Hydroxyethyl Starch 130-0.4 (Voluven) Monograph

8/12/2019 Hydroxyethyl Starch 130-0.4 (Voluven) Monograph

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6% Hydroxyethyl Starch 130/0.4 in 0.9% NaCl

(Voluven

6% Hydroxyethyl Starch 130/0.4 in 0.9% Sodiu! Chloride (Voluven"National #ru$ ono$ra&h

Se&te!'er 011V) *har!acy +ene,it- ana$e!ent Service- edical )dvi-ory *anel and V SN *har!aci-t

xecutive-The purpose of VA PBM Services drug monographs is to provide a comprehensive drug review for making formularydecisions. These documents will be updated when new clinical data warrant additional formulary decision. ocumentswill be placed in the Archive section when the information is deemed to be no longer current.

C2 V S2 ) 5#e-cri&tionThe FDA approved hydroxyethyl starch 6% 130/0.4 (Voluven ! "n late #00$ or the prophylax"s andtreat&ent o hypovole&"a. 't "s a&on a nu&)er o hydroxyethyl starch solut"ons ava"la)le "n the *+.,ydroxyethyl 6% 130/0.4 "s o ten re erred to as a th"rd- enerat"on or ne er enerat"on starch and asdeveloped "th the oal o reduc"n no n adverse e ects that can occur "th older hydroxyethyl starchsolut"ons "nclud"n severe delayed-onset prur"t"s "&pa"red coa ulat"on and renal dys unct"on. +tarches"th h" her &olecular e" ht h" her de ree o &olar su)st"tut"on and h" her #/ 6 rat"o have reater

pers"stence "th"n the "ntravascular space )ut are also )el"eved to )e assoc"ated "th a reater r"s or t"ssueaccu&ulat"on and adverse events. ,ydroxyethyl starch 130/0.4 has a lo er &olecular e" ht a lo erde ree o &olar su)st"tut"on )ut a h" her #/ 6 rat"o.

#o-in$,ydroxyethyl starch 130/0.4 "s ut"l"2ed or &a"nta"n"n and/or restor"n "ntravascular volu&e and "sad&"n"stered )y "ntravenous "n us"on.The da"ly dose and "n us"on rate depend upon an "nd"v"dual s )lood loss on the &a"ntenance or restorat"ono he&odyna&"cs and on he&od"lut"on. The ad&"n"strat"on o hydroxyethyl starch 130/0.4 can )e repeatedover several days.ecause there "s a r"s or anaphylacto"d react"ons "th Voluven the "n"t"al 10-#0 &l should )e "n usedslo ly h"le care ully o)serv"n the pat"ent or adverse events.'n adults up to 50 &l/ o )ody e" ht can )e ad&"n"stered da"ly result"n "n an approx"&ate &ax"&u&da"ly dose o 3 500 &l o Voluven "n a $0 person.

,,icacy (Critically ll/Se&tic or Sur$icalA nu&)er o cl"n"cal tr"als have )een conducted "n h"ch the e "cacy and sa ety o , + 130/0.4 asco&pared to a var"ety o crystallo"d (e. . nor&al sal"ne 7"n er s lactate etc.! or collo"dal (e. . otherstarches al)u&"n elat"n 8not ava"la)le "n the *+9 and dextran! solut"ons "n the sett"n o cr"t"cal"llness/seps"s or sur ery. ( Because of the serious allegations against r. !oachim Boldt of fabricatingevidence" not obtaining #$B approval" etc." none of the trials in which r. Boldt is listed as a contributorwere included.%

'n cr"t"cally "ll or sept"c pat"ents there are l"&"ted data co&par"n 6% , + 130/0.4 to other collo"ds orcrystallo"ds (ava"la)le "n the *+!. There ore "t "s d" "cult to deter&"ne hether , + 130/0.4 o ers anyadvanta e or d"sadvanta es over the other products used or lu"d resusc"tat"on "n sept"c pat"ents. Ava"la)leu"del"nes support the use o e"ther collo"ds or crystallo"ds "thout a pre erence or lu"d type due to a lac

o ev"dence prov"n d" erences "n relevant outco&es )et een products. ecause o "ncons"stent datare ard"n the e ect o , + solut"ons on renal unct"on "n pat"ents "th seps"s t o cl"n"cal tra"ls have )eendes" ned and are under ay to help ans er that :uest"on; &'S(Scandinavian Starch for Severe Sepsis)SepticShock Trial* comparing '+ ,-S /0)0.1 to crystalloids in 200 patients with severe sepsis. The primaryoutcome measure in this trial is a composite of mortality and end(stage kidney failure. A second trial&3rystalloid versus ,ydro4yethyl Starch Trial 53,-ST%* is comparing '+ ,-S /0)0.1 to crystalloids5saline% in 6"000 critically ill patients in the intensive care unit. The primary endpoint of this trial is death

from all causes at 70 days. Secondary endpoints include renal failure" S89A score" use of renalreplacement therapy" #3: stay" etc. The 3,-ST study began in April ;0 0.

