Anna Drosou, MD, Anna Falabella, MD, Robert S. Kirsner, MD
Wounds 15(5):149-166, 2003. 2003 Health Management u!l"#at"ons, $n#. osted 06%11%2003 Abstract and Introduction Abstract &nt"se't"#s ha(e long and #ommonl) !een used on *ounds to '+e(ent o+ t+eat "n,e#t"on. Ho*e(e+, #"t"ng #)toto-"#"t) data, man) autho+s ha(e ad("sed aga"nst the"+ use on o'en *ounds. .h"s a+t"#le d"s#usses ant"se't"#s and the"+ use on o'en *ounds, as *ell +e("e*s +ele(ant an"mal stud"es and #l"n"#al t+"als e-am"n"ng the e,,e#ts o, #ommonl) used ant"se't"#s, "n#lud"ng "od"ne #om'ounds ('o("done "od"ne and #ade-ome+ "od"ne), #hlo+he-"d"ne, h)d+ogen 'e+o-"de, a#et"# a#"d, and s"l(e+ #om'ounds. .h"s a+t"#le e-am"nes the"+ e,,e#ts on *ound heal"ng and +ee'"thel"/at"on and the"+ e,,"#a#) on +edu#"ng !a#te+"al num!e+ "n *ounds and "n#"den#e o, *ound "n,e#t"ons. .he autho+s ,ound des'"te #)toto-"#t) data, most ant"se't"#s ha(e not !een sho*n to #lea+l) "m'ede heal"ng, es'e#"all) ne*e+ ,o+mulat"ons l"0e #ade-ome+ "od"ne (*h"#h s'eeds heal"ng) and no(el s"l(e+ del"(e+) s)stems. .hese #om'ounds a''ea+ to !e +elat"(el) sa,e and e,,"#"ent "n '+e(ent"ng "n,e#t"on "n human *ounds. 1"(en th"s +e("e*, the +ole o, ant"se't"#s on *ounds and the"+ +ole "n *ound #a+e management should !e +e#ons"de+ed. Introduction &nt"se't"#s a+e agents that dest+o) o+ "nh"!"t the g+o*th and de(elo'ment o, m"#+oo+gan"sms "n o+ on l"("ng t"ssue. 2nl"0e ant"!"ot"#s that a#t sele#t"(el) on a s'e#","# ta+get, ant"se't"#s ha(e mult"'le ta+gets and a !+oade+ s'e#t+um o, a#t"("t), *h"#h "n#lude !a#te+"a, ,ung", ("+uses, '+oto/oa, and e(en '+"ons. 31,24 5e(e+al ant"se't"# #atego+"es e-"st, "n#lud"ng al#ohols (ethanol), an"l"des (t+"#lo#a+!an), !"guan"des (#hlo+he-"d"ne), !"s'henols (t+"#losan), #hlo+"ne #om'ounds, "od"ne #om'ounds, s"l(e+ #om'ounds, 'e+o-)gens, and 6uate+na+) ammon"um #om'ounds. 314
.he most #ommonl) used '+odu#ts "n #l"n"#al '+a#t"#e toda) "n#lude 'o("done "od"ne, #hlo+he-"d"ne, al#ohol, a#etate, h)d+ogen 'e+o-"de, !o+"# a#"d, s"l(e+ n"t+ate, s"l(e+ sul,ad"a/"ne, and sod"um h)'o#hlo+"te. &nt"se't"# uses and "nd"#at"ons (a+). 5e(e+al ant"se't"# agents ma"nl) ,o#us on #leans"ng "nta#t s0"n and a+e used ,o+ '+e''"ng 'at"ents '+eo'e+at"(el) and '+"o+ to "nt+amus#ula+ "n7e#t"ons o+ (enous 'un#tu+es, '+e- and 'osto'e+at"(e s#+u!!"ng "n the o'e+at"ng +oom, and hand *ash"ng !) med"#al 'e+sonnel. 5ome also #onta"n dete+gents, *h"#h +ende+ them too ha+sh ,o+ use on non"nta#t s0"n. 334 .he use,ulness o, ant"se't"#s on "nta#t s0"n "s *ell esta!l"shed and !+oadl) a##e'ted. Ho*e(e+, the use o, ant"se't"#s as '+o'h)la#t"# ant"-"n,e#t"(e agents ,o+ o'en *ounds, su#h as la#e+at"ons, a!+as"ons, !u+ns, and #h+on"# ul#e+s, has !een an a+ea o, "ntense #ont+o(e+s) ,o+ se(e+al )ea+s. .*o o,,"#"al gu"del"nes ha(e !een +eleased +e#entl) #on#e+n"ng ant"se't"# use on *ounds. o("done "od"ne has !een 8ood and 9+ug &dm"n"st+at"on (89&)-a''+o(ed ,o+ sho+t-te+m t+eatment o, su'e+,"#"al and a#ute *ounds. 344 .he statement "n#ludes that 'o("done "od"ne has not !een ,ound to e"the+ '+omote o+ "nh"!"t *ound heal"ng. :n the othe+ hand, gu"del"nes ,o+ the t+eatment o, '+essu+e ul#e+s !) the 25 9e'a+tment o, Health and Human 5e+("#es st+ongl) d"s#ou+age the use o, ant"se't"#s and '+omote the use o, no+mal sal"ne ,o+ #leans"ng '+essu+e ul#e+s. 354 $n #l"n"#al '+a#t"#e, ant"se't"#s a+e !+oadl) used ,o+ !oth "nta#t s0"n and *ounds, although #on#e+ns a+e +a"sed !ased u'on the"+ e,,e#t on human #ells and *ound heal"ng. :'"n"ons a+e #on,l"#t"ng. 5ome autho+s st+ongl) d"sa''+o(e the use o, ant"se't"#s "n o'en *ounds. 36-;4 :n the othe+ hand, othe+s !el"e(e ant"se't"#s ha(e a +ole "n *ound #a+e, and the"+ use ma) ,a(o+ *ound heal"ng #l"n"#all). 39,104 Reasons to Use Antiseptics on Wounds .he ma"n +at"onale ,o+ us"ng ant"se't"#s on o'en *ounds "s '+e(ent"on and t+eatment o, "n,e#t"on and, the+e,o+e, "n#+eased +ate o, the heal"ng '+o#ess. $t "s esta!l"shed that "n,e#t"ons ma) dela) heal"ng, #ause ,a"lu+e o, heal"ng, and e(en #ause *ound dete+"o+at"on. 3114 M"#+o!"al 'athogens dela) *ound heal"ng th+ough se(e+al d",,e+ent me#han"sms, su#h as 'e+s"stent '+odu#t"on o, "n,lammato+) med"ato+s, meta!ol"# *astes, and to-"ns, and ma"ntenan#e o, the a#t"(ated state o, neut+o'h"ls, *h"#h '+odu#e #)tol)t"# en/)mes and ,+ee o-)gen +ad"#als. 3124 .h"s '+olonged "n,lammato+) +es'onse #ont+"!utes to host "n7u+) and dela)s heal"ng. Mo+eo(e+, !a#te+"a #om'ete *"th host #ells ,o+ nut+"ents and o-)gen ne#essa+) ,o+ *ound heal"ng. 3134 Wound "n,e#t"on #an also lead to t"ssue h)'o-"a, +ende+ the g+anulat"on t"ssue hemo++hag"# and ,+ag"le, +edu#e ,"!+o!last num!e+ and #ollagen '+odu#t"on, and damage +ee'"thel"/at"on. 3<,14-164
=onse6uentl), although #+eat"on o, an o't"mal en("+onment ,o+ the *ound heal"ng '+o#ess "s #u++entl) the '+"ma+) o!7e#t"(e o, *ound #a+e, add+ess"ng "n,e#t"on st"ll 'la)s a #+"t"#al +ole "n *ound management. 9es'"te the un"(e+sal a##e'tan#e o, the det+"mental +ole o, "n,e#t"on on *ound heal"ng, the e-a#t s"gn","#an#e o, "n#+eased !a#te+"al load on *ounds "s st"ll an a+ea o, de!ate. &ll #h+on"# *ounds a+e #olon"/ed !) !a#te+"a 'o'ulat"on, and "t "s 0no*n #olon"/ed *ounds #an heal. 31<,1;4 Ho*e(e+, "n add"t"on to #l"n"#al "n,e#t"on, "t seems that !a#te+"al num!e+ a!o(e a #+"t"#al #on#ent+at"on #an de#+ease the *ound heal"ng +ate and ma) ha(e delete+"ous e,,e#ts on the *ound heal"ng '+o#ess. .he +ole o, !a#te+"a "n the #h+on"#"t) o, nonheal"ng *ounds "s unde+ "n(est"gat"on. >"0el), a state o, !a#te+"al #ontam"nat"on that #an '+odu#e su!#l"n"#al t"ssue damage e-"sts. 3194
.h"s ma) !e #aused !) shea+ num!e+ o+ !) othe+ '+o'e+t"es o, the !a#te+"al '+o#ess. $n#+eased !a#te+"al num!e+s "n '+essu+e ul#e+s ha(e !een "m'l"#ated as s"gn","#ant 'a+t"#"'ants o, #h+on"# ul#e+at"on. 3204 5e(e+al stud"es ha(e demonst+ated that !a#te+"al num!e+ a!o(e 105 o+ 106 o+gan"sms 'e+ g+am #an #ause lo#al d"sease to s0"n o+ #an dela) *ound heal"ng. 321-244
?uant","#at"on o, !a#te+"a *"th"n *ounds "s not the sole '+ed"#to+ o, the +"s0 o, "n,e#t"on, s"n#e se(e+al "nd"("dual"/ed ,a#to+s, su#h as '+esen#e o, ,o+e"gn mate+"al and #on#om"tant d"seases, #an de#+ease the a!"l"t) o, the hosts to de,end themsel(es. Mo+eo(e+, the natu+e o, the *ound and the ("+ulen#e o, m"#+o!es "n(ol(ed a+e "m'o+tant. 3254 $n add"t"on to use o, ant"se't"#s to +edu#e !a#te+"al load o, a *ound, se(e+al othe+ a''+oa#hes ha(e !een de(elo'ed, "n#lud"ng de!+"dement, #leans"ng and 'ulsat"ng 7et la(age ,o+ +emo(al o, the de("tal"/ed t"ssue, and a''l"#at"on o, to'"#al ant"!"ot"#s. ¬he+ a+gument ,o+ the use o, ant"se't"#s on *ounds to '+e(ent *ound "n,e#t"on "s that ant"se't"#s ma) !e '+e,e+a!le to to'"#al ant"!"ot"#s *"th +ega+d to de(elo'ment o, !a#te+"al +es"stan#e. &nt"!"ot"# +es"stan#e o, s0"n *ound ,lo+a has eme+ged as a s"gn","#ant '+o!lem, and measu+es to '+e(ent "t should !e ta0en. 3264 1ene+all), ant"se't"#s a"m at el"m"nat"ng all 'athogen"# !a#te+"a o, the *ound, *h"le ant"!"ot"#s a+e e,,e#t"(e onl) to #e+ta"n !a#te+"a that a+e sens"t"(e to them. <hough +es"stan#e to*a+d ant"se't"#s has !een +e'o+ted, "t "s to a s"gn","#antl) lesse+ deg+ee than +e'o+ted *"th ant"!"ot"# usage. 31;4 &##o+d"ng to M#9onnell, et al., some a#6u"+ed me#han"sms o, +es"stan#e (es'e#"all) to hea() metals) a+e #l"n"#all) s"gn","#ant, !ut "n most #ases the +esults ha(e !een s'e#ulat"(e. 314 Mo+eo(e+, de(elo'ment o, +es"stan#e aga"nst 'o("done "od"ne, *h"#h "s the most #ommonl) used ant"se't"# toda), does not e-"st. 32<4
a)ne, et al., state that the sens"!le use o, ant"se't"#s #ould hel' de#+ease the usage o, ant"!"ot"#s, '+ese+("ng the"+ ad(antage ,o+ #l"n"#all) #+"t"#al s"tuat"ons. 32;4 &nt"se't"#s a+e also #ons"de+ed su'e+"o+ to to'"#al ant"!"ot"#s *hen the"+ +ates o, #aus"ng #onta#t sens"t"/at"on a+e #om'a+ed. &m"nogl)#os"des, es'e#"all) neom)#"n, ha(e a mu#h h"ghe+ sens"t"/at"on +ate #om'a+ed to 'o("done "od"ne. 334 Mo+eo(e+, 'at"ents alle+g"# to one ant"!"ot"# ma) a#6u"+e #+oss-alle+g) to othe+ ant"!"ot"#s, as *ell. .he sens"t"/at"on +ate to 'o("done "od"ne, the most #ommonl) used ant"se't"#, has !een ,ound to !e onl) 0.<3 'e+#ent. 334 Arguments Against Antiseptics & ma"n #on#e+n ,o+ #l"n"#"ans '+"o+ to a''l)"ng a to'"#al agent on an o'en *ound "s sa,et). &gents that a+e #)toto-"# o+ #ause dela) "n *ound heal"ng a+e used *"th +ese+(at"on. .he st+ongest a+gument aga"nst the use o, ant"se't"#s on *ounds "s that ant"se't"#s ha(e !een ,ound, '+"ma+"l) us"ng in-vitro models, to !e #)toto-"# to #ells essent"al to the *ound heal"ng '+o#ess, su#h as ,"!+o!lasts, 0e+at"no#)tes, and leu0o#)tes. 329-314 Ho*e(e+, th"s #)toto-"#"t) a''ea+s to !e #on#ent+at"on de'endent, as se(e+al ant"se't"#s "n lo* #on#ent+at"ons a+e not #)toto-"#, although the) +eta"n the"+ ant"!a#te+"al a#t"("t) in vitro. 