WHO guidelines

for the management of

postpartum haemorrhage
and retained placenta
WHD guIdelInes
for the management of
postpartum haemorrhage
and retaIned placenta
WHD LIbrary CataloguIngInPublIcatIon 0ata:
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+036
1.Placenta, FetaIned therapy. 2.Postpartum hemorrhage dIagnosIs. J.Postpartum hemorrhage therapy.
4.DbstetrIc labor complIcatIons. 5.CuIdelInes. .World Health DrganIzatIon.
S8N 978 92 4 159851 4 (NL| classIcatIon: WQ JJ0)
7$!./*($")3*01$#/%3+'830'.+$9::;
All rIghts reserved. PublIcatIons of the World Health DrganIzatIon can be obtaIned from WHD Press, World
Health DrganIzatIon, 20 Avenue AppIa, 1211 Ceneva 27, SwItzerland (tel.: +41 22 791 J264; fax: +41 22 791
4857; emaIl: bookorders@who.Int). Fequests for permIssIon to reproduce or translate WHD publIcatIons
- whether for sale or for noncommercIal dIstrIbutIon - should be addressed to WHD Press, at the above
address (fax: +41 22 791 4806; emaIl: permIssIons@who.Int).
The desIgnatIons employed and the presentatIon of the materIal In thIs publIcatIon do not Imply the
expressIon of any opInIon whatsoever on the part of the World Health DrganIzatIon concernIng the legal
status of any country, terrItory, cIty or area or of Its authorItIes, or concernIng the delImItatIon of Its
frontIers or boundarIes. 0otted lInes on maps represent approxImate border lInes for whIch there may not
yet be full agreement.
The mentIon of specIc companIes or of certaIn manufacturers' products does not Imply that they
are endorsed or recommended by the World Health DrganIzatIon In preference to others of a sImIlar
nature that are not mentIoned. Errors and omIssIons excepted, the names of proprIetary products are
dIstInguIshed by InItIal capItal letters.
All reasonable precautIons have been taken by the World Health DrganIzatIon to verIfy the InformatIon
contaIned In thIs publIcatIon. However, the publIshed materIal Is beIng dIstrIbuted wIthout warranty of
any kInd, eIther expressed or ImplIed. The responsIbIlIty for the InterpretatIon and use of the materIal lIes
wIth the reader. n no event shall the World Health DrganIzatIon be lIable for damages arIsIng from Its use.
PrInted In France.
<.+0)+0,
=35>%/.&+($ ?
@)01.(,$ 9
A5.4)$.-$01)$%&'()*'+),$ B
CD'()+5)$3+($/)5.22)+(30'.+,$ E
F6$ G'3%+.,',$.-$HH"$ E
1. Should blood loss be routInely quantIed durIng management of the thIrd stage of
labour for the purpose of dIagnosIng PPH: 4
=6$ @3+3%)2)+0$.-$30.+'5$HH"$ I
1. |edIcal InterventIons for management of PPH 5
2. NonmedIcal InterventIons for management of PPH 12
J. SurgIcal InterventIons In the treatment of PPH 16
<6$ @3+3%)2)+0$.-$/)03'+)($4*35)+03$ ?J
1. Should uterotonIcs be offered as treatment for retaIned placenta: 17
2. Should IntraumbIlIcal veIn InjectIon of oxytocIn wIth or wIthout salIne be offered
as treatment for retaIned placenta: 18
J. Should antIbIotIcs be offered after manual extractIon of the placenta as part of the
treatment of retaIned placenta: 19
G6$ <1.'5)$.-$K&'($-./$/)4*35)2)+0$./$/),&,5'030'.+$ 9:
1. Should crystalloIds be offered for uId replacement In women wIth PPH: 20
C6$ ")3*01$,L,0)2,$3+($./%3+'830'.+3*$'+0)/D)+0'.+,$ 9?
1. Should health care facIlItIes have a protocol for management of PPH: 21
2. Should health care facIlItIes have a formal protocol for referral of women
dIagnosed as havIng PPH: 21
J. Should sImulatIon of PPH treatment be part of traInIng programmes for