*pdated vers"ons &ay )e ound at .p)&.va. ov or va .p)&.va. ov(+epte&)er #011!

1
http://www.pbm.va.gov/http://www.pbm.va.gov/http://www.pbm.va.gov/


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(Voluven

'n the s"x "ncluded cl"n"cal tr"als "nvolv"n sur "cal pat"ents cl"n"cal outco&es d"d not d" er s" n" "cantly )et een 6% , + 130/0.4 and e"ther crystallo"d or collo"ds ad&"n"stered (, + 6$0/0.$5 al)u&"n 6%Dextran $0! "n per"operat"ve or postoperat"ve )lood loss trans us"on re:u"re&ents or or an unct"on. 'nseveral stud"es d" erences "n certa"n var"a)les (e. . levels o #-hour postoperat"ve nad"r Factor V''' or von


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(Voluven

*lace in hera&yAt present the place "n therapy or 6% , + 130/0.4 (Voluven ! "s unclear as "t has not )een sho n to )esuper"or "n sa ety or e "cacy co&pared to other a ents and )ecause data are very l"&"ted part"cularly "n

pat"ents "th seps"s. +"nce the &ax"&u& approved da"ly dose or lu"d resusc"tat"on "s h" her or 6% , +130/0.4 (50 &l/ /day! than other ava"la)le starches (#0&l/ /day! 6% , + 130/0.4 "s an opt"on or those

pat"ents re:u"r"n lar e a&ounts o crystallo"d and/or collo"d solut"ons ( #0&l/ /day! or as an alternat"veto al)u&"n. ,o ever s"nce there are also l"&"ted pu)l"shed data "n pat"ents rece"v"n &ax"&u& da"ly doseso 6% , + 130/0.4 (Voluven ! pat"ents rece"v"n these h" her doses should )e closely &on"tored oradverse events "nclud"n )leed"n delayed onset prur"t"s and renal "&pa"r&ent.

N 8#2C 8NFor years there has )een on o"n de)ate re ard"n the "deal lu"d replace&ent strate y or "ntravascularlu"d resusc"tat"on "n cr"t"cally "ll pat"ents. For exa&ple use o collo"ds versus crystallo"ds and &orerecently collo"d versus collo"d due to the "despread use o collo"dsE a ro "n nu&)er o ava"la)lecollo"d products (e. . hydroxyethyl starches , +G dextran and al)u&"n!E and the assu&pt"on that collo"dsare &ore e ect"ve than crystallo"ds at restor"n "ntravascular lu"d volu&e desp"te a lac o ev"dence tosupport that assu&pt"on. There are a nu&)er o , + products ava"la)le "n the *n"ted +tates. The"r a)"l"tyto pers"st "n the "ntravascular space "s dependent upon a nu&)er o actors "nclud"n &ean &oleculare" ht (to a lesser de ree! &olar su)st"tut"on and pattern o hydroxyethylat"on o lucose su)un"ts (rat"oo #/ 6!. , + products "th a h" her &ean &olecular e" ht a h" her de ree o &olar su)st"tut"on and ah" her rat"o o #/ 6 have lon er hal -l"ves and pers"st lon er "n the "ntravascular space. These actors arealso thou ht to contr")ute to reater t"ssue accu&ulat"on o , + and a reater r"s or "&pa"r&ent ocoa ulat"on and renal unct"on. Voluven has a lo er &ean &olecular e" ht than other ava"la)le , +

products a lo er de ree o &olecular su)st"tut"on )ut a h" her #/ 6 rat"o. 't as developed "th the oalthat these character"st"cs &" ht result "n a s"&"lar volu&e )ene "t or lu"d resusc"tat"on or volu&ereplace&ent )ut a lo er r"s or adverse events espec"ally on coa ulat"on and "dney unct"on.

The purposes o th"s &ono raph are to (1! evaluate the ava"la)le ev"dence o sa ety tolera)"l"ty e "cacycost and other phar&aceut"cal "ssues that ould )e relevant to evaluat"n 6% hydroxyethyl starch 130/0.4"n 0.H% sod"u& chlor"de (Voluven ! or poss")le add"t"on to the VA =at"onal For&ularyE (#! de "ne "ts

role "n therapyE and (3! "dent" y para&eters or "ts rat"onal use "n the VA.

