Treatments For Secondary Postpartum Haemorrhage (Review)

Treatments for secondary postpartum haemorrhage (Review)
Alexander J, Thomas PW, Sanghera J

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2009, Issue 3
http://www.thecochranelibrary.com
Treatments for secondary postpartum haemorrhage (Review)
Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
T A B L E O F C O N T E N T S
1 HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1 ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2 BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3 OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3 METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4 RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5 DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5 AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5 ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5 REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8 CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12 DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12 APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13 WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13 HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13 CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
13 DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
14 SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
14 DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
14 INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
i Treatments for secondary postpartum haemorrhage (Review)
[Intervention Review]
Treatments for secondary postpartum haemorrhage
Jo Alexander
1
, Peter W Thomas
2
, Jill Sanghera
3
1
School of Health and Social Care, Bournemouth University, Bournemouth, UK.
2
Dorset Research and Development Support Unit,
Poole Hospital NHS Trust, Poole, UK.
3
Institute of Health and Community Studies, Bournemouth University, Bournemouth, UK
Contact address: Jo Alexander, School of Health and Social Care, Bournemouth University, Christchurch Road, Bournemouth, Dorset,
BH1 3LG, UK. jalexand@bournemouth.ac.uk. (Editorial group: Cochrane Pregnancy and Childbirth Group.)
Cochrane Database of Systematic Reviews, Issue 3, 2009 (Status in this issue: Unchanged)
DOI: 10.1002/14651858.CD002867
This version rst published online: 21 January 2002 in Issue 1, 2002.
Last assessed as up-to-date: 30 January 2008. (Help document - Dates and Statuses explained)
This record should be cited as: Alexander J, Thomas PW, Sanghera J. Treatments for secondary postpartum haemorrhage. Cochrane
Database of Systematic Reviews 2002, Issue 1. Art. No.: CD002867. DOI: 10.1002/14651858.CD002867.
A B S T R A C T
Background
Secondary postpartum haemorrhage is any abnormal or excessive bleeding from the birth canal occurring between 24 hours and 12
weeks postnatally. In developed countries, 2%of postnatal women are admitted to hospital with this condition, half of themundergoing
uterine surgical evacuation. Data are not available from developing countries.
Objectives
To evaluate the relative effectiveness and safety of the treatments used for secondary postpartum haemorrhage.
Search strategy
We searched the Cochrane Pregnancy and Childbirth Groups Trials Register (31 January 2008), the reference lists of trial reports and
reviews and sought further sources from the rst named authors of the papers identied.
Selection criteria
All randomised or quasi-randomised comparisons between drug therapies, surgical therapies and placebo or no treatment for the
management of secondary postpartum haemorrhage occurring between 24 hours and three months following a pregnancy of at least
24 weeks gestation.
Data collection and analysis
Two authors scrutinised reports of possibly eligible studies. The third author acted as an advisor or arbitrator.
Main results
Of the 47 papers (36 studies) identied, none met the inclusion criteria.
Authors conclusions
No information is available from randomised controlled trials to inform the management of women with secondary postpartum
haemorrhage. This topic may have received little attention because it is perceived as being associated with maternal morbidity rather than
mortality in developed countries; it is only recently that the extent and importance of postnatal maternal morbidity has been recognised.
A well-designed randomised controlled trial comparing the various therapies for women with secondary postpartum haemorrhage
against each other and against placebo or no treatment groups is needed.
1 Treatments for secondary postpartum haemorrhage (Review)
P L A I N L A N G U A G E S U M M A R Y
Treatments for secondary postpartum haemorrhage
No randomised controlled trials to inform the management of women with secondary postpartum haemorrhage
Sometimes women experience abnormal or excessive bleeding from the birth canal between 24 hours and 12 weeks after giving birth,
and this is called secondary postpartum haemorrhage. It is usually caused by a tear, an infection, or by fragments of the placenta
or membranes, or both, remaining in the uterus and causing infection or preventing the uterus from contracting. It can be painful,
disruptive to daily life with a new baby and can exacerbate extreme tiredness. Although the specic incidence is not known, in low-
income countries it is probably a serious cause of maternal mortality. In high-income countries, about 2% of women are admitted to
hospital with this condition. Treatments may include giving drugs to treat infection and/or control bleeding and/or a variety of surgical
procedures. Studies could have compared an individual treatment to another, combinations of treatments to others, and any individual
or combination of treatments to either a placebo or no treatment group. However, no trials were identied and so there is no good
evidence on which to base guidance. A well-designed trial is needed.
B A C K G R O U N D
Secondary postpartum haemorrhage is dened as any abnormal
or excessive bleeding from the birth canal occurring between 24
hours (Dewhurst 1966) and 12 weeks (Rome 1975) postnatally
and, as this denition includes no reference to the volume of blood
loss or the condition of the woman, the spectrum of the condi-
tion can vary from inconvenient to fatal. However, in developed
countries around 1% of postnatal women undergo surgical uter-
ine evacuation (evacuation of retained products of conception)
for secondary postpartum haemorrhage (ACOG 1990; Dewhurst
1966; Glazener 1999) and a further 1% are admitted to hospi-
tal but managed conservatively (Alexander 1997; Glazener 1999).
Leaving aside any physical morbidity, it is generally acknowledged
that the postnatal period is a time of signicant psychological up-
heaval for women and their families even without the added dis-
ruption of needing medical treatment and possibly admission to,
or extra time in, hospital (Raphael-Leff 1991). Secondary post-
partum haemorrhage is, however, a topic that has received little
attention because it is perceived as being associated with mater-
nal morbidity rather than mortality in developed countries (King
1989); it is only relatively recently that the importance of post-
natal maternal morbidity has been recognised (MacArthur 1991).