health care provIders: 22
HH"$53/)$4301M3L,$ 99
N),)3/51$O24*'530'.+,$ 9E
H*3+,$-./$*.53*$3(34030'.+$.-$01)$/)5.22)+(30'.+,$ 9P
H*3+,$-./$,&44./0'+%$'24*)2)+030'.+$.-$01),)$/)5.22)+(30'.+,$ 9P
QNFGC$03R*),$ 9P
A. 0IagnosIs of PPH 27
8. |anagement of atonIc PPH 28
C. |anagement of retaIned placenta JJ
0. ChoIce of uId for replacement or resuscItatIon J8
N)-)/)+5),$ E:
Annex 1. ScopIng document wIth average scores 47
Annex 2. Search strategy 50
Annex J. CFA0E methodology 51
Annex 4. LIst of partIcIpants 54
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
'D
F5>+.M*)(%)2)+0,
ThIs document was prepared by 0r A. |etIn Culmezoglu, 0r Joo Paulo Souza and 0r 0orIs Chou (WHD 0epartment
of FeproductIve Health and Fesearch), 0r |atthews |athaI (WHD 0epartment of |akIng Pregnancy Safer),
0r Suzanne HIll (WHD EssentIal |edIcInes and PharmaceutIcal PolIcIes) and 0r Edgardo Abalos (Centro FosarIno
de EstudIos PerInatales, FosarIo, ArgentIna), on the basIs of dIscussIons at the WHD TechnIcal ConsultatIon on
the |anagement of Postpartum Haemorrhage and FetaIned Placenta, held In Ceneva on 18-21 November 2008.
The document was nalIzed after consIderatIon of all comments and suggestIons from the partIcIpants of the
ConsultatIon to earlIer drafts and an Internal WHD revIew.
WHD gratefully acknowledges the contrIbutIons of the ChaIr of the ConsultatIon (0r PIsake LumbIganon) and of
the InternatIonal panel of experts who provIded Input to the ConsultatIon. The assIstance of Centro FosarIno de
EstudIos PerInatales, FosarIo, ArgentIna, and of |s |ary Ellen Stanton are also gratefully acknowledged.
The process leadIng to the preparatIon of these guIdelInes was nancIally supported by the WHD 0epartment of
FeproductIve Health and Fesearch and the UnIted States Agency for nternatIonal 0evelopment (USA0).
WHD SecretarIat wIll revIew the questIons below In the update of thIs guIdelIne planned for 2010-2011.
G)5*3/30'.+,$.-$'+0)/),0
SIx temporary advIsors (Hany AbdelAleem, JennIfer 8lum, FIchard 0erman, Justus Hofmeyr, PIsake LumbIganon
and Tran Son Thach) and one observer (8everly WInIkoff) declared that they had receIved grants for conductIng
research and made presentatIons on the research they conducted regardIng the use of mIsoprostol and other
aspects of PPH preventIon and management whIch were revIewed durIng the meetIng. None of these grants was
from commercIal entItIes. Dne observer, |s |ary Ellen Stanton, declared that she may present an organIzatIon's
posItIon (USA0) If requIred In thIs eld.
The Interests declared reect the academIc Interest and opInIons of the experts and the SecretarIat does not
belIeve that there are any undeclared commercIal or nancIal Interests among the guIdelIne revIew group.
The two observers dId not partIcIpate In the votIng processes and were not asked to approve or provIde comments
to the document.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
?
$=35>%/.&+(
Dne of the |IllennIum 0evelopment Coals set by the UnIted NatIons In 2000 Is to
reduce maternal mortalIty by threequarters by 2015. f thIs Is to be achIeved,
maternal deaths related to postpartum haemorrhage (PPH) must be sIgnIcantly
reduced. n support of thIs, health workers In developIng countrIes need to have
access to approprIate medIcatIons and to be traIned In relevant procedures. 8ut
beyond thIs, countrIes need evIdencebased guIdelInes on the safety, qualIty,
and usefulness of the varIous InterventIons. These wIll provIde the foundatIon for
the strategIc polIcy and programme development needed to ensure realIstIc and
sustaInable ImplementatIon of approprIate InterventIons.
PPH Is generally dened as blood loss greater than or equal to 500 ml wIthIn 24 hours
after bIrth, whIle severe PPH Is blood loss greater than or equal to 1000 ml wIthIn
24 hours. PPH Is the most common cause of maternal death worldwIde. |ost cases of
morbIdIty and mortalIty due to PPH occur In the rst 24 hours followIng delIvery and
these are regarded as prImary PPH whereas any abnormal or excessIve bleedIng from
the bIrth canal occurrIng between 24 hours and 12 weeks postnatally Is regarded as
secondary PPH.
PPH may result from faIlure of the uterus to contract adequately (atony), genItal
tract trauma (I.e. vagInal or cervIcal laceratIons), uterIne rupture, retaIned placental
tIssue, or maternal bleedIng dIsorders. UterIne atony Is the most common cause and
consequently the leadIng cause of maternal mortalIty worldwIde.
n practIce, blood loss after delIvery Is seldom measured and It Is not clear whether
measurIng blood loss Improves the care and outcome for the women. n addItIon,
some women may requIre InterventIons to manage PPH wIth less blood loss than
others If they are anaemIc.
FIsk factors for PPH Include grand multIparIty and multIple gestatIon. However,
PPH may occur In women wIthout IdentIable clInIcal or hIstorIcal rIsk factors. t
Is therefore recommended that actIve management of the thIrd stage of labour be
offered to all women durIng chIldbIrth, whenever a skIlled provIder Is assIstIng wIth
the delIvery (1). ActIve management should Include: (I) admInIstratIon of a uterotonIc
soon after the bIrth of the baby; (II) clampIng of the cord followIng the observatIon
of uterIne contractIon (at around J mInutes); and (III) delIvery of the placenta by
controlled cord tractIon, followed by uterIne massage.
Even wIth these efforts to prevent PPH, some women wIll stIll requIre treatment for
excessIve bleedIng. |ultIple InterventIons (medIcal, mechanIcal, InvasIve nonsurgIcal
and surgIcal procedures), requIrIng dIfferent levels of skIll and technIcal expertIse,
may be attempted to control bleedIng. For the purposes of these guIdelInes, It Is
assumed that the patIent wIth PPH Is beIng treated by a healthcare worker In a
medIcal facIlIty. Efforts In the communIty to prevent and treat PPH are not covered
here.
EffectIve treatment of PPH often requIres sImultaneous multIdIscIplInary
InterventIons. The health care provIder needs to begIn resuscItatIve efforts quIckly,
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
9
establIsh the cause of the haemorrhage, and possIbly obtaIn the assIstance of other
care provIders, such as an obstetrIcIan, anaesthetIst or radIologIst. AvoIdIng delays
In dIagnosIs and treatment wIll have a sIgnIcant Impact on sequelae and chance
of survIval. These guIdelInes therefore Include "care pathways" (or algorIthms) for
management of PPH, as a practIcal guIde for clInIcIans. (A looseleaf Insert of these
care pathways has been Included for use as a wall chart.)
ThIs document Is not Intended to be a comprehensIve guIde on management of PPH
and retaIned placenta. Father, It reects the questIons that were regarded as hIgh
prIorIty by a multIdIscIplInary panel of InternatIonal health workers and consumers.
$@)01.(,
Staff from the WHD 0epartments of FeproductIve Health and Fesearch, |akIng
Pregnancy Safer, and EssentIal |edIcInes and PharmaceutIcal PolIcIes drafted
questIons on InterventIons and a lIst of possIble outcomes In the treatment of atonIc
postpartum haemorrhage and retaIned placenta (Annex 1).
These questIons and outcomes were sent by emaIl to an InternatIonal panel of
experts (mIdwIves, obstetrIcIans, neonatologIsts, researchers, methodologIsts,
consumers and programme experts). |embers of the panel were InvIted to comment
on the relevance of the questIons and outcomes, and were asked to rate each of
them on a scale of 1 to 9. A crItIcal outcome was dened as an outcome wIth an
average score between 7 and 9. QuestIons and outcomes that scored between 4 and
6 were consIdered Important but not crItIcal, whIle those that scored less than 4
were consIdered not Important (2). Panel members were also encouraged to revIse
the questIons or suggest new questIons and outcomes.
Two remInders were sent to the members of the panel. The results of the scopIng
exercIse were sent to all respondents for revIew. All of the responses were revIewed
by WHD staff. The responses and scores are presented In Annex 1. n the preparatIon
of the care pathways for management of PPH and retaIned placenta, questIons that
scored lower than crItIcal poInts In the scopIng exercIse were Included In the search
for evIdence and appraIsal process.
Centro FosarIno de EstudIos PerInatales (CFEP), a WHD CollaboratIng Centre In
|aternal and PerInatal Health, was commIssIoned to search, revIew and grade the
evIdence to answer the questIons, usIng the CFA0E (CradIng of FecommendatIons,
Assessment, 0evelopment and EvaluatIon) methodology (Annex J). The InItIal search
for evIdence was conducted In November 2007. Fecords were searched In the
Cochrane lIbrary, Pubmed, Embase, and LIlacs. The search terms used are gIven
In Annex 2. Ad hoc searches In Pubmed were also conducted before the TechnIcal
ConsultatIon to make sure that relevant studIes were not mIssed and that studIes
IdentIed by experts In the eld were Included.
CFA0E tables were prepared for the hIghest level of evIdence avaIlable; systematIc
revIews and randomIzed controlled trIals (FCTs) or, In theIr absence, observatIonal
studIes were used. When FCTs were avaIlable, observatIonal study data were not
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
B
summarIzed In the CFA0E tables. However, they were mentIoned In the evIdence
summary and taken Into account In the recommendatIon. CFA0E tables were not
prepared for case serIes or reports.
The draft CFA0E tables were revIewed by the WHD SecretarIat together wIth CFEP
staff. FecommendatIons relatIng to the questIons and outcomes proposed were then
drafted ahead of the TechnIcal ConsultatIon. A draft of the methodology, results, and
recommendatIons was sent for revIew to a subgroup of the experts partIcIpatIng In
the TechnIcal ConsultatIon before the meetIng.
G)5','.+S23>'+%$(&/'+%$01)$0)51+'53*$5.+,&*030'.+
For each questIon, the partIcIpants In the TechnIcal ConsultatIon dIscussed the draft
text prepared by the SecretarIat, wIth the aIm of reachIng a consensus. Consensus
was dened as agreement by the majorIty of partIcIpants, provIded that those who
dIsagreed dId not feel strongly about theIr posItIon. Any strong dIsagreements were
recorded as such.
0urIng the meetIng, In addItIon to the documentatIon prepared by the SecretarIat,
prelImInary results from four unpublIshed trIals were made avaIlable. WhIle the
presentatIon of the most recent data from large trIals was welcomed and used to
Inform the recommendatIons, some partIcIpants expressed a need for more tIme
to revIew these results before makIng recommendatIons. The CFA0E tables In thIs
document Include evIdence from the search as well as the data presented and
dIscussed durIng the TechnIcal ConsultatIon.
The system used to establIsh the strength and rankIng of the recommendatIons
Involved assessIng each InterventIon on the basIs of: (I) desIrable and undesIrable
effects; (II) qualIty of avaIlable evIdence; (III) values and preferences related to
InterventIons In dIfferent settIngs; and (Iv) cost of optIons avaIlable to health care
workers In dIfferent settIngs.
$
A5.4)$.-$01)$%&'()*'+),
The draft questIons and lIst of outcomes related to the treatment of PPH and
management of retaIned placenta were sent to 144 experts from all parts of the
world. Fesponses were receIved from 60 of these experts: 46 physIcIans,
7 mIdwIves, and 7 nonclInIcIans (polIcymakers, researchers and consumers),
representIng all 6 WHD regIons.
There were J9 questIons In 6 domaIns:
assessment of blood loss (1 questIon);
drugs for atonIc PPH (1J questIons);
nondrug InterventIons for atonIc PPH:
- mechanIcal (6 questIons);
- radIologIcal (1 questIon);
- surgIcal (8 questIons);
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
E
retaIned placenta (4 questIons);
organIzatIonal and educatIonal InterventIons (5 questIons);
crystalloId versus colloId uIds for resuscItatIon (1 questIon). ThIs questIon was
Included followIng a suggestIon from the respondents durIng the survey.
The average scores for questIons and outcomes are shown In Annex 1.
t should be noted that not all outcomes are applIcable to all questIons. As mentIoned
above, questIons that scored less than 7 are also Included In the guIdelInes.
$
CD'()+5)$3+($/)5.22)+(30'.+,
F6$ G'3%+.,',$.-$HH"
?6$ A1.&*($R*..($*.,,$R)$/.&0'+)*L$T&3+0'U)($(&/'+%$23+3%)2)+0$.-$
01)$01'/($,03%)$.-$*3R.&/$-./$01)$4&/4.,)$.-$('3%+.,'+%$HH"V
Several related studIes that looked at measurement of blood loss followIng chIldbIrth,
wIth the objectIve of ensurIng tImely dIagnosIs of PPH and ImprovIng health
outcomes, were assessed. No study was found that dIrectly addressed the questIon.
A&223/L$.-$)D'()+5)
\sucl versus qucnttctve methods ]or estmctny blood loss c]ter vcyncl delvery
Dne FCT (J) compared vIsual estImatIon of blood loss wIth measurement of
blood collected In a plastIc drape. SIx observatIonal studIes (4-9), wIth a total of
594 partIcIpants, compared vIsual estImatIon wIth known values In the delIvery
room or In sImulated scenarIos. Three studIes (10-12) compared vIsual or quantIed
estImatIons wIth laboratory measurement In JJ1 vagInal delIverIes.
n the FCT (J), vIsual estImatIon underestImated blood loss when compared wIth
drape measurement (mean dIfference 99.71 ml) (page 27, CFA0E Table A1). 7Isual
methods underestImated blood loss when compared wIth known sImulated volumes.
Trcnny courses on estmctny blood loss c]ter vcyncl delvery
Dne FCT (1J) compared the accuracy of estImatIon of blood loss by 45 nurses
attendIng a course on blood loss estImatIon and 45 nurses not attendIng the course.
n thIs small FCT (1J), wIth seven sImulated scenarIos, blood loss was accurately
estImated by 75.55 of the nurses attendIng a traInIng course compared wIth 24.44
wIthout traInIng (relatIve rIsk (FF) J.09; 95 condence Interval (C) 1.80-5.J0)
(page 27, CFA0E Table A2).
n three studIes (14-16), a total of 486 staff members of maternIty servIces vIsually
estImated blood loss In sImulated scenarIos before and after traInIng courses. The
three uncontrolled studIes (14-16) show results In the same dIrectIon as the FCT.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
I
N)5.22)+(30'.+
After chIldbIrth, blood loss and other clInIcal parameters should be closely monItored.
At present, there Is InsufcIent evIdence to recommend quantIcatIon of blood loss
over clInIcal estImatIon.$WX&3*'0L$.-$)D'()+5)Y$*.M6$A0/)+%01$.-$/)5.22)+(30'.+Y$
,0/.+%Z
N)23/>,
The partIcIpants IdentIed several prIorIty research topIcs related to the denItIon
and dIagnosIs of PPH.
What quantIty of blood loss should be the marker for dIagnosIs of PPH:
0oes the act of quantIfyIng blood loss alter (or lead to Improved) clInIcal outcomes
for the mother and her baby:
WhIch clInIcal consequences of blood loss are of greatest value for the dIagnosIs
and treatment of PPH:
=6$ @3+3%)2)+0$.-$30.+'5$HH"
As a general preventIve approach, the use of oxytocIn for actIve management of the
thIrd stage of labour Is strongly recommended, because It reduces PPH by more than
60 (17).
?6$ @)('53*$'+0)/D)+0'.+,$-./$23+3%)2)+0$.-$HH"
The ConsultatIon was asked to assess the value of Injectable uterotonIcs (oxytocIn,
ergometrIne, xed dose combInatIon of oxytocIn and ergometrIne, carbetocIn and
Injectable prostaglandIn), mIsoprostol (tablet form used vIa oral, sublIngual and
rectal routes), Injectable tranexamIc acId and Injectable recombInant factor 7a In
the management of PPH thought to be due to uterIne atony.
For oxytocIn, ergometrIne and prostaglandIn F2o, the ConsultatIon agreed wIth the
doses recommended In the WHD guIde, Mcncyny complcctons n preyncncy cnd
chldbrth (18), as gIven In Table 1 (overleaf).
The recommendatIons below may also be used In cases of PPH due to uterIne
atony followIng caesarean sectIon. The ConsultatIon acknowledged that these
recommendatIons were based prImarIly on data followIng vagInal bIrth, and that
specIc data on PPH due to uterIne atony followIng caesarean sectIon were scarce
and not evaluated separately from data on vagInal bIrths.
!"#$ %&'(&$)*+,-*-.'(/$/&-)01$2+$-33+,+1$'.$*&+$4"."5+4+.*$-3$667$
1)+$*-$)*+,'.+$"*-.89
A&223/L$.-$)D'()+5)
Except for the specIc mIsoprostol trIals evaluated In sectIon (b), the evIdence
has been extrapolated from research on preventIon of PPH. SystematIc revIews
comparIng the effects of oxytocIn wIth ergometrIne (19), a xeddose combInatIon
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
P
of oxytocIn and ergometrIne (20), carbetocIn (21) and prostaglandIns (22) In the
preventIon of PPH were revIewed. The guIdelInes on preventIon of postpartum
haemorrhage publIshed by WHD synthesIzed and graded the evIdence and made
recommendatIons (1). That publIcatIon Includes the relevant CFA0E tables.
Separate CFA0E tables were not prepared for thIs questIon and the evIdence Is
summarIzed below narratIvely. Dne FCT comparIng oxytocIn to ergometrIne In
600 women (2J) was publIshed subsequent to the systematIc revIew and publIcatIon
of the WHD guIdelInes.
[3R*)$?6 0rug doses for management of PPH
DxytocIn
ErgometrIne/
|ethylergometrIne
15|ethyl
prostaglandIn F2a
0ose and route 7: nfuse 20 unIts In 1 l
7 uIds at 60 drops per
mInute
| or 7 (slowly): 0.2 mg |: 0.25 mg
ContInuIng dose 7: nfuse 20 unIts In 1 l
7 uIds at 40 drops per
mInute
Fepeat 0.2 mg | after
15 mInutes
f requIred, gIve 0.2 mg
| or 7 (slowly every
4 hours
0.25 mg every
15 mInutes
|axImum dose Not more than J l of
7 uIds contaInIng
oxytocIn
5 doses (Total 1.0 mg) 8 doses (Total 2 mg)
PrecautIons/
contraIndIcatIons
0o not gIve as an 7
bolus
PreeclampsIa,
hypertensIon, heart
dIsease
Asthma
ProstaglandIn F2a should not be gIven Intravenously. t may be fatal. Mcncyny complcctons n
preyncncy cnd chldbrth. Ceneva, World Health DrganIzatIon, 2000, page S28, table S-8.
7 Intravenous
| Intramuscular
Dxytocn vs eryometrne
Dne trIal (24) Included In the systematIc revIew reported on the crItIcal outcomes
of blood loss of 1000 ml and need for blood transfusIon. There was no dIfference
In IncIdence of blood loss 1000 ml (FF 1.09, 95C 0.45-2.66). 8lood transfusIon was
gIven to 2 of 78 women receIvIng oxytocIn compared wIth 1 of 146 women receIvIng
ergometrIne (FF J.74, 95C 0.J4-40.64). No sIgnIcant dIfference was observed In
the use of addItIonal uterotonIcs In two trIals In the systematIc revIew (24, 25): In
J5 of 557 women gIven oxytocIn and 46 of 651 women gIven ergometrIne (FF 1.02,
95 C 0.67-1.55).
n the later NIgerIan trIal (2J), the use of addItIonal uterotonIcs was reported In
18 of 297 patIents receIvIng oxytocIn In the thIrd stage of labour compared wIth
J0 of J0J receIvIng ergometrIne (FF 0.61, 95C 0.J5-1.07). The IncIdence of adverse
sIdeeffects was sIgnIcantly lower In women receIvIng oxytocIn than In those gIven
ergometrIne; for vomItIng, the FF was 0.09 and the 95 C 0.05-0.16); for elevated
blood pressure, FF was 0.01 and 95 C 0.00-0.15).
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
J
Dxytocneryometrne xed dose combncton vs oxytocn
WIth regard to blood loss 1000 ml, decreased blood loss was observed In the
group gIven the xeddose combInatIon of oxytocIn (5 U) and ergometrIne (0.5 mg)
although the dIfference was not statIstIcally sIgnIcant (Peto odds ratIo (DF) 0.78,
95C 0.58-1.0J). n four studIes that reported on the use of blood transfusIon, there
was no sIgnIcant dIfference and wIde condence Interval compatIble wIth eIther
dIrectIon of effect (Peto DF 1.J7, 95C 0.89-2.10). Three studIes reported a slIght,
but statIstIcally sIgnIcant, lower use of addItIonal uterotonIcs In the group receIvIng
xed dose oxytocInergometrIne combInatIon (FF 0.8J, 95C 0.72-0.96). Four studIes
reported on the IncIdence of sIdeeffects, notably a hIgher IncIdence of elevated
dIastolIc blood pressure In the group gIven the oxytocInergometrIne xed dose
combInatIon (FF 2.40, 95C 1.58-J.64).
Dxytocneryometrne xed dose combncton vs eryometrne
None of the crItIcal outcomes was addressed In the studIes.
Ccrbetocn vs oxytocn
No data on blood loss 1000 ml, blood transfusIon or surgIcal treatments were
avaIlable. For the other prIorIty outcomes, the use of addItIonal uterotonIcs was
sImIlar In the two groups (FF 0.9J, 95C 0.44-1.94), but there was less use of uterIne
massage In the carbetocIn group (FF 0.70, 95 C 0.51-0.94). 0ata on sIdeeffects
were too lImIted to allow any judgements to be made (nausea: FF 0.66, 95C
0.22-2.00; vomItIng: FF 0.07, 95C 0.00-1.25; headache: FF 0.51, 95C 0.20-1.J0).
Ccrbetocn vs Dxytocneryometrne xed dose combncton
Df 150 women gIven carbetocIn and 150 gIven oxytocInergometrIne xed dose
combInatIon, only one woman gIven the combInatIon experIenced blood loss \1000 ml
(26). Use of addItIonal uterotonIcs was sImIlar, wIth wIde condence Intervals (FF 1.J,
95C 0.56-J.1J), but the occurrence of sIdeeffects was lower In the carbetocIn
group (nausea: FF 0.18, 95C 0.04-0.78; hypertensIon up to 60 mInutes postpartum:
FF 0.11, 95C 0.0J-0.47). n a smaller observatIonal study (27), fewer women In the
carbetocIn group had a blood loss of 1000 ml (1 of 55 gIven carbetocIn and 9 of 62
gIven the combInatIon (FF 0.12, 95C 0.15-0.94)).
lntrcmusculcr prostcylcndns vs n]ectcble uterotoncs)
No dIfference was observed In the rIsk of blood transfusIon between these two
treatments (FF 1.05, 95C 0.J9-2.86). Use of addItIonal uterotonIcs was not
sIgnIcantly dIfferent between the prostaglandIn group (4 of 106) and the Injectable
uterotonIc group (2 of 116) (FF 2.05, 95C 0.J9-10.92). 7omItIng was observed In
15 of 10J patIents receIvIng prostaglandIn and 1 of 107 patIents receIvIng Injectable
uterotonIcs (FF 10.74, 95C 2.06-56.02).
Sulprostone vs n]ectcble uterotoncs
Two FCTs conducted In the Netherlands (28, 29) reported on estImated blood loss
of \1000 ml. There was a nonsIgnIcant reductIon In the rIsk of severe PPH In both
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
]
lowrIsk (28) and hIghrIsk women (29) (FF 0.41, 95C 0.14-1.20) In women receIvIng
sulprostone. The 7an Selm study (29) was termInated early because of concerns
regardIng myocardIal InfarctIons In women treated wIth sulprostone and mIfeprIstone.
Ccrboprost vs msoprostol
No evIdence was found relatIng to the prIorIty outcomes regardIng blood loss. Df
60 patIents In the carboprost group, none receIved a blood transfusIon compared
wIth 1 of 60 In the mIsoprostol group (FF 0.JJ, 95C 0.01-8.02) (J0). No patIents In
the carboprost group reported shIverIng, compared wIth 5 In the mIsoprostol group
(FF 0.09, 95C 0.01-1.61).
Msoprostol vs n]ectcble uterotoncs
When compared wIth Injectable uterotonIcs there was an Increase In the rIsk of
blood loss of 1000 ml In women receIvIng oral mIsoprostol (400-800 g) (FF 1.J2,
95C 1.16-1.51), but no statIstIcally sIgnIcant dIfference In the IncIdence of severe
morbIdIty, IncludIng maternal death (FF 1.00, 95C 0.14-7.10). These trIals dId not
report the outcome of InvasIve or surgIcal treatments.
N)5.22)+(30'.+,
For management of PPH, oxytocIn should be preferred over ergometrIne
alone, a xeddose combInatIon of ergometrIne and oxytocIn, carbetocIn,
and prostaglandIns. WX&3*'0L$.-$)D'()+5)Y$D)/L$*.M$0.$*.M6$A0/)+%01$.-$
/)5.22)+(30'.+Y$,0/.+%6Z
f oxytocIn Is not avaIlable, or If the bleedIng does not respond to oxytocIn,
ergometrIne or oxytocInergometrIne xeddose combInatIon should be offered
as secondlIne treatment. WX&3*'0L$.-$)D'()+5)Y$D)/L$*.M 0. *.M6$A0/)+%01$.-$
/)5.22)+(30'.+Y$,0/.+%6Z
f the above secondlIne treatments are not avaIlable, or If the bleedIng does
not respond to the secondlIne treatment, a prostaglandIn should be offered as
the thIrd lIne of treatment. WX&3*'0L$.-$)D'()+5)Y$D)/L$*.M$0.$*.M6$A0/)+%01$.-$
/)5.22)+(30'.+Y$,0/.+%6Z
N)23/>,
The above recommendatIons are based largely on data from preventIon trIals or
case serIes. However, data from treatment FCTs were avaIlable for mIsoprostol
versus oxytocIn.
The pharmacokInetIcs, bIoavaIlabIlIty and mode of actIon of oxytocIn and
ergometrIne and the uterotonIc effects of mIsoprostol In other obstetrIc and
gynaecologIcal uses were consIdered by the partIcIpants In the ConsultatIon In
makIng the recommendatIons.
|Isoprostol may be consIdered as a thIrd lIne of treatment for the management of
PPH, because of Its ease of admInIstratIon and low cost compared wIth Injectable
prostaglandIns (see also sectIon (b)).
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
;
The ConsultatIon noted that the cost of carbetocIn was hIgh compared wIth the
other optIons. |oreover, It found no evIdence that carbetocIn has a sIgnIcant
advantage over oxytocIn.
!2#$ :&-)01$4'/-;,-/*-0$2+$-33+,+1$'.$*&+$4"."5+4+.*$-3$667$1)+$*-$
)*+,'.+$"*-.89
The ConsultatIon made recommendatIons relatIng to two separate scenarIos: women
who receIved prophylactIc oxytocIn durIng the thIrd stage of labour and those who
dId not.
W'Z$ A1.&*($2',.4/.,0.*$R)$.--)/)($-./$01)$23+3%)2)+0$.-$HH"$'+$M.2)+$M1.$
13D)$/)5)'D)($4/.41L*350'5$.^L0.5'+$(&/'+%$01)$01'/($,03%)$.-$*3R.&/V
A&223/L$.-$)D'()+5)
Four trIals assessed the use of mIsoprostol as an adjunct followIng actIve
management of the thIrd stage of labour wIth oxytocIn (J1-J4). The three publIshed
trIals (J1-JJ) were relatIvely small, wIth a total of 465 women partIcIpatIng. The
unpublIshed WHDCynuIty trIal (J4) Included 1400 women In ArgentIna, Egypt, South
AfrIca, ThaIland and 7Iet Nam. n three trIals (J1, JJ, J4), 600 g of mIsoprostol
was admInIstered orally or sublIngually, whIle In the fourth trIal (J2) 1000 g was
admInIstered orally, sublIngually or rectally. The results of the WHDCynuIty trIal (J4)
were presented to the ConsultatIon and are Included In the CFA0E table (page 28,
CFA0E Table 81).
Taken altogether, when mIsoprostol as an adjunct was compared wIth placebo In
women receIvIng other standard treatments, there were no statIstIcal dIfferences
In the crItIcal outcomes of addItIonal blood loss 500 ml (FF 0.8J, 95C 0.64-1.07),
addItIonal blood loss 1000 ml (FF 0.76, 95C 0.4J-1.J4) and blood transfusIon
(FF 0.96, 95C 0.77-1.19). SImIlarly, In the large WHDCynuIty trIal (J4), the crItIcal
outcomes of addItIonal blood loss 500 ml (FF 1.01, 95C 0.78-1.J0), addItIonal blood
loss 1000 ml (FF 0.76, 95C 0.4J-1.J4) and blood transfusIon (FF 0.89, 95C 0.69-
1.1J) were not clInIcally or statIstIcally sIgnIcantly dIfferent In the two groups.
N)5.22)+(30'.+
There Is no added benet of offerIng mIsoprostol as adjunct treatment for PPH In
women who have receIved oxytocIn durIng the thIrd stage of labour. Where oxytocIn
Is avaIlable, and Is used In the management of the thIrd stage of labour, oxytocIn
alone should be used In preference to adjunct mIsoprostol for the management
of PPH. WX&3*'0L$.-$)D'()+5)Y$2.()/30)$0.$1'%16$A0/)+%01$.-$/)5.22)+(30'.+Y$
,0/.+%6Z
N)23/>
The recommendatIon Is based maInly on data from one large unpublIshed randomIzed
controlled trIal (J4).
W''Z$ A1.&*($2',.4/.,0.*$R)$.--)/)($3,$3$0/)302)+0$-./$HH"$'+$M.2)+$M1.$('($+.0$
/)5)'D)$4/.41L*350'5$.^L0.5'+$(&/'+%$01)$01'/($,03%)$.-$*3R.&/V
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
?:
A&223/L$.-$)D'()+5)
The evIdence relatIng to thIs questIon came from one large FCT conducted In
Ecuador, Egypt and 7Iet Nam (J5), whIch compared 800 g of mIsoprostol gIven
sublIngually wIth 40 U of oxytocIn gIven Intravenously. UnpublIshed trIal results
were presented to the ConsultatIon (page 29, CFA0E Table 82). Women who receIved
mIsoprostol had a sIgnIcantly Increased rIsk of addItIonal blood loss 500 ml
(FF 2.66, 95C 1.62-4.J8) and of needIng addItIonal therapeutIc uterotonIcs (FF 1.79,
95C 1.19-2.69). There were few cases of addItIonal blood loss 1000 ml (5 of 488 In
the group gIven mIsoprostol and J of 489 gIven oxytocIn). There was an Increased rIsk
of blood transfusIon In the mIsoprostol group, of borderlIne statIstIcal sIgnIcance
(FF 1.54, 95C 0.97-2.44).
FegardIng sIdeeffects, 66 of 488 women receIvIng mIsoprostol had a body
temperature above 40 `C, compared wIth none of 490 gIven oxytocIn. |ost of the
cases of hIgh temperature occurred In Ecuador, where J6 of the women gIven
mIsoprostol had a temperature above 40 `C. There were no cases In Egypt. Seven of
the women wIth hIgh temperature had delIrIum.
1
N)5.22)+(30'.+
n women who have not receIved oxytocIn as a prophylactIc durIng the thIrd stage
of labour, oxytocIn alone should be offered as the drug of choIce for the treatment
of PPH. WX&3*'0L$.-$)D'()+5)Y$2.()/30)$0.$1'%16$A0/)+%01$.-$/)5.22)+(30'.+Y$
,0/.+%6Z
N)23/>,
EvIdence of the superIorIty of oxytocIn over mIsoprostol for the treatment of PPH
came from one large trIal, whIch showed oxytocIn to have hIgher effectIveness
and fewer sIdeeffects.
The ConsultatIon recognIzed that oxytocIn may not be avaIlable In all settIngs.
t encouraged health care decIsIonmakers In these settIngs to strIve to make
oxytocIn and other Injectable uterotonIcs avaIlable. However, because the use of
a uterotonIc Is essentIal for the treatment of PPH due to atony, It consIdered that
mIsoprostol may be used untIl oxytocIn can be made avaIlable.
The ConsultatIon noted that the doses of mIsoprostol used In the trIals on
preventIon of PPH ranged from 200 g to 800 g, admInIstered orally, sublIngually
or rectally. n the PPH treatment trIals, doses from 600 g to 1000 g were
admInIstered orally, sublIngually or rectally. SIdeeffects, prImarIly hIgh fever
and shIverIng, were assocIated wIth hIgher doses; few lIfethreatenIng events
have been reported. Hence, doses of 1000-1200 g are not recommended. The
ConsultatIon noted that the largest trIal of mIsoprostol for treatment of PPH
(J5) reported use of a dose of 800 g, gIven sublIngually. The majorIty of the
partIcIpants felt that, In the treatment of PPH, where the rst and second
lIne uterotonIcs are not avaIlable or have faIled, as a last resort 800 g can be
used. However, three members strongly dIsagreed wIth thIs conclusIon because
1
FInal numbers were conrmed after the meetIng by CynuIty.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
??
of concerns about safety. 8ecause of the dIsagreement the dIscussIon of dose Is
Included here, rather than as a recommendatIon.
n vIew of the uncertaInty and dIsagreement among the partIcIpants regardIng the
safe dose of mIsoprostol, WHD wIll commIssIon a further revIew of mIsoprostol
doses and routes of admInIstratIon.
!(#$ :&-)01$*,".+<"4'($"('1$2+$-33+,+1$'.$*&+$*,+"*4+.*$-3$667$1)+$*-$
)*+,'.+$"*-.89
TranexamIc acId Is an antIbrInolytIc agent that has been on the market for several
decades. AntIbrInolytIc agents are wIdely used In surgery to reduce blood loss.
A systematIc revIew of randomIzed controlled trIals of antIbrInolytIc agents In
electIve surgery showed that tranexamIc acId reduced the rIsk of blood transfusIon
by J9 (J6). Another Cochrane revIew showed that tranexamIc acId reduced heavy
menstrual bleedIng wIthout sIdeeffects (J7).
A&223/L$.-$)D'()+5)
There have been no FCTs on the use of tranexamIc acId for the treatment of PPH
followIng vagInal delIvery that address the prIorIty outcomes. TranexamIc acId has
been evaluated as prophylaxIs followIng caesarean sectIon In one FCT (J8). The
average blood loss In the two hours after the caesarean sectIon was 42.7540.45 ml
In the study group and 7J.9877.09 ml In the control group.
Dne case report was found of a woman gIven tranexamIc acId for treatment of
massIve postpartum haemorrhage after caesarean sectIon (J9).
N)5.22)+(30'.+
TranexamIc acId may be offered as a treatment for PPH If: (I) admInIstratIon of
oxytocIn, followed by secondlIne treatment optIons and prostaglandIns, has faIled to
stop the bleedIng; or (II) It Is thought that the bleedIng may be partly due to trauma.
WX&3*'0L$.-$)D'()+5)Y$D)/L$*.M6$A0/)+%01$.-$/)5.22)+(30'.+Y$M)3>6Z
N)23/>,
EvIdence for thIs recommendatIon was extrapolated from the lIterature on surgery
and trauma, whIch shows tranexamIc acId to be a safe optIon In traumarelated
bleedIng.
The benets of use of tranexamIc acId In PPH treatment should be InvestIgated In
research studIes.
!1#$ :&-)01$,+(-42'.".*$3"(*-,$=>>"$2+$-33+,+1$'.$*&+$*,+"*4+.*$-3$
667$1)+$*-$)*+,'.+$"*-.89
Fecently, recombInant factor 7a (rF7a) has generated Interest as an optIon for
treatment of PPH, maInly In IndustrIalIzed countrIes. The evIdence regardIng Its use
In the treatment of PPH Is lImIted to revIews of case reports and case serIes (40, 41)
and two observatIonal studIes (42,4J) (page J0, CFA0E Table 8J).
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
?9
HossaIn (4J) descrIbed a retrospectIve cohort study of J4 patIents wIth more than
1500 ml blood loss In whIch 18 were treated wIth rF7a. Ahonen (42) compared the
outcomes of 26 women who receIved rF7a to those of 22 women treated In the
same tIme perIod for PPH wIthout rF7a.
8oth studIes Included women who had had caesarean sectIon as well as women
who had had a vagInal bIrth. The causes of PPH Included uterIne atony as well as
abnormal placentatIon, retaIned placenta, and cervIcal or vagInal laceratIons. The
women had receIved conventIonal treatments, such as uterotonIcs, uterIne massage,
arterIal lIgatIon and, In some cases, hysterectomy prIor to the admInIstratIon of
rF7a.
The rIsk of maternal death appeared to be lower In women treated wIth rF7a
(DF 0.J8, 95C 0.09-1.60), and remaIned lower followIng adjustment for baselIne
haemoglobIn and actIvated partIal thromboplastIn tIme (aPTT) (DF 0.04, 95C 0.002-
0.8J) (4J). The rIsk of subsequent need for hysterectomy Is dIfcult to ascertaIn,
as the drug was admInIstered as a 'last resort' treatment. The authors note that as
condence In Its use Increased, rF7a began to be offered prIor to hysterectomy. n
Ahonen's report (42), 8 women receIved rF7a followIng hysterectomy, but none of
the remaInIng 18 women treated wIth rF7a subsequently underwent hysterectomy.
A hIgh rate of thrombotIc events (185 events In 165 treated patIents) has been
reported In patIents receIvIng rF7a for offlabel use (44). Ahonen (42) descrIbed
one report of a pulmonary embolus; the woman was subsequently dIagnosed wIth
antIthrombIn decIency.
The ConsultatIon dIscussed the evIdence from observatIonal studIes and heard about
ongoIng research on rF7a.
N)5.22)+(30'.+
The ConsultatIon agreed that there was not enough evIdence to make any
recommendatIon regardIng the use of recombInant factor 7a for the treatment of
PPH. FecombInant factor 7a for the treatment of PPH should be lImIted to women
wIth specIc haematologIcal IndIcatIons.
N)23/>
Use of rF7a could be lIfesavIng, but It Is also assocIated wIth lIfethreatenIng sIde
effects. |oreover, recombInant factor 7a Is expensIve to buy and may be dIfcult to
admInIster.