32<4 5"n#e the in-vitro +esults a+e not al*a)s '+ed"#t"(e o, *hat ma) ha''en in vivo, nume+ous stud"es ha(e !een #ondu#ted on an"mal and human models. .he +esults o, these stud"es a+e #on,l"#t"ng and *"ll !e '+esented late+ "n the a+t"#le. & se#ond +eason aga"nst the use o, ant"se't"#s on o'en *ounds, as ,"+st stated !) 8lem"ng "n 1919, 3324 "s that ant"se't"#s a+e not as e,,e#t"(e aga"nst !a#te+"a that +es"de "n *ounds as the) a+e aga"nst !a#te+"a in vitro. .he '+esen#e o, e-udate, se+um, o+ !lood seems to de#+ease the"+ a#t"("t). Ho*e(e+, "n '+a#t"#e, se(e+al !a#te+"olog"#al stud"es ha(e sho*n that ant"se't"#s #an de#+ease !a#te+"al #ounts *"th"n *ounds. 333,344 $n o+de+ to d+a* #on#lus"ons +ega+d"ng the a''+o'+"ateness and use,ulness o, ant"se't"# use on *ounds, the autho+s ha(e #hosen to +e("e* the +esults o, an"mal and human stud"es o, the most #ommon ant"se't"#s used #u++entl). Iodine Compounds 5"n#e the ,"+st d"s#o(e+) o, the natu+al element "od"ne "n 1;11 !) the #hem"st @e+na+d =ou+to"s, "od"ne and "ts #om'ounds ha(e !een !+oadl) used ,o+ '+e(ent"on o, "n,e#t"on and t+eatment o, *ounds. 3354 Ho*e(e+, mole#ula+ "od"ne #an !e (e+) to-"# ,o+ t"ssues, so ,o+mulat"ons #om'osed !) #om!"nat"on o, "od"ne *"th a #a++"e+ that de#+eases "od"ne a(a"la!"l"t) *e+e de(elo'ed. o("done "od"ne (A-$) +esults ,+om the #om!"nat"on o, mole#ula+ "od"ne and 'ol)("n)l')++ol"done. o("done "od"ne "s a(a"la!le "n se(e+al ,o+ms (solut"on, #+eam, o"ntment, s#+u!). .he s#+u! ,o+m #onta"ns dete+gent and should !e used onl) on "nta#t s0"n. =ade-ome+ "od"ne #ons"sts o, s'he+"#al h)d+o'h"l"# !eads o, #ade-ome+-sta+#h, *h"#h #onta"n "od"ne, "s h"ghl) a!so+!ent, and +eleases "od"ne slo*l) "n the *ound a+ea. $t "s a(a"la!le as an o"ntment and as a d+ess"ng. Bume+ous stud"es ha(e !een #ondu#ted "n o+de+ to dete+m"ne the sa,et) and e,,"#a#) o, "od"ne #om'ounds on *ound heal"ng. Eects o Iodine Compounds on t!e "acterial #oad o Wounds $o%idone iodine. 5e(e+al an"mal stud"es ha(e e-am"ned the e,,e#ts o, 'o("done "od"ne on the !a#te+"al load o, *ounds (.a!le 1). .hese +esults ha(e not '+o(en the e,,"#a#) o, 'o("done "od"neC ho*e(e+, the +esults o, nume+ous #l"n"#al t+"als sho* that "t "s e,,e#t"(e "n +edu#"ng the !a#te+"al load o, *ounds. Dodehea(e+, et al., 3364 stud"ed the !a#te+"#"dal a#t"("t) o, 'o("done "od"ne solut"on "n #ontam"nated *ounds "n Ha+tle) gu"nea '"gs and the 'otent"al the+a'eut"# !ene,"t. <hough the) ,ound that "t #an s"gn","#antl) +edu#e !a#te+"al load 10 m"nutes a,te+ the a''l"#at"on o, the ant"se't"#, th"s e,,e#t d"d not 'e+s"st. 8ou+ da)s a,te+ a s"ngle A-$ a''l"#at"on, the+e *as no de#+eased +ate o, "n,e#t"on o+ de#+eased !a#te+"a num!e+. ¬he+ stud) 33<4 that e(aluated #ontam"nated 12-hou+ old la#e+at"ons "n a gu"nea '"g model ,a"led to ,"nd an) de#+ease o, *ound !a#te+"al #ounts a,te+ "++"gat"on *"th A-$ "n #om'a+"son to no+mal sal"ne. Ho*e(e+, the autho+s ment"on that th"s ma) !e due to the ,o+mat"on o, a '+ote"na#eous *ound #oagulum and 'o"nt out that e(en 'a+ente+al ant"m"#+o!"als a+e "ne,,e#t"(e "n '+e(ent"ng "n,e#t"on "n an"mal models ", adm"n"ste+ed alone mo+e than th+ee hou+s a,te+ *ound"ng. Ho*e(e+, most o, the human t+"als 'e+,o+med '+o(e the e,,"#a#) o, 'o("done "od"ne "n #l"n"#al s"tuat"ons. 1eo+g"ade, et al., 33;4 a''l"ed A-$ o"ntment on !u+n *ounds "n 50 'at"ents and sho*ed that #ont+ol o, !a#te+"al g+o*th *as e,,e#t"(e. .he+e *as not a #ont+ol g+ou' "n th"s stud)C ho*e(e+, the #ont+ol o, !a#te+"al g+o*th sho*ed a s"gn","#ant #o++elat"on to the ,+e6uen#) o, A-$ a''l"#at"on. 1+a(ett, et al., 3394 stud"ed the e,,e#t o, one-'e+#ent A-$ solut"on "n the '+e(ent"on o, "n,e#t"on "n sutu+ed la#e+at"ons "n 395 'at"ents. .he"+ data suggest that use o, one-'e+#ent A-$ solut"on '+"o+ to sutu+"ng +edu#es the "n#"den#e o, *ound "n,e#t"on. $n a +e#ent stud) 3404 on #l"n"#all) non"n,e#ted (enous leg ul#e+s, the #om!"nat"on o, A-$ *"th h)d+o#ollo"d d+ess"ng *as sho*n to +edu#e !a#te+"al #lum's, neut+o'h"l"# (as#ul"t"s, and 'hago#)t"# "n,"lt+at"on and "n#+ease the heal"ng +ate "n #om'a+"son to the h)d+o#ollo"d d+ess"ng alone. :ne o, the most #"ted stud"es "s the one #ondu#ted !) A"l7anto 3414 "n su+g"#al *ounds "n 294 'ed"at+"# 'at"ents. He ,ound that a ,"(e-'e+#ent A-$ ae+osol, *h"#h #onta"ned some e-#"'"ents (gl)#e+ol, #"t+ate-'hos'hate !u,,e+, 'ol)o-)eth)lated non)l'henol), "n#+eased the "n,e#t"on +ate. $n o+de+ to e-'la"n these +esults, he used the #ellst"# method, *h"#h #ons"sts o, 'la#"ng a #ellulose s'onge "ns"de a s"l"#one-+u!!e+ tu!e !et*een the *ound edges. Wound e-udate ,"lls the s'onge, and #ells m"g+ate "nto the s'onge. He ,ound that the ,"(e-'e+#ent ae+osol #aused '+onoun#ed leu0o#)te m"g+at"on, a ,"(e-'e+#ent solut"on *"thout e-#"'"ents #aused sl"ghte+ "nh"!"t"on, *h"le the one-'e+#ent solut"on *as '+a#t"#all) no d",,e+ent to the #ont+ol (sal"ne). 5u!se6uentl), s'+a)"ng *ounds *"th a one-'e+#ent A-$ solut"on had no e,,e#t on *ound heal"ng *h"le "t s"gn","#antl) de#+eased "n,e#t"on +ate. $nte+est"ngl), 'o("done "od"ne has !een ,ound to ha(e "n#+eased !a#te+"#"dal a#t"("t) "n lo*e+ #on#ent+at"ons. 3424 =on(e+sel), some stud"es ha(e not #on,"+med those '+e("ousl) ment"oned +esults. A-$ soa0"ng *as not ,ound to s"gn","#antl) de#+ease !a#te+"al #ounts "n a#ute, t+aumat"#, #ontam"nated *ounds that +e6u"+ed de!+"dement, *h"le sal"ne soa0"ng #aused "n#+eased #ounts. A-$ solut"on *as not ,ound to !e an e,,e#t"(e su!st"tute to *ound #lean"ng and de!+"dement. 3434 Ho*e(e+, A-$ "++"gat"on has !een sho*n to !e e,,e#t"(e "n se(e+al othe+ stud"es, 344-464 so "t "s not o!("ous ", the la#0 o, e,,e#t o, A-$ "n th"s stud) should !e att+"!uted to the ant"se't"# "tsel, o+ to the method used. $n anothe+ stud) *"th "n,e#ted #h+on"# '+essu+e ul#e+s, A-$ solut"on *as ,ound to +edu#e !a#te+"al le(els !ut *as no mo+e e,,e#t"(e than sal"ne. 34<4 Cade&omer iodine. .he e,,"#a#) o, #ade-ome+ "od"ne has !een sho*n "n !oth an"mal and human models (.a!le 2). Me+t/, et al., 34;4 e-am"ned the e,,e#t o, #ade-ome+ "od"ne d+ess"ng on 'a+t"al-th"#0ness *ounds "n s'e#","# 'athogen-,+ee '"gs #ontam"nated *"th o+ *"thout meth"#"ll"n- +es"stant Staphylococcus aureus (MD5&). &''l"ed da"l), #ade-ome+ "od"ne *as ,ound to s"gn","#antl) +edu#e MD5& and total !a#te+"a "n the *ounds "n #om'a+"son to no t+eatment #ont+ol and (eh"#le (#ade-ome+) at all t"me 'o"nts stud"ed (1, 2, and 3 da)s a,te+ "no#ulat"on). .he +edu#t"on *as most '+onoun#ed at da) 3. $n an un#ont+olled small stud) se+"es (n E 19), 9an"elsen, et al., 3494 used #ade-ome+ "od"ne "n ul#e+s #olon"/ed *"th Pseudomonas aeruginosa and ,ound negat"(e #ultu+es "n 65 'e+#ent and <5 'e+#ent o, 'at"ents a,te+ 1 and 12 *ee0s o, t+eatment, +es'e#t"(el). Eects o Iodine Compounds on t!e Wound 'ealing $rocess $o%idone iodine. >"te+atu+e +ega+d"ng the e,,e#t o, 'o("done "od"ne on *ound heal"ng "n an"mal *ound models "s #on,l"#t"ng. Deasons ,o+ th"s d"s#+e'an#) ma) !e d",,e+en#es "n the 'a+amete+s o, *ound heal"ng e(aluated, the (a+"et) o, assessment t"mes, "od"ne #on#ent+at"ons and #ont+ol g+ou's, and the d"(e+s"t) o, an"mal *ound models ('a+t"al th"#0ness, ,ull th"#0ness, !u+n *ounds, "s#hem"# *ounds, et#.). .he t)'e o, an"mal used a''ea+s to !e o, "m'o+tan#e, as d",,e+ent an"mals sho* d",,e+ent heal"ng +es'onses. >oose-s0"nned an"mals (m"#e, +a!!"ts, gu"nea '"gs) heal ma"nl) th+ough #ont+a#t"on, *h"le the '+"ma+) me#han"sm o, heal"ng "n t"ght- s0"nned an"mals ('"gs) "s e'"thel"/at"on, and heal"ng "n t"ght-s0"nned an"mals mo+e #losel) +esem!les the human heal"ng +es'onse. 3504 $t should !e em'has"/ed that none o, the an"mal stud"es e-am"ned the e,,e#t o, 'o("done "od"ne "n #h+on"# *ound models, as an an"mal model e6u"(alent to human #h+on"# *ounds does not e-"st. @+"e,l), "n some stud"es 'o("done "od"ne *as ,ound to #ause no "nh"!"t"on on *ound +e-e'"thel"/at"on, 351,524 *h"le "n othe+s "t +eta+ded heal"ng. 3534 &s ,a+ as the tens"le st+ength o, the *ound "s #on#e+ned, A-$ has !een +e'o+ted to #ause "n#+ease, 3544 +edu#t"on, 3564 ha(e no e,,e#t, 3554 and #ause e"the+ +edu#t"on o+ no e,,e#t de'end"ng on the assessment t"me. 3294 $t has also !een ,ound to ha(e no e,,e#t on #ollagen 3564 and g+anulat"on t"ssue '+odu#t"on o+ nons"gn","#ant +edu#t"on. 35<4 Mo+eo(e+, "t has !een sho*n to "n#+ease +e(as#ula+"/at"on. 3534 $n anothe+ stud) measu+"ng the #o+neal to-"#"t) o, ant"se't"#s, 'o("done "od"ne *as ,ound to !e nonto-"# "n +a!!"t #o+neas. 35;4 =l"n"#al stud"es e(aluat"ng the "n,luen#e o, A-$ "n *ound heal"ng a+e nume+ous. Most o, them ha(e sho*n no de#+ease o, the *ound heal"ng +ate ,+om the use o, 'o("done "od"ne. .he a,o+ement"oned stud) !) A"l7anto 3414 ,ound no e,,e#t on *ound heal"ng *hen a one-'e+#ent solut"on "s used. B"edne+ 3594 +e("e*ed the #)toto-"#"t) o, A-$ and #on#luded that Fthe no+mal #ou+se o, *ound heal"ng (su#t"on !l"ste+ 3604 ) as *ell as the d"stu+!ed one (Mohs the+a') 3614 and !u+ns 3624 ) "s not negat"(el) "n,luen#ed !) A-$.F "G+a+d-8+an#h"mont, et al., 3404 e-am"ned the e,,e#t o, A-$ "n #om!"nat"on *"th h)d+o#ollo"d d+ess"ng on (enous leg ul#e+s. .he #ont+ol g+ou' *as t+eated *"th #om'+ess"on h)d+o#ollo"d d+ess"ngs alone. 