It seems likely that this morbidity may include anaemia, which
would be worsened by secondary postpartum haemorrhage, and
serve to add to the extreme tiredness that many postnatal women
experience (Bick 1995).
Secondary postpartum haemorrhage, which appears frequently to
be linked with genital tract infection, still results in maternal death
indeveloped countries albeit very occasionally. Inthe UK, one ma-
ternal death occurred due to secondary postpartum haemorrhage
between 1994 and 1996 (DoH 1999), but none between 2000
and 2002 (CEMACH 2004). It seems likely that related maternal
deaths are more common in developing countries, but data do not
appear to be available.
If secondary postpartum haemorrhage is sufciently severe to re-
sult in admission to hospital, treatment usually falls into two broad
categories: drug treatment or surgery, or both (Alexander 1997;
Weisenberg-Smith1993). The rationale for these treatments ap-
pears to be that the uterus has failed to contract adequately to
prevent bleeding from the placental site, the underlying cause of
this being retained products or intrauterine infection, or both (
Crowley 1984; King 1989; Rome 1975). However, the underlying
cause of the condition is often not established. Drug therapy con-
sists of oxytocics or antibiotics, or both; hormonal preparations
may also be given to regulate bleeding (RCOG 1994). Antibi-
otic regimens used for endometritis (inammation of the lining
of the womb causing pain) after delivery are the subject of a sepa-
rate review (French 2004) but clearly endometritis and secondary
postpartum haemorrhage are not mutually exclusive conditions.
Surgery might involve evacuation of retained products (see above),
cervical dilatation, repair of cervical tear or uterine rupture, molar
pregnancy treatment and, rarely, hysterectomy.
There is evidence to suggest that endometritis is increased among
women who have prelabour rupture of membranes at term (
Novak-Antolic 1997) or who are delivered by caesarean section (
Calhoun 1995; Milligan 1992; Stovall 1998). Events in the im-
mediately preceding pregnancy, which have been suggested as pre-
disposing a woman to secondary postpartum haemorrhage, are
the mother smoking at the time the antenatal history was taken (
Marchant 2006); multiple pregnancy (King 1989; Thorsteinsson
1970); threatened miscarriage (Marchant 2006;Thorsteinsson
1970); antepartum haemorrhage (Thorsteinsson 1970); hospital
admission during the third trimester (Marchant 2006); precipi-
tate labour of less than two hours (Thorsteinsson 1970); the ad-
ministration of intravenous ergometrine (0.5 mg) as preventative
management for the third stage of labour (Begley 1990); pro-
longed third stage (Lester 1956; Marchant 2006; Thorsteinsson
1970); incomplete placenta or membranes passed at birth, or
both (Dewhurst 1966; Lester 1956; Marchant 2006; Rome 1975;
Thorsteinsson 1970); primary postpartum haemorrhage (Rome
1975); and not breastfeeding (Marchant 2006). A previous his-
tory of secondary postpartum haemorrhage predisposes to a re-
currence (Dewhurst 1966; Marchant 2006; Thorsteinsson 1970)
and it has been suggested that it is more common amongst mul-
tiparous women (see Glazener 1995; King 1989).
There has been no systematic review to assess the relative effec-
tiveness of treatments for secondary postpartum haemorrhage.
O B J E C T I V E S
To evaluate the relative effectiveness and safety of the treatments
used for secondary postpartum haemorrhage.
M E T H O D S
Criteria for considering studies for this review
Types of studies
All randomised comparisons between drug therapies, surgical
therapies and placebo or no treatment for the management of
secondary postpartum haemorrhage were eligible for inclusion.
Quasi-randomised studies (for example, alternate allocation, allo-
cation by hospital number, etc) were also eligible for inclusion.
Types of participants
Women from 24 hours to three months following a pregnancy of
at least 24 weeks gestation with a diagnosis of secondary postpar-
tumhaemorrhage. Any denition of secondary postpartumhaem-
orrhage would have been accepted providing the criteria used were
made clear within the paper concerned. Studies were eligible what-
ever the location in which treatment was received and whatever
the length of the follow up.
Types of interventions
There are three types of drug treatment (antibiotics, oxytocics and
hormone therapy) and a variety of surgical treatments. We would
have assumed that variations in the effectiveness of drug treat-
ments within these broad bands were not important (for example,
different types of hormone therapy). Control groups could have
been given placebo or no treatment. Potentially studies could have
compared an individual treatment to another, combinations of
treatments to others, and any individual or combination of treat-
ments to either type of control group. All were of interest but
specically:
antibiotics versus oxytocics;
antibiotics versus hormone therapy;
antibiotics versus placebo;
antibiotics versus no treatment;
antibiotics and oxytocics versus hormone therapy;
antibiotics and hormone therapy versus oxytocics;
antibiotics and oxytocics versus placebo;
antibiotics and oxytocics versus no treatment;
antibiotics and hormone therapy versus placebo;
antibiotics and hormone therapy versus no treatment;
oxytocics versus hormone therapy;
oxytocics versus placebo;
oxytocics versus no treatment;
oxytocics and hormone therapy versus antibiotics;
oxytocics and hormone therapy versus placebo;
oxytocics and hormone therapy versus no treatment;
oxytocics, hormone therapy and antibiotics versus
placebo;
oxytocics, hormone therapy and antibiotics versus no
treatment;
hormone therapy versus placebo;
hormone therapy versus no treatment;
evacuation of retained products of conception versus
each type of drug treatment;
evacuation of retained products of conception versus no
treatment or placebo separately;
other surgical interventions separately versus each type
of drug treatment;
other surgical interventions separately versus no treat-
ment or placebo separately.