*H) )C8 8:5/*H) )C8; N CS 1


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(Voluven

H S Solution(+rand

Concentration andSolvent

olecular7ei$ht

(=ilodalton-

olarSu'-titution a C /C6 atio '

#o-e (,a-t or -lo>de$radation

Voluven 6% "n 0.H% =a l 130 0.4 H/1 50 &l/ 3500 &J( ast!

,extend 6% "n )alancedelectrolytes

6$0 0.$5 4.5/1 #0 &l/ 1500 &J(slo !

,etastarch 6% "n 0.H% =a l 450 0.$ 5/1 #0 &l/ 1500(slo !

,espan 6% "n 0.H% =a l 600 0.$5 5/1 #0 &l/ 1500 &J(slo !

6% solut"ons are "so-oncot"c 10% solut"ons are hyperoncont"c (volu&e e ect exceed"n "n used volu&e! in vivoaColar su)st"tut"on (hydroxylat"on o lucose un"ts! slo s do n de radat"on o the , + &olecule )y alpha-a&ylaseand prolon s "ntravascular retent"on.

) Battern o hydroxylat"on can s" n" "cantly alter phar&aco "net"cs ( # vs. 6 car)on ato&s!. 'nh")"t"on o en2y&at"cde radat"on o the , + &olecule )y alpha-a&ylase "s "nh")"ted to a reater de ree " hydroxylat"on occurs at the # vs.6 car)on ato&. There ore solut"ons "th a h" her #/ 6 rat"o are expected to )e de raded &ore slo ly.

a'le *har!aco=inetic- (*; o, Hydroxyethyl Starche- (H S *roduct- (Sin$le n,u-ion in

Healthy Volunteer-4

H S Solution #o-e :ra! C!ax (!$/!l ? (hr Clearance(!l/!in

n,u-ion i!e (!in

Voluven(130/0.4!

#6.3 3.$ 1#.K 31.4 30

,extend(6$0/0.$5!

0.6/ 13 46.4LL 0.HK #0

,etastarch(450/0.$!

30 $.K 300LL =7 60

L,espan(600/0.$5!

=7 =7 =7 =7 =7

L=7Inot reported )ut &ay assu&e s"&"lar phar&aco "net"cs to ,extend s"nce C< C+ and de ree o su)st"tut"on ares"&"lar. D" erence "s )alanced solut"on vs. sal"ne solut"onLL7eported &ean T1/# at $-10 days or ,extend and $-#K days a ter ,etastarch. ,al -l"ves should not )e "nterpreted asdurat"on o volu&e e ect.

a'le 3 *har!aco=inetic- (*; o, Hydroxyethyl Starche- (H S *roduct- ( ulti&le n,u-ion- inHealthy Volunteer- 4

H S Solution Cu!ulative #o-e :ra!(day- treated

*la-!a Conc.4 hr- a,ter la-tdo-e (!$/!l

? (hr Clearance(!l/!in

)2C (!$/!l #ay 1v-. a-t #ay

Voluven(130/0.4!

500 (10! M0.5 H.1 ##.K 3#.K vs. 35.$

,extend(6$0/0.$5!

=' =' =' =' ='

,etastarch(450/0.$!

H0 (3! H.6 =7 M1 =7 vs. than on day1

L,espan

(600/0.$5!

=7 =7 =7 =7 =7

L=7Inot reported )ut &ay assu&e s"&"lar phar&aco "net"cs to ,extend s"nce C< C+ and de ree o su)st"tut"on ares"&"lar. D" erence "s )alanced solut"on vs. sal"ne solut"on. ='Inot "ncluded "n study. ,al -l"ves should not )e"nterpreted as durat"on o volu&e e ect.

'n or&at"on ro& the &anu acturer states that ollo "n "sovole&"c exchan e o 500 &J o , + 130/0.4 "nhealthy volunteers )lood volu&e "s &a"nta"ned or approx"&ately s"x hours. ased upon the "n or&at"on"n Ta)les # and 3 , + 130/0.4 does not appear to accu&ulate "th &ult"ple "n us"ons. ,o ever cl"n"caldata are needed to deter&"ne hether s" n" "cant advanta es o , + 130/0.4 ex"st over other , + products"n ter&s o sa ety and e "cacy.


4


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(Voluven

@#) )** 8V # N# C) 8NS6% hydroxyethyl starch 130/0.4 "n 0H% sod"u& chlor"de (Voluven ! as approved )y the FDA "n late#00$ or the prophylax"s and treat&ent o hypovole&"a.