2s"ng 'lan"met+"# e(aluat"on, the) sho*ed that the +ate o, leg ul#e+ heal"ng *as a##ele+ated "n the A-$-t+eated g+ou' "n #om'a+"son to #ont+ol, es'e#"all) the ,"+st ,ou+ *ee0s o, t+eatment. >ee, et al., "n a non#ont+olled stud) ,ound +edu#t"on o, "n,e#t"on and '+omot"on o, heal"ng "n 'at"ents *"th long-stand"ng (6 months to 16 )ea+s) de#u!"tus and stas"s ul#e+at"ons. 3634 Hnutson, et al., 3644 +e'o+ted the"+ ,"(e-)ea+ e-'e+"en#e and #on#luded that the #om!"nat"on o, suga+ and A-$ enhan#ed heal"ng o, !u+ns, *ounds, and ul#e+s and +edu#ed the +e6u"+ements ,o+ s0"n g+a,t"ng, ant"!"ot"#s, and the hos'"tal #osts. Ho*e(e+, the) do not ment"on *hat Fstanda+d #a+eF the#ont+ol g+ou' +e#e"(edC ne"the+ "s "t #lea+ ", th"s "m'+o(ement "s due to A-$, to suga+, o+ to the #om!"nat"on. Ma)e+, et al., 394 +e("e*ed the in-vivo stud"es e-am"n"ng the e,,e#ts o, the (a+"ous A-$ ,o+mulat"ons on *ound heal"ng. .he) +e'o+ted ,"(e human stud"es us"ng A-$ solut"on, th+ee *"th A-$ o"ntment, and th+ee *"th A-$ #+eam. $n all these stud"es, A-$ *as not ,ound to negat"(el) "n,luen#e *ound heal"ng "n #om'a+"son to the #ont+ol g+ou' o+ to othe+ t+eatments. @u+n *ounds a+e, "n man) *a)s, d",,e+ent than the othe+ a#ute *ounds, and the) ha(e a h"ghe+ +"s0 o, "n,e#t"on that not onl) #an dela) *ound heal"ng !ut also #an #ause a s"gn","#ant +"s0 ,o+ the 'at"entIs l",e. 5teen 3654 +e("e*ed the use o, A-$ "n the t+eatment o, !u+ns. &,te+ +e("e*"ng in- vitro an"mal and human stud"es, he #on#luded that A-$ has #on#ent+at"on-de'endent #)toto-"#"t). .he h"ghe+ the #om'le-"t) o, the s)stem stud"ed (in-vivo J ex-vivo J in-vitro stud"es) the less dete#ta!le the e,,e#ts a+e. He d"d not e-#lude the 'oss"!"l"t) that A-$ ma) #ause sl"ght +eta+dat"on "n *ound heal"ng !ut !el"e(ed the !ene,"ts o, the m"#+o!"#"dal e,,e#ts o, A-$ should not !e "gno+ed. 5"n#e la+ge a+eas usuall) need to !e t+eated "n !u+n 'at"ents, +"s0s o, s)stem"# to-"#"t) o, "n#+eased A-$ a!so+'t"on *e+e +e("e*ed, as *ell. 8o+ se(e+al mo+e +e("e*s o, A-$ use on *ounds, see +e,e+en#es 9, 10, 2<, 66, and 6<. Cade&omer iodine. $n an"mal models, #ade-ome+ "od"ne has !een +e'o+ted to "n#+ease e'"de+mal +egene+at"on and e'"thel"al"/at"on "n !oth 'a+t"al-th"#0ness and ,ull-th"#0ness *ounds. 333,6;4 Ho*e(e+, #ade-ome+ "od"ne a''ea+s to ha(e no e,,e#t on g+anulat"on t"ssue ,o+mat"on, neo(as#ula+"/at"on, o+ *ound #ont+a#t"on. 3594 =ade-ome+ "od"ne has also !een the su!7e#t o, man) #l"n"#al stud"es. $n these stud"es, #ade-ome+ "od"ne has !een ,ound to !e e,,e#t"(e and !ene,"#"al to *ound heal"ng. B"ne #l"n"#al t+"als #om'a+"ng the e,,e#ts o, #ade-ome+ "od"ne *"th othe+ t+eatments on #h+on"# (enous ul#e+s sho*ed enhan#ement o, *ound heal"ng. .he othe+ t+eatments that *e+e #om'a+ed to #ade-ome+ "od"ne "n#luded (a+"ous Fstanda+d t+eatmentF (#leans"ng *"th d"luted h)d+ogen 'e+o-"de o+ d"lute 'otass"um 'e+manganate !aths and #o(e+"ng *"th e"the+ /"n# 'aste d+ess"ngs o+ nonadhe+ent d+ess"ngs, ma"nl) 'a+a,,"n-"m'+egnated o+ sal"ne d+ess"ngs, o+ sal"ne *et-to-d+) #om'+ess"(e d+ess"ngs, o+ gent"an ("olet and 'ol)m)-"n-!a#"t+a#"n o"ntment, o+ su''o+t !andag"ng%sto#0"ng and a d+) d+ess"ng), 369-<44 de-t+anome+, 3<54 and h)d+o#ollo"d d+ess"ng o+ 'a+a,,"n gau/e d+ess"ngs. 3<64 $n one stud), no #ont+ol g+ou' *as used, s"n#e the ma"n 'u+'ose o, the stud) *as to e-am"ne the sa,et) o, #ade-ome+ "od"ne *"th +ega+d to de(elo'ment o, sens"t"("t). 3<<4 $n se(e+al stud"es, the ul#e+s had !een +e#al#"t+ant to '+e("ous t+eatments. &ll stud"es ,ound #ade-ome+ "od"ne not onl) to #ause no "nh"!"t"on on *ound heal"ng !ut to a##ele+ate "t. Mo+eo(e+, o!se+(at"ons o, +edu#t"on o, 'a"n, +emo(al o, 'us, de!+"s, and e-udate, and st"mulat"on o, g+anulat"on t"ssue ,o+mat"on *e+e made. 3<14 .he +edu#t"on o, e-udate #ould !e #ons"de+ed an e-'e#ted a#t"on o, #ade-ome+ "od"ne, s"n#e #ade-ome+ "od"ne "s des"gned to a!so+! la+ge 6uant"t"es o, e-udate (ea#h g+am #an a!so+! 3m> o, ,lu"d) and then +esults "n slo* +elease o, "od"ne. &'el6("st, et al., 3<;4 e-am"ned the e,,e#ts o, #ade-ome+ "od"ne "n #a("t) ,oot ul#e+s "n d"a!et"# 'at"ents and ,ound no #l"n"#al d",,e+en#e "n #om'a+"son to othe+ t+eatments (gentam"#"n solut"on, st+e'todo+nase%st+e'to0"nase, o+ d+) sal"ne gau/e) !ut #ons"de+a!le less #osts. $n a +andom"/ed t+"al, Mo!e+g, et al., 3<94 #om'a+ed #ade-ome+ "od"ne (n E 16) *"th standa+d t+eatment (n E 1;) "n 'at"ents *"th de#u!"tus ul#e+s. =ade-ome+ "od"ne s"gn","#antl) +edu#ed 'us, de!+"s, and 'a"n o, the ul#e+s and a##ele+ated the heal"ng +ate. &,te+ e"ght *ee0s o, t+eatment, the ul#e+ a+eas *e+e +edu#ed !) <6 and 5< 'e+#ent "n the #ado-eme+ "od"ne and standa+d t+eatment g+ou', +es'e#t"(el). 5"- ul#e+s t+eated *"th #ade-ome+ "od"ne *e+e #om'letel) healed, *h"le onl) one *"th standa+d t+eatment *as healed. 5umma+"/"ng the +e("e* o, nume+ous in-vivo stud"es o, "od"ne #om'ounds the autho+s #an #on#lude that "n humans A-$ and #ade-ome+ "od"ne do not ha(e a negat"(e "n,luen#e on *ound heal"ng, *h"le #ade-ome+ "od"ne #auses an a##ele+at"on o, heal"ng "n #h+on"# human *ounds. @oth #an !e e,,e#t"(e "n +edu#"ng !a#te+"a num!e+ and de#+eas"ng "n,e#t"ons. Desults ,+om an"mal stud"es de'end on man) (a+"a!les and should !e "nte+'+eted *"th #aut"ousness. 5tud"es o, A-$ ha(e mo+e #on,l"#t"ng +esults, es'e#"all) *"th an"mal models, and ha(e #aused #on#e+n on man) #l"n"#"ans. Be(e+theless, the +esults ,+om the stud"es e(aluat"ng #ade-ome+ "od"ne a+e #lea+ and lea(e no dou!t that th"s ne*e+ "od"ne #om'ound "s e,,e#t"(e *"thout ha("ng an) negat"(e "n,luen#e on *ound heal"ng +ate. $n(e+sel), an a##ele+at"on o, *ound heal"ng has !een o!se+(ed. '(drogen $ero&ide & th+ee-'e+#ent solut"on o, h)d+ogen 'e+o-"de "s #ommonl) used as a *ound ant"se't"#. .he th+ee-'e+#ent solut"on demonst+ates in-vitro !+oad-s'e#t+um e,,"#a#). $ts g+eatest a#t"("t) "s to*a+ds 1+am-'os"t"(e !a#te+"a, !ut the '+esen#e o, #atalase "n these !a#te+"a ma0es d"lut"ons !elo* th+ee 'e+#ent less e,,e#t"(e. 314 $n a s"m"la+ ,ash"on, #atalases '+esent "n t"ssues #an +ende+ h)d+ogen 'e+o-"de e(en less !a#te+"#"dal in vivo. 364 <hough h)d+ogen 'e+o-"de "s (e+) #ommonl) used, su+'+"s"ngl) ,e* stud"es ha(e !een #ondu#ted to e-am"ne "ts e,,e#t on the *ound heal"ng '+o#ess and "ts e,,"#a#) as a *ound ant"se't"# (.a!le 3). &n"mal and human stud"es ha(e sho*n h)d+ogen 'e+o-"de to ha(e no negat"(e e,,e#t on *ound heal"ng. >"nea*ea(e+, et al., 3294 d"d not ,"nd +eta+dat"on o, +ee'"thel"/at"on "n a +at model a,te+ "++"gat"on o, the *ound *"th th+ee-'e+#ent h)d+ogen 'e+o-"de. Ho*e(e+, at the in-vitro #om'onent o, the same stud), he ,ound m"n"mal !a#te+"#"dal e,,e#t o, h)d+ogen 'e+o-"de. 1+u!e+, et al., 3524 ,ound a##ele+at"on o, +ee'"thel"/at"on "n a +at model and "n a #l"n"#al t+"al. Ho*e(e+, !ullae *e+e ,o+med on o+ a!out the da) o, heal"ng "n most o, the 'at"ents, suggest"ng 'oss"!l) that h)d+ogen 'e+o-"de should not !e used "n ne*l) ,o+med e'"thel"um. $n anothe+ stud) !) .u+, et al., 3;04 h)d+ogen 'e+o-"de *as ,ound to s"gn","#antl) "n#+ease the !lood ,lo* "n "s#hem"# ul#e+s "n a gu"nea '"g model. .he "n#+eased !lood ,lo* ma) !e due to ne* (essel ,o+mat"on th+ough a#t"(at"on o, metallo'+ote"nases. $nte+est"ngl), the !lood ,lo* *as "n#+eased e(en "n 'la#es d"stant to the lo#al a''l"#at"on o, h)d+ogen 'e+o-"de. Bo e-'lanat"on *as g"(en ,o+ th"s ,"nd"ng. Ho*e(e+, the autho+s ,ound no d",,e+en#e "n the *ound-heal"ng +ate. .h"s ma) !e due to the l"m"ted sens"t"("t) o, the method the) used to e(aluate the #l"n"#al +es'onse (("sual dete+m"nat"on o, the non-ne#+ot"# a+ea). $n a #l"n"#al stud) e(aluat"ng the e,,e#t"(eness o, h)d+ogen 'e+o-"de on +edu#"ng the "n,e#t"on +ate o, a''ende#tom) *ounds, no to-"# e,,e#ts *e+e ,ound, !ut "t *as ,ound to !e "ne,,e#t"(e. 3;14
