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31/07/13

Evolution of hemostatic agents in surgical practice

Evolution of hemostatic agents in surgical practice


Chandru P. Sundaram and Alison C. Keenan

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Abstract
Objective:
T opica l h em ost a t ic a g en t s a r e u sed in a w ide v a r iet y of su r g ica l set t in g s, a n d t h e ev olu t ion of t h is cla ss of su r g ica l t ools is a n in t er est in g t opic. W e r ev iew ed a n d ou t lin ed t h e h ist or ica l pr og r ess of t opica l h em ost a t s in t o pr esen t da y su r g er y a n d u r olog y , a n d h ig h lig h t oppor t u n it ies for fu t u r e r esea r ch .

Materials and Methods:


A MEDLINE sea r ch of a ll a v a ila ble lit er a t u r e con cer n in g sev er a l cla sses of t opica l h em ost a t ic a g en t s w a s per for m ed. Fibr in s sea la n t s, Gela t in spon g e h em ost a t ics, cy a n oa cr y la t e a dh esiv es, ox idized r eg en er a t ed cellu lose, a n d m icr ofibr illa r colla g en w er e in clu ded. Refer en ces w er e ch osen fr om a br oa d r a n g e of su r g ica l lit er a t u r e.

Results:
T opica l h em ost a t ic a g en t s h a v e h ist or ica lly t a k en a dv a n t a g e of a w ide v a r iet y of m ech a n ism s for h em ost a sis. Fibr in sea la n t s h a v e a r ich h ist or y a n d la r g e pot en t ia l for fu r t h er a pplica t ion s. Gela t in spon g e h em ost a t ics h a v e been w idely u sed sin ce t h eir in t r odu ct ion , bu t h a v e ch a n g ed lit t le. Cy a n oa cr y la t e a dh esiv es h a v e a u n iqu e m ech a n ism a n d oppor t u n it y for n ov el a pplica t ion s of ex ist in g pr odu ct s. Ox idized cellu lose w a s or ig in a l in t h e u se of pla n t -ba sed com pon en t s. Micr ofibr illa r colla g en h em ost a t s h a v e ev olv ed t o a w ide v a r iet y of for m a t s.

Conclusions:
A r ev iew of t h e ev olu t ion of t opica l h em ost a t ic a g en t s h ig h lig h t s oppor t u n it ies for pot en t ia l n ov el r esea r ch . Fibr in sea la n t s m a y h a v e t h e m ost oppor t u n it y for a dv a n cem en t , a n d u n der st a n din g t h e h ist or y of t h ese pr odu ct s is u sefu l. W it h t h e dr iv e in u r olog y for m in im a lly in v a siv e su r g ica l t ech n iqu es, a da pt a t ion of t opica l h em ost a t ic a g en t s t o t h is su r g ica l a ppr oa ch w ou ld be v a lu a ble a n d offer s a n oppor t u n it y for n ov el con t r ibu t ion s.
Key words: Fibr in

sea la n t , g elfoa m , h em ost a t ic a g en t s, m icr ofibr illa r colla g en , ox idized r eg en er a t ed

cellu lose

INTRODUCTION
A s a n y su r g eon w ou ld a g r ee, h em ost a sis is of cr it ica l im por t a n ce du r in g a ll su r g ica l pr ocedu r es. A fu n da m en t a l pr in ciple of g ood su r g ica l t ech n iqu e is m in im iza t ion of blood loss, a n d pr esen t da y su r g eon s h a v e a w ide v a r iet y of a g en t s a n d t ools t o a id t h em in t h is en dea v or . Few u r olog ic su r g eon s w ou ld be ea g er t o u n der t a k e r en a l pr ocedu r es w it h ou t t h e u biqu it ou s elect r osu r g ica l u n it . A lt h ou g h u sed less fr equ en t ly t h a n sim ple elect r oca u t er y , t opica l h em ost a t ic a g en t s a r e u sefu l in m in im izin g blood loss a n d in t u r n su r g ica l m or bidit y . A lt h ou g h n o a id in h em ost a sis ca n n eg a t e t h e im por t a n ce of g ood su r g ica l t ech n iqu e, ev en t h e m ost t a len t ed su r g eon h a s en cou n t er ed per sist en t bleedin g w h ich h a s r equ ir ed focu sed a t t en t ion . Oft en a t opica l h em ost a t ic a g en t is h elpfu l in t h ese sit u a t ion s, a n d t h e ev olu t ion of t h ese a g en t s is a n in t er est in g t opic in su r g ica l h ist or y . In t h is a r t icle, w e r ev iew t h e h ist or y a n d ev olu t ion of select ed h em ost a t ic a g en t s a n d h ig h lig h t a r ea s w it h pot en t ia l for fu t u r e a dv a n cem en t s. Specia l a t t en t ion is pa id t o t h e fibr in sea la n t s, w h ich h a v e a n in t er est in g h ist or y a n d sig n ifica n t pot en t ia l for n ov el u r olog ic r esea r ch .
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Evolution of hemostatic agents in surgical practice

