L [ J t . ( ) o l ) Y L ) R . A I N A ( ] LA N l )
U S E O I . F . I R I t I NS t , t L r r N 1
H E M O ( ] L o I } I N L O S S A I l . O R T O T A L K N I , I JA R ' I I i I I . o P I - A S T Y
No. of Patients
Testedat Baseline
(Pos./Neg.)
No. of Patients
Testedat 3 Mo.
(Pos./Neg.)
No. of Patients
Testedat 6 Mo.
(Pos./Neg.)
A n t i - H l VA b
36 (0/36)
42 (O/42\
47 (o/4!)
Anti'HAV Ab
46 (7/39\
42 (4/38)
38 (4/34).
Anti HCVAb
43 (o/43)
42 (o/42]|
4L (O/47],
A n t i - H B cA b
40 (4/36\
37 (3/341
4r (2/39)
Anti-HbsAg
46 (O/46\
42 (O/42)
40 (o/40)
ViralMarker
lgG
tgM
A n t i ' H l VA t )
Anti-HAVAb
7 (o/r)
r (r/o\
hours after the
twclvc hotrrs,starting twelveto twenty-firr'rr
thron-rbosis'
opcratiou,fbr prophylaxisirgainst deep-vcin
0
o
of fibrin sealantwereuoted.Ninc paticnts(16%r)in the librinsealantgroup reccivedtransfusions(fotrrteentrnits of bloocl
patients(50%')in
or blood products)cotnparedwith firurteer.r
or blood prodof
bltlod
r-rnits
(twenty-seve
n
the controlgroup
patient(4olt1
one
in
=
developcci
herlratonla
trcts)(p 0.19).A
i'
the cor.rtrol
patie'ts
i'
tbtrr
a'd
group
in the hbrin-sealant
any of thc
for
seroctlnversion
had
(14%).
patients
No
group
markerstested(TableI).
Results
r T - t h c l r c r r t r r t c t rt t t t dc < t n t r ogl r ( ) u P \( c o n s i s t i n og i t w e n t y y )c r cs t r t i s t i I f i u " a n . l t w e n n ' - c i g hpt l t i c r t t s ,r e s p e c t i v e lw
height'
weight,
age,
gender,
tcl
resPect
rvith
callyhomogcnous
mediprior
and
history,
medical
to
rcgard
with
,rbnornralitics
cations,witl.rone exception:eightpatientsin the fibrin-sealant
Discussion
acid prior to surgeryas opgroup were taking acetylsalicylic
groLrphad lessbloodydrainT n this stud%the fibrin-sealant
in the controlgroup'
poscclto four patier.rts
i' the
I aeei' the initial twelvehoursand a smallerdecrease
the amount of
Within twelve hours postoperatively,
conthe
did
than
the
surgery
levelon the day after
drainagewas 184.5+ 28.9mL (unadjustedtneanand standard henioglobin
hemostatic
of
such
use
the
that
argued
trol gioup. It has been
error) i.t the fibrin-sealantgroup (informationavailablefor
becauseof
n-laybe unnecessary
ug.ni, du.ing ioint replacerne+t
+
control
the
in
mL
54.6
408.3
and
twenty-threepatients)
autologous
with
replirced
be
can
blood
lost
which
tf,e easewith
group (information availablefor twenty-threepatients)'In
bloodo.While autologouspredonatedblood is not
predonated
the
on
level
hemoglobin
mean
the
group,
ih. db.in-...lant
transmission,the ratesof
the risk of viral disease
with
associated
first postoperativeday was 1I 4.8 X 2-7glL ( information avail(the nvo factors
overgrowth
bacterial
and
error
administrative
(20'l
!2'l
of 14.9o/o
ableior twenty-twopatients),a decrease
posttransfusion
immediate
with
associated
frequently
most
I
n
t
h
e
l i t h t h e b a s e l i n e( 1 3 4 ' 9t 2 ' 6 g / L ) '