*8 N ) 8@@< )+ 2S S*n no n.

C2 N V) @8 2 ) 5 ) N) V S =on-synthet"c collo"ds; ,u&an al)u&"n (4-5% #0-#5%!+ynthet"c collo"ds; Dextran 10% 40 ,etastarches (e. . ,espan ,extend!

#8S): )N# )# N S ) 8N,ydroxyethyl starch 130/0.4 "s ut"l"2ed or &a"nta"n"n and/or restor"n "ntravascular volu&e and "sad&"n"stered )y "ntravenous "n us"on. The da"ly dose and "n us"on rate depend upon an "nd"v"dual s )loodloss on the &a"ntenance or restorat"on o he&odyna&"cs and on he&od"lut"on. The ad&"n"strat"on ohydroxyethyl starch 130/0.4 can )e repeated over several days.

ecause there "s a r"s or anaphylacto"d react"ons "th Voluven the "n"t"al 10-#0 &J should )e "n usedslo ly h"le care ully o)serv"n the pat"ent or adverse events.

'n adults up to 50 &J/ o )ody e" ht can )e ad&"n"stered da"ly result"n "n an approx"&ate &ax"&u&da"ly dose o 3 500 &J o Voluven "n a $0 person.

'+ ,ydro4yethyl Starch /0)0.1 5' gm% in 0.7+ Sodium 3horide 5700 mg% in water for in%? @a 1" 3l 1" p, 1( . . 3alculated osmolarity /02 m8smol)> p, ad


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(Voluven

Ceasures o t"ssue per us"on-&ean arter"al pressure (CAB! lactate central venous oxy en saturat"oncentral venous pressure ( VB! stro e volu&e (+V! pul&onary cap"llary ed e pressure (B


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(Voluven

and per used cap"llary dens"ty as reater "n the , + vs. =++ roup (pM0.005!. #1 ,o ever other outco&e&easures such as +OFA T'++ and ac"d-)ase para&eters ere not d" erent. J"&"tat"ons o th"s study"nclude lac o val"dated &easure&ents or su)l"n ual &"croc"rculat"on (as a &ar er or t"ssue per us"on! atthe t"&e o study co&&ence&ent. +a&ple s"2e as adPusted do n ard once &ore data or th"s &easureas pu)l"shed. F"nally pat"ents "n the =++ roup had )asel"ne h" her seru& creat"n"ne values than , +rec"p"ents (#.# vs. 1.# respect"vely! and conse:uently &ay have )een a s"c er roup o pat"ents.

'n the second study #0 pat"ents "th seps"s ere ollo ed or "ve days "n the "ntens"ve care un"t. Bat"entsere rando&"2ed to rece"ve 6% , + 130/0.4 or #0% hu&an al)u&"n (,A! u"ded )y &easures o

he&odyna&"c status (B


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(Voluven

d" erences )et een collo"ds.o Tr"als ocused on outco&es "th appropr"ate po er to d"scern a &ortal"ty )ene "t o collo"d

resusc"tat"on "n sept"c or he&orrha "c shoc "th "nte rated phar&acoecono&"c analyses.o l"n"cal tr"als des" ned to exa&"ne )oth cl"n"cally relevant outco&es and phys"olo "c e ects o

collo"ds and crystallo"ds on or an unct"on "nclud"n lun lu"d )alance "n pat"ents "th or at r"sor acute lun "nPury (AJ'! or adult resp"ratory d"stress syndro&e (A7D+!.

+eps"s +u&&ary;There are l"&"ted data co&par"n 6% , + 130/0.4 to other collo"ds or crystallo"ds ava"la)le "n the *+.There ore "t "s d" "cult to deter&"ne hether , + 130/0.4 o ers any advanta e or d"sadvanta es over theother products used or lu"d resusc"tat"on "n sept"c pat"ents. Ava"la)le u"del"nes support the use o e"thercollo"ds or crystallo"ds "thout a pre erence or lu"d type due to a lac o ev"dence prov"n d" erences "nrelevant outco&es )et een products. ecause o "ncons"stent data re ard"n the e ect o , + solut"ons onrenal unct"on "n pat"ents "th seps"s t o cl"n"cal tra"ls have )een des" ned and are under ay to helpans er that :uest"on.