A REVIEW OF HEMOSTASIS
Hem ost a sis is a com plex pr ocess r equ ir in g t h e delica t ely coor din a t ed a ct iv a t ion of pla t elet s a n d pla sm a clot t in g fa ct or s t o for m a pla t elet -fibr in clot .[1 ] T h is ca n be div ided in t o t w o dist in ct pr ocesses, pr im a r y a n d secon da r y h em ost a sis. Pr im a r y h em ost a sis r esu lt s in t h e for m a t ion of soft pla t elet plu g s, w h ich in t u r n a r e st a bilized a n d cr oss-lin k ed du r in g secon da r y h em ost a sis. Of cen t r a l im por t a n ce in bot h pr im a r y a n d secon da r y h em ost a sis is t h e a ct iv a t ion of t h e clot t in g ca sca de, w h ich ca n be br ok en dow n in t o t w o ba sic pa t h w a y s, t h e in t r in sic pa t h w a y a n d t h e ex t r in sic pa t h w a y .[2 ] T h e in t r in sic pa t h w a y is a ct iv a t ed by colla g en , w h ich is ex posed w h en a blood v essel is da m a g ed. T h e ex t r in sic pa t h w a y is sim ila r ly a ct iv a t ed by t issu e da m a g e a n d t h e r esu lt a n t r elea se of t issu e fa ct or . T h e in t r in sic a n d ex t r in sic pa t h w a y s con v er g e in t o t h e com m on pa t h w a y , w h ich beg in s w it h t h e con v er sion of Fa ct or X t o X a , a n d u lt im a t ely r esu lt s in t h e con v er sion of pr ot h r om bin t o t h r om bin , w h ich is in t eg r a l in clot st a biliza t ion v ia fibr in .[3 ] T h e com m on pa t h w a y is fa cilit a t ed by Fa ct or V , w h ich su r g eon s oft en t h in k of du e t o t h e r ela t iv ely com m on h er it a ble coa g u la t ion disor der , Fa ct or V Leiden .[4 ] T h e ph y siolog y of h em ost a sis is w ell-u n der st ood, a n d h ist or ica lly m a n y t opica l h em ost a t ic a g en t s h a v e been desig n ed t o m im ic or ex ploit t h e en zy m es a n d m olecu les cen t r a l t o t h e pr ocess.