g / L ) c o m p a r e cw
the use of
with
associated
those
with
compnrable
aie
deaths)
postfirst
the
Iontrol giorlp, the mean hemoglobinlevel on
have
studies
recent
of
homologousblood'. Moreover,authors
operativJday was 104.9+ 2.6 glL (informationavailablefor
reblood
homologous
of
arguedthat ..singautologousillstead
(27'3 ! 2'l glL)
of 20-7o/o
twenty-four patients),a decrease
On
costn'
additional
considerable
at
,l.-rlt,in little healthbenefit
comparedwith the baseline(132.2!2.5 glL)'
the other hand, evenwith current safetyguidelinesand the imwas
the
drainage
that
time
the
for
After adjustment
of nucleicacid testing,thereremainsa risk of homeasured,the drainagewithin twelvehours postoperatively plementation
human immunodeficiency
transfusion-transmitted
less(950loconfidence mologous
in the fibrin-sealantgroup was 55-6%o
t'irus''"'' Thus, there
hepatitis-C
and
=
virus,
hepatitis-B
(P
virus,Iimits = 27.1 to 7-3.0)than that in the control group
benefitsto minimizand
economic
health
strong
be
continueio
0.002). After adjustment for preoperativehemoglobin levtype'
any
of
rates
transfusion
postoperative
ing
in hemoglobin on the first postoperative
els, the clecrease
Another potential advantageof improved hemostatic
less(957oconfiday in the fibrin-sealantgroup was28-9o/o
techniquesis that they may help to reducethe prevalenceof
dencelimits = 10.2to 43.7)than that in the control group
the seriousand sometimesfatal thromboernboliceventsasso( p= o . o o s).
ciated with this procedure" by allowing prophylaxisagainst
Differencesbetween the fibrin-sealantgroup and the
deep-veinthrombosisto be startedearlier.It has been argued
control group with regard to transfusion requirementsand
more intensive prophyla-xisagainst deep-vein
adverseiu.t-tit following surgery did not reach significance thai earlier,
needed'.Unfortunately,the use of anticoaguis
thrombosis
with the numbers available;however,trendsin favor of the use
rll
r505
I
I
T r r E j o u l t N , \ L o I l | o N h & I o r N r S u l r c E I { y. l B l s . o l { c
V o L U t v r [8 3 , A . N u M r ] E Rl 0 . O ( ; T o B u R2 0 0 1
U s r io l , F I r l R r NS c a r - l N ' r ' T oR E D U c EB L o o r ) y D l { A T N A GAEN n
H I]I\4O(] I,o ItI N Lo s s A F.I.ER'fo TAI, K r. LL A R.IH Ro PLAs'I.Y
lants [or routine prophylaxis can lre associatedwith increased
blood loss''. A rirndornized, controlled, clinical trial was recently condrrcted in Israel with usc of ir protocol sintilar kr the
onc r-rsc<l
in thc present stucly, cxccpt tl.rat patients reccived
anticoasulation therapy preoperatively as I,vcllirs postoperatively'. In that stutly, fibrin scalant rvasshown to sigrrificantly
r c d u c c b l o o t l l o s s ( p < 0 . 0 0 t ) , h c n r o g l o b i nl e v c l s( p < 0 . 0 0 1 ) ,
irrrrltransfusion rccluiremcnts(p = 0.004) firllowing total kncc
arthroirlasty.