Types of outcome measures
Primary outcomes
(Subgroup analyses - see below- would have been limited to these.)
Cessation of abnormal vaginal bleeding (however deter-
mined by trialist) without need for further treatment;
serious maternal morbidity (as dened by trialist) or
death;
blood transfusion(s);
hysterectomy;
evacuationof retained products (whenthis had not been
the intervention);
additional treatments;
cessation of signs of infection (however determined by
trialist).
Secondary outcomes
Post-treatment ultrasound ndings;
days in hospital as a result of secondary postpartum
haemorrhage;
interval from randomisation to cessation of abnormal
bleeding;
side-effects of treatment (for example, nausea, vomiting,
hypertension, allergic reactions, uterine perforation);
economic outcomes;
womens level of satisfaction;
breast milk pharmacokinetics.
Search methods for identication of studies
Electronic searches
We searched the Cochrane Pregnancy and Childbirth Groups Tri-
als Register by contacting the Trials Search Co-ordinator (31 Jan-
uary 2008).
The Cochrane Pregnancy and Childbirth Groups Trials Register
is maintained by the Trials Search Co-ordinator and contains trials
identied from:
1. quarterly searches of the Cochrane Central Register of
Controlled Trials (CENTRAL);
2. weekly searches of MEDLINE;
3. handsearches of 30 journals and the proceedings of ma-
jor conferences;
4. weekly current awareness alerts for a further 44 journals
plus monthly BioMed Central email alerts.
Details of the search strategies for CENTRAL and MEDLINE,
the list of handsearched journals and conference proceedings, and
the list of journals reviewed via the current awareness service can
be found in the Specialized Register section within the edito-
rial information about the Cochrane Pregnancy and Childbirth
Group.
Trials identied through the searching activities described above
are given a code (or codes) depending on the topic. The codes are
linked to review topics. The Trials Search Co-ordinator searches
the register for each reviewusing these codes rather than keywords.
We did not apply any language restrictions.
Data collection and analysis
The full papers of the 36 studies identied by the search strategy
were considered against the selection criteria independently by
two of the authors blind to their authorship, journal of publication
and results. We used a data extraction sheet. The third investigator
acted as an advisor or arbitrator, or both. Where contact addresses
were available, we wrote to the rst named authors of the studies,
requesting details of any further work that they knew of.
If any of the studies had met our inclusion criteria, we would
have used the Review Manager software (RevMan 2000) to enter
the data and to check the accuracy of data entry. We would have
also used the methods outlined in the Cochrane Handbook for
Systematic Reviews of Interventions (Clarke 2000). For full details
of planned methods, see Appendix 1.
R E S U L T S
Description of studies
See: Characteristics of excluded studies.
Of the 36 studies (47 papers) identied by the literature search,
the seven papers identied from their reference lists and ve iden-
tied following responses from rst named authors, none were
considered suitable for inclusion in the review. Details of the latter
twelve papers are given in the Discussion section below. None
of the studies focused on the management of secondary postpar-
tum haemorrhage and none mentioned excessive bleeding in the
diagnostic criteria or denition of the condition being studied. It
had been intended to include only studies of women between 24
hours and three months postdelivery; in the event, very fewstudies
identied how long it was since the women had delivered.
Of the 36studies identiedby the literature review, nine concerned
the management of endometritis following caesarean section, 15
the management of endometritis in general and 11 the prophylaxis
of primary or secondary postpartum haemorrhage, endometritis,
endocervicitis, and perineal infection. Of the 24 studies concern-
ing the management of endometritis, 21 studied the use of antibi-
otics alone, one the use of cervical dilatation alone, one the use
of antibiotics alone but with both groups also undergoing cervical
dilatation and one the continued versus the non-continued use
of antibiotics. One study was a comparison of uterotonic drugs
for women of about three to ve days postnatally, but solely to
compare breast milk pharmacokinetics.
Of the 36 studies identied, 32 stated that allocation had been
randomised, but for only 12 were some details of the randomisa-
tion process described. In the remaining four studies the alloca-
tion was quasi-random. For details of the excluded studies, see the
Characteristics of excluded studies table.
Risk of bias in included studies
No randomised trials were included.
Effects of interventions
No randomised trials were included.
D I S C U S S I O N
A letter was sent to the rst named author of 33 of the 36 studies.
A usable contact address was not available for the remaining three
papers. A second letter/e-mail and letter were sent to the non-
responders; eight replies were received.
Of the seven papers identied from the reference lists of the
36 studies, and the ve identied following responses from rst
named authors, two were non-randomised trials of different oxy-
tocic drugs for the management of the third stage of labour, ve
were case-study reports (three concerning secondary postpartum
haemorrhage (PPH), one primary and secondary PPH and one
primary PPH) and three were case series (one examining organisms
causing endometritis; one its presenting symptoms and timing;
and one the management of intractable primary PPH). One, trans-
lated, paper was a randomised comparison of uterotonic drugs for
women at one to ve days postpartum who had not needed oxy-
tocic drugs.
A U T H O R S C O N C L U S I O N S
Implications for practice
No information is available from randomised controlled trials to
inform the management of women with secondary postpartum
haemorrhage.
Implications for research
A well-designed randomised controlled trial comparing the vari-
ous drug and surgical therapies for women with secondary post-
partum haemorrhage against each other and against placebo or no
treatment groups is needed. When devising exclusion criteria the
severity of blood loss will need careful consideration.
A C K N O W L E D G E M E N T S
We are grateful for the comments and encouragement that we
received from Sally Marchant, Jo Garcia, Cathryn Glazener and
Tim Hillard in relation to the original review. We would also like
to thank the Consumer Panel for their valuable input.