FIBRIN SEALANTS
T opica l h em ost a t ic a g en t s in t h e m oder n su r g ica l er a ca n be t r a ced t o 1 9 0 9 , w h en Ber g el fir st discu ssed t h e u se of t opica l fibr in for h em ost a sis.[5 ] T h is ev olv ed in t o a cla ss of pr epa r a t ion s k n ow n a s fibr in sea la n t s. Ea r ly fibr in sea la n t s com bin ed bov in e t h r om bin w it h h u m a n pla sm a for t opica l a pplica t ion .[6 ] W idespr ea d su r g ica l u sa g e w a s in it ia lly lim it ed, bu t in 1 9 3 8 pu r ified t h r om bin beca m e a v a ila ble t h r ou g h a dv a n cem en t s in t h e t ech n olog y of pr ot ein sepa r a t ion .[7 ] T h a t t ech n olog y a cceler a t ed r esea r ch a n d dev elopm en t of fibr in sea la n t s, a n d r epor t s of a ppa r en t ly su ccessfu l u sa g e of su ch a g en t s beg a n t o a ppea r in t h e su r g ica l lit er a t u r e in t h e 1 9 4 0 s. Y ou n g a n d Meda w a r r epor t ed t h e u se of fibr in sea la n t t o r epa ir per iph er a l n er v es in 1 9 4 0 .[8 ] In 1 9 4 4 , Cr on k it e et al. r epor t ed t h e u sa g e of com bin ed fibr in og en a n d t h r om bin in im pr ov in g sk in g r a ft su r v iv a l a n d a dh esion in t h e g r a ft in g of soldier s w it h sev er e bu r n in ju r ies.[9 ] A lt h ou g h ex cit in g , t h e ea r ly for m u la t ion s w er e fr a u g h t w it h pr oblem s, n a m ely t h eir pot en t ia lly in fect iou s n a t u r e. A ll ea r ly fibr in sea la n t s w er e der iv ed fr om h u m a n pla sm a com pon en t s, a n d a s w it h a ll h u m a n -der iv ed pr odu ct s a t t h e t im e, pr epa r a t ion s of h u m a n fibr in og en a n d t h r om bin w er e a sou r ce of t r a n sm ission of v ir a l h epa t it is, a n d som e ea r ly pa t ien t s t r ea t ed w it h fibr in -ba sed h em ost a t ic a g en t s con t r a ct ed h epa t it is. In a n effor t t o m in im ize t h e r isk of v ir a l t r a n sm ission , bov in e t h r om bin w a s su bst it u t ed for h u m a n t h r om bin in m a n y su bsequ en t pr epa r a t ion s. T h is r esu lt ed in som e pa t ien t s dev elopin g coa g u lopa t h ies a ssocia t ed w it h t h e u se of bov in e t h r om bin r ela t ed t o im m u n e-m edia t ed pr odu ct ion of t h r om bin a n d Fa ct or V in h ibit or s.[1 0 ,1 1 ] T h e r isk of v ir a l t r a n sm ission , in a ddit ion t o t h e coa g u lopa t h ies, seen w it h bov in e t h r om bin u sa g e led t o sig n ifica n t ly decr ea sed a ppea l, a n d w or k on t h ese sea la n t s essen t ia lly cea sed for a n u m ber of y ea r s. In t er est w a s r ev iv ed in t h e la t e 1 9 6 0 s w it h a dv a n cem en t s in t ech n olog y a llow in g for t h e isola t ion a n d con cen t r a t ion of clot t in g fa ct or s fr om h u m a n pla sm a . Cr y opr ecipit a t e beca m e w idely a v a ila ble, a n d in 1 9 7 2 , Ma t r a s com bin ed cr y opr ecipit a t e w it h pu r ified bov in e t h r om bin t o pr odu ce t h e fir st m oder n it er a t ion of a fibr in sea la n t .[1 2 ] Resea r ch con t in u ed, a n d t h e fir st com m er cia lly a v a ila ble fibr in sea la n t w a s a ppr ov ed in Eu r ope in 1 9 8 2 . Despit e r epor t ed su ccess a m on g Eu r opea n a n d Ja pa n ese su r g eon s w it h u se of fibr in sea la n t s, t h e A m er ica n Food a n d Dr u g A dm in ist r a t ion (FDA ) did n ot follow in a ppr ov in g t h e pr odu ct beca u se of t h e per ceiv ed r isk of v ir a l t r a n sm ission fr om t h e pooled pla sm a com pon en t .[7 ] A s u se by for eig n su r g eon s con t in u ed, A m er ica n su r g eon s im plem en t ed t h e u se of n on com m er cia l for m s of fibr in sea la n t t h r ou g h ou t t h e 1 9 9 0 s. Most of t h ese su r g eon s g en er a t ed sea la n t s w h ich w er e cr ea t ed t h r ou g h com bin in g pa t ien t s ow n pla sm a clot t in g fa ct or s t h r ou g h a u t olog ou s don a t ion , w it h bov in e t h r om bin .[1 3 ] Pr og r ess w a s m a de in r edu cin g t h e
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Evolution of hemostatic agents in surgical practice