5"m"la+l), "n anothe+ #l"n"#al stud) "n human !l"ste+ *ounds #ontam"nated *"th Staphylococcus aureus, h)d+ogen 'e+o-"de *as ,ound not to +eta+d the heal"ng !ut ne"the+ d"d "t de#+ease !a#te+"al load. 3;24 $n #on#lus"on, h)d+ogen 'e+o-"de a''ea+s not to negat"(el) "n,luen#e *ound heal"ng, !ut "t "s also "ne,,e#t"(e "n +edu#"ng the !a#te+"al #ount. Ho*e(e+, "t ma) !e use,ul as a #hem"#al de!+"d"ng agent. .he &me+"#an Med"#al &sso#"at"on #on#luded that the e,,e+(es#en#e o, h)d+ogen 'e+o-"de m"ght '+o("de some me#han"#al !ene,"t "n loosen"ng de!+"s and ne#+ot"# t"ssue o, the *ound. 3134 Acetic Acid &#et"# a#"d "s ,+e6uentl) used "n *ounds as a 0.25-'e+#ent o+ 0.5-'e+#ent solut"on. $t "s !a#te+"#"dal aga"nst man) 1+am-'os"t"(e and 1+am-negat"(e o+gan"sms, es'e#"all) Pseudomonas aeruginosa. Bo dela) o, +ee'"thel"/at"on has !een ,ound "n an"mal and human models. 3524 <hough one stud) ,ound that a#et"# a#"d "n"t"all) dela)ed +ee'"thel"/at"on, a,te+ the e"ghth da), th"s e,,e#t d"d not 'e+s"st. $n the same stud), "t *as not sho*n to "n,luen#e tens"le *ound st+ength. 3294 $n t*o human un#ont+olled stud"es, a#et"# a#"d *as ,ound to !e !ene,"#"al "n *ounds "n,e#ted *"th Pseudomonas aeruginosa. 3;3,;44 $n a stud) *"th 'at"ents *"th (enous leg ul#e+s, 3;54 gau/e d+ess"ngs *etted *"th a#et"# a#"d *e+e sho*n to e,,e#t"(el) de#+ease the num!e+ o, Staphylococcus aureus and 1+am-negat"(e +ods. seudomonas *as not +edu#ed s"gn","#antl). <hough se(e+al in-vitro stud"es ,ound a#et"# a#"d to !e #)toto-"#, 331,;64 the in-vivo stud"es do not #on,"+m these ,"nd"ngs. .he autho+s !el"e(e that a#et"# a#"d #an #ont"nue !e"ng used to'"#all) "n #ontam"nated *ounds *he+e an agent "s needed "n o+de+ to el"m"nate the #han#es o, "n,e#t"on (.a!le 4). C!lor!e&idine =hlo+he-"d"ne has !een #ommonl) used "n d"s"n,e#tant and ant"se't"# solut"ons. =hlo+he-"d"ne ant"se't"# solut"ons a+e used ma"nl) "n u+olog), g)ne#olog), dent"st+), and "n the t+eatment o, *ounds. $t "s h"ghl) !a#te+"#"dal. 5e(e+al an"mal stud"es ha(e tested the e,,"#a#) and sa,et) o, #hlo+he-"d"ne on *ounds (.a!le 5). $t has !een ,ound to ha(e m"ld "nh"!"to+) e,,e#ts on *ound heal"ng "n gu"nea '"gs. 3;<4
=hlo+he-"d"ne d"a#etate *as ,ound to a##ele+ate *ound heal"ng "n ,ull-th"#0ness *ounds "n !eagles. 3;;4 =hlo+he-"d"ne *as also ,ound to !e +elat"(el) sa,e ,o+ use as a su+g"#al *ound "++"gat"on solut"on, s"n#e onl) the h"ghe+ #on#ent+at"ons tested (0.05K) #aused sl"ght t"ssue to-"#"t) "n +ats. 3;94 >o*e+ #on#ent+at"ons (0.02K) a+e +e#ommended ,o+ *ound "++"gat"on. $n othe+ stud"es, "t *as ,ound to #ause "nh"!"t"on o, g+anulat"on t"ssue "n gu"nea '"gs 35<4 and de#+eased tens"le st+ength o, *ounds "n +ats. 3904 Ho*e(e+, @+ennan, et al., ,ound no de#+ease "n #ollagen '+odu#t"on "n a +at model, 3914 and 5hahan, et al., also "n a +at model, ,ound de#+eased tens"le st+ength 4; hou+s a,te+ the t+eatment and s"gn","#antl) "n#+eased st+ength at 96 hou+s, s"n#e #hlo+he-"d"ne de#+eased the heal"ng t"me. 3924 $n human stud"es, #hlo+he-"d"ne +"nses *e+e sho*n e,,e#t"(e "n +edu#"ng m"#+o!"al #om'l"#at"ons *hen used 'e+"o'e+at"(el) "n 'at"ents that +e#e"(ed dental "m'lants. 3934 =on(e+sel), "n anothe+ stud), "t *as ,ound to !e "ne,,e#t"(e to +edu#e *ound se's"s +ate and length o, hos'"tal sta) "n 'at"ents that had unde+gone a''end"#e#tom). 3944 .he autho+s s'e#ulate that +e"n,e#t"on ,+om *"th"n as an e-'lanat"on ,o+ the la#0 o, #hlo+he-"d"ne e,,"#"en#). =hlo+he-"d"ne a''ea+s to !e +elat"(el) sa,e *"th l"ttle e,,e#t on the *ound heal"ng '+o#ess, and "ts use ma) ,a(o+ heal"ng o, o'en *ounds "n +"s0 ,o+ "n,e#t"on. Ho*e(e+, the +esults ,+om stud"es to date a+e "nsu,,"#"ent to d+a* #on#lus"ons a!out the use o, #hlo+he-"d"ne on o'en *ounds. Mo+e human t+"als need !e 'e+,o+med to assess "ts e,,"#a#) and sa,et). Sil%er Compounds 5"l(e+ #om'ounds ha(e *"del) !een used as *ound ant"se't"#s, ma"nl) "n !u+ns. 5"l(e+ sul,ad"a/"ne (559) and s"l(e+ n"t+ate (&gB:3) a+e among the most #ommonl) used. 5"l(e+ sul,ad"a/"ne "s the most !+oadl) used t+eatment ,o+ the '+e(ent"on o, "n,e#t"on "n 'at"ents *"th !u+n *ounds. 395,964 =om!"nat"ons o, 559 *"th #e+"um n"t+ate 39<4 and nano#+)stall"ne s"l(e+ +eleas"ng s)stems (&#t"#oatL, Westa"m @"omed"#al, M-ete+, Be* Hano(e+) 39;4 ha(e !een de(elo'ed "n o+de+ to "n#+ease "ts e,,"#a#) and%o+ +edu#e "ts to-"#"t). Be*e+ s"l(e+ ,o+mulat"ons a''ea+ to "n#+ease the +ate and deg+ee o, m"#+o!"al 0"ll"ng, de#+ease e-udate ,o+mat"on, and #an +ema"n a#t"(e ,o+ da)s. 3994 &n"mal stud"es e-am"n"ng the e,,e#ts o, 559 and &gB:3 on *ounds ha(e sho*ed no s"gn","#ant e,,e#t 3534 on e'"thel"/at"on +ate (.a!le 6). 559 *as also ,ound to "n#+ease the +ate o, neo(as#ula+"/at"on. 3534 $n anothe+ stud) "n +ats, s"l(e+ #om'ounds *e+e ,ound to '+omote *ound heal"ng, +edu#e the "n,lammato+) and g+anulat"on 'hases o, heal"ng, and "n,luen#e metal "on !"nd"ng. 31004 Mo+eo(e+, 1e+onemus, et al., 3514 ,ound "n#+eased +ee'"thel"/at"on +ate "n domest"# '"gs *"th the use o, 559. Net, >e"t#h, et al., 31014 ,ound 559 to #ause "nh"!"t"on o, *ound #ont+a#t"on "n an a#ute *ound +at model. >"0e*"se, B"edne+, et al., 35<4 ,ound a sl"ght, nons"gn","#ant +edu#t"on o, g+anulat"on t"ssue ,o+mat"on *"th the use o, &gB:3. &mong human stud"es, the autho+s '+esent onl) those on 'at"ents su,,e+"ng ,+om *ounds othe+ than !u+ns, as the+e "s #u++entl) no #ont+o(e+s) ,o+ the use o, s"l(e+ #om'ounds on !u+n 'at"ents, as ment"oned a!o(e. Hu#an, et al., 34<4 e-am"ned the e,,e#ts o, 559 on !a#te+"al #ounts "n 'at"ents *"th "n,e#ted #h+on"# '+essu+e ul#e+s. He ,ound 559 to !e e,,e#t"(e "n de#+eas"ng the !a#te+"a !elo* 105%g+ t"ssue "n all the ul#e+s t+eated. $n a +andom"/ed t+"al *"th (enous ul#e+s, 559 one-'e+#ent #+eam *as '+o(ed to stat"st"#all) +edu#e the ul#e+ s"/e #om'a+ed to the 'la#e!o, 31024 *h"le "n anothe+ stud) "t *as ,ound to !e *ell tole+ated and e,,e#t"(e on *ound #leans"ng and g+anulat"on t"ssue ,o+mat"on. 31034 >"("ngstone, et al., 31044 stud"ed the e,,e#t o, &gB:3 and an ant"!"ot"# solut"on (neom)#"n 'lus !a#"t+a#"n) on +edu#"ng autogenous s0"n g+a,t loss due to "n,e#t"on "n 'at"ents *"th the+mal "n7u+). .he) ,ound !oth med"#at"ons to !e e,,e#t"(e "n #om'a+"son to the #ont+ol g+ou' (D"nge+Is la#tate solut"on), !ut the ant"!"ot"# solut"on *as asso#"ated *"th the +a'"d eme+gen#e o, d+ug-+es"stant o+gan"sms, *h"le &gB:3 *as not. Bano#+)stall"ne s"l(e+ #om'ounds ha(e !een ,ound to "n#+ease the +ee'"thel"/at"on +ate o, meshed autog+a,ts 31054 and a''ea+ to !e '+om"s"ng ,o+ the t+eatment o, othe+ #h+on"# *ounds as *ell. .he ant"-"n,lammato+) e,,e#ts o, s"l(e+ #ould !e asso#"ated *"th the (eh"#le, *h"#h +edu#es *ound d+)"ng, +edu#"ng the+e,o+e "n,lammat"on (mo"st *ounds ha(e !een ,ound to !e s"gn","#antl) less l"0el) to !e "n,e#ted). 31114 Mo+e #l"n"#al t+"als a+e needed ,o+ the e(aluat"on o, nano#+)stall"ne s"l(e+. 5umma+"/"ng, "t a''ea+s that s"l(e+ #om'ounds do not ha(e a negat"(e e,,e#t on *ounds and ma)!e a##ele+ate *ound heal"ng #l"n"#all). .he"+ in-vivo ant"m"#+o!"al a#t"("t) "s not "n 6uest"on. Discussion .he use o, ant"se't"#s on *ounds "s #u++entl) !e"ng ("e*ed *"th s0e't"#"sm. Desults ,+om in- vitro stud"es ha(e sho*n that ant"se't"#s a+e to-"# not onl) aga"nst !a#te+"a and othe+ m"#+oo+gan"sms !ut also aga"nst human #ells essent"al to the *ound heal"ng +es'onse. .hese ,"nd"ngs +esulted "n a se+"es o, an"mal and human stud"es "n o+de+ to e(aluate the in-vivo a#t"("t) o, ant"se't"#s. Ho*e(e+, "t seems that "n human su!7e#ts, '+onoun#ed #)toto-"#"t), ,ound in vitro, *as not #on,"+med. $n the ma7o+"t) o, #l"n"#al t+"als, ant"se't"#s a''ea+ to !e sa,e and *e+e not ,ound to negat"(el) "n,luen#e *ound heal"ng. .he"+ ant"m"#+o!"al e,,"#"en#), *"th the e-#e't"on o, h)d+ogen 'e+o-"de, seems sat"s,a#to+) as *ell. Dandom"/ed #ont+olled stud"es to e(aluate the e,,e#t o, ea#h ant"se't"# on the d",,e+ent 0"nds o, *ounds (a#ute, (enous, d"a!et"#, o+ '+essu+e ul#e+s) a+e "nd"#ated to '+o("de g+eate+ e("den#e +ega+d"ng the !ene,"ts o, ant"se't"# use on *ounds. M,,o+ts to de(elo' su'e+"o+ ant"se't"# ,o+mulat"ons a+e l"0el) to and should #ont"nue. 9e(elo'ment o, #ade-ome+ "od"ne, *h"#h not onl) does not negat"(el) "n,luen#e *ound heal"ng !ut also a##ele+ates heal"ng e(en "n non"n,e#ted *ounds, and de(elo'ment o, "m'+o(ed s"l(e+ del"(e+) s)stems, *h"#h +elease s"l(e+ mo+e e,,"#"entl) than '+e("ous ,o+mulat"ons *h"le enhan#"ng +e-e'"thel"/at"on, a+e 'a+ad"gms o, the the+a'eut"# 'otent"al o, ant"se't"#s. Aeh"#les that #ont+"!ute to the ma"ntenan#e o, an o't"mal mo"st en("+onment ma) !e mo+e a''+o'+"ate as del"(e+) s)stems o, ant"se't"#s than the #u++ent ones, s"n#e mo"st en("+onments +esult "n !oth "n#+eased *ound heal"ng +ate and enhan#ement o, ant"m"#+o!"al 'enet+at"on to *ounds. &nt"se't"#s need not !e om"tted ,+om the the+a'eut"# a+mamenta+"um o, *ound #a+e. $n 'at"ents and *ound t)'es *"th h"gh +"s0 o, "n,e#t"on, ant"se't"#s ma) !e used to '+e(ent *ound "n,e#t"on that *ould ha(e delete+"ous e,,e#ts on *ound heal"ng. &nt"se't"#s '+esent ad(antages o(e+ to'"#al ant"!"ot"#s, s"n#e the) do not #ause the eme+gen#e o, d+ug-+es"stant !a#te+"a and ha(e !