R E F E R E N C E S
References to studies excluded from this review
Andersen 1998 {published data only}
Andersen B, Andersen L, Sorensen T. Methylergometrine during the
early puerperium; a prospective randomized double blind study. Acta
Obstetricia et Gynecologica Scandinavica 1998;77:547.
Andrinopoulos 1983 {published data only}
Andrinopoulos GC, Mendenhall HW. Prostaglandin F2 in the man-
agement of delayed postpartum hemorrhage. American Journal of
Obstetrics and Gynecology 1983;15:2178.
Apuzzio 1985a {published data only}
ApuzzioJJ, GaneshV, Pelosi MA, LandauI, Kaminetzky HA, Kamin-
ski Z, et al.Comparative clinical evaluation of ceftizoxime with clin-
damycin and gentamicin and cefoxitin in the treatment of postce-
sarean endomyometritis. Surgery, Gynecology and Obstetrics 1985;
161:51822.
Apuzzio 1985b {published data only}
Apuzzio J, Kaminski Z, Gamesh V, Louria D. Comparative clinical
evaluation of ticarcillin plus clavulanic acid versus clindamycin plus
gentamicin in treatment of post-cesarean endomyometritis. Ameri-
can Journal of Medicine 1985;79:1647.
Arabin 1982 {published data only}
Arabin B, Ruttgers H, Kubli F. Inuence of a routine use of
methergine on puerperal infection and breast feeding. Proceedings
of 8th European Congress of Perinatal Medicine; 1982 Sept 7-10;
Brussels, Belgium. 1982:81.
Arabin 1986 {published data only}
Arabin B, Ruttgers H, Kubli F. Effects of routine administration of
methylergometrin during the puerperium on involution, maternal
morbidity, and lactation. Geburtshilfe und Frauenheilkunde 1986;46:
21520.
Arredondo-Garcia {published data only}
Arrendondo-Garcia JL, Figueroa-Damian R, Ortiz-Ibarra FJ, Sosa-
Gonzalez IA. Endometritis etiology:diagnosis and treatment. Expe-
rience of the Instituto Nacional de Perinatologia. Current Therapeu-
tic Research 1993;54(5):52939.
Baumgarten 1983 {published data only}
Baumgarten K, Schmidt J, Horvat A, Neumann M, Cerwenka R,
Gruber W, et al.Uterine motility after post-partum application of
sulprostone and other oxytocics. European Journal of Obstetrics &
Gynecology and Reproductive Biology 1983;16:18192.
Bhattacharya 1988 {published data only}
Bhattacharya P, Devi PK, Jain S, Kanthamani CR, Raghavan KS.
Prophylactic use of 15(S)15 methyl PGF2alpha by intramuscular
route for control of postpartum bleeding - a comparative trial with
methylergometrine. Acta Obstetricia et Gynecologica Scandinavica
Supplement 1988;145:135.
Bischoff 1956 {published data only}
Bischoff P, UpchurchK, Carter J. The use of sulsoxazole creaminthe
postpartum patient. American Journal of Obstetrics and Gynecology
1956;71:1135.
Briggs 1989 {published data only}
Briggs GG, Ambrose P, Nageotte MP. Gentamicin dosing in postpar-
tum women with endometritis. American Journal of Obstetrics and
Gynecology 1989;160:30913.
Cormier 1988 {published data only}
Cormier P, Leng JJ, Janky E, Brouste V, Duthil B. Antibiotic prophy-
laxis with cefotetan in the prevention of post-partum and post-abor-
tum infectious complications in endo-uterine investigations. Revue
Francaise de Gynecologie et d Obstetrique 1988;83:82932.
Corson 1977 {published data only}
Corson SL, Bolognese RJ. Postpartum uterine atony treated with
prostaglandins. American Journal of Obstetrics and Gynecology 1977;
129(8):9189.
Del Priore 1996 {published data only}
Del Priore G, Jackson-Stone M, Shim EK, Garnkel J, Eichmann
MA, Frederiksen MC. A comparison of once-daily and 8-hour gen-
tamicin dosing in the treatment of postpartum endometritis. Obstet-
rics & Gynecology 1996;87:9941000.
Dinsmoor 1991 {published data only}
Dinsmoor MJ, Newton ER, Gibbs RS. A randomized, double-blind,
placebo-controlled trial of oral antibiotic therapy following intra-
venous antibiotic therapy for postpartum endometritis. Obstetrics &
Gynecology 1991;77:602.
Faro 1987 {published data only}
Faro S, Phillips LE, Baker JL, Goodrich KH, Turner RM, Riddle
GD. Comparative efcacy and safety of mezlocillin, cefoxitin, and
clindamycin plus gentamicin in postpartum endometritis. Obstetrics
& Gynecology 1987;69:7606.
Faro 1988 {published data only}
Faro S, Martens M, Phillips LE, Hamill H, Smith D, Riddle G. Ticar-
cillin disodium/clavulanate potassium vs clindamycin/gentamicin in
the treatment of postpartum endometritis. Journal of Reproductive
Medicine 1988;33:6036.
Fernandez 1990 {published data only}
Fernandez H, Claquin C, Guibert M, Papiernik E. Suspected post-
partum endometritis: a controlled clinical trial of single-agent an-
tibiotic therapy with amox-CA (augmentin R) vs ampicillin-metron-
idazole plus or minus aminoglycoside. European Journal of Obstetrics
& Gynecology and Reproductive Biology 1990;36:6974.
Fernandez 1993 {published data only}
Fernandez H, GagnepainA, Bourget P, Peray P, FrydmanR, Papiernik
E, et al.Antibiotic prophylaxis against postpartum endometritis af-
ter vaginal delivery: a prospective randomized comparison between
Amox-CA (Augmentin) and abstention. European Journal of Obstet-
rics & Gynecology and Reproductive Biology 1993;50:16975.
