328

InternationalJournalofGynecologyandObstetrics134(2016)324

ContentslistsavailableatScienceDirect

InternationalJournalofGynecologyandObstetrics
journalhomepage:www.elsevier.com/locate/ijgo

CLINICALARTICLE

Randomizedcontrolledtrialcomparingcarbetocin,misoprostol,and
oxytocinforthepreventionofpostpartumhemorrhagefollowingan
electivecesareandelivery
AhmedE.H.Elbohoty,WalidE.Mohammed,MohamedSweed ,AhmedM.BahaaEldin,
AshrafNabhan,KarimH.I.Abd-El-Maeboud
DepartmentofObstetricsandGynecology,FacultyofMedicine,AinShamsUniversity,Abbasia,Cairo,Egypt

article info

a b s t r a c t

Articlehistory:
Received19October2015
Receivedinrevisedform4January2016
Accepted17May2016

Objective:Tocomparetheeffectivenessandsafetyofcarbetocin,misoprostol,andoxytocinforthepreventionof
postpartumhemorrhagefollowingcesareandeliveries.Methods:Adouble-blindrandomizedcontrolledtrial
enrolledpatientswithasingletonpregnancyscheduledforanelectivecesareandeliveryatamaternityhospital
inCairo,Egypt,betweenOctober1,2012andJune30,2013.Participantswererandomizedusingacomputergeneratedsequencetoreceivetreatmentwithcarbetocin,misoprostol,oroxytocin.Theprimaryoutcomewas
theoccurrenceofuterineatonynecessitatingadditionaluterotonics.Per-protocolanalyseswereperformed.
Patients,investigators,anddataanalystsweremaskedtotreatmentassignments.
Results:Thepresentstudyenrolled263patients;datawereanalyzedfrom88patientstreatedwithcarbetocin,89treatedwithmisoprostol,
and86womentreatedwithoxytocin.Furtheruterotonicswereneededforthetreatmentof5(6%)patients
whoweretreatedwithcarbetocin,20(22%)patientstreatedwithmisoprostol,and11(13%)patientstreated
withoxytocin.Inthepreventionofuterineatony,carbetocinwascomparablewithoxytocin(RR0.41,95%CI
0.14 1.25) andsuperiortomisoprostol(RR0.21,95%CI0.07 0.58). Conclusion:Additionaluterotonicswere
needed less frequently by patients treated with carbetocin. Carbetocin was comparable to oxytocin and
superiortomisoprostolinthepreventionofuterineatonyfollowinganelectivecesareandelivery.
ClinicalTrials.gov:NCT02053922
2016InternationalFederationofGynecologyandObstetrics.PublishedbyElsevierIrelandLtd.Allrightsreserved.

Keywords:
Atony
Carbetocin
Cesareandelivery
Misoprostol
Oxytocin
Postpartumhemorrhage

1. Introduction

Oxytocinistheuterotonicagentthatismostwidelyusedandhasthe
greatestavailability[6 ].Oxytocinhasarapidonsetofaction,agoodsafety
Globally,cesareandeliveryisoneofthemostcommonmajoroperprole,andhasbeenshowntodecreasetheincidenceofPPHby40%[7].
10minutes),necessitating
ationsthatwomenundergo,andthecesareandeliveryrateisincreasing Nevertheless,oxytocinhasashorthalf-life(4
worldwide [1]. Postpartum hemorrhage (PPH) following cesarean continuousintravenousinfusion.Moreover,saturationofmyometrial
delivery is a signicant problem and a major cause of maternal
oxytocinreceptorscouldreduceitseffectiveness,andexcessivedosing
mortality[2 ].WHOdenesPPHasbloodlossofatleast500mLwithin
canleadtocoronary-arterycontractionandhypotension;additionally
24 hoursofdelivery[3 ].
waterintoxicationcanoccurowingtoitsanti-diureticeffects[6 ].
Patients benet from reductions in operative blood loss during
Alternativetreatmentshavebeeninvestigated,includingprostaglancesareandeliverythroughdecreasedpostoperativemorbidityandre- dins,suchasmisoprostol,andoxytocinagonists,suchascarbetocin[8].
duced exposure to the risks associated with blood transfusions [4 ].MisoprostolisaprostaglandinE
1 analoguewithstronguterotonicproperThecommonestcauseofhemorrhageduringdeliveryisuterineatony; tiesandhas beensuggestedasanalternativetoinjectableuterotonic
consequently,ithasgenerallybeenagreedthat,duringdelivery,active agentsforpreventingPPH[9].Itischeap,heatstable,andcanbeadminmanagement of the third stage of labor is preferable to expectant isteredthroughmultipleroutes;however,itisknowntobelesseffective
management[5].Activemanagementofthirdstageoflaborincludes
thanoxytocininpreventingPPH[10].Inlow-resourcesettings,patients
controlled cord traction for the expulsion of the placenta during
canbeatriskofPPHifoxytocinisstoredinsuboptimalconditionsunless
a cesarean delivery and the administration of intramuscular or
thereisareadilyavailablealternative,suchasmisoprostol[10,11].
intravenousoxytocin[3 ].
Carbetocin,along-actingoxytocinanalogue,hasbeenreportedto
decreasetheneedforadditionaluterotonicsduringcesareandeliveries

