The Case for Tocolysis

8/17/2019 The Case for Tocolysis

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The case for tocolysisin threatened preterm labour

Clinical Work of Obstetrics and Gynecology

RSUD Tanjung!"U

#edical $aculty%slamic Uni&ersity 'l'(har #ataram

)*+,

tutor: dr. Dony Rosmana Bimantara SpOG

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abstract The ai!ure o toco!ytics to impro"e neonata! outcomes inp!acebo#contro!!ed tria!s has $ron%!y been interpreted ase"idence that they do not $or&

'hi!e de!i"ery is une(ui"oca!!y pro!on%ed by )* hours+ *8hours and , days+ the time %ained $as not e-p!oited tooptimise neonata! outcome

The !ar%est p!acebo#contro!!ed study sho$ed c!ear trendsto$ards better sur"i"a! in etuses )8 $ee&s+ !o$er rates ocerebra! pa!sy and hi%her Bay!ey menta! scores

ina!!y+ there is the Or$e!!ian ana!o%y that toco!ytics don0t$or&+ but some $or& better than others

De"e!opment o toco!ytics that are sae or mother and babyshou!d aci!itate ade(uate!y#po$ered p!acebo#contro!!edstudies

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%-TRODUCT%O-

There are three re(uirements o a toco!ytica%ent:that it de!ays !abour

that it is sae or mother and etus

that it impro"es perinata! outcome

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.RO"O-G'T%O- O$ G/ST'T%O-2 recent meta#ana!ysis identi3ed 1, p!acebo#

contro!!ed tria!s concernin% the use otoco!ytics or the treatment o preterm !abourin"o!"in% ))8* $omenthe use o a toco!ytic dru% $as associated $ith

si%ni3cant!y reduced odds o de!i"ery :$ithin )* hours 4OR .*,+ 7 .)9.,,

$ithin *8 hours 4OR .5,+ 7 .89.8

$ithin , days 4OR .6+ 7 .89.5

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These e;ects $ere on!y si%ni3cant or beta#a%onists+ atosiban+ and indomethacin

Despite its popu!arity in


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#'T/R-'" '-D $/T'" S'$/T0 2d"erse e;ects rom toco!ytics !ar%e!y resu!t rom

their non#speci3city or uterine musc!e

betasympathomimetic receptors:materna! pa!pitations 4*8= "s 5= p!acebo

tremor 4= "s *=

hyper%!ycaemia 4= "s. 6=

headache 4)= "s. 6=

nausea 4)= "s. 1)=dyspnoea 41*= "s. 1=

"omitin% 41= "s. 8=

chest pain 41= "s. 1=

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beta#a%onists>u!monary oedema occurs rare!y 41 in )66+

based on three cases in ,, treated $omen

yc!o#o-y%enase 4O? inhibitorseta! o!i%uria and ducta! constriction

7ndomethacin

neonata! necrotisin% enteroco!itis 4)= "s. 8=intra"entricu!ar haemorrha%e 4)8= "s. =

patent ductus arteriosus 46)= "s. **=

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o-ytocin/ "asopressin anta%onistnausea 411= "s. 5= p!acebo as its on!y side

e;ect

7n !ar%e randomised comparati"e tria!sbeta#a%onists+ atosiban $as associated $ith a

1#o!d reduction in materna! cardio"ascu!arside e;ects 48= "s. 81=

much !o$er rate o discontinuation due to sidee;ects 41= "s. 15=

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./R%-'T'" OUTCO#/ The !ac& o e;ect o toco!ytics on perinata! outcome in

the randomised studies has been $ron%!y interpretedas de3niti"e proo that they ha"e no e;ect

2!thou%h it has been &no$n or near!y t$o decadesthat a course o corticosteroid therapy @)*9*8 hours respiratory distress syndrome 4RDS

peri"entricu!ar haemorrha%e and neonata! death

corticosteroids $ere inre(uent!y %i"en in these tria!s

$hich is hard!y surprisin% %i"en that preterm !abour isproportionate!y more common at !ater %estations

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/1%D/-C/ O$ 2/-/$%T $RO#

TOCO"0S%Stria! o any toco!ytic a%ent.