+ur ery;l"n"cal Tr"als; +"x stud"es co&par"n 6% , + 130/0.4 to crystallo"ds or other collo"ds "n pat"entsunder o"n elect"ve sur ery ere "ncluded. #4-#6 #K 3H-40 +tudy endpo"nts "ncluded one or &ore o theollo "n ; sur "cal )lood loss need or trans us"on o )lood products in vitro assess&ent o e ect oncoa ulat"on (us"n thro&)elasto raphy 8T @9! volu&e o collo"d or crystallo"d "n used and renalunct"on. 'n eneral the stud"es ere s&all and o short durat"on ran "n ro& 36-140 pat"ents andollo ed or 1-#K days post-op. 'n add"t"on althou h &ax"&u& doses o , + 130/0.4 are 50 &l/ /day(approx"&ately 3500 &l "n a $0 pat"ent! &ost stud"es "n used )et een 500 and 1500 &l "th theexcept"on o the study )y @handh" et al #6 and Cu htar #K et al. "n h"ch &ax"&u& da"ly doses ereexa&"ned.

T o o the s"x stud"es "nvolve a co&par"son o 6% , + 130/0.4 to lactated r"n ers (7J! (nI140 A @sur ery! #4 or 5% al)u&"n (nI36 &"tral valve sur ery! #5 as a co&ponent o card"opul&onary )ypass

pr"&"n solut"ons. 'n the , + 130/0.4 vs. 7J co&par"son no d" erences ere o)served "n post-op )loodloss use o resh ro2en plas&a t"&e to extu)at"on ' * stay creat"n"ne clearance or t"&e to d"schar e. At#4 hrs post-op *= and seru& creat"n"ne (+ r! ere stat"st"cally h" her "n the , + vs. 7J roup (46 vs.3# & /dJ and 1.4 vs. 1.1 & /dJ respect"vely pI0.001!. reat"n"ne clearance as not d" erent at $# hours

)et een roups )ut )asel"ne values ere h" her "n the , + vs. 7J roup ( asel"ne; $6 &l/&"n 7J vs. K#&l/&"n , + $# hrs post-op; 6K &l/&"n 7J vs. 64 &l/&"n , +!. 'nternat"onal nor&al"2ed rat"o ('=7!values ere h" her "n the 7J roup vs. , + at 1# and #4 hours post-op (1.3H vs. 1.05 81# hr9 and 1.3K vs.1.1# 8#4 hr! respect"vely )ut d" erences "n )lood loss ere not o)served. 'n the second )ypass pr"&"nstudy , + 130/0.4 as co&pared to 5% al)u&"n "n 36 pat"ents hav"n elect"ve &"tral valve replace&ent. #5

'n th"s study there ere no d" erences "n rate o clot develop&ent or stren th o clot ()oth ere e:uallyreduced ro& )asel"ne! lu"ds ad&"n"stered or )lood products "n used or chan e "n pro-"n la&&atory&ar ers )et een roups. The re&a"n"n our stud"es are "ncluded "n Ta)le 4 )elo ;

a'le 4 Su!!ary o, H S 130/0.4 v-. Colloid or Cry-talloid- in *atient- havin$ lective Sur$ery

ntervention nd&oint-/ e-ult- Co!!ent-:handi 6 (nB100CaPor orthoped"csur ery h"p and sp"ne&ost co&&on(4K hrs post-op #K days

post-op or sa ety!

, + 130/0.4(Voluven! vs., + 6$0/0.$5(6% ,etastarch!

Br"&ary; Total volu&e o collo"d re:u"red orvolu&e expans"on. =o d" erences ound.Other; Total lu"d "nput/output use ovasoact"ve &eds. =o d" erence "n lu"d "nputor ur"ne output "n the "ntent to treat populat"onand hen ad&"n"strat"on o "nd"v"dual typeso lu"d or )lood products as assessed.,o ever hen the "n used totals o p7 shole )lood and salva ed )lood ereco&)"ned there as a d" erence "n avor o

Althou h sl" ht d" erences "n # hr post-op nad"r FV''' and von


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(Voluven

, + 130 (pI0.0#H6!. # hr post-op nad"r actorV''' as 1H% lo er "n , + 130 vs. 6$0(pI0.04HH!. 'n pat"ents rece"v"n 1000 &l ostudy collo"d # hr post-op FV''' nad"r aslo er "n the , + 6$0 vs. 130 (pI0.04H! and

nad"r von


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(Voluven

on coa ulat"on? to "&prove )ene "to study "ntervent"onQ *nl" ely s"ncecoa ulat"on "n )oth roups ould )eless a ected.