Corresponding author at: 4 Hosni Osman st., El-Sefarat, Nasr City, Cairo, Egypt.comparedwithoxytocin[12].A100- gdoseofcarbetocinhasbeenrecommendedforpreventingPPH[6 ].Carbetocinhasbeenrecommended
Tel.:+201001222047;fax:+200224346058.
E-mailaddress:
drmsweed@med.asu.edu.eg(M.Sweed).
for PPH prevention following elective cesarean deliveries [ 13].An
http://dx.doi.org/10.1016/j.ijgo.2016.01.025
0020-7292/2016InternationalFederationofGynecologyandObstetrics.PublishedbyElsevierIrelandLtd.Allrightsreserved.

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325

advantageofcarbetocinoveroxytocinisthat,owingtoitslonghalf-life,
Patientsinthecarbetocingroupweretreatedwithasingle1-mLamitisadministratedasasingleintravenousdose,whileoxytocinrequires pouleofcarbetocin(100 g/mL)(Pabal;Draxis/Multipharma,Egypt)
repeatedadministrationorcontinuousinfusionoverseveralhours,with addedto10cm3salinethatwasadministeredintravenouslyfollowing
variationsindoses[2 ].
thedeliveryoftheneonate[3 ].Patientsassignedtothemisoprostol
Theaimofthepresentstudywastoevaluatetheeffectivenessand
group received two sublingual misoprostol tablets (each tablet
sideeffectsofcarbetocin,misoprostol,andoxytocinintheprevention 200 g)(Misotac;SigmaPharmaceuticals,Egypt)followingthecesareofPPHinpatientsundergoingelectivecesareandeliveries.
andelivery[4 ].Patientswhoreceivedoxytocintherapyreceivedasingle
1-mLampouleofoxytocin(10IU/mL)(Syntocinon;NovartisPharma,
3
2. Materialsandmethods
Berne,Switzerland)addedto10cm
salinethatwasadministeredslowly intravenously following neonatal delivery; additionally, these
The present prospective randomized double-blind trial was
patientsreceived20IUoxytocinaddedto500mLsalineadministered
conductedatAin-ShamsUniversityMaternityHospital,Cairo,Egypt,
as an intravenous infusion over 4 hours [3 ].Patientsin each group
between October 1, 2012 and June 30, 2013. Patients attending thealso received placebos of the other treatment modalities that were
prenatalclinicatAin-ShamsUniversityMaternityHospitalwhowere
administeredaccordingtothesamemethodoftheotherstudydrugs.
Additional uterotonics (intravenous oxytocin 10 IU or other
scheduledtoundergoanelectivecesareandeliverywereconsidered
forenrollment.Patientswereeligibleiftheyhadasingletonpregnancy ecbolics) were administered if uterine atony was detected through
37 weeks). The
physicalexaminationbytheseniorregistrarandthepresenceofcontinthat had reached full term (duration of pregnancy
exclusioncriteriaincludedhypersensitivitytooxytocin,carbetocin,or uouspostpartumbleeding.
prostaglandins; contraindication to treatment with prostaglandins
Surgicaltowelswereweighedwiththeirwrappingbeforeandafter
cantheart disease;severe asthma; deliveryusingahighlyaccuratedigitalbalance.Thedifferenceinmass
(e.g. glaucoma);history of signi
epilepsy;historyorevidenceofliver,renal,orvasculardisease;history betweenthedryandsoakedtowelswascalculated.Operativeblood
ofcoagulopathy,thrombocytopenia,oranticoagulanttherapy;HELLP losswascalculatedusingthreeparameters:(A)thevolumeofthesucsyndromeoreclampsia;placentalabruption;orcontraindicationtospi- tion bottle contents (mL), (B) the difference in towel mass (g), and
nalanesthesia(carbetocinislicensedforusewithregionalanesthesia (C) the amnioticfluid volume (mL). Intraoperative blood loss (mL)
wascalculatedas:
only).Approvalforthestudyprotocolwasobtainedfromtheethical
committee of the department of Obstetrics and Gynecology at
Ain-Shams University and written informed consent was obtained
fromallparticipants.
Intraoperativebloodloss
= ( A + B) C [15].
Patientsfulllingtherecruitmentcriteriawererandomlyassignedto
treatmentwithcarbetocin,misoprostol,oroxytocinusingMedCalcversion13.2.2(MedCalcSoftware,Ostend,Belgium).Randomizationwas
Postpartumbloodlossduringthe rst24hoursafterdeliverywas
performedina1:1:1ratiousingacomputer-generatedsequence.Num- measured by weighing used wound dressings after 24 hours and