96$ _.+S2)('53*$'+0)/D)+0'.+,$-./$23+3%)2)+0$.-$HH"
A range of mechanIcal InterventIons to compress or stretch the uterus have been
proposed, eIther as temporIzIng measures or as denItIve treatment. These
InterventIons are summarIzed below.
!"#$ :&-)01$)*+,'.+$4"//"5+$2+$-33+,+1$'.$*&+$*,+"*4+.*$-3$6679
UterIne massage as a therapeutIc measure Is dened as rubbIng of the uterus
manually over the abdomen sustaIned untIl bleedIng stops or the uterus contracts.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
?B
nItIal rubbIng of the uterus and expressIon of blood clots Is not regarded as
therapeutIc uterIne massage.
A&223/L$.-$)D'()+5)
There have been no FCTs on the use of uterIne massage In the treatment of PPH. A
case report serIes (45) and IndIrect evIdence from one systematIc revIew (46) on the
use of uterIne massage In PPH preventIon were found.
n one FCT of the prophylactIc use of uterIne massage InvolvIng 200 women,
massage was assocIated wIth a nonsIgnIcant decrease In IncIdence of blood loss
500 ml (FF 0.52, 95C 0.16-1.67) and a sIgnIcant reductIon In the use of addItIonal
uterotonIcs (FF 0.20, 95C 0.08-0.50) (page J1, CFA0E Table 84).
N)5.22)+(30'.+
UterIne massage should be started once PPH has been dIagnosed. WX&3*'0L$.-$
)D'()+5)Y$D)/L$*.M6$A0/)+%01$.-$/)5.22)+(30'.+Y$,0/.+%6Z
N)23/>,
UterIne massage to ensure the uterus Is contracted and there Is no bleedIng Is a
component of actIve management of the thIrd stage of labour for the preventIon
of PPH.
The low cost and safety of uterIne massage were taken Into account In makIng thIs
recommendatIon strong.
!2#$ :&-)01$2'4".)"0$)*+,'.+$(-4;,+//'-.$2+$-33+,+1$'.$*&+$*,+"*4+.*$
-3$6679
A&223/L$.-$)D'()+5)
No FCTs on the use of bImanual uterIne compressIon In the treatment of PPH were
IdentIed. Dne case report (47) was found.
N)5.22)+(30'.+
8Imanual uterIne compressIon may be offered as a temporIzIng measure In the
treatment of PPH due to uterIne atony after vagInal delIvery. WX&3*'0L$.-$)D'()+5)Y$
D)/L$*.M6$A0/)+%01$.-$/)5.22)+(30'.+Y$M)3>6Z
N)23/>
The ConsultatIon noted that health care workers would need to be approprIately
traIned In the applIcatIon of bImanual uterIne compressIon and that the procedure
may be paInful.
!(#$ :&-)01$)*+,'.+$;"(?'.5$2+$-33+,+1$'.$*&+$*,+"*4+.*$-3$6679
A&223/L$.-$)D'()+5)
No FCTs on the use of uterIne packIng In the treatment of PPH were found. Seven
case serIes and one case report (48-55), wIth a total of 89 women (the largest
Involved JJ women), and four overvIews were IdentIed. Success rates (I.e. no need
for hysterectomy or other InvasIve procedure) rangIng from 75 to 100 are reported
In these studIes.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
?E
N)5.22)+(30'.+
UterIne packIng Is not recommended for the treatment of PPH due to uterIne
atony after vagInal delIvery.$WX&3*'0L$.-$)D'()+5)Y$D)/L$*.M6$A0/)+%01$.-$
/)5.22)+(30'.+Y$M)3>6Z
N)23/>
The ConsultatIon noted that there was no evIdence of benet of uterIne packIng and
placed a hIgh value on concerns regardIng Its potentIal harm.
!1#$ :&-)01$'.*,")*+,'.+$2"00--.$-,$(-.1-4$*"4;-."1+$2+$-33+,+1$'.$
*&+$*,+"*4+.*$-3$6679
A&223/L$.-$)D'()+5)
There have been no FCTs on the use of uterIne tamponade In the treatment of
PPH. NIne case serIes and twelve case reports, evaluatIng 97 women (56-76), and
two revIews were IdentIed (77, 78). The Instruments used Included Sengstaken
8lakemore and Foley catheters, 8akrI and Fusch balloons, and condoms.
Case serIes have reported success rates (I.e. no need for hysterectomy or other
InvasIve procedure) rangIng from 71 to 100.
N)5.22)+(30'.+
n women who have not responded to treatment wIth uterotonIcs, or If uterotonIcs
are not avaIlable, IntrauterIne balloon or condom tamponade may be offered In
the treatment of PPH due to uterIne atony.$WX&3*'0L$.-$)D'()+5)Y$*.M6$A0/)+%01$.-$
/)5.22)+(30'.+Y$M)3>6Z
N)23/>
The ConsultatIon noted that the applIcatIon of thIs InterventIon requIres traInIng
and that there are rIsks assocIated wIth the procedure, such as InfectIon. The use
of uterIne balloon or condom tamponade In the treatment of PPH was consIdered a
research prIorIty.
!+#$ :&-)01$+<*+,."0$"-,*'($(-4;,+//'-.$2+$-33+,+1$'.$*&+$*,+"*4+.*$
-3$6679
A&223/L$.-$)D'()+5)
No trIals were found descrIbIng the use of external aortIc compressIon In the
treatment of PPH. A prospectIve study was performed In AustralIa to determIne the
haemodynamIc effects of external aortIc compressIon In nonbleedIng postpartum
women (79). Successful aortIc compressIon, as documented by absent femoral pulse
and unrecordable blood pressure In a lower lImb, was achIeved In 11 of 20 subjects.
The authors concluded that the procedure Is safe In healthy subjects and may be
of benet as a temporIzIng measure In treatment of PPH whIle resuscItatIon and
management plans are made. Subsequently, one case report from AustralIa descrIbed
the use of Internal aortIc compressIon as a temporIzIng measure to control severe
PPH due to placenta percreta at the tIme of caesarean sectIon (80).
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
?I
N)5.22)+(30'.+
External aortIc compressIon for the treatment of PPH due to uterIne atony after
vagInal delIvery may be offered as a temporIzIng measure untIl approprIate care Is
avaIlable.$WX&3*'0L$.-$)D'()+5)Y$D)/L$*.M6$A0/)+%01$.-$/)5.22)+(30'.+Y$M)3>6Z
N)23/>,
External aortIc compressIon has long been recommended as a potentIal lIfesavIng
technIque, and mechanIcal compressIon of the aorta, If successful, slows down
blood loss.
The ConsultatIon placed a hIgh value on the procedure as a temporIzIng measure
In treatment of PPH.
!3#$ :&-)01$.-.;.+)4"*'($".*'/&-(?$5",4+.*/$2+$-33+,+1$'.$*&+$
*,+"*4+.*$-3$6679
A&223/L$.-$)D'()+5)
There have been no FCTs on the use of pneumatIc or nonpneumatIc antIshock
garments In the treatment of PPH. Case studIes and case serIes have, however, been
publIshed and summarIzed (81-87). The use of nonpneumatIc antIshock garments
(NASCs) has been reported In a beforeandafter study of 6J4 women wIth obstetrIc
haemorrhage (4J wIth uterIne atony) In Egypt (88).
Women treated wIth an NASC had a medIan blood loss 200 ml lower (range
J00-100 ml lower) than women who receIved standard treatment (hydratIon wIth
Intravenous uIds, transfusIon, uterotonIcs, vagInal or abdomInal surgery, as needed)
In the "before" perIod (I.e. before the IntroductIon of NASC). The rIsk of blood
transfusIon was hIgher In those treated wIth NASC (FF 1.2J, 95C 1.06-1.4J); the
rIsk of surgIcal procedures was not statIstIcally sIgnIcantly dIfferent (FF 1.J5, 95C
0.90-2.02) (page J1, CFA0E Table 85).
A cluster FCT (|Iller S, personal communIcatIon) Is under way In ZambIa and
ZImbabwe to examIne whether early applIcatIon of an NASC by mIdwIves prIor to
transfer to a referral hospItal can decrease morbIdIty and mortalIty. No data were
avaIlable for revIew.
N)5.22)+(30'.+
The ConsultatIon decIded not to make a recommendatIon on thIs questIon.
N)23/>
The ConsultatIon noted that research was ongoIng to evaluate the potentIal benets
and harms of thIs InterventIon, and decIded not to make a recommendatIon untIl
these research results become avaIlable.
!5#$ :&-)01$)*+,'.+$",*+,8$+42-0'@"*'-.$2+$-33+,+1$'.$*&+$*,+"*4+.*$
-3$6679
Percutaneous transcatheter arterIal embolIzatIon of the uterIne artery has been
reported from InstItutIons that have adequate radIologIcal facIlItIes for thIs
InterventIon.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
?P
A&223/L$.-$)D'()+5)
There have been no FCTs on the use of arterIal embolIzatIon In the treatment
of PPH. Dne retrospectIve cohort study (89) compared 15 women treated wIth
embolIzatIon wIth 14 women receIvIng other treatments for PPH. The majorIty of
these patIents had been transferred from local hospItals. Ten of 1J women were
successfully treated for PPH wIth arterIal embolIzatIon. Df 11 women orIgInally
treated wIth conservatIve surgIcal methods, two subsequently underwent arterIal
embolIzatIon; one of these was successful whIle the second patIent eventually
requIred hysterectomy. EIghteen case serIes and 15 case reports (90-122) have been
publIshed, descrIbIng the InterventIon In J40 women. StudIes report success rates
(I.e. no need for hysterectomy or other InvasIve procedures) rangIng from 82 to
100 (page J2, CFA0E Table 86).
N)5.22)+(30'.+
f other measures have faIled and resources are avaIlable, uterIne artery embolIzatIon
may be offered as a treatment for PPH due to uterIne atony. WX&3*'0L$.-$)D'()+5)Y$
D)/L$*.M6$A0/)+%01$.-$/)5.22)+(30'.+Y$M)3>6Z
N)23/>
UterIne artery embolIzatIon requIres sIgnIcant resources, In terms of cost of
treatment, facIlItIes and traInIng of health care workers.
B6$ A&/%'53*$'+0)/D)+0'.+,$'+$01)$0/)302)+0$.-$HH"
A wIde range of surgIcal InterventIons have been reported to control postpartum
haemorrhage that Is unresponsIve to medIcal or mechanIcal InterventIons. They
Include varIous forms of compressIon sutures, lIgatIon of the uterIne, ovarIan or
Internal IlIac artery, and subtotal or total hysterectomy.
A&223/L$.-$)D'()+5)
There have been no FCTs on the use of uterIne compressIve sutures In the treatment
of PPH. ThIrteen case serIes and twelve case reports descrIbIng a total of 11J women
were IdentIed (12J-147). EIght overvIews on compressIon sutures have also been
publIshed (77, 78, 148-15J). The 8Lynch technIque seems to be the most commonly
reported procedure. Success rates (I.e. no need for hysterectomy or other InvasIve
procedure) range from 89 to 100.
SImIlarly, no FCTs on the use of selectIve artery lIgatIon In treatment of PPH
were IdentIed. Twentyone case serIes and 1J case reports have been publIshed,
descrIbIng the InterventIon In 5J2 women (12J, 154-186). StudIes report success
rates (I.e. no need for hysterectomy or other InvasIve procedure) rangIng from
62 to 100.
N)5.22)+(30'.+
f bleedIng does not stop In spIte of treatment wIth uterotonIcs, other conservatIve
InterventIons (e.g. uterIne massage), and external or Internal pressure on the uterus,
surgIcal InterventIons should be InItIated. ConservatIve approaches should be trIed
rst, followed - If these do not work - by more InvasIve procedures. For example,
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
?J
compressIon sutures may be attempted rst and, If that InterventIon faIls, uterIne,
uteroovarIan and hypogastrIc vessel lIgatIon may be trIed. f lIfethreatenIng
bleedIng contInues even after lIgatIon, subtotal (also called supracervIcal or total
hysterectomy) should be performed. WX&3*'0L$.-$)D'()+5)Y$+.$-./23*$,5')+0'U5$
)D'()+5)$.-$R)+)U0$./$13/26$A0/)+%01$.-$/)5.22)+(30'.+Y$,0/.+%6Z
N)23/>
The ConsultatIon acknowledged that the level of skIll of the health care provIders wIll
play a role In the selectIon and sequence of the surgIcal InterventIons.
<6$ @3+3%)2)+0$.-$/)03'+)($4*35)+03
?6$ A1.&*($&0)/.0.+'5,$R)$.--)/)($3,$0/)302)+0$-./$/)03'+)($4*35)+03V
A&223/L$.-$)D'()+5)
Dne doubleblInd FCT was found that compared sulprostone wIth placebo In
50 women wIth retaIned placenta (187). DrIgInally desIgned to recruIt over 100
patIents, the trIal was stopped prematurely and sulprostone was gIven to all
remaInIng cases.
The authors reported a lower rIsk of manual removal of the placenta (FF 0.51, 95C
0.J4-0.86) and a sImIlar rIsk of blood transfusIon In the two groups (FF 0.81, 95C
0.JJ-2.00) (page JJ, CFA0E Table C1). There Is no empIrIcal evIdence for or agaInst
the use of other uterotonIcs for treatment of retaIned placenta.
N)5.22)+(30'.+,
f the placenta Is not expelled spontaneously, clInIcIans may offer 10 U of
oxytocIn In combInatIon wIth controlled cord tractIon. W_.$-./23*$,5')+0'U5$
)D'()+5)$.-$R)+)U0$./$13/26$A0/)+%01$.-$/)5.22)+(30'.+Y$M)3>6Z
ErgometrIne Is not recommended, as It may cause tetanIc uterIne contractIons,
whIch may delay expulsIon of the placenta. WX&3*'0L$.-$)D'()+5)Y$D)/L$*.M6$
A0/)+%01$.-$/)5.22)+(30'.+Y$M)3>6Z
The use of prostaglandIn E2 (dInoprostone or sulprostone) Is not recommended.
WX&3*'0L$.-$)D'()+5)Y$D)/L$*.M6$A0/)+%01$.-$/)5.22)+(30'.+Y$,0/.+%6Z
N)23/>,
The ConsultatIon found no empIrIcal evIdence to support recommendatIon
of uterotonIcs for the management of retaIned placenta In the absence of
haemorrhage. The above recommendatIon was reached by consensus.
The WHD guIde, Mcncyny complcctons n preyncncy cnd chldbrth (18), states
that If the placenta Is not expelled wIthIn J0 mInutes after delIvery of the baby,
the woman should be dIagnosed as havIng retaIned placenta. SInce there Is no
evIdence for or agaInst thIs denItIon, the delay used to dIagnose thIs condItIon Is
left to the judgement of the clInIcIan.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
?]
The same guIde also recommends that, In the absence of haemorrhage, the
woman should be observed for a further J0 mInutes followIng the InItIal
J0 mInutes, before manual removal of the placenta Is attempted. The
ConsultatIon noted that, In the absence of bleedIng, spontaneous expulsIon of the
placenta can stIll occur; thus, a conservatIve approach Is advIsed and the tImIng
of manual removal as the denItIve treatment Is left to the judgement of the
clInIcIan.
The recommendatIon about prostaglandIn E2 Is based on the lack of evIdence, as
well as concerns regardIng adverse events, notably cardIac events.
96$ A1.&*($'+0/3S&2R'*'53*$D)'+$'+`)50'.+$.-$.^L0.5'+$M'01$./$M'01.&0$
,3*'+)$R)$.--)/)($3,$0/)302)+0$-./$/)03'+)($4*35)+03V
A&223/L$.-$)D'()+5)
Dne systematIc revIew on umbIlIcal veIn InjectIon for the management of retaIned
placenta has been publIshed (188). FCTs comparIng the use of IntraumbIlIcal
veIn InjectIon of salIne wIth expectant management (four studIes, 41J women),
IntraumbIlIcal veIn InjectIon of salIne+oxytocIn wIth expectant management
(ve studIes, 454 women), and IntraumbIlIcal veIn InjectIon of salIne+oxytocIn wIth
salIne (ten studIes, 649 women) were IdentIed.
The results of one unpublIshed study (189) were made avaIlable to the ConsultatIon
by the InvestIgators. n thIs multIcentre trIal, 577 women In PakIstan, Uganda and the
UnIted KIngdom were randomIzed to receIve eIther IntraumbIlIcal veIn InjectIon of
50 U of oxytocIn In J0 ml of salIne (n=292) or matchIng placebo (n=285).
lntrcumblccl ven n]ecton o] sclne versus expectcnt mcncyement
There were no sIgnIcant dIfferences In rates of manual removal of the placenta
(FF 0.97, 95C 0.8J-1.19), blood loss 500 ml (FF 1.04, 95C 0.55-1.96), blood loss
1000 ml (FF 0.7J, 95C 0.17-J.11), or blood transfusIon (FF 0.76, 95C 0.41-1.J9)
(page J4, CFA0E Table C2).
lntrcumblccl ven n]ecton o] sclne+oxytocn versus expectcnt mcncyement
There was a slIghtly lower rate of manual removal of the placenta In the group gIven
salIne+oxytocIn, although the dIfference was not statIstIcally sIgnIcant (FF 0.86,
95C 0.72-1.01). Fates of blood loss 500 ml (FF 1.5J, 95C 0.78-2.67), blood loss
1000 ml (FF 1.29, 95C 0.J8-4.J4), and blood transfusIon (FF 0.89, 95C 0.5-1.58)
were sImIlar wIth wIde condence Intervals (page J5, CFA0E Table CJ).
lntrcumblccl ven n]ecton o] sclne+oxytocn versus sclne
There was a lower rIsk of manual removal of the placenta In the group gIven
salIne+oxytocIn (FF 0.79, 95C 0.69-0.91). No dIfferences were found In rates of
blood loss 500 ml (FF 1.4J, 95C 0.8J-2.45), blood loss 1000 ml (FF 1.71, 95C
0.45-6.56) or blood transfusIon (FF 1.17, 95C 0.6J-2.19) and the condence Intervals
were wIde because there were few events (page J6, CFA0E Table C4).
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
?;
The unpublIshed FELEASE trIal (189) data showed no benet of IntraumbIlIcal veIn
InjectIon of salIne wIth oxytocIn over placebo In terms of manual removal of the
placenta (FF 0.98, 95C 0.87-1.12), blood loss 500 ml (FF 0.98, 95C 0.78-1.2J),
blood loss 1000 ml (FF 1.09, 95C 0.67-1.76) and blood transfusIon (FF 0.77, 95C
0.46-1.26) (page J7, CFA0E Table C5).
N)5.22)+(30'.+,
ntraumbIlIcal veIn InjectIon of oxytocIn wIth salIne may be offered for the
management of retaIned placenta. WX&3*'0L$.-$)D'()+5)Y$2.()/30)6$A0/)+%01$.-$
/)5.22)+(30'.+Y$M)3>6Z
f, In spIte of controlled cord tractIon, admInIstratIon of uterotonIcs and
IntraumbIlIcal veIn InjectIon of oxytocIn+salIne, the placenta Is not delIvered,
manual extractIon of the placenta should be offered as the denItIve treatment.
W_.$-./23*$3,,),,2)+0$.-$T&3*'0L$.-$)D'()+5)6$A0/)+%01$.-$/)5.22)+(30'.+Y$
,0/.+%6Z
N)23/>,
0urIng the dIscussIon on thIs topIc, a new metaanalysIs of the avaIlable data
was performed, by IncludIng data from the recent large unpublIshed study wIth
the exIstIng publIshed metaanalysIs. SensItIvIty analyses by qualIty of data and a
xedversusrandomeffects analysIs were also conducted. n all these secondary
analyses, the summary estImate reected a modest effect, wIth the relatIve rIsk
of manual removal beIng 0.89 (95C 0.81-0.98) wIth a xedeffect model and 0.82
(95C 0.68-0.98) wIth a randomeffect model. The ConsultatIon was concerned
about the possIbIlIty of publIcatIon bIas In the metaanalysIs, and was splIt
between makIng a weak recommendatIon and not recommendIng IntraumbIlIcal
veIn InjectIon of oxytocIn+salIne.
The ConsultatIon recommended by a majorIty the use of umbIlIcal veIn InjectIon
of oxytocIn+salIne for retaIned placenta. n makIng the recommendatIon, the
ConsultatIon consIdered the advantages of avoIdIng an InvasIve InterventIon, such
as manual removal of the placenta, and the low cost and absence of any sIde
effects wIth umbIlIcal veIn InjectIon. t was noted that a potentIal dIsadvantage
was that thIs InterventIon may delay the admInIstratIon of other effectIve
InterventIons. These consIderatIons should be taken Into account In the local
adaptatIon of these guIdelInes.
B6$ A1.&*($3+0'R'.0'5,$R)$.--)/)($3-0)/$23+&3*$)^0/350'.+$.-$01)$
4*35)+03$3,$43/0$.-$01)$0/)302)+0$.-$/)03'+)($4*35)+03V
A&223/L$.-$)D'()+5)
A systematIc revIew of antIbIotIc prophylaxIs after manual removal of the placenta,
publIshed In 2006, found no FCTs (190).
Dne retrospectIve study (191) of 550 patIents evaluated prophylactIc antIbIotIc
therapy In IntrauterIne manIpulatIons (such as forceps delIvery, manual removal of
the placenta and exploratIon of the cavIty of the uterus) durIng vagInal delIvery.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
9:
N)5.22)+(30'.+
A sIngle dose of antIbIotIcs (ampIcIllIn or rstgeneratIon cephalosporIn) should be
offered after manual removal of the placenta.$WX&3*'0L$.-$)D'()+5)Y$D)/L$*.M6$
A0/)+%01$.-$/)5.22)+(30'.+Y$,0/.+%6Z
N)23/>,
0Irect evIdence of the value of antIbIotIc prophylaxIs after manual removal of
the placenta was not avaIlable. The ConsultatIon consIdered IndIrect evIdence of
the benet of prophylactIc antIbIotIcs from studIes of caesarean sectIon (192) and
abortIon, and observatIonal studIes of other IntrauterIne manIpulatIons.
Current practIce suggests that ampIcIllIn or rstgeneratIon cephalosporIn may be
admInIstered when manual removal of the placenta Is performed.
ThIs questIon was IdentIed as a research prIorIty for settIngs In whIch
prophylactIc antIbIotIcs are not routInely admInIstered and those wIth low
InfectIous morbIdIty.
G6$ <1.'5)$.-$K&'($-./$/)4*35)2)+0$./$/),&,5'030'.+
?6$ A1.&*($5/L,03**.'(,$R)$.--)/)($-./$K&'($/)4*35)2)+0$'+$M.2)+$
M'01$HH"V
FluId replacement Is an Important component of resuscItatIon for women wIth PPH,
but the choIce of uId Is controversIal. Although outsIde the InItIal scope of these
guIdelInes, thIs questIon was put to the ConsultatIon In vIew of Its Importance.
A&223/L$.-$)D'()+5)
There have been no FCTs comparIng the use of colloIds wIth other replacement uIds
for resuscItatIon of women wIth PPH. There Is IndIrect evIdence from a Cochrane
revIew that evaluated 6J trIals on the use of colloIds In the resuscItatIon of crItIcally
Ill patIents who requIred volume replacement secondary to trauma, burns, surgery,
sepsIs and other crItIcal condItIons (19J). A total of 55 trIals reported data on
mortalIty for the followIng comparIsons.
Collods versus crystcllods
No statIstIcal dIfference In the IncIdence of mortalIty was found when albumIn
or plasma proteIn fractIon (2J trIals, 7754 patIents, FF 1.01, 95C 0.92-1.10),
hydroxyethyl starch (16 trIals, 6J7 patIents, FF 1.05, 95C 0.6J-1.75), modIed
gelatIn (11 trIals, 506 patIents, FF 0.91, 95C 0.49-1.72), or dextran (nIne trIals, 8J4
patIents, FF 1.24, 95C 0.94-1.65) were compared wIth crystalloIds (page J8, CFA0E
Table 01).
Collod versus hypertonc crystcllod
Dne trIal, whIch compared albumIn or plasma proteIn fractIon wIth hypertonIc
crystalloId, reported one death In the colloId group (FF 7.00, 95C 0.J9-126.92).
Two trIals that compared hydroxyethyl starch and modIed gelatIn wIth crystalloIds
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
9?
observed no deaths among the 16 and 20 partIcIpants, respectIvely (page J9,
CFA0E Table 02).
Collods n hypertonc crystcllod versus sotonc crystcllod
The outcome of death was reported In eIght trIals, IncludIng 128J patIents, whIch
compared dextran In hypertonIc crystalloId wIth IsotonIc crystalloId (FF 0.88, 95C
0.74-1.05) and In one trIal wIth 14 patIents (page J9, CFA0E Table 0J).
N)5.22)+(30'.+
ntravenous uId replacement wIth IsotonIc crystalloIds should be used In preference
to colloIds for resuscItatIon of women wIth PPH. WX&3*'0L$.-$)D'()+5)Y$*.M6$A0/)+%01$
.-$/)5.22)+(30'.+Y$,0/.+%6Z
N)23/>
AvaIlable evIdence suggests that hIgh doses of colloIds, whIch are more expensIve
than IsotonIc crystalloIds, may cause adverse effects.
C6$ ")3*01$,L,0)2,$3+($./%3+'830'.+3*$'+0)/D)+0'.+,
?6$ A1.&*($1)3*01$53/)$-35'*'0'),$13D)$3$4/.0.5.*$-./$23+3%)2)+0$.-$HH"V
A&223/L$.-$)D'()+5)
The lIterature search dId not reveal any research evIdence for or agaInst the use
of PPH management protocols. Although no systematIc revIew was carrIed out, the
ConsultatIon consIdered that management protocols are generally useful and unlIkely
to be harmful.
N)5.22)+(30'.+
Health care facIlItIes should adopt a formal protocol for the management of PPH.
WX&3*'0L$.-$)D'()+5)Y$+.$-./23*$)D'()+5)$/)D')M)(a$5.+,)+,&,6$A0/)+%01Y$,0/.+%6Z
N)23/>
The ConsultatIon acknowledged that the ImplementatIon of formal protocols Is a
complex process, whIch wIll requIre local adaptatIon of general guIdelInes.
96$ A1.&*($1)3*01$53/)$-35'*'0'),$13D)$3$-./23*$4/.0.5.*$-./$/)-)//3*$.-$
M.2)+$('3%+.,)($3,$13D'+%$HH"V
A&223/L$.-$)D'()+5)
The lIterature search dId not reveal any research evIdence for or agaInst the use
of PPH referral protocols. Although no systematIc revIew was carrIed out, the
ConsultatIon consIdered that referral protocols are generally useful and unlIkely to be
harmful.
N)5.22)+(30'.+
Health care facIlItIes should adopt a formal protocol for patIent referral to a hIgher
level of care. WX&3*'0L$.-$)D'()+5)Y$+.$-./23*$)D'()+5)$/)D')M)(a$5.+,)+,&,6$
A0/)+%01$.-$/)5.22)+(30'.+Y$,0/.+%6Z
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
99
B6$ A1.&*($,'2&*30'.+$.-$HH"$0/)302)+0$R)$43/0$.-$0/3'+'+%$
4/.%/322),$-./$1)3*01$53/)$4/.D'()/,V
A&223/L$.-$)D'()+5)
The lIterature search dId not reveal any research evIdence for or agaInst the use of
PPH sImulatIon programmes. Although no systematIc revIew was carrIed out, the
ConsultatIon consIdered that PPH sImulatIon programmes are generally useful and
unlIkely to be harmful.
N)5.22)+(30'.+
SImulatIons of PPH treatment may be Included In preservIce and InservIce traInIng
programmes. WX&3*'0L$.-$)D'()+5)Y$+.$-./23*$)D'()+5)$/)D')M)(a$5.+,)+,&,6$
A0/)+%01$.-$/)5.22)+(30'.+Y$M)3>6Z
N)23/>,
ThIs recommendatIon Is extrapolated from nonobstetrIc lIterature.
The ConsultatIon placed a hIgh value on the costs of sImulatIon programmes
acknowledgIng that there are dIfferent types of sImulatIon programmes. Some
of those programmes are hItech, computerIzed and costly whIle others are less
expensIve and more lIkely to be affordable In low and mIddle Income countrIes.
The ConsultatIon IdentIed Improvement In communIcatIon between health care
provIders and patIents and theIr famIly members as an Important prIorIty In traInIng
of health care provIders In PPH management.
The ConsultatIon IdentIed thIs area as a research prIorIty.
$
HH"$53/)$4301M3L,
Postpartum haemorrhage can present In dIfferent clInIcal scenarIos. 8leedIng may
be ImmedIate and In large amounts, It may be slow and unresponsIve to treatments,
or It may be assocIated wIth systemIc problems, such as clottIng dIsorders. The
recommendatIons related to PPH preventIon, namely, actIve management of the thIrd
stage of labour, should be routInely applIed (1).
t Is crItIcal that health workers remaIn vIgIlant durIng the mInutes and hours
followIng bIrth, In order to IdentIfy problems quIckly. The care pathways presented
(see Insert) assume the presence of a skIlled caregIver and a facIlIty wIth basIc
surgIcal capacIty. A stepwIse approach Is recommended. The InItIal step Is to
assess the woman and take ImmedIate nonspecIc lIfesavIng measures, such as
resuscItatIon, callIng for help and monItorIng vItal sIgns. The second step Is to gIve
dIrectIve therapy followIng the dIagnosIs of PPH. n a gIven clInIcal sItuatIon, not
all dIagnostIc assessments can be done sImultaneously. The caregIver should assess
the sItuatIon accordIng to the cIrcumstances surroundIng the bIrth and ImmedIate
subsequent events.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
9B
The causes of PPH can be broadly classIed Into problems wIth uterIne tone (atony),
retaIned placenta, trauma (of the lower genItal tract and uterus), and coagulatIon
problems, whIch may be preexIstIng or acquIred as a result of other pathology (such
as dIssemInated Intravascular coagulatIon). f the bIrth was assIsted wIth forceps or
vacuum extractIon, the lIkelIhood of trauma wIll be hIgher. AlternatIvely, If labour
was prolonged, uterIne atony may be more lIkely. The care pathways suggest startIng
wIth the more effectIve, less InvasIve and less costly measures and, If those faIl to
stop the bleedIng, movIng towards InvasIve and more costly methods that requIre
expertIse and specIc facIlItIes.
t Is acknowledged that some facIlItIes wIll not have the expertIse and equIpment
to undertake all the steps on the care pathways. The recommendatIons represent
essentIal steps that should be undertaken at facIlIty level. n facIlItIes wIth more
lImIted capacIty, transfer of women wIth haemorrhage to a hIgher care facIlIty should
be organIzed wIthout delay.
@)01.(.*.%L
The followIng algorIthms were revIewed:
|anagIng complIcatIons In pregnancy and chIldbIrth (18).
AlgorIthm presented as an attachment to the Textbook o] postpcrtum hemorrhcye (194).
AlgorIthm of the SocIety of DbstetrIcIans and CynaecologIsts, Canada (195).
French PPH management guIdelIne (196).
ArgentInIan PPH management algorIthm (197).
CuIdelIne for the management of postpartum haemorrhage In the communIty
(versIon 2.1.1) of Cood Hope HospItal (198).
EssentIal DEC CuIdelInes for dIstrIct hospItals, South AfrIca (199).
CuIdelInes for obstetrIc care at CoronatIon, Johannesburg and NatalspruIt
HospItals, South AfrIca (200).
0raft care pathways were produced by the SecretarIat and adjusted accordIng to the
recommendatIons made by the ConsultatIon on uterotonIcs, mechanIcal measures to
compress or stretch the uterIne musculature, other pharmaceutIcal approaches, such
as tranexamIc acId, and surgery.
The ConsultatIon agreed to follow the stepwIse approach adopted In the CanadIan
guIdelInes. ThIs approach IdentIes the InItIal measures, and moves to more
InvasIve, costly and rIsky InterventIons only If the dIrected therapy for the dIagnosed
pathology faIls. The approach taken by the ConsultatIon assumes that more than one
pathology may exIst In one patIent, and that the care provIder should be vIgIlant
In lookIng for other pathologIes. The potentIal exIstence of addItIonal pathologIes
wIll be more relevant If the InItIal therapeutIc approaches faIl, as the possIbIlIty
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
9E
of both an exIstIng (undIagnosed) pathology and the development of a new one
(e.g. coagulopathy) Increase as tIme passes.
TherapeutIc approaches related to partIally retaIned placenta, traumatIc
haemorrhage and coagulopathIes are Included In the care pathways but not In the
recommendatIons. For these, there was no formal search for evIdence, appraIsal and
revIew, and the recommendatIons In the care pathways reect the consensus of the
ConsultatIon.
The ConsultatIon consIdered It Important to hIghlIght the emergency resuscItatIon
measures In the care pathways. WhIle not all PPH cases are assocIated wIth massIve
blood loss and shock, the health care worker should be aware that large blood losses
can occur wIthIn a short perIod and that vIgIlance Is needed at all tImes.
Some InterventIons are recommended as temporIzIng measures, especIally durIng
transfer of the patIent to a hIgher level of care; occasIonally, bleedIng may stop wIth
some of these measures.
t should be noted that for some categorIes, such as uterIne atony, there Is
a hIerarchy wIthIn the InterventIons lIsted In each group of dIrectIve therapy
(uterotonIcs, mechanIcals, surgery, etc.), startIng wIth the more effectIve, less
expensIve methods wIth a larger safety margIn.
$
N),)3/51$'24*'530'.+,
The ConsultatIon noted the questIons for whIch the qualIty of evIdence was low or
very low. n general, the fact that recommended practIces are based on evIdence
of low or very low qualIty would suggest that further research Is needed. However,
those areas may not be of hIgh prIorIty, for varIous reasons. The ConsultatIon agreed
that the followIng questIons should be consIdered as hIgh prIorIty for research In
the InternatIonal communIty. (The lIst below Is In order of dIscussIon, not level of
prIorIty.)
?6$ F55&/35L$.-$R*..($*.,,$3,,),,2)+0
The ConsultatIon agreed that quantIcatIon of blood loss Is Important, and that It
may be useful to study the level of blood loss that Is consIdered as requIrIng actIve
management of PPH (I.e. when should treatment be started:). The large data set
compIled by CynuIty from theIr varIous studIes could be scrutInIzed for thIs purpose
before any prImary research Is undertaken.
96$ O+0)/D)+0'.+,
!"#$ A+1'("*'-./
The dosage of mIsoprostol generated a lot of dIscussIon and dIsagreement, because
of concerns over safety. nvestIgatIon of the effects of lower doses of mIsoprostol was
suggested. However, gIven that oxytocIn Is clearly superIor, such studIes could only
be conducted In places that have no access to oxytocIn.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
9I
ClarIcatIon of the role of tranexamIc acId In PPH and obstetrIc haemorrhage was
IdentIed as a prIorIty. Some clInIcIans In the ConsultatIon mentIoned that they
already use tranexamIc acId, whIle others dId not. There seems to be uncertaInty
among clInIcIans and an absence of evIdence. The ConsultatIon was Informed that a
large multIcentre trIal Is planned.
!2#$ 6,-(+1),+/
UterIne massage Is recommended for routIne care of women In the ImmedIate
postnatal perIod up to two hours. However, It has not been evaluated as a
therapeutIc optIon In a clearly dened way. SInce thIs Is a sImple InterventIon that
can even be selfadmInIstered, the ConsultatIon consIdered that evaluatIng strategIes
to traIn health workers and mothers In the use of uterIne massage would be worth
whIle.
8alloon or condom tamponade for the treatment of PPH Is hIghly valued by some
practItIoners, but not used at all by others. The ConsultatIon consIdered that thIs
InterventIon can be hIghly effectIve, but may also have potentIal complIcatIons; It
should be rIgorously evaluated as a prIorIty.
The ConsultatIon noted the lack of evIdence regardIng the role of antIbIotIcs
followIng manual extractIon of a retaIned placenta. n settIngs where antIbIotIcs are
not currently routInely admInIstered, It may be worth whIle to evaluate the benets
and harms.
!(#$ B,"'.'.5$;,-5,"44+/
The ConsultatIon noted that there was no prImary evIdence on the effectIveness of
traInIng programmes In obstetrIc haemorrhage and agreed that evaluatIons of such
programmes should be a prIorIty, sInce they requIre nancIal and human resources.
!1#$ >4;0+4+.*"*'-.$,+/+",(&
The ConsultatIon noted that some strategIes for ImplementatIon of guIdelInes have
been shown to be effectIve. However, there may be a need for new prImary research
projects In dIfferent contexts to study the ImplementatIon of these partIcular
recommendatIons.
$
H*3+,$-./$*.53*$3(34030'.+$.-$01)$
/)5.22)+(30'.+,
The WHD 0epartment of FeproductIve Health and Fesearch works wIth InternatIonal
partners, IncludIng Its collaboratIng centres and WHD country and regIonal ofces, to
promote the dIssemInatIon and adaptatIon of Its recommendatIons. SpecIcally, the
0epartment has been collaboratIng wIth the UnIted NatIons PopulatIon Fund (UNFPA)
sInce 2004 In a StrategIc PartnershIp Programme to support countrylevel adaptatIon
and ImplementatIon of sexual and reproductIve health guIdelInes. The 0epartment
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
9P
has also publIshed a document, outlInIng the prIncIples and processes of guIdelIne
adaptatIon and ImplementatIon (201).
The text of the recommendatIons and remarks poInts out where local adaptatIon
mIght be consIdered.
$
H*3+,$-./$,&44./0'+%$'24*)2)+030'.+$.-$
01),)$/)5.22)+(30'.+,
These recommendatIons have been developed In collaboratIon wIth external partners
and the nternatIonal FederatIon of DbstetrIcIans and CynaecologIsts (FCD). The
current document wIll be dIstrIbuted to all WHD regIonal and country ofces. 0urIng
2009-2010, the recommendatIons wIll be presented In scIentIc meetIngs and a short
summary wIll be publIshed In a peerrevIewed journal. They wIll also be Included
on the 0epartment's WebsIte and In The WHD Reproductve Heclth Lbrcry, onlIne
and on C0FD|, whIch reaches around 50 000 health workers. The care pathways for
the management of PPH and retaIned placenta have been produced on a wallchart
Included In thIs publIcatIon and wIll be sent to all WHD country and regIonal ofces
and InternatIonal partners.
The WHD SecretarIat wIll collect comments on the qualIty, userfrIendlIness
and ImplementatIon of these recommendatIons by seekIng feedback from Its
collaboratIng InstItutIons and WHD country and regIonal ofces. An update of the
recommendatIons Is planned for 2010-2011.
$
QNFGC$03R*),
A. 0IagnosIs of PPH (Tables A1 and A2)
8. |anagement of atonIc PPH (Tables 81b86)
C. |anagement of retaIned placenta (Tables C1bC5)
0. ChoIce of uId for replacement or resuscItatIon (Tables 01S0J)
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
9J
F
6
$
G
'
3
%
+
.
,
'
,
$
.
-
$
H
H
"
[
3
R
*
)
$
F
?
.