Bu)l"shed 7ev"e s o Flu"ds *sed Dur"n +ur ery;There are three pu)l"shed rev"e s o the use o 6% , + 130/0.4 "n pat"ents under o"n sur ery. 7ev"e s

pooled analyses or &eta-analyses co&par"n , + 130/0.4 to a s"n le replace&ent lu"d not ava"la)le "n the*.+. ere not "ncluded. +ee Ta)le 5 or deta"ls;

a'le E. *u'li-hed evie>- o, H S 130/0.4 in Sur$ical *atient-#e-cri&tion/@indin$- Co!!ent-

oo!ton$ et al 4 009'V lu"ds or a)do&"nalaort"c sur ery

-3K tr"als 15KH pat"ents "ncluded.- o&pare the phys"olo "c e ects o crystallo"d andcollo"d replace&ent lu"ds to deter&"ne " there "sev"dence to support an opt"&al lu"d or replace&entor a)do&"nal aort"c sur ery.-Br"&ary outco&e co&pared as death.-Other para&eters co&pared; card"ac resp"ratoryhe&atolo "c and len th o stay.Authors co&&ents;-Jac o stud"es report"n death as pr"&ary outco&e-Jac o ev"dence to support a >)est lu"d?replace&ent dur"n or a ter a)do&"nal aort"c sur ery.-=o s"n le lu"d a ected any outco&e &easure &orethan another lu"d across a ran e o outco&es-Cany d" erent lu"d replace&ents used so eresults could )e pooled.-'&portant outco&e &easures should "nclude need orallo ene"c )lood trans us"on or an a"lure len th ostay "n ' * or hosp"tal.

- ochrane 7ev"e-Jac o ev"dence support"n clear advanta eso one lu"d replace&ent therapy over another -Althou h , + 130/0.4 as "ncluded "n therev"e l"&"ted nu&)er o stud"es.

*iaFFa et al 43 010"cacy sa ety o , +

-7ev"e o e "c"ency o , + 130/0.4 o plas&asu)st"tut"on vs. other collo"ds- lood loss and r"s o )leed"n "th , + 130/0.4-e ect on coa ulat"on (la) &easures-T @! &"n"&al.-7enal sa ety o , + 130.0.4-"nade:uate ev"dencehether d" erences ex"st )et een , + products-Bul&onary &echan"cs o , + 130/0.4 vs. othercollo"ds-type o lu"d does not a ect pul&onary

per&ea)"l"ty/ede&a , + &ay reduce per&ea)"l"ty-'n la&&atory response to sur ery- , + &ay reduce"n la&&atory response a ter sur ery vs. crystallo"ds(paper used to support as retracted!

-+u)Pect"ve not syste&at"c rev"e o , +130/0.4 dur"n sur ery-+everal o the retracted papers "nclud"noldt as an author ere "ncluded "n the rev"eand helped to support so&e o the conclus"ons(e. . "n la&&atory response to sur ery etc.!

aGa et al 44 011ard"ac sur ery does, + 130/0.4 "&pa"rcoa ulat"on less than othercollo"dsQ

-1# relevant papers ere "ncluded (H cl"n"cal tr"als 3in vitro stud"es!-3 in vitro stud"es; de&onstrate no s" n" "cant a ect on

platelet var"a)les (T @! and aster clot or&at"on "th, + 130/0.4

-H cl"n"cal stud"es; , + 130/0.4 , + #00/0.5 andelat"n all a ect coa ulat"on s"&"larly result"n "n nod" erences "n )lood loss a ter card"ac sur ery.

-'ncluded tr"als used pr"&ar"ly , + 130/0.4 vs.other collo"ds not ava"la)le "n the *+.,o ever s"nce crystallo"ds and al)u&"n ereco&parators the rev"e as "ncluded.-Althou h surro ate &easures o coa ulat"on

(T @ para&eters! ere not s" n" "cantlya ected )y , + 130/0.4 d" erences "n )leed"n outco&es d"d not d" er ro& , +#00/0.5 and elat"n (ne"ther ava"la)le "n the*+!

@u"del"nes or Flu"d 7eplace&ent "n +ur "cal Bat"ents;+riti-h Con-en-u- :uideline- on ntravenou- @luid hera&y ,or )dult Sur$ical *atient-ith ex&ected 'loodlo-- LE00 !l'nclus"on;under o"n elect"ve

H S 130/0.4 v-. H S6D0/0.DEollo"d ad&"n"strat"ondeter&"ned )y VBand arter"al )lood

pressure. ( VB M10&&, collo"ds

NB110 enrolled 10 >ithdra>n 'e,ore-ur$ery. NB100 co!&leted -tudy.Cost co&&on sur ery as o the h"p orsp"ne.Br"&ary Outco&e;, + 130; 16#3 &l, + 6$0; 15K4 &l (=+!