bered,sealedenvelopeswereprepared,witheachenvelopecontaining subtractingthedryweightofthepads.A100-gincreaseinmasswas
oneofthethreestudydrugsandplacebosfortheothertwodrugs.Tabconsideredequivalentto100mLofbloodoramnioticfluid.Thehemoletplacebos,containinghydrogenatedcastoroil,hypromellose,micro- globin level was tested in the laboratory of the study institution by
crystallinecellulose,andsodiumstarchglycolatewerepreparedtobe obtainingacompletebloodanalysis24hoursafterdelivery.Anycompliidenticalinsize,color,shape,andpackingtothetabletstudydrug.Intra- cationsoccurringduringthepostoperativeperiodwererecorded.
Theprimaryoutcomewastheoccurrenceofuterineatonyrequiring
venous placebo ampoules containing normal saline were prepared
and were identical in shape and packing to the intravenous study theuseofadditionaluterotonics.Secondaryoutcomemeasuresincluded
drugs used. All envelopes were prepared by Sigma Pharmaceuticalstotalbloodloss,thedifferenceinhemoglobinlevelbeforeand24hours
andwerealreadysealedwhenreceivedbytheresearchteam.Anenve- afterdelivery,andthedevelopmentofanyadverseevents.Detailsofadlopewasallocatedtoeachpatientusingthecomputer-generatedseverseeventswereobtainedthroughverbalinterviewswithpatientsand
quence.Therandomizationprotocolwasconcealedfromtheresearch throughobservationsmadebycaregiversandtheattendingregistrar.
teamandtheprimaryinvestigatorcontactedacentralcoordinatinginAminimumsamplesizeof241participantswascalculatedusingPAS
canceof0.05and
vestigatortoidentifytheenvelopetobedistributedtoeachpatient.
11 (NCSS,Kaysville,Utah,USA)toprovideatestsigni
Consequently,patients,investigators,anddataanalystsweremasked apowerof0.8.Thetargetstudygroupsizewassetat90patientsineach
togroupassignmentsandunmaskingonlyoccurredafterdataanalysis studyarmtoaccountforwithdrawalsandotherpatientexclusions.
Data were analyzed on a per-protocol basis using SPSS version
wascompleted.
Prior to cesarean delivery, the amnioticfluid index (AFI) was
21 (IBM, Armonk, NY, USA) and MedCalc version 12.5 (MedCalc
Software, Ostend, Belgium). Comparisons were made between the
estimatedusingabdominalultrasonographyonthedayofdeliveryor
Wallis test,
thedaybeforedelivery.Theuteruswasdividedintofourquadrants;
three groups with an analysis of variance test, Kruskal
denceintervals
therightandleftquadrantswerede nedbythelineanigra,andthe
or 2 test, asappropriate.Relativeriskswith95% con
upperandlowerquadrantsweredenedbytheumbilicus.Themaxiwere calculated to compare the risks of developing uterine atony or
fluidineachquadrantwasmeasured developing PPH between the three treatment groups. Results were
mumverticaldiameterofamniotic
incentimeters.Thesumofthesefourquadrantswasusedtocalculate
reported as mean SD or number (percentage) and
P b 0.05 was
cant.
considered statistically signi
theAFI[14].ThevolumeofamnioticfluidinmLwasestimatedbymultiplyingtheAFIby30[15].Hemoglobinconcentrationsandhematocrit
valueswereobtainedforeachpatientbeforecesareandelivery.
3. Results
Lowersegmentcesareandeliverieswereperformedunderspinal
anesthesiabyaseniorregistrarwhohadpreviouslyperformedatleast
Intotal,324patientswereconsideredforinclusionandwere270en300cesareandeliveryprocedures.Theplacentawasremovedbycord rolledinthepresentstudy(90ineachtreatmentarm).Inthecarbetocin
traction and uterine compression. The uterus was exteriorized and treatment arm, two patients were excluded after receiving general
compressed during closure. Closure was achieved using continuousanesthesia;onepatientwasexcludedfromthemisoprostolarmafter
unlockedVicryl0sutures(Ethicon,Somerville,NJ,USA)intwolayers.
accidentlybreakingadrugampouleandfourpatientswereexcluded
Peritoneum and muscle layers were not closed, and the sheath wasfrom the oxytocin treatment arm (two patients received general
closedusingthesamesuturematerial.
anesthesia and two accidentally broke drug ampoules) (Fig. 1). No