Figueroa-Damian 1992 {published data only}
Figueroa-Damian R, Angel-Muller E, Sosa-Gonzalez i, Arredondo-
Garcia JL. Gyneco-obstetrical infections by anaerobic bacteria [In-
fecciones ginecoobstetricas por bacterias anaerobias]. Ginecologia y
Obstetricia de Mexico 1992;60:16270.
Figueroa-Damian 1996 {published data only}
Figueroa-Damian R, Villagrana-Zesati R, San Martin-Herrasti
J, Arredondo-Garcia J. Comparison of therapeutic efcacy of
piperacillin/tazobactam vs. ampicillin plus gentamicin in the treat-
ment of post-cesarean endometritis [Comparacion de la ecacia ter-
apeutica de piperacilina/tazobactam vs ampicilina mas gentamicina
en el tratamiento de endometritis poscesarea]. Ginecologia y Obste-
tricia de Mexico 1996;64:2148.
Friedman 1957 {published data only}
Friedman EA. Comparative clinical evaluation of postpartum oxyto-
cics. American Journal of Obstetrics and Gynecology 1957;73:1306
13.
Gall 1996 {published data only}
Gall
S, Koukol DH. Ampicillin/sulbactam vs clindamycin/gentamicin in
the treatment of postpartum endometritis. Journal of Reproductive
Medicine 1996;41:57580.
Gibbs 1988 {published data only}
Gibbs RS, Dinsmoor MJ, Newton ER, Ramamurthy RS. A ran-
domized trial of intrapartum vs immediate postpartum treatment of
women with intra-amniotic infection. Obstetrics & Gynecology 1988;
72:8238.
Goldstein 1986 {published data only}
Goldstein AI, Kent DR, David A. Prostaglandin E2 vaginal supposi-
tories in the treatment of intractable late-onset postpartum haemor-
rhage - a case report. Journal of Reproductive Medicine 1983;28(6):
4256.
Greenberg 1987 {published data only}
Greenberg RN, Reilly PM, Weinandt WJ, Wilson KM, Bollinger
M, Ojile JM. Comparison trial of clindamycin with aztreonam or
gentamicin in the treatment of postpartum endometritis. Clinical
Therapeutics 1987;10:369.
Groeber 1960 {published data only}
Groeber WR, Bishop EH. Methergine and ergonovine in the third
stage of labour. Obstetrics & Gynecology 1960;15(1):858.
Grunberger 1983 {published data only}
Grunberger W. Postpartum uterus involution and lactation levels in
randomized comparison between Prostin E2 tablets and Methergin-
Dragees [Postpartale Uterusinvolution und Laktationsmengen im
randomisierten Vergleich von ProstinE2Tabletten mit Methergin
Dragees]. Gynakologische Rundschau 1983;23:1007.
Lancheros 1997 {published data only}
Lancheros S, Gaitan H. Comparison between two therapeutic sched-
ules: gentamicin plus gentamicyn and peoxacin plus metronidazol
in post-cesarean endometritis treatment. A clinical trial. Acta Obste-
tricia et Gynecologica Scandinavica 1997;76:28.
Ledee 2001 {published data only}
Ledee N, Ville Y, Musset D, Mercier F, Frydman R, Fernandez H.
Management in intractable obstetric haemorrhage: an audit on 61
cases. European Journal of Obstetrics & Gynecology and Reproductive
Biology 2001;94(2):18996.
Maccato 1991 {published data only}
Maccato ML, Faro S, Martens MG, Hammill HA. Ciprooxacin
vs gentamicin/clindamycin for postpartum endometritis. Journal of
Reproductive Medicine 1991;36:85761.
Martens 1989 {published data only}
Martens MG, Faro S, Hammill HA, Maccato M, Riddle G, Smith D.
Ampicillin/sulbactam vs clindamycin in the treatment of postpartum
endomyometritis. Southern Medical Journal 1989;82:39.
McGregor 1989 {published data only}
McGregor JA, Christensen FB. A comparison of ampicillin plus sul-
bactam vs clindamycin and gentamicin for treatment of postpartum
infection. International Journal of Gynecology & Obstetrics 1989;S2:
359.
Mitra 1997 {published data only}
Mitra A, WhittenK, Laurent S, AndersonW. Arandomized, prospec-
tive study comparing once-daily gentamicin versus thrice-daily gen-
tamicin in the treatment of puerperal infection. American Journal of
Obstetrics and Gynecology 1997;177:78692.
Moodie 1976 {published data only}
Moodie JE, Moir DD. Ergometrine, oxytocin and extradural anal-
gesia. British Journal of Anaesthesia 1976;48:571.
Morales 1989 {published data only}
Morales WJ, Collins EM, Angel JL, Knuppel RA. Short course of an-
tibiotic therapy in treatment of postpartumendomyometritis. Amer-
ican Journal of Obstetrics and Gynecology 1989;161:56872.
Paraskevaides 1993 {published data only}
Paraskevaides E, Stuart B, Gardeil F. Secondary postpartum haem-
orrhage from nondehisced lower caesarean section scar: a case for
hysteroscopy. Australian and New Zealand Journal of Obstetrics and
Gynaecology 1993;33(4):427.
Perry 1997 {published data only}
Perry K, Theilman G, Coker K, Martin J. A prospective random-
ized trial comparing Gentamicin administered every 8 hours versus
Gentamicin administered every 24 hours for the treatment of postce-
sarean section endometritis. American Journal of Obstetrics and Gy-
necology 1997;176:S59.