5 pts "n , + 130 had Hser"ous AD s vs. H pts "n, + 6$0 had 11 ser"ousAD s.3 ser"ous coa ulopath"esere reported "n , +6$0 and none "n , +


21


22/25


(Voluven

( aGorortho&edic-ur$ery

orthoped"c sur ery"th an expected

)lood loss o 500&l.

xclus"on; Aller y to, + coa ulat"ond"sorder renaldys unct"on or anur"anot related tohypovole&"a severecard"ac d"sease(=N,A class ''' or'V! unsta)le an "naor pre nancy.

"n used!. +tudy collo"dsere stopped or VB15 &&,Br"&ary Outco&e;Total volu&e o collo"d

solut"on re:u"red or"ntraoperat"ve volu&eresplace&ent+econdary Outco&e;Total lu"d"nput/output use ovasoact"ve &edsBr"&ary +a etyOutco&e;Ber"operat"ve red )loodcell loss ("nduct"on oanesthes"a to 4K hrs

post-op nad"r actorV''' act"v"ty nad"rvA Br"or"?su) roupsE no d" erence "n crystallo"dad&"n or VB.+econdary Outco&e;

=o d" erence "n lu"d "nput )et eenroups "th the except"on o hen7 s hole )lood and salva ed )loodere co&)"ned "n avor o , + 130(pI0.0#H6 only or pts rece"v"n thelu"d type and pI0.1H16 or all pts!'n those pts rece"v"n 1000 &l o , +130 or 6$0 the only d" erence "n lu"d"nput as hen 7 s hole )lood andsalva ed )lood ere co&)"ned(pI0.0345 only "n pts rece"v"n thatlu"d type pI0.140K or all pts!.

=o d" erence "n vasoact"ve therapyBr"&ary +a ety Outco&es;alculated 7 loss and est"&ated

)lood loss ere not d" erent )et eenroups.

=ad"r actor V''' as 1H% lo er "n the, + 6$0 vs. , + 130 roup ( &B0.0499!# hrs post-op. 'n the roup rece"v"n1000 &l o collo"d FV''' nad"r aslo er "n , + 6$0 vs. 130 roup(pI0.04H! # hrs post-op

=ad"r v


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ex&loratory and notcon,ir!atory. )- are-ult the @#)revie>er concludedthat the -u&erior -a,ety

o, H S 130 over H S6D0 could not 'econcluded 'a-ed u&onthe-e data. D

u=htar A

7 =I40 up to 4days post-op

(*atient-under$oin$ livin$donor livertran-&lantation

*t- >ith end


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(Voluven

#4 hr ollo up

(*atient-receivin$ #)*and under$oin$

8*C)+

OB A sur ery andta "n clop"do reland asp"r"n (DABT!"th"n 5 days osur ery. A s"n le

sur eon per or&edall operat"ons.

xclus"on;e&er ency sur eryC' h"story ocard"ac sur eryh"story o )leed"nd"athes"s or l"verdys unct"on ePect"onract"on M40%h )M1# /dl pltsM100 000 && 3

a)nor&al aBTT'=7 + r 1.4 & /dlor uses olycoprote"n '')/'''a"nh")"tors

&l/ /d or crystallo"dto &a"nta"n ' #.#J/&"n +vO# 60%and ur"nary output 0.5&l/ /h.

'n the , + roup "&ax da"ly dose o 30&l/ d"d not &a"nta"nthese he&odyna&"c

para&eters a )alanced&ult"ple electrolyte-conta"n"n solut"on as"ven.

=orep"nephr"nen"tropruss"de and "needed vasopress"nere used to &a"nta"nCAB )et een 60-K0&&, .Br"&ary Outco&e;D" erence "n

per"operat"ve )loodloss de "ned as the

)lood loss dur"nsur ery "th"n the"rst #4hr post-opOther Outco&es;Total "n used lu"dur"ne output"ntraoperat"ve and #4hr

post-op trans us"onre:u"re&ents

per&anent stro e renaldys unct"on (e"ther;+ r # &l/dl 50%reduct"on "n est"&ated@F7 vs. )asel"ne andne re:u"re&ent or77T Bost-op C' andlen th ohosp"tal"2at"on.T @ var"a)les (sta eso )lood clot or&at"on"n a raph"c or&at!ere also &easured

d" er )et een roups or hen separated"nto )leed"n "n the O7 or #4hr "n the' *;Overall; 1 0#K &l (crystallo"d! vs. H$K&l (, +! pI0.4K3

O7; #1K &l (crystallo"d! vs. #3# , + pI0.63$' * (#4 hr!; K10 &l (crystallo"d! vs. $53(, +! pI0.353

Other outco&e &easures;There ere no d" erences "n trans used

p7 s FFB or nu&)ers o pat"entsre:u"r"n trans us"on o e"ther )lood

product.Core crystallo"d as "n used "n thecrystallo"d vs. , + roup;K 34# &l vs. 6 6H4 &l (pM0.001!Cean , + volu&e "ven; 1 45K &l "nthe , + vs. none "n the crystallo"droup. (pM0.001!