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Fig.1. Flowofparticipantsthroughthestudy.

signicant differences in patient demographic data were recorded group required a blood transfusion but did not require any further
between the three groups (Tab l e 1). Recognizable risk factors for surgicalintervention(Table2).
PPH were recorded in 220 patients (83.6%); the most common risk
Theincidenceofheatsensation,metallictaste,fever,andshivering
factorswereanemia,previouscesareandelivery,multiplepregnancy, wereallhighestinthemisoprostolgroup;theincidenceofabdominal
polyhydramnios,andmacrosomia.
painwashighestinthecarbetocingroup(Table4).
Theuseofadditionaluterotonicswaslowestinthecarbetocingroup
(P =0.004)(Table2).Therelativeriskofneedingadditionaluterotonics
wasloweramongpatientstreatedwithcarbetocincomparedwithpa- 4. Discussion
tientstreatedwithmisoprostol(P =0.003).Nosigni cantdifference
cantlylowerratesofusingadwasobservedintherelativeriskofneedingadditionaluterotonicsbeThepresentstudydemonstratedsigni
tween patients in the carbetocin and oxytocin groups
P=
( 0.114),
ditionaluterotonicsfollowingcesareandeliveriesinpatientstreatedwith
and between the patients in the misoprostol and oxytocin groups carbetocincomparedwithpatientstreatedwithmisoprostoloroxytocin;
(P =0.097)(Table3).Thecalculatedeffectsizeforuseofadditional
the relative risk of needing additional uterotonics was comparable
uterotonics was 0.198. The power of the study with this effect size,betweenthecarbetocinandoxytocintreatmentarms,andwaslowerin
inasampleof270patientswithanalphalevelof0.05,wascalculated
thecarbetocintreatmentarmthaninthemisoprostolarm.Thefrequency
tobe82.5%.
of patients experiencing postpartum blood loss of500
1000 mL and
Nosignicantdifferencewasobservedbetweenthethreegroupsin N1000 mLwas signicantlyloweramongcarbetocin-treated patients
thetotalbloodloss(P=0.054),althoughhigherbloodlosswasnotedin comparedwiththemisoprostol-treatedandoxytocin-treatedpatients.
patientstreatedwithmisoprostol.TherelativeriskofdevelopingPPH
Misoprostolusewasassociatedwithgreaterdecreasesinhemoglobin
wassignicantlylowerinthecarbetocingroupwhencomparedwith
levelscomparedwiththeotherdrugs.
boththemisoprostolandoxytocingroups(Table3).Theincidenceof
Choicesinpostpartumuterotonicsareinfluencedprimarilybythe
bloodlossof500 1000 mLand N1000 mLwerehighestinthepatients
effectiveness of drugs; however many additional factors should be
treatedwithmisoprostol(bothP =0.001);themisoprostoltreatment
considered,includingpotentialadverseeventsand,particularlyinlowgroupalsodemonstratedthegreatestdecreaseinhemoglobinlevelsfol-resourcesettings,cost-effectiveness.Oxytocinhasbeenconsideredthe
lowingdelivery(P =0.001).Onepatientintheoxytocingrouprequired rst-linedrugfortheprophylaxisofPPHowingtoitseffectivenessand
le[16].ThepresentstudyinvestigateddiffurthersurgicalinterventionintheformoftheapplicationofB-Lynch
favorableadverse-effectpro
compression sutures to control PPH due to uterine atony; the sameferentuterotonicsforthepreventionofPPHfollowingelectivecesarean
patient required a blood transfusion. A patient in the misoprostol deliveriesinalow-resourcesetting.Thealternativestooxytocinincluded