Ritodrine >!acebo > "a!ue


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These trends are not seen $ith other a%ents

the tria!s $ith atosiban are sma!!er and

conounded by rescue toco!ysis ater as !itt!eas an hour

$hi!e perinata! outcome ater indomethacin is!i&e!y to be conounded by ad"erse dru%

e;ects on the etus

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T3/ '-%#'" $'R# '-'"OG0 ar!y attempts at meta#ana!ysis identi3ed a

number o methodo!o%ica! concerns $ith these

tria!sa!! $ere unb!inded

most !ac&ed intention#to#treat ana!ysis

some used ca!cium anta%onists as second#!inetherapy

and others inc!uded non#contractin% patients $ithruptured membranes

Cetaana!ysis o these tria!s comparin% ca!ciumanta%onists $ith beta#a%onists re"ea!ed

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CO-C"US%O- '-D $UTUR/

STUD%/S The neonata! e;ects o short#term

pro!on%ation o %estation $ith toco!ytic a%entsha"e not been ade(uate!y e"a!uated inp!acebo#contro!!ed tria!s

$hich ha"e been characterised by !o$corticosteroid usa%e+ no in#utero transer+enro!ment at !ate %estations+ and !ac& opo$er

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bene3cia! e;ect is su%%ested by:Bayesian trends to$ards reduced neonata!

morbidity and morta!ity+ and impro"ed !on%#term outcome in the beta#a%onist tria!s and

randomised tria!s sho$in% that ca!ciumanta%onists impro"e neonata! outcome andde!ay de!i"ery more e;ecti"e!y than beta#

a%onists The de"e!opment o toco!ytics that are sae or

the mother and baby shou!d aci!itate suchtria!s.

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ourna! 2na!ysis.roblem4

2 recent meta#ana!ysis identi3ed 1, p!acebo#contro!!edtria!s concernin% the use o toco!ytics or the treatment o

preterm !abour in"o!"in% ))8* $omen in


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Comparison4

ourna! : 2d"erse e;ects o toco!ytic therapy+ the conc!usion othis Fourna! is The idea! !abour#inhibitin% a%ents $ou!d e-c!usi"e!ytar%et the myometrium or the !abour stimu!us itse!. 7t $ou!d be

ora!!y acti"e $ith a rapid onset o action and !on% duration. Thea%ent $ou!d be de"oid o materna! and eta! side e;ects and$ou!d be hi%h!y e;ecti"e

Out Come4

The neonata! e;ects o short#term pro!on%ation o %estation $ith

toco!ytic a%ents ha"e not been ade(uate!y e"a!uated in p!acebo#contro!!ed tria!s+ $hich ha"e been characterised by !o$corticosteroid usa%e+ no in#utero transer+ enro!ment at !ate%estations+ and !ac& o po$er. The de"e!opment o toco!ytics thatare sae or the mother and baby shou!d aci!itate such tria!s.

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References1. Gyet"ai + Hannah C+ Hodnett D+ Oh!sson 2. Toco!ytics or preterm !abor: asystematic re"ie$. Obstet Gyneco! 1I*:869 8,,.

). Hannah C. Search or best toco!ytic or preterm !abour. Jancet )I56:6 9,.

. Roya! o!!e%e o Obstetricians and Gynaeco!o%ists. Toco!ytic dru%s or $omen inpreterm !abour. Guide!ine


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1.Ducsay 2+ Thompson S+ 'u 2T+


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1.Jamont R+ Dun!op >D+ ro$!ey >+ Je"ene C7+ !der CG. omparati"e morta!ity and

morbidity o inants transerred in utero or postnata!!y. >erinat Ced 18I11:)9 ).

).Romero R+ Sibai B+ SancheE#Ramos J+ et a!. 2n o-ytocin receptor anta%onist 4atosiban in thetreatment o preterm !abor: a randomiEed+ doub!e#b!ind+ p!acebo#contro!!ed tria! $ithtoco!ytic rescue. 2m Obstet Gyneco! )I18):11,9 118.

)1.innstrom O+ O!ausson >O+ Sedin G+ et a!. The S$edish nationa! prospecti"e study on

e-treme!y !o$ birth$ei%ht 4JB' inants. 7ncidence+ morta!ity+ morbidity and sur"i"a! inre!ation to !e"e! o care. 2cta >aediatr 1,I86:59 511.

)).;er SB+ Cout(uin C+ arine D+ et a!.


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The Case for Tocolysis