+oade+ ant"m"#+o!"al s'e#t+um and lo*e+ sens"t"/at"on +ates. $n #on#lus"on, a,te+ +e("e* o, the l"te+atu+e, most ant"se't"#s, es'e#"all) ne*e+ ,o+mulat"ons, a''ea+ to !e +elat"(el) sa,e and e,,"#"ent "n '+e(ent"ng "n,e#t"on "n human *ounds. .he ad(antages o, ant"se't"#s on *ounds ma) out*e"gh 'oss"!le d"sad(antages, and the"+ 'os"t"on "n *ound #a+e management should !e +e#ons"de+ed. )ables )able *. $o%idone iodine Aut!or Wound )(pe Species +umber o Wounds )reated Control,Comparator Eect on 'ealing Eect on Inection @ennett, et al. 310<4 a+t"al th"#0ness "gs 4; (; *ounds ,o+ ea#h g+ou') Ma,en"de a#etateC sod"um h)'o#hlo+"teC h)d+ogen 'e+o-"deC a#et"# a#"dC no t+eatment Bo e,,e#t (;1K +ee'"thel"al"/at"on, *"th 1K $, a,te+ 4 da)s (s. 69K ,o+ the no t+eatment g+ou', nons"gn","#ant d",,e+en#e) 5l"ghtl) de#+eased !a#te+"al #ounts, ()et st"ll J105, stat"st"#al d",,e+en#e ,+om #ont+ol not #al#ulated) 8umal, et al. 31104 >eg ul#e+s Humans 34 (1< 'at"ents) Bo t+eatmentC s"l(e+ sul,ad"a/"neC #hlo+he-"d"ne (all g+ou's t+eated *"th h)d+o#ollo"d d+ess"ng) $n#+ease (4-1;K "m'+o(ement o, heal"ng +ate, 2-9 *ee0s ,aste+ (s. unt+eated, ' O 0.01) B%& Ho*ell, et al. 33<4 =ontam"nated la#e+at"ons (*"th S. aureus) 1u"nea '"gs 4; (12 an"mals) 5al"neC #e,a/ol"nC no t+eatment B%& Bo e,,e#t (4.63 log 5. au+eus +e#o(e+ed ,+om *ounds 2 h a,te+ "++"gat"on (s. 5.4<, 6.13, and 6.3< ,o+ no t+eatment, #e,a/ol"n, and sal"ne g+ou's, +es'e#t"(el)C nons"gn","#ant d",,e+en#e) 1eo+g"ades, et al. 33;4 @u+ns Humans 50 B%& B%& 9e#+ease (<<K o, *ound #ultu+es d"d not ha(e !a#te+"al g+o*th a,te+ ?$9 a''l"#at"on (s. 42K and 33K ,o+ the @$9%.$9 and ?:9%?9 a''l"#at"on g+ou's, ' O 0.001) 1e+on"mus, et al. 3514 a+t"al th"#0ness "gs 600 *ounds ("n 4 an"mals, 300 ,o+ ea#h g+ou') Bo t+eatment Bo "n,luen#e (4.55 da)s needed ,o+ 50K o, *ounds to +ee'"thel"al"/e *"th 'ha+mad"ne 39- 12K $ solut"on4 (s. 4.6 ,o+ #ont+ol, +elat"(e +ate o, heal"ng P1KC nons"gn","#ant d",,e+en#e) B%& 1+a(ett, et al. 3394 5utu+ed la#e+at"ons Humans 395 Bo t+eatment (all *ounds *e+e "n"t"all) "++"gated *"th sal"ne) B%& 9e#+ease (1K +ate o, 'u+ulent *ounds and 5.4<K *ound se's"s +ate (s. 6.19K and 15.4K at the #ont+ol g+ou') 1+u!e+, et al. 3524 a+t"al and ,ull th"#0ness Dats 40 (20 ,o+ ea#h g+ou') 5al"ne Bo e,,e#t (12.2 and 9.3 da)s mean heal"ng t"me ,o+ !etad"ne (s. 12.4 and 9.5 ,o+ sal"ne "n 'a+t"al- th"#0ness *ounds "n +ats and humansC 19.2 (s. 19.5 "n ,ull- th"#0ness *ounds "n +ats, nons"gn","#ant d",,e+en#e) B%& Humans 20 (10 ,o+ ea#h g+ou') Hasha)a', et al. 3564 $n#"s"onal M"#e 120 (2 an"mals) Aeh"#leC ste+o"dsC no t+eatment 9e#+eased st+ength%no e,,e#t on #ollagen (334g+ !u+st"ng st+ength (s. 404, 439, and 322 at the (eh"#le, no t+eatment, and ste+o"d g+ou's, +es'e#t"(el)C ' O 0.05 (s. no t+eatment g+ou') B%& H7olseth, et 8ull th"#0ness M"#e 23 (13 Bo t+eatment 9e#+ease (11.; B%& al. 3534 #ont+ol, 10 $) da)s ,o+ #om'lete +ee'"thel"/at"on (s. <.2 ,o+ #ont+ol, ' O 0.01) Hnutson, et al. 3644 @u+ns, #h+on"# *ounds Humans <59 (90 $ solut"on and suga+, 515 $ solut"on, $ o"ntment and suga+, 154 standa+d t+eatment) 5tanda+d the+a') $n#+ease (0K need ,o+ s0"n g+a,t ,o+ the t+"'le #om!"nat"on g+ou', 4.5K ,o+ the $ sol%suga+ g+ou' (s. 40.3K ,o+ the #ont+ol g+ou') 9e#+ease Hu#an, et al. 34<4 +essu+e ul#e+s Humans 40 (15 559, 15 A-$, 14 sal"ne) 5al"neC A-$ B%& Bo e,,e#t (60K o, 'at"ents +es'onded to t+eatment a,te+ 14 da)s (s. 60K and 90K at the sal"ne and 559 g+ou's) >amme+s, et al. 3434 &#ute hea("l) #ontam"nated Humans 33 5al"neC no t+eatment B%& Bo e,,e#t (!a#te+"al #ounts s"m"la+ to no t+eatment g+ou' a,te+ 10 m"nC sal"ne soa0"ng "n#+eased !a#te+"al #ounts, ' O . 0001) >ee, et al. 3634 9e#u!"tus ul#e+sC stas"s ul#e+s Humans 1; B%& $n#+ease (6<K o, ul#e+s #u+ed a,te+ 6 *0s, 33K o, ul#e+s "m'+o(ed) 9e#+ease (2 out o, 14 "n,e#ted les"ons #ont"nued !e"ng "n,e#ted a,te+ 6 *0s, ' O 0.001) Menton, et al. 3544 $n#"s"onal 1u"nea '"gs 120 (60 an"mals) 5al"neC 5hu+-=lensC 95 ;9009 9e#+ease (!etad"ne su+g"#al s#+u! s"gn","#antl) dela)ed e'"de+mal and de+mal heal"ng (s. all g+ou's, !ut "n#+eased s"gn","#antl) tens"le st+ength a,te+ 21 da)s (s. all g+ou's) B%& Me+t/, et al. 310;4 a+t"al th"#0ness "gs 54 (9 an"mals) 9"st"lled *ate+C al#ohol <0K B%& 9e#+ease (5.94 log !a#te+"al #ounts a,te+ 24 h+ (s. <.53 and <.2; at the *ate+ and al#ohol g+ou's, ' O 0.05) Mull"0en, et al. 3554 $n#"s"onal Dats 341 D"nge+Qs solut"on Bo e,,e#t on st+ength (1<.52 gm%mm2 tens"le st+ength a,te+ 1 *0 (s. 1<.90 at the D"nge+Qs solut"on g+ou'C nons"gn","#ant d",,e+en#e) B%& B"edne+ 35<4 8ull th"#0ness 1u"nea '"gs 10 ,o+ ea#h g+ou' Bo t+eatment Bo e,,e#t (nons"gn","#ant de#+ease !) 19K o, th"#0ness o, the g+anulat"on la)e+ "n #om'a+"son to #ont+ol) B%& "e+a+d- 8+a#h"mont, et al. 3404 Aenous ul#e+s Humans 30 (15 'at"ents) Bo t+eatment (!oth g+ou's t+eated *"th h)d+o#ollo"d d+ess"ngs) $n#+ease ("n#+eased heal"ng +ate *"th A-$ t+eatment, es'e#"all) du+"ng the ,"+st 4 *ee0s o, t+eatment, ' O 0.05) 9e#+ease (less neut+o'h"l"# (as#ul"t"s, and !a#te+"al #lum's "n A- $ t+eated g+ou', s"gn","#an#e not #al#ulated) Dodehea(e+, et al. 3364 =ontam"nated 1u"nea '"gs 5al"ne B%& 9e#+ease (R) (1.31 log +edu#t"on o, !a#te+"a 10 m"n a,te+, ' O 0.001C no e,,e#t 4 da)s a,te+ a s"ngle a''l"#at"onC no e,,e#t on "n,e#t"on +ate) 5e(e+)ns, et al. 3;94 8emo+al (essels se#t"on Dats 150 an"mals 5al"ne, #hlo+he-"d"ne .o-"#"t) (ma+0ed d",,e+en#e o, 10K $ solut"ons on h"stolog"#al assessment, damage to (as#ula+ endothel"um and th+om!os"s, (s. sal"ne, and #hlo+he-"d"ne) B%& 5"ndela+, et al. 3464 5u+g"#al Humans 500 (242 $, 25; #ont+ol) 5al"ne B%& 9e#+ease (2.9K *ound se's"s +ate (s. 15.1K "n the #ont+ol g+ou', ' O 0.001) A"l7ando 3414 5u+g"#al Humans 294 5al"ne Bo e,,e#t (#ell mo+'holog) s"m"la+ to sal"ne- "m'eded #ont+ol) 9e#+ease (2.6K "n,e#t"on +ate *"th 1K $ solut"on a,te+ a''ende#tom) (s. ;.5K at the #ont+ol g+ou'C ho*e(e+, 19K "n,e#t"on +ate *"th 5K $ solut"on (s. ;K at the #ont+ol g+ou') )able -. Cade&omer iodine Aut!or Wound )(pe Species +umber o Wounds )reated Control Eect on 'ealing Eect on Inection &'el6("st, et al. 3<;4 9"a!et"# ul#e+s Humans 25 (12 =$, 13 #ont+ol) 5tanda+d t+eatment Bo d",,e+en#e !et*een g+ou's B%& 9an"elsen, et al. 3494 Aenous ul#e+s *"th P. aeruginosa Humans 1< B%& B%& 9e#+ease !a#te+"al #ounts (65K o, 't had negat"(e . ae+ug"nosa #ultu+es a,te+ 1 *0) 8lo)e+, et al. 3<<4 Aenous ul#e+s Humans 30 (ul#e+s dete+"o+at"ng o+ stat"# "n the"+ e-"st"ng t+eatment) B%& $n#+ease (15 out o, 1; ul#e+s healed o+ +edu#ed "n s"/e, *h"le 3 "n#+eased) (9e#+easeS) (e+)thema, e-udate, 'us, and de!+"s *e+e +edu#ed ,+om !asel"ne) Hansson, et al. 3<64 Aenous ul#e+s Humans 153 H)d+o#ollo"d d+ess"ng o+ 'a+a,,"n gau/e $n#+ease (62K mean +edu#t"on o, ul#e+ a+ea (s. 41K and 24K "n the h)d+o#ollo"d and 'a+a,,"n gau/e g+ou's) B%& Ha+#u', et al. 3<44 Aenous ul#e+s Humans <2 5tanda+d t+eatment (d+) d+ess"ng T to'"#al ant"!a#te+"al #leanse+) $n#+ease (36K de#+ease o, ul#e+ s"/e a,te+ 4 *0s (s. 10K "n the standa+d t+eatment g+ou', ' O 0.01) (9e#+easeS) (de#+ease o, edema, e+)thema, e-udate, 'us, de!+"s, 'a"n, ' O 0.05-' O 0.001) Hollo*a), et al. 3<24 Aenous ul#e+s Humans <5 (3; =$, 3< #ont+ol) 5tanda+d t+eatment (*et-to-d+) d+ess"ngs) $n#+ease (0.95T0.12#m2%*0 ul#e+ heal"ng (s. 0.41T0.13 "n the standa+d t+eatment, ' O 0.0025) (Bo e,,e#t- de#+easeS) (not stat"st"#all) s"gn","#ant) >amme et, al. 36;4 8ull th"#0ness "gs 36 (12 =$, 12 #ade-ome+, 12 sal"ne) =ade-ome+ and 5al"ne $n#+ease ("n#+ease "n +ee'"thel"al"/at"on 6 and 9 da)s a,te+ t+eatment, ' O 0.05) B%& >audans0a, et al. 3694 Aenous ul#e+s Humans 60 (30 =$, 30 #ont+ol) 5tanda+d t+eatment (#leans"ng *"th d"lute h)d+ogen 'e+o-"de and #o(e+"ng *"th a /"n# 'aste d+ess"ng) $n#+ease (<4K mean +edu#t"on o, ul#e+ a+ea a,te+ 6 *0s (s. 54K "n the standa+d t+eatment, ' O 0.01) (9e#+easeS) (de#+eased de!+"s, e-udate, e+)thema, and edema, ' O 0.05-' O 0.001) Me+t/, et al. 3334 a+t"al th"#0ness "gs 120 (,o+ the e'"thel"al"/at"on stud)C 40 "n ea#h g+ou') &"+ e-'osed and o"ntment !ase #ont+ol $n#+ease (4.6 da)s ,o+ #om'lete e'"thel"al"/at"on o, 50K o, the *ounds (s. 4.9 and 5.< da)s ,o+ o"ntment !ase #ont+ol and a"+ e-'osed *ounds, s"gn","#ant) 9e#+ease !a#te+"al #ounts (s"gn","#ant +edu#t"on o, 5. au+eus #ounts at 24, 4;, and <2 hou+s and o, . ae+ug"nosa at 4; hou+s) 1; (S. aureus o+ P. aeruginosa "no#ulated *ounds ,o+ the !a#te+"olog"#al stud)C 6 "n ea#h g+ou') Mo!e+g, et al. 3<94 9e#u!"tus ul#e+s Humans 34 (1; =$, 16 #ont+ol) 5tanda+d t+eatment (sal"ne d+ess"ngs, de!+"d"ng agents o+ non adhes"(e d+ess"ngs) $n#+ease (<6K de#+ease "n ul#e+ s"/e a,te+ ; *ee0s o, t+eatment, (s. 5<K de#+ease "n the standa+d t+eatment g+ou', ' O 0.05) (9e#+easeS) (9e#+ease o, 'a"n, 'us, and de!+"s, ' O 0.005) :+m"ston, et al. 3<34 Aenous ul#e+s Humans 60 (30 =$, 30 #ont+ol) 5tanda+d t+eatment (gent"an ("olet and 'ol)m)-"n- !a#"t+a#"n o"ntment) $n#+ease (0.;9#m2%*0 ul#e+ heal"ng (s. 0.46 "n the standa+d t+eatment, ' O 0.0001) (Bons"gn","#ant de#+easeS) 50og, et al. 3<14 Aenous ul#e+s Humans <4 (36 =$, 3; #ont+ol) 5tanda+d t+eatment (most #ommonl) 'a+a,,"n- "m'+egnated $n#+ease (34K de#+ease "n ul#e+ s"/e a,te+ 6 *ee0s o, t+eatment, (s. 5K "n#+ease "n the standa+d 9e#+ease ("n 16 out o, 23 't "n,e#t"on *as #lea+ed "n #om'a+"son to 0 out o, 1; "n d+ess"ngs) t+eatment g+ou') the standa+d t+eatment g+ou') .a+(a"nen, et al. 3<54 Aenous ul#e+s Humans 2< (14 =$, 13 #ont+ol) 9e-t+anome+ $n#+ease (64K o, 't healed a,te+ ; *0s (s. 50K "n the de-t+anome+ g+ou') (Bo e,,e#t) (+edu#t"on o, e+)thema, e-udate, and 'us ,+om !asel"ne, nons"gn","#ant d",,e+en#e !et*een g+ou's) S =ade-ome+ "od"ne de#+eased one o+ mo+e o, 'us and de!