Table1
a
Patientcharacteristics.
Variable

Carbetocin-treatedpatients(n=88)

Misoprostol-treatedpatients(n=89)

Oxytocin-treatedpatients(n=86)

P value

Age,y
Weight,kg
BMI
Durationofpregnancyatenrollment,wk
Gravidity
Parity
PPHriskfactorspresent

28.05.5
86.013.3
33.05.2
38.40.8
3 (1 8)
1 (0 5)
70 (80)

27.95.2
85.313.3
32.85.4
38.40.8
3 (1 9)
1 (0 6)
77 (87)

27.75.5
84.211.2
32.24.3
38.30.8
3 (1 7)
1 (0 6)
73 (85)

0.922b
0.633b
0.541b
0.639b
0.973c
0.988c
0.424d

Abbreviations:BMI,bodymassindex(calculatedasweightinkilogramsdividedbysquareofheightinmeters);PPH,postpartumhemorrhage.
a
ValuesaregivenasmeanSD,median(interquartilerange),ornumber(percentage),unlessindicatedotherwise.
b
Analysisofvariancetest.
c
Kruskal Wallistest.
d 2
test.

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Table2
a
Postpartumoutcomes.
Outcomemeasure

Carbetocin-treatedpatients(n=88)

Misoprostol-treatedpatients(n=89)

Oxytocin-treatedpatients(n=86)

P value

Bloodloss,mL
Bleedingof500 1000mL
BleedingN1000mL
Hemoglobindecrease,g/dL
Additionaluterotonics
Bloodtransfusion
Additionalsurgicalinterventions

437(168 1194)
18 (20)
3 (3)
6.0(3.0 16.0)
5 (6)
0
0

583(178 1184)
42 (47)
7 (8)
10.0( 3.0to19.0)
20 (22)
1 (1)
0

439(188 1079)
29 (34)
5 (6)
7.0( 3.0to16.0)
11 (13)
1 (1)
1 (1)

0.054b
0.001c
0.001c
0.001b
0.004c
NAd
NAd

Abbreviation:NA,notapplicable.
a
Valuesaregivenasmedian(range)ornumber(percentage),unlessindicatedotherwise.
b
Kruskal Wallistest.
c 2
test.
d
No P valuewascalculatedowingtotheverylowincidence.