7
I
s
u
a
l

v
e
r
s
u
s

q
u
a
n
t
I
t
a
t
I
v
e

m
e
t
h
o
d
s

f
o
r

e
s
t
I
m
a
t
I
n
g

b
l
o
o
d

l
o
s
s

a
f
t
e
r

v
a
g
I
n
a
l

d
e
l
I
v
e
r
y

(
J
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
d
'
,
&
3
*
$
)
,
0
'
2
3
0
'
.
+
@
)
3
,
&
/
)
(
$
)
,
0
'
2
3
0
'
.
+
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
@
)
3
+
$
R
*
.
.
(
$
*
.
,
,
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
S
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
2
S
e
r
I
o
u
s
J
F
e
p
o
r
t
I
n
g

b
I
a
s
4
6
1
6
2
-
|
e
a
n

d
I
f
f
e
r
e
n
c
e

-

9
9
.
7
1

(
-
1
5
7
.
1
9

t
o

-
4
2
.
2
J
)

7
e
r
y

l
o
w

m
p
o
r
t
a
n
t
?

|
e
t
h
o
d

o
f

a
l
l
o
c
a
t
I
o
n

c
o
n
c
e
a
l
m
e
n
t

n
o
t

d
e
s
c
r
I
b
e
d
.
9

F
e
l
a
t
e
d

t
o

s
e
t
t
I
n
g
s

w
h
e
r
e

I
t

I
s

f
e
a
s
I
b
l
e

t
o

u
s
e

t
h
e

d
r
a
p
e

m
e
t
h
o
d
.
B

W
I
d
e

r
a
n
g
e
.
E

n
t
e
r
v
e
n
t
I
o
n

n
o
t

b
l
I
n
d
e
d
.
[
3
R
*
)
$
F
9
.