Pond 1979 {published data only}
Pond DG, Bernstein EP, Love KR, Morgan JR, Velland H, Smith
JA. Comparison of ampicillin with clindamycin plus gentamicin in
the treatment of postpartum uterine infection. Canadian Medical
Association Journal 1979;120:5337.
Rodriguez-Ballestero {published data only}
Rodriguez-Ballesteros R, Alarcon-Aburto V, De Los Angeles Madri-
gal-De La Campa M, Valerio-Castro E. Antibiotics short course in
post-cesarean endometritis treatment [Esquema corto de antibioticos
en el tratamiento de endometritis posterior a cesarea]. Ginecologia y
Obstetricia de Mexico 1996;64:35962.
Rubin 1961 {published data only}
Rubin A. Use of a sulfonamide vaginal cream post partum. A con-
trolled blind study of 700 patients. American Journal of Obstetrics
and Gynecology 1961;82:8602.
Sen 1980 {published data only}
Sen P, Apuzzio J, Reyelt C, Kaminski T, Levy F, Kapila R, et
al.Prospective evaluation of combinations of antimicrobial agents for
endometritis after cesarean section. Surgery, Gynecology and Obstet-
rics 1980;151:8992.
Sorrell 1981 {published data only}
Sorrell TC, Marshall JR, Yoshimori R, Chow AW. Antimicrobial
therapy of postpartumendomyometritis. II. Prospective randomized
trial of mezlocillin vs ampicillin. American Journal of Obstetrics and
Gynecology 1981;141:24651.
Takagi 1976 {published data only}
Takagi S, Yoshida T, Togo Y, Tochigi H, Abe M, Sakata H, et al.The
effects of intramyometrial injection of prostaglandin F2 on severe
postpartum haemorrhage. Prostaglandins 1976;12(4):56579.
Vogel 2004 {published data only}
Vogel D, Burkhardt T, RentschK, Schweer H, Watzer B, Zimmerman
R, et al.Misoprostol versus methylergometrine: pharmacokinetics in
human milk. American Journal of Obstetrics and Gynecology 2004;
191:216873.
Walss-Rodriguez 1990 {published data only}
Walss-Rodriguez RJ, Rocha-Avila LC. Puerperal deciduometritis.
Importance of mechanical cervical dilatation. Ginecologia y Obstetri-
cia de Mexico 1990;58:2703.
Whitten 1997 {published data only}
Whitten K, Mitra A, Laurent S, Anderson B. Arandomized, prospec-
tive study comparing once daily Gentamicin with thrice daily Gen-
tamicin in the treatment of puerperal endometritis. AmericanJournal
of Obstetrics and Gynecology 1997;176:S32.
Additional references
ACOG 1990
American College of Obstetrics and Gynecology. Diagnosis and
management of postpartum haemorrhage. International Journal of
Gynecology & Obstetrics 1990;36:15963.
Alexander 1997
Alexander J, Garcia J, Marchant S. The BLiPP Study - a sur-
vey and case control study. Final report to the South and West
NHS Executive Research and Development Committee (Response
mode). Bournemouth: Institute of Health and Community Studies.
Bournemouth University, 1997. [: ISBN 1858990947]
Begley 1990
Begley CM. Acomparison of active and physiological management
of the third stage of labour. Midwifery 1990;6:317.
Bick 1995
Bick DE, MacArthur C. The extent, severity and effect of health
problems after childbirth. British Journal of Midwifery 1995;3(1):
2731.
Calhoun 1995
Calhoun BC, Brost B. Emergency management of sudden puerperal
fever. Obstetrics and Gynecology Clinics of North America 1995;22(2):
35767.
CEMACH 2004
Condential Enquiry into Maternal and Child Health. Why mothers
die 2000-2002. The sixth report of the Condential Enquiries into
Maternal Deaths in the United Kingdom. London: RCOG Press,
2004.
Clarke 2000
Clarke M, Oxman AD, editors. Cochrane Reviewers Handbook
4.1.1 [updated December 2000]. In: The Cochrane Library
[database on CDROM]. The Cochrane Collaboration. Oxford: Up-
date Software 2001, Issue 2.
Crowley 1984
Crowley J. Post-delivery bleeding due to group B beta-haemolytic
streptococcal infection. New Zealand Medical Journal 1984;97:377.
Dewhurst 1966
Dewhurst CJ. Secondary postpartum haemorrhage. Journal of Ob-
stetrics & Gynaecology of the British Commonwealth 1966;73:538.
DoH 1999
Department of Health. Why mothers die - report on condential en-
quiries into maternal deaths in the United Kingdom 1994-1996. Lon-
don: Department of Health, 1999.
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French LM, Smaill FM. Antibiotic regimens for endometritis af-
ter delivery. Cochrane Database of Systematic Reviews 2004, Issue 4.
[DOI: 10.1002/14651858.CD001067.pub2]
Glazener 1995
Glazener CMA, Abdalla M, Stroud P, Naji S, Templeton A, Russel
IT. Postnatal maternal morbidity: extent, causes, prevention and
treatment. British Journal of Obstetrics and Gynaecology 1995;102:
2827.
Glazener 1999
Glazener CMA. Investigation of postnatal experience and care in
Grampian [Unpublished PhD thesis]. Aberdeen: University of Ab-
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King PA, Duthie SJ, Dong ZG, Ma HK. Secondary postpartum
haemorrhage. Australian and New Zealand Journal of Obstetrics and
Gynaecology 1989;29(4):3948.
Lester 1956
Lester WM, Bartholomew RA, Colvin ED, Grimes WH, Fish JS,
Galloway WH. The role of retained placental fragments in immediate
and delayed postpartum hemorrhage. American Journal of Obstetrics
and Gynecology 1956;72(6):121426.
MacArthur 1991
MacArthur C, Lewis M, Knox EG. Health after childbirth. London:
HMSO, 1991.