inthepresentstudywereonehighlycost-effectivedrug(misoprostol) was more effective than oxytocin alone in reducing intra- and postandalongactingsingle-doseoxytocinagonist(carbetocin).
operativehemorrhageduringcesareandeliveries[9].Othertrialsand
Intheauthors experience,oxytocinandmisoprostolarethemost
reviewshaveexaminedtheeffectivenessofmisoprostolduringvaginal
deliveries.Varyingresults have been reported; however, misoprostol
commonlyuseduterotonicsinEgyptespecially,inruralareas,while
carbetocinisarelativelynewalternativeinthissetting.Tothebestof
hasnotbeenfoundtobesuperiortooxytocininreducingpostpartum
ourknowledge,thisisthe rsttrialtocomparethesethreeagents.A
bloodlossandtheuseofadditionaluterotonicsingeneral[23,24].
recent Egyptian study [17 ] that enrolled 380 patients compared
Carbetocin is a recent innovation in the prevention of PPH [5 ].
combinationsublingualmisoprostolandoxytocininfusionwithintrave- Carbetociniscurrentlyapprovedforthepreventionofuterineatony
nouscarbetocininthepreventionofPPHduringcesareandeliveryin
aftercesareandeliveryunderspinalorepiduralanesthesiain23coun
high-riskpatients.Theauthorsconcludedthatcombinedmisoprostol
tries [5 ]. Carbetocin is characterized by a longer duration of action
oxytocinwasaseffectiveasintravenouscarbetocininreducingtheneed thanoxytocinandhasbeendemonstrated,inmanystudies[5,25],to
foradditionaluterotonics[17].
havefewadverseeffects.Fewstudiesareavailablethathavecompared
Inthepresentstudy,oxytocinwasmoreeffectivethanmisoprostol carbetocinandoxytocin.Asystematicreviewof11studies[5 ]included
in reducing blood loss during cesarean delivery and in reducing thefourstudiesthatcomparedcarbetocin(100gadministeredintraveneedforpostoperativeuterotonics;additionally,adverseeffectswere nously)withoxytocininpatientsundergoingacesareandelivery.In
foundtobemorecommonwithmisoprostolthanwithoxytocin.Arecomparison with oxytocin, carbetocin demonstrated a statistically
cent systematic review [18 ] that compared sublingual misoprostolsignicantreductionintheuseofadditionaluterotonics.However,no
cant difference was reported between carbetocin
withplacebooroxytocinforreducingPPHrevieweddatafrom72trials
statistically signi
includingatotalof52678patients.Generally,sublingualmisoprostol and oxytocin in terms of the risk of patients experiencing PPH
wasmoreeffectivethanplaceboinreducingbloodlossfollowingdeliv- (500 1000-mLbloodloss)orseverePPH( N1000-mLbloodloss)[5].
ery;however,misoprostolwasnobetterthanconventionalinjectable Onestudyhasfoundcarbetocintobeaseffectiveasacombinationof
uterotonics,especiallyinlow-riskstudypopulations[18].
misoprostol plus oxytocin in the reduction of PPH and the use of
Additionally,thissystematicreview[18]includedonly11studies
additional uterotonics [17 ]. To the best of our knowledge, no other
thatspecicallyinvestigatedcesareandeliveriesandthesetrialstested studieshavecomparedcarbetocinwithmisoprostolandfewclinical
misoprostolaloneorcombinedwithoxytocinagainstoxytocinalone.
trialshavebeenregisteredwiththisasanexplicitaim.
600-gtobeasefSomestudieshavedemonstratemisoprostol400
Inthepresentstudy,alowerrelativeriskofexperiencingPPHwas
g
fectiveasoxytocin[4,15,19],andacombinationofmisoprostol200
demonstratedforcarbetocintreatmentincomparisonwithoxytocin
with oxytocin has been demonstrated to reduce blood loss and the buttherewasnosigni cantdifferencebetweenthetwointherelative
needforadditionaluterotonics[20,21 ].AChinesestudy[22 ]reported riskofdevelopinguterineatony.Carbetocinwasdemonstratedtobe
that a 600-g dose of misoprostol was superior to oxytocin in the superiortomisoprostolinpreventingbothPPHanduterineatony.Conprevention of postpartum bleeding. Another systematic review [9],sequently,itissuggestedthatcarbetocincanbeconsideredasuperior
whichexaminedtheuseofprophylacticmisoprostolduringcesarean
choicetomisoprostolandoxytocin.Moreover,carbetocindemonstrated
deliveries, included data from 17 studies (3174 patients). Generally,
a lower incidence of several common adverse effects, including
when compared to oxytocin, misoprostol alone did not demonstrateabdominalpainduetouterinecontractions.Additionally,carbetocin
any signicant improvements in the prevention of intra- and post- hasalongdurationofaction,producingrhythmicuterinecontractions
oxytocin
operativehemorrhage[9];however,combinationmisoprostol
for60minutesfollowingintravenousadministration[6 ].