T
r
a
I
n
I
n
g

c
o
u
r
s
e
s

o
n

e
s
t
I
m
a
t
I
n
g

b
l
o
o
d

l
o
s
s

a
f
t
e
r

v
a
g
I
n
a
l

d
e
l
I
v
e
r
y

(
1
J
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
,
&
R
`
)
5
0
,
$
2
3
>
'
+
%
$
3
5
5
&
/
3
0
)
$
)
,
0
'
2
3
0
'
.
+
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
F
0
0
)
+
(
'
+
%
$
0
/
3
'
+
'
+
%
$
5
.
&
/
,
)
$
.
+
$
R
*
.
.
(
$
*
.
,
,
$
)
,
0
'
2
3
0
'
.
+
<
.
+
0
/
.
*
,
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
=
*
.
.
(
$
*
.
,
,
$
)
,
0
'
2
3
0
)
(
$
3
5
5
&
/
3
0
)
*
L
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
S
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
2
S
e
r
I
o
u
s
J
N
o
n
e
J
4
/
4
5

(
7
5
.
6

)
1
1
/
4
5

(
2
4

)
F
F

J
.
0
9

(
1
.
8
0
-
5
.
J
0
)
5
2
2

m
o
r
e

p
e
r

1
0
0
0
4

7
e
r
y

l
o
w
N
o
t

I
m
p
o
r
t
a
n
t
?

|
e
t
h
o
d
s

o
f

r
a
n
d
o
m
I
z
a
t
I
o
n

a
n
d

a
l
l
o
c
a
t
I
o
n

c
o
n
c
e
a
l
m
e
n
t

n
o
t

d
e
s
c
r
I
b
e
d
.
9

L
I
m
I
t
e
d

t
o

s
e
t
t
I
n
g
;

m
a
y

b
e

d
I
f

c
u
l
t

t
o

g
e
n
e
r
a
l
I
z
e
.
B

W
I
d
e

c
o
n

d
e
n
c
e

I
n
t
e
r
v
a
l
s
.
E

5
2
2

m
o
r
e

c
a
s
e
s

p
e
r

1
0
0
0

a
c
c
u
r
a
t
e
l
y

e
s
t
I
m
a
t
e
d
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
9]
=
6
$
@
3
+
3
%
)
2
)
+
0
$
.
-
$
3
0
.
+
'
5
$
H
H
"
[
3
R
*
)
$
=
?
6
$
A
d
j
u
n
c
t

u
s
e

o
f

m
I
s
o
p
r
o
s
t
o
l

I
n

w
o
m
e
n

w
h
o

r
e
c
e
I
v
e
d

p
r
o
p
h
y
l
a
c
t
I
c

o
x
y
t
o
c
I
n

I
n

t
h
e

t
h
I
r
d

s
t
a
g
e

o
f

l
a
b
o
u
r

(
J
4
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
H
/
'
2
3
/
L
$
.
&
0
5
.
2
)
,
<
.
+
0
/
.
*
,
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
F
(
(
'
0
'
.
+
3
*
$
R
*
.
.
(
$
*
.
,
,
$
\
I
:
:
$
2
*
4
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
1
7
0
/
9
2
9

(
1
8
.
J

)
2
0
0
/
9
5
0

(
2
1
.
1

)
F
F

0
.
8
J

(
0
.
6
4
-
1
.
0
7
)
2
9

f
e
w
e
r

p
e
r

1
0
0
0

H
I
g
h
C
r
I
t
I
c
a
l
F
(
(
'
0
'
.
+
3
*
$
R
*
.
.
(
$
*
.
,
,
$
\
?
:
:
:
$
2
*
J
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
1
N
o
n
e
2
0
/
8
9
9

(
2
.
2

)
2
7
/
9
1
5

(
J
.
1

)
F
F

0
.
7
6

(
0
.
4
J
-
1
.
J
4
)
7

f
e
w
e
r

p
e
r

1
0
0
0







|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
=
*
.
.
(
$
0
/
3
+
,
-
&
,
'
.
+
4
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
1
J
8
/
9
2
7

(
1
4
.
9

)
1
4
7
/
9
4
9

(
1
4
.
5

)
F
F

0
.
9
6

(
0
.
7
7
-
1
.
1
9
)
6

f
e
w
e
r

p
e
r

1
0
0
0

H
I
g
h
C
r
I
t
I
c
a
l
"
L
,
0
)
/
)
5
0
.
2
L
J
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
7
e
r
y

s
e
r
I
o
u
s
1
N
o
n
e
5
/
9
0
0

(
0
.
6

)
5
/
9
1
9

(
0
.
4

)
F
F

0
.
9
J

(
0
.
1
6
-
5
.
4
1
)
0

f
e
w
e
r

p
e
r

1
0
0
0





L
o
w
C
r
I
t
I
c
a
l
F
(
(
'
0
'
.
+
3
*
$
&
0
)
/
.
0
.
+
'
5
,
J
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
2
5
J
/
8
9
4

(
2
8
.
J

)
2
7
1
/
9
1
0

(
2
8
.
J

)
F
F

0
.
9
6

(
0
.
8
4
-
1
.
1
)
1
1

f
e
w
e
r

p
e
r

1
0
0
0

H
I
g
h
C
r
I
t
I
c
a
l
A
1
'
D
)
/
'
+
%
4
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
1
N
o
n
e
5
5
6
/
9
2
8

(
5
9
.
9

)
2
7
0
/
9
4
8

(
1
7
.
7

)
F
F

2
.
2
4

(
1
.
7
2
-
2
.
9
1
)
2
1
9

m
o
r
e

p
e
r

1
0
0
0
!
!
!
!
!
!
!
!
!
|
o
d
e
r
a
t
e

m
p
o
r
t
a
n
t
?

W
I
d
e

c
o
n

d
e
n
c
e

I
n
t
e
r
v
a
l
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
9;
[
3
R
*
)
$
=
9
.

|
I
s
o
p
r
o
s
t
o
l

v
s

o
x
y
t
o
c
I
n

f
o
r

t
r
e
a
t
m
e
n
t

o
f

p
o
s
t
p
a
r
t
u
m

h
a
e
m
o
r
r
h
a
g
e

I
n

w
o
m
e
n

w
h
o

d
I
d

n
o
t

r
e
c
e
I
v
e

p
r
o
p
h
y
l
a
c
t
I
c

o
x
y
t
o
c
I
n

I
n

t
h
e

t
h
I
r
d

s
t
a
g
e

o
f

l
a
b
o
u
r

(
J
5
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
@
'
,
.
4
/
.
,
0
.
*
#
^
L
0
.
5
'
+
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
F
(
(
'
0
'
.
+
3
*
$
R
*
.
.
(
$
*
.
,
,
$
\
I
:
:
$
2
*
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
5
2
/
4
8
8

(
1
0
.
7

)
1
9
/
4
8
9

(
4

)
F
F

2
.
7
4

(
1
.
6
4
-
4
.
5
6
)
6
9

m
o
r
e

p
e
r

1
0
0
0

H
I
g
h
C
r
I
t
I
c
a
l
F
(
(
'
0
'
.
+
3
*
$
R
*
.
.
(
$
*
.
,
,
$
\
?
:
:
:
$
2
*
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
7
e
r
y

s
e
r
I
o
u
s
1
N
o
n
e
5
/
4
8
8

(
1

)
J
/
4
8
9

(
0
.
6

)
F
F

1
.
6
7

(
0
.
4
-
6
.
9
5
)
4

m
o
r
e

p
e
r

1
0
0
0

L
o
w
C
r
I
t
I
c
a
l
=
*
.
.
(
$
0
/
3
+
,
-
&
,
'
.
+
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
2
N
o
n
e
4
J
/
4
8
8

(
8
.
8

)
2
8
/
4
8
9

(
6

)
F
F

1
.
5
4

(
0
.
9
7
-
2
.
4
4
)
J
2

m
o
r
e

p
e
r

1
0
0
0

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
F
(
(
'
0
'
.
+
3
*
$
&
0
)
/
.
0
.
+
'
5
,
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
5
9
/
4
8
9

(
1
2
.
1

)
J
J
/
4
8
8

(
7

)
F
F

1
.
7
9

(
1
.
1
9
-
2
.
6
9
)
5
5

m
o
r
e

p
e
r

1
0
0
0

H
I
g
h
C
r
I
t
I
c
a
l
[
)
2
4
)
/
3
0
&
/
)
$
f
$
E
:
$
g
<
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
J
S
e
r
I
o
u
s
4
S
t
r
o
n
g

a
s
s
o
c
I
a

t
I
o
n
5
6
4
/
4
8
8

(
1
J
.
1

)
0
/
4
8
9

(
0

)
F
F

1
2
9
.
2
7

(
8
.
0
1
-
2
8
8
J
.
1
)
0

m
o
r
e

p
e
r

1
0
0
0

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
?

F
r
o
m

a

4
0

r
e
d
u
c
t
I
o
n

t
o

a

s
e
v
e
n
f
o
l
d

I
n
c
r
e
a
s
e
.
9

F
r
o
m

a

J

r
e
d
u
c
t
I
o
n

t
o

a

2
.
5

f
o
l
d

I
n
c
r
e
a
s
e
.
B

F
e
s
u
l
t
s

c
o
n
c
e
n
t
r
a
t
e
d

I
n

o
n
e

s
e
t
t
I
n
g
.
E

A
l
t
h
o
u
g
h

s
I
g
n
I

c
a
n
t
,

c
o
n

d
e
n
c
e

I
n
t
e
r
v
a
l
s

a
r
e

w
I
d
e
.
I

L
a
r
g
e

e
f
f
e
c
t

I
n

t
h
e

I
n
t
e
r
v
e
n
t
I
o
n

g
r
o
u
p
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
B:
[
3
R
*
)
$
=
B
6
$
F
e
c
o
m
b
I
n
a
n
t

f
a
c
t
o
r

7

a

f
o
r

t
r
e
a
t
m
e
n
t

o
f

p
o
s
t
p
a
r
t
u
m

h
a
e
m
o
r
r
h
a
g
e

(
4
2
,

4
J
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
/
h
d
O
O
3
<
.
+
0
/
.
*
,
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
_
)
)
(
$
-
.
/
$
,
&
/
%
'
5
3
*
$
0
/
)
3
0
2
)
+
0
2
D
b
s
e
r
v
a
t
I
o
n
a
l

s
t
u
d
y
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
1
,

2
S
e
r
I
o
u
s

J
N
o
n
e
8
/
J
6
4
(
2
2
.
2

)
1
J
/
J
8

(
J
4
.
2

)
D
F

0
.
5
9

(
0
.
1
9
-
1
.
7
7
)
1
2
2

f
e
w
e
r

p
e
r

1
0
0
0

(
f
r
o
m

2
6
4

f
e
w
e
r

t
o

1
8
1

m
o
r
e
)

7
e
r
y

l
o
w
C
r
I
t
I
c
a
l
"
L
,
0
)
/
)
5
0
.
2
L
2
D
b
s
e
r
v
a
t
I
o
n
a
l

s
t
u
d
y
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
1
,

2
S
e
r
I
o
u
s

J
N
o
n
e
1
J
/
J
6
5
(
J
6
.
1

)
1
J
/
J
2

(
4
0
.
6

)
D
F

0
.
9
8

(
0
.
J
4
-
2
.
5
7
)
2
2

f
e
w
e
r

p
e
r

1
0
0
0

(
f
r
o
m


2
4
4

f
e
w
e
r

t
o

J
6
6

m
o
r
e
)

7
e
r
y

l
o
w
C
r
I
t
I
c
a
l
G
)
3
0
1
1
D
b
s
e
r
v
a
t
I
o
n
a
l

s
t
u
d
y
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
1
,

2
S
e
r
I
o
u
s

J
N
o
n
e
5
/
5
0

(
1
0

)
8
/
4
4

(
1
8
.
2

)
D
F

0
.
J
8

(
0
.
0
9
-
1
.
6
)
6
1
0
7

f
e
w
e
r

p
e
r

1
0
0
0

(
f
r
o
m

1
6
J

f
e
w
e
r

t
o

8
8

m
o
r
e
)

7
e
r
y

l
o
w
C
r
I
t
I
c
a
l
H
/
.
5
)
(
&
/
)
S
/
)
*
3
0
)
(
$
5
.
2
4
*
'
5
3
0
'
.
+
,
1
D
b
s
e
r
v
a
t
I
o
n
a
l

s
t
u
d
y
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s

J
N
o
n
e
1
/
2
6
7
(
6
.
J

)
0
/
2
2

(
0

)
D
F

2
.
6
5

(
0
.
1
0
-
6
8
.
J
0
)
0

p
e
r

1
0
0
0

(
f
r
o
m

0

f
e
w
e
r

t
o

0

m
o
r
e
)

L
o
w
C
r
I
t
I
c
a
l
?

S
t
u
d
y

I
n
c
l
u
d
e
d

P
P
H

f
o
l
l
o
w
I
n
g

v
a
g
I
n
a
l

d
e
l
I
v
e
r
y

a
n
d

c
a
e
s
a
r
e
a
n

s
e
c
t
I
o
n
.
9

S
t
u
d
y

I
n
c
l
u
d
e
d

P
P
H

d
u
e

t
o

u
t
e
r
I
n
e

a
t
o
n
y
,

c
e
r
v
I
c
a
l

t
e
a
r
s
,

l
a
c
e
r
a
t
I
o
n
s
,

a
b
n
o
r
m
a
l

p
l
a
c
e
n
t
a
t
I
o
n
,

a
n
d

m
e
d
I
c
a
l

o
r

p
r
e
g
n
a
n
c
y

r
e
l
a
t
e
d

d
I
s
o
r
d
e
r
s
.
B

W
I
d
e

c
o
n

d
e
n
c
e

I
n
t
e
r
v
a
l
.
E

H
o
s
s
a
I
n

s
t
u
d
y

(
4
J
)

d
I
d

n
o
t

I
n
d
I
c
a
t
e

t
I
m
I
n
g

o
f

r
F
7

a

a
d
m
I
n
I
s
t
r
a
t
I
o
n

I
n

r
e
l
a
t
I
o
n

t
o

n
e
e
d

f
o
r

p
r
o
c
e
d
u
r
e
.
I

A
h
o
n
e
n

s
t
u
d
y

(
4
2
)

I
n
c
l
u
d
e
d

8

w
o
m
e
n

w
h
o

r
e
c
e
I
v
e
d

r
F
7

a

a
f
t
e
r

h
y
s
t
e
r
e
c
t
o
m
y
;

t
h
e
y

a
r
e

n
o
t

I
n
c
l
u
d
e
d

h
e
r
e
.

N
o

w
o
m
e
n

r
e
q
u
I
r
e
d

h
y
s
t
e
r
e
c
t
o
m
y

f
o
l
l
o
w
I
n
g

r
F
7

a

a
d
m
I
n
I
s
t
r
a
t
I
o
n
.
P

A
u
t
h
o
r
s

a
l
s
o

r
e
p
o
r
t
e
d

D
F

o
f

m
a
t
e
r
n
a
l

m
o
r
t
a
l
I
t
y

a
d
j
u
s
t
e
d

f
o
r

b
a
s
e
l
I
n
e

h
a
e
m
o
g
l
o
b
I
n

a
n
d

a
P
T
T

(
D
F
=
0
.
0
4
,

9
5

:

0
.
0
0
2
-
0
.
8
J
)
.
J

D
n
e

r
e
p
o
r
t
e
d

c
a
s
e

o
f

p
u
l
m
o
n
a
r
y

e
m
b
o
l
I
s
m

I
n

p
a
t
I
e
n
t

s
u
b
s
e
q
u
e
n
t
l
y

d
I
a
g
n
o
s
e
d

w
I
t
h

a
n
t
I
t
h
r
o
m
b
I
n

d
e

c
I
e
n
c
y
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
B?
[
3
R
*
)
$
=
E
.

U
t
e
r
I
n
e

m
a
s
s
a
g
e

f
o
r

t
r
e
a
t
m
e
n
t

o
f

p
o
s
t
p
a
r
t
u
m

h
a
e
m
o
r
r
h
a
g
e

(
4
6
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
i
0
)
/
'
+
)
$
2
3
,
,
3
%
)
<
.
+
0
/
.
*
,
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
=
*
.
.
(
$
*
.
,
,
$
\
I
:
:
$
2
*
$
W
-
.
*
*
.
M
S
&
4
$
?
$
1
.
&
/
a
$
R
*
.
.
(
$
5
.
*
*
)
5
0
)
(
$
'
+
$
4
*
3
,
0
'
5
$
(
/
3
4
)
,
Z
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
S
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
2
S
e
r
I
o
u
s
J
N
o
n
e
4
/
9
8

(
4
.
1

)
8
/
1
0
2

(
8

)
F
F

0
.
5
2

(
0
.
1
6
-
1
.
6
7
)
J
8

f
e
w
e
r

p
e
r

1
0
0
0

7
e
r
y

l
o
w
c
r
I
t
I
c
a
l
F
(
(
'
0
'
.
+
3
*
$
&
0
)
/
.
0
.
+
'
5
s
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
S
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
2
S
e
r
I
o
u
s
J
N
o
n
e
5
/
9
8

(
5
.
1

)
2
6
/
1
0
2

(
2
5

)
F
F

0
.
2
0

(
0
.
0
8
-
0
.
5
0
)
2
0
0

f
e
w
e
r

p
e
r

1
0
0
0

7
e
r
y

l
o
w
?

P
o
s
s
I
b
I
l
I
t
y

o
f

a
s
s
e
s
s
m
e
n
t

b
I
a
s
.

S
m
a
l
l

s
a
m
p
l
e

s
I
z
e
.
9

n
t
e
r
v
e
n
t
I
o
n

I
s

f
o
r

P
P
H

p
r
e
v
e
n
t
I
o
n
,

n
o
t

t
r
e
a
t
m
e
n
t
.
B

W
I
d
e

c
o
n

d
e
n
c
e

I
n
t
e
r
v
a
l
.
[
3
R
*
)
$
=
I
.

N
o
n
p
n
e
u
m
a
t
I
c

a
n
t
I
s
h
o
c
k

g
a
r
m
e
n
t

f
o
r

t
r
e
a
t
m
e
n
t

o
f

p
o
s
t
p
a
r
t
u
m

h
a
e
m
o
r
r
h
a
g
e

(
8
8
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
_
F
A
Q
<
.
+
0
/
.
*
,
$
W
R
)
-
.
/
)
Z
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
@
)
(
'
3
+
$
R
*
.
.
(
$
*
.
,
,
$
W
/
3
+
%
)
$
.
-
$
,
5
.
/
)
,
$
b
$
R
)
0
0
)
/
$
'
+
(
'
5
3
0
)
(
$
R
L
$
*
)
,
,
Z
1
8
e
f
o
r
e

a
n
d

a
f
t
e
r

s
t
u
d
y
S
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
S
e
r
I
o
u
s

N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
1
8
0
1
4
9

|
e
d
I
a
n

d
I
f
f
e
r
e
n
c
e

-
2
0
0

m
l

(
-
J
0
0

t
o

-
1
0
0

m
l
)

7
e
r
y

l
o
w

m
p
o
r
t
a
n
t
=
*
.
.
(
$
0
/
3
+
,
-
&
,
'
.
+
1
8
e
f
o
r
e

a
n
d

a
f
t
e
r

s
t
u
d
y
S
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
1
5
5
/
2
0
6

(
7
5
.
2

)
9
6
/
1
5
8

(
6
0
.
8

)
F
F

1
.
2
J

(
1
.
0
6
-
1
.
4
J
)
1
4
0

m
o
r
e

p
e
r

1
0
0
0

(
f
r
o
m

J
6

m
o
r
e

t
o

2
6
1

m
o
r
e
)

7
e
r
y

l
o
w
C
r
I
t
I
c
a
l
A
&
/
%
'
5
3
*
$
4
/
.
5
)
(
&
/
)
,
1
8
e
f
o
r
e

a
n
d

a
f
t
e
r

s
t
u
d
y
S
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
S
e
r
I
o
u
s
2
N
o
n
e
5
1
/
2
0
6

(
2
4
.
8

)
2
9
/
1
5
8

(
1
8
.
4

)
F
F

1
.
J
5

(
0
.
9
0
-
2
.
0
2
)
6
4

m
o
r
e

p
e
r

1
0
0
0

(
f
r
o
m

1
8

f
e
w
e
r

t
o

1
8
8

m
o
r
e
)

7
e
r
y

l
o
w
C
r
I
t
I
c
a
l
?

"
8
e
f
o
r
e

a
n
d

a
f
t
e
r
"

d
e
s
I
g
n
.
9

F
r
o
m

a

1
0

r
e
d
u
c
t
I
o
n

t
o

a

t
w
o
f
o
l
d

I
n
c
r
e
a
s
e
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
B9
[
3
R
*
)
$
=
P
.

U
t
e
r
I
n
e

a
r
t
e
r
y

e
m
b
o
l
I
z
a
t
I
o
n

f
o
r

t
r
e
a
t
m
e
n
t

o
f

p
o
s
t
p
a
r
t
u
m

h
a
e
m
o
r
r
h
a
g
e

(
8
9
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
i
0
)
/
'
+
)
$
3
/
0
)
/
L
$
)
2
R
.
*
'
8
3
0
'
.
+
<
.
+
0
/
.
*
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
"
L
,
0
)
/
)
5
0
.
2
L
1
D
b
s
e
r
v
a
t
I
o
n
a
l

s
t
u
d
y
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
S
e
r
I
o
u
s
1
S
e
r
I
o
u
s
2
N
o
n
e
4
/
1
5
J
(
2
6
.
7

)
2
/
9

(
2
2
.
2

)
D
F

1
.
2
7

(
0
.
1
8
-
8
.
8
9
)
4
8

m
o
r
e

p
e
r

1
0
0
0

7
e
r
y

l
o
w
C
r
I
t
I
c
a
l
H
/
.
5
)
(
&
/
)
S
/
)
*
3
0
)
(
$
5
.
2
4
*
'
5
3
0
'
.
+
1
D
b
s
e
r
v
a
t
I
o
n
a
l

s
t
u
d
y

N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
2
N
o
n
e
1
/
1
5
4

(
6
.
7

)
0
/
1
4

(
0

)
D
F

1
.
9
7

(
0
.
0
0
7
-
5
4
.
8
4
)
0

p
e
r

1
0
0
0

L
o
w
C
r
I
t
I
c
a
l
1

S
t
u
d
y

I
n
c
l
u
d
e
d

w
o
m
e
n

w
h
o

g
a
v
e

b
I
r
t
h

b
y

c
a
e
s
a
r
e
a
n

s
e
c
t
I
o
n

a
s

w
e
l
l

a
s

w
o
m
e
n

w
h
o

h
a
d

v
a
g
I
n
a
l

d
e
l
I
v
e
r
y
.
2

W
I
d
e

c
o
n

d
e
n
c
e

I
n
t
e
r
v
a
l
.
J

n
c
l
u
d
e
s

w
o
m
e
n

t
r
e
a
t
e
d

w
I
t
h

e
m
b
o
l
I
z
a
t
I
o
n

a
f
t
e
r

c
o
n
s
e
r
v
a
t
I
v
e

s
u
r
g
I
c
a
l

m
e
t
h
o
d
s
.
4

A
d
v
e
r
s
e

e
v
e
n
t

w
a
s

r
a
s
h

c
a
u
s
e
d

b
y

c
o
n
t
r
a
s
t

m
a
t
e
r
I
a
l
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
BB
<
6
$
@
3
+
3
%
)
2
)
+
0
$
.
-
$
/
)
0
3
'
+
)
(
$
4
*
3
5
)
+
0
3
[
3
R
*
)
$
<
?
.