r isk of v ir a l t r a n sm ission t h r ou g h h u m a n blood pr odu ct s, a n d u lt im a t ely in 1 9 9 8 , T isseel a n d Hem a seel fibr in sea la n t s w er e a ppr ov ed for clin ica l u se by t h e A m er ica n FDA . T h e m ost r ecen t v a r ia t ion on fibr in sea la n t s ca m e in 2 0 0 3 , w h en t h e A m er ica n Red Cr oss, in con ju n ct ion w it h OMRIX Bioph a r m a ceu t ica ls, r elea sed Cr ossea l, a fibr in sea la n t m a n u fa ct u r ed en t ir ely fr om n on a n im a l com pon en t s. Cr ossea l con t a in s h u m a n fibr in og en a n d t h r om bin , a n d la ck s t h e bov in e a pr ot in in com pon en t fou n d in t h e ot h er fibr in sea la n t s.[1 4 ] Pu blish ed r epor t s of clin ica l a pplica t ion s for fibr in sea la n t s w er e in it ia lly la r g ely lim it ed t o ca r dia c a n d v a scu la r su r g er y , or a l a n d m a x illofa cia l su r g er y , a n d r econ st r u ct iv e pla st ic su r g er y , bu t r ecen t ly , m or e a n d m or e a pplica t ion s a r e bein g discu ssed in t h e u r olog ic lit er a t u r e. Mu eller et al. pr esen t ed a n in t er est in g ser ies of eig h t pa t ien t s in w h ich t h e fibr in sea la n t T isseel w a s u sed t o cr ea t e u r et er a l obst r u ct ion du r in g la pa r oscopic plu ck n eph r ou r et er ect om y .[1 5 ] A s a h em ost a t ic a g en t , Zh a n g et al. pu blish ed a m odified t ech n iqu e of r en a l a r t er y a n a st a m osis u t ilizin g fibr in sea la n t in a ser ies of r en a l t r a n spla n t a t ion s in r a t s.[1 6 ] Gopa l et al. a n d A m br iz-Gon za lez et al. r epor t ed decr ea sed fist u la a n d com plica t ion r a t es, r espect iv ely , w h en fibr in sea la n t s a r e u sed ov er su t u r e lin es du r in g h y pospa dia s r epa ir .[1 7 ,1 8 ] Fu r t h er pu blica t ion s in t h e u r olog ic lit er a t u r e r epor t t h e u t ilit y of fibr in g lu e in t u beless per cu t a n eou s r en a l su r g er y , a s w ell a s in t h e r epa ir of com plica t ed v esicov a g in a l fist u la s a s a n a lt er n a t iv e t o t h e m a r t iu s fla p.[1 9 ,2 0 ] A lt h ou g h fibr in sea la n t w a s on e of t h e fir st m oder n h em ost a t ic a g en t s t o be u sed in clin ica l pr a ct ice, t h e slow dev elopm en t of t h e t ech n olog y a n d in it ia l obst a cles t o FDA a ppr ov a l a n d su bsequ en t lim it ed a v a ila bilit y h a v e lea d t o a r ela t iv e pa u cit y of pr ospect iv e clin ica l r esea r ch w it h fibr in sea la n t s. T h e u t ilit y of effect iv e h em ost a sis in a t opica l biolog ic a g en t com bin ed w it h effect iv e t issu e sea la n t is of u n den ia ble in t er est t o a n y u r olog ic su r g eon . A s a n u n der st u died m a t er ia l, fibr in sea la n t s offer a n ex cit in g a r en a of pot en t ia lly n ov el clin ica l u r olog ic r esea r ch . Giv en t h a t T isseel a n d ot h er sea la n t s a r e n ow w idely com m er cia lly a v a ila ble, t h e pot en t ia l for la r g e pr ospect iv e r a n dom ized clin ica l t r ia ls in com m on u r olog ic pr ocedu r es, su ch a s per cu t a n eou s r en a l su r g er y a n d u r et er a l a n a st a m osis, is qu it e ex cit in g . Per h a ps ev en m or e in t er est in g t h a n t h e h em ost a t ic u ses of fibr in sea la n t s a r e t h e t h er a peu t ic possibilit ies. T h e pot en t ia l for fu r t h er ev olu t ion in t h e a pplica t ion of fibr in sea la n t s h a s been sh ow n in biom a t er ia ls r esea r ch u t ilizin g fibr in sea la n t s for t opica l deliv er y of a n t ibiot ics, ch em ot h er a peu t ics, a n d a n a lg esics, w h ich offer s y et a n ot h er in t er est in g oppor t u n it y for n ov el r esea r ch .[2 1 ]