Table3
RelativeriskofdevelopinguterineatonyandPPH.
Variable
Riskofdevelopinguterineatony
Carbetocinvsoxytocin
Misoprostolvsoxytocin
Carbetocinvsmisoprostol
RiskofdevelopingPPH( 500mL)
Carbetocinvsoxytocin
Misoprostolvsoxytocin
Carbetocinvsmisoprostol

cient
Regressioncoef

Standarderror

0.890
0.681
1.571

0.562
0.411
0.526

0.114
0.097
0.003

0.41(0.14 1.25)
1.98(0.88 4.42)
0.21(0.07 0.58)

0.735

0.333
0.307
0.329

0.027
0.041
b0.001

0.48(0.25 0.92)
1.87(1.03 3.42)
0.26(0.13 0.49)

0.628
1.363

P value

Relativerisk(95%condenceinterval)

Abbreviation:PPH,postpartumhemorrhage.

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Table4
a
Adverseevents.
Adverseevent

Carbetocin-treatedpatients(n=88)

Misoprostol-treatedpatients(n=89)

Oxytocin-treatedpatients(n=86)

P valueb

Headache
Heatsensation
Abdominalpain
Palpitations
Metallictaste
Fever
Shivering
Nausea
Vomiting
Pruritus

20 (23)
14 (16)
72 (82)
17 (19)
5 (6)
12 (14)
8 (9)
12 (14)
6 (7)
4 (5)

24 (27)
34 (38)
47 (53)
24 (27)
14 (16)
31 (35)
28 (31)
12 (13)
9 (10)
4 (4)

24 (28)
17 (20)
44 (51)
44 (51)
2 (2)
12 (14)
16 (19)
12 (14)
7 (8)
2 (2)

0.706
0.001
b0.001
b0.001
0.003
b0.001
0.001
0.996
0.728
0.779

a
b

Valuesaregivenasnumber(percentage)unlessindicatedotherwise.
2 test.

[10] Ho f meyrGJ , GlmezogluAM . Misop r os t ol f or t hepreven t ionand t reatmen t ofpo stOnelimitationofthepresentstudywascomparingcarbetocinand

41 .
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oxytocintomisoprostolwithoutincludingacombinationofmisoprostol [11] Ela ti A , Week s A.Mi s op r o st o l fo r themanagemen t o f po s tpartumhaemo r rhage . BM J
plus oxytocin as a comparator. Combining both drugs could have
201 1;342:d2877 .
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producedcomparableeffectstocarbetocinaloneandcouldbeagood
versusoxy t ocin f or t hepreventiono f postpartumhaemorrhagefo ll owingcaesa r ean
low-costalternativetocarbetocin,whichisexpensive,inlow-resource
s ec t ion: t here s ul ts o f adouble-b li ndrandomised t rial . B J OG2010;117 ( 8):929 36 .
settingslikeEgypt.
[13] LeducD,SenikasV,LalondeAB,BallermanC,BiringerA,DelaneyM,etal.Active
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Inconclusion,carbetocinappearstobeanattractivealternativeto
hemorrhage. J Ob s te t GynaecolCan2009;31(10 ) :980 93.
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PPHfollowingcesareandelivery.
amniotic uidvo l umeinintrauterinepo c ke ts. Ob st e t Gyneco l 1997;90(6 ) :1007 10.

Conflictonterest
Theauthorshavenoconflictsonterest.
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