'l'hus,
f l b r i n s e a l a n tr c d u c c s[ r k r o t l yr l r a i n l g c t i r l l o w i n g
t o t r r lk n e c a r t h r o p l a s t ya n d r n i n i u r i z c sc j c c r c a s cisr r p , r 5 1 . , U . r l t i v c h c r n < l g k t b i nl c v e l s . F i b r i n s c a l a n t n r a y l h c i l i t a t c n t o r e
a g u r c s s i v ca n t i c o a g t r l a t i o nt o r c r l u c c t l r c p r . c v a lnec c o i p o s t o p c r a t i v e c l c c p - v c i n t h r o m t r o s i s , p u l n t o u a r v e n r b o l u s ,a n c l
't'his
clcathfirllowing knce arthroplasty.
s t u c l yc o n l l r r n s t h c
v i r r l s a l ' c t ya n c l l o w r a t c o f c o r t r p l i c a t i o n sa s s o c i a t c tw
l ith ti[ r l i n s c a l a n t .:
-fissue
AdhesiveCenter, University of \uirginia Health systcm, MI{4
Iluilding, Roorn 3122, Charlottesville,VA22908. E-rn:ril addressfor
G.W.Wrng: [email protected]
i
I
j
D . S .I I u n g t ' r l i r r d ,M t )
M.A. Mont, N4D
D c p a r t r n e n to f O r t h o p a c d i cS u r g e r y J o h n sH o p k i n s U n i v e r s i t y ,p r o f e s s i o n i r l( ) { l l c c t l u i l c l i n g ,S u i t eG l , 5 6 0 1 L o c h l { a v c n l l o u l e v r r r c l ,l a l t i m o r c ,
NIt)21219
O . C i .S i r v o r yM
, [)
I ILrghston
S p o r t sM e d i c i n eC l i n i c , 6 2 6 2 V e t e r a r r P
s a r k w a y ,P . O .I l o x 9 5 1 7 ,
( ) o l r r n r b u s(,l A 3 I 9 0 t l
A . ( i . I l o s c n b c r g ,M D
[ ) c p a r t n ] e n t o f O r t h o p a e d i c S u r g e r y ,l { u s l r P r e s b y t e r i a n , s t .[ , t r k c ' s
M c d i c a l ( l c n t e r , 1 7 2 5W e s t H a r r i s o n S t r c e t ,S u i t e 1 0 6 3 ,O h i c a g o ,
I t . 6 0 ( iI 2
Although none of thc authors has receivedor will receivebcr.rclltsfirr pers o n a lo r p r o f i s s i o n a lu s ef i o m a c o n t m e r c i a lp a r t y r c l a t e dd i r e c t l y o r
i r r d i r c c t l yt o t h e s u b j e c to f t h i s a r t i c l e ,b e n e f i t sh a v eb c c n o r w i l l b c
received,but are clirectcdsolely to a researchftrnd, foundation, eclucirt i o n a l i n s t i t u t i o n ,o r o t h e r n o n p r o f i t o r g a n i z a t i o nw i t h w h i c h o n e o r
n r o r c o f t h c a u t h o r si s a s s o c i a t e dF. u n d s r v e r er e c e i v e di n t o t a l o r p a r t i a l
s u p p o r t o l ' t h e r e s e a r c ho r c l i n i c a ls t u d v p r e s e n t e di n t h i s a r t i c l e . ' t ' h c
f i r n c l i n gs ( ) u r c ew a s O m r i x B i o p h a r m a c e u t i c a l s .
NoIt: llll) authors thaifk Ji[] Patrie for hrs assislaIce wltl ilte stdtisttaal analvsrs.
( i . f . W ; r r r gM
, I)
S . ( i .l i u r k s , l l S N
S . 1 . i.V l a y c r sI,) h l )
\ V .l ) . S p ( ) t n i t z ,r \ , I1)
n""lor,
white RH,RomanoPS. Zhou H, RodrigoJ. Eargarw. Incrdencc,^o , .l"tutf
c o u r s eo f t h r o m b o e m b o loi cu t c o m e sf o l l o w i ntgo t a lh i p o r k n e ea r t h r o p l a s t y .
]
Arcltlntem Med 1998:158:1525-31
i
gA
. -^;^^f rfi^
Rrdn<aviah
M
GnrrhEn
R,,'n^,,{
T trih/i^ -^-t-^f
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resternotomy
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"^::::---"'
' or
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1 9 8 9 ; 9 7 : 1 9 42 0 3 .
]
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i