GELATIN HEMOSTATIC AGENTS


Fibr in sea la n t s w er e on e of t h e fir st m oder n h em ost a t ic a g en t s, bu t t h eir in it ia lly lim it ed u se open ed t h e door for ot h er n ov el h em ost a t ic pr odu ct s, m a n y of w h ich a r e n ow m or e fa m ilia r t o m ost su r g eon s. Gela t in -ba sed h em ost a t ic a g en t s a r e a bu n da n t in m oder n oper a t in g r oom s, a n d w er e fir st in t r odu ced in t h e 1 9 4 0 s a s Gelfoa m . In t h eir fu n da m en t a l for m , g ela t in -ba sed h em ost a t ic a g en t s h a v e u n der g on e v er y lit t le ev olu t ion sin ce t h eir in t r odu ct ion . Gelfoa m a n d Su r g ifoa m a r e st ill offer ed in sim ila r pr epa r a t ion s a s t h eir in it ia l r elea se. Gelfoa m is a pu r ified por k sk in g ela t in , a n d it s h em ost a t ic pr oper t ies, a lt h ou g h n ot en t ir ely u n der st ood, a r e felt t o be m or e ph y sica l r a t h er t h a n r ela t ed t o dir ect effect s on t h e clot t in g ca sca de.[2 2 ] Gelfoa m ca n be u sed in sev er a l w a y s, eit h er in dr y spon g e for m , m oist en ed w it h in ject a ble sodiu m ch lor ide solu t ion , or , com m on ly , sa t u r a t ed w it h t opica l pu r ified t h r om bin . T h e com bin ed a pplica t ion w it h t opica l t h r om bin is on e of t h e few a dv a n cem en t s m a de w it h g ela t in -ba sed h em ost a t ic a g en t s. T h e a ddit ion of t h r om bin ca n en h a n ce t h e h em ost a t ic pr oper t ies of g ela t in spon g e h em ost a t ics, bu t pla in Gelfoa m or Su r g ifoa m is a ffor da ble a n d r ea dily a ccessible. It is con sider ed a m ediocr e h em ost a t by som e su r g eon s, bu t h a s been n ot ed t o h a v e su ccess w h en u sed in it s pla in for m for h em ost a sis in t u beless per cu t a n eou s n eph r olit h ot om y .[2 3 ] A pr oper t y of g ela t in spon g e h em ost a t ics is t h e a bilit y t o a bsor b u pw a r ds of 4 0 t im es it s w eig h t in blood or flu ids, a n d it s ca pa cit y t o ex pa n d u p t o 2 0 0 % in vivo .[2 2 ] T h is ca n be con st r u ed a s a
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Evolution of hemostatic agents in surgical practice

n eg a t iv e pr oper t y in som e set t in g s. A n ot h er m a jor a dv a n cem en t in t h e field of g ela t in -ba sed h em ost a t ic a g en t s ca m e in t h e dev elopm en t of t h e pr odu ct Flosea l. A ppr ov ed for com m er cia l u se in t h e US in 1 9 9 9 , Flosea l com bin es h u m a n -der iv ed t h r om bin w it h bov in e-der iv ed g ela t in m a t r ix g r a n u les w h ich a r e m ix ed a t t h e t im e of u se.[2 4 ] T h e m a jor ev olu t ion of t h is pr odu ct is t h e liqu id n a t u r e of Flosea l v s g ela t in spon g e, a s w ell a s a n ov el cr osslin k in g of t h e g ela t in m a t r ix g r a n u les t h a t m in im izes in vivo ex pa n sion of t h e pr odu ct .[2 5 ] A lt h ou g h t h is is n ot a n im por t a n t pr oper t y of a h em ost a t ic a g en t in som e su r g ica l a ppr oa ch es, t h e liqu id n a t u r e of t h e pr odu ct does fa cilit a t e a pplica t ion , especia lly in m in im a lly in v a siv e su r g er y . A s w it h g ela t in spon g e a g en t s, Flosea l is a bsor ba ble a n d w ell-t oler a t ed. Ra r e r epor t s of a bscess for m a t ion or g r a n u lom a for m a t ion h a v e been r epor t ed w it h t h e u se of g ela t in -ba sed a g en t s; h ow ev er , som e of t h ese h a v e been a t t r ibu t ed t o t h e r a diolog ic a ppea r a n ce on post oper a t iv e im a g in g of g ela t in spon g es.[2 6 ,2 7 ] A ccessibilit y , ea se of u se, a n d effect iv e h em ost a sis m a k e g ela t in -ba sed h em ost a t ic a g en t s a popu la r t ool in r edu cin g su r g ica l m or bidit y fr om blood loss.