+"s, e-udate, 'a"n, and e+)thema, *h"#h a+e #ons"de+ed as #l"n"#al "nd"#ato+s o, "n,e#t"on. )able .. '(drogen pero&ide Aut!or Wound )(pe Species +umber o Wounds )reated Control Eect on 'ealing Eect on Inection @ennett, et al. 310<4 a+t"al th"#0ness "gs 4; (; *ounds ,o+ ea#h g+ou') Ma,en"de a#etateC sod"um h)'o#hlo+"teC 'o("done "od"neC a#et"# a#"dC no t+eatment Bo e,,e#t (69K +ee'"thel"al"/at"on a,te+ 4 da)s (s. 69K ,o+ the no t+eatment g+ou') 9e#+eased !a#te+"al #ounts, (O105 (s. J105 at the #ont+ol g+ou', stat"st"#al d",,e+en#e not #al#ulated) 1+u!e+, et al. 3524 a+t"al and ,ull th"#0ness Dats 40 (20 ,o+ ea#h g+ou') 5al"ne $n#+ease (10.2 and ;.4 da)s mean heal"ng t"me (s. 12.4 and 9.5 ,o+ sal"ne "n 'a+t"al-th"#0ness *ounds "n +ats and humansC 1< (s. 19.5 "n ,ull- th"#0ness *ounds "n +ats, p O 0.05 ,o+ the an"mal stud), nons"gn","#ant d",,e+en#e ,o+ the human stud)) B%& Humans 20 (10 ,o+ ea#h g+ou') >au, et &''ende#tom) Humans 21< (109 Bo t+eatment B%& Bo e,,e#t al. 3;14 H, 10; #ont+ol) (21 't de(elo'ed "n,e#t"on (s. 26 o, the #ont+ol g+ou') >e)den, et al. 3;24 @l"ste+ *ounds (#ontam"nated) Humans 144 (24 (oluntee+s *"th 3 *ounds 'e+ ,o+ea+m) Bo t+eatment, t+"'le ant"!"ot"# Bo e,,e#t (14.3 da)s ,o+ heal"ng (s. 13.2 and 9.4 "n the no t+eatment and t+"'le ant"!"ot"# g+ou') Bo e,,e#t (6.< log S. aureus #ounts (s. <.1 and 0.4 "n the no t+eatment and t+"'le ant"!"ot"# g+ou') .u+, et al. 3;04 $s#hem"# ul#e+s 1u"nea '"gs 34 la#e!o #+eam Bo e,,e#t (("sual e(aluat"on o, 'e+#ent nonne#+ot"# *ound su+,a#e sho*ed no d",,e+en#e !et*een g+ou's)C "n#+eased !lood ,lo* ((as#ula+ 'e+,us"on measu+ed *"th lase+ 9o''le+ (elo#"mete+ *as "n#+eased, p O 0.01) B%& )able /. Acetic acid Aut!or Wound )(pe Species +umber o Wounds )reated Control,Comparator Eect on 'ealing Eect on Inection @ennett, et al. 310<4 a+t"al th"#0ness "gs 4; (; *ounds ,o+ ea#h g+ou') Ma,en"de a#etateC sod"um h)'o#hlo+"teC h)d+ogen 'e+o-"deC 'o("done "od"neC no t+eatment Bo e,,e#t (<<K +ee'"thel"al"/at"on a,te+ 4 da)s (s. 69K ,o+ the no t+eatment g+ou', nons"gn","#ant d",,e+en#e) Bo e,,e#t (J105, stat"st"#al d",,e+en#e ,+om #ont+ol not #al#ulated) 1+u!e+, et al. 3524 a+t"al and ,ull th"#0ness Dats 40 (20 ,o+ ea#h g+ou') 5al"ne Bo e,,e#t (12 and 9.3 da)s mean heal"ng t"me (s. 12.4 and 9.5 ,o+ sal"ne "n 'a+t"al- th"#0ness *ounds "n +ats and B%& Humans 20 (10 ,o+ ea#h g+ou') humansC 1;.6 (s. 19.5 "n ,ull- th"#0ness *ounds "n +ats, nons"gn","#ant d",,e+en#e) Hansson, et al. 3;54 Aenous ul#e+s Humans 45 &lum"num a#etota+t+ateC 'otass"um 'e+manganateC #hlo+am"ne B%& 9e#+ease (a#et"# a#"d 0.25K +edu#ed !oth S. aureus and 1+am- negat"(e +ods, p O 0.002 and p O 0.03. seudomonas, +oteus, S. epidermidis, and S. hemolyticus *e+e not s"gn","#antl) +edu#ed, p J 0.05) 5loss, et al. 3;44 @u+ns o+ so,t t"ssue *ounds Humans 16 B%& B%& 9e#+ease (el"m"nated P. aeruginosa #ounts "n 14 out o, 16 'at"ent *"th"n 2 *ee0s) h"ll"'s, et al. 3;34 5u'e+,"#"al Humans 20 (10 a#et"# a#"d, 10 #ont+ol) =hlo+he-"d"ne o+ h)'o#hlo+"te B%& 9e#+ease (mean g+o*th ,ell ,+om 4.1 to 0.< a,te+ < da)s (s. 3.3 to 3.4 "n the #ont+ol g+ou') )able 0. C!lor!e&idine Aut!or Wound )(pe Species +umber o Wounds )reated Control,Comparator Eect on 'ealing Eect on Inection @+ennan, et al. 3914 8ull th"#0ness Dats 540 (45 an"mals *"th 4 *ounds ea#h, ,o+ ea#h g+ou': #hlo+he-"d"ne, sal"ne, #hlo+am"ne .) 5al"ne, #hlo+am"ne Bo e,,e#t (no d",,e+en#e ,+om sal"ne on #ollagen '+odu#t"on and on h"stolog"# e-am"nat"on) B%& =+oss,"ll, et al. 3944 &''end"#e#tom) *ounds Humans 2;; (9< #hlo+he-"d"ne, 5al"ne, no t+eatment Bo e,,e#t on hos'"tal sta) Bo e,,e#t (o(e+all se's"s 9< sal"ne, 92 no t+eatment) (a(e+age sta) o, ;.2 da)s ,o+ non"n,lamed a''end"#es (s. ;.3 and ;.; ,o+ sal"ne and no t+eatment g+ou's, nons"gn","#ant d",,e+en#e) +ate 13.2K (s. 12.2K and 14.1K ,o+ sal"ne and no t+eatment g+ou's, nons"gn","#ant d",,e+en#e) 8umal, et al. 31104 >eg ul#e+s Humans 34 Bo t+eatmentC s"l(e+ sul,ad"a/"neC 'o("done "od"ne (all g+ou's t+eated *"th h)d+o#ollo"d d+ess"ng) Bo e,,e#t (m"ld "m'+o(ement o, heal"ng +ate (s. unt+eated, -1-5K, non s"gn","#ant) B%& >am!e+t, et al. 3934 9ental "m'lants Humans 2641 (595 'at"ents) 5al"ne B%& 9e#+ease (4.1K "n,e#t"ous #om'l"#at"ons (s. ;.<K "n the #ont+ol g+ou') 5aatman, et al. 3;<4 $n#"s"onal *ounds, a!+as"ons 1u"nea '"gs 1<5 5al"ne (eh"#le (4K =H> s0"n #leanse+, t"n#tu+e 0.5K =H> "n <0K "so'+o'anolol, 0.5K =H> "n *ate+, 4K =H> "n *ate+, sal"ne, s0"n #leanse+, t"n#tu+e) M"ld de#+ease (4K #hlo+he-"d"ne g+ou's m"ldl) de#+eased heal"ng +ate at da)s 6 and 9 at "n#"s"onal *ounds and at all t"me 'o"nts at a!+as"ons (s. sal"neC no d",,e+en#e !et*een #hlo+he-"d"ne and (eh"#lesC no d",,e+en#es among g+ou's a,te+ 21 da)s o, t+eatment) B%& Mo!a#0en, et al. 3904 $n#"s"onal *ounds Dats 130 (65 +ats, ea#h *"th 1 *ound ,o+ t+eatment and 1 ,o+ #ont+ol) 5al"ne, (eh"#le 9e#+ease tens"le st+ength (s"gn","#ant de#+ease (s. !oth sal"ne and (eh"#le, a,te+ < da)s, p O 0.001 and p O 0.01 ,o+ 0.1K and 0.02 K #hlo+he-"d"ne B%& solut"ons) B"edne+, et al. 35<4 8ull th"#0ness 1u"nea '"gs 10 ,o+ ea#h g+ou' Bo t+eatment 9e#+eased g+anulat"on (66K de#+ease o, th"#0ness o, the g+anulat"on la)e+ "n #om'a+"son to #ont+ol, p O 0.001) B%& 5an#he/, et al. 3;;4 8ull th"#0ness @eagle dogs 5al"ne, 'o("done "od"ne $n#+ease (la+ge+ healed *ound a+ea on da)s < and 14, "n#+eased #ont+a#t"on on da)s <, 14 and 21 (s. sal"ne) 9e#+ease !a#te+"al #ounts (0.05K #hlo+he-"d"ne solut"on s"gn","#antl) +edu#ed !a#te+"al #ounts (s. $ and sal"ne) 5e(e+)ns, et al. 3;94 8emo+al (essels se#t"on Dats 150 an"mals 5al"ne, 'o("done "od"ne Bo to-"#"t) (no d",,e+en#e o, 0.02K and 0.001K #hlo+he-"d"ne solut"ons on h"stolog"#al assessment o, #ollagen and elast"# ,"!e+s, (s. sal"ne. Bons"gn","#ant to-"#"t) o, 0.05K solut"on) B%& 5hahan, et al. 3924 8ull th"#0ness Dats ;0 (40 an"mals) 5al"ne $n#+ease (+edu#ed tens"le *ound st+ength *"th 0.12K #hlo+he-"d"ne solut"on at 4;h, 12< (s. 150C "n#+eased at 96h, 202 (s. 1;3, +esult"ng "n sho+te+ heal"ng t"me, p O 0.05) B%& )able 1. Sil%er compounds Aut!or Wound )(pe Species +umber o Wounds )reated Control,Comparator Eect on 'ealing Eect on Inection @"sho', et al. 31024 Aenous stas"s ul#e+s Humans ;6 (2; 559 1K #+eam, 29 #o''e+ t+"'e't"de #o''e+, 29 'la#e!o) la#e!o, #o''e+ t+"'e't"de #om'le- $n#+ease (44K de#+ease "n les"on s"/e (s. 1;.< and 22.5 ,o+ the othe+ g+ou's, ' O 0.05) B%& 8umal, et al. 31104 >eg ul#e+s Humans 34 Bo t+eatmentC #hlo+he-"d"neC 'o("done "od"ne (all g+ou's t+eated *"th h)d+o#ollo"d d+ess"ng) Bo e,,e#t (m"ld "m'+o(ement o, heal"ng +ate (s. unt+eated, 2- <K, nons"gn","#ant d",,e+en#e ) B%& 1e+on"mus, et al. 3514 a+t"al th"#0ness "gs 600 *ounds ("n 4 an"mals, 200 ,o+ ea#h g+ou') Bo t+eatmentC (eh"#le $n#+ease (3.1 da)s needed ,o+ 50K o, *ounds to +ee'"thel"al"/e *"th 5"l(ad"ne (1K sul,ad"a/"ne s"l(e+) (s. 4.3 ,o+ unt+eated #ont+ol and 3.4 ,o+ (eh"#le, +elat"(e +ate o, heal"ng P25K) B%& H7olseth, et al. 3534 8ull th"#0ness M"#e 46 (13 #ont+ol, 1; s"l(e+ sul,ad"a/"ne, 15 s"l(e+ n"t+ate) Bo t+eatment Bo e,,e#t (<.1and ;.9 da)s ,o+ #om'lete +ee'"thel"/at"on *"th s"l(e+ sul,ad"a/"ne and s"l(e+ n"t+ate (s. <.2 ,o+ #ont+ol, nons"gn","#ant d",,e+en#e) B%& Hu#an, et al. 34<4 +essu+e ul#e+s Humans 40 (15 559, 15 A-$, 14 sal"ne) 5al"ne, A-$ B%& 9e#+ease (90K o, 'at"ents +es'onded to t+eatment a,te+ 14 da)s (s. 60K at the sal"ne and A-$ g+ou's, ' O 0.022) >ansdo*n, et al. 31004 $n#"s"onal Dat 50 (10 *ounds ,o+ ea#h g+ou') 9e"on"/ed *ate+ (s"l(e+ n"t+ate 0.01K, 0.1K, 1K, 559 0.5g, de"on"/ed *ate+) $n#+ease (all *ounds #om'letel) #losed !) da) ; ,o+ 1K, 0.1K s"l(e+ n"t+ate and 559 (s. hal, *ounds #losed ,o+ the 0.01K s"l(e+ n"t+ate and *ate+ g+ou's, s"gn","#an#e not #al#ulated) B%& >e"t#h, et al. 31014 8ull th"#0ness Dats 40 (10 ,o+ ea#h g+ou': 5"l(e+ sul,ad"a/"ne, 5"l(a/"ne, a"+ e-'osed, ma,en"de a#etate) &"+ e-'osedC ma,en"de a#etate 9e#+ease (de#+eased *ound #ont+a#t"on *"th s"l(e+ #om'ounds "n #om'a+"son to #ont+ol, es'e#"all) the ,"+st 10 da)s o, t+eatment, ' O 0.05) 9e#+ease (de#+eased !a#te+"al #ounts "n t+eatment g+ou's, stat"st"#al s"gn","#an#e not g"(en) >"("ngstone, et al. 31044 1+a,t"ng a,te+ !u+n "n7u+) Humans 52 (19 s"l(e+ n"t+ate, 1; neom)#"n P !a#"t+a#"n, 15 +"nge+Qs la#tate) D"nge+Qs la#tate, Beom)#"n 'lus !a#"t+a#"n B%& 9e#+ease (16K g+a,t ,a"lu+e, mostl) due to "n,e#t"on, (s. 33K and 53K ,o+ to'"#al ant"!"ot"#s and D"nge+Qs la#tate g+ou's, ' E 0.02C 1 out o, 3 "n,e#t"on #ases o, eme+gen#e o, ant"!"ot"#- +es"stant !a#te+"a at the s"l(e+ n"t+ate g+ou' (s. 6 out o, 6 and 4 out o, ; ,o+ the othe+ g+ou's, ' O 0.05) B"edne+, et al. 35<4 8ull th"#0ness 1u"nea '"gs 10 ,o+ ea#h g+ou' Bo t+eatment Bo e,,e#t (nons"gn","#ant de#+ease !) B%& 25K o, th"#0ness o, the g+anulat"on la)e+ *"th &gB:3 solut"on "n #om'a+"son to #ont+ol) :lson, et al. 31064 a+t"al th"#0ness "gs <2 (24 ,o+ ea#h g+ou': s"l(e+ #oated d+ess"ng mo"stened on#e, da"l), and 'et+olatum gau/e) et+olatum gau/e $n#+ease (100K and 96K o, *ounds +ee'"thel"al"/ed !) da) < on s"l(e+-t+eated g+ou's (s. 33K ,o+ 'et+olatum gau/e g+ou', ' O 0.0001) B%& :u(+) 31034 Aenous ul#e+s Humans <1 B%& $n#+ease (40 ul#e+s healed, 25 "m'+o(ed, 4 +ema"ned sta!le and 1 *o+sened a,te+ 45 da)s *"th sul,ad"a/"ne t+eatment) B%& (no "n,e#t"ons o!se+(ed) .