Marchant 2006
Marchant S, Alexander J, Thomas P, Garcia J, Brocklehurst P, Keene
J. Risk factors for hospital admission related to excessive and/or pro-
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childbirth. Paediatric and Perinatal Epidemiology 2006;20:392402.
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1992;1:603.
Novak-Antolic 1997
Novak-Antolic Z, Pajntar M, Verdenik I. Rupture of the membranes
and postpartum infection. European Journal of Obstetrics & Gynecol-
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man and Hall, 1991.
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Windows. Oxford, England: The Cochrane Collaboration, 2000.
Rome 1975
Rome RM. Secondary postpartum haemorrhage. British Journal of
Obstetrics and Gynaecology 1975;82:28992.
Stovall 1998
Stovall TG, Ambrose SE, Ling FW, Anderson GD. Short-course an-
tibiotic therapy for the treatment of chorioamnionitis and postpar-
tum endomyometritis. American Journal of Obstetrics and Gynecology
1998;159(2):4047.
Thorsteinsson 1970
Thorsteinsson VT, Kempers RD. Delayed postpartum bleeding.
American Journal of Obstetrics and Gynecology 1970;107(4):56571.
Weisenberg-Smith1993
Weisenberg-Smith S. Literature review of secondary postpartum
bleeding. National Perinatal Epidemiology Unit, Oxford, Unpub-
lished 1993.
Indicates the major publication for the study

C H A R A C T E R I S T I C S O F S T U D I E S
Characteristics of excluded studies [ordered by study ID]
Andersen 1998 Not concerning treatment of secondary postpartum haemorrhage.
Andrinopoulos 1983 Case study report, not a RCT.
Apuzzio 1985a Not concerning treatment of secondary postpartum haemorrhage.
Apuzzio 1985b Not concerning treatment of secondary postpartum haemorrhage.
Arabin 1982 Not concerning treatment of secondary postpartum haemorrhage.
Arabin 1986 Not concerning treatment of secondary postpartum haemorrhage.
Arredondo-Garcia Not concerning treatment of secondary postpartum haemorrhage.
Baumgarten 1983 Not concerning treatment of secondary postpartum haemorrhage.
Bhattacharya 1988 Not concerning treatment of secondary postpartum haemorrhage.
Bischoff 1956 Not concerning treatment of secondary postpartum haemorrhage.
Briggs 1989 Not concerning treatment of secondary postpartum haemorrhage.
Cormier 1988 Not concerning treatment of secondary postpartum haemorrhage.
Corson 1977 Not concerning treatment of secondary postpartum haemorrhage.
Del Priore 1996 Not concerning treatment of secondary postpartum haemorrhage.
Dinsmoor 1991 Not concerning treatment of secondary postpartum haemorrhage.
Faro 1987 Not concerning treatment of secondary postpartum haemorrhage.
Faro 1988 Not concerning treatment of secondary postpartum haemorrhage.
Fernandez 1990 Not concerning treatment of secondary postpartum haemorrhage.
Fernandez 1993 Not concerning treatment of secondary postpartum haemorrhage.
Figueroa-Damian 1992 Not concerning treatment of secondary postpartum haemorrhage.
(Continued)
Figueroa-Damian 1996 Not concerning treatment of secondary postpartum haemorrhage.
Friedman 1957 Not concerning treatment of secondary postpartum haemorrhage.
Gall 1996 Not concerning treatment of secondary postpartum haemorrhage.
Gibbs 1988 Not concerning treatment of secondary postpartum haemorrhage.
Goldstein 1986 Case study report, not a RCT.
Greenberg 1987 Not concerning treatment of secondary postpartum haemorrhage.
Groeber 1960 Not concerning treatment of secondary postpartum haemorrhage.
Grunberger 1983 Not apparently concerning treatment of secondary postpartum haemorrhage.
Lancheros 1997 Not concerning treatment of secondary postpartum haemorrhage.
Ledee 2001 Concerning treatment of both primary and secondary postpartum haemorrhage. Audit of 61 case studies.
Maccato 1991 Not concerning treatment of secondary postpartum haemorrhage.
Martens 1989 Not concerning treatment of secondary postpartum haemorrhage.
McGregor 1989 Not concerning treatment of secondary postpartum haemorrhage.
Mitra 1997 Not concerning treatment of secondary postpartum haemorrhage.
Moodie 1976 Not concerning treatment of secondary postpartum haemorrhage.
Morales 1989 Not concerning treatment of secondary postpartum haemorrhage.
Paraskevaides 1993 Case study report, not a RCT.
Perry 1997 Not concerning treatment of secondary postpartum haemorrhage.
Pond 1979 Not concerning treatment of secondary postpartum haemorrhage.
Rodriguez-Ballestero Not concerning treatment of secondary postpartum haemorrhage.
Rubin 1961 Not concerning treatment of secondary postpartum haemorrhage.
Sen 1980 Not concerning treatment of secondary postpartum haemorrhage.
(Continued)
Sorrell 1981 Not concerning treatment of secondary postpartum haemorrhage.
Takagi 1976 Concerning treatment of both primary and secondary postpartum haemorrhage. Case study report, not a
RCT.
Vogel 2004 Not apparently concerning treatment of secondary postpartum haemorrhage.
Walss-Rodriguez 1990 Not concerning treatment of secondary postpartum haemorrhage.
Whitten 1997 Not concerning treatment of secondary postpartum haemorrhage.
RCT = randomised controlled trial
D A T A A N D A N A L Y S E S
This review has no analyses.