CYANOACRYLATE ADHESIVES
Cy a n oa cr y la t e a dh esiv es w er e dev eloped by Dr . Ha r r y Coov er of Koda k La bor a t or ies in 1 9 4 2 , du r in g ex per im en t s t o desig n a clea r pla st ic su it a ble for g u n sig h t s. T h e m a t er ia l w a s u n su ccessfu l in t h is a pplica t ion , a n d w a s a ba n don ed.[2 8 ] In 1 9 4 9 , A ir dis sy n t h esized cy a n oa cr y la t e, a n d r ecog n izin g it s u n iqu e pr oper t ies, su bm it t ed t h e m a t er ia l for US pa t en t .[2 9 ] In 1 9 5 9 , Coov er et al. r epor t ed on t h e a dh esiv e pr oper t ies of cy a n oa cr y la t es, a n d su g g est ed t h eir a pplica t ion a s su r g ica l a dh esiv es.[3 0 ] In 1 9 6 5 , W a t son a n d Ma g u da u sed cy a n oa cr y la t e a dh esiv e for t y m pa n ic m em br a n e r epa ir , a n d t h er e w er e r epor t s t h a t cy a n oa cr y la t es w er e u sed a s t issu e a dh esiv es a n d h em ost a t ic a g en t s on ba t t lefields du r in g t h e V iet n a m W a r .[3 1 ] Ea st m a n su bm it t ed a n a pplica t ion for a ppr ov a l t o t h e FDA for cy a n oa cr y la t es a s a w ou n d a dh esiv e in 1 9 6 4 , bu t issu es w it h t issu e ir r it a t ion a n d br it t len ess pr ev en t ed a ppr ov a l. Fin a lly , in 1 9 9 8 , a ft er sig n ifica n t r edesig n , cy a n oa cr y la t es w er e a ppr ov ed by t h e FDA in t h e for m of 2 -oct y l cy a n oa cr y la t e. Ma r k et ed a s Der m a bon d, 2 -oct y l cy a n oa cr y la t e, h a s been sh ow n t o be a g ood t issu e a dh esiv e, a n d t o h a v e a n t im icr obia l pr oper t ies. Liqu id cy a n oa cr y la t e con sist s of cy a n oa cr y la t e m on om er s, w h ich poly m er ize in t o lon g ch a in s in t h e pr esen ce of h y dr ox y l ion s. W a t er con t a in in g h u m a n t issu e a ct iv a t es t h e poly m er iza t ion of cy a n oa cr y la t e m on om er s, a n d is bon ded t og et h er a s t h e g lu e r a pidly set s. T h e pr oper t y of n ea r ly in st a n t a n eou s bon din g m a k es cy a n oa cr y la t es a n effect iv e h em ost a t ic a g en t a n d t issu e a dh esiv e. Cu r r en t ly , m u lt iple br a n ds a n d for m a t s of cy a n oa cr y la t e a dh esiv es a r e a v a ila ble, a n d a r e w idely u sed for cor n ea l per for a t ion r epa ir , sk in la cer a t ion r epa ir , esoph a g ea l a n d g a st r ic v a r icea l r epa ir , sk in g r a ft in g , a n d v a scu la r r epa ir . T est in i et al. r epor t ed sig n ifica n t ly r edu ced m or bidit y w h en u sin g h u m a n fibr in g lu e or N-bu t y l-2 -cy a n oa cr y la t e a dh esiv e for m esh fix a t ion du r in g in g u in a l h er n ia r epa ir w h en com pa r ed w it h su t u r e.[3 2 ] Elm or e et al. r epor t t h e u se of 2 -oct y l-cy a n oa cr y la t e in su t u r eless cir cu m cision w it h g ood r esu lt , n eg a t in g t h e r isk of su t u r e t r a ck s or sin u ses.[3 3 ] A n in g et al. r ecen t ly r epor t ed a n ov el u se of cy a n oa cr y la t e a dh esiv e for t h e per cu t a n eou s a bla t ion of a la t e u r in a r y fist u la a ft er pa r t ia l n eph r ect om y .[3 4 ] Cy a n oa cr y la t es a r e becom in g in cr ea sin g ly popu la r for t h e su t u r eless closu r e of sm a ll sk in in cision s, a n d a s su r g eon s fr om a ll fields becom e m or e com for t a ble w it h t h e pr oper t ies of t h ese a dh esiv es, cy a n oa cr y la t es a r e lik ely t o be pu t t o in cr ea sin g ly in n ov a t iv e u ses.