U
t
e
r
o
t
o
n
I
c
s

f
o
r

m
a
n
a
g
e
m
e
n
t

o
f

r
e
t
a
I
n
e
d

p
l
a
c
e
n
t
a

(
1
8
7
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
i
0
)
/
.
0
.
+
'
5
,
<
.
+
0
/
.
*
,
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
@
3
+
&
3
*
$
/
)
2
.
D
3
*
$
.
-
$
0
1
)
$
4
*
3
5
)
+
0
3
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
7
e
r
y

s
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
1
J
/
2
4

(
5
4
.
2

)
4
/
2
6

(
1
5

)
F
F

0
.
5
1

(
0
.
J
4
-
0
.
8
6
)
7
J

f
e
w
e
r

p
e
r

1
0
0
0

L
o
w
C
r
I
t
I
c
a
l
=
*
.
.
(
$
0
/
3
+
,
-
&
,
'
.
+
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
7
e
r
y

s
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
6
/
2
4

(
2
5

)
8
/
2
6

(
J
0

)
F
F

0
.
8
1

(
0
.
J
J
-
2
.
0
0
)
5
7

f
e
w
e
r

p
e
r

1
0
0
0

L
o
w
C
r
I
t
I
c
a
l
?

T
h
e

s
t
u
d
y

w
a
s

s
t
o
p
p
e
d

p
r
e
m
a
t
u
r
e
l
y

a
f
t
e
r

"
t
h
e

n
u
l
l

h
y
p
o
t
h
e
s
I
s

o
f

e
q
u
a
l

e
f
f
e
c
t
I
v
e
n
e
s
s

o
f

b
o
t
h

t
r
e
a
t
m
e
n
t
s

w
a
s

r
e
j
e
c
t
e
d
"
.

n
t
e
r
I
m

a
n
a
l
y
s
e
s

w
e
r
e

m
a
d
e

a
f
t
e
r

e
a
c
h

5

c
o
n
s
e
c
u
t
I
v
e

p
a
t
I
e
n
t
s
.

S
m
a
l
l

s
a
m
p
l
e

s
I
z
e
.

1
5

o
f

w
o
m
e
n

e
x
c
l
u
d
e
d

f
r
o
m

a
n
a
l
y
s
e
s
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
BE
[
3
R
*
)
$
<
9
.

n
t
r
a
u
m
b
I
l
I
c
a
l

v
e
I
n

I
n
j
e
c
t
I
o
n

o
f

s
a
l
I
n
e

s
o
l
u
t
I
o
n

v
s

e
x
p
e
c
t
a
n
t

m
a
n
a
g
e
m
e
n
t

f
o
r

r
e
t
a
I
n
e
d

p
l
a
c
e
n
t
a

(
1
8
8
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
O
+
0
/
3
&
2
R
'
*
'
5
3
*
$
D
)
'
+
$
'
+
`
)
5
0
'
.
+
$
.
-
$
,
3
*
'
+
)
$
,
.
*
&
0
'
.
+
C
^
4
)
5
0
3
+
0
$
2
3
+
3
%
)
2
)
+
0
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
@
3
+
&
3
*
$
/
)
2
.
D
3
*
$
.
-
$
0
1
)
$
4
*
3
5
)
+
0
3
4
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
1
1
4
/
2
0
6

(
5
5
.
J

)
1
1
9
/
2
0
7

(
5
8

)
F
F

0
.
9
7

(
0
.
8
J
-
1
.
1
9
)
1
7

f
e
w
e
r

p
e
r

1
0
0
0
H
I
g
h
C
r
I
t
I
c
a
l
=
*
.
.
(
$
*
.
,
,
$
\
I
:
:
$
2
*
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
1
N
o
n
e
1
5
/
6
2

(
2
4
.
2

)
1
4
/
6
0

(
2
J
.
J

)
F
F

1
.
0
4

(
0
.
5
5
-
1
.
9
6
)
9

m
o
r
e

p
e
r

1
0
0
0

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
=
*
.
.
(
$
*
.
,
,
$
\
?
:
:
:
$
2
*
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
2
N
o
n
e
J
/
6
2

(
4
.
8

)
4
/
6
0

(
7

)
F
F

0
.
7
J

(
0
.
1
7
-
J
.
1
1
)
1
8

f
e
w
e
r

p
e
r

1
0
0
0

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
=
*
.
.
(
$
0
/
3
+
,
-
&
,
'
.
+
2
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
S
e
r
I
o
u
s
J
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
4
N
o
n
e
1
5
/
1
1
8

(
1
2
.
7

)
1
9
/
1
1
0

(
1
7

)
F
F

0
.
7
6

(
0
.
4
1
-
1
.
J
9
)
4
0

f
e
w
e
r

p
e
r

1
0
0
0

L
o
w
C
r
I
t
I
c
a
l
?

A
n
y
t
h
I
n
g

f
r
o
m

a

4
5

r
e
d
u
c
t
I
o
n

t
o

a

t
w
o
f
o
l
d

I
n
c
r
e
a
s
e
.
9

A
n
y
t
h
I
n
g

f
r
o
m

a
n

8
J

r
e
d
u
c
t
I
o
n

t
o

a

t
h
r
e
e
f
o
l
d

I
n
c
r
e
a
s
e
.
B

N
o

e
v
e
n
t
s

I
n

o
n
e

t
r
I
a
l
.
E

A
n
y
t
h
I
n
g

f
r
o
m

a

5
9

r
e
d
u
c
t
I
o
n

t
o

a

J
9

I
n
c
r
e
a
s
e
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
BI
[
3
R
*
)
$
<
B
.

n
t
r
a
u
m
b
I
l
I
c
a
l

v
e
I
n

I
n
j
e
c
t
I
o
n

o
f

s
a
l
I
n
e

+

o
x
y
t
o
c
I
n

v
s

e
x
p
e
c
t
a
n
t

m
a
n
a
g
e
m
e
n
t

f
o
r

r
e
t
a
I
n
e
d

p
l
a
c
e
n
t
a

(
1
8
8
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
O
+
0
/
3
&
2
R
'
*
'
5
3
*
$
D
)
'
+
$
'
+
`
)
5
0
'
.
+
$
M
'
0
1
$
,
3
*
'
+
)
$
j
$
.
^
L
0
.
5
'
+
C
^
4
)
5
0
3
+
0
$
2
3
+
3
%
)
2
)
+
0
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
@
3
+
&
3
*
$
/
)
2
.
D
3
*
$
.
-
$
0
1
)
$
4
*
3
5
)
+
0
3
5
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
1
1
7
/
2
J
4

(
5
0

)
1
2
9
/
2
2
0

(
5
9

)
F
F

0
.
8
6

(
0
.
7
2
-
1
.
0
1
)
8
2

f
e
w
e
r

p
e
r

1
0
0
0

H
I
g
h
C
r
I
t
I
c
a
l
=
*
.
.
(
$
*
.
,
,
$
\
I
:
:
$
2
*
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
1
N
o
n
e
2
5
/
7
0

(
J
5
.
7

)
1
4
/
6
0

(
2
J

)
F
F

1
.
5
J

(
0
.
7
8
-
2
.
6
7
)
1
2
1

m
o
r
e

p
e
r

1
0
0
0

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
8
*
.
.
(
$
*
.
,
,
$
\
?
:
:
:
$
2
*
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
2
N
o
n
e
6
/
7
0

(
8
.
6

)
4
/
6
0

(
6
.
7

)
F
F

1
.
2
9

(
0
.
J
8
-
4
.
J
4
)
1
9

m
o
r
e

p
e
r

1
0
0
0
|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
=
*
.
.
(
$
0
/
3
+
,
-
&
,
'
.
+
2
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
S
e
r
I
o
u
s
J
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
4
N
o
n
e
1
8
/
1
2
0

(
1
5

)
1
9
/
1
1
7

(
1
6

)
F
F

0
.
8
9

(
0
.
5
-
1
.
5
8
)
1
7

f
e
w
e
r

p
e
r

1
0
0
0

L
o
w
C
r
I
t
I
c
a
l
?

A
n
y
t
h
I
n
g

f
r
o
m

a

2
2

r
e
d
u
c
t
I
o
n

t
o

a

t
h
r
e
e
f
o
l
d

I
n
c
r
e
a
s
e
.
9

A
n
y
t
h
I
n
g

f
r
o
m

a

6
2

r
e
d
u
c
t
I
o
n

t
o

a

m
o
r
e

t
h
a
n

f
o
u
r
f
o
l
d

I
n
c
r
e
a
s
e
.
B

N
o

e
v
e
n
t
s

I
n

o
n
e

t
r
I
a
l
.
E

A
n
y
t
h
I
n
g

f
r
o
m

a

5
0

r
e
d
u
c
t
I
o
n

t
o

a

5
8

I
n
c
r
e
a
s
e
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
BP
[
3
R
*
)
$
<
E
.

n
t
r
a
u
m
b
I
l
I
c
a
l

v
e
I
n

I
n
j
e
c
t
I
o
n

o
f

s
a
l
I
n
e

+

o
x
y
t
o
c
I
n

v
s

s
a
l
I
n
e

f
o
r

r
e
t
a
I
n
e
d

p
l
a
c
e
n
t
a

(
1
8
8
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
O
+
0
/
3
&
2
R
'
*
'
5
3
*
$
D
)
'
+
$
'
+
`
)
5
0
'
.
+
$
.
-
$
,
3
*
'
+
)
$
j
$
.
^
L
S
0
.
5
'
+
O
+
0
/
3
&
2
R
'
*
'
5
3
*
$
D
)
'
+
$
'
+
`
)
5
0
'
.
+
$
.
-
$
,
3
*
'
+
)
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
@
3
+
&
3
*
$
/
)
2
.
D
3
*
$
.
-
$
0
1
)
$
4
*
3
5
)
+
0
3
1
0
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
S
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
1
5
8
/
J
J
5

(
4
7
.
2

)
1
8
4
/
J
1
4

(
5
9

)
F
F

0
.
7
9

(
0
.
6
9
-
0
.
9
1
)
1
2
J

f
e
w
e
r

p
e
r

1
0
0
0

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
=
*
.
.
(
$
*
.
,
,
$
\
I
:
:
$
2
*
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
2
N
o
n
e
2
5
/
7
0

(
J
5
.
7

)
1
5
/
6
0

(
2
5

)
F
F

1
.
4
J

(
0
.
8
J
-
2
.
4
5
)
1
0
7

m
o
r
e

p
e
r

1
0
0
0

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
=
*
.
.
(
$
*
.
,
,
$
\
?
:
:
:
$
2
*
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
J
N
o
n
e
6
/
7
0

(
8
.
6

)
J
/
6
0

(
5

)
F
F

1
.
7
1

(
0
.
4
5
-
6
.
5
6
)
J
5

m
o
r
e

p
e
r

1
0
0
0

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
=
*
.
.
(
$
0
/
3
+
,
-
&
,
'
.
+
2
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
S
e
r
I
o
u
s
4
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
5
N
o
n
e
1
8
/
1
2
0

(
1
5

)
1
5
/
1
1
8

(
1
J

)
F
F

1
.
1
7

(
0
.
6
J
-
2
.
1
9
)
2
2

m
o
r
e

p
e
r

1
0
0
0

L
o
w
C
r
I
t
I
c
a
l
?

H
e
t
e
r
o
g
e
n
e
I
t
y
:

2

=

4
5
.
5

.
9

A
n
y
t
h
I
n
g

f
r
o
m

a

2
7

r
e
d
u
c
t
I
o
n

t
o

a

2
.
5

f
o
l
d

I
n
c
r
e
a
s
e
.
B

A
n
y
t
h
I
n
g

f
r
o
m

a

5
5

r
e
d
u
c
t
I
o
n

t
o

a

m
o
r
e

t
h
a
n

s
I
x
f
o
l
d

I
n
c
r
e
a
s
e
.
E

N
o

e
v
e
n
t
s

I
n

o
n
e

t
r
I
a
l
.
I

A
n
y
t
h
I
n
g

f
r
o
m

a

J
7

r
e
d
u
c
t
I
o
n

t
o

a

t
w
o
f
o
l
d

I
n
c
r
e
a
s
e
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
BJ
[
3
R
*
)
$
<
I
.

n
t
r
a
u
m
b
I
l
I
c
a
l

v
e
I
n

I
n
j
e
c
t
I
o
n

o
f

5
0

U

o
x
y
t
o
c
I
n
+
J
0

m
l

s
a
l
I
n
e

v
s

p
l
a
c
e
b
o

f
o
r

r
e
t
a
I
n
e
d

p
l
a
c
e
n
t
a

(
1
8
9
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
O
+
0
/
3
&
2
R
'
*
'
5
3
*
$
D
)
'
+
$
'
+
`
)
5
0
'
.
+
$
.
-
$
I
:
$
O
i
$
.
^
L
0
.
5
'
+
$
'
+
$
,
3
*
'
+
)
H
*
3
5
)
R
.
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
@
3
+
&
3
*
$
/
)
2
.
D
3
*
$
.
-
$
0
1
)
$
4
*
3
5
)
+
0
3
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
1
7
9
/
2
9
2

(
6
1
.
J

)
1
7
7
/
2
8
5

(
6
2
.
1

)
F
F

0
.
9
8

(
0
.
8
7
-
1
.
1
2
)
1
2

f
e
w
e
r

p
e
r

1
0
0
0

(
f
r
o
m

8
1

f
e
w
e
r

t
o

7
5

m
o
r
e
)

H
I
g
h
C
r
I
t
I
c
a
l
8
l
o
o
d

l
o
s
s

\
5
0
0

m
l
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
1
N
o
n
e
9
9
/
2
9
2

(
J
J
.
9

)
9
9
/
2
8
5

(
J
4
.
7

)
F
F

0
.
9
8

(
0
.
7
8
-
1
.
2
J
)
7

f
e
w
e
r

p
e
r

1
0
0
0

(
f
r
o
m

7
6

f
e
w
e
r

t
o

8
0

m
o
r
e
)

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
8
l
o
o
d

l
o
s
s

\
1
0
0
0

m
l
1
r
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
2
N
o
n
e
J
1
/
2
9
2

(
1
0
.
6

)
2
8
/
2
8
5

(
9
.
8

)
F
F

1
.
0
9

(
0
.
6
7
-
1
.
7
6
)
9

m
o
r
e

p
e
r

1
0
0
0

(
f
r
o
m

J
2

f
e
w
e
r

t
o

7
4

m
o
r
e
)

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
8
l
o
o
d

t
r
a
n
s
f
u
s
I
o
n
1
r
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
J
N
o
n
e
4
J
/
2
9
2

(
1
4
.
7

)
J
6
/
2
8
5

(
1
2
.
6

)
F
F

0
.
7
7

(
0
.
4
6
-
1
.
2
6
)
2
9

f
e
w
e
r

p
e
r

1
0
0
0

(
f
r
o
m

6
8

f
e
w
e
r

t
o

J
J

m
o
r
e
)

|
o
d
e
r
a
t
e
C
r
I
t
I
c
a
l
?

A
n
y
t
h
I
n
g

f
r
o
m

a

2
2

r
e
d
u
c
t
I
o
n

t
o

a

2
J

I
n
c
r
e
a
s
e
.
9

A
n
y
t
h
I
n
g

f
r
o
m

a

J
J

r
e
d
u
c
t
I
o
n

t
o

a

7
6

I
n
c
r
e
a
s
e
.
B

A
n
y
t
h
I
n
g

f
r
o
m

a

5
4

r
e
d
u
c
t
I
o
n

t
o

a

2
6

I
n
c
r
e
a
s
e
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
B]
G
6
$
<
1
.
'
5
)
$
.
-
$
K
&
'
(
$
-
.
/
$
/
)
4
*
3
5
)
2
)
+
0
$
.
/
$
/
)
,
&
,
5
'
0
3
0
'
.
+
[
3
R
*
)
$
G
?
.

C
o
l
l
o
I
d
s

v
s

c
r
y
s
t
a
l
l
o
I
d
s

f
o
r

u
I
d

r
e
p
l
a
c
e
m
e
n
t

I
n

c
r
I
t
I
c
a
l
l
y

I
l
l

p
a
t
I
e
n
t
s

(
1
9
J
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
<
.
*
*
.
'
(
,
<
/
L
,
0
3
*
*
.
'
(
,
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
G
)
3
0
1
$
W
3
*
R
&
2
'
+
$
.
/
$
4
*
3
,
2
3
$
4
/
.
0
)
'
+
$
-
/
3
5
0
'
.
+
$
D
,
$
5
/
L
,
0
3
*
*
.
'
(
,
Z
2
J
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
7
8
2
/
J
8
7
0

(
2
0
.
2

)
7
7
8
/
J
8
8
4

(
2
0

)
F
F

1
.
0
1

(
0
.
9
2
-
1
.
1
)
2

m
o
r
e

p
e
r

1
0
0
0

(
f
r
o
m

1
6

f
e
w
e
r

t
o

2
0

m
o
r
e
)

H
I
g
h
C
r
I
t
I
c
a
l
G
)
3
0
1
$
W
1
L
(
/
.
^
L
)
0
1
L
*
$
,
0
3
/
5
1
$
D
,
$
5
/
L
,
0
3
*
*
.
'
(
,
Z
1
6
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
2
4
/
J
7
5

(
6
.
4

)
1
8
/
2
6
2

(
6
.
9

)
F
F

1
.
0
5

(
0
.
6
J
-
1
.
7
5
)
J

m
o
r
e

p
e
r

1
0
0
0

H
I
g
h
C
r
I
t
I
c
a
l
G
)
3
0
1
$
W
2
.
(
'
U
)
(
$
%
)
*
3
0
'
+
$
D
,
$
5
/
L
,
0
3
*
*
.
'
(
,
Z
1
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
1
J
/
2
2
4

(
5
.
8

)
1
5
/
2
8
2

(
5
.
J

)
F
F

0
.
9
1

(
0
.
4
9
-
1
.
7
2
)
4

f
e
w
e
r

p
e
r

1
0
0
0

H
I
g
h
C
r
I
t
I
c
a
l
G
)
3
0
1
$
W
(
)
^
0
/
3
+
$
D
,
$
5
/
L
,
0
3
*
*
.
'
(
,
Z
9
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
N
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
N
o

s
e
r
I
o
u
s

I
n
c
o
n
s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
N
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
N
o
n
e
9
6
/
4
1
2

(
2
J
.
J

)
5
7
/
4
2
2

(
1
J
.
5

)
F
F

1
.
2
4

(
0
.
9
4
-
1
.
6
5
)
J
2

m
o
r
e

p
e
r

1
0
0
0

H
I
g
h
C
r
I
t
I
c
a
l
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
B;
[
3
R
*
)
$
G
9
.

C
o
l
l
o
I
d
s

v
s

h
y
p
e
r
t
o
n
I
c

c
r
y
s
t
a
l
l
o
I
d
s

f
o
r

u
I
d

r
e
p
l
a
c
e
m
e
n
t

I
n

c
r
I
t
I
c
a
l
l
y

I
l
l

p
a
t
I
e
n
t
s

(
1
9
J
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
<
.
*
*
.
'
(
"
L
4
)
/
0
.
+
'
5
$
5
/
L
,
0
3
*
*
.
'
(
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
G
)
3
0
1
,
$
W
3
*
R
&
2
'
+
$
.
/
$
4
*
3
,
2
3
$
4
/
.
0
)
'
+
$
-
/
3
5
0
'
.
+
$
D
,
$
1
L
4
)
/
0
.
+
'
5
$
5
/
L
,
0
3
*
*
.
'
(
,
Z
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
7
e
r
y

s
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
7
e
r
y

s
e
r
I
o
u
s
N
o
n
e
J
/
1
9

(
1
5
.
8

)
0
/
1
9

(
0

)
F
F

7
.
0
0

(
0
.
J
9
-
1
2
6
.
9
2
)
0

p
e
r

1
0
0
0

7
e
r
y

l
o
w
C
r
I
t
I
c
a
l
G
)
3
0
1
,
$
W
1
L
(
/
.
^
L
)
0
1
L
*
$
,
0
3
/
5
1
$
D
,
$
5
/
L
,
0
3
*
*
.
'
(
,
Z
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
7
e
r
y

s
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
7
e
r
y

s
e
r
I
o
u
s
1
N
o
n
e
0
/
8

(
0

)
0
/
8

(
0

)
F
F

0

(
0
-
0
)
0

p
e
r

1
0
0
0

7
e
r
y

l
o
w
C
r
I
t
I
c
a
l
G
)
3
0
1
,
$
W
2
.
(
'
U
)
(
$
%
)
*
3
0
'
+
$
D
,
$
1
L
4
)
/
0
.
+
'
5
$
5
/
L
,
0
3
*
*
.
'
(
,
Z
1
F
a
n
d
o
m
I
z
e
d

t
r
I
a
l
7
e
r
y

s
e
r
I
o
u
s
1
N
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
N
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
S
e
r
I
o
u
s
1
N
o
n
e
0
/
1
0

(
0

)
0
/
1
0

(
0

)
F
F

0

(
0
-
0
)
0

p
e
r

1
0
0
0

7
e
r
y

l
o
w
C
r
I
t
I
c
a
l
?

U
n
d
e
r
p
o
w
e
r
e
d

s
t
u
d
y
.
[
3
R
*
)
$
G
B
.

C
o
l
l
o
I
d

I
n

h
y
p
e
r
t
o
n
I
c

c
r
y
s
t
a
l
l
o
I
d

v
s

I
s
o
t
o
n
I
c

c
r
y
s
t
a
l
l
o
I
d

f
o
r

u
I
d

r
e
p
l
a
c
e
m
e
n
t

I
n

c
r
I
t
I
c
a
l
l
y

I
l
l

p
a
t
I
e
n
t
s

(
1
9
J
)
X
&
3
*
'
0
L
$
3
,
,
)
,
,
2
)
+
0
A
&
2
2
3
/
L
$
.
-
$
U
+
(
'
+
%
,
O
2
4
.
/
0
3
+
5
)
_
.
6
$
.
-
$
4
3
0
'
)
+
0
,
C
-
-
)
5
0
X
&
3
*
'
0
L
_
.
6
$
.
-
$
,
0
&
(
'
)
,
G
)
,
'
%
+
c
'
2
'
0
3
0
'
.
+
,
O
+
5
.
+
,
'
,
0
)
+
5
L
O
+
(
'
/
)
5
0
+
)
,
,
O
2
4
/
)
5
'
,
'
.
+
#
0
1
)
/
$
5
.
+
,
'
(
)
/
3
0
'
.
+
,
<
.
*
*
.
'
(
$
'
+
$
1
L
4
)
/
0
.
+
'
5
$
5
/
L
,
0
3
*
*
.
'
(
O
,
.
0
.
+
'
5
$
5
/
L
,
0
3
*
*
.
'
(
N
)
*
3
0
'
D
)
$
W
;
I
e
$
<
O
Z
F
R
,
.
*
&
0
)
G
)
3
0
1
,
$
W
3
*
R
&
2
'
+
$
.
/
$
4
*
3
,
2
3
$
4
/
.
0
)
'
+
$
-
/
3
5
0
'
.
+
$
D
,
$
5
/
L
,
0
3
*
*
.
'
(
,
Z
1
r
a
n
d
o
m
I
z
e
d

t
r
I
a
l
v
e
r
y

s
e
r
I
o
u
s
1
n
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
n
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
s
e
r
I
o
u
s
n
o
n
e
1
/
7

(
1
4
.
J

)
2
/
7

(
2
8
.
6

)
F
F

0
.
5
0

(
0
.
0
6
-
4
.
J
J
)
1
4
J

f
e
w
e
r

p
e
r

1
0
0
0

7
e
r
y

l
o
w
c
r
I
t
I
c
a
l
G
)
3
0
1
,
$
W
(
)
^
0
/
3
+
$
D
,
$
'
,
.
0
.
+
'
5
$
5
/
L
,
0
3
*
*
.
'
(
,
Z
8
r
a
n
d
o
m
I
z
e
d

t
r
I
a
l
n
o

s
e
r
I
o
u
s

l
I
m
I
t
a
t
I
o
n
s
2
n
o

s
e
r
I
o
u
s

I
n
c
o
n

s
I
s
t
e
n
c
y
n
o

s
e
r
I
o
u
s

I
n
d
I
r
e
c
t
n
e
s
s
n
o

s
e
r
I
o
u
s

I
m
p
r
e
c
I
s
I
o
n
n
o
n
e
1
8
2
/
6
6
7

(
2
7
.
J

)
1
7
9
/
6
1
6

(
2
9
.
1

)
F
F

0
.
8
8

(
0
.
7
4
-
1
.
0
5
)
J
4

f
e
w
e
r

p
e
r

1
0
0
0

H
I
g
h
c
r
I
t
I
c
a
l
?