=o d" erences "n ur"ne output erenoted.Authors noted that '=7 as elevated

post-op "n the , + vs. crystallo"d roup(pM0.0#K! )ut st"ll "n the nor&al ran e.,e&o lo)"n levels ere stat"st"callylo er "n the , + vs. crystallo"d roup.oth '=7 and he&o lo)"n ere s"&"lar

)et een roups at )asel"ne.*se o vasopressors as not d" erent

)et een roups.One pat"ent "n the , + roup developedrenal a"lure re:u"r"n d"alys"s. Otherendpo"nts or &or)"d"ty d"d not d" er(e. . len th o stay etc.!.T @ &easure&ent de&onstrated s"&"lare ects on coa ulat"on "&pa"r&ent anddurat"on o e ect 1! t"&e to "n"t"al ")r"nor&at"on #! rap"d"ty o ")r"n cross-l"n "n 3! speed o clot or&at"on and4! clot stren th and act"v"ty o ")r"n and

platelets.

o&&ents; *nsure hatBlas&a +olut"on Aconta"ns and hether "t"s ava"la)le "n the *+.

=ot clear " )alanced&ult"ple-electrolyte"soton"c solut"on(crystallo"d! used "n, + roup as the sa&eas the crystallo"dco&parator., + da"ly dose l"&"tas lo er "n th"s studyvs. the FDA approved&ax dose (30 &l/ /dvs. 50 &l/ /drespect"vely!. ect onvar"ous study var"a)les&" ht )e d" erent "thh" her , + doses.Bo er calculat"ons ere

)ased solely upon theexpectat"on o a standarddev"at"on o #50 &l and

)lood loss o 150 &l orreater to )e cons"dereds" n" "cant. Bo ercalculat"ons ere )asedupon pr"&ary endpo"nto )lood loss and notoutco&es or other&easures.

Overall no d" erence "nendpo"nts )et een , +and crystallo"d roups "n

pat"ents rece"v"n DABTand hav"n OB Aexcept '=7 as sl" htlyh" her and he&o lo)"nlo er "n the , + vs.crystallo"d roup.*nsure " h" her dose ovolu&e replace&entus"n , + "ll produces"&"lar e ects.

dol-e= 40

7 OJ + =I$K30 days post-opor AD s

(*atient--cheduled ,orelective hi&-ur$ery under-&inal ane-the-ia

*atient- E


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xclus"on; A+Aclass ''' (severesyste&"c d"sease! or'V (severe syste&"c

d"sease constantthreat to l" e! heartor "dney a"lurerheu&ato"d arthr"t"sno n clott"nd"sorder use oeneral anesthes"ause o cell saver onar ar"n orclop"do rel oraller y to studycollo"ds.

collo"ds and e ect oncoa ulat"on us"n7OT C as assessed.L*nclear the h"erarchyo the endpo"nts.

,,ectE00 !l E9D 60D E34 6A1*o-tere 'ein$ retracted -ince + a&&roval could not 'e veri,ied. he current li-t include- AA-tudie- in >hich #r. +oldt i- included a- an author. htt& //>>>.ox,ordGournal-.or$/ourPGournal-/Gac/eic% 0Goint% 0-tate!ent% 0on% 0retraction-% 04!ar 011.&d,
http://www.oxfordjournals.org/our_journals/jac/eic%20joint%20statement%20on%20retractions%204mar2011.pdfhttp://www.oxfordjournals.org/our_journals/jac/eic%20joint%20statement%20on%20retractions%204mar2011.pdfhttp://www.pbm.va.gov/http://www.oxfordjournals.org/our_journals/jac/eic%20joint%20statement%20on%20retractions%204mar2011.pdfhttp://www.oxfordjournals.org/our_journals/jac/eic%20joint%20statement%20on%20retractions%204mar2011.pdf

Hydroxyethyl Starch 130-0.4 (Voluven) Monograph

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Transcript of Hydroxyethyl Starch 130-0.4 (Voluven) Monograph