OXIDIZED REGENERATED CELLULOSE


A n ew it er a t ion of t opica l h em ost a t ic w a s la u n ch ed in t o t h e clin ica l m a r k et in 1 9 6 0 w it h t h e r elea se of Su r g icel. T h is t opica l a g en t w a s en t ir ely u n iqu e in t h e m a r k et , a s it w a s n ot der iv ed fr om h u m a n or a n im a l sou r ces. Su r g icel is a pla n t -ba sed t opica l h em ost a t ic, m a de by r eg en er a t in g pu r e pla n t -der iv ed cellu lose in t o a k n it t ed fa br ic w h ich is t h en ox idized.[3 5 ] T h e ox idized cellu lose fa br ic ca n be t opica lly a pplied a n d a ct s a s a sca ffold for clot for m a t ion . Ox idized r eg en er a t ed cellu lose t opica l h em ost a t ic a g en t s h a v e, lik e g ela t in -ba sed pr odu ct s, ev olv ed lit t le sin ce t h eir in t r odu ct ion ,
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bu t a r e st ill qu it e effect iv e a n d com m on ly u sed. Su r g icel bolst er s a r e a popu la r a dju v a n t t o con t r ollin g su r g ica l bleedin g du r in g pa r t ia l n eph r ect om y .[3 6 ] A n ot h er com m on fea t u r e bet w een t h e ox idized cellu lose h em ost a t ics a n d g ela t in -ba sed h em ost a t ics is a n a ppea r a n ce on post oper a t iv e im a g in g t h a t ca n be con cer n in g for a bscess.[3 7 ] Su r g icel ca n in fa ct h a v e a r in g en h a n cin g a ppea r a n ce on com pu t ed t om og r a ph y sca n , a n d per h a ps som e of t h e m ost clin ica lly sig n ifica n t a dv a n cem en t s in t h e u se of t h is h em ost a t ic a r e in bet t er u n der st a n din g of it s r a diolog ica l fea t u r es, t h er eby r edu cin g t h e m or bidit y of u n n ecessa r ily in t er v en in g on a pr esu m ed a bscess.

MICROFIBRILLAR COLLAGEN
A m or e r ecen t ly dev eloped a n d a ppr ov ed a ddit ion t o t h e m a r k et of h em ost a t ic a g en t s is colla g en ba sed pr odu ct s. A v it en e, a t opica l m icr ofibr illa r colla g en h em ost a t ic, w a s in t r odu ced in t h e US in t h e ea r ly 1 9 7 0 s. Micr ofibr illa r colla g en pr odu ct s a r e m a de by pu r ify in g bov in e colla g en a n d pr ocessin g it in t o m icr ocr y st a ls, w h ich ca n t h en be m a n ipu la t ed in t o h em ost a t ic a g en t s in a w ide v a r iet y of for m a t s. T h e br a n d A v it en e w a s fir st la u n ch ed in a flou r for m , a n d it is st ill com m on ly u sed in t h e t opica l pow der for m . A ll m a n n er of colla g en -ba sed h em ost a t ics en joy ed w idespr ea d ea r ly u se a s t h ey w er e felt t o be m or e effect iv e t h a n g ela t in -ba sed h em ost a t s. Colla g en -ba sed pr odu ct s a ct iv a t e t h e in t r in sic pa t h w a y of t h e coa g u la t ion ca sca de, w h er ea s g ela t in h em ost a t s a r e t h ou g h t t o in du ce h em ost a sis t h r ou g h ph y sica l pr oper t ies a lon e.[3 8 ] In sev er a l r a n dom ized t r ia ls, pr im a r ily in t h e ca r diot h or a cic su r g ica l lit er a t u r e, m icr ofibr illa r colla g en h em ost a t s h a v e been sh ow n t o be su per ior t o ox idized cellu lose in h em ost a sis, a n d in deed w er e sh ow n t o h a v e st a t ist ica lly sig n ifica n t r edu ct ion s in m ea su r ed blood loss w h en com pa r ed w it h ox idized cellu lose.[3 8 ] T h e pr im a r y im pr ov em en t s a n d ch a n g es m a de in t h e field of colla g en h em ost a t ics h a v e been in t h e r elea se of n ew for m a t s. A s pr ev iou sly st a t ed, t h e fir st colla g en h em ost a t , A v it en e w a s in it ia lly a v a ila ble in a flou r for m , a n d t oda y t h e pr odu ct lin e h a s ex pa n ded t o a n on w ov en w eb m a t er ia l, a s w ell a s a spon g e for m a t . In Ma y 2 0 0 0 , t h e m ost r ecen t a ddit ion , t h e spon g e for m A v it en e Ult r a foa m Colla g en , w a s a ppr ov ed by t h e A m er ica n FDA .[3 9 ]