U
n
d
e
r
p
o
w
e
r
e
d

t
r
I
a
l
.
9

A
s

e
v
a
l
u
a
t
e
d

b
y

t
h
e

C
o
c
h
r
a
n
e

r
e
v
I
e
w
e
r
.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
E:
$
N)-)/)+5),
1. WHD recommendctons ]or the preventon o] postpcrtum hcemorrhcye. Ceneva, World Health DrganIzatIon, 2007 (http://
whqlIbdoc.who.Int/hq/2007/WHD_|PS_07.06_eng.pdf, accessed 4 |ay 2009).
2. AtkIns 0 et al. CradIng qualIty of evIdence and strength of recommendatIons. 8rtsh Medccl 1ourncl, 2004, J28:1490-1494.
C,0'230'.+$.-$R*..($*.,,
J. Patel A et al. 0rape estImatIon vs. vIsual assessment for estImatIng postpartum hemorrhage. lnternctoncl 1ourncl o] 6ynecoloyy
cnd Dbstetrcs, 2006, 9J:220-224.
4. Toledo P et al. The accuracy of blood loss estImatIon after sImulated vagInal delIvery. Anesthesc cnd Anclyesc, 2007, 105:17J6
-1740.
5. 8uckland SS, Homer CS. EstImatIng blood loss after bIrth: usIng sImulated clInIcal examples. Women 8rth, 2007, 20(2):85-88.
6. Larsson C et al. EstImatIon of blood loss after caesarean sectIon and vagInal delIvery has low valIdIty wIth a tendency to
exaggeratIon. Actc Dbstetrcc et 6ynecoloycc Sccndncvcc, 2006, 85(12):1448-1452.
7. 8ose P, Fegan F, Paterson8rown S. mprovIng the accuracy of estImated blood loss at obstetrIc haemorrhage usIng clInIcal
reconstructIons. 81D6: An lnternctoncl 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 2006, 11J(8):919-924.
8. Prasertcharoensuk W, SwadpanIch U, LumbIganon P. Accuracy of the blood loss estImatIon In the thIrd stage of labour.
lnternctoncl 1ourncl o] 6ynecoloyy cnd Dbstetrcs, 2000, 71(1):69-70.
9. HIggIns PC. |easurIng nurses' accuracy of estImatIng blood loss. 1ourncl o] Advcnced Nursny, 1982, 7(2):157-162.
10. Tourn C et al. ntrt de l'utIlIsatIon d'un sac de recueIl dans le dIagnostIc des hmorragIes de la dlIvrance. Usefulness of a
collectIng bag for the dIagnosIs of postpartum hemorrhage. 1ourncl de 6yncoloye, Dbsttrque et 8oloye de lc Reproducton,
2004, JJ:229-2J4.
11. Chua S et al. 7alIdatIon of a labouratory method of measurIng postpartum blood loss. 6ynecoloyc cnd Dbstetrc lnvestycton,
1998, 46:J1-JJ.
12. 0uthIe SJ et al. 0Iscrepancy between labouratory determInatIon and vIsual estImatIon of blood loss durIng normal delIvery.
Europecn 1ourncl o] Dbstetrcs cnd 6ynecoloyy cnd Reproductve 8oloyy, J8(2):119-124.
1J. Sukprasert | et al. ncrease accuracy of vIsual estImatIon of blood loss from educatIon programme. 1ourncl o] the Medccl
Assoccton o] Thclcnd, 2006, 89(Suppl. 4): S54S59.
14. 0Ildy CA Jrd et al. EstImatIng blood loss: can teachIng sIgnIcantly Improve vIsual estImatIon: Dbstetrcs cnd 6ynecoloyy, 2004,
4(J):601-606.
15. LuegenbIehl 0L. mprovIng vIsual estImatIon of blood volume on perIpads. MCN. The Amerccn 1ourncl o] Mcterncl Chld Nursny,
1997, 22(6):294-298.
16. LuegenbIehl 0L et al. StandardIzed assessment of blood loss. MCN. The Amerccn 1ourncl o] Mcterncl Chld Nursny, 1990,
15(4):241-244.
@3+3%)2)+0$.-$30.+'5$HH"
17. PrendIvIlle WJ, Elbourne 0, |c0onald S. ActIve versus expectant management In the thIrd stage of labour. Cochrcne 0ctcbcse o]
Systemctc Revews, 2000; ssue 2. Art. No.: C0000007.
@)('53*$'+0)/D)+0'.+,$-./$HH"
18. Mcncyny complcctons n preyncncy cnd chldbrth: c yude ]or mdwves cnd doctors. Ceneva, World Health DrganIzatIon, 2007.
19. Cotter A, Ness A, Tolosa J. ProphylactIc oxytocIn In the thIrd stage of labour. Cochrcne 0ctcbcse o] Systemctc Revews, 2001;
ssue 4. Art. No.: C0001808.
20. |c0onald S, Abbott J|, HIggIns SP. ProphylactIc ergometrIneoxytocIn versus oxytocIn for the thIrd stage of labour. Cochrcne
0ctcbcse o] Systemctc Revews, 2004; ssue 1. Art. No.:C0000201.
21. Su LL, Chong S, Samuel |. DxytocIn agonIsts for preventIng postpartum haemorrhage. Cochrcne 0ctcbcse o] Systemctc Revews,
2007; ssue J. Art. No.:C0005457.
22. Culmezoglu A| et al. ProstaglandIns for preventIng postpartum haemorrhage. Cochrcne 0ctcbcse o] Systemctc Revews, 2007;
ssue J. Art. No.:C0000494.
2J. DrjI E et al. A randomIzed comparatIve study of prophylactIc oxytocIn versus ergometrIne In the thIrd stage of labour.
lnternctoncl 1ourncl o] 6ynecoloyy cnd Dbstetrcs, 2008, 101(2):129-1J2.
24. de Croot AN et al. A placebocontrolled trIal of oral ergometrIne to reduce postpartum hemorrhage. Actc Dbstetrcc et
6ynecoloycc Sccndncvcc, 1996, 75(5):464-468.
25. Howard WF, |cFadden PF, Keettel WC. DxytocIc drugs In the fourth stage of labor. 1AMA: The 1ourncl o] the Amerccn Medccl
Assoccton, 1964, 189: 411-41J.
26. Leung SW et al. A randomIzed trIal of carbetocIn versus syntometrIne In the management of the thIrd stage of labour. 8rtsh
1ourncl o] Dbstetrcs cnd 6yncecoloyy, 2006, 11J(12):1459-1464.
27. Ngan L, Keong W, |artIns F. CarbetocIn versus a combInatIon of oxytocIn and ergometrIne In control of postpartum blood loss.
lnternctoncl 1ourncl o] 6yncecoloyy cnd Dbstetrcs, 2007, 97(2): 152-15J.
28. Poeschmann FP, 0oesburg WH, Eskes TK. A randomIzed comparIson of oxytocIn, sulprostone and placebo In the management of
the thIrd stage of labour. 8rtsh 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 1991, 98(6):528-5J0.
29. 7an Selm |, KanhaI HH, KeIrse |J. PreventIng the recurrence of atonIc postpartum hemorrhage: a doubleblInd trIal. Actc
Dbstetrcc et 6ynecoloycc Sccndncvcc, 1995, 74(4):270-274.
J0. Nellore 7, |Ittal S, 0adhwal 7. Fectal mIsoprostol vs. 15methyl prostaglandIn F2 alpha for the preventIon of postpartum
hemorrhage. lnternctoncl 1ourncl o] 6ynecoloyy cnd Dbstetrcs, 2006, 94(1):45-46.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
E?
J1. Walraven C et al. |Isoprostol In the treatment of postpartum haemorrhage In addItIon to routIne management: a placebo
randomIzed controlled trIal. 8rtsh 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 2004, 111(9):1014-1017.
J2. Hofmeyr CJ et al. |Isoprostol for treatIng postpartum haemorrhage: a randomIzed controlled trIal SFCTN7226JJ57. 8MC
Preyncncy Chldbrth, 2004, 4(1):16.
JJ. ZuberI NF et al. |Isoprostol In addItIon to routIne treatment of postpartum hemorrhage: a hospItalbased randomIzed
controlled trIal In KarachI, PakIstan. 8MC Preyncncy Chldbrth, 2008 8:40.
J4. |Isoprostol to treat Postpartum Haemorrhage (PPH): a randomIsed controlled trIal. SFCTNJ4455240 (http://apps.who.Int/
trIalsearch/TrIal.aspx:TrIal0=SFCTNJ4455240).
J5. |Isoprostol for the Treatment of PrImary Postpartum Hemorrhage CynuIty Health Projects. http://clInIcaltrIals.gov/show/
NCT00116J50.
[/3+)^32'5$35'(
J6. Henry 0A et al. AntIbrInolytIc use for mInImIsIng perIoperatIve allogeneIc blood transfusIon. Cochrcne 0ctcbcse o] Systemctc
Revews, 2007; ssue 4. Art. No.: C0001886.
J7. Lethaby A, Farquhar C, Cooke. AntIbrInolytIcs for heavy menstrual bleedIng. Cochrcne 0ctcbcse o] Systemctc Revews, 2000;
ssue 4. Art. No.: C0000249.
J8. CaI | et al. ClInIcal observatIon of blood loss reduced by tranexamIc acId durIng and after caesarIan sectIon: a multIcenter,
randomIzed trIal. Europecn 1ourncl o] Dbstetrcs, 6ynecoloyy, cnd Reproductve 8oloyy, 2004, 112(2):154-157.
J9. As AK, Hagen P, Webb J8. TranexamIc acId In the management of postpartum haemorrhage. 8rtsh 1ourncl o] Dbstetrcs cnd
6yncecoloyy, 1996, 10J(12):1250-1251.
N)5.2R'+3+0$-350./$dOO3
40. FranchInI |, LIppI C, FranchI |. The use of recombInant actIvated factor 7 In obstetrIc and gynaecologIcal haemorrhage.
8rtsh 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 2007, 114(1): 8-15.
41. FranchInI | et al. A crItIcal revIew on the use of recombInant factor 7a In lIfethreatenIng obstetrIc postpartum hemorrhage.
Semncrs n Thromboss cnd Hemostcss, 2008, J4(1):104-112.
42. Ahonen J, Jokela F, KortIla K. An open nonrandomIzed study of recombInant actIvated factor 7 In major postpartum
haemorrhage. Actc Dbstetrcc et 6ynecoloycc Sccndncvcc, 2007, 51(7):929-9J6.
4J. HossaIn N et al. Use of recombInant actIvated factor 7 for massIve postpartum haemorrhage. Actc Dbstetrcc et 6ynecoloycc
Sccndncvcc, 2007, 86(10): 1200-1206.
44. D'Connell KA et al. ThromboembolIc adverse events after use of recombInant human coagulatIon factor 7a. 1AMA: The
1ourncl o] the Amerccn Medccl Assoccton, 2006, 295(J):29J-298.
_.+S2)('53*$'+0)/D)+0'.+,$-./$HH"
i0)/'+)$23,,3%)
45. AbdelAleem H et al. UterIne massage and postpartum blood loss. lnternctoncl 1ourncl o] 6ynecoloyy cnd Dbstetrcs, 2006,
9J(J):2J8-2J9.
46. Hofmeyr CJ, AbdelAleem H, AbdelAleem |A. UterIne massage for preventIng postpartum haemorrhage. Cochrcne 0ctcbcse o]
Systemctc Revews, 2008; ssue J. Art. No.: C00064J1.
='23+&3*$&0)/'+)$5.24/),,'.+
47. KovavIsarch E, KosolkIttIwong S. 8Imanual uterIne compressIon as a major technIque In controllIng severe postpartum
hemorrhage from uterIne atony. 1ourncl o] the Medccl Assoccton o] Thclcnd, 1997, 80(4):266-269.
i0)/'+)$435>'+%
48. 8agga FJ et al. UterovagInal packIng wIth rolled gauze In postpartum hemorrhage. Medsccpe 6enercl Medcne, 2004, 6(1):50.
49. Haq C, Tayyab S. Control of postpartum and post abortal haemorrhage wIth uterIne packIng. The 1ourncl o] the Pckstcn
Medccl Assoccton, 2005, 55(9):J69-J71.
50. Hester J0. Postpartum hemorrhage and reevaluatIon of uterIne packIng. Dbstetrcs cnd 6ynecoloyy, 1975, 45(5):501-504.
51. Hsu SF et al. Use of packIng In obstetrIc hemorrhage of uterIne orIgIn. The 1ourncl o] Reproductve Medcne, 200J, 48(2):69-
71.
52. NaqvI S, |akhdoom T. ConservatIve management of prImary postpartum haemorrhage. 1ourncl o] the Colleye o] Physccns cnd
SuryeonsPckstcn, 2004, 14(5):296-297.
5J. Nwagha U, Dkaro J|, Nwagha TU. ntraoperatIve uterIne packIng wIth mops: an effectIve, but under utIlIzed method of
controllIng post partum haemorrhage - experIence from South Eastern NIgerIa. Nyercn 1ourncl o] Medcne, 2005, 14(J):279-
282.
54. Wax JF, Channell JC, 7andersloot JA. PackIng of the lower uterIne segment - new approach to an old technIque. lnternctoncl
1ourncl o] 6yncecoloyy cnd Dbstetrcs, 199J, 4J(2):197-198.
55. WIttIch AC et al. UterIne packIng In the combIned management of obstetrIcal hemorrhage. Mltcry Medcne, 1996,
161(J):180-182.
=3**..+$0324.+3()
56. Akhter S, 8egum |F, KabIr J. Condom hydrostatIc tamponade for massIve postpartum hemorrhage. lnternctoncl 1ourncl o]
6yncecoloyy cnd Dbstetrcs, 2005, 90(2):1J4-1J5.
57. Akhter S et al. Use of a condom to control massIve postpartum hemorrhage. Medsccpe 6enercl Medcne, 200J, 5(J):J8.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
E9
58. 8agga F et al. Postpartum hemorrhage In two women wIth ImpaIred coagulatIon successfully managed wIth condom catheter
tamponade. lndcn 1ourncl o] Medccl Scences, 2007, 61(J):157-160.
59. Chan C et al. The use of a Sengstaken8lakemore tube to control postpartum hemorrhage. lnternctoncl 1ourncl o] 6ynecoloyy
cnd Dbstetrcs,1997, 58(2):251-252.
60. CondIe FC, 8uxton EJ, Payne ES. Successful use of Sengstaken8lakemore tube to control massIve postpartum haemorrhage.
8rtsh 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 1994, 101(11):102J-1024.
61. Condous CS et al. The "tamponade test" In the management of massIve postpartum hemorrhage. Dbstetrcs cnd 6ynecoloyy,
200J, 101(4):767-772.
62. 0abelea 7, Schultze P|, |c0ufe FS Jr. ntrauterIne balloon tamponade In the management of postpartum hemorrhage.
Amerccn 1ourncl o] Pernctoloyy, 2007, 24(6):J59-J64.
6J. 0anso 0, FegInald P. CombIned 8lynch suture wIth IntrauterIne balloon catheter trIumphs over massIve postpartum
haemorrhage. 8rtsh 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 2002, 109(8):96J.
64. 0e Loor JA, van 0am PA. Foley catheters for uncontrollable obstetrIc or gynecologIc hemorrhage. Dbstetrcs cnd 6ynecoloyy,
1996, 88(4 Pt 2):7J7.
65. Coldrath |H. UterIne tamponade for the control of acute uterIne bleedIng. Amerccn 1ourncl o] Dbstetrcs cnd 6ynecoloyy,
198J, 147(8):869-872.
66. kechebelu J, DbI FA, Joekechebelu NN. The control of postpartum haemorrhage wIth IntrauterIne Foley catheter. 1ourncl o]
Dbstetrcs cnd 6yncecoloyy, 2005, 25(1):70-72.
67. Japaraj FP, Faman S. Sengstaken8lakemore tube to control massIve postpartum haemorrhage. The Medccl 1ourncl o]
Mclcysc, 200J, 58(4):604-607.
68. Johanson F et al. |anagement of massIve postpartum haemorrhage: use of a hydrostatIc balloon catheter to avoId laparotomy.
8rtsh 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 2001, 108(4):420-422.
69. Katesmark |, 8rown F, Faju KS. Successful use of a Sengstaken8lakemore tube to control massIve postpartum haemorrhage.
8rtsh 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 1994, 101(J):259-260.
70. KerIakos F, |ukhopadhyay A. The use of the Fusch balloon for management of severe postpartum haemorrhage. 1ourncl o]
Dbstetrcs cnd 6yncecoloyy, 2006, 26(4):JJ5-JJ8.
71. |arcovIcI , ScoccIa 8. Postpartum hemorrhage and IntrauterIne balloon tamponade. A report of three cases. 1ourncl o]
Reproductve Medcne, 1999, 44(2):122-126.
72. Nelson WL, D'8rIen J|. The uterIne sandwIch for persIstent uterIne atony: combInIng the 8Lynch compressIon suture and an
IntrauterIne 8akrI balloon. Amerccn 1ourncl o] Dbstetrcs cnd 6ynecoloyy, 2007, 196(5):e9-10.
7J. Seror J, Allouche C, ElhaIk S. Use of Sengstaken8lakemore tube In massIve postpartum hemorrhage: a serIes of 17 cases. Actc
Dbstetrcc et 6ynecoloycc Sccndncvcc, 2005, 84(7):660-664.
74. SvIgos J. A sImple alternatIve measure to control severe post partum haemorrhage. The Austrclcn cnd New Zeclcnd 1ourncl o]
Dbstetrcs cnd 6yncecoloyy, 2004, 44(6):588
75. Turner C0. UterIne haemorrhage controlled by an IntrauterIne balloon Insufated wIth hot water. Hosptcl Medcne, 2002,
6J(7):4J8.
76. 7erkuyl 0A. Fast and easy provIsIonal treatment of severe postpartum haemorrhage. 8rtsh 1ourncl o] Dbstetrcs cnd
6yncecoloyy, 2007, 114(7):908-909.
77. Condous CS, Arulkumaran S. |edIcal and conservatIve surgIcal management of postpartum hemorrhage. 1ourncl o] Dbstetrcs
cnd 6yncecoloyy Ccncdc, 200J, 25(11): 9J1-9J6.
78. 0oumouchtsIs SK et al. SystematIc revIew of conservatIve management of postpartum hemorrhage: what to do when medIcal
treatment faIls. Dbstetrccl cnd 6ynecoloyccl Survey, 2007, 62(8): 540-547.
C^0)/+3*$3./0'5$5.24/),,'.+
79. FIley 0P, 8urgess FW. External abdomInal aortIc compressIon: a study of a resuscItatIon manoeuvre for postpartum
haemorrhage. Ancesthesc cnd lntensve Ccre, 1994, 22(5): 571-575.
80. Keogh J, Tsokos N. AortIc compressIon In massIve postpartum haemorrhage - an old but lIfesavIng technIque. The Austrclcn
cnd New Zeclcnd 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 1997, J7(2): 2J7-2J8.
_.+4+)&230'5$3+0'S,1.5>$%3/2)+0,
81. 8rees C et al. NonInatable antIshock garment for obstetrIc hemorrhage. lnternctoncl 1ourncl o] 6ynecoloyy cnd Dbstetrcs,
2004, 87(2):119-124.
82. Celler SE, Adams |C, |Iller S. A ContInuum of care model for postpartum hemorrhage. lnternctoncl 1ourncl o] Fertlty cnd
Women's Medcne, 2007, 52(2-J):97-105.
8J. HensleIgh PA. AntIshock garment provIdes resuscItatIon and haemostasIs for obstetrIc haemorrhage. 8rtsh 1ourncl o]
Dbstetrcs cnd 6yncecoloyy, 2002, 109(12):1J77-1J84.
84. |Iller S, Lester F, HensleIgh P. PreventIon and treatment of postpartum hemorrhage: new advances for lowresource settIngs.
1ourncl o] Mdw]ery cnd Women's Heclth, 2004, 49(4):28J-92.
85. |Iller S, |artIn H8, |orrIs JL. AntIshock garment In postpartum haemorrhage. 8est Prcctce cnd Resecrch. Clnccl Dbstetrcs
cnd 6yncecoloyy, 2008, 22(6):1057-1074.
86. Tsu 70, Langer A, AldrIch T. Postpartum hemorrhage In developIng countrIes: Is the publIc health communIty usIng the rIght
tools: lnternctoncl 1ourncl o] 6yncecoloyy cnd Dbstetrcs, 2004, 85 (Suppl 1):S42-51.
87. Zhang 8Z. AntIshock trousers In the management of gynecologIc and obstetrIc hemorrhagIc shock. Zhonyhuc Fu Chcn Ke Zc
Zh, 198J, 18(4):229-2J1.
88. |Iller S et al. FIrst aId for obstetrIc haemorrhage: the pIlot study of the nonpneumatIc antIshock garment In Egypt. 8rtsh
1ourncl o] Dbstetrcs cnd 6yncecoloyy, 2006, 11J(4): 424-429.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
EB
i0)/'+)$3/0)/L$)2R.*'830'.+
89. 7andelet P et al. LImIts to arterIal embolIzatIon treatment of severe postpartum hemorrhage. Anncles ]rcncses
d'cnesthse et de Rcnmcton, 2001, 20(4):J17-J24.
90. ErIksson LC et al. |assIve postpartum hemorrhage treated wIth transcatheter arterIal embolIzatIon: technIcal aspects and
longterm effects on fertIlIty and menstrual cycle. Actc Rcdoloycc, 2007, 48(6):6J5-642.
91. SoncInI E et al. UterIne artery embolIzatIon In the treatment and preventIon of postpartum hemorrhage. lnternctoncl 1ourncl
o] 6yncecoloyy cnd Dbstetrcs, 2007, 96(J):181-185.
92. ong SP, Cheung K8. |anagement of prImary postpartum haemorrhage wIth arterIal embolIsatIon In Hong Kong publIc hospItals.
Hony Kony Medccl 1ourncl = Xcnyycny Y Xue Zc Zh / Hony Kony Accdemy o] Medcne, 2006, 12(6):4J7-441.
9J. 7egas C et al. SelectIve pelvIc arterIal embolIzatIon In the management of obstetrIc hemorrhage. Europecn 1ourncl o]
Dbstetrcs, 6ynecoloyy, cnd Reproductve 8oloyy, 2006, 127(1):68-72.
94. Djala K et al. ArterIal embolIzatIon and prophylactIc catheterIzatIon for the treatment for severe obstetrIc hemorrhage. Actc
Dbstetrcc et 6ynecoloycc Sccndncvcc, 2005, 84(11):1075-10806
95. Tsang |Let al. ArterIal embolIsatIon In Intractable prImary postpartum haemorrhage: case serIes. Hony Kony Medccl 1ourncl =
Xcnyycny Y Xue Zc Zh / Hony Kony Accdemy o] Medcne. 2004, 10(5):J01-J06.
96. 8loom A et al. ArterIal embolIsatIon for persIstent prImary postpartum haemorrhage: before or after hysterectomy: 8rtsh
1ourncl o] Dbstetrcs cnd 6yncecoloyy 2004, 111(8):880-884.
97. 8oulleret C et al. HypogastrIc arterIal selectIve and superselectIve embolIzatIon for severe postpartum hemorrhage: a
retrospectIve revIew of J6 cases. Ccrdovcsculcr cnd lnterventoncl Rcdoloyy, 2004, 27(4):J44-J48.
98. 0escargues C et al. |enses, fertIlIty and pregnancy after arterIal embolIzatIon for the control of postpartum haemorrhage.
Humcn Reproducton, 2004, 19(2):JJ9-J4J.
99. Hong T| et al. UterIne artery embolIzatIon: an effectIve treatment for Intractable obstetrIc haemorrhage. Clnccl Rcdoloyy,
2004, 59(1):96-101.
100. Cheng et al. AngIographIc embolIzatIon for emergent and prophylactIc management of obstetrIc hemorrhage: a fouryear
experIence. 1ourncl o] the Chnese Medccl Assoccton: 1CMA, 200J, 66(12):727-7J4.
101. Chung JW et al. Percutaneous transcatheter angIographIc embolIzatIon In the management of obstetrIc hemorrhage. The
1ourncl o] Reproductve Medcne, 200J, 48(4):268-276.
102. 0eux JF et al. s selectIve embolIzatIon of uterIne arterIes a safe alternatIve to hysterectomy In patIents wIth postpartum
hemorrhage: A1R. Amerccn 1ourncl o] Roentyenoloyy, 2001, 177(1):145-149.
10J. Chen C, |a 8, Fang . Transcatheter arterIal embolIzatIon In Intractable postpartum hemorrhage. Zhonyhuc Fu Chcn Ke Zc Zh,
2001, J6(J):1JJ-1J6.
104. Pelage JP et al. SelectIve arterIal embolIzatIon of the uterIne arterIes In the management of Intractable postpartum
hemorrhage. Actc Dbstetrcc et 6ynecoloycc Sccndncvcc, 1999, 78(8):698-70J.
105. Hansch E et al. PelvIc arterIal embolIzatIon for control of obstetrIc hemorrhage: a veyear experIence. Amerccn 1ourncl o]
Dbstetrcs cnd 6ynecoloyy, 1999, 180(6 Pt 1):1454-1460.
106. Pelage JP et al. |anagement of severe postpartum hemorrhage usIng selectIve arterIal embolIzatIon. 1ourncl de
6yncoloye, Dbsttrque et 8oloye de lc Reproducton, 1999, 28(1):55-61.
107. amashIta et al. Transcatheter arterIal embolIzatIon of obstetrIc and gynaecologIcal bleedIng: efcacy and clInIcal outcome.
8rtsh 1ourncl o] Rcdoloyy, 1994, 67(798):5J0-5J4.
108. Soyer P et al. 8Ilateral persIstent scIatIc artery: a potentIal rIsk In pelvIc arterIal embolIzatIon for prImary postpartum
hemorrhage. Actc Dbstetrcc et 6ynecoloycc Sccndncvcc, 2005, 84(6):604-605.
109. degaard E, QvIgstad E, Klw NE ntractable postpartum haemorrhage treated wIth selectIve arterIal embolIzatIon. Tdsskr]t
]or den Norske Lceye]orenny, 200J, 12J(19):2715-2716.
110. CottIer JP et al. UterIne necrosIs after arterIal embolIzatIon for postpartum hemorrhage. Dbstetrcs cnd 6ynecoloyy, 2002,
100(5 Pt 2):1074-1077.
111. PIrard C et al. UterIne necrosIs and sepsIs after vascular embolIzatIon and surgIcal lIgatIon In a patIent wIth postpartum
hemorrhage. Fertlty cnd Sterlty, 2002, 78(2):412-41J.
112. |urakamI F et al. Transcatheter arterIal embolIzatIon for postpartum massIve hemorrhage: a case report. Clnccl lmcyny,
2000, 24(6):J68-J70.
11J. DeI PL et al. ArterIal embolIzatIon for bleedIng followIng hysterectomy for Intractable postpartum hemorrhage. lnternctoncl
1ourncl o] 6yncecoloyy cnd Dbstetrcs, 1998, 62(1):8J-86.
114. Hsu F, Wan L. Successful management of Intractable puerperal hematoma and severe postpartum hemorrhage wIth 0C
through transcatheter arterIal embolIzatIon - two cases. Actc Dbstetrcc et 6ynecoloycc Sccndncvcc, 1998, 77(1):129-1J1.
115. Clanz H. Percutaneous catheter embolIzatIon In lIfe threatenIng obstetrIcal hemorrhage - a case report. 6eburtshl]e und
Frcuenhelkunde, 1996, 56(9):504-507.
116. 0evroede F et al. ArterIal embolIzatIon of postpartum hemorrhage. 1ourncl 8elye 0e Rcdoloye, 1995, 78(6):JJ7-JJ8.
117. |arpeau L et al. The role of pelvIc arterIal embolIzatIon In the treatment of severe postpartum hemorrhages. 1ourncl de
6yncoloye, Dbsttrque et 8oloye de lc Reproducton, 1992, 21(2):2JJ-2J5.
118. HorI A et al. Transcatheter arterIal embolIzatIon for postpartum hemorrhage. Rnsho Hoshcsen [Clnccl Rcdoyrcphy], 1990,
J5(5):645-647.
119. to | et al. AngIographIc arterIal embolIzatIon for control of Intractable postpartum hemorrhage. Nppon Scnkc Fu]nkc
6ckkc Zcssh, 1989, 41(11):1859-1862.
120. amashIta et al. Transcatheter arterIal embolIzatIon In postpartum hemorrhage. Nhon lycku Hshcsen 6ckkc Zcssh
[Nppon Actc Rcdoloycc], 1986, 46(8):1007-1011.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
EE
121. 8rown 8J et al. Uncontrollable postpartum bleedIng: a new approach to hemostasIs through angIographIc arterIal embolIzatIon.
Dbstetrcs cnd 6ynecoloyy, 1979, 54(J):J61-J65.
122. Heaston 0K et al. Transcatheter arterIal embolIzatIon for control of persIstent massIve puerperal hemorrhage after bIlateral
surgIcal hypogastrIc artery lIgatIon. A1R. Amerccn 1ourncl o] Roentyenoloyy, 1979, 1JJ(1):152-154.
<.24/),,'D)$,&0&/),
12J. ApI |, ApI D, ayla |. FertIlIty after 8Lynch suture and hypogastrIc artery lIgatIon. Fertlty cnd Sterlty, 2005, 84(2):509.
124. 8Lynch C et al. The 8Lynch surgIcal technIque for the control of massIve postpartum haemorrhage: an alternatIve to
hysterectomy: FIve cases reported. 8rtsh 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 1997, 104(J):J72-J75.
125. Cardone A et al. A new uterIne suture technIque for postpartum hemorrhage. Mnervc 6necoloycc, 2007, 59(J):J4J-J46.
126. CotzIas C, CIrlIng J. UterIne compressIon suture wIthout hysterotomy - why a nonabsorbable suture should be avoIded. 1ourncl
o] Dbstetrcs cnd 6yncecoloyy, 2005, 25(2):150-152.
127. 0acus J7 et al. SurgIcal treatment of uterIne atony employIng the 8Lynch technIque. The 1ourncl o] McternclFetcl Medcne,
2000, 9(J):194-196.
128. 0anso 0, FegInald P. CombIned 8lynch suture wIth IntrauterIne balloon catheter trIumphs over massIve postpartum
haemorrhage. 8rtsh 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 2002, 109(8):96J.
129. Flam F, Sennstrm |. Postpartum atony. A sImple method prevents lIfethreatenIng hemorrhages. Lckcrtdnnyen, 1998,
95(49):5650-5651.
1J0. ChezzI F et al. The Hayman technIque: a sImple method to treat postpartum haemorrhage. 8rtsh 1ourncl o] Dbstetrcs cnd
6yncecoloyy, 2007, 114(J):J62-J65.
1J1. Coddard F, Stafford |, SmIth JF. The 8Lynch surgIcal technIque for the control of massIve postpartum haemorrhage: an
alternatIve to hysterectomy: FIve cases reported. 8rtsh 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 1998, 105(1):126.
1J2. Habek 0 et al. Successful of the 8Lynch compressIon suture In the management of massIve postpartum hemorrhage: case
reports and revIew. Archves o] 6ynecoloyy cnd Dbstetrcs, 2006, 27J(5):J07-J09.
1JJ. Holtsema H et al. The 8Lynch technIque for postpartum haemorrhage: an optIon for every gynaecologIst. Europecn 1ourncl o]
Dbstetrcs, 6ynecoloyy, cnd Reproductve 8oloyy, 2004, 115(1):J9-42.
1J4. |alIbary A|. |odIed 8Lynch technIque for the control of massIve postpartum hemorrhage. An alternatIve to hysterectomy.
Scud Medccl 1ourncl, 2004, 25(12):1999-2000.
1J5. |azhar S8, asmIn S, Culzar S. |anagement of massIve postpartum hemorrhage by "8Lynch" brace suture. 1ourncl o] the
Colleye o] Physccns cnd Suryeons Pckstcn, 200J, 1J(1):51-52.
1J6. Nelson WL, D'8rIen J|. The uterIne sandwIch for persIstent uterIne atony: combInIng the 8Lynch compressIon suture and an
IntrauterIne 8akrI balloon. Amerccn 1ourncl o] Dbstetrcs cnd 6ynecoloyy, 2007, 196(5):e9-10.
1J7. Duahba J et al. UterIne compressIon sutures for postpartum bleedIng wIth uterIne atony. 8rtsh 1ourncl o] Dbstetrcs cnd
6yncecoloyy, 2007, 114(5):619-622.
1J8. PereIra A, et al. CompressIve uterIne sutures to treat postpartum bleedIng secondary to uterIne atony. Dbstetrcs cnd
6ynecoloyy, 2005, 106(J):569-572.
1J9. PIerzyskII P et al. 8 lynch suture for post partum heamorrhage due to uterIne atony. 6nekoloyc Polskc, 2006, 77(2):146-
150.
140. Saha F et al. 8Lynch brace suture sImple surgIcal technIque for managIng postpartum haemorrhage - report of three cases.
Kcthmcndu 0nversty Medccl 1ourncl (K0M1), 2005, J(4):418-420.
141. Tjalma WA, Jacquemyn . CompressIon sutures Instead of emergency perIpartum hysterectomy. Europecn 1ourncl o]
Dbstetrcs, 6ynecoloyy, cnd Reproductve 8oloyy, 2005, 118(2):258.
142. Treloar EJ et al. UterIne necrosIs followIng 8Lynch suture for prImary postpartum haemorrhage. 8rtsh 1ourncl o] Dbstetrcs
cnd 6yncecoloyy, 2006, 11J(4):486-488.
14J. TsItlakIdIs C et al. Ten year followup of the effect of the 8Lynch uterIne compressIon suture for massIve postpartum
hemorrhage. lnternctoncl 1ourncl o] Fertlty cnd Women's Medcne, 2006, 51(6):262-265.
144. 7angsgaard K. "8Lynch suture" In uterIne atony. 0yeskr]t ]or Lceyer, 2000, 162(24):J468.
145. Wergeland H, AlagIc E, LkvIk 8. Use of the 8Lynch suture technIque In postpartum hemorrhage. Tdsskr]t ]or 0en Norske
Lye]orenny: Tdsskr]t ]or Prcktsk Medcn, Ny Rkke, 2002, 122(4):J70-J72.
146. Wohlmuth CT, Cumbs J, QuebralvIe J. 8Lynch suture: a case serIes. lnternctoncl 1ourncl o] Fertlty cnd Women's Medcne,
2005, 50(4):164-17J.
147. Wu HH, eh CP. UterIne cavIty synechIae after hemostatIc square suturIng technIque. Dbstetrcs cnd 6ynecoloyy, 2005, 105(5
Pt 2):1176-1178.
148. PrIce N, 8Lynch C. TechnIcal descrIptIon of the 8Lynch brace suture for treatment of massIve postpartum hemorrhage and
revIew of publIshed cases. lnternctoncl 1ourncl o] Fertlty cnd Women's Medcne, 2005, 50(4), 148-16J.
149. Allam |S, 8Lynch C. The 8Lynch and other uterIne compressIon suture technIques. lnternctoncl 1ourncl o] 6ynecoloyy cnd
Dbstetrcs, 2005, 89(J): 2J6-241.
150. ElHamamy E, 8Lynch C. A worldwIde revIew of the uses of the uterIne compressIon suture technIques as alternatIve to
hysterectomy In the management of severe postpartum haemorrhage. 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 2005, 25(2):
14J-149.
151. Sergent F et al. ntractable postpartum haemorrhages: where Is the place of vascular lIgatIons, emergency perIpartum
hysterectomy or arterIal embolIzatIon:. 6yncoloye, Dbsttrque et Fertlt, 2004, J2(4): J20-J29.
152. TamIzIan D, Arulkumaran S. The surgIcal management of postpartum haemorrhage. 8est Prcctce cnd Resecrch. Clnccl
Dbstetrcs cnd 6yncecoloyy, 2002, 16(1): 81-98.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
EI
15J. Hayman FC, Arulkumaran S, Steer PJ. UterIne compressIon sutures: surgIcal management of postpartum hemorrhage.
Dbstetrcs cnd 6ynecoloyy, 2002, 99(J): 502-506.
A)*)50'D)$3/0)/L$*'%30'.+
154. Abd Fabbo SA. StepwIse uterIne devascularIzatIon: a novel technIque for management of uncontrolled postpartum hemorrhage
wIth preservatIon of the uterus. Amerccn 1ourncl o] Dbstetrcs cnd 6ynecoloyy, 1994, 171(J):694-700.
155. 8olbos C, SIndos |. The 8olbos technIque for the management of uncontrollable Intracaesarean uterIne bleedIng. Archves o]
yynecoloyy cnd obstetrcs, 2005, 272(2):142-144.
156. Casele HL, LaIfer SA. Successful pregnancy after bIlateral hypogastrIc artery lIgatIon. A case report. The 1ourncl o]
Reproductve Medcne, 1997, 42(5):J06-J08.
157. Chattopadhyay SK, 0eb Foy 8, Edrees 8. SurgIcal control of obstetrIc hemorrhage: hypogastrIc artery lIgatIon or
hysterectomy: lnternctoncl 1ourncl o] 6ynecoloyy cnd Dbstetrcs, 1990, J2(4):J45-J51.
158. CInco Arenas JE et al. LIgatIon of hypogastrIc arterIes In obstetrIcs and gynecology. Feport of 6 cases. 6necoloyc y
Dbstetrcc de Mexco,1967, 22(1JJ):1407-1417.
159. Clark SL et al. HypogastrIc artery lIgatIon for obstetrIc hemorrhage. Dbstetrcs cnd 6ynecoloyy, 1985, 66(J):J5J-J56.
160. 0as 8N, 8Iswas AK. LIgatIon of Internal IlIac arterIes In pelvIc haemorrhage. 1ourncl o] Dbstetrcs cnd 6yncecoloyy Resecrch,
1998, 24(4):251-254.
161. 0ubay |L, Holshauser CA, 8urchell FC. nternal IlIac artery lIgatIon for postpartum hemorrhage: recanalIzatIon of vessels.
Amerccn 1ourncl o] Dbstetrcs cnd 6ynecoloyy, 1980, 1J6(5):689-691.
162. Evans S, |cShane P. The efcacy of Internal IlIac artery lIgatIon In obstetrIc hemorrhage. Suryery 6ynecoloyy cnd Dbstetrcs,
1985, 160(J):250-25J.
16J. Fahmy K. UterIne artery lIgatIon to control postpartum hemorrhage. lnternctoncl 1ourncl o] 6yncecoloyy cnd Dbstetrcs,
1987, 25(5):J6J-J67.
164. Fernandez H et al. nternal IlIac artery lIgatIon In postpartum hemorrhage. Europecn 1ourncl o] Dbstetrcs, 6ynecoloyy, cnd
Reproductve 8oloyy, 1988, 28(J):21J-220.
165. HebIsch C, Huch A. 7agInal uterIne artery lIgatIon avoIds hIgh blood loss and puerperal hysterectomy In postpartum
hemorrhage. Dbstetrcs cnd 6ynecoloyy, 2002, 100(J):574-578.
166. JoshI 7| et al. nternal IlIac artery lIgatIon for arrestIng postpartum haemorrhage. 8rtsh 1ourncl o] Dbstetrcs cnd
6yncecoloyy, 2007, 114(J):J56-J61.
167. KhelI A et al. TherapeutIc lIgature of hypogastrIc arterIes: color 0oppler followup 1ourncl o] Rcdoloyy, 2000, 81(6):607-
610.
168. Lde N et al. |anagement In Intractable obstetrIc haemorrhage: an audIt study on 61 cases. Europecn 1ourncl o] Dbstetrcs,
6ynecoloyy, cnd Reproductve 8oloyy, 2001, 94(2):189-196.
169. LI T et al. A useful technIque for the control of severe caesarean hemorrhage: report of three cases. Chcny 6uny Medccl
1ourncl, 2002, 25(8):548-552.
170. LIberman CIa, Serova Ta. Arrest of atonIc hemorrhage n J parturIents by bIlateral lIgatIon of the uterIne arterIes.
Akusherstvo ynekoloyc, 196J, J9:129-1J0.
171. LIkeman FK. The boldest procedure possIble for checkIng the bleedIng - a new look at an old operatIon, and a serIes of 1J
cases from an AustralIan hospItal. The Austrclcn cnd New Zeclcnd 1ourncl o] Dbstetrcs cnd 6yncecoloyy, 1992, J2(J):256-
262.
172. NIzard J et al. FertIlIty and pregnancy outcomes followIng hypogastrIc artery lIgatIon for severe postpartum haemorrhage.
Humcn Reproducton, 200J, 18(4):844-848.
17J. D'Leary JA. UterIne artery lIgatIon In the control of postcaesarean hemorrhage. 1ourncl o] Reproductve Medcne, 1995,
40(J):189-19J.
174. Papp Z et al. HypogastrIc artery lIgatIon for Intractable pelvIc hemorrhage. lnternctoncl 1ourncl o] 6yncecoloyy cnd
Dbstetrcs, 2006, 92(1):27-J1.
175. Papp Z et al. 8Ilateral hypogastrIc artery lIgatIon for control of pelvIc hemorrhage, reductIon of blood ow and preservatIon of
reproductIve potentIal. ExperIence wIth 117 cases Drvos hetlcp, 2005, 146(24):1279-1285.
176. PhIlIppe HJ, d'Dreye 0, LewIn 0. 7agInal lIgature of uterIne arterIes durIng postpartum hemorrhage. lnternctoncl 1ourncl o]
6ynecoloyy cnd Dbstetrcs, 1997, 56(J):267-270.
177. PIrard C et al. UterIne necrosIs and sepsIs after vascular embolIzatIon and surgIcal lIgatIon In a patIent wIth postpartum
hemorrhage. Fertlty cnd Sterlty, 2002, 78(2):412-41J.
178. FezguI | et al. HypogastrIc artery lIgatIon followIng obstetrIcal hemorrhage. Apropos of 1 case. Lc Tunse mdccle, 1986,
64(J):261-26J.
179. Foman H et al. UterIne devascularIzatIon and subsequent major IntrauterIne synechIae and ovarIan faIlure. Fertlty cnd
Sterlty, 2005, 8J(J):755-757.
180. Saggara |, Classer ST, Stone |L. LIgatIon of the Internal IlIac vessels In the control of postpartum hemorrhage: report of a
case. Dbstetrcs cnd 6ynecoloyy, 1960, 15:698-701.
181. ShIn FK, Stecker ||, mbesI SC. PerIpheral nerve IschaemIa after Internal IlIac artery lIgatIon. 1ourncl o] Neuroloyy,
Neurosuryery, cnd Psychctry, 2001, 70(J):411-412.
182. TImoshenko L8, ZhItskII |D. A case of puerperal death due to abrInogenemIa, unsuccessfully treated by lIgatIon of the
uterIne vessels. Pedctr ckusherstvo ynekoloy, 196J, 58:5J-54.
18J. TsIrul'nIkov |S. mmedIate and remote results of lIgatIon of uterIne vessels durIng postpartum hemorrhage. Akusherstvo
ynekoloy, 1970, 46(7):59-61.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
EP
184. TsIrulnIkov |S. LIgatIon of the uterIne vessels durIng obstetrIcal hemorrhages. mmedIate and longterm results (author's
transl). 1ourncl de 6yncoloye, Dbsttrque et 8oloye de lc Reproducton, 1979, 8(8):751-75J.
185. Tsvetkov TS et al. StepwIse uterIne devascularIzatIon In postpartum hemorrhages. Akusherstvo ynekoloy, 2004,
4J(1):95.
186. amashIta T et al. Case report of pregnancy and delIvery after extraperItoneal lIgatIon of the Internal IlIac artery. Scn]u]nkc
no ]ssc, 1970, 19(4):427-428.
N)03'+)($4*35)+03
187. van 8eekhuIzen HJ et al. Sulprostone reduces the need for the manual removal of the placenta In patIents wIth retaIned
placenta: a randomIzed controlled trIal. Amerccn 1ourncl o] Dbstetrcs cnd 6ynecoloyy, 2006, 194(2):446-450.
188. CarrolI C, 8ergel E. UmbIlIcal veIn InjectIon for management of retaIned placenta. Cochrcne 0ctcbcse o] Systemctc Revews,
2001, ssue 4. Art. No.: C0001JJ7.
189. The Felease TrIal: a randomIsed trIal of umbIlIcal veIn oxytocIn versus placebo for the treatment of retaIned placenta. http://
Isrctn.org/SFCTN1J204258.
190. ChongsomchaI C, LumbIganon P, LaopaIboon |. ProphylactIc antIbIotIcs for manual removal of retaIned placenta In vagInal
bIrth. Cochrcne 0ctcbcse o] Systemctc Revews, 2006, ssue 2. Art. No.: C0004904.
191. CrIscuolo JL et al. The value of antIbIotIc prophylaxIs durIng IntrauterIne procedures durIng vagInal delIvery. A comparatIve
study of 500 patIents. 1ourncl 0e 6yncoloye, Dbsttrque et 8oloye de lc Reproducton, 1990, 19(7):909-918.
192. SmaIll F, Hofmeyr CJ. AntIbIotIc prophylaxIs for cesarean sectIon. Cochrcne 0ctcbcse o] Systemctc Revews, 2002, ssue J. Art.
No.:C00009JJ.
</L,03**.'($&,)
19J. Perel P, Foberts C. ColloIds versus crystalloIds for uId resuscItatIon In crItIcally Ill patIents. Cochrcne 0ctcbcse o] Systemctc
Revews, 2007, ssue 4. Art. No.: C0000567.
Q&'()*'+),
194. Lynch C8 et al., ed. Textbook o] postpcrtum hemorrhcye.KIrkmahoe, SapIens PublIshIng, 2006 (www.sapIenspublIshIng.com/
medIcalpublIcatIons.php1).
195. Schuurmans N, |acKInnon C, Lane C, Etches 0. J Soc Dbstet Cynaecol Can 2000, 22(4):271-81.
196. FranoIs A, CourtoIs F. |anagement of blood products In the event of postpartum hemorrhage. 1ourncl de 6yncoloye,
Dbsttrque et 8oloye de lc Reproducton, 2004, JJ(8 Suppl):4S1-4S1J6.
197. ArgentIna PPH management algorIthm, 2008
198. 6udelne ]or the mcncyement o] postpcrtum hcemorrhcye n the communty (versIon 2.1.1). 8IrmIngham, Cood Hope HospItal,
NHS Trust, 2005.
199. EssentIal DEC CuIdelInes for dIstrIct hospItals, South AfrIca, 1999
200. CuIdelInes for obstetrIc care at CoronatIon, Johannesburg and NatalspruIt HospItals. Johannesburg, UnIversIty of the
WItwatersrand, 1995.
201. ntroducIng WHD's sexual and reproductIve health guIdelInes and tools Into natIonal programmes. PrIncIples and processes of
adaptatIon and ImplementatIon. Ceneva, World Health DrganIzatIon, 2007 (WHD/FHF/07.9).
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
EJ
F++)^$?6$A5.4'+%$(.5&2)+0$M'01$3D)/3%)$,5./),
A5.4'+%$/),&*0,Y$@3+3%)2)+0$.-$HH"$(&)$0.$&0)/'+)$30.+L$3+($/)03'+)($4*35)+03
0ear colleagues,
Please nd for your revIew, the overall (averaged) responses to our questIons and outcomes related to the
management of:
(1) postpartum haemorrhage due to uterIne atony;
(2) retaIned placenta followIng an uncomplIcated delIvery.
n separate analysIs, Items shaded were scored 7 by at least one category of respondents (nurse mIdwIves,
physIcIans, or nonclInIcIans).
H/.4.,)($T&),0'.+,
F6$ =*..($*.,,$),0'230'.+$-./$01)$23+3%)2)+0$.-$HH"
Score the Importance of the questIon
In the management of PPH on a scale
from 1 to 9, where 1 = not Important,
9 = crItIcal
Should blood loss be routInely quantIed durIng delIvery for the
approprIate management of PPH due to uterIne atony, Instead of vIsual
estImatIon of blood loss:
6.06
=6$ @)('53*$'+0)/D)+0'.+,$-./$01)$23+3%)2)+0$.-$HH"
AssumptIons
ClInIcIans may perform several InterventIons sImultaneously (I.e. uterIne massage whIle medIcatIons are admInIstered).
ClInIcIans are aware of standard contraIndIcatIons of medIcatIons (although thIs wIll be reIterated In the nal guIdelIne
and any derIvatIve products).
For each drug lIsted score the
Importance of determInIng Its efcacy
as a uterotonIc (wIth or wIthout
postpartum haemorrhage) on a scale
from 1 to 9, where 1=not Important,
9=crItIcal
G/&%$W'+$5*'+'53**L$355)40)($(.,),$3+($/.&0),$.-$3(2'+',0/30'.+Z
_))($0.$
()0)/2'+)$
)-U535L
CarbetocIn 5.98
Carboprost (PCF
2a
) 4.85
ErgometrIne 5.4J
|Isoprostol 6.92
DxytocIn 5.J0
rFactor 7a 5.95
SyntometrIne
(xed dose combInatIon 5U oxytocIn + 0.5 mg ergometrIne maleate)
5.20
Sulprostone (PCE
2
) 5.20
TranexamIc acId 5.72
For each questIon, please rate Its
Importance In the management of PPH
on a scale from 1 to 9, where 1=not
Important, 9=crItIcal
Should certaIn combInatIons of medIcatIons be admInIstered In the
treatment of PPH:
6.92
Should medIcatIons be admInIstered In a sequentIal manner: 7.41
Should use of one type of prostaglandIn preclude use of other prosta
glandIns:
5.84
Should the route of mIsoprostol admInIstratIon vary If used as a rst
lIne (stand alone) treatment versus a second lIne treatment (In addItIon
to, or sequentIally wIth other medIcatIons):
5.72
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
E]
<6$O+0)/D)+0'.+,$-./$01)$23+3%)2)+0$.-$HH"
For each procedure lIsted please
score the relatIve Importance of
determInIng Its efcacy In the
management of PPH on a scale from
1 to 9, where 1=not Important,
9=crItIcal
O+0)/D)+0'.+ H/.5)(&/)
_))($0.$
()0)/2'+)$
)-U535L
Non surgIcal UterIne fundal massage 7.02
8Imanual uterIne massage 6.75
UterIne packIng 6.47
UterIne tamponade 6.90
External aortIc compressIon 6.40
AntIshock garments 6.78
FadIologIc UterIne artery embolIzatIon 6.44
ConservatIve surgIcal
InterventIons
CompressIve uterIne sutures 6.90
UterIne artery lIgatIon 6.24
HypogastrIc (Internal IlIac) artery lIgatIon 5.92
0enItIve Subtotal hysterectomy 5.J9
Total hysterectomy 5.5J
For each questIon please score Its
Importance In the management of PPH
on a scale from 1 to 9, where 1=not
Important 9=crItIcal
Should non surgIcal InterventIons be attempted as a temporIzIng
measure:
7.7J
Should InvasIve InterventIons be attempted sequentIally: 7.60
Should one surgIcal InterventIon be consIdered over others: 6.76
G6$O+0)/D)+0'.+,$-./$01)$23+3%)2)+0$.-$/)03'+)($4*35)+03
For each questIon, please score
It's relatIve Importance In the
management of retaIned placenta
on a scale from 1 to 9, where 1=not
Important 9=crItIcal
Should uterotonIcs be admInIstered If retaIned placenta has been
dIagnosed (usually after J0 mInutes):
7.58
Should IntraumbIlIcal veIn InjectIon of oxytocIn/salIne be admInIstered
after clInIcal dIagnosIs of retaIned placenta:
6.76
Should a retaIned placenta be manually extracted after J0 mInutes: 6.92
Should antIbIotIcs be routInely admInIstered followIng manual
extractIon of a retaIned placenta:
7.JJ
C6$[1)$/.*)$.-$1)3*01$,L,0)2,$3+($'+,0'0&0'.+,$'+$01)$23+3%)2)+0$.-$HH"$(&)$0.$&0)/'+)$30.+L
For each questIon please score
It's relatIve Importance In the
management of PPH on a scale from 1
to 9, where 1=not Important 9=crItIcal
Should each health system/InstItutIon have a formal protocol for the
management of PPH:
8.51
Should only physIcIans prescrIbe/admInIster uterotonIcs: 4.17
Should only physIcIans perform InterventIons (nonsurgIcal and
surgIcal):
5.49
Should each facIlIty have a formal protocol for the referral of patIents: 8.27
Should specIc traInIng courses wIth sImulatIon of the management
of PPH be offered to staff attendIng delIverIes for the approprIate
management of PPH, Instead of routIne currIcula traInIng:
7.9J
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
E;
H/.4.,)($.&05.2),,
O24./03+5)
Please score the Importance of
each IndIvIdual outcome In the
management of PPH, on a scale
from 1 to 9, where 1=not Important
9=crItIcal
|easurement
and magnItude
of blood loss
Accuracy In blood loss assessment 6.68
|ean blood loss 5.70
An addItIonal blood loss \500 ml
(followIng InItIal PPH dIagnosIs)
7.17
An addItIonal blood loss \1000 ml
(followIng InItIal PPH dIagnosIs)
7.76
Please do not attempt to rank the
outcomes
Postpartum anaemIa (Hg8 11.0 g/dl) 6.49
8lood transfusIon 7.25
Need for
contInued
treatment
AddItIonal uterotonIcs
7.44
HH"$
23+3%)2)+0$
.-0)+$'+D.*D),$
3$,0)4SM',)$
4/.%/),,'.+k$,.$
0130$+))($-./$
.+)$4/.5)(&/)$
23L$R)$,))+$3,$
3+$.&05.2)$.-$
3+.01)/
nvasIve nonsurgIcal treatment (uterIne packIng,
bImanual uterIne massage, tamponade)
7.21
SurgIcal treatment (arterIal lIgatIon, compressIve
uterIne sutures)
7.57
AddItIonal nonsurgIcal InterventIons (external
aortIc compressIon and compressIon garments)
6.82
ArterIal embolIzatIon 6.61
Hysterectomy for PPH 7.69
Adverse
outcomes
Nausea, vomItIng or shIverIng 5.48
|aternal temperature greater than J8`C 5.92
|aternal temperature greater than 40`C 7.54
0elayed InItIatIon of breastfeedIng 5.68
Prolonged hospItalIzatIon 6.70
Procedure related complIcatIons 7.26
nfectIon 7.48
Severe morbIdIty (IncludIng coagulopathy, organ
faIlure and CU admIssIon)
8.60
|aternal transfer 7.JJ
Systems FeductIon of tIme from decIsIon makIng to
ImplementatIon
8.20
AvaIlabIlIty of drugs and treatment 8.57
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
I:
F++)^$96$A)3/51$,0/30)%L
The search strategy aImed to IdentIfy references dealIng wIth the treatment of PPH. No lImIts were placed
on the search regardIng type of study, language or tIme frame.
n November 2007, the Cochrane lIbrary, Pubmed, Embase, and LIlacs were searched usIng the followIng terms:
oxytocIn
ergometrIne
syntometrIne
mIsoprostol
carboprost
sulprostone
factor 7a
tranexamIc acId
carbetocIn
bImanual or manual
massage
packIng
tamponade
balloon
catheter
8akrI or 8lakemore or Foley or condom
compressIve or compressIon or 8Lynch
(arterIal or vessel or vascular or artery or arterIes) and lIgatIon
antI shock garments
postpartum or post partum
hemorrhage or haemorrhage or bleedIng.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
I?
[3R*)$?6 CFA0E qualIty assessment crIterIa
QualIty of evIdence Study desIgn Lower If HIgher If
HIgh FandomIzed trIal Study qualIty:
SerIous lImItatIons: -1
7ery serIous lImItatIons: -2
mportant InconsIstency: -1
0Irectness:
Some uncertaInty: -1
|ajor uncertaInty: -2
Sparse data: -1
HIgh probabIlIty of reportIng bIas: -1
Strong assocIatIon:
Strong, no plausIble confounders,
consIstent and dIrect evIdence: +1
7ery strong, no major threats to valIdIty
and dIrect evIdence: +2
EvIdence of a dose-response gradIent: +1
All plausIble confounders would have
reduced the effect: +1
|oderate
Low DbservatIonal study
7ery low Any other evIdence
|ove up or down the IndIcated number of grades.
A statIstIcally sIgnIcant relatIve rIsk 2 (or 0.5), based on consIstent evIdence from two or more observatIonal studIes, wIth no
plausIble confounders.
A statIstIcally sIgnIcant relatIve rIsk 5 (or 0.2) based on dIrect evIdence wIth no major threats to valIdIty.
F++)^$B6$QNFGC$2)01.(.*.%L
The CradIng of FecommendatIons Assessment, 0evelopment and EvaluatIon (short CFA0E) WorkIng
Croup began In the year 2000 as an Informal collaboratIon of people wIth an Interest In addressIng the
shortcomIngs of present gradIng systems In health care. The workIng group has developed a common,
sensIble and transparent approach to gradIng qualIty of evIdence and strength of recommendatIons. CrItIcal
elements of usIng the CFA0E system Is descrIbed below. |ore InformatIon on CFA0E methodology Is
presented at the web sIte http://www.gradeworkInggroup.org/Index.htm.
<1)5>*',0$-./$()D)*.4'+%$3+($%/3('+%$/)5.22)+(30'.+,
0ene the populatIon, InterventIon and alternatIve, and the relevant outcomes.
SummarIze the relevant evIdence (relyIng on systematIc revIews).
f reports of randomIzed trIals are avaIlable, start by assumIng hIgh qualIty. f reports of welldone
observatIonal studIes are avaIlable, assume low qualIty. Then check for:
b serIous methodologIcal lImItatIons (lack of blIndIng, concealment, hIgh loss to followup,
stopped early);
b IndIrectness In populatIon, InterventIon, or outcome (use of surrogates);
b InconsIstency In results;
b ImprecIsIon In estImates.
f there are lImItatIons, downgrade FCTs from hIgh to moderate, low or very low and observatIonal
studIes to very low.
f no randomIzed trIals are avaIlable but welldone observatIonal studIes are avaIlable (IncludIng IndIrectly
relevant trIals and welldone observatIonal studIes), start by assumIng low qualIty. Then check:
b for large or very large treatment effect;
b whether all plausIble confounders would dImInIsh effect of InterventIon;
b for doseresponse gradIent.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
I9
Crade up to moderate or even hIgh, dependIng on specIal strengths.
StudIes startIng at very low are not upgraded. DbservatIonal studIes wIth lImItatIons are not upgraded.
Dnly observatIonal studIes wIth no threats to valIdIty can be upgraded.
0ecIde on best estImates of benets, harms, burden and costs for relevant populatIons.
0ecIde on whether the overall benets are worth the potentIal harms, burden and costs for the relevant
populatIon and decIde how clear and precIse thIs balance Is.
A0/)+%01$.-$/)5.22)+(30'.+,
The strength of a recommendatIon reects the degree of condence that the desIrable effects outweIgh the
undesIrable effects. 0esIrable effects can Include benecIal health outcomes, lower burden and cost savIngs.
UndesIrable effects can Include harms, hIgher burden and extra costs. 8urdens are the demands of adherIng
to a recommendatIon that patIents or caregIvers (e.g. famIly) may nd onerous, such as havIng to undergo
more frequent tests or requIrIng a longer tIme to recover.
Although the degree of condence Is actually a contInuum, two categorIes are used: ,0/.+% and M)3>.
A ,0/.+%$/)5.22)+(30'.+ Is one for whIch the group Is condent that the desIrable effects of adherence
outweIgh the undesIrable effects.
A M)3>$/)5.22)+(30'.+ Is one for whIch the group concludes that the desIrable effects of adherence
probably outweIgh the undesIrable effects, but Is not condent about these tradeoffs. Feasons for not beIng
condent may Include:
absence of hIgh qualIty evIdence;
presence of ImprecIse estImates of benets or harms;
uncertaInty or varIatIon In how dIfferent IndIvIduals value the outcomes;
small benets;
the benets may not be worth the costs (IncludIng the costs of ImplementIng the recommendatIon).
0espIte the lack of a precIse threshold for goIng from a strong to a weak recommendatIon, the presence
of Important concerns about one or more of the above factors make a weak recommendatIon more lIkely.
Croups should consIder all of these factors and make the reasons for theIr judgements explIcIt.
FecommendatIons should specIfy the perspectIve that Is taken (e.g. IndIvIdual patIent, health care system or
socIety) and whIch outcomes were consIdered (IncludIng costs).
C^324*),$.-$'24*'530'.+,$.-$3$,0/.+%$/)5.22)+(30'.+$3/)Y
h./$430')+0,: |ost patIents would want the recommended course of actIon and only a small proportIon
would not.
h./$5*'+'5'3+,: |ost patIents should receIve the recommended course of actIon. Adherence to thIs
recommendatIon Is a reasonable measure of good qualIty care.
h./$4.*'5LS23>)/,: The recommendatIon can be adapted as a polIcy In most sItuatIons. QualIty
InItIatIves could use thIs recommendatIon to measure varIatIons In qualIty.
C^324*),$.-$'24*'530'.+,$.-$3$M)3>$/)5.22)+(30'.+$3/)Y
h./$430')+0,: The majorIty of patIents would want the recommended course of actIon, but many would not.
h./$5*'+'5'3+,: 8e prepared to help patIents to make a decIsIon that Is consIstent wIth theIr own values.
h./$4.*'5LS23>)/,: There Is a need for substantIal debate and Involvement of stakeholders.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
IB
[3R*)$96 0ecIdIng on strength of a recommendatIon
O,,&) N)5.22)+()($4/.5),,
X&3*'0L$.-$)D'()+5)
?6$ X&3*'0L$.-$)D'()+5) Strong recommendatIons usually requIre hIgher qualIty evIdence for all the
crItIcal outcomes. The lower the qualIty of evIdence, the less lIkely Is a
strong recommendatIon.
=3*3+5)$.-$R)+)U0,$3+($13/2
96$ N)*30'D)$'24./03+5)$.-$01)$.&05.2),
a. benets of therapy
b. harm of treatment
c. burdens of therapy
Seek evIdence about the relatIve and actual values that patIents place on
outcomes (crItIcal; Important but not crItIcal; not Important). Seek evIdence
about varIabIlIty In preferences and values among patIents and other
stakeholders. The relatIve Importance of the outcomes should be Included
In the consIderatIons before recommendatIons are made. f values and
preferences vary wIdely, a strong recommendatIon becomes less lIkely.
B6$ =3,)*'+)$/',>,$.-$.&05.2),
a. benets of therapy
b. harm of treatments
c. burdens of therapy
ConsIder the baselIne rIsk for an outcome. s the baselIne rIsk goIng to make
a dIfference: f yes, then consIder makIng separate recommendatIons for
dIfferent populatIons.
The hIgher the baselIne rIsk, the hIgher the magnItude of potentIal benet
and the hIgher the lIkelIhood of a strong recommendatIon.
E6$ @3%+'0&()$.-$/)*30'D)$/',>
a. benets (reductIon In FF)
b. harms (Increase In FF)
c. burden
ConsIder the relatIve magnItude of the net effect. Large relatIve effects
wIll lead to a hIgher lIkelIhood of a strong recommendatIon If the balance of
benet, harms and burden go In the same dIrectIon. f they go In opposIte
dIrectIons and the relatIve magnItude of effects Is large (large benets
comIng wIth large rIsk of adverse effects), the recommendatIon Is more
lIkely to be weak.
I6$ FR,.*&0)$23%+'0&()$.-$01)$)--)50
a. benets
b. harms
c. burden
Large absolute effects are more lIkely to lead to strong recommendatIon.
P6$ H/)5','.+$.-$01)$),0'230),$.-$01)$)--)50,
a. benets of therapy
b. harms of treatments
c. burdens of therapy
The greater the precIsIon the more lIkely the recommendatIon Is strong.
J6$ h350./,$0130$2.('-L$)--)50,$'+$,4)5'U5$,)00'+%,l
c.53*$-350./,$0130$23L$3--)50$0/3+,*30'.+$.-$01)$
)D'()+5)$'+0.$4/350'5)
The more sImIlar the settIng and patIents for whIch one Is makIng a
recommendatIon to the settIng and patIents generatIng the evIdence, the
more lIkely the recommendatIon Is strong.
]6$ <.,0, ConsIder that Important benets should come at a reasonable cost. The
hIgher the Incremental cost, all else beIng equal, the less lIkely that the
recommendatIon In favour of an InterventIon Is strong.
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
IE
G/$C(%3/(.$FR3*.,
Centro FosarIno de EstudIos PerInatales (CFEP)
FosarIo, Santa F
ArgentIna
G/$"3+L$FR()*$F*))2
Professor of DbstetrIcs and Cynecology
Faculty of |edIcIne, AssIut UnIversIty
0epartment of DbstetrIcs and Cynecology,
AssIut UnIversIty HospItal
AssIut
Egypt
@,$G)R./31$F/2R/&,0)/
PATH
WashIngton, 0C
USA
@,$m)++'-)/$=*&2
CynuIty Health Projects
New ork, N
USA
G/$@'51)*$=.&*D3'+
|aternIt
HpItaux UnIversItaIres de Cenve
Ceneva
SwItzerland
G/$Q&'*1)/2)$<)5300'
DbstetrIcs UnIt
0epartment of DbstetrIcs and Cynecology
School of |edIcal ScIences
State UnIversIty of CampInas
CampInas, So Paulo
8razIl
G/$G./',$<1.&
8ethesda, |0
USA
N'513/($m6$G)/23+
ChaIr, 0epartment of DbstetrIcs and Cynecology
ChrIstIana Care Health ServIces
0Irector, Center for Women and ChIldren's Health Fesearch
ClInIcal Professor, 0epartment DbstetrIcs and Cynecology
Jefferson |edIcal College
Newark, 0elaware
USA
G/$G'3+3$C*R.&/+)
Professor of Health Care EvaluatIon
|edIcal StatIstIcs UnIt
London School of HygIene and TropIcal |edIcIne
London
UnIted KIngdom
@,$Q'**$QL0)
Fesearch AssocIate
Cochrane Pregnancy and ChIldbIrth Croup
UnIversIty of LIverpool
LIverpool Women's HospItal NHS Trust
LIverpool
UnIted KIngdom
F++)^$E6$c',0$.-$43/0'5'43+0,
G/$m&,0&,$".-2)L/
0Irector
UnIversIty of the WItwatersrand/
UnIversIty of Fort Hare/Eastern Cape 0epartment of Health
EffectIve Care Fesearch UnIt
East London, Eastern Cape
South AfrIca
G/$F+(/n$=6$c3*.+()
ExecutIve 7IcePresIdent
The SocIety of DbstetrIcIans and CynaecologIsts of Canada
Dttawa
Canada
G/$H',3>)$c&2R'%3+.+
Convenor,ThaI Cochrane Network
Faculty of |edIcIne
Khon Kaen UnIversIty
Khon Kaen
ThaIland
G/$C+/'T&)$#L3/8&+
ChaIrman, 0epartment of DbstetrIcs and Cynecology
Faculty of |edIcIne
PontIcIa UnIversIdad CatolIca de ChIle
SantIago
ChIle
G/$o31'(3$X&/),1'
DbstetrIcIan/CynaecologIst
SenIor Lecturer
0epartment of DbstetrIcs/Cynaecology
UnIversIty of NaIrobI
Kenya
H/.-),,./$A&/3,3>$[3+))43+'51,>&*
0ean, College of PublIc Health ScIences
Chulalongkorn UnIversIty
8angkok
ThaIland
G/$[/3+$A.+$[1351
0Irector
Hung 7uong HospItal
Ho ChI |Inh CIty
7Iet Nam
G/$m&3+$<3/*.,$d38T&)8
nstItuto NacIonal de EndocrInologa
HospItal "Cmdte. Fajardo"
Havana
Cuba
G/$m)3+$m.,n$!.*.2RL
0epartment of Cynecology and DbstetrIcs
ClInIques UnIversItaIres de KInshasa
KInshasa
0emocratIc FepublIc of Congo
!"#$%&'()*'+),$-./$01)$23+3%)2)+0$.-$4.,043/0&2$13)2.//13%)$3+($/)03'+)($4*35)+03
II
#=ACNdCNA
@,$@3/L$C**)+$A03+0.+
SenIor FeproductIve Health AdvIsor
Center for PopulatIon, Health and NutrItIon
UnIted States Agency for nternatIonal 0evelopment
WashIngton, 0C
USA
G/$=)D)/*L$!'+'>.--
CynuIty Health Projects
New ork, N
USA
O_dO[CG$=i[$i_F=cC$[#$F[[C_G
G/$o3/>.$F*U/)D'5
SenIor Lecturer
0epartment of DbstetrIcs and Cynaecology
LIverpool Women's HospItal
LIverpool
UnIted KIngdom
G/$"3,,3+$=3pFT))*
KIng KhalId NatIonal Cuard HospItal
0epartment of DbstetrIcs and Cynecology
Jeddah
SaudI ArabIa
G/$C5>13/0$=&5123++
KIllarney
Johannesburg
South AfrIca
G/$h/3+5)$G.++3L
SenIor Program Dfcer, |aternal Health
ntegrated Health SolutIons 0evelopment
8Ill E |elInda Cates FoundatIon
G/$m'2$_)'*,.+
0ean, NHF Faculty TraInees
Professor of DbstetrIcs and Cynaecology
School of FeproductIve and 0evelopmental |edIcIne
UnIversIty of LIverpool;
JoInt CoordInatIng EdItor
Cochrane Pregnancy E ChIldbIrth Croup
UnIversIty 0epartment
LIverpool Women's HospItal
LIverpool
UnIted KIngdom
G/$c3>,12'$A),13(/'
Professor, 0epartment of DbstetrIcs and Cynaecology
ChrIstIan |edIcal College HospItal
7ellore
ndIa
G/$cL++$A'R*)L
AssocIate Professor
LIllIan Carter Center for nternatIonal NursIng
0Irector, Center for Fesearch on |aternal and Newborn SurvIval
Nell Hodgson Woodruff School of NursIng
Emory UnIversIty
Atlanta, CA
USA
G/$@3/0'+$!1'00*)
KIng's Court
London
UnIted KIngdom
H/.-),,./$X'3+$q&
0epartment of |aternal and ChIld Health
School of PublIc Health
Fudan UnIversIty
ShanghaI
ChIna
!"#$NCQO#_Fc$#hhO<C
G/$F>`)23*$@3%0L2.D3
W&+3R*)$0.$300)+(Z
FeproductIve Health E Fesearch
WHD FegIonal Dfce for SouthEast AsIa
World Health House
ndraprastha Estate
New 0elhI
ndIa
!"#$AC<NC[FNOF[
G/$F6$@)0'+$Qr*2)8.%*&
ScIentIst
FeproductIve Health and Fesearch
TechnIcal CooperatIon wIth CountrIes
G/$A&83++)$"'**
ScIentIst
|edIcInes PolIcy, EssentIal drugs and TradItIonal |edIcIne
PolIcy, Access and FatIonal Use
G/$@3001)M,$@3013'
|edIcal Dfcer
|akIng Pregnancy Safer
Norms and TechnIcal Support
G/$@3/'.$@)/'3*('
CoordInator
FeproductIve Health and Fesearch
|aternal and PerInatal Health
G/$m.s.$H3&*.$A.&83
|edIcal Dfcer
FeproductIve Health and Fesearch
TechnIcal CooperatIon wIth CountrIes