+edget, et al. 39;4 @u+ns Humans 30 5"l(e+ n"t+ate (s. &#t"#oatL B%& 9e#+ease (5 *ounds *"th J105 #ounts "n &#t"#oat- t+eated *ounds (s. 16 "n s"l(e+ n"t+ate g+ou' and 1 se#onda+) !a#te+em"a (s. 5) Reerences 1. M#9onnell 1, Dussell &9. &nt"se't"#s and d"s"n,e#tants: &#t"("t), a#t"on and +es"stan#e. Clinical Microbiology Reviews 1999C12(1):14<-<9. 2. .a)lo+ 9M. $na#t"(at"on o, un#on(ent"onal agents o, the t+ansm"ss"!le degene+at"(e en#e'halo'ath"es. $n: Dussell &9, Hugo W@, &)l",,e 1&U (eds). Principles and Practice of isinfection, Preservation and Sterili!ation, "hird #dition. :-,o+d, Mngland: @la#0*ell 5#"en#e, 1999. 3. B"edne+ D. =)toto-"#"t) and sens"t"/at"on o, 'o("done "od"ne and othe+ ,+e6uentl) used ant"-"n,e#t"(e agents. ermatology 199<C195(5u''l 2):;9-92. 4. 56 8ede+al Deg"ste+ 33644 at 33662. 5. @e+gst+om B, @ennet M&, =a+lson =M, et al. Clinical Practice $uideline %umber &'( "reatment of Pressure )lcers. Do#0("lle, M9: 25 9e'a+tment o, Health and Human 5e+("#es. &gen#) ,o+ Health =a+e ol"#) and Desea+#hC 1994. &H=D u!l"#at"on 95- 0652. 6. @+o*n =9, V"tell" U&. & +e("e* o, to'"#al agents ,o+ *ounds and methods o, *ound"ng. * ermatol Surg +ncol 1993C19:<32-<. <. Dodehea(e+ 1. =ont+o(e+s"es "n to'"#al *ound management. ,+)%S 19;9C1:19-2<. ;. :!e+g M5, >"ndse) 9. 9o not 'ut h)d+ogen 'e+o-"de o+ 'o("done "od"ne on *ounds. -*C 19;<C141:2<-;. 9. Ma)e+ 9&, .sa'ogas MU. o("done-"od"ne and *ound heal"ng: & #+"t"#al +e("e*. ,+)%S 1993C5(1):14-23. 10. 1oldenhe"m 9. &n a''+a"sal o, 'o("done-"od"ne and *ound heal"ng. Postgrad Med * 1993C69(53):59<-5105. 11. 9o* 1, @+o*ne &, 5"!!ald D1. $n,e#t"on "n #h+on"# *ounds: =ont+o(e+s"es "n d"agnos"s and t+eatment. +st.,ound Manang 1999C45(;):23-40. 12. >aato M, B""n"0os0" U, >und!e+g =, et al. $n,lammato+) +ea#t"on "n !lood ,lo* and e-'e+"mental *ounds "no#ulated *"th Staphylococcus aureus. #ur Surg Res 19;;C20:33. 13. Dodehea(e+ 1.. Wound #leans"ng, *ound "++"gat"on, *ound d"s"n,e#t"on. $n: H+asne+ 9, Hane 9. Chronic ,ound Care( - Clinical Source /oo0 for 1ealthcare Professionals, Second #dition. Wa)ne, &: Health Management u!l"#at"ons, $n#., 199<:9<-10;. 14. @u#0nall .. .he e,,e#t o, lo#al "n,e#t"on u'on *ound heal"ng: &n e-'e+"mental stud). /r * Surg 19;0C6<:;51. 15. Do!son M. 9"stu+!an#es o, *ound heal"ng. -nn #merg Med 19;;C1:12<4. 16. Do!son M, 5ten!e+g @, He+gge+s U. Wound heal"ng alte+at"ons #aused !) "n,e#t"on. Clin Plastic Surg 1990C1<:4;5. 1<. 1"l#h+"st @, Deed =. .he !a#te+"olog) o, #h+on"# (enous ul#e+s t+eated *"th o##lus"(e h)d+o#ollo"d d+ess"ngs. /r * ermatol 19;9C121(3):33<-44. 1;. M+"0sson 1, M0lund &, Hall"ngs >. .he #l"n"#al s"gn","#an#e o, !a#te+"al g+o*th "n (enous leg ul#e+s. Scand * 2nfect is 19;4C16:1<5-;0. 19. He+manns U8, a6uet , &++ese UM, et al. >a #)toto-"#"tG !GnG,"6ue des ant"se't"6ues. Rev Med 3iege 1999C54(<):600-5. 20. Hegge+s U. 9e,"n"ng "n,e#t"on "n #h+on"# *ounds: 9oes "t matte+R * ,ound Care 199;C<(;):3;9-92. 21. Mle0 59. M-'e+"mental sta'h)lo#o##al "n,e#t"ons "n the s0"n o, man. -nn %4 -cad Sci 1056C65:;5-90. 22. H+"/e0 .U, o!son M9, Hho M. @a#te+"al g+o*th and s0"n g+a,t su+("(al. Surg 5orum 196<C1;:51;. 23. >oo0"ng!"ll 9, M"lle+ 5M, Hno*les D=. @a#te+"olog) o, #h+on"# leg ul#e+s. -rch ermatol 19<;C114:1<65-;. 24. @end) DH, Bu##"o &, Wol,e M, et al. Delat"onsh"' o, 6uant"tat"(e *ound !a#te+"al #ounts to heal"ng o, de#u!"t): M,,e#t o, to'"#al gentam"#"n. -ntimicrob -gents Chemother 1964C14<-55. 25. Me+t/ M, :("ngton >1. Wound heal"ng m"#+o!"olog). ermatologic Clinics 1993C4:<39- 4<. 26. =ols0) &5, H"+sne+ D5, He+del 8&. &nal)s"s o, ant"!"ot"#s sus#e't"!"l"t"es o, s0"n *ound ,lo+a o, hos'"tal"/ed de+matolog) 'at"ents. -rch ermatol 199;C134:1006-9. 2<. 8le"s#he+ W, De"me+ H. o("done-"od"ne "n ant"se's"s: 5tate o, the a+t. ermatology 199<C195(5u''l 2):3-9. 2;. a)ne 9B, 1"!son 5&W, >e*"s D. &nt"se't"#s: & ,o+gotten *ea'on "n the #ont+ol o, ant"!"ot"# +es"stant !a#te+"a "n hos'"tal and #ommun"t) sett"ngs. * Roy Soc 1ealth 199;C11;(1):1;-22. 29. >"nea*ea(e+ W, Ho*a+d D, 5ou#) 9, et al. .o'"#al ant"m"#+o!"al to-"#"t). -rch Surg 19;5C120(3):26<-<0. 30. 1+een!e+g >, $ngalls UW. @a#te+"#"de%leu0o#"de +at"o: & te#hn"6ue ,o+ the e(aluat"on o, d"s"n,e#tants. * -m Pharmaceutical -ssociation 195;CW>A$$:531-3. 31. =oo'e+ M>, >a-e+ U&, Hans!+ough U8. .he #)toto-"# e,,e#ts o, #ommonl) used to'"#al ant"m"#+o!"al agents on human ,"!+o!lasts and 0e+at"no#)tes. * "rauma 1991C31(6):<<5- ;4. 32. 8lem"ng &. .he a#t"on o, #hem"#al and 'h)s"olog"#al ant"se't"#s "n a se't"# *ound. /r * Surg 1919C<:99-129. 33. Me+t/ M, 9a("s 5, @+e*e+ >, 8+an/en >. =an ant"m"#+o!"als !e e,,e#t"(e *"thout "m'a"+"ng *ound heal"ngR .he e(aluat"on o, a #ade-ome+ "od"ne o"ntment. ,+)%S 1994C6(6):1;4-93. 34. 50og M, &mes7o @, .+oeng ., et al. & +andom"/ed t+"al #om'a+"ng #ade-ome+ "od"ne and standa+d t+eatment "n the out'at"ent management o, #h+on"# (enous ul#e+s. /rit Med * 19;3C109:<<-;3. 35. 8le"s#he+ W, De"me+ H. o("done "od"ne "n ant"se's"sX5tate o, a+t. ermatology 199<C195(5u''l 2):3-9. 36. Dodehea(e+ 1, @ellam) W, Hod) M, et al. @a#te+"#"dal a#t"("t) and to-"#"t) o, "od"ne- #onta"n"ng solut"ons "n *ounds. -rch Surg 19;2C11<:1;1-5. 3<. Ho*ell UM, 5ta"+ .:, Ho*ell &W, et al. .he e,,e#t o, s#+u!!"ng and "++"gat"on *"th no+mal sal"ne, 'o("done "od"ne, and #e,a/ol"n on *ound !a#te+"al #ounts "n a gu"nea '"g model. -m * #merg Med 1993C11:134-;. 3;. 1eo+g"ade B1, Ha++"s W&. :'en and #losed t+eatment o, !u+ns *"th 'o("done "od"ne. Plast Reconstr Surg 19<3C52(5):640-4. 39. 1+a(ett &, 5te+ne+ 5, =l"nton UM, et al. & t+"al o, 'o("done "od"ne "n the '+e(ent"on o, "n,e#t"on "n sutu+ed la#e+at"ons. -nn #merg Med 19;<C16(2):16<%4<-1<1%51. 40. "G+a+d-8+an#h"mont =, a6uet , &++ese UM, et al. Heal"ng +ate and !a#te+"al ne#+ot"/"ng (as#ul"t"s "n (enous leg ul#e+s. ermatology 199<C194:3;3-<. 41. A"l7anto U. 9"s"n,e#t"on o, su+g"#al *ounds *"thout "nh"!"t"on o, *ound heal"ng. -rch Surg 19;0C115:253-6. 42. @e+0elman D>, Holland @W, &nde+son D>. $n#+eased !a#te+"#"dal a#t"("t) o, d"lute '+e'a+at"ons o, 'o("done "od"ne solut"ons. * Clin Microbiol 19;2C15:635-9. 43. >amme+s D>, 8ou++G M, =alahan M>, et al. M,,e#t o, 'o("done "od"ne and sal"ne soa0"ng on !a#te+"al #ounts "n a#ute, t+aumat"#, #ontam"nated *ounds. -nn #merg Med 1990C19(6):<09%155-<14%160. 44. latt U, @u#0nall D&. &n e-'e+"mental e(aluat"on o, ant"se't"# *ound "++"gat"on. * 1osp 2nfect 19;4C5:1;1-;. 45. Mld+"#h D8, =uste+ U, Madden U, et al. 5tud"es "n management o, the #ontam"nated *ound: $$$. &ssessment o, the e,,e#t"(eness o, "++"gat"on *"th ant"se't"#s agents. -m * Surg 1969C11;:21-30. 46. 5"ndela+ W8, Mason 1D. $++"gat"on o, su!#utaneous t"ssue *"th 'o("done-"od"ne solut"on ,o+ '+e(ent"on o, su+g"#al *ound "n,e#t"ons. Surg $ynecol +bstet 19<9C14;:22<-31. 4<. Hu#an U:, Do!son M=, Hegge+s U, et al. =om'a+"son o, s"l(e+ sul,ad"a/"ne, 'o("done "od"ne and 'h)s"olog"# sal"ne "n the t+eatment o, #h+on"# '+essu+e ul#e+s. * -m $eriatr Soc 19;1CWW$W(5):232-5. 4;. Me+t/ M, :l"(e"+a-1and"a M8, 9a("s 5=. .he e(aluat"on o, a #ade-ome+ "od"ne *ound d+ess"ng on meth"#"ll"n +es"stant Staphylococcus aureus "n a#ute *ounds. ermatol Surg 1999C25:;9-93. 49. 9an"elsen >, =he++) 1W, Ha+d"ng H, Dollman :. =ade-ome+ "od"ne "n ul#e+s #olon"/ed !) Pseudomonas aeruginosa. * ,ound Care 199<C6(4):169-<2. 50. 5ull"(an ., Maglste"n WH, 9a("s 5=, Me+t/ . .he '"g as a model ,o+ human *ound heal"ng. ,ound Repair Regen 2001C9(2):66-<6. 51. 1e+onemus D1, Me+t/ M, Maglste"n WH. Wound heal"ng: .he e,,e#ts o, to'"#al ant"m"#+o!"al agents. -rch ermatol 19<9C15:1311-4. 52. 1+u!e+ D, A"stnes >, a+doe D. .he e,,e#t o, #ommonl) used ant"se't"#s on *ound heal"ng. Plast Reconstr Surg 19<5C55(4):4<2-6. 53. H7olseth 9, 8+an0 UM, @a+0e+ UH, et al. =om'a+"son o, the e,,e#ts o, #ommonl) used *ound agents on e'"thel"al"/at"on and neo(as#ula+"/at"on. * -m College Surgeons 1994 5e'tC1<9:305-12. 54. Menton 9B, @+o*n M. .he e,,e#ts o, #omme+#"al *ound #leanse+s on #utaneous *ound heal"ng "n gu"nea '"gs. ,+)%S 1994C6:21-<. 55. Mull"0en U@, Heale) B&, 1lo*a#0" U. o("done "od"ne and tens"le st+ength o, *ounds "n +ats. * "rauma 19;0C20(4):323-4. 56. Hasha)a' &, @ee/hold 9, W"seman U, @e#0 W=. M,,e#t o, 'o("done-"od"ne de+matolog"# o"ntment on *ound heal"ng. "he -merican Surgeon 1995C61:4;6-91. 