SUMMARY
Fibr in sea la n t s, g ela t in -ba sed pr odu ct s, ox idized cellu lose, a n d colla g en pr odu ct s a r e t h e m a jor cla sses of t opica l h em ost a t ic a g en t s t h a t h a v e ev olv ed ov er t h e la st 1 0 0 y ea r s. T h r ee of t h ese cla sses h a v e been r ela t iv ely st a t ic sin ce t h eir dev elopm en t , w it h ch a n g es m ost ly t o for m a t a n d pr epa r a t ion . T h e ev olu t ion of fibr in sea la n t s, con v er sely , h a s been slow bu t st ea dy ov er t h e la st cen t u r y , a n d h olds t h e g r ea t pr om ise for fu t u r e a da pt a t ion s. T h is is especia lly ex cit in g , w h en con sider ed in t h e con t ex t of cu r r en t su r g ica l pr a ct ice. Su r g er y of a ll k in ds, bu t ev en m or e so Ur olog ic su r g er y , is u n der g oin g a per iod of r a pid g r ow t h a n d ev olu t ion of t ech n iqu es, in st r u m en t a t ion , a n d t h eor y , dr iv en by t h e m oder n pu sh for m in im a lly in v a siv e su r g er y . A s n ew dev ices a n d su r g ica l sy st em s r ea ch clin ica l pr a ct ice w it h im pr essiv e speed, t h er e n eeds t o be a con cu r r en t pr essu r e for t h e a da pt a t ion of su r g ica l t ools a n d dr u g s. Hem ost a sis is a lw a y s cr it ica lly im por t a n t in a n y su r g ica l a ppr oa ch , a n d it ca n pr ov e pa r t icu la r ly ch a llen g in g in m in im a lly in v a siv e su r g er y . For ex a m ple, in la pa r oscopic pa r t ia l n eph r ect om y , con t r ol of su r g ica l bleedin g ca n be t h e m ost t ech n ica lly ch a llen g in g st ep in t h e oper a t ion .[4 0 ] W ell-desig n ed, effect iv e t opica l h em ost a t ic a g en t s a r e in v a lu a ble in m in im a lly in v a siv e su r g ica l pr a ct ice. Mu lt iple differ en t m ediu m s a n d cla sses of t opica l h em ost a t ics a r e pr im e su bject s for a da pt a t ion t o u r olog ic su r g ica l a ppr oa ch es of t h e fu t u r e. In pa r t icu la r , fibr in sea la n t h em ost a t ic a g en t s h a v e a r ich h ist or y a n d la r g e pot en t ia l for fu r t h er r ein v en t ion .

Footnotes
Source of Support: Nil Conflict of Interest: None declared.
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Evolution of hemostatic agents in surgical practice

Article information
Indian J Urol. 2010 Jul-Sep; 26(3): 374378. doi: 10.4103/0970-1591.70574 PMCID: PMC2978438 Chandru P. Sundaram and Alison C. Keenan Department of Urology, Indiana University School of Medicine, Indianapolis For correspondence: Dr. Chandru P. Sundaram, Indiana University School of Medicine, 535 N, Barnhill Dr. Suite 420, Indianapolis, IN 46202. E-mail: sundaram/at/iupui.edu Copyright Indian Journal of Urology This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Articles from Indian Journal of Urology : IJU : Journal of the Urological Society of India are provided here courtesy of Medknow Publications

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