B
e

r
e
a
d
y

a
t

a
l
l

t
i
m
e
s

t
o

t
r
a
n
s
f
e
r

t
o

a

h
i
g
h
e
r
-
l
e
v
e
l

f
a
c
i
l
i
t
y

i
f

t
h
e

p
a
t
i
e
n
t

i
s

n
o
t

r
e
s
p
o
n
d
i
n
g

t
o

t
h
e

t
r
e
a
t
m
e
n
t

o
r

a

t
r
e
a
t
m
e
n
t

c
a
n
n
o
t

b
e

a
d
m
i
n
i
s
t
e
r
e
d

a
t

y
o
u
r

f
a
c
i
l
i
t
y
.
S
t
a
r
t

i
n
t
r
a
v
e
n
o
u
s

o
x
y
t
o
c
i
n

i
n
f
u
s
i
o
n

a
n
d

c
o
n
s
i
d
e
r
:





!

u
t
e
r
i
n
e

m
a
s
s
a
g
e
;
!

b
i
m
a
n
u
a
l

u
t
e
r
i
n
e

c
o
m
p
r
e
s
s
i
o
n
;

!

e
x
t
e
r
n
a
l

a
o
r
t
i
c

c
o
m
p
r
e
s
s
i
o
n
;

a
n
d

!

b
a
l
l
o
o
n

o
r

c
o
n
d
o
m

t
a
m
p
o
n
a
d
e
.

T
r
a
n
s
f
e
r

w
i
t
h

o
n
g
o
i
n
g

i
n
t
r
a
v
e
n
o
u
s

u
t
e
r
o
t
o
n
i
c

i
n
f
u
s
i
o
n
.

A
c
c
o
m
p
a
n
y
i
n
g

a
t
t
e
n
d
a
n
t

s
h
o
u
l
d

r
u
b

t
h
e

w
o
m
a
n

s

a
b
d
o
m
e
n

c
o
n
t
i
n
u
o
u
s
l
y

a
n
d
,

i
f

n
e
c
e
s
s
a
r
y
,

a
p
p
l
y

m
e
c
h
a
n
i
c
a
l

c
o
m
p
r
e
s
s
i
o
n
.
O
x
y
t
o
c
i
n

t
r
e
a
t
m
e
n
t

o
f

c
h
o
i
c
e
E
r
g
o
m
e
t
r
i
n
e

i
f

o
x
y
t
o
c
i
n

i
s

u
n
a
v
a
i
l
a
b
l
e

o
r

b
l
e
e
d
i
n
g

c
o
n
t
i
n
u
e
s

d
e
s
p
i
t
e

o
x
y
t
o
c
i
n
P
r
o
s
t
a
g
l
a
n
d
i
n
s

i
f

o
x
y
t
o
c
i
n

o
r

e
r
g
o
m
e
t
r
i
n
e

a
r
e

u
n
a
v
a
i
l
a
b
l
e

o
r

b
l
e
e
d
i
n
g

c
o
n
t
i
n
u
e
s

d
e
s
p
i
t
e

o
x
y
t
o
c
i
n

a
n
d

e
r
g
o
m
e
t
r
i
n
e
T
r
a
n
e
x
a
m
i
c

a
c
i
d
-

2
0
-
4
0

|
U

l
n

l

l
l
t
r
e

o
f

l
n
t
r
a
v
e
n
o
u
s

n
u
l
d

a
t

6
0

d
r
o
p
s

p
e
r

m
l
n
u
t
e
,

a
n
d

l
0

|
U

l
n
t
r
a
m
u
s
c
u
l
a
r
l
y
-

C
o
n
t
i
n
u
e

o
x
y
t
o
c
l
n

l
n
f
u
s
l
o
n

(
2
0

|
U

l
n

l

l
l
t
r
e

o
f

l
n
t
r
a
v
e
n
o
u
s

n
u
l
d

a
t

4
0

d
r
o
p
s

p
e
r

m
l
n
u
t
e
)

u
n
t
l
l

h
a
e
m
o
r
r
h
a
g
e

s
t
o
p
s
-

0
.
2

m
g

l
n
t
r
a
m
u
s
c
u
l
a
r
l
y

o
r

l
n
t
r
a
v
e
n
o
u
s
l
y

(
s
l
o
w
l
y
)
,


o
r

S
y
n
t
o
m
e
t
r
l
n
e
'

l

m
l
-

A
f
t
e
r

l
5

m
l
n
u
t
e
s
,

r
e
p
e
a
t

e
r
g
o
m
e
t
r
l
n
e

0
.
2

m
g

l
n
t
r
a
m
u
s
c
u
l
a
r
l
y
-

I
f

r
e
q
u
i
r
e
d
,

a
d
m
l
n
l
s
t
e
r

0
.
2

m
g

i
n
t
r
a
m
u
s
c
u
l
a
r
l
y

o
r

i
n
t
r
a
v
e
n
o
u
s
l
y

(
s
l
o
w
l
y
)

e
v
e
r
y

4

h
o
u
r
s
-

D
o

n
o
t

e
x
c
e
e
d

l

m
g

(
o
r

v
e

0
.
2

m
g

d
o
s
e
s
)


M
i
s
o
p
r
o
s
t
o
l
:


-

2
0
0
-
8
0
0

g

s
u
b
l
l
n
g
u
a
l
l
y
-

D
o

n
o
t

e
x
c
e
e
d

8
0
0

g

P
r
o
s
t
a
g
l
a
n
d
i
n

F
2

:


-

0
.
2
5

m
g

l
n
t
r
a
m
u
s
c
u
l
a
r
l
y
-

P
e
p
e
a
t

a
s

n
e
e
d
e
d

e
v
e
r
y

l
5

m
l
n
u
t
e
s

0
.
2
5

m
g

i
n
t
r
a
m
u
s
c
u
l
a
r
l
y
-

D
o

n
o
t

e
x
c
e
e
d

2

m
g

(
o
r

e
l
g
h
t

0
.
2
5

m
g

d
o
s
e
s
)
-

l

g

l
n
t
r
a
v
e
n
o
u
s
l
y

(
t
a
k
l
n
g

l

m
l
n
u
t
e


t
o

a
d
m
l
n
l
s
t
e
r
)
-

I
f

b
l
e
e
d
i
n
g

c
o
n
t
i
n
u
e
s
,



r
e
p
e
a
t

l

g

a
f
t
e
r

3
0

m
l
n
u
t
e
s
U
t
e
r
i
n
e

a
t
o
n
y
:
u
t
e
r
u
s

s
o
f
t

a
n
d

r
e
l
a
x
e
d

P
l
a
c
e
n
t
a

n
o
t

d
e
l
i
v
e
r
e
d

T
r
e
a
t

f
o
r

w
h
o
l
e

r
e
t
a
i
n
e
d

p
l
a
c
e
n
t
a

!

O
x
y
t
o
c
i
n
!

C
o
n
t
r
o
l
l
e
d

c
o
r
d

t
r
a
c
t
i
o
n
!

|
n
t
r
a
u
m
b
l
l
l
c
a
l

v
e
l
n

l
n
[
e
c
t
l
o
n

(
l
f

n
o

b
l
e
e
d
l
n
g
)


















I
f

w
h
o
l
e

p
l
a
c
e
n
t
a

s
t
i
l
l

r
e
t
a
i
n
e
d


















!

M
a
n
u
a
l

r
e
m
o
v
a
l

w
i
t
h

p
r
o
p
h
y
l
a
c
t
i
c

a
n
t
i
b
i
o
t
i
c
s
P
l
a
c
e
n
t
a

d
e
l
i
v
e
r
e
d

i
n
c
o
m
p
l
e
t
e

T
r
e
a
t

f
o
r

r
e
t
a
i
n
e
d

p
l
a
c
e
n
t
a

f
r
a
g
m
e
n
t
s
!

O
x
y
t
o
c
i
n
!

M
a
n
u
a
l

e
x
p
l
o
r
a
t
i
o
n

t
o

r
e
m
o
v
e

f
r
a
g
m
e
n
t
s
!

G
e
n
t
l
e

c
u
r
e
t
t
a
g
e

o
r

a
s
p
i
r
a
t
i
o
n


















I
f

b
l
e
e
d
i
n
g

c
o
n
t
i
n
u
e
s


















!

M
a
n
a
g
e

a
s

u
t
e
r
i
n
e

a
t
o
n
y
L
o
w
e
r

g
e
n
i
t
a
l

t
r
a
c
t

t
r
a
u
m
a
:
e
x
c
e
s
s
l
v
e

b
l
e
e
d
l
n
g

o
r

s
h
o
c
k

c
o
n
t
r
a
c
t
e
d

u
t
e
r
u
s

T
r
e
a
t

f
o
r

l
o
w
e
r

g
e
n
i
t
a
l

t
r
a
c
t

t
r
a
u
m
a

!

P
e
p
a
l
r

o
f

t
e
a
r
s

!

E
v
a
c
u
a
t
i
o
n

a
n
d

r
e
p
a
i
r

o
f

h
a
e
m
a
t
o
m
a


















I
f

b
l
e
e
d
i
n
g

c
o
n
t
i
n
u
e
s


















!

T
r
a
n
e
x
a
m
i
c

a
c
i
d
U
t
e
r
i
n
e

r
u
p
t
u
r
e

o
r

d
e
h
i
s
c
e
n
c
e
:
e
x
c
e
s
s
l
v
e

b
l
e
e
d
l
n
g

o
r

s
h
o
c
k

T
r
e
a
t

f
o
r

u
t
e
r
i
n
e

r
u
p
t
u
r
e

o
r

d
e
h
i
s
c
e
n
c
e
!

L
a
p
a
r
o
t
o
m
y

f
o
r

p
r
i
m
a
r
y

r
e
p
a
i
r

o
f

u
t
e
r
u
s
!

H
y
s
t
e
r
e
c
t
o
m
y

i
f

r
e
p
a
i
r

f
a
i
l
s


















I
f

b
l
e
e
d
i
n
g

c
o
n
t
i
n
u
e
s


















!

T
r
a
n
e
x
a
m
i
c

a
c
i
d
U
t
e
r
i
n
e

i
n
v
e
r
s
i
o
n
:
u
t
e
r
i
n
e

f
u
n
d
u
s

n
o
t

f
e
l
t

a
b
d
o
m
i
n
a
l
l
y

o
r

v
i
s
i
b
l
e

i
n

v
a
g
i
n
a

T
r
e
a
t

f
o
r

u
t
e
r
i
n
e

i
n
v
e
r
s
i
o
n

!

|
m
m
e
d
l
a
t
e

m
a
n
u
a
l

r
e
p
l
a
c
e
m
e
n
t
!

H
y
d
r
o
s
t
a
t
i
c

c
o
r
r
e
c
t
i
o
n
!

M
a
n
u
a
l

r
e
v
e
r
s
e

i
n
v
e
r
s
i
o
n



(
u
s
e

g
e
n
e
r
a
l

a
n
a
e
s
t
h
e
s
i
a

o
r

w
a
i
t

f
o
r

e

e
c
t




o
f

a
n
y

u
t
e
r
o
t
o
n
l
c

t
o

w
e
a
r

o
n
)















































I
f

l
a
p
a
r
o
t
o
m
y

c
o
r
r
e
c
t
i
o
n

n
o
t

s
u
c
c
e
s
s
f
u
l














































!

H
y
s
t
e
r
e
c
t
o
m
y
C
l
o
t
t
i
n
g

d
i
s
o
r
d
e
r
:
b
l
e
e
d
i
n
g

i
n

t
h
e

a
b
s
e
n
c
e

o
f


a
b
o
v
e

c
o
n
d
i
t
i
o
n
s

T
r
e
a
t

f
o
r

c
l
o
t
t
i
n
g

d
i
s
o
r
d
e
r

!

T
r
e
a
t

a
s

n
e
c
e
s
s
a
r
y

w
i
t
h

b
l
o
o
d

p
r
o
d
u
c
t
s