A P P E N D I C E S
Appendix 1. Planned methods
Sifting studies
This will be carried out by the Contact person and a co-author independently and blind to authorship. The abstracts of all identied
studies will be assessed against the Selection criteria. Those that obviously do not satisfy themwill be discarded. The remainder will be
retrieved in full and their eligibility assessed without consideration of their results. Disagreements will be resolved by discussion between
two authors and, if necessary, with the third author. If disagreement persists, we will seek a nal decision from the Topic Editor.
Critical appraisal of studies
Both authors will assess all trials for methodological quality independently. Quality of allocation concealment will be assessed using
scores A (adequate concealment), B (uncertainty about adequacy of concealment) and C (not adequately concealed) as described in
the Cochrane Handbook for Systematic Reviews of Interventions (Clarke 2000). All trials will be included in the primary analyses
regardless of score. Quality will be taken into account in a sensitivity analysis where the robustness of the results will be tested by
removing the lower quality studies.
Since there is the potential for blinding of allocation in these trials, we will also score trials according to whether they were double-
blinded (0 = no, 1 = yes but only stated, 2 = yes described and appropriate), and we will identify those trials which did not provide
a description of withdrawals and dropouts. These quality assessments will be used for descriptive purposes, and to inform further
sensitivity analyses.
Data extraction
Two authors will independently extract data for each eligible trial. The data will be entered on printed data sheets with prespecied
outcomes. Completed data sheets will be compared and any discrepancies resolved before analysis. If agreement cannot be reached, we
will seek a nal decision from the Topic Editor.
Any data that do not t the outcomes prespecied by the authors will be collected, clearly labelled as not prespecied and reported.
In order to minimise the risk of bias, we plan to base our conclusions on the prespecied outcomes only. Data needed for subgroup
analysis will also be collected.
Analysis
All primary outcomes are dichotomous, and will be compared individually between the (potentially) 20 drug treatment and control
group combinations. The effect of each treatment on each outcome in each study will be summarised by odds ratios and 95%condence
intervals. Results will be displayed graphically. Heterogeneity betweenstudies for each particular treatment or control group combination
and particular outcome will be tested using a chi-squared test. If not signicant, a xed-effect model will be assumed, and the results
from the studies pooled using the Mantel-Haenszel method. If signicant, we will assess whether variation between studies can be
explained by differences in methodological quality, or (cautiously, because of interpretational difculties in comparing non-randomised
groups) differences in population or intervention. The use of a random-effects model will also be considered.
Of interest will be whether there is heterogeneity between studies investigating treatment and placebo compared with treatment and
no treatment, for each of the types of treatment. If there is no evidence of heterogeneity, we will also take a broader view and conduct
an additional meta-analysis combining the placebo controlled and no treatment controlled studies. A similar approach will be taken
for studies investigating the effect of hormone therapy; if there is evidence of heterogeneity between studies using oestrogen therapy
and those using progesterone therapy, then separate meta-analyses will be conducted.
If there are sufcient studies, funnel plots will be used to assess the risk of publication bias.
A 5% level of statistical signicance will be used throughout. It is recognised that there are potentially a large amount of signicance
tests to be done, and accordingly an increased chance of type I errors. Interpretation of results will be done cautiously, particularly
where P values are greater than 0.01 or results are inconsistent, or both.
A number of formal subgroup analyses will be done. Greater interpretational weight will be given to subgroups identiable within
studies rather than between studies (where interpretation is much less reliable). Parity (primiparae versus multiparae), whether rupture
of membranes had occurred prior to the onset of labour or not, the type of delivery (normal vaginal; vaginal operative including breech;
caesarean section) and whether the placenta or membranes, or both, were complete will be included in the subgroup analysis. Specic
tests of the treatment x subgroup interactions (using logistic regression) will be carried out to aid proper interpretation of the subgroup
analysis.
We will conduct sensitivity analyses to assess the robustness of the results. This may involve the removal of smaller studies (publication
bias), or studies of relatively poor methodological quality, or both. It may also include assessment of publication bias, or other types of
bias by looking at robustness of the results under various scenarios that assume certain levels of bias.
W H A T S N E W
Last assessed as up-to-date: 30 January 2008.
12 February 2008 Amended Converted to new review format.
31 January 2008 New search has been performed Search updated. One new trial identied and excluded (Grunberger 1983).
H I S T O R Y
Protocol rst published: Issue 4, 2000
Review rst published: Issue 1, 2002
C O N T R I B U T I O N S O F A U T H O R S
Jo Alexander and Peter Thomas developed and wrote the protocol. Jo Alexander and Jill Sanghera identied relevant papers and reviewed
them against the prespecied selection criteria. Peter Thomas arbitrated when consensus could not be reached. Jo Alexander, Peter
Thomas and Jill Sanghera wrote the nal review. Jill Sanghera was not a contributor to this update.
D E C L A R A T I O N S O F I N T E R E S T
None known.
S O U R C E S O F S U P P O R T
Internal sources
School of Health and Social Care, Bournemouth University, UK.
External sources
Dorset Research and Development Support Unit, Poole Hospital, UK.
D I F F E R E N C E S B E T W E E N P R O T O C O L A N D R E V I E W
The title of the protocol which preceded this review was Drug treatment for secondary postpartum haemorrhage. As the search terms
used would also have identied any papers concerning surgical treatment, when the rst named authors were written to, they were
asked for details of any further work that they knew of concerning either drug or surgical treatments. This review therefore covers both.
I N D E X T E R M S
Medical Subject Headings (MeSH)
Postpartum Hemorrhage [
therapy]
MeSH check words
Female; Humans; Pregnancy

Treatments For Secondary Postpartum Haemorrhage (Review)

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Treatments for secondary postpartum haemorrhage (Review)

Alexander J, Thomas PW, Sanghera J

Indicates the major publication for the study

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