5<. B"edne+ D, 5#ho', M. $nh"!"t"on o, *ound heal"ng !) ant"se't"#s. /r * ermatol 19;6C115(5u''l 31):41-4. 5;. Ma#Dae 5M, @+o*n @, Mdelhause+ H8. .he #o+neal to-"#"t) o, '+esu+g"#al ant"se't"#s. -m * +phthalmol 19;4C9<:221-32. 59. B"edne+ D. =)toto-"#"t) and sens"t"/at"on o, 'o("done-"od"ne and othe+ ,+e6uentl) used ant"-"n,e#t"(e agents. ermatology 199<C195(5u''l 2):;9-92. 60. Ho', H, 1+and) D, 5tahl-@a)l"ss =, 8"t/ma+t"n D. .he e,,e#t o, !etad"ne #+eam (s. s"l(adene #+eam on +ee'"thel"al"/at"on "n un"n,e#ted e-'e+"mental *ounds. Proc /urn -ssoc 1991C23:166. 61. Do!"ns , 9a) => U+, >e* D&. & mult"(a+"ate anal)s"s o, ,a#to+s a,,e#t"ng *ound heal"ng t"me. ermatol Surg +ncol 19;4C10:219-22. 62. 9e Ho#0 M, (an de+ Me+*e &M, 5*a+ts =. & #om'a+at"(e stud) o, 'o("done "od"ne #+eam and s"l(e+ sul,ad"a/"ne "n the to'"#al t+eatment o, !u+ns. $n: 5el*)n 5 (ed). +o#eed"ngs o, .he 8"+st &s"an%a#","# =ong+ess o, Med"#"ne 5e+("#es. >ondon, 2H: Do)al 5o#"et) o, Med"#"ne 5e+("#es, 199;:65-<1. 63. >ee @N, .+a"no+ 85, .hoden WD. .o'"#al a''l"#at"on o, 'o("done-"od"ne "n the management o, de#u!"tus and stas"s ul#e+s. * -m $eriatr Soc 19<9C2<(<):302-6. 64. Hnutson D&, Me+!"t/ >&, =+ee0mo+e M&, et al. 2se o, suga+ and 'o("done-"od"ne to enhan#e *ound heal"ng: 8"(e )ea+sI e-'e+"en#e. Southern Medical *ournal 19;1C<4(11):1329-35. 65. 5teen M. De("e* o, 'o("done "od"ne use "n the t+eatment o, !u+ns. Postgrad Med * 1993C69(5u''l 3):5;4-592. 66. Vamo+a >. =hem"#al and m"#+o!"olog"# #ha+a#te+"st"#s and to-"#"t) o, 'o("done "od"ne solut"ons. -m * Surg 19;6C151:400-5. 6<. @u+0s D$. o("done "od"ne solut"on "n *ound t+eatment. Physical "herapy 199;C<;(2):212-;. 6;. >amme MB, 1usta,sson .:, M"ddel0oo' M. =ade-ome+ "od"ne sho*s st"mulat"on o, e'"de+mal +egene+at"on "n e-'e+"mental ,ull th"#0ness *ounds. -rch ermatol Res 199;C290:1;-24. 69. >audans0a H, 1usta(son @. $n-'at"ent t+eatment o, #h+on"# (a+"#ose (enous ul#e+s. & +andom"/ed t+"al o, #ade-ome+ "od"ne (e+sus standa+d d+ess"ngs. * 2nternat Med Research 19;;C16:42;-35. <0. H"llst+om >. $odoso+! #om'a+ed to standa+d t+eatment "n #h+on"# (enous ul#e+sX& mult"#ente+ stud). -cta Chir Scand 19;;C5u''l 544:53-6. <1. 50og M, &+nes7o @, .+oeng ., et al. & +andom"/ed t+"al #om'a+"ng #ade-ome+ "od"ne and standa+d t+eatment "n the out-'at"ent management o, #h+on"# (enous ul#e+s. /r * ermatol 19;3C109:<<-;3. <2. Hollo*a) 1&, Uohansen HH, @a+nes DW, "e+#e 1M. Mult"#ente+ t+"al o, #ade-ome+ "od"ne to t+eat (enous stas"s ul#e+s. ,estern * Med 19;9C151(1):35-;. <3. :+m"ston M=, 5e)mou+ M. U, Aenn 1M, =ohen D$, 8o- U&. =ont+olled t+"al o, $odoso+! "n #h+on"# (enous ul#e+s. /r Med * 19;5C291:30;-10. <4. Ha+#u' UW, 5aul &. & stud) o, the e,,e#t o, #ade-ome+ "od"ne "n the t+eatment o, (enous leg ul#e+s. /r * Clin Prac 19;6C40(9):360-4. <5. .a+(a"nen H. =ade-ome+ "od"ne ($odoso+!) #om'a+ed *"th de-t+anome+ (9e!+"san) "n the t+eatment o, #h+on"# leg ul#e+s. -cta Chir Scand 19;;C5u''l 544:5<-9. <6. Hansson =. .he e,,e#ts o, #ade-ome+ "od"ne 'aste "n the t+eatment o, (enous leg ul#e+s #om'a+ed *"th h)d+o#ollo"d d+ess"ng and 'a+a,,"n gau/e d+ess"ng. 2nternat * ermatol 199;C3<:390-6. <<. 8lo)e+ =, W"l0"nson U9. .+eatment o, (enous leg ul#e+s *"th #ade-ome+ "od"ne *"th 'a+t"#ula+ +e,e+en#e to "od"ne sens"t"("t). -cta Chir Scand 19;;C5u''l 544:60-1. <;. &'el6("st U, Dagna+son .enn(all 1. =a("t) ,oot ul#e+s "n d"a!et"# 'at"ents: & #om'a+at"(e stud) o, #ade-ome+ "od"ne and standa+d t+eatment. &n e#onom"# anal)s"s alongs"de a #l"n"#al t+"al. -cta erm 6enereol 1996C<6(3):231-5. <9. Mo!e+g 5, Ho,,man >, 1+enne+t M>, Holst &. & +andom"/ed t+"al o, #ade-ome+ "od"ne "n de#u!"tus ul#e+s. * -m $eriatrics Soc 19;3C31(;):462-5. ;0. .u+ M, @olton >, =onstant"ne @M. .o'"#al h)d+ogen 'e+o-"de t+eatment o, "s#hem"# ul#e+s "n the gu"nea '"g: @lood +e#+u"tment "n mult"'le s0"n s"tes. *-- 1995C33(2:1):21<-21. ;1. >au WN, Wong 5H. Dandom"sed, '+os'e#t"(e t+"al o, to'"#al h)d+ogen 'e+o-"de "n a''ende#tom) *ound "n,e#t"on. -m * Surg 19;1C142:393-<. ;2. >e)den UU, @a+telt BM. =om'a+"son o, to'"#al ant"!"ot"# o"ntments, a *ound '+ote#tant and ant"se't"#s "n the t+eatment o, human !l"ste+ *ounds #ontam"nated *"th Staphylococcus aureus. * 5am Pract 19;<C24(6):601-4. ;3. h"ll"'s $, >o!o &V, 8e+nade/ D, 1unda+a B5. &#et"# a#"d "n the t+eatment o, su'e+,"#"al *ounds "n,e#ted !) Pseudomonas aeruginosa. 3ancet 196;C1:11-3. ;4. 5loss UM, =um!e+land B, M"lne+ 5M. &#et"# a#"d used ,o+ the el"m"nat"on o, Pseudomonas aeruginosa ,+om !u+n and so,t t"ssue *ounds. * R -rmy Med Corps 1993C139(2):49-51. ;5. Hansson =, 8ae+gemann U. .he e,,e#t o, ant"se't"# solut"ons on m"#+oo+gan"sms "n (enous leg ul#e+s. -cta erm 6enereol 1995C<5(1):31-3. ;6. >"nea*ea(e+ W, M#Mo++"s 5, 5ou#) 9, Ho*a+d D. =ellula+ and !a#te+"al to-"#"t"es o, to'"#al ant"m"#+o!"als. Plast Reconstr Surg 19;5C<5:394-6. ;<. 5aatman D&, =a+lton WW, Hu!!en H, et al. & *ound heal"ng stud) o, #hlo+he-"d"ne d"glu#onate "n gu"nea '"gs. 5undamental 7 -pplied "oxicology 19;6C6(1):1-6. ;;. 5an#he/ $D, 5*a"m 58, Bus!aum HM, et al. M,,e#ts o, #hlo+he-"d"ne d"a#etate and 'o("done "od"ne on *ound heal"ng "n dogs. 6et Surg 19;;C1<(6):291-5. ;9. 5e(e+)ns &M, >e7eune &, Do#ou- 1, >e7eune 1. Bon-to-"# ant"se't"# "++"gat"on *"th #hlo+he-"d"ne "n e-'e+"mental +e(as#ula+"/at"on "n the +at. * 1osp 2nfect 1991C1<:19<- 206. 90. Mo!a#0en H, Wengst+om =. $nte+,e+en#e *"th heal"ng o, +at s0"n "n#"s"ons t+eated *"th #hlo+he-"d"ne. -cta ermatoveener (5to#0holm) 19<4C54:29-34. 91. @+ennan 55, 8oste+ MM, >ea'e+ 9U. &nt"se't"# to-"#"t) "n *ounds heal"ng !) se#onda+) "ntent"on. * 1osp 2nfect 19;6C;(3):263-<. 92. 5hahan MH, =huang &H, @+ennan W&, et al. .he e,,e#t o, #hlo+he-"d"ne "++"gat"on on the tens"le *ound st+ength. * Periodontol 1993C64(;):<19-22. 93. >am!e+t M, Mo+"s H8, :#h" 5. .he "n,luen#e o, 0.12K #hlo+he-"d"ne glu#onate +"nses on the "n#"den#e o, "n,e#t"ous #om'l"#at"ons and "m'lant su##ess. * +ral Maxillofac Surg 199<C55(12 5u''l 5):25-30. 94. =+oss,"ll M, Hall D, >ondon 9. .he use o, #hlo+he-"d"ne ant"se's"s "n #ontam"nated su+g"#al *ounds. /rit * Surg 1969C56(12):906-;. 95. Hlasen HU. & h"sto+"#al +e("e* o, the use o, s"l(e+ "n the t+eatment o, !u+ns. $$. Dene*ed "nte+est ,o+ s"l(e+. /urns 2000C26(2):131-;. 96. Mona,o WW, West M&. =u++ent t+eatment +e#ommendat"ons ,o+ to'"#al !u+n the+a'). rugs 1990 5e'C40(3):364-<3. 9<. 9e 1+a#"a =1. &n o'en stud) #om'a+"ng to'"#al s"l(e+ sul,ad"a/"ne and to'"#al s"l(e+ sul,ad"a/"ne-#e+"um n"t+ate "n the t+eatment o, mode+ate and se(e+e !u+ns. /urns 2001 8e!C2<(1):6<-<4. 9;. .+edget MM, 5han0o*s0) H&, 1+oene(eld &, @u++ell D. & mat#hed-'a"+, +andom"/ed stud) e(aluat"ng the e,,"#a#) and sa,et) o, &#t"#oat s"l(e+-#oated d+ess"ng ,o+ the t+eatment o, !u+n *ounds. * /urn Care Rehabil 199;C19(6):531-<. 99. 9eml"ng DH, 9e5ant" >. M,,e#ts o, s"l(e+ on *ound management. ,+)%S 2001C13(1):5-15. 100. >ansdo*n &@, 5am'son @, >au'atta+a0asem , Autt"("+o7ana &. 5"l(e+ a"ds heal"ng "n the ste+"le s0"n *ound: M-'e+"mental stud"es "n the la!o+ato+) +at. /r * ermatol 199<C13<(5):<2;-35. 101. >e"t#h $:, Hu#u0#ele!" &, Do!son M=. $nh"!"t"on o, *ound #ont+a#t"on !) to'"#al ant"m"#+o!"als. -ust % 8 * Surg 1993 &'+C63(4):2;9-93. 102. @"sho' U@, h"ll"'s >1, Mustoe .&, et al. & '+os'e#t"(e +andom"/ed e(aluato+- !l"nded t+"al o, t*o 'otent"al *ound heal"ng agents ,o+ the t+eatment o, (enous stas"s ul#e+s. * 6asc Surg 1992 &ugC16(2):251-<. 103. :u(+) &. 3& t+"al o, s"l(e+ sul,ad"a/"ne "n the lo#al t+eatment o, (enous ul#e+4. Phlebologie 19;9 Bo(-9e#C42(4):6<3-9. 104. >"("ngstone 9H, =+)e+ H1, M"lle+ 8@, et al. & +andom"/ed '+os'e#t"(e stud) o, to'"#al ant"m"#+o!"al agents on s0"n g+a,ts a,te+ the+mal "n7u+). Plast Reconstruct Surg 1990C;6(6):1059-64. 105. 9eml"ng DH, 9e5ant" >. .he +ate o, +ee'"thel"al"/at"on a#+oss meshed s0"n g+a,ts "s "n#+eased *"th e-'osu+e to s"l(e+. /urns 2002C2;(3):264-6. 106. :lson MM, W+"ght U@, >am H, @u++ell DM. Heal"ng o, 'o+#"ne dono+ s"tes #o(e+ed *"th s"l(e+-#oated d+ess"ngs. #ur * Surg 2000C166:4;6-9. 10<. @ennett >>, Dosen!lum D5, e+lo( =, et al. &n in vivo #om'a+"son o, to'"#al agents on *ound +e'a"+. Plast Reconstruct Surg 2001C10;(3):6<5-;5. 10;. Me+t/ M, &l(a+e/ :M, 5me+!e#0 DA, Maglste"n WH. & ne* in vivo model ,o+ the e(aluat"on o, to'"#al ant"se't"#s on su'e+,"#"al *ounds. -rch ermatol 19;4C120:5;- 62. 109. @+ennan 55, >ea'e+ 9U. .he e,,e#t o, ant"se't"#s on the heal"ng *ound: & stud) us"ng the +a!!"t ea+ #ham!e+. /r * Surg 19;5C<2:<;0-2. 110. 8umal $, @+aham =, a6uet , "e+a+d-8+an#h"mont =, "e+a+d 1M. .he !ene,"#"al to-"#"t) 'a+ado- o, ant"m"#+o!"als "n leg ul#e+ heal"ng "m'a"+ed !) a 'ol)m"#+o!"al ,lo+a: & '+oo,-o,-#on#e't stud). ermatology 2002C204(5u''l 1):<0-4. 111.Hut#h"nson UU, M#1u#0"n M. :##lus"(e d+ess"ngs: & m"#+o!"olog"# and #l"n"#al +e("e*. -m * 2nfect Control 1990